American Handbook of Psychiatry Vol 4

American
Handbook of Psychiatry
Volume Four
Silvano Arieti, Editor-in-Chief
Organic Disorders and Psychosomatic Medicine
Morton F. Reiser, Editor

e-Book 2015 International Psychotherapy Institute
From American Handbook of Psychiatry: Volume 4 edited by Silvano Arieti, Morton F. Reiser
Copyright © 1975 by Basic Books
All Rights Reserved
Created in the United States of America

Part One: Organic Disorders
1. Physical Illness, The Patient And His Environment: Psychosocial

Foundations Of Medicine Zbignew J. Lipowski
2. Delirium And Related Problems Stanley S. Heller and Donald S. Kornfeld
3. Aging and Psychiatric Diseases of Late Life Ewald W. Busse
4. The Neuropathology Associated With The Psychoses Of Aging Armando

Ferraro
5. Neurosyphilitic Conditions: General Paralysis, General Paresis,

Dementia Paralytica Walter L. Bruetsch
6. Postencephalitic States Or Conditions Henry Brill
7. Head Injury Kenneth Tuerk, Irving Fish, and Joseph Ransohoff
8. Functional Disturbances In Brain Damage Kurt Goldstein
9. Psychiatric Conditions Associated With Focal Lesions Of The Central

Nervous System D. Frank Benson and Norman Geschwind
10. The Neural Organization Of Language: Aphasia And Neuropsychiatry

Jason W. Brown
11. Aphasia: Behavioral Aspects J.P. Mohr and Murray Sidman
www.freepsychotherapybooks.org 4
12. Psychiatric Disturbances Associated with Endocrine Disorders Edward
J. Sachar
13. Epilepsy: Neuropsychological Aspects Gilbert H. Glaser
14. Psychoses Associated with Drug Use Malcolm B. Bowers, Jr. and Daniel
X. Freedman
15. Alcoholism: A Biobehavioral Disorder Nancy K. Mello and Jack H.

Mendelson
16. Psychosis Associated With Hereditary Disorders I. Herbert Scheinberg
17. Mental Disorders with Huntington's Chorea

A. Clinical Aspects John R. Whittier
B. Neuropathology Leon Roizin and Mavis A. Kaufman
18. MENTAL RETARDATION I. Nature and Manifestations Sterling D.

Garrard and Julius B. Richmond
19. MENTAL RETARDATION II. Care and Management Sterling D. Garrard

and Julius B. Richmond
20. Biomedical Types Of Mental Deficiency George A. Jervis
Part Two: Psychosomatic Medicine
21. Changing Theoretical Concepts In Psychosomatic Medicine Morton F.

Reiser
22. Autonomic Psychophysiology: Peripheral Autonomic Mechanisms And

Their Central Control Herbert Weiner
23. The Principles Of Autonomic Function In The Life Of Man And Animals
Myron A Hofer
24. CLINICAL PSYCHOPHYSIOLOGY Psychoendocrine Mechanisms John W.

Mason
25. Psychosocial And Epidemiological Concepts In Medicine John J.

Schwab
26. Psychological Aspects Of Cardiovascular DiseaseChase Paterson

Kimball
with a subsection on Psychophysiological and Psychodynamic
Problems of the Patient with Structural Heart Disease Morton F.
Reiser and Hyman Bakst
27. Psychological Aspects Of Gastrointestinal Disorders George L. Engel
28. Psychosomatic Aspects Of Bronchial Asthma Peter H. Knapp
29. Disorders Of Immune Mechanisms Raul C. Shiavi and Marvin Stein
30. Musculoskeletal Disorders Donald Oken
31. Obesity Albert J. Stunkard
32. Anorexia Nervosa Hilde Bruch
33. Disturbances of The Body-Image Lawrence C. Kolb
34. Complex Problems of Pain As Seen In Headache, Painful Phantom, and

Other States Shervert H. Frazier
35. Sleep Disorders and Disordered Sleep Robert L. Williams and Ismet
Karacan
36. The Teaching Of Psychosomatic Medicine Consultation-Liaison

Psychiatry F. Patrick McKegney
Hyman Bakst, M.D.
Associate Attending in Medicine, Beth-Israel Hospital, New York; Assistant Clinical
Professor of Medicine, Mount Sinai School of Medicine of the City University of New
York.
Frank Benson, M.D.

Director, Neurohehavioral Center, Boston Veterans’ Administration Hospital;
Professor of Neurology, Boston University School of Medicine.
Malcolm B. Bowers, Jr., M.D.

Associate Professor of Psychiatry, Yale University School of Medicine, New Haven;
Chief of Psychiatry, Yale-New Haven Hospital.
Henry Brill, M.D.

Regional Director, New York State Department of Mental Hygiene, Hauppaauge,
New York; Clinical Professor of Psychiatry, Downstate Medical Center at Stony
Brook, New York.
Jason W. Brown, M.D.

Associate Clinical Professor of Neurology, New York University Medical Center,
New York.
Hilde Bruch, M.D.

Professor of Psychiatry, Baylor College of Medicine, Houston.
Walter L. Bruetsch, M.D.

Professor Emeritus, Neurology and Neuropathology, Indiana University School of
Medicine, Indianapolis; Former Director, Research Laboratories, Central State
Hospital, Indianapolis.
Ewald W. Busse, M.D.

J. P. Gibbons Professor of Psychiatry, Duke University, Durham, North Carolina;
Associate Provost and Director, Medical and Allied Health Education, Duke
University Medical Center.
George L. Engel, M.D.
Professor of Psychiatry and Professor of Medicine, University of Rochester School
of Medicine, Rochester, New York.
Armando Ferraro, M.D.

Retired; Formerly, Clinical Professor of Psychiatry, College of Physicians and
Surgeons, Columbia University, New York; Formerly, Head of the Research
Department of Neuropathology, New York State Psychiatric Institute, New York.
Irving Fish, M.D.

Assistant Professor of Neurology (Pediatrics) and Acting Director, Division of
Pediatric Neurology, New York University Medical Center, New York.
Shervert H. Frazier, M.D.

Psychiatrist-in-Chief, McLean Hospital, Belmont, Massachusetts; Professor of
Psychiatry, Harvard Medical School, Boston.
Daniel X. Freedman, M.D.

Louis Block Professor of Biological Sciences and Chairman, Department of
Psychiatry, University of Chicago Pritzker School of Medicine.
Sterling D. Garrard, M.D.

Chief of the Medical Division, Walter E. Fernald State School, Waltham,
Massachusetts; Director, University Affiliated Program, Eunice Kennedy Shriver
Center for Mental Retardation, Waltham.
Norman Geschwind, M.D.

James Jackson Putnam Professor of Neurology, Harvard Medical School, Boston.
Gilbert H. Glaser, M.D.

Professor of Neurology and Chairman, Department of Neurology, Yale University
School of Medicine, New Haven; Neurologist-in-Chief, Yale-New Haven Hospital.
Kurt Goldstein, M.D.
Stanley S. Heller, M.D.
Assistant Professor of Clinical Psychiatry, College of Physicians and Surgeons,
Columbia University, New York; Director, Psychiatric Consultation Service, St.
Luke’s Hospital, New York.
Myron A. Hofer, M.D.

Associate Attending Psychiatrist, Montefiore Hospital and Medical Center, Bronx,
New York; Associate Professor of Psychiatry, Albert Einstein College of Medicine,
Bronx.
George A. Jervis, M.D.

Director, Institute of Basic Research in Mental Retardation, Richmond, New York;
Clinical Professor of Psychiatry, College of Physicians and Surgeons, Columbia
University, New York.
Ismet Karacan, M.D., Med.D.Sc.

Professor of Psychiatry, Baylor College of Medicine, Houston; Associate Chief of
Staff for Research, Veterans’ Administration Hospital, Houston.
Mavis A. Kaufman, M.D.

Pathologist, New York State Psychiatric Institute, New York; Associate Professor of
Neuropathology, College of Physicians and Surgeons, Columbia University, New
York.
Chase Patterson Kimball, M.D.

Professor of Psychiatry, Medicine, and Behavioral Science, University of Chicago
Pritzker School of Medicine.
Peter H. Knapp, M.D.

Associate Chairman, Division of Psychiatry, Boston University School of Medicine.
Lawrence C. Kolb, M.D.

Professor and Chairman, Department of Psychiatry, College of Physicians and
Surgeons, Columbia University, New York; Director, New York State Psychiatric
Institute, New York.
Donald S. Kornfeld, M.D.
Chief, Psychiatric Consultation Service, Columbia- Presbyterian Medical Center,
New York; Professor of Clinical Psychiatry, College of Physicians and Surgeons,
Columbia University, New York.
Zbigniew J. Lipowski, M.D.

Professor of Psychiatry, Dartmouth Medical School, Hanover, New Hampshire;
Director, Psychiatric Consultation Service, Dartmouth-Hitchcock Medical Center.
Patrick McKegney, M.D.

Professor, Department of Psychiatry, University of Vermont College of Medicine,
Burlington; Director, Consultation-Liaison Service, University of Vermont.
John W. Mason, M.D.

Chief, Department of Neuroendocrinology, Division of Neuropsychiatry, Walter
Reed Army Institute of Research, Walter Reed Army Medical Center, Washington.
Nancy K. Mello, Ph.D.

Lecturer, Harvard Medical School, Boston; Psychologist, McLean Hospital, Belmont,
Massachusetts.
Jack H. Mendelson, M.D.

Professor of Psychiatry, Harvard Medical School, Boston; Director, Alcohol and
Drug Abuse Research Center, McLean Hospital, Belmont, Massachusetts.
J.P. Mohr, M.D.

Assistant Neurologist, Massachusetts General Hospital, Boston; Assistant Professor
of Neurology, Harvard Medical School, Boston.
Donald Oken, M.D.

Professor and Chairman, Department of Psychiatry, Upstate Medical Center, State
University of New York, Syracuse.
Joseph Ransohoff, M.D.

Professor and Chairman, Department of Neurosurgery, New York University
Medical Center, New York; Director, Neurosurgery, Bellevue Hospital Center, New
York.
Morton F. Reiser, M.D.
Professor and Chairman, Department of Psychiatry, Yale University School of
Medicine, New Haven.
Julius B. Richmond, M.D.

Professor of Child Psychiatry and Human Development, and Professor of
Preventive and Social Medicine in the Faculty of Public Health and the Faculty of
Medicine, Harvard Medical School, Boston; Director, Judge Baker Guidance Center,
Boston.
Leon Roizin, M.D.

Chief of Psychiatric Research (Neuropathology), New York State Psychiatric
Institute, New York; Professor of Neuropathology, College of Physicians and
Surgeons, Columbia University, New York.
Edward J. Sachar, M.D.

Professor of Psychiatry and Neuroscience, Albert Einstein College of Medicine,
Bronx, New York.
Herbert Scheinberg, M.D.

Professor of Medicine, Albert Einstein College of Medicine, Bronx, New York;
Visiting Physician, Bronx Municipal Hospital Center.
Raul C. Schiavi, M.D.

Associate Professor of Psychiatry, Mount Sinai School of Medicine of the City
University of New York; Associate Attending Psychiatrist, Mount Sinai Hospital,
New York.
John J. Schwab, M.D.

Professor and Chairman, Department of Psychiatry and Behavioral Sciences,
University of Louisville School of Medicine, Louisville, Kentucky.
Murray Sidman, Ph.D.

Professor of Psychology, Northeastern University, Boston; Director of Behavioral
Research, Eunice Kennedy Shriver Center for Mental Retardation of the Walter E.
Femald State School, Waltham, Massachusetts.
Marvin Stein, M.D.
Professor and Chairman, Department of Psychiatry, Mount Sinai School of Medicine
of the City University of New York.
Albert J. Stunkard, M.D.

Professor of Psychiatry, Stanford University School of Medicine, Stanford,
California.
Kenneth Tuerk, M.D.

Assistant Professor of Neurosurgery, School of Medicine, University of California at
San Francisco; Assistant Chief of Neurosurgery, San Francisco General Hospital, San
Francisco.
Herbert Weiner, M.D.

Chairman, Department of Psychiatry, Montefiore Hospital and Medical Center,
Bronx, New York; Professor of Psychiatry and Neuroscience, Albert Einstein
College of Medicine, Bronx.
John R. Whittier, M.D.

Director of Psychiatric Research, Creedmoor Institute for Psychobiologic Studies,
New York State Department of Mental Hygiene, Queens Village, New York;
Assistant Clinical Professor of Psychiatry, College of Physicians and Surgeons,
Columbia University, New York.
Robert L. Williams, M.D.

D. C. and Irene Ellwood Professor and Chairman of Psychiatry, Baylor College of
Medicine, Houston, Texas; Chief, Psychiatry Service, Methodist Hospital Texas
Medical Center, Houston, Texas.
Chapter 1
Physical Illness, The Patient And His

Environment: Psychosocial Foundations Of
Medicine
Zbigniew J. Lipowski
Introduction
The dominant focus of this Volume is on mind-body-environment

interrelationships as they determine health and disease. Whether we talk of
psychosomatic medicine, of organic brain syndromes, or of psychosocial

aspects of physical illness, we are looking at different facets of the same basic
theme, namely the interplay between man as a psychobiological unit and his
environment as it pertains to health and disease.
The present Chapter has a twofold purpose: to outline briefly the
contemporary conceptions of disease, and to provide a comprehensive
framework for organizing our knowledge about human experience and
behavior in physical illness and disability. The writer’s approach to both these
topics is both holistic and ecological. The holistic viewpoint sees body and
personality as two integral aspects of a larger whole: The person. Soma and
psyche are constructs reflecting two different modes of abstraction and

methodological approaches to the study of man, the biophysical and the
psychological, respectively. These different approaches involve two distinct
languages for description of the phenomena studied and for the formulation
of relevant explanatory statements. Human body and personality constitute a

unit shaped by continuous interplay between man’s genetic endowment and
his social and physical environment. The ecological perspective stresses the
ways in which environment influences man and he in turn affects it. Mind,
body, and environment are viewed as elements of a dynamically interacting
system. Human health and disease are a continuum of psychobiological states
determined to a varying extent by biophysical, psychological, and social
variables. These states involve all levels of human organization, from the
molecular to the symbolic. This view is equally valid for what, in our dualistic
language, we call psychiatric and physical, or mental and organic disorders.
A traditional approach in medicine has been to distinguish sharply
between etiological and reactive factors in disease. This distinction still has
some practical value in the search for specific causal agents and for
preventive action. Yet dichotomies like “etiological” versus “reactive,”
“organic” versus “mental,” or “psychosomatic” versus “somatopsychic,” are
becoming less sharp now with the emergence of multicausal and dynamic
conceptions of disease and the recognition of complex feedback mechanisms.
For practical purposes, however, it is still useful to talk of psychological

responses to physical illness, while keeping in mind that they are an integral
part of it.
To reflect contemporary trends in both medicine and psychiatry it is
appropriate to introduce this Volume with a conceptual bridge between
medicine and behavioral sciences, and psychiatry, which has its roots in both.
We shall call this approach psychobiological ecology of man. To develop it, we
need to cross interdisciplinary boundaries in quest of a unified knowledge of
mind-body-environment transactions. This quest has emerged as one of the

most important scientific challenges of our times.
The major sections of this chapter are:
1. Contemporary conceptions of health and disease in man.
2. Determinants of psychological reaction to disease.
3. Modes of psychological response to physical disease, injury, and

disability.
4. Personal meanings of illness.
5. The stages of illness and related challenges.
6. Terminal illness and management of the dying patient.
The above schema is an attempt to organize a complex and fragmented
field for didactic purposes. It is a formidable task, but it is worth attempting
to bring together a body of observations, concepts, and hypotheses equally

relevant for the psychiatrist and other health professionals, as well as for
behavioral scientists concerned with matters of human health and disease.
Contemporary Conceptions of Health and Disease in Man
The concept of disease has undergone repeated changes throughout the

history of medicine. A unified concept of it has been gaining ground in the
1970s. It reflects the influence of psychosomatic and ecological thought, as
well as of social pressures for both personalized and universally available

medical and psychiatric care. Current emphasis on a comprehensive approach
to the prevention of disease and management of patients favors the holistic
and ecological approaches. Social trends and involvement of behavioral

scientists in medicine have combined to endorse psychosomatic thought
which enriched the medical model of man as a biological organism with a
psychosocial perspective of him as a person and a member of a given social
group with which he interacts. The definition of disease in a recent medical

dictionary reflects a contemporary concept of it. Disease is the “sum total of
the reactions, physical and mental, made by a person to a noxious agent
entering his body from without or arising within . . . , an injury, a congenital or
hereditary defect, a metabolic disorder, a food deficiency or a degenerative
process.”
The above definition conceives of disease as a state having no separate
existence apart from a patient, a person. This is still a controversial point.

Feinstein advocates a distinction between the meaning of the terms “disease”
and “illness,” respectively. The former refers to data described in impersonal
terms: anatomical, chemical, microbiological, physiological, etc.; the latter
designates clinical phenomena, such as the host’s subjective sensations (i.e.,

symptoms), and certain objective findings (i.e., signs).
In this writer’s opinion the dictionary definition of disease is preferable
to Feinstein’s. For one thing, his concept of disease leaves out many
psychiatric disorders which are not at this time describable in “impersonal”
terms and would thus constitute nondiseases. Feinstein’s distinction between
disease and illness has a limited application and does not do justice to the
contemporary trends to define disease, at least in part, by subjective and
social as well as biophysical criteria. To avoid semantic confusion we use the
terms “illness” and “disease” interchangeably.
The concept of disease is intimately related to prevailing views on
etiology and pathological mechanisms. We note that the dictionary definition
quoted above confines the range of causal factors to the biological, physical,
and chemical ones. This leaves out psychosocial factors as a class of potentially
noxious and pathogenic agents. Symbolic stimuli emanating from man’s
environment and impinging on him as information may be no less noxious

than the other etiological factors listed. Information evaluated by the
recipient in terms of personal threat, loss, failure, or punishment, or eliciting
conflicts and frustration with their concomitant affects, may result in

disturbed homeostasis and some degree of adaptive failure. The latter
involves biological, psychological, and social aspects. These facts reflect man’s
unique capacity to create symbols in thought and language, and respond to
them at all levels of his organization. This capacity is predicated on cerebral

activity which not only subserves mental activity but also mediates between
man’s environment and his internal milieu which it controls and on which it is
also dependent. We shall elaborate these concepts further while discussing

psychological stress. They are also mentioned in Chapter 2 (p. 97), in which
causes and psychological effects of cerebral damage and dysfunction will be
discussed.
A unified concept of disease, elaborated by Dubos, Engel, and Wolff,
takes full cognizance of man’s capacity for symbolic activity, which adds a
crucial dimension to his adaptation to the social and physical environments,
and to maintenance of health, as well as susceptibility to disease. As Wolff put
it: “It is unprofitable to establish a separate category of illness to be defined
psychosomatic or to separate sharply—as regards genesis—psychiatric,
medical, and surgical diseases.” This view has been influenced by the general
system theory and is rapidly replacing earlier, reductionist concepts of static,
single-factor, unilinear causal sequences, be they expressed as germ theory or
psychogenesis.
The characteristics of the unified approach to disease may be
formulated in the following postulates, equally applicable to somatic and

psychiatric disorders:
Relativity of the Concepts Health and Disease
There is no sharp boundary between health and disease, between

normality and abnormality. They are relative concepts defined by changing
statistical, subjective, and social criteria, as well as by abstract, utopian
notions of an ideal state and varying degrees of deviation from it. For Dubos
health implies “a modus vivendi enabling imperfect men to achieve a
rewarding and not too painful existence while they cope with an imperfect
world.” Disease connotes “failures or disturbances in the organism as a whole
or any of its systems.” Thus health and disease are viewed as states
constituting a continuum divided by an arbitrarily and conventionally defined
boundary.
Multifactorial Etiology
No disease is caused by a single factor, although one factor may

outweigh all the others in determining a given disease state. Etiologic factors
include enduring predispositions or vulnerabilities of genetic and acquired
origin, as well as current susceptibility, psychic and/or somatic, of the
individual to noxious agents ranging from physical, chemical, and biological to

symbolic, which exert a strain on his current adaptive capacities. These causal
factors vary in their respective relevance from case to case, and evaluation of
their relative contribution to a patient’s malfunction and discomfort
constitutes the process of comprehensive diagnosis.
Ecologic Viewpoint
The study of every disease must include the person, his body, and his
human and nonhuman environment as essential components of the total
system. This involves the employment of methodologies, explanatory

concepts, and terminologies derived from physical, biological, and behavioral
sciences. For reasons of research strategy these different components are
broken down and studied in isolation from those belonging to the other
levels. But the determinants of health and disease in an individual always
involve complex interactions between him and his total environment (See
references 38, 64, 74, 75, 122, 174, and 201).
Disease as Dynamic State
It is customary to distinguish etiological and reactive aspects of disease
as if they represented two different categories of phenomena. This is largely
an artifact, although it has some heuristic value. The whole constellation of
factors listed under Multifactorial Etiology above continues to influence the

course of any disease. There is dynamic interplay among these factors and
numerous feedback loops having a beneficial or deleterious effect on the
disease as a process and on its outcome. This is particularly true of the
currently prevalent chronic diseases, in many of which the point of onset
cannot be identified. In them it is quite arbitrary to distinguish between
causal and reactive factors.
Psychosocial Stress
When the meaning of any information input, internal or external, is

construed by the subject in terms of threat of, or actual loss or injury to his
psychic and/or physical integrity, we talk of psychological stress. This
theoretical construct has been plagued by ambiguity, despite numerous

attempts at its clear formulation. The most lucid and comprehensive
discussion of psychological stress has been given by Lazarus, that of social
stress, by Levine and Scotch. Semantic confusion, however, should not
obscure the mass of accumulated evidence, clinical and experimental, that
events and situations in an individual’s life affect his health. When such
events are interpreted by the subject in terms of meanings mentioned above
and result in disturbances of his psychological and/or somatic homeostasis
straining his current adaptive and coping capacities, we can apply the term
psychological stress. It is a general concept encompassing disturbing stimuli

(stressors), their cognitive assessment, and the resulting emotional,
physiological, and coping responses.
Psychological stress need not have pathological consequences unless it
is sustained, or of such a magnitude for a given person at a given time that it

results in a breakdown of adaptive mechanisms, somatic, psychological, or
both. Such a breakdown has been expressed in the concept of general
susceptibility to disease. Whether the latter occurs and what form it takes is
determined by a variety of factors, enduring and current, residing within the
individual (host) and in his social and physical environment. Recent

psychosomatic research has used a three-pronged approach to the
investigation of the chain of events leading from a social stimulus to disease.

The first approach emphasizes epidemiological methods, and focuses on
temporal relationships between specific life changes, or demanding life
situations, e.g. family or occupational, in groups of individuals and their
morbidity. The second approach takes as its starting point an individual’s
psychological state, the realm of thought and feeling, in response to life events
and situations which are disturbing to him. The third approach aims at
identifying physiological mechanisms and pathways mediating between
symbolic stimuli, a disturbed psychic state, and evidence of pathology and/or
dysfunction in a given organ or tissue.
Enge distinguishes three broad classes of psychologically stressful
events: loss or threat of loss of psychic objects, i.e. people, possessions, ideals,
etc., having ego-sustaining value for the person; actual or threatened injury to
the body; and frustration of drives. This list is not exhaustive. One could add to
it the disorienting rate of social change; value, choice, and decision conflicts;
wants, created by the existing economic system, coupled with aroused
expectations and inability to meet them; status inconsistency, and a host of
other social situations and events which cannot be reduced to Engel’s three
main categories. It must be emphasized, however, that despite observed
similarities of people’s responses to external events, the ultimately decisive
factor is the individual’s evaluation of his perceptions, and his personal
interpretation of them.
Bodily injury or illness, or threat of either, constitute one of the major

sources of psychological stress. This view links etiological factors with
reactive ones. Thus, psychosocial factors may not only contribute to disease
onset, but illness itself includes psychosocial responses which may increase
or reduce the initial psychological stress and thus influence the course and
outcome of the illness (See references 20, 36, 40, 64, 74, 75, 82, 92, 94, 111,
121, 126, 171, 204, 210, 211, 215, 216, 224, and 226).
Determinants of Psychological Reaction to Disease
The multiple determinants of every patient’s psychological reaction to
his physical illness, injury, defect, and/or disability may be assigned to the
following classes:
1. Intrapersonal factors, which include biological variables, such as

age, sex, and constitution; and psychological, i.e., personality
in all its aspects, past experience with illness in oneself and
others, etc. Both these classes of variables inherent in the
person include his enduring psychobiological
predispositions and states as well as those obtaining at the
onset of illness and throughout its duration.
2. Interpersonal factors, i.e., nature of patient’s relationships with

other people, especially family and health professionals, both
before and during his illness.
3. Pathology-related factors, i.e., spatio-temporal characteristics of

disease or injury and the subjective meaning they have for
the patient in relation to his past history, knowledge, values,
and current adaptive capacity.
4. Sociocultural and economic factors, i.e., values and attitudes toward

illness as such and specific diseases prevalent in the patient’s
social milieu; beliefs about medical care delivery and its
practitioners; economic consequences of illness for patient;
etc.
5. Nonhuman environmental factors, i.e., physical aspects of

environment in which patient lives during his illness.
The varying influence of the above factors determines the unique
quality of the experience and behavior of every patient in any given episode
of illness. No single set of generalizations can fully account for the individual
nuances of response to illness. Yet generalizations are practically useful to

allow grouping of patients showing common features and as a basis for the
clinical approach to every individual. Each of the five classes of determinants
must be taken into account for a comprehensive diagnosis and management.
Intrapersonal Factors
These are the psychobiological characteristics of the patient and his

premorbid life history as experienced by him. Those aspects of his past
experience are relevant which influence the meaning for him and his attitude
toward his particular illness or disability and its consequences.
The psychological impact of any illness differs depending on its timing
in a person’s life cycle. The experience of being sick and the psychological
resources to cope with disability are different in a child, adolescent, or an old
person. Thus age is an important variable.
Illness, disability, or injury in childhood (See references 32, 105, 109,

138, 169, and 208) deserve special attention. They may interfere with the
child’s maturation and optimal psychological development. The quality of the
illness experience, influenced by the behavior of the important adults toward
the sick child, may determine his reactions to illness in later life, such as
excessive fear of, sense of weakness and shame in relation to, or, on the
contrary, eager acceptance and even simulation of illness as a psychologically
rewarding state. A child has a limited repertoire of cognitive and other coping
strategies available to him, and his usual defense is regression. Yet, as
Langford points out, such regression is “strategic withdrawal for regrouping

of strengths” rather than a pathological development. Most children cope
with illness surprisingly well and may come out of it with increased maturity
and vigor. To achieve this favorable outcome, however, the child needs the
understanding and support of those taking care of him, particularly if the
illness is severe, prolonged, and requiring hospitalization.
Physical illness during adolescence imposes an additional stress at a

time when the tasks of gaining independence from the parents and
developing a stable body and self-image provide a formidable challenge. Some
adolescents tend to fear the passivity and dependence imposed by the illness
and may readily interpret it as a punishment for sexual and aggressive
feelings and activities. Others may welcome it. Physical illness during
adolescence is particularly likely to engender intense conflicts and anxiety.
They may be manifested directly or take the form of lack of cooperation with
health professionals, and denial of and attempted flight from illness.
Examples of this are provided by juvenile diabetics and adolescents suffering

from malignant neoplasms.
Illness, even relatively mild, in a middle-aged person who has enjoyed
good health, may trigger off thoughts of approaching old age, infirmity, and
death. Such associations may evoke an emotional response more intense than
the nature of the illness would warrant. This intensity may be further
enhanced if the illness occurs close to the age at which a parent or other
significant person died.
Old age frequently adds an important variable influencing the response
to illness: some degree of brain damage and consequent proneness to
cerebral decompensation. The latter often complicates physical illness and

hospitalization in persons over 65 years. Cognitive disorganization impairs
rational evaluation of the illness and environment, and adds a source of

psychological stress and disorganizing anxiety. There is also the grave hazard
of extension of the irreversible brain damage.
Thus, the psychological impact of illness or disability varies with the

developmental phases of the human life cycle. A congenital deformity or
functional handicap will help shape a person’s body image and influence the
direction of growth of his personality. Acquired at any stage from birth on an
injury or illness carries a potential for psychological growth as well as for

crippling maladjustment. Anything that disturbs functions of the body affects
the psyche and vice versa.
The patient’s sex influences reaction to diseases which impair bodily
attributes or functions valued for their enhancement of the sex role. Injury or
deformity which mars esthetic quality of the body is likely to have more
serious emotional significance for a woman than a man. He is more likely to
be affected by any chronic illness which enforces dependence on others and
interferes with capacity for work, a source of gratification in its own right. In
either sex, disease affecting sexual function or secondary sex characteristics

may undermine his or her sexual role and identity, and intensify related
unconscious conflicts. Unconscious symbolic meaning of the affected body
part may have a sexual connotation, and injury to it, the nose for example,
may be unconsciously interpreted as castration with consequent anxiety or
depression.
The patient’s personality style influences the meaning and experience of
illness, as many authors have emphasized. Myocardial infarction, for example,
evokes different responses in an obsessional, schizoid, paranoid, hysterical, or
impulsive personality type. Personality attributes comprise the individual’s
cognitive and perceptual style, such as field dependence or independence; his
unconscious conflicts, characteristic ego defenses, and coping styles with
psychological stress of any type; ego strength, intelligence, values, and

knowledge; body image and self-concept; and other relatively enduring
qualities which all play a major part in determining the total psychological
response to disease. These factors influence behavior to all facets and at all
stages of illness, and hence their assessment should be part of a

comprehensive diagnosis as a basis for an individually tailored management
plan for every patient. The clinical relevance of these variables will be
discussed in more concrete terms in the subsequent sections.
Apart from enduring personality characteristics, the patient’s
psychobiological state at the onset and during the course of his illness must
also be taken into account. His level of consciousness and his cognitive and
perceptual capacity, will influence his ability to appraise his illness, diagnostic
procedures, etc. His ability to cope with the illness also depends on his
current mood, state of unconscious and conscious conflicts, and stability of
life situation. It has been observed that the greater are the magnitude of life
change and the related conflicts, adaptive demands, and affective arousal, the
more likely is an illness to occur and be severe. This suggests that
psychosocial stress plays a dual part in that it both enhances susceptibility to
illness and impairs the host’s capacity to cope with it physiologically and
psychologically. Since illness itself changes the quality of subjective
experience, producing unpleasant mood and disturbing perceptions and
thoughts, a vicious circle results. Increasing psychophysiological arousal and

distress may readily ensue and add to the initial psychological stress (See
references 9, 42, 82, 83, 102, 143, and 193).
Interpersonal Factors
The quality of the individual’s interpersonal relationships before and
after the onset of his illness exerts a profound effect on his experience and
coping capacity. When illness comes on, as it often does, in a setting of
interpersonal, say marital, conflict, or of loss of a close person, or work-

related stress, its impact tends to be greater, its course more stormy and the
recovery protracted or absent. Findings of higher than average morbidity and
mortality rates among the recently bereaved, for example may reflect both
increased susceptibility to disease and reduced ability and/or willingness to

cope with it. Loss of an important relationship, whether actual, anticipated or
even imagined, is said to be a common trigger for the so-called giving up-given
up complex. That psychological state, consisting of negative appraisals of self
and environment, and concomitant affects of helplessness or hopelessness,
has been observed to be a common antecedent of many illnesses. It appears
that the more intense those affects are, the greater the tendency to give up the
struggle for survival, psychologically and biologically.
Increasing attention has been given lately to the crucial importance of
family relationships in influencing the course and outcome of illness. These
factors will be discussed in more detail later. It suffices to stress at this point
that viewing the patient apart from his social context results in an incomplete
picture of illness and its deficient management.
Relationships between the patient and the health professionals with

whom he comes into contact invariably influence, for better or worse, the
course and outcome of his illness. Other relevant relationships include those
with employers, friends, neighbors, etc., who constitute the patient’s social
milieu. All these factors will be considered in some detail in the later sections.
Pathology-Related Factors
The nature and characteristics of the pathological process or injury are

a class of biological variables pertaining to the integrity of the body and its
functions. These factors acquire psychological significance as they, and/or
their consequences, give rise to perceptions, thoughts, feelings,
communications, and actions. There is some indication that subliminal
interoceptive stimuli may influence conscious psychic processes and dream
contents and thus provide clues to a still covert pathological process. It would
be valuable for preventive medicine if such clues could be reliably identified,

but this is not yet feasible.
Variables, such as the site and extent of the lesion, rate of onset and
progression, the kind and degree of functional derangement, as well as
duration of the pathological process, all influence the patient’s emotional
response. Specific organs and physiological functions have different

psychological significance and symbolic value for each person, related to his
unique life experience, body image, and personality. These values may have
little relevance to the issue of survival. Injury to the face or an abdominal scar
may have greater subjective significance than impairment of organs essential
for survival. The particular experiential history of the patient, his conscious
and unconscious conflicts and beliefs, sociocultural influences, and other
factors, determine what significance and value he attaches to the given body
part or function. The extent to which the disease process changes one’s
somatic sensory input and body image also influences how one responds to
disease or injury. Last but not least, impairment of cerebral function by

disease, its nature, and the degree of its reversibility or compensability, is
important (See references 11, 23, 32, 52, 78, 124, 125, 129, 177, 183, 186,
194, 202, 210, 216, and 218).
An organ or biological function has especial subjective significance for a
person when it:
1. constitutes a source of pleasure, pride, self-esteem, and effective

coping with the environment;
2. helps maintain satisfying relationships with others;
3. helps alleviate intrapsychic conflicts and thus protects against

experience of painful affects;
4. enhances sense of personal identity, self-concept, and stability of

his body image;
5. helps maintain social roles and occupational capacity;
6. has unconscious symbolic meaning which imparts to it a vital value

in his psychic economy.
Any disease, injury, or disability which jeopardizes or destroys such

personal values has an intense subjective meaning for and emotional effects
on the patient.
Sociocultural and Economic Factors
This is the domain of values, beliefs, and attitudes related to matters of
health and disease. They are generally shared by members of a given social
group and class, and affect every patient’s emotional response to illness, as
well as his illness behavior. These factors have been studied extensively by
medical sociologists (See references 84, 98, 146, 147, 161, and 206).
Everyone holds views about the significance, etiology, likely effects, and
prognosis of the more prevalent diseases. Such beliefs influence the meaning
of his illness for the patient and what he does or fails to do about it. His
behavior also expresses his image of the health professionals and medical
institutions. If this image is largely unfavorable, the patient tends to avoid
seeking medical help and resorts to folk medicine and self-medication.
Members of the lower socioeconomic groups tend to be wary of doctors and
hospitals, less likely to evaluate symptoms as indicative of disease, and more
likely to trust their own understanding of health. Poor people from city slums
or rural areas have often different medical values and customs from those of
health professionals and other members of the higher socioeconomic groups.

These factors, combined with the cost of medical care, contribute to the
medically deprived position of the poor.
Attitudes in a patient’s social milieu toward being sick, as well as
derogatory and fearful views of certain diseases, influence his willingness to

accept the sick role, and reveal his symptoms to others. Some diseases carry a
stigma and to suffer from one of them may evoke shame, guilt, self-
devaluation, and social withdrawal. Such responses add to the other stresses
of illness, and promote attempts at its concealment. Venereal diseases,
epilepsy, leprosy, or tuberculosis are often stigmatized because of their

negative moral connotation, fears of contagiousness, and/or frightening
outward manifestations. Cancer is so dreaded at all levels of American society
that about 60 percent of adults queried in a large poll stated that they would
conceal it from others. Many people believe that cancer is contagious and fear
contracting it from or transferring it to members of their family. Such fears
are particularly strong in patients suffering from an illness believed to be
contagious who harbor conflicts over hostile impulses and feel guilty about
them. If such an illness intensifies the patient’s hostility, he may have
unconscious wishes to infect others and suffer intense guilt as a consequence.
Knowledge of scientific medicine varies with socioeconomic grouping
and is usually lowest in those with a low level of education and income. Yet
irrational beliefs about medical matters are not confined to any class. Nor
does possession of medical knowledge automatically ensure rational behavior

in illness, as any physician who has treated his colleagues can testify.
Nonhuman Environmental Factors
Psychological effects of the physical environment in which the sick
person lives, be it home or hospital, are an important, although neglected
subject. Various hospital environments affect the patients. Esthetic qualities
of the surroundings, quantity and quality of the sensory input, and
appearance of diagnostic and therapeutic implements may influence the

patient’s mood and at times arouse anxiety or facilitate cognitive
disorganization on account of their novelty, unfamiliarity, monotony, etc.
The above list of determinants of psychological reactions to disease is
not meant to be exhaustive. Their outline underscores the large number and
diversity of variables which influence the experience and behavior of the sick.
Modes of Psychological Response to Disease
We will describe patients’ responses to disease, in both their subjective
and observable aspects. Three such overlapping aspects will be distinguished:
1. The intrapsychic (experiential), which refers to what the patient

perceives, thinks, and feels, that is to perceptual, affective,
and cognitive components of his subjective response to his
illness;
2. The behavioral, that is, how the patient communicates with others
and acts in regard to his illness;
3. The social, which concerns his interactions with others, particularly

his family and the health professionals.
The Intrapsychic (Experiential) Aspect
Disease and the suffering it causes are universal components of the
human condition. Stripped of its abstract, scientific connotations, “disease”

and “illness” are labels for an essentially personal experience, one known only
through introspection. It may be communicated to others and has to be
received with empathy to result in meaningful information. Such procedure is

often dismissed as unscientific and the data as anecdotal. Yet this is not a
valid reason to leave out of account what matters the most to every patient, to
every one of us, personally. The subjective aspects of illness may be described
and studied in two distinct ways: as a total experience, by obtaining

introspective reports; and atomistically by applying scientific psychological
terminology and observation methods, and breaking down the patient’s
experience as an integrated whole into its perceptual, cognitive, and emotional
components. The former method will be briefly discussed first.
An illness colors to some extent the sick person’s experience of his body,
self, and environment, his values and goals. Novelists, like Proust or Chechov,
writers of diaries, and some existentialists, have written sensitive accounts of

how the sick feel. Of particular interest are autobiographical descriptions of
specific illness experiences written by physicians. While every episode of

illness is a unique experience, certain common trends may be discerned.
Narrowing of interests, ego-centricity, increased attention and
responsiveness to bodily perceptions and functions, irritability, increased
sense of insecurity and longing for human support and closeness, are
commonly reported inner changes. There is often an unpleasant change in the
general body feeling, or coenesthesis, experienced as malaise or the feeling of

sickness, usually associated with an active pathology. Negative emotional
experiences are not invariably reported, however. Some sufferers from
chronic illness or disability experience an increased awareness of esthetic

and intellectual values and enhanced intensity of spiritual life in general.
Perceptual, Cognitive, and Affective Components of Response
Perception of all the sensory input relevant to one’s illness depends on
the attributes of the perceiving individual, the characteristics of perception

itself, and the situation in which the patient finds himself. The quality,
intensity, and spatiotemporal features of the perception are important. A
sudden attack of vertigo, bleeding, severe pain, or marked shortness of breath
are more likely to force an appraisal of what is happening with greater

urgency than a painless lump or transient bowel dysfunction. Yet already at
this stage the characteristics of the perceiving individual come into play.
One such characteristic is the perceptual style, whether conceptualized
as perceptual reactance, that is, augmentation or reduction of what is being
perceived; as repression-sensitization; or some other hypothesized continuum
of perceptual reactivity. Habitual augmenters tend to perceive somatic
sensations, such as pain, more keenly and appraise them more readily in
terms of threat or harm than the reducers. The latter find it easier to ignore
and deny the significance of their symptoms. Sensitizers are liable to report
greater frequency and/or severity of symptoms, and higher total numbers of

complaints and visits to physicians, than repressors. These observations seem
to represent differences in perception concerning illness and corresponding
responses to it.
Individuals differ with regard to their responsiveness to somesthetic
stimuli. Some may mislabel their interoceptive cues. These individual

differences reflect early learning of both somatic responses and their
symbolic, linguistic equivalents. The latter are influenced by sociocultural and
ethnic factors.
Cognition refers to thinking, concept formation, and problem-solving.
Cognitive aspects of the psychological response reflect an individual’s
cognitive style. Two such styles pertain to illness experience: vigilant focusing
on and need to explain illness-related perceptions and events; and
minimization, that is, a habitual tendency to play down the significance of any
perceived bodily changes, etc.
Cognitive evaluation of illness is partly conscious and partly
unconscious. Unconscious cognition involves primary process thinking, that is
one characterized by distortions of facts according to the person’s wishes,
conflicts, fears, repressed memories and fantasies, etc.
Different organs and bodily functions have unconscious symbolic
meanings derived from early childhood experiences and never influenced by
factual knowledge. Thus, perception of abdominal distension due to a

malignancy may arouse unconscious fantasies of pregnancy, for example.
Much has been written about unconscious sexual symbols of the nose, neck,
eyes, or teeth. Any body orifice may symbolically represent a female genital.
Illness may be interpreted, consciously or not, as just or unjust punishment

for repudiated wishes or actions which had aroused feelings of guilt; as
enemy; challenge; weakness; irreparable damage; or as value. Such subjective
views of illness or injury influence the patient’s conscious attitude, feelings,

and overt behavior.
An almost universal cognitive response to illness is an attempt to
explain its origin. Two most common modes of explanation are to blame
oneself or another person or nonhuman agent for having caused the disease.
Such beliefs about etiology may vary from rational and scientifically sound
ones to irrational and delusional. In any case, to “explain” the origins and
mechanisms of the illness may offer a comforting illusion of mastery over it
and help reduce ambiguity, uncertainty and anxiety. Yet this is not always so.
Sometimes the evolved explanation may result in a sense of guilt, grievance,
and anguish.
The emotional responses to illness vary in quality, intensity, and
duration. They both reflect and influence the personal meaning of illness, the
nature and degree of symptoms and disability, and the degree of support the
patient gets from his environment. Anxiety, grief, depression, shame, guilt,
anger—these are the affects most often elicited. Less common are apathy,
indifference, elation, or euphoria. Whether one judges a patient’s affective
response as normal or not depends on its appropriateness, that is, degree of
correspondence to the severity of the pain, losses, and suffering. Such
judgment is obviously value-laden and the borderline between normal and
abnormal responses is an arbitrary one. Practically more important is the

degree to which the affective response impairs a patient’s capacity for
recovery and/or adjustment. Pathological emotional responses which are
components of identifiable psychiatric syndromes, neurotic or psychotic, are

discussed in detail in a paper devoted to the psychopathology related to
physical illness.
The Behavioral Aspect
The communications and actions of the patient in relation to his illness

comprise the behavioral aspect of his total psychological response. Mechanic
introduced the concept “illness behavior” to designate “the ways in which
given symptoms may be differentially perceived, evaluated, and acted (or not
acted) upon by different kinds of persons.” Yet perception and evaluation of
symptoms do not logically belong to behavior as usually defined in

psychology, but communications and actions do. Illness behavior should be
confined to the latter.
Communicative Behavior
What the patient communicates regarding his symptoms or distress,

when he does it, to whom and how, is important for delivery of medical care
and a satisfactory doctor-patient relationship. Communication is a two-way
process, modified by the manner in which messages are responded to by the
recipients. In the case of illness, the patient’s communications influence and
are influenced by the responses of his doctors, family members, or other
concerned persons. This aspect of illness behavior has attracted considerable
attention in the 1970s because of its relevance to the diagnostic decision and
the patient’s compliance with medical recommendations (See references 1,
39, 149, 196, 213, 228, 230, and 231).
Only selected examples of studies in this area are mentioned here. Zola
emphasizes the influence of sociocultural factors on the manner in which
patients communicate their symptoms to the doctor. He found that Irish and
Italian patients attending outpatient clinics of a general hospital presented
their complaints differently. The Irish tended to understate their difficulties,
to refer their complaints mostly to the eyes, ears, nose, and throat, and to
deny that they felt pain. Italians, on the contrary, dramatized their complaints,
referred symptoms to many parts of the body, and claimed that their distress
interfered with their social relationships. More Italians were labelled as
“psychiatric problems” by the doctors, suggesting that the way in which
symptoms are communicated tends to influence diagnostic reasoning. Zola

observes that the doctor “can block or reject the patient’s communication by
his very reaction, or lack of reaction, to the patient’s concerns” and thus
obtain inaccurate and misleading information. Similar conclusion was
reached by Duff and Hollingshead from their study of medical inpatients.
Zborowski studied responses to pain manifested verbally and

nonverbally by patients of Old American, Jewish, Irish, and Italian origin.
Patients of Jewish and Italian origin tended to be more emotional while
experiencing and communicating pain than the Anglo-Saxons (Old
Americans). They also tended to emphasize their perception of pain and its
severity. The Old Americans and Irish tended to play down pain, report it
unemotionally, and describe it typically as stabbing and sharp. The Irish were
vague and confused in their description of perceptions and feelings about

pain. Italians related more often than others that their pain was constant
rather than intermittent. They and the Jewish patients made no effort to
conceal their pain, and manifested it by crying, moaning, etc., suggesting their
desire to communicate their suffering both verbally and nonverbally.
Patients often communicate selectively what they believe the doctors
are interested in, namely somatic complaints. This expectation may make the
patient express his psychological distress in terms of somatic complaints and
metaphors. Such skewed communication readily leads to diagnostic errors,
and unnecessary and costly investigations of nonexistent organic disease.
Another source of diagnostic error is provided by patients who complain in

terms of psychological distress and withhold information about their somatic
symptoms. Others habitually express their disturbed feelings in somatic
terms. Such somatizing patients predominate in the lower economic classes

and the rural areas.
Special problems are presented by patients suffering from disorders of
communication, for example aphasia, or those who communicate in an

idiosyncratic idiom, as many schizophrenics do, or overdramatize their
symptoms as an expression of hysterical personality. Such patients may fail to
make themselves understood or believed with possible errors in diagnosis.
COPING BEHAVIOR
The actions taken by the patient in relation to his illness are an aspect of
his overall coping behavior. The concept of coping designates “instrumental
behavior and problem-solving capacities of persons in meeting life demands
and goals.” A narrower definition confines it specifically to strategies of
dealing with psychological stress. Physical illness and disability are a category
of psychological stress with one crucial characteristic: the primary source of
stressors lies within the person’s body boundaries. Coping in this context may
be defined as cognitive and psychomotor activities which a sick person
employs to preserve his bodily and psychic integrity, to recover reversibly
impaired function, and compensate to the attainable limit for residual
irreversible impairment. One may distinguish behavioral coping styles and

strategies. The former refer to enduring dispositions to act in a certain manner
in response to threat or loss involving one’s body. Strategies refer to the
actual techniques which the patient employs in dealing with a particular

illness or disability. They are a resultant of both his coping style and current
situational constraints. The latter include the particular form of disability
suffered from, say paraplegia or aphasia, as well as the whole constellation of

intrapersonal and environmental factors accompanying a given illness
episode. Behavioral coping styles may be classified as tackling, capitulating,
and avoiding.
Tackling means a tendency to adopt an active attitude toward
challenges and tasks imposed by illness or disability. In its extreme form, it is
manifested by a tendency to “fight” illness at any cost. The patient acts as if
the disease was an enemy to be combated and may engage in behavior
inimical to his health, for example by continuing strenuous physical activity in

the presence of coronary artery disease or rheumatoid arthritis. Adaptive
manifestations of this style include rationally modulated activities aimed at
early recovery, or compensation for residual disability. Timely seeking of

medical advice, compliance with therapeutic regimens, active information-
seeking, searching for substitute skills and gratifications to replace the lost
ones—these are desirable coping strategies reflecting the tackling style.
Capitulating refers to one’s habitual way of dealing with threats and
losses by adopting a passive stance and either withdrawal from or dependent

clinging to others. Patients displaying this style create problems for
physicians because of their inadequate cooperation, or excessive demands for
support, reassurance and care-taking, respectively. This way of coping should

not be confused with adaptive passivity during the acute stage of any serious
illness.
Avoiding pertains to active attempts to get away from the exigencies

and challenges of the illness. It is characteristically displayed by individuals
for whom acceptance of illness, hospitalization, treatment, etc., signifies a

severe threat to their self-concept as independent or invulnerable, or, on the
contrary, excessively vulnerable. Its intrapsychic concomitant is usually
either a marked degree of denial of illness or of manifest anxiety.
Coping behavior in patients has been studied in particular detail in
relation to such conditions as chronic illness and disability, severe burns,
acute poliomyelitis, diabetes, and other illnesses. It is a clinically useful
universal concept as it allows the physician to identify a given patient’s

dispositions and actual techniques for dealing with his illness, and intervene
to encourage adaptive ones. Excellent examples of such intervention are given
by Hackett and Weisman who describe psychiatric techniques of managing
psychological disturbances related to surgery.
The Social Aspect
The social aspect of the patient’s response to illness refers to his

interactions with concerned others, especially his family and health
professionals. This aspect has been studied extensively by sociologists, who

have proposed relevant explanatory hypotheses and introduced organizing
theoretical constructs. The most influential of the latter has been that of the
sick role, developed by Parsons. As Kasl and Cobb put it, “Parsons observed
with great insight that when one becomes ill, one does not simply drop one’s
customary roles—the role of parent, spouse, or provider; one actually adopts

a new role which supersedes the others.” Parsons called this the sick role. This
concept is reviewed here as it is pertinent to the patient’s interactions with
his social environment.
The concept of any role involves two kinds of expectations: That the
individual will adopt certain attitudes and follow certain actions; and that
others should behave toward him according to explicit and implicit rules. The
sick role implies the following expectations: 1. Exemption from the

responsibilities and obligations of the premorbid social roles (for example, as
wage earner) in relation to the nature and severity of illness; 2. Obligation to
seek the health and comply with advice of competent persons; and 3.
Surrender of the sick role as soon as possible. It is thus expected that playing
the sick role has a time limit and the patient should do his best to achieve
functional recovery. This is in accordance with the prevailing values and

norms of the American society, which extol self-reliance, individual initiative,
efficiency, and achievement. The sick role is a deviant one, but distinguished
from other deviant roles by the fact that the sick person is not held
responsible for his condition.
The sick role is a heuristically fertile concept, which provides a
sociological framework for the study of illness as an indispensable

complement to the biological and psychological approaches. The concept has
been criticized on theoretical and practical grounds. The main criticisms are
that it is inadequate for the study of minor as well as of incurable and
stigmatized diseases; and that it is not applicable to illness behavior not
involving contact with physicians. It is also not applicable to the
characteristics of other cultures. These criticisms do not detract from the
originality and methodological value of Parsons’ contribution.
The patient may take one of several courses of action with regard to
acceptance of the sick role: (1) He may accept it realistically, as society

expects him to do, and surrender it upon recovery; (2) He may attempt to
reject or avoid it, even if this is harmful to him; (3) He may adopt it readily
and refuse to give it up despite the doctor’s opinion that he is fit to do so; and
(4) He may strive to avoid it, then give in to and cling to it. All these patterns
of sick role behavior are encountered in clinical practice and influence the
course, duration, and outcome of any illness or injury. They are determined
by the interplay between the patient, his illness, and his social environment. A
person who views dependence, helplessness, and physical incapacity as
threatening or degrading has difficulty in accepting the sick role and engaging
in rational illness behavior. Interaction between the patient and members of
his family on the one hand, and the health professionals on the other,
influences his sick role behavior and will now be discussed.
The Patient and His Family
The relationship between illness and family dynamics may be
approached from several overlapping points of view: (1) The influence of
family interaction, say marital conflict, on the development of illness or
injury;
The role of the family in the learning of particular modes of illness
behavior. For example, children may adopt through identification and
imitation specific attitudes toward the sick role as well as predisposition to

evaluate given symptoms or types of disability as threatening, shameful, etc.
Children rewarded for being ill may acquire a tendency to view illness as a
potential source of gratification;
The impact of illness in a given family member on the stability of the
family as a whole; (4) The interactions between the sick member and other
members of the family as they affect the patient and his spouse, children,
parents or siblings; and (5) The influence of the family dynamics on the
timing of seeking medical consultation and hospitalization.
All these aspects of the relationship between illness and family
interactions have been studied and there is growing appreciation of their

importance for medicine. Only selected observations and theoretical
formulations may be touched upon here.
An influential set of theoretical formulations in this area has been
contributed by Parsons and Fox. They pointed out that the modern American
family by virtue of its small size and relative isolation is exceptionally

vulnerable to the impact of illness of one of its members. The illness in the
mother is disturbing because of her unifying and emotionally supporting role
within the family. Her illness may deprive husband and children of her
customary support, while imposing additional stresses and demands on her.
Illness of the father, as the main provider and status-bearer, undermines the
social and economic position of the family as a whole, and by attracting
mother’s concerns deprives the children of her support. Illness of a child

could increase marital strain and enhance sibling rivalry, for example. The
intrafamily dynamics could be further disturbed if the sick member used his
illness as a strategy aimed at escape and relief from obligations and demands
within and outside the family. The adjustment to illness and disability
involves learning by the patient how to be sick and by the family how to
respond to his sickness. Both these tasks are demanding and may evoke
disruptive emotional responses.
Many studies have focused on the impact of severe illness in a child on

family dynamics. Friedman et al. (See references 30, 57, 138, 169, and 208)
made a detailed analysis of parents’ reactions and coping strategies in
response to neoplastic disease, mostly leukemia, in a child. The common

sequence of parental reactions began with a feeling of shock when diagnosis
was disclosed, followed by a tendency to self-blame and guilt for imaginary
errors of omission and neglect with regard to early manifestations of disease.
Such guilt feelings tended to be transient and gave way to seeking of
information about the illness and its etiology as an attempt at mastery of an

uncontrollable situation. The coping behavior of the parents included defense
mechanisms of isolation of affect, intellectualization, and, less often, denial.
Poor operation of such defenses was associated with manifest anxiety and
depression which hampered a parent’s ability to care for the sick child. Hope
in the parents was common and gradually gave way to anticipatory grief,
manifested by somatic symptoms, apathy, and preoccupation with thoughts
about the ill child.
As part of this study an attempt was made to assess the degree of

psychological stress in the parents by determining urinary 17-
hydroxycorticosteroid levels and relate them to the observed coping behavior
and affects. It was found that the excretion rates were relatively stable and
the investigators concluded that the more any defense mechanism protected
the individual from the impact of the chronic stress of a child’s illness, the
lower and less fluctuating would be the associated 17-OHCS levels. Such
levels were among the lowest in parents who displayed marked denial
mechanisms.
This study stands out as one of the most thorough of its kind and is
using a psychophysiological approach. It shows that a person’s coping
strategies have both psychological and physiological aspects and
consequences for him.
The impact of specific diseases and disabilities in adults on the family
interaction has been less extensively studied. A few representative examples
will be cited to emphasize the diversity of the related problems which await
further research.
Disability in husbands and fathers has been studied from the point of
view of the patients. The latter reported the main changes in their family
relationships in the following order: (1) greater responsibilities for the wives
in the management of the home; (2) reduction of social and recreational
activities; (3) more duties for the children around the house; (4) incurred
debts; (5) changed plans for a larger family; (6) necessity of wife’s
employment; (7) increased marital discord; (8) changed plans for children’s
education; and (9) changed living accommodation. The disabled head of the
family perceived significant shifts in the respective roles of the family
members, with his own role being undermined in the process. There was also
evidence of marital friction and decline in social and economic status of the
family. Shifts of roles within the family may create conflicts when the husband
eventually recovers and claims his previous dominant role and its
prerogatives. This writer has observed psychological decompensation in
several wives as a result of such repeated role reversal.
The impact of chronic illness upon the spouse was studied in a sample of
men and women belonging mostly to the lower class. The healthy spouses
reported new or increased symptoms, such as nervousness or fatigue. There
were indications of increased interpersonal conflict (role tension) expressed
by irritability and readiness to feel depressed in both partners. Greater

symptomatic distress of the patient caused more emotional tension in the
spouse, and vice versa.
An interesting relationship has been observed among physical
disability, and need and marriage satisfaction in couples in which the wife
was severely disabled. “Severe disability” was defined as a physical
impairment interfering with homemaking activities. Some of the women were
bedridden and unable to move. The physical condition of the disabled woman
was not a reliable predictor of need or marriage satisfaction in either partner.
Greater mobility of the wife did not invariably result in greater need or
marriage satisfaction. There was no simple relationship between the wife’s
level of functional mobility and the husband’s need satisfaction. Severe
disability provided the patient with a less ambiguous role and thus less
conflict and demand for efforts to improve her ability to meet obligations. The
disabled woman’s sexual satisfaction was positively correlated with her

marriage satisfaction. Physical condition of disabled persons had little effect
on marital sexual activity. Similar observations have been made in
paraplegics and quadriplegics.
In general, the following conclusions may be drawn from the available
studies: (1) Evaluation of any patient is incomplete without a detailed inquiry
into his family interactions and the ways and degree in which they are
affected by the patient’s illness and, in turn, affect him; (2) The quality of
communications between the patient and his family members should be
assessed in a marital couple or family interview. There is often skewed
communication, and in cases of fatal illness a conspiracy of silence, which
imposes a strain on all concerned; (3) In the case of a married patient it is
essential to inquire into the effect of the disabling illness on the respective
roles of the couple, their sexual adjustment, and the related marital tensions.
The sense of sexual identity of either partner may be undermined as a result
of illness and reactivate related intrapsychic conflicts. This may occur if the
wife is forced to play a more active role both as breadwinner and sexual
partner (for example, husband’s paraplegia or painful back may preclude his
taking an active role during sexual intercourse). The reverse situation and
role shift may occur if the husband of a disabled woman has to assume
housekeeping and other functions conflicting with his self-concept as a male;

(4) The response of a “healthy” family member may aid and abet the
maintenance of the sick role. Or, on the contrary, a hostile response toward the
ill member may prompt him to attempt to give up the sick role prematurely.
When the former interaction is at play, the healthy member, be it parent or
spouse, may derive gratification from playing a supporting and nurturing
role. He or she may then interfere with treatment of the patient, foster his
dependence, and decompensate psychologically if the patient recovers; (5)
Chronic or fatal illness and disability often tend to accentuate ambivalence in
the relationship between the sick member and the one most concerned with
his care. Negative aspects of the ambivalence are then a source of guilt and
provoke renewed attempts at compensation with resulting increased
resentment leading to more guilt, etc. Such a vicious circle is commonly
observed, increases psychological stress for both partners, and predisposes to
pathological forms of grief when the sick member dies; (6) Illness does not
always disorganize a family, but at times helps it to rally together and

consolidate itself.
The Patient and Health Professionals:

The Doctor-Patient Relationship
The importance of the doctor-patient relationship for the course and
outcome of the illness has long been recognized and there is extensive
literature on the subject. Only some salient theoretical models and studies are
mentioned here.
Henderson proposed an early model of doctor-patient interaction. He
defined it concisely: “A physician and a patient taken together make up a
social system. They do so because they are two and because they have
relations of mutual dependence.” Parsons has carried a sociological analysis
of the doctor-patient system further. He points out that the role of the
physician “centers on his responsibility for the welfare of the patient in the
sense of facilitating his recovery from illness to the best of the physician’s
ability.” A doctor’s judgment confers on a sick person the status of a “patient.”
This is a prerogative of the physician’s social role.
The social role of the physician is only one aspect of the doctor-patient
relationship. The analysis of the latter should include three basic elements:
(1) The individual predispositions of the physician, including his unconscious
motivations and responses; (2) His internalized standards of professional
behavior; and (3) The specific stimulus complex provided by the patient.
Szasz and Hollender describe three types of doctor-patient relationship:
activity-passivity, in which the patient is helpless and passive and the
physician treats him in a manner similar to that of the parent of a helpless

infant; guidance-cooperation, implying that the patient is capable of following
directions and exercising judgment. He is, however, expected to comply with
the physician as a competent guide. This model has its prototype in the
relationship of the parent and his child (or adolescent); mutual participation,
a model most appropriate for the management of chronic illness in which the
patient is largely responsible for his care and consults the doctor only
occasionally. The physician helps the patient to help himself. This is a
relationship between two adults.
While each of the above models is appropriate for certain types or
stages of illness as well as in relation to the patient’s age, intelligence and

cognitive clarity, the actual relationship may be inappropriate for the given
patient and situation. Thus a comprehending adult may be treated as if he
were a child. Such a relationship may be initiated by either doctor or patient,
but willing cooperation of both is needed for the inappropriate relationship to
become established and flourish. How can this happen? The answer lies in the
fact that neither doctors nor patients are just rational adults and that both are
influenced by unconscious motives related to dependent, sexual and/or
power needs. The degree to which such elements enter into the doctor-
patient relationship influences its quality and therapeutic efficacy. We speak

of transference and countertransference in this relationship to mean distortion
of the mutual perceptions of the doctor and patient, respectively, and

consequently of their relationship, by the significant past relationships of
each of them. Such influence is usually unconscious and may result in intense
feelings of attraction, suspicion, hostility, competition, regressive
dependence, etc., which tend to impair the professional relationship.
Transference and countertransference do not mean conscious feelings of
liking, trust, sympathy, or antipathy which are universal aspects of human
relationships. They refer only to distortion of present relationships in terms of
the past, usually childhood ones.
A common aspect of the doctor-patient relationship is ambivalence,

which may be mutual. The doctor lends himself to contradictory feelings by
virtue of his role itself. He is in some respects an authority, a judge and bearer
of good or bad news related to the patient’s future, to matters of suffering and
death. The doctor may feel attracted to a patient, or repulsed and exploited by
his demands, lack of progress, irrational behavior, or ingratitude. A
physician’s knowledge and therapeutic efficacy are limited, giving rise to
doubts, sense of failure and other self-devaluating feelings which for some are
hard to bear. The hallmarks of the patient’s situation are uncertainty and, if
treatment is undertaken, dependence on the doctor’s judgment, competence,
and information he chooses to transmit. This unique type of social

relationship may arouse mutual mixed feelings in both partners. Whether
such feelings remain within manageable bounds, or acquire disturbing
intensity, depends both on the personality of the patient and the doctor’s
maturity, attitude, and conduct. A measure of self-awareness can certainly

help the physician to avoid countertransference reactions burdensome for
him and antitherapeutic for the patient.
One of the crucial aspects of the doctor-patient relationship is the
quality of their mutual communications, verbal and nonverbal. This subject
was discussed in an earlier section dealing with the patients’ communicative
behavior (see p. 20). The other side of the dialogue is what the doctor
communicates to the patient, how he does it, where and when. Studies
relevant to this topic lead to the following conclusions: Information given by
physician to patient affects the quality and course of treatment. The patient’s
compliance with medical advice is closely related to the degree of his
satisfaction with having his need for information met. Insufficient,
contradictory, or confusing information results in the patient’s dissatisfaction
and noncompliance. The patient’s postoperative course is improved by

providing information before surgery. The degree of the information about
illness transmitted by the physician to the patient depends on characteristics
(personality, ethnic, cultural ) of the physician and patient, and on the

situation in which the information is communicated. If the doctor succeeds in
giving accurate information in a manner understandable and emotionally
acceptable to the patient and his family, he has a better chance of obtaining a
meaningful history and cooperation.
The quality of the doctor-patient relationship influences—for better or

worse—the patient’s response to his illness and its course and outcome. To
some extent the same holds true for other health professionals, especially
nurses involved in his care during hospitalization.
Personal Meanings of Illness
The central unifying concept in a discussion of psychological response
to disease, injury, or disability is that of the personal meaning which illness in

all its aspects has for the patient. It refers to the subjective significance of all
the information input, internal and external, which the patient receives and
appraises in the light of his values, beliefs, memories, conflicts, etc. The
meaning is a product of the interplay between the patient, his illness and
environment. It links conceptually the determinants and modes of the
psychological response to disease. Symptoms, diagnostic label, lesion,
functional impairment, doctors’ statements, and other facets of the total

illness experience are appraised by the patient, consciously and
unconsciously. This process of evaluation, resulting in meaning, continues
unabated throughout the course of every illness. It is a dynamic process
reflecting continuity of the information inputs. One could talk of many
changing meanings, but it is helpful to identify a dominant personal meaning
of the illness or disability as a whole.
What his illness means to a patient is influence by the determinants
listed earlier (see p. 7), as well as by the quality of the emotional response
elicited in and results of actions taken by him. The evolved meaning modifies
and is in turn modified by the patient’s emotions and perceptions. The
dynamic interplay among these factors and the related feedback effects
contribute to the complexity of this subject and the difficulty in explaining it
clearly. Some clinical examples may illustrate it.
To understand why a patient feels and acts in a particular manner it is
necessary to gain insight into what his particular illness or disability means to
him. For example, people who value their physical appearance highly are
prone to psychological breakdown as a result of mutilation or disfigurement.
Impairment of intellectual or perceptual functions by disease of the brain, or
sensory organs or pathways, will disrupt the main adaptive coping
mechanisms and source of pride and security in any individual for whom
intellectual achievement or perceptual clarity are indispensable conditions

for self-esteem, pleasure, a sense of competence, and economic security. A
man whose major source of gratification is sexual prowess and ability to
procreate is likely to be disturbed by impotence due to spinal injury, diabetes,

or prostatectomy, for example. Mastectomy, hysterectomy, or masculinization
induced by hormones in a woman may have similar emotional effects, as well

as revive latent intrapsychic conflicts over her sexual identity and role.
Persons who attach particular importance to personal cleanliness as part of an

obsessional personality style are liable to feel dirty and devalued after
construction of a colostomy. Urinary or fecal incontinence may have similar
effects. Some paraplegic patients seen by the writer were more disturbed by
loss of sphincter control than by paralysis.
Such examples may be multiplied. In each of them the specific personal
meaning of the disease, dysfunction, etc., for the particular individual is a
crucial factor in determining his emotional and behavioral responses. The

latter are also influenced by the attitudes of the patient’s environment to both
his illness and behavior. In general, there is no organ or physiological function
whose disturbance, damage, or loss could not disturb a given individual’s
sense of security and personal worth because of its personal value-laden

meaning for him. The psychological impact of illness or disability depends in
part on the individual’s vulnerability related to his personality and past
experience.
Categories of Meaning
It is helpful for clinical assessment of patients to distinguish four broad
categories of subjective meaning of illness, injury, disability, and its

consequences for the patient:
1. threat 2. loss 3. gain or relief 4. insignificance.
Threat implies anticipation of harm to one’s physical and/or psychic
integrity whose occurrence would cause suffering. Such anticipation may
follow perception of any bodily change if this is interpreted by the person as

signifying danger to him. At times, no threat is perceived until the patient is
told by a doctor that an illness is present. Tendency to interpret somatic
perceptions as threatening varies widely and appears to be an enduring
personality trait acquired through earlier learning. Some people respond with
alarm to any novel somatic perception or even one, say palpitations, which
they may have been told repeatedly to disregard as harmless. Others equally
consistently minimize and ignore even obvious and painful bodily changes.
Anticipation of danger, whether realistic or not, characteristically

evokes anxiety or fear. To avoid semantic confusion, the term anxiety is used
exclusively in this discussion. This affect is accompanied by individually
varied patterns of physiological arousal which may give rise to somatic

perceptions, such as palpitations, sweating, shortness of breath, etc. These
may, in turn, be interpreted as danger signals and result in augmentation of
anxiety—an example of a positive feedback. Anxiety tends to increase
vigilance to threat and to set off cognitive and behavioral activities aimed at
avoidance, tackling, or minimization of the anticipated danger, and thus
reduction of the unpleasant experience of the anxiety state itself. The coping
strategies employed by people to reduce or eliminate anxiety include the

unconsciously operating ego mechanisms of defense as well as deliberate
actions, such as intake of drugs or alcohol, compulsive overwork or sexual
activity. Thus threat and anxiety have both physiological and behavioral
consequences which may be adaptive or harmful. Excessive physiological
arousal may complicate and exacerbate an existent pathological process, and

precipitate cardiac decompensation or fatal arrhythmia in a patient with
heart disease, for example. Coping with anxiety may harm the individual, if he
engages in actions inimical to his health. Excessive intensity of the aroused

anxiety may lead to delay or, on the contrary, undue haste in seeking medical
help. A moderate degree of anxiety results in optimal adjustment to illness
and its consequences.
Loss in this context means not only actual damage to the person’s bodily
integrity, that is loss of body parts and functions, but also symbolic losses
resulting from disease or disability. Such losses refer to deprivation of
personally significant needs and values. The latter are related chiefly to self-
esteem, security, and gratification of needs. Any illness or disability may result
in partial or total loss of gratification derived from eating; from physical,
sexual, or intellectual activities; esthetic qualities of physical appearance, and
so forth. These various activities and attributes lost evoke an emotional
response in proportion to their subjective value and importance to the

individual.
The common emotional response to real or anticipated loss, whether
concrete or symbolic, takes the form of grief. This may merge imperceptibly
into a depressive syndrome. Less often, reaction to loss may take the form of
any psychiatric disorder, neurotic or psychotic, or antisocial behavior, or
somatic illness. Grief is a normal affective reaction to any type of loss,

including that of a bodily part or function. Its intensity and duration are
roughly proportional to the subjective importance of the loss. Grief is
considered by many authors as a necessary step in the work of mourning
which results in eventual acceptance and adjustment to what is irreparably

lost. The desirability of grieving is often taken for granted in the literature,
especially that inspired by psychoanalytic theory. Lack of grief in the face of
loss is usually assigned to the working of the mechanism of denial, which is

also invoked when a person shows no anxiety in response to threat. Yet
absence of anxiety may be a sign of good adjustment and is not always
presumptive evidence of the operation of denial. Lack of grief may mean that
the given event was not perceived by the patient as a loss. More systematic
research is needed in this area to validate the prevailing hypotheses and
caution is indicated in accepting them as universally valid facts.
Gain or relief refer to a personal significance of illness, conscious or
unconscious, as a source of psychological, social and/or economic advantage

for the patient. From the psychological viewpoint, any illness or disability
may facilitate resolution, gratification, or avoidance of intrapsychic conflicts
over disavowed impulses: aggressive, sexual, dependent or power-seeking.
Illness may provide a legitimate reason for avoidance of conflictual situations
and actions. An epileptic, for example, may avoid contacts with the opposite
sex on the grounds that he might develop a seizure in the presence of his
partner, or that he is unfit to be married, have children, etc. Another patient
may justify outbursts of anger or avoidance of competitive situations by
invoking his particular illness or disability. Open expression of dependent

needs and demands for their gratification may be legitimized in the patient’s
view by the special status conferred on him by his disease or disability. Thus
illness may provide rationalization for either avoidance of or indulgence in
behavior which the patient could not otherwise face or engage in without
conflict. In other cases, a painful or otherwise disabling illness may satisfy a
psychological, usually unconscious, need for suffering as atonement for

unacceptable impulses or fantasies. When such psychic factors are present,
the patient may have a vested interest in maintaining his illness and react
adversely to its improvement. The patient’s manifest attitude to his illness
may be entirely at variance with his unconscious view of it and its

psychological advantages. He may deplore in good faith that he is ill and
clamor for relief and cure, while his nonverbal behavior may express the
opposite attitude of which he is unaware and which he may explicitly deny.
From the social viewpoint, illness may provide a patient with a strategy
used to avoid social demands and responsibilities, and secure attention,
support, and compliance of others, especially his family members. Some
patients derive a sense of identity, pride, and satisfaction from being ill,
particularly if the illness is unusual and attracts attention and curiosity of

others, including doctors. A patient with a rare disease may attract much
medical attention, be repeatedly displayed and discussed by physicians, and
puzzle them. He may learn to enjoy the exhibitionistic aspects of such interest
and the perplexity of the doctors. For some individuals this may be the only
claim to distinction. They are not likely to give up these advantages readily.
One may propose this generalization: A patient’s overall response to
illness and disability, and his motivation to get well, are related to the
subjectively experienced losses and/or gains derived from the illness.
Insignificance refers to a relative absence of personal meaning of one’s
illness or symptoms. Early symptoms of a neoplasm, for example, may be
ignored by the patient if they do not signify a threat to him. This may be a
result of incorrect appraisal due to lack of medical knowledge, but may also
stem from indifference to symptoms in someone who is withdrawn,
depressed, apathetic, or who believes himself invulnerable.
Illness experience and behavior change as illness progresses and full
recovery, a downward course, or some degree of permanent disability follow.
The view of illness as a process involving a time dimension may be clarified if
we describe it as comprising a series of phases or stages. As the patient moves
from one stage to the next, he faces novel tasks which impose demands upon
him.
Stages of Illness
The terms “acute” and “chronic” are commonly used in medical and
psychiatric practice and connote rate of onset, duration, and reversibility of
disease. These terms are ambiguous. It is difficult to identify clearly any group
of individuals as the chronically ill, or the acutely ill, or those with disabilities.
Within most diagnostic categories there are patients who are more disabled
than ill, more acutely ill than chronically ill, and so on. The term “chronic
illness”, as commonly used, is synonymous with disability.
We will attempt to give a meaningful presentation here of a patient’s
progress, the changing tasks, stresses, and pitfalls he has to face on the road
to recovery, or when chronic illness, disability, or fatal disease preclude

return to full health. Not every patient goes through all the stages. His illness
may become arrested at any of them. An acute phase may never occur. There
are only three possible outcomes: recovery, chronicity, or death. The

following stages will be described:
1. symptom perception,
2. decision making,
3. medical contact,
4. acute illness,
5. convalescence or rehabilitation,
6. chronic illness or disability.
The Symptom-Perception Stage
Psychological characteristics of this phase of any illness are: perception
of change within one’s body boundaries and its evaluation.
Traditionally, a symptom has been defined as a manifestation of disease
apparent to the patient himself; a sign denotes a manifestation of disease that
only the physician perceives. This distinction is misleading. Enge proposes

that “the presence of a complaint must be regarded as presumptive evidence
of disease.” A symptom is a phenomenon belonging to the realm of subjective
perception which may or may not be observable by others, or communicated

to them as a complaint. A sign connotes an inference made by a qualified
observer that what the patient reports and/or the observer notices directly,
or discovers by means of special techniques, indicates the presence of a
particular disease. Such an inference may be made not only by a doctor, but at
times also by a lay observer, and may be at variance with what the patient
perceives, reports, or even explicitly denies.
A person’s interpretation of the significance of his symptoms

determines his affective responses and subsequent action or lack of it.
Symptoms are perceived and evaluated differentially by different individuals
and in different social situations. Such differences reflect both culturally and
socially learned responses, and the subject’s personality.
Sociocultural differences result in different patterns of response to
symptoms of illness. For instance, upper-class persons are more likely than
lower-class members to see themselves as ill when they experience particular
symptoms. Ethnic factors were discussed before in relation to studies by Zola
and Zborowski. As symptoms become more severe, continuous, unfamiliar,

and unpredictable in their course, however, the sociocultural and ethnic
factors become less important. Pain, the commonest symptom, is likely to
motivate a search for a medical consultation.
A different approach to the perception and evaluation of symptoms uses
the concept of body image as a basis for explanatory hypotheses and research
methodology. Every individual has a unique concept of his body as a
psychological object. Alterations of body perception which occur in illness are
responded to cognitively and emotionally in a manner and intensity which
are partly dependent on the subject’s body concept. Sensations arising from
areas assigned high significance in the person’s body gestalt are more likely
to be registered and interpreted. The vast literature on the body image has
recently been reviewed by Fisher, and the concept itself critically analyzed by
Shontz. The reader is referred to these sources as well as to Chapter 33 of this
Volume.
A psychodynamic approach to somatic symptoms is represented by a
study by Silverman. He claims that the development of physical symptoms,
regardless of whether they are due to organic disease, is related to “an

insufficiency of the psychological systems for handling the stimulus influx
mobilized by stress.” This study represents an attempt to explore an
important dimension of somatic symptoms, namely their unconscious

symbolic meaning and determinants. This area of investigation still suffers
from the lack of reliable methods of validating the proposed links between
observation records on the one hand, and inferences made from them, on the
other. In general, the more the meaning of perceived symptoms is influenced

by unconscious needs, fantasies, and conflicts, the more irrational,
idiosyncratic, and unpredictable is the patient’s overt response. Panic,
massive denial, and disregard of the likely significance of symptoms, their

delusional misinterpretations, marked delay or, on the contrary, undue haste
in seeking medical help—these are familiar examples of responses to
symptoms which are more influenced by unconscious factors than by rational
reasoning and knowledge.
Experiential factors related to previous illness episodes in oneself, or in
a person close to the patient, tend to influence the meaning of symptoms and
affective response to them. One who lost a close relative by cancer or heart
disease may become sensitized to and fearful of any associatively linked
symptom in himself. This may be an expression of identification with or guilt
toward the deceased individual.
Physicians commonly speak of “organic” or “functional” symptoms. This
distinction is meaningless since every illness has both physiological and

psychic components and the crucial question is how much both of them
contribute to the patient’s clinical picture. It may help the clinician to assess
such a relative contribution if he has a clear grasp of complaints which
indicate psychic distress regardless of whether a physical illness is present.

The following classification may serve as a guide to complaints or symptoms
pertaining to the body, but indicative of psychological distress or disorder.
Such symptoms are variously referred to as “psychogenic,”

“psychophysiological,” “psychosomatic,” or “somatization reactions”—all
vague and misused terms.
1. Physiological correlates of affective arousal such as anxiety or anger,
or somatic manifestations of an affective disorder, mainly depressive or
anxiety syndromes, e.g., pain, palpitations, diarrhea, hyperventilation
syndrome, polyuria, etc. Of course, none of these symptoms is pathognomonic
of a psychiatric disorder.
2. Somatic expression and communication of ideational, often conflict-
related, mental contents, which originate at the symbolic level of organization
and attempt to imitate a physical illness to meet the patient’s psychosocial
needs. These are the conversion symptoms.
3. Secondary symbolic elaborations, manifested as conversion
symptoms, of perceived somatic changes of any etiology, e.g., hysterical fits

coexisting with epilepsy.
4. Excessive preoccupation with bodily sensations, functions and
appearance, often accompanied by increased sensitivity to normally
subliminal somesthetic sensations. This is hypochondriasis (See references 96,

97, 128, 167, and 177).
5. Nosophobia, that is morbid fear of disease, such as cancer, venereal or

heart disease, etc.
6. Somatic delusions, that is, false convictions of bodily change,
disfigurement or disease, e.g., of changing one’s sexual characteristics or
having parasites, expressive of unconscious fantasies and signifying
schizophrenic or depressive psychosis, or occurring transiently in delirium.
7. Communication of psychological distress in bodily metaphors, e.g. “my
heart is heavy,” “my head is empty.”
8. Psychogenic body image disturbances, that is, subjective sense of
change in color, shape, weight, size, position, etc., of the body and/or its parts.
Such symptoms occur in association with schizophrenia, depression, severe
anxiety states, and the depersonalization syndrome.
9. Somatic symptoms representing residues of earlier responses to

stress, or memories of somatic symptoms experienced during a forgotten
childhood illness and re-experienced through associative links with a current
psychosocial stress.
The above symptoms may be present alone or coexist with and mask
those of a physical illness, just as the latter may be present as a disorder of
mood or higher mental functions. At any given time, symptoms may be

manifestations of primarily organic pathology, the affective response to it and
the associated physiological arousal, and of the symbolic meaning of the other
symptoms. A patient may experience combinations of symptoms having
different mechanisms and diagnostic significance.
The Decision-Making Stage
A patient’s response to his symptoms has a bearing on his decision to
seek medical help. studies of medical care in the United States and England
show that in a population of 1000 adults over sixteen years of age, in an
average month 750 experience an episode of illness, but only 250 of these
consult a doctor. In certain population groups, such as the aged, nine out of
ten illness episodes are not treated by a physician. At least three sets of
factors influence the patient’s decision to seek medical help: (1) his objective
clinical disorder and symptoms, as well as his perception, knowledge, beliefs,
and attitudes about having a particular disorder; (2) his attitudes and
expectations of the doctor and medical services; and (3) his definitions of
“health,” “sickness,” and need for medical care. These factors vary in the
population and reflect individual, ethnic, and sociocultural variables

discussed earlier.
Many people seek medical consultation during periods of life stress.
Psychophysiological reactions evoked by such stress are a source of

discomfort and may also prompt attention to symptoms which were
previously ignored. Life stress may foster the adoption of the sick role
regardless of presence or absence of a physiological change or dysfunction.
The onset of a psychiatric disorder in response to psychosocial stress may
bring the patient to a doctor, but be expressed in terms of the somatic
complaints listed earlier.
The patient’s decision-making process is practically important for two
reasons: (1) It has a bearing on preventive medicine and timely utilization of
medical facilities; and (2) It is related to overuse of medical care. The former
problem has been studied lo identify psychosocial causes of delay in seeking
medical help for serious conditions, mostly cancer and heart disease (See
references 19, 27, 61, 63, 67, 71, 90, and 91).
Delay may be computed from the date of first appearance of symptoms
or from the time a symptom is recognized by the patient as requiring medical
attention. It is this latter, “avoidable,” delay which has attracted particular
attention. Many different factors have been suggested as influencing delay: 1.
age, older patients being more likely to delay; 2. ethnic factors; 3. lower
socioeconomic status; 4. site of symptoms, those noticeable by others may lead

to greater delay; 5. personality variables.
Most studies identify two sets of relevant factors: excessive anxiety

related to the appraisal of symptoms as highly threatening; and ignorance,
minimization, and/or denial of the significance of symptoms accompanied by
low anxiety (See references 19, 27, 61, 63, 67, and 71). Denial and extreme
anxiety may not, however, be the only relevant factors. Severe depression
related to a life crisis may make some patients relatively indifferent to
somatic symptoms, or be accompanied by self-destructive or masochistic
tendencies with resulting inaction. A schizophrenic may be indifferent to pain
of a myocardial infarction, for example.
Excessive use of medical facilities has been less often studied than delay,
even though undue tendency to respond to subjective discomfort by seeking
medical help contributes to the cost of medical care. Such behavior may be a
manifestation of hypochondriasis. Some patients suffering from anxiety
neurosis may displace their anxiety from inner conflicts onto somatic
concerns and fear of disease. A doctor may reinforce such fears by telling the
patient that he has a “weak heart” or “tired blood,” for example. Many patients
come to medical clinics or doctors’ offices because they need sympathetic

advice about psychosocial problems. If the doctor ignores this need, the
patient may continue to return to him and present ever new somatic
symptoms until a doctor opens up a discussion of the patient’s real concerns,
or attaches a medical label to his complaints. In the latter case the patient may
“organize” his illness and enter a long-term “patient career.” Such patients are
likely to become chronic attenders of clinics, etc., and are often called “crocks”
by the exasperated doctors. Early inquiry into the reasons underlying the
patient’s complaints and the timing of his visits may lead to a talk about his
psychosocial problems, usually family or job related. This may satisfy the
patient’s need and prevent repeated and fruitless attendance.
The Medical Contact Stage
Once a person has decided to consult a doctor, a new element enters the
picture: patient-doctor interaction. This aspect of illness has been discussed
earlier and only a few additional comments need be added.
Both the patient and physician bring certain expectations into their
encounter. They are partly related to their respective social roles which
consist of conventionally defined attitudes, rights, and duties assigned to each

participant. Patients tend to evaluate the physician by nonprofessional
criteria which are influenced by their cultural background and conceptions of
what constitutes a good doctor. Surveys indicate that people single out
competence, interest in patients, and a sympathetic and concerned manner,
as the chief qualities of a good doctor. The success of a visit to a physician,
judged by the patient’s satisfaction and willingness to comply with the

doctor’s advice, depends to a large extent on whether the patient’s
expectations are met.
For the doctor, the purpose of a consultation is to arrive at a diagnosis.
“The satisfaction felt by the physician when he is able to assign a name,
hopefully the correct one, to the patient’s illness is matched only by the
layman’s relief when he hears that he is suffering from aplastic anemia and
not leukemia.” This wry comment reflects a deplorable aspect of current
medical practice. To diagnose means more than attach a medical label. It also
includes an assessment of the patient’s personality and current level of

psychological functioning; his family, occupational, social, and economic
situation; and his attitude toward his illness and symptoms. To achieve a
comprehensive diagnosis the doctor observes the patient’s appearance and

verbal and nonverbal behavior, takes an extensive history, and performs a
manual and instrumental examination. These aspects of a medical
consultation cannot be discussed in detail here. The reader is referred to
selected references (See references 14, 45, 46, 49, 108, and 154).
The doctor’s diagnostic reasoning process and the decision reached are
influenced by his interaction and communication with the patient. These, in
turn, are affected by the doctor’s personality and whether he is physical-
minded or psychological-minded, respectively. The former is typically less
reflective, introspective, and interested in abstract psychological ideas than

the latter. These personality characteristics determine if the doctor pays
attention and tries to deal with his patients’ psychosocial concerns.
Whatever the result of the doctor’s diagnostic reasoning may be, he has
to convey his opinion and advice to the patient. The manner in which he does
it influences the patient’s affective response and his cooperation or lack of it.
The doctor should state his findings and opinions clearly, bearing in mind the
kind of person he is dealing with. The patient’s ability to comprehend and his
need for information and likely reaction to it have to be assessed. An

intelligent, obsessional patient needs more information to allay his anxiety
than one whose intellectual capacity and need for understanding are less.
Medical jargon, ambiguous statements, or vague innuendoes may increase the
patient’s anxiety and open the way to misinterpretations. A patient who

habitually minimizes and denies the significance of danger must be
recognized and given an unambiguous statement of what the physician thinks
and recommends. Disclosure of diagnosis of a serious and potentially fatal

illness will be discussed later (see p. 50). When no evidence of organic disease
is found, the patient should be told so and asked about other possible reasons
for his symptoms. To tell him that his complaints are “imaginary” or
“functional” and he is really well, only serves to antagonize him and belies his
subjective perception of ill health. The doctor should state that while there is
no evidence of organic illness, there must be a reason for the patient’s

discomfort, possibly related to his life situation. In this way an inquiry into
the latter and possible preparation for a psychiatric consultation may be

broached.
The Acute Illness Stage
An acute illness implies relatively sudden onset and brief duration. A
mild, commonplace acute illness is usually self-limited and may not even
bring a patient to the doctor. If the illness is serious, however, it drastically
interrupts a person’s way of life and readily arouses fears of death, incapacity,
dependence on others, and personal losses discussed earlier. Pain, if present,
adds to the other stresses. The patient often responds with shock, disbelief,
and sometimes attempts at escape from the threatening situation. Thus a

patient with an acute myocardial infarction may attempt to continue his
activities and dismiss his symptoms as “indigestion” or some other harmless
condition. He may display unconcern and even bravado which mask his
anxiety and may be mistaken for courage. An acutely ill patient needs the
doctor’s emotional support and reassuring firmness.
The characteristics of this phase, or type, of illness are: adoption of
some degree of dependence on others; confinement at home or a hospital; and

uncertainty about the outcome. The latter may be full recovery, death, or
some degree of irreversible damage and thus chronicity. An acute illness may
be a transient or terminal phase of a chronic one. Since the other aspects of
illness have been discussed before, we will focus on one common feature of
acute illness: hospitalization and the hospital as a social milieu with which the
patient interacts.
Response to Hospitalization
Admission to a medical ward is for many a novel and anxiety-provoking
experience, for some a welcome respite. As an inpatient one becomes a
member of a specific social milieu in which the chief roles are played by the
health professionals. A person accustomed to privacy and independence has
to surrender them, and his freedom of action is curtailed by the authority of
doctors and nurses. He is subjected to often irksome rules. Members of the
clinical team decide what is wrong with him, what investigations and
therapies he is to undergo, what restrictions to observe, and what behavior is
acceptable or not. The physical environment itself is for many unfamiliar and
often frightening. The patient brings to this situation his habitual attitudes
toward and modes of coping with novelty, dependence, passive submission,

authority figures, and uncertainty—hallmarks of his condition as a
hospitalized patient. Most people manage to adjust to this situation, some
enjoy it, some find it distressing. The patient engages in interactions with
other patients and ward personnel, and the more anxious and/or angry he is,
the more likely is he to fall into conflict with some member of the ward
community. He is then liable to be branded a “management problem” or a

“difficult patient,” and referred for a psychiatric consultation.
The mere event of admission to a medical ward may be a source of

stress. Corticosteroid and catecholamine responses, respectively, were
studied in two groups of normal adults admitted to a hospital research ward.
Urinary 17-hydroxycorticosteroids, epinephrine, and norepinephrine values
were higher on the day of admission than later in hospitalization. This
suggests that hospital admission involves elements of novelty, threat, and
unpredictability which are associated with stress and psycho-physiological

arousal.
Ward rounds and laboratory procedures may be emotionally stressful.
Yet predictions of what may disturb a given patient are not easy. This is
illustrated by a study of women awaiting breast biopsy for suspected cancer.
Despite the obvious uncertainty and unpredictability of this situation for the
patients, the majority of them did not show manifest breakdown of
psychological defenses. This was reflected in the normal range of
hydrocortisone production rates. Thus it is incorrect to assume a priori that

what to an observer may appear as “stress” actually evokes emotional distress
in a given individual or group. The distress depends on how a potentially
threatening situation is individually perceived, interpreted, and defended

against. Some patients react with excessive emotions to hospitalization,
investigations, surgery, etc.
It is largely up to the doctors and nurses to ensure that a medical ward

should have a therapeutic effect. To prevent psychological crises in the ward
milieu it is important to ensure maintenance of communication between

patients and staff. This helps prevent interpersonal conflicts related to fears,
mutual distrust, and distorted perceptions among members of the ward
community. Some physicians and nurses readily provoke in many of their
patients unduly dependent, hostile, anxious, or seductive responses which
interfere with professional relationships. Such complications are avoidable

and may call for a clarifying and mediating intervention of a psychiatric
consultant.
Understanding of the patient’s personality and some degree of
psychological self-awareness on the part of the staff facilitate therapeutic and
preventive actions. The latter, called by some “adaptive intervention” or
“therapeutic manipulation,” involve personality diagnosis, suggestion, and
clarification. The use of such methods need not be confined to psychiatric
consultants. Properly trained nurses may apply some of these techniques, for
example in group therapy sessions for the inpatients in a general hospital.
Such intervention may help them adjust to hospitalization, illness,
investigative and therapeutic procedures, etc.
There is a growing trend to create a therapeutic social milieu in the
general hospital. This involves attention by the staff to the patients’ emotional
needs and their fears and uncertainties, which are often either unexpressed
spontaneously or acted out in behavior disruptive of ward routine.
The Convalescent or Rehabilitation Stage
Physiological recovery from illness should lead to surrender of the sick
role. This applies to all acute and fully reversible illness as well as that which
leaves physically nondisabling residual damage. When convalescence and/or
rehabilitation is indicated, the patient should cooperate. Yet psychosocial
factors may interfere with these goals and prolong disability beyond the
physiological recovery and despite the doctor’s judgment that the patient is
well. A physical illness or injury may be followed by some degree of disability

due to psychosocial factors, that is, by psychological invalidism. Intrapsychic
as well as socioeconomic factors may contribute.
Intrapsychic Factors
Ruesch studied a sample of patients with delayed recovery. He

frequently found conflicts over dependency and aggression in men, and
conflicts related to self-love and the feminine role in women. The men tended
to be dependent and passive, the women dominant, aggressive, and
overprotective. The sick role provided these patients with a primary gain, that
is reduction of intensity of intrapsychic conflicts and related unpleasant
affects. When physical illness or injury occurred in a setting of psychological

stress or interpersonal conflict, recovery was delayed. Psychologically
traumatic implications of disease or therapeutic procedures had the same
effect.
Other studies of patients with delayed recovery from a variety of
infections, or cardiovascular and other diseases generally concur with
Ruesch’s findings. Severe psychological trauma in their early lives, proneness
to depression, and a disturbed life situation and depression before or after
illness, characterizes many patients who have prolonged convalescence. Slow
recovery from infectious mononucleosis was correlated with lower scores of
ego-strength. Protracted convalescence in women who underwent radical

mastectomy could be predicted by Bard. He found a correlation between the
extent of dependence and that of the delayed recovery after surgery. A sample
of patients who had suffered a myocardial infarction showed that the
subjective meaning of the heart attack was an important determinant of

disability. They believed themselves to be damaged, fragile and vulnerable.
Thus enduring personality factors as well as the concurrent affective
state related to illness and/or interpersonal problems may delay recovery.

The concepts of primary and secondary gains are important. Secondary gains
refer to psychological, social and/or economic advantages which a patient

may derive from any illness. One should make a distinction, however,
between conscious or unconscious predilection to illness on the one hand, and
persistence of somatic symptoms related to affective arousal on the other. In

the first case motivational and attitudinal factors play the primary role; in the
second case, the patient’s physical illness merges with a psychological one,
such as anxiety, depressive, conversion, or hypochondriacal neurosis, and
related perception of symptoms. This distinction is important for treatment. If
the patient suffers from an anxiety state, for example, psychotherapy and use
of psychotropic drugs may help accelerate his recovery.
Social and Economic Factors
The doctor-patient relationship plays a part in delayed recovery and
rehabilitation. The amount and quality of information which the physician
transmits to the patient is important. This is well illustrated by the effects of

the extent of medical information given to patients suffering from a first
coronary occlusion. The nature and adequacy of information given to such
patients is associated with the frequency and timing of return to work.

Anxiety and depression are common in these patients and related to the
inability of doctors to confront and answer patients’ questions about the
meaning and implications of their illness. Treating patients’ symptoms related
to psychological distress as if they were manifestations of continuing physical

illness is a common blunder which fosters psychological invalidism. The
whole area of the personal meaning for the patient of the doctor’s therapeutic
methods; of prescription for drugs and the drugs themselves; of placebo

effect; and the patient’s compliance with therapeutic regimen, such as intake
of prescribed drugs, is attracting more attention because of its relevance for

the evaluation of treatment and its cost.
Many studies illustrate the importance of adequate information and
instruction given to patients by the doctors. Lack, vagueness, or incorrectness
of such information is a highly significant factor in avoidable prolonged
disability. Ambiguity and uncertainty often enhance anxiety and foster unduly
cautious, if not frankly phobic, attitudes in the patients toward resumption of
their premorbid occupational, sexual, and recreational roles (See references
12, 101, 141, 155, and 221). Close follow-up after discharge from the hospital
is crucial for prevention of such invalidism.
The response of the patient’s family may also contribute to delayed
recovery. A healthy member may reinforce the patient’s secondary gains from
being sick by meeting his dependent needs to a much greater extent than
when he was well. Anxiety in the spouse may increase that of the patient. If
there is convergence between the latter’s motivation, conscious or
unconscious, to remain ill and a gratifying family response to his persisting

complaints, prolonged psychogenic disability may ensue.
Social security disability programs, workmen’s compensation insurance,
compensation and medical malpractice suits, and other economic incentives

may contribute to the patient’s secondary gains and invalidism.
The Chronic-Illness Stage
Chronic illness implies a significant degree of irreversibility of the
pathological process or damage to the body and the related disability. It is an
ill-defined category and includes such diverse conditions as congenital
defects, acquired injuries and illnesses leaving residual damage, and
incurable diseases with a progressive or remitting course. It is difficult and
misleading to generalize about such diverse pathological conditions. Their
importance lies in the fact that chronic illnesses are the leading cause of
morbidity in advanced societies. The literature on the psychological aspects
of specific types of chronic illness and disability is extensive (See references 6,
32, 60, 144, and 225).
To discuss meaningfully psychological responses to chronic illness or
disability, one has to classify categories according to several criteria:
1. Time of onset. It is important if the given defect, disease, or

disability was present at or acquired after birth. If the latter,
then at what point in the person’s life cycle did it appear? We
do not deal here with congenital defects or deformities, since
they must be considered part of the individual’s somatic
endowment and not a stage of an illness.
2. Rate of onset: acute or gradual. The latter allows the patient more
time to develop coping mechanisms and is usually less
traumatic psychologically than the former.
3. Presence or absence of progression. If the disability results from an
accident, for example, and a stable condition ensues, the
patient is dealing with some form and degree of permanent
disability, loss of function, or disfigurement, to which he has
to adjust. If the pathological condition is potentially
progressive, this adds an element of uncertainty about the
future. Many people find uncertainty more distressing than a
serious but definite loss. Sufferers from many chronic
illnesses, such as multiple sclerosis, find it hard to plan for
the future which for them is unpredictable. A terminal illness
adds the challenge of facing early death.
4. Degree of reversibility of and/or compensability for the impaired

function. These factors determine realistic planning for
rehabilitation and adjustment, and the setting of goals
toward which the patient may strive and whose achievement
may be a source of pride and enhanced self-esteem.
We will describe some of the more commonly observed response
patterns to severe disability and fatal illness, especially cancer, respectively.
Much of what was discussed in relation to the other stages of illness is equally
relevant to the present stage and will not be repeated.
Chodoff offers a classification and description of patterns of

psychological adjustment to chronic illness and disability. It will be used as a
general framework and basis for discussion. The proposed three major
response patterns are:
1. Insightful acceptance, characterized by a lack of bitterness and
hostility, and of a sense of personal devaluation. The patient copes adaptively,
cooperates with rehabilitation plans, tries to learn substitute skills, and find
new sources of gratification. This is the most desirable response both for the
patient and those concerned with his care.
2. The denial pattern, characterized by negation of objective facts of
illness, for example of paralysis; of significance of disability, such as the need
to be cared for or to avoid certain activities; and of one’s emotional response
to illness, like anxiety, depression, or anger. Denial may be applied to one or
all of the above aspects of illness and vary in extent. It may be explicitly or
implicitly expressed. As such it is neither necessarily pathological nor
maladaptive. Some degree of it may help maintain optimal psychic adaptation.
Denial is pathological only if it concerns obvious facts and/or prevents the
patient from behaving in a manner respecting his limitations and

requirements of treatment.
3. The regressive pattern is characterized by exaggerated dependence
and passivity, often with thinly veiled anger and hostility. A regressed patient
plays up his disability and demands maximum attention and care from his
environment. He exaggerates his helplessness and suffering and uses his
illness as a strategy to manipulate others by playing on their sympathy or

feelings of guilt. This pattern is most often observed in hysterical
personalities who are typically overly dependent and dramatize their feelings,
as well as is some people who overemphasize their physical prowess and
independence.
Such classifications are deficient in several respects. They are static and
obscure clinical observations that the chronically ill and disabled go through
various phases of psychological response. Patients may experience shock,

denial, grief, anger, apathy, and euphoria, that is, display a wide spectrum of
emotional reactions and defensive strategies before settling in one or another
response pattern. In practice one must consider the changing, dynamic
aspects of every patient’s illness behavior. General classifications tend to
ignore inherent personality assets which are present to some extent in every
patient and must be used to the best advantage in his rehabilitation. If a

patient is just labelled as a “denier” or “regressed,” this may lead to
therapeutic nihilism and failure to tap whatever usable personality resources
he may possess. Even small gains in a sense of self-esteem and meaningful

existence in the severely disabled are a worthwhile goal of rehabilitation
efforts. Categorizing patients in terms of their ego mechanisms of defense

gives no indication of what specific affects they are defending against. Is it
anxiety, grief, shame, guilt, envy, resentment, or hopelessness? Identification

of the specific affective response in the individual patient may offer important
clues for therapeutic intervention, be it individual or group psychotherapy,
behavior therapy, or use of psychotropic drugs.
In conclusion, generalizations or labels should not obviate the need for

repeated evaluation of each patient’s psychological assets and liabilities as a
basis for an individually tailored and periodically reassessed management
approach (See references 26, 53, 59, 60, 81, 144, and 225).
The same holds for every patient regardless of the nature of his disease
or disability. Patients suffering from cancer provide another important
example. There is a vast literature on psychological aspects of cancer, with

126 citations in English between 1970-1973 alone. There too we see attempts
to classify psychological response patterns which cancer patients evolve. Such
descriptive categories may serve only as guidelines in evaluating a given

patient’s most dominant concerns and emotional reaction at a given time.
Few patients display an invariable response pattern throughout their illness
and its treatment. One must be sensitive to shifts in the psychological
responses and encourage the most adaptive ones. Problems of

communicating diagnosis of cancer, patterns of communication, and
psychological aspects of the management of cancer cannot be discussed here.
The question whether psychological factors influence prognosis of cancer

patients has attracted attention. In one study, those with a most favorable
outcome had a high proportion of individuals who had strong hostile drives
without loss of emotional control. Others report that cancer patients who
were aware of the nature of their illness lived longer than those who were
not, while those who suffered from concomitant depression tended to die
sooner than those not depressed.
Conclusion
The same general determinants of psychological responses operate at
all stages and in all types of physical illness. A multifactorial scheme for the
clinical evaluation and study of such responses has been proposed in this
Chapter. This general model is applicable to any disease or injury, acute or
chronic, mild or severe. The relative weight of the different factors obviously
varies from patient to patient, but they all contribute to illness experience and
behavior. Assessment of these factors is a necessary part of comprehensive
diagnosis as a basis for efficient clinical management of all patients.
Terminal Illness and Its Management
Terminal illness connotes impending death. Finality replaces

uncertainty about the future. It is the last phase of the human life cycle
evoking intense psychological responses in patients, their families, and the

health professionals. Its specific problems justify a separate discussion.
The scientific study of attitudes toward death and the experience of
dying has a short history. Few systematic studies had been published until
about twenty years ago. By 1964, a bibliography on death and bereavement
listed 321 entries of which about one-third had been published after 1960. A
more recent annotated bibliography on death and dying deals with the more
important works which had appeared up to 1969. This upsurge of scientific

interest in death and dying continues and is one of the most remarkable
developments in contemporary culture. We now have a body of factual
knowledge which allows formulation of guidelines for the management of the

dying. We first discuss briefly some salient observations and then principles
of management.
One should first distinguish different foci of studies related to death and
dying: (1) of psychological and cultural attitudes toward death in the general
population; (2) of the fear of death, one’s own or of others; (3) of the concept
of death in various populations, such as children; (4) of thanatophobia; (5) of
the attitudes, experiences and communications of the moribund patient; and
(6) of the actual experience of dying.
Only the last two types of studies can be considered here. The reader is
referred to several recent books which together offer comprehensive
coverage of the whole subject (See references 13, 48, 107, 165, 220, and 219).
Weisman and Kastenbaum have written a lucid account of a study of the
terminal phase of life. Their method, “the psychological autopsy,” was an
interdisciplinary conference that attempted to reconstruct the preterminal
and terminal phases of life of a recently deceased patient and evaluate the
role of psychosocial factors in his death. Their patient sample consisted of
eighty elderly men and women, inmates of a hospital for the aged.
The authors emphasize that dying is a natural event in the life cycle.
There is a distinct preterminal period that may be regarded as a
developmental phase serving as preparation for and adaptation to impending
death. The dying process must not be viewed as a “mental health problem.”
Four attitudes toward death could be distinguished: 1. acceptance; 2. apathy;

3. apprehension; and 4. anticipation, i.e. acceptance plus an explicit wish for
death. Acceptance was more often the attitude of well-adjusted patients,
while death anxiety was associated with moderately severe organic and
psychiatric deterioration.
Those findings were obtained retrospectively and from a restricted
patient population. It would be erroneous to generalize from them. Thus,

observations of terminal cancer patients revealed that nearly all of them were
deeply concerned about dying, depressed, and frightened. Kubler-Ross, in her
valuable book On Death and Dying, reports on a study of over 200 terminal
patients. She describes five major stages in the psychological response to the
awareness of dying: (1) Denial and isolation. This initial phase was present in
both those who were told that they would die and those who came to this
conclusion independently. A characteristic verbal response was: “No, not me,
it cannot be true.” Denial was at least partially used by almost all patients
during the first stage of terminal illness, and intermittently later on. It was, for
a time, a healthy way of dealing with an uncomfortable and inexorable
situation. Denial sustained to the end did not bring distress. Most patients,
however, gradually gave up denying the reality of their situation and
displayed other responses; (2) Anger. When denial could no longer be

maintained, it was often replaced by feelings of anger, rage, envy, and
resentment. The typical question at this stage was: “Why me?” The patients
readily projected their anger and blame on family and staff. They were
aggrieved by and found fault with everything. Such hostile behavior was
aggravated by angry responses of family and the ward staff; (3) Bargaining.
This stage was characterized by patients’ attempts to avert their fate by being
amiable and cooperative as if this could be rewarded by postponement or

warding off death; (4) Depression. When progression of his disease was
unmistakable, the patient reacted with a sense of loss and grief. Reactive grief
or depression was related to the losses of body parts through surgery and the
symbolic losses of self-esteem, etc., accompanied by feelings of guilt or shame.

Preparatory depression, on the contrary, signified anticipation of the ultimate
loss of life itself. This second type of depression was a necessary stage in
coming to terms with the impending loss of all the love objects; and (5)
Acceptance. This stage required time to be achieved and help in working
through the preceding stages. The patient was neither depressed nor angry,
but almost devoid of feeling and increasingly detached. He tended to be silent
and wished to be left alone. Hope usually persisted through all the stages. If a
patient gave up hoping, it was usually a sign' of imminent death.
Death has different meanings for different individuals: the personified
destroyer; relief from pain; reunion with one’s family; loss of control;
punishment; loneliness. Attitudes toward death can vary in the same
individual, ranging from fear, defiance, and denial, to uneasy resignation and
calm acceptance. For some, the approach of death may become a stimulus to
psychological growth and creativity.
Descriptions of the subjective experience of dying have been obtained
from patients resuscitated after cardiac arrest. They related a pleasant feeling
as though they were entering a peaceful sleep. None of them recalled any fear
or other unpleasant feeling while losing consciousness. It seems that “biologic
death” is not an unpleasant experience. Psychological complications tend to
occur if the dying person suffers from unresolved feelings of guilt; a sense of
unfulfillment or wasted opportunities; and a marked susceptibility to
separation anxiety. These are conditions in which psychiatric consultation,
sometimes supplemented by talks with a clergyman may help alleviate the

patient’s anguish. The incidence of “psychopathological” reactions in terminal
patients is unknown. Some patients are delirious or comatose in the final
stages of life.
The Management of the Dying Patient
The doctor’s personal attitude toward his own death influences his
views on how the dying patient should be managed. Death is an ultimate
challenge to the physician’s knowledge and skill and a disturbing reminder of
their limitations. Some doctors experience their failure to save the patient as
a personal defeat and humiliation. They may respond with feelings of guilt,
shame, and resentment. To cope with his own emotions, the doctor may
simply avoid the patient, or become awkward and detached in his contacts
with him. The doctor’s withdrawal tends to increase the patient’s sense of
helplessness and loneliness. Often the patient, his family, and the doctor
attempt to maintain the denial of the impending dissolution and an awkward
game of mutual deception and avoidance of facing the facts takes the place of
open communication. How can this common and regrettable situation be
avoided? We may offer some general clinical guidelines.
1. The issue to be faced and settled by all concerned is that of
communication of diagnosis and its consequences. The perennially
controversial question is: “To tell or not to tell?” It is remarkable that

extensive polls conducted among physicians and laymen, respectively, reveal
almost diametrically opposite views on this issue. Eighty to ninety percent of
healthy subjects, as well as cancer patients, questioned responded that they
wished to be told that they had cancer or another fatal illness. However, 40
percent of dying patients, who were asked if they wanted to be told when they
would die, answered in the negative. And how about the doctors? Of 219
physicians questioned by Oken, ninety percent said that they did not disclose
diagnosis of cancer as a usual policy. In a general poll of 5000 American
doctors, twenty-two percent said that they never told patients that they had
cancer. Yet doctors usually affirm that they would personally want to be told
if critically ill.
Whether or not the patient is told that he has cancer, or another fatal
illness, he sooner or later guesses the truth from the nonverbal cues. How
should this problem be handled? The question is not whether to tell, but who
should do it, how and when. Communication should be the responsibility of
someone close to the patient and his family. Time must be allowed for the
facts to sink in and for questions to arise. The patient should not be told that
there is no more that can be done for him. The way the news is broken should
depend on the patient’s personality, intelligence, religion, and the indirect
clues he provides about how he is likely to deal with the disclosure. Some
should not be told until a strong relationship with a staff member has
developed. Clearly, a general rule of thumb has no place here.
2. The management involves sustained and supportive communication
after the disclosure of diagnosis.
3. Some patients benefit from psychological intervention and
counseling. The latter should have the following aims: Encouragement of
competent behavior, that is, helping the patient maintain his remaining
competence and capacity for achievement; preservation of rewarding
relationships with the family and friends; maintenance of a dignified self-image
by providing environment, activities, and relationships enhancing the
patient’s sense of his own worth; attainment of an acceptable death by helping
the patient resolve his intrapsychic conflicts and emphasizing his
achievements and autonomy.
4. Communication with and support of the patient’s family.
In summary, management of the dying patient is one of the most
important and demanding tasks for all health professionals involved in his
care. Adequate communication with the patient, sustained contact and

emotional support to the very end are mandatory. These tasks belong to the
health professionals in attendance, and not primarily to the psychiatrist. His
role should be confined to consulting and therapeutic intervention in selected
cases only. The management of the dying must be adapted to their individual
needs and capacities. The physician must also at times face the decision when
to withhold treatment and distinguish between prolongation of life and
prolonging dying.
Conclusion
There is a major increase of interest in the psychological aspects of
death and the process of dying. This area of study is far from finished and its
results are still inconclusive. It imposes serious emotional demands upon the
investigator, who can hardly remain detached and separate research from
therapy. There are many modes of dying. The patient’s age, sex, personality,
circumstances of his terminal illness, his religious beliefs, the degree of
support he receives from his environment, his state of consciousness, and
amount of physical pain are all significant factors.
Bibliography
Abrams, R. D. “The Patient with Cancer—His Changing Pattern of Communication,” N. Engl. J.

Med., 274 (1966), 317-322.
Achte, K. and J. L. Vaukhonen. Cancer and Psyche. Part 1: Psychic Factors in Cancer. Helsinki:
Monograph from the Psychiatric Clinic of the Helsinki University Central Hospital,
1970.
Balint, M. The Doctor, His Patient and the Illness. London: Pitman, 1957.
Bard, M. “The Use of Dependence for Predicting Psychogenic Invalidism following Radical
Mastectomy,” J.Nerv. Ment. Dis., 122 (1955). 152-160.
Bard, M. and R. B. Dyk. “The Psychodynamic Significance of Beliefs Regarding the Cause of Serious
Illness,” Psychoanal. Rev. 43 (1956), 146-162.
Barker, R. G., B. A. Wright, L. Meyerson et al. Adjustment to Physical Handicap and Illness. New
York: Social Science Research Council, 1953.
Bellak, L., ed. Psychology of Physical Illness. New York: Grune & Stratton, 1952.
Bibring, G. L. “Psychiatry and Medical Practice in a General Hospital,” N. Engl. J. Med., 254 (1956).
366-372.
Black, P., ed. Physiological Correlates of Emotion. New York: Academic, 1970.
Bloom, S. W. The Doctor and His Patient. New York: Russell Sage Foundation, 1963.
Book, H. E. “Sexual Implications of the Nose,” Compr. Psychiatry, 12 (1971), 450-455.
Brewerton, D. A. and J. W. Daniel. “Factors Influencing Return to Work,” Br. Med. J., 4 (1971), 277-
281.
Brim, O. G., Jr., H. E. Freeman, S. Levine et al., eds. The Dying Patient. New York: Russell Sage
Foundation, 1970.
Browne, K. and P. Freeling. The Doctor-Patient Relationship. Edinburgh: E. & S. Livingstone, 1967.
Burch, G. E., N. P. De Pasquale, and J. H. Phillips. “What Death Is Like,” Am. Heart J., 76 (1968),
438-439.
Bursten, B. “Family Dynamics, the Sick Role, and Medical Hospital Admissions,” Family Process, 4
(1965), 206-216.
_____. “Psychosocial Stress and Medical Consultation,” Psychosomatics, 6 (1965), 100-106.
Byrne, D., M. A. Steinberg, and M. S. Schwartz. “Relationship Between Repression-Sensitization

and Physical Illness,” J. Abnorm. Psychol., 73 (1968), 154-155.
Cameron, A. and J. Hinton. “Delay in Seeking Treatment for Mammary Tumors,” Cancer, 21
(1968), 1121-1126.
Canter, A., J. B. Imboden, and L. E. Cluff. “The Frequency of Physical Illness as a Function of Prior
Psychological Vulnerability and Contemporary Stress,” Psychosom. Med., 28 (1966),
344-350.
Cappon, D. “Attitudes of and Towards the Dying,” Can. Med. Assoc. J., 87 (1962), 693-700.
Carey, W. B. “Psychologic Sequelae of Early Infancy Health Crises,” Clin. Pediatr., 8 (1969), 459-
463.
Cassell, W. A. “Individual Differences in Somatic Perception,” in Advances in Psychosomatic

Medicine, Vol. 8, Z. J. Lipowski, ed., Psychosocial Aspects of Physical Illness, pp. 86-
104. Basel: Karger, 1972.
Chester, R. “Health and Marriage Breakdown: Experience of a Sample of Divorced Women,” B. J.

Prev. Soc. Med., 25 (1971), 231-235.
Chodoff, P. “Adjustment to Disability. Some Observations on Patients with Multiple Sclerosis,” J.

Chronic Dis., 9 (1959), 653-670.
_____. “Understanding and Management of the Chronically Ill Patient. Part 1. Who Are the
Chronically Ill?” Am. Practitioner, 13 (1962), 136-144.
Cobb, B., R. L. Clark, Jr., C. McGuire et al. “Patient Responsible Delay in Cancer Treatment; Social
Psychological Study,” Cancer, 7 (1954), 920-926.
Coelho, G. V., D. A. Hamburg, R. Moos et al., eds. Coping and Adaptation. A Behavioral Sciences
Bibliography. Chevy Chase, Md.: National Institute of Mental Health, 1970.
Crandell, D. L. and B. P. Dohrenwend. “Some Relations Among Psychiatric Symptoms, Organic

Illness, and Social Class,” A. J. Psychiatry, 123 (1967), 1527-1537.
Crawford, C. O., ed. Health and the Family. New York: Macmillan, 1971.
Croog, S. H., S. Levine, and Z. Lurie. “The Heart Patient and the Recovery Process,” Soc. Sci. Med., 2
(1968), 111-164.
Cruickshank, W. M., ed. Psychology of Exceptional Children and Youth. 3rd ed., Englewood Cliffs,
N.J.: Prentice-Hall, 1971.
Davis, H. K. and R. L. Zapalac. “The Immature Personality with a Physical Illness,” South. Med. J., 61
(1968), 985-989.
Davis, M. S. “Variation in Patients’ Compliance with Doctors’ Orders: Medical Practice and Doctor
—Patient Interaction,” Psychiatry Med., 2 (1971), 31-54.
DeWolfe, A. S., R. P. Barrell, and J. W. Cummings. “Patient Variables in Emotional Response to

Hospitalization for Physical Illness,” J. Consult. Psychol., 30 (1968), 68-72.
Dodge, D. L. and W. T. Martin. Social Stress and Chronic Illness. Notre Dame, Ind.: University of
Notre Dame Press, 1970.
Druss, R. G., J. F. O’Connor, J. F. Prudden et al. “Psychologic Response to Colectomy,” Arch. Gen.
Psychiatry, 18 (1968), 53-59.
Dubos, R. Man, Medicine, and Environment. New York: Praeger, 1968.
Duff, R. S. and A. B. Hollingshead. Sickness and Society. New York: Harper & Row, 1968.
Eliot, R. S., ed. Stress and the Heart. Mount Kisco, N.Y.: Futura, 1974.
Engel G. L. “ ‘Psychogenic’ Pain and the Pain-Prone Patient,” Am.J. Med., 26 (1959), 899-918.
_____. “A Unified Concept of Health and Disease,” Perspect. Biol. Med., 3 (1960), 459-485.
_____. Psychological Development in Health and Disease. Philadelphia: Saunders, 1962.
_____. “Conversion Symptoms,” in C. M. MacBryde and R. S. Blacklow, eds., Signs and Symptoms, pp.
650-668, 5th ed., Philadelphia: Lippincott, 1970.
Engle, R. L., Jr. and B. J. Davis. “Medical Diagnosis: Present, Past, and Future,” Arch. Intern. Med.,
112 (1963), 512-519.
Faucett, R. L. “Psychiatric Interview as Tool of Medical Diagnosis,” JAMA, 162 (1956), 537.
Feifel, H. The Meaning of Death. New York: McGraw-Hill, 1959.
_____. “Attitudes toward Death: A Psychological Perspective,” J. Cons. Clin. Psychol., 33 (1969), 292-
295.
Feinstein, A. R. Clinical Judgment. Baltimore: Williams & Wilkins, 1967.
Fink, S. L., J. K. Skipper, Jr., and P. Hallenbeck. “Physical Disability and Problems in Marriage,” J.
Marriage Family, 30, 64-73.
Fischer, W. F. Theories of Anxiety. New York: Harper & Row, 1970.
Fisher, S. Body Experience in Fantasy and Behavior. New York: Appleton-Century-Crofts, 1970.
Fogel, M. L. and R. H. Rosillo. “Correlation of Psychological Variables and Progress in Physical

Rehabilitation. II. Motivation, Attitudes, and Flexibility of Goals,” Dis. Nerv. Syst., 30
(1969), 593-600.
Fox, R. C. Experiment Perilous: Physicians and Patients Facing the Unknown. Glencoe, Ill.: Free
Press, 1959.
_____. “Medical Evolution” in J. J. Loubser et al., eds., Explorations in Social Science Theory, pp. 1-52.
New York: Free Press, 1973.
Freidson, E. Profession of Medicine. New York: Dodd-Mead, 1970.
Friedman, S. B., P. Chodoff, J. W. Mason et al. “Behavioral Observations on Parents Anticipating

the Death of a Child,” Pediatrics, 32 (1963), 610-625.
Friedman, S. B., J. W. Mason, and D. Hamburg. “Urinary 17-Hydroxysteroid Levels in Parents of
Children with Neoplastic Disease: A Study of Chronic Psychological Stress,”
Psychosom. Med., 25 (1963), 364-376.
Garner, H. H. Psychosomatic Management of the Patient with Malignancy. Springfield, Ill.: Charles
C. Thomas, 1966.
Garrett, J. F. and E. S. Levine, eds. Psychological Practices with the Physically Disabled. New York:
Columbia University Press, 1962.
Gold, M. A. “Causes of Patient’s Delay in Diseases of the Breast,” Cancer, 17 (1964), 564-577.
Golden, J. S. and G. D. Johnston. “Problems of Distortion in Doctor—Patient Communications,”

Psychiatry Med., 1 (1970), 127-149.
Goldsen, R. K. “Patient Delay in Seeking Cancer Diagnosis: Behavioral Aspects,” J. Chronic Dis., 16
(1963), 427-436.
Gordon, G., O. W. Anderson, H. P. Brehm et al. Disease, the Individual, and Society. New Haven,
Conn.: College & University Press, 1968.
Gussow, Z. “Behavioral Research in Chronic Disease: A Study of Leprosy,” J. Chronic Dis., 17

(1964), 179-189.
Guttman, L. “The Married Life of Paraplegics and Tetraplegics,” Paraplegia, 2, 182-188.
Hackett, T. P. and N. H. Cassem. “Factors Contributing to Delay in Responding to the Signs and
Symptoms of Acute Myocardial Infarction,” Am. J. Cardiol., 24 (1969), 651-658.
Hackett, T. P. and A. D. Weisman. “Psychiatric Management of Operative Syndromes: 1. The

Therapeutic Consultation and the Effect of Noninterpretive Intervention,”
Psychosom. Med., 22 (1960), 267.
_____. “Psychiatric Management of Operative Syndromes: II. Psychodynamic Factors in

Formulation and Management,” Psychosom. Med., 22 (1960), 356.
Hamburg, D. A., B. Hamburg, and S. De-Goza. “Adaptive Problems and Mechanisms in Severely
Burned Patients,” Psychiatry, 16 (1953), 11-20.
Hammerschlag, C. A., S. Fisher, J. De-Cosse et al. “Breast Symptoms and Patient Delay:
Psychological Variables Involved,” Cancer, 17 (1964), 1480-1485.
Harper, A. C. “Towards a Job Description for Comprehensive Health Care—a Framework for
Education and Management,” Soc. Sci. Med., 7 (1973), 291-303.
Henderson, L. J. “The Patient and Physician as a Social System,” N. Engl. J. Med., 212 (1935), 819-
823.
Hinkle, L. E., Jr. “Relating Biochemical, Physiological, and Psychological Disorders to the Social
Environment,” Arch. Environ. Health, 16 (1968), 77-82.
Hinkle, L. E., Jr., W. N. Christenson, D. Kane et al. “An Investigation of the Relation between Life
Experience, Personality Characteristics, and General Susceptibility to Illness,”
Psychosom. Med., 20 (1958), 278.
Holland, J. “Psychologic Aspects of Cancer,” in J. F. Holland and E. Frei, eds., Cancer Medicine.
Philadelphia: Lea & Febiger, 1973.
Honeyman, M. S., H. Rappaport, M. Reznikoff et al. “Psychological Impact of Heart Disease in the
Family of the Patient,” Psychosomatics, 9 (1968), 34-37.
Horowitz, M. J. Psychosocial Function in Epilepsy. Springfield, Ill.: Charles C. Thomas, 1970.
Hughes, G. M., ed. Homeostasis and Feedback Mechanisms. New York: Academic, 1964.
Imboden, J. B. “Psychosocial Determinants of Recovery,” in Advances in Psychosomatic Medicine,

Vol. 8, Z. J. Lipowski, ed., Psychosocial Aspects of Physical Illness, pp. 142-155. Basel:
Karger, 1972.
Jaco, E. G., ed. Patients, Physicians, and Illness. Glencoe, Ill.: Free Press, 1958.
Janis, I. L. Psychological Stress. New York: Wiley, 1958.
Janis, I. L. and H. Leventhal. “Psychological Aspects of Physical Illness and Hospital Care,” in B.
Wolman, ed., Handbook of Clinical Psychology, pp. 1360-1.377. New York: McGraw-
Hill, 1965.
Jenkins, D. C. and S. J. Zyzanski. “Dimensions of Belief and Feeling Concerning Three Diseases,
Poliomyelitis, Cancer, and Mental Illness: A Factor Analytic Study,” Behav. Sci., 13
(1968), 372-381.
Kahana, R. J. “Studies in Medical Psychology: A Brief Survey,” Psychiatry Med., 3 (1972), 1-22.
Kahana, R. J. and G. L. Bibring. “Personality Types in Medical Management,” in E. N. Zinberg, ed.,

Psychiatry and Medical Practice in a General Hospital, pp. 108-123. New York:
International Universities Press, 1964.
Kalish, R. A. “Death and Bereavement: An Annotated Social Science Bibliography Through 1964,”
SK & F Psychiatr. Rept., March-April, 1965.
_____. “Death and Dying. A Briefly Annotated Bibliography,” in O. G. Brim, E. Freeman, S. Levine et
al., eds., The Dying Patient. New York: Russell Sage Foundation, 1970.
Kaplan, S. M. “Laboratory Procedures as an Emotional Stress,” JAMA, 161 (1956), 677-681.
Kasl, S. V. and S. Cobb. “Health Behavior, Illness Behavior and Sick-role Behavior. 1. Health and
Illness Behavior,” Arch Environ. Health, 12 (1966), 246-266.
_____. “Health Behavior, Illness Behavior and Sick-role Behavior. 2. Sick-role Behavior,” Arch.
Environ. Health, 12 (1966), 531-541.
Katz, J. L., H. Weiner, T. F. Gallagher et al. “Stress, Distress, and Ego Defenses,” Arch. Gen.
Psychiatry, 23 (1970), 131-142.
Kaufman, R. M., A. N. Franzblau, and D. Kairys. “The Emotional Impact of Ward Rounds,” J. Mount
Sinai Hosp., 23 (1956), 782-803.
Kellner, R. “Psychiatric Ill Health Following Physical Illness,” Br. J. Psychiatry, 112, (1966), 71-73.
Kelly, W. D., and S. R. Friesen. “Do Cancer Patients Want To Be Told?” Surgery, 27 (1950), 822-
826.
Kenyon, F. E. “Hypochondriasis: A Clinical Study,” Br. J. Psychiatry, 110 (1964), 467.
_____. “Hypochondriasis: A Survey of Some Historical, Clinical, and Social Aspects,” Br. J. Med.
Psychol., 38 (1965), 117.
King, S. H. Perceptions of Illness and Medical Practice. New York: Russell Sage Foundation, 1962.
Kleck, R. “Physical Stigma and Nonverbal Cues Emitted in Face-to-Face Interaction,” Hum. Rel., 21
(1968), 19-28.
Klein, R. F., A. Dean, and M. D. Bogdonoff. “The Impact of Illness Upon the Spouse,” J. Chronic Dis.,
20 (1967), 241—248.
Klein, R. F., A. Dean, M. L. Willson et al. “The Physician and Postmyocardial Infarction Invalidism,”
JAMA, 194 (1965), 123-128.
Kollar, E. J. “Psychology of the Acutely Sick and Injured,” Int. Psychiatry Clin., 3 (1966), 83-91.
Koos, E. L. The Health of Regionville. New York: Columbia University Press, 1954.
Kornfeld, D. S. “The Hospital Environment: Its Impact on the Patient,” in Advances in

Psychosomatic Medicine, Vol. 8, Z. J. Lipowski, ed., Psychosocial Aspects of Physical
Illness, pp. 252-270. Basel: Karger, 1972.
Koski, M. L. “The Coping Processes in Childhood Diabetes,” Acta Paediatr. Scand., Suppl. 198
(1969).
Krant, M. J. “The Organized Care of the Dying Patient,” Hosp. Practice, 7 (1972), 101-108.
Kubler-Ross, E. On Death and Dying. London: Macmillan, 1969.
Lain-Entralgo, P. Doctor and Patient. London: Weidenfeld & Nicolson, 1969.
Langford, W. S. “The Child in the Pediatric Hospital: Adaptation to Illness and Hospitalization,”
Am. J. Orthopsychiatry, 31 (1961), 667-684.
Langlois, P. and V. Teramoto. “Helping Patients Cope with Hospitalization,” Nurs. Outlook, 19
(1971), 334-336.
Lazarus, R. S. Psychological Stress and the Coping Process. New York: McGraw-Hill, 1966.
Lazarus, R. S. “Psychological stress and coping in adaptation and illness,” Psychiatry Med. (in
press).
Levine, S. and N. A. Scotch, eds. Social Stress. Chicago: Aldine, 1970.
Lipowski, Z. J. “Delirium, Clouding of Consciousness and Confusion,” J. Nerv. Ment. Dis., 145
(1967), 227-255.
_____. “Review of Consultation Psychiatry and Psychosomatic Medicine. 1. General Principles,”

Psychosom. Med., 29 (1967), 153-171.
_____. “Review of Consultation Psychiatry and Psychosomatic Medicine. 2. Clinical Aspects,”

Psychosom. Med., 29 (1967), 201-224.
_____. “Review of Consultation Psychiatry and Psychosomatic Medicine. 3. Theoretical Issues,”

Psychosom. Med., 30 (1968), 395-422.
_____. “Psychosocial Aspects of Disease,” Ann. Intern. Med., 71 (1969), 1197-1206.
_____. “New Perspective in Psychosomatic Medicine,” Can. Psychiatr. Assoc. J., 15 (1970), 515-525.
_____. “Physical Illness, the Individual and the Coping Processes,” Psychiatry Med. 1 (1970), 91-
102.
Lipowski, Z. J., ed. Psychosocial Aspects of Physical Illness, Vol. 8 of Advances in Psychosomatic
Medicine. Basel: Karger, 1972.
_____. “Psychosomatic Medicine in a Changing Society: Some Current Trends in Theory and
Research,” Compr. Psychiatry, 14 (1973), 203-215.
_____. “Consultation-Liaison Psychiatry: An Overview,” Am. J. Psychiatry, 131 (1974), 623-630.
_____. “Organic Brain Syndromes: An Overview and Classification,” in F. D. Benson and D. Blumer,
eds., Psychiatric Aspects of Neurologic Disorders. New York: Grune & Stratton,
forthcoming.
_____. “Psychiatry of Somatic Diseases: Epidemiology, Pathogenesis, Classification,” Compr.

Psychiatry, in press.
_____. “Psychophysiological Cardiovascular Disorders,” in A. M. Freedman, H. I. Kaplan, and B.

Sadock, eds., Comprehensive Textbook of Psychiatry, 2nd ed. Baltimore: Williams &
Wilkins, forthcoming.
Lipowski, Z. J. and R. Z. Kiriakos. “Borderlands Between Neurology and Psychiatry: Observations

in a Neurological Hospital,” Psychiatry Med., 3 (1972), 131-147.
Lipsitt, D. R. “Medical and Psychological Characteristics of ‘Crocks,’ ” Psychiatry Med., 1 (1970),

15-25.
Little, C. J. “The Athlete’s Neurosis—A Deprivation Crisis,” Acta Psychiatr. Scand., 45 (1969 b 187-
197.
Little, S. “Psychology of Physical Illness in Adolescents,” Pediatr. Clin. North Am., 7 (1960), 85-96.
Livsey, C. G. “Family Therapy: Role of the Practicing Physician,” in E. T. Lisansky, and B. R.

Shochet, eds., Psychiatry in Medical Practice, pp. 806-820. New York: Harper & Row,
1969.
_____. “Physical Illness and Family Dynamics,” in Advances in Psychosomatic Medicine, Vol. 8, Z. J.
Lipowski, ed., Psychosocial Aspects of Physical Illness, pp. 237-251. Basel: Karger,
1972.
Lowy, F. “Patients Who Somatize,” Paper presented at 52nd Annu. Meet, of the Ontario Psychiatr.
Assoc., Toronto, Ont.: January 29, 1972.
Ludwig, E. G. and G. Gibson. “Self Perception of Sickness and the Seeking of Medical Care,” J.
Health Soc. Behav., 10 (1969), 125-133.
Mabry, J. H. “Lay Concepts of Etiology,” J. Chronic Dis., 17 (1964), 371-386.
MacGregor, F. C. Transformation and Identity. New York: Quadrangle, 1974.
MacNalty, A. S., ed. The British Medical Dictionary. Philadelphia: Lippincott, 1963.
Maddison, D. and B. Raphael. “Social and Psychological Consequences of Chronic Disease in

Childhood,” Med. J. Aust., 2 (1971), 1265-1270.
Maddison, D. and A. Viola. “The Health of Widows in the Year Following Bereavement,” J.
Psychosom. Res., 12 (1968),297— 306.
Marra, J. and F. Novis. “Family Problems in Rehabilitation Counseling,” Personnel Guidance J., 38
(1959), 40-42.
Martin, H. L. “The Significance of Discussion with Patients about Their Diagnosis and its
Implications,” Br. J. Med. Psychol., 40 (1967), 233.
Mason, J. W., E. J. Sachar, J. Fishman et al. “Corticosteroid Responses to Hospital Admission,” Arch.
Gen. Psychiatry, 13 (1965), 1-8.
Matarazzo, R. G., J. D. Matarazzo, and G. Saslow. “The Relationship between Medical and
Psychiatric Symptoms,” J. Abnorm. Soc. Psychol., 62 (1961), 55-61.
McDaniel, J. W. Physical Disability and Human Behavior. New York: Pergamon, 1969.
McKinlay, J. B. “The Concept of ‘Patient Career’ as a Heuristic Device for Making Medical Sociology
Relevant to Medical Students,” Soc. Sci. Med., 5 (1971), 441-460.
Mechanic, D. Medical Sociology. New York: Free Press, 1968.
_____. “The Concept of Illness Behavior,” J. Chronic Dis., 15 (1962), 189-194.
Meissner, W. W. “Family Dynamics and Psychosomatic Processes,” Family Process, 5 (1966), 142-
161.
Melzack, R. and W. S. Torgerson. “On the Language of Pain,” Anesthesiology, 34 (1971), 50-59.
Mering, O. von, and L. Kasdan. Anthropology and the Behavioral and Health Sciences. Pittsburgh:
University of Pittsburgh Press, 1970.
Meyer, R. J. and R. J. Haggerty. “Streptococcal Infections in Families,” Pediatrics, 29 (1962), 539-

549.
Moore, D. C., C. P. Holton, and G. W. Marten. “Psychologic Problems in the Management of

Adolescents with Malignancy. Experiences with 182 Patients,” Clin. Pediatr., (1969),
464-473.
Moos, R. H. and G. F. Solomon. “Personality Correlates of the Degree of Functional Incapacity of

Patients with Physical Disease,” J. Chronic Dis., 18 (1965), 1019-1038.
Morgan, W. L., Jr. and G. L. Engel. The Clinical Approach to the Patient. Philadelphia: Saunders,
1969.
Nagle, R., R. Gangola, and I. Picton-Robinson. “Factors Influencing Return to Work after
Myocardial Infarction,” Lancet, 2 (1971), 454-456.
Oken, D. “What to Tell Cancer Patients,” JAMA, 175 (1961), 1120-1128.
Olsen, E. H. “The Impact of Serious Illness on the Family System,” Postgrad. Med., 47 (1970), 169-
174.
Orbach, C. E., M. Bard, and A. M. Sutherland. “Fear and Defensive Adaptations to the Loss of Anal
Sphincter Control,” Psychoanal. Rev., 44 (1957), 121-175.
Palmer, R. S. “Psychiatry and Internal Medicine,” N. Engl. J. Med., 263 (1960), 14-18.
Parkes, C. M. Bereavement. New York: International Universities Press, 1972.
Parsons, T. The Social System. Glencoe, Ill.: Free Press, 1951.
Parsons, T. and R. Fox. “Illness, Therapy, and the Modem Urban American Family,” J. Soc. Issues, 8
(1952), 31-44.
Payne, E. C., Jr. and M. J. Krant. “The Psychosocial Aspects of Advanced Cancer,” JAMA, 210 (1969),
1238-1242.
Pearsall, M. Medical Behavioral Science: A Selected Bibliography of Cultural Anthropology, Social

Psychology, and Sociology in Medicine. Lexington, Ky.: University of Kentucky Press,
1963.
Pearson, L., ed. Death and Dying. Cleveland: Press of Case Western Reserve University, 1969.
Petrie, A. Individuality in Pain and Suffering. Chicago: University of Chicago Press, 1967.
Pilowsky, I. “Primary and Secondary Hypochondriasis,” Acta Psychiatr. Scand., 46 (1970), 273-
285.
Pinner, M. and B. F. Miller, eds. When Doctors Are Patients. New York: Norton, 1952.
Prugh, D. G., E. M. Staub, H. H. Sands et al. “A Study of the Emotional Reactions of Children and
Families to Hospitalization and Illness,” Am. J. Orthopsychiatry, 23 (1953), 70-106.
Psychological Aspects of Cancer, January 1970-March 1973. Washington, D.C.: U.S. Department of
Health, Education and Welfare, 1973.
Rahe, R. H. “Subjects’ Recent Life Changes and Their Near-future Illness Susceptibility,” in
Advances in Psychosomatic Medicine, Vol. 8, Z. J. Lipowski, ed., Psychosocial Aspects
of Physical Illness, pp. 2-19. Basel: Karger, 1972.
Rees, D. W. and S. G. Lutkins. “Mortality of Bereavement,” Br. Med. J., 4 (1967), 13-16.
Rickels, K., R. W. Downing, and M. H. Downing. “Personality Differences between Somatically and
Psychologically Oriented Neurotic Patients,” J. Nerv. Ment. Dis., 142 (1966), 10-18.
Rogers, E. S. Human Ecology and Health. New York: Macmillan, 1960.
Rosner, B. L. “The Use of Valid Psychological Complaints to Screen, Minimize or Deny Serious
Somatic Illness,” J. Nerv. Ment. Dis., 143 (1966), 234.
Ruesch, J. Chronic Disease and Psychological Invalidism. Berkeley: University of California Press,
1951.
Schilder, P. The Image and Appearance of the Human Body. New York: International Universities
Press, 1950.
Schmale, A. H., Jr. “Giving Up as a Final Common Pathway to Changes in Health,” in Advances in
Schmale, A. H., Jr. and G. L. Engel. “The Giving up—Given up Complex Illustrated on Film,” Arch.
Gen. Psychiatry, 17 (1967), 135-145.
Schoenberg, B., A. C. Carr, D. Peretz et al. Loss and Grief: Psychological Management in Medical
Practice. New York: Columbia University Press, 1970.
Seidman, F. and C. Swift. “Psychologic Aspects of Juvenile Diabetes Mellitus,” in H. S. Traisman,

ed., Management of Juvenile Diabetes, pp. 162-170. St. Louis, Mo.: Mosby, 1971.
Senescu, R. A. “The Development of Emotional Complications in the Patient with Cancer,” J.

Chronic Dis., 16 (1963), 813-832.
Shontz, F. C. “Severe Chronic Illness”, in J. F. Garrett and E. S. Levine, eds., Psychological Practices
with the Physically Disabled. New York: Columbia University Press, 1962.
_____. Perceptual and Cognitive Aspects of Body Experience. New York: Academic, 1969.
_____. “Physical Disability and Personality: Theory and Recent Research,” Psycholog. Aspects
Disability, 17 (1970), 51-69.
Silverman, S. Psychological Aspects of Physical Symptoms. New York: Appleton-Century-Crofts,

1968.
_____. Psychological Cues in Forecasting Physical Illness. New York: Appleton-Century-Crofts, 1970.
Sperling, M. “Transference Neurosis in Patients with Psychosomatic Disorders,” Psychoanal. Q., 36

(1967), 342-355.
Spielberger, C. D., ed. Anxiety: Current Trends in Theory and Research. New York: Academic, 1972.
Stallones, R. A. “Community Health,” Science, 175 (1972), 839.
Starkey, P. D. “Sick-role Retention as a Factor in Nonrehabilitation,” J. Couns. Psychol., 15 (1967),

75-79.
Stavraky, K. M., C. W. Buck, S. J. Lott et al. “Psychological Factors in the Outcome of Human
Cancer,” J. Psychosom. Res., 12 (1968), 251-259.
Stern, R. M. and D. J. Higgins. “Perceived Somatic Reactions to Stress: Sex, Age and Familial
Occurrence,” J. Psychosom. Res., 13 (1969), 77-82.
Sternbach, R. H. Pain: A Psychophysiological Analysis. New York: Academic, 1968.
Stevenson, I. “Single Physical Symptoms as Residues of an Earlier Response to Stress,” Ann.

Intern. Med., 70 (1969), 1231-1237.
Stoeckle, J. D. and G. E. Davidson. “Communicating Aggrieved Feelings in the Patient’s Initial Visit
to a Medical Clinic,” J. Health Human Behav., 4 (1963), 199-206.
Stoeckle, J. D., I. K. Zola, and G. E. Davidson. “On Going to See the Doctor, the Contributions of the
Patient to the Decision to Seek Medical Aid,” J. Chronic Dis., 16 (1963), 975-989.
Straus, R. “Behavioral Science in the Medical Curriculum,” Ann. N.Y. Acad. Sci., 128 (1965), 599-
606.
Suchman, E. A. “Stages of Illness and Medical Care,” J. Health Human Behav., 6 (1965), 114-128.
_____. “Health Attitudes and Behavior,” Arch. Environ. Health, 20 (1970), 105-110.
Susser, M. Causal Thinking in the Health Sciences. New York: Oxford University Press, 1973.
Szasz, T. S. Pain and Pleasure. New York: Basic Books, 1957.
Szasz, T. S. and M. H. Hollender. “A Contribution to the Philosophy of Medicine: The Basic Models
of the Doctor-Patient Relationship,” Am. Med. Assoc. Arch. Intern. Med., 97 (1956),
585.
Thurlow, J. H. “Illness in Relation to Life Situation and Sick-role Tendency,” J. Psychosom. Res., 15
(1971), 73-88.
Tolson, W. W., J. W. Mason, E. J. Sachar et al. “Urinary Catecholamine Responses Association with
Hospital Admission in Normal Human Subjects,” J. Psychosom. Res., 8 (1965), 365-
372.
Twaddle, A. C. “The Concepts of the Sick Role and Illness Behavior,” in Advances in Psychosomatic
Medicine, Vol. 8, Z. J. Lipowski, ed. Psychosocial Aspects of Physical Illness, pp. 162-
179. Basel: Karger, 1972.
Van Den Berg, J. H. The Psychology of the Sickbed. Pittsburgh: Duquesne University Press, 1966.
Vernon, D. T. A., J. M. Folley, R. R. Sipowicz et al. The Psychological Responses of Children to

Hospitalization and Illness. Springfield, Ill.: Charles C. Thomas, 1965.
Verwoerdt, A. Communication with the Fatally Ill. Springfield, Ill.: Charles C. Thomas, 1966.
_____. “Psychopathological Responses to the Stress of Physical Illness,” in Advances in
Visotsky, H. M., D. A. Hamburg, M. A. Goss et al. “Coping Behavior under Extreme Stress,” Arch.
Gen. Psychiatry, 5 (1961), 423-448.
Von Bertalanffy, L. General System Theory. New York: Brazillier, 1968.
Waitzkin, H. and J. D. Stoeckle. “The Communication of Information about Illness,” in Advances in

Walton, H. J. “Effect of the Doctor’s Personality on His Style of Practice,” J. R. Coll. Gen. Pract., 16
(1968), 113-126.
Wan, T. “Status Stress and Morbidity: A Sociological Investigation of Selected Categories of Work-
Limiting Chronic Conditions,” J. Chronic Dis., 24 (1971), 453-468.
Warm, J. S. and E. A. Alluisi. “Behavioral Reactions to Infection: Review of the Psychological

Literature,” Percept. Mot. Skills, 24 (1967), 755-783.
Weinstein, M. R. “The Illness Process,” JAMA, 204 (1968), 209-213.
Weinstein, S., R. Vetter, and E. Sersen. “Physiological and Experiential Concomitants of the
Phantom,” quoted in J. W. McDaniel, Physical Disability and Human Behavior, p. 32.
New York: Pergamon, 1969.
Weisman, A. D. On Dying and Denying. New York: Behavioral Publ., 1972.
Weisman, A. D. and R. Kastenbaum. “The Psychological Autopsy,” Community Ment. Health J.,
Monogr. 4 (1968).
Wishnie, H. A., T. P. Hackett, and N. H. Cassem. “Psychological Hazards of Convalescence

Following Myocardial Infarction,” JAMA, 215 (1971), 1292-1296.
Witkin, H. A., R. B. Dyk, H. F. Paterson et al. Psychological Differentiation. New York: Wiley, 1962.
Wolff, H. G. “A Concept of Disease in Man,” Psychosom. Med., 24 (1962), 25-30.
_____. Stress and Disease. 2nd ed. rev., S. Wolf and H. Goodell, eds., Springfield, Ill.: Charles C.
Thomas, 1968.
Wright, B. Physical Disability: A Psychological Approach. New York: Harper & Row, 1960.
Wyler, A. R., M. Masuda, and T. H. Holmes. “Magnitude of Life Events and Seriousness of Illness,”
Psychosom. Med.., 33 (1971). 115.
Zabarenko, R. N., L. Zabarenko, and R. A. Pittenger. “The Psychodynamics of Physicianhood,”

Psychiatry, 33 (1970), 102-118.
Zborowski, M. People in Pain. San Francisco: Jossey-Bass, 1969.
Zinker, J. C. and S. L. Fink. “The Possibility of Psychological Growth in a Dying Person,” J. Gen.
Psychol., 77 (1966), 185-199.
Zola, I. K. “Problems of Communication, Diagnosis, and Patient Care: The Interplay of Patient,
Physician and Clinic Organization,” J. Med. Educ., 38 (1963), 829.
_____. “Culture and Symptoms: An Analysis of Patients’ Presenting Complaints,” Am. Sociol. Rev., 31
(1966), 615-630.
_____. “Studying the Decision to See a Doctor,” in Advances in Psychosomatic Medicine, Vol. 8, Z. J.
Lipowski, ed., Psychosocial Aspects of Physical Illness, pp. 216-236. Basel: Karger,
1972.
Chapter 2
Delirium And Related Problems
Stanley S. Heller and Donald S. Kornfield
The Golden Bough, by Sir James Frazier, began as a study of the rule of
succession to the priesthood at Ariccia in the Alban Hills of Italy. However, to
understand this, Frazier was required to continually examine larger
questions, until he ended with twelve volumes and a comprehensive theory of
primitive religion. At one time, an article about delirium might have been
simple; all that would have been required was to catalogue the myriad
syndromes that affect the brain, as though the severity of the central nervous
system insult explained all. But the story turns out to be a good deal more
complicated than that. The investigation of the multitude of factors actually

responsible for delirium production has raised general and profound
questions concerning the nature of brain function, the mechanisms of sleep

and dreams, the importance of man’s environment, the interaction of mind
and body, and the mode of action of licit and illicit drugs. Delirium is the
psychosomatic syndrome par excellence, a final pathway of often coexistent
physical and psychological disturbance. Yet, as recently as 1967, Lipowski
lamented that delirium was the “Cinderella of English-language psychiatry:
taken for granted, ignored and not considered worthy of study.” New
developments in brain physiology, the advent of Rapid Eye Movement

technology (REM) allowing new insight into sleep and dreaming, research
into sensory deprivation and overstimulation, the model psychoses of
hallucinogenic drugs, the development of medical-surgical techniques causing

delirium, e.g., open-heart surgery, or preventing it, e.g., renal dialysis, have all
combined to cause considerably more interest in this increasingly complex
subject. Ten years ago it was simpler; intensive care units (ICU) could be built
without windows since patients would be unconscious or semiconscious and
not need them. It is now recognized that of all the facilities of a general
hospital, the ICU and recovery rooms need windows the most.
There used to be a saying that to understand syphilis was to understand
all of medicine. To understand delirium fully requires us to understand fully

the patient’s world: physical, environmental, social, and intrapsychic. The
concept of multidetermination is as applicable to delirium as to symptom or
dream formation. We will begin by looking at the syndrome in general terms,
and then turn to the specific situations in the general hospital where delirium
is most likely to occur.
History
Delirium is such a ubiquitous phenomenon that it was well known to
the ancient world. The Greeks and Romans clearly identified an acute
reversible brain syndrome distinguishable from chronic mental illness, and
called it “phrenitis” or “phrensy.” Fever was a common cause, and
Hippocrates noted visual hallucinations and picking at bed sheets. Plato and
Aristotle noted the similarity of dreams to the visions of the mentally ill.
Celsus saw the relationship between mind and body, realizing that delirium
was caused by debilitating systemic illness, and was a serious prognostic sign
auguring death. Delirium tremens was described by Aretaeus and Galen and
in the fifth century by Cassius Felix.
The Talmud, compiled in the first five hundred years a.d., describes a
reversible syndrome of “Kordiakos,” attributed to drinking new wine from a

vat. When convulsions were described, light wine was prescribed for therapy,
and this might very well also have been related to delirium tremens.
Delirium was of course known to poets and writers before it attracted

the attention of modern scientists. As has been noted, Shakespeare eloquently
describes Falstaff’s final illness in Henry V. “For often I saw him fumble with
the sheets and play with flowers and smile upon his fingers’ ends, I knew
there was but one way, for his nose was sharp as a pen, and a’babbled of
green fields.” (II, iii). He also recognized the role of psychological stress, “The
king has kill’d his heart.” (II, i).
In the modern era, Thomas Willis’s conceptualization has been

summarized by Lipowski. Wilson realized that delirium could be produced by
infection, intoxication, malnutrition, and visceral disorders. Postsurgical
delirium was described by Pare in the sixteenth century, and investigated by

Dupuytren in 1819. The nineteenth century witnessed great interest in the
phenomenon of hallucinations, as schizophrenia was delineated, and the
effect of hashish studied.
Freud’s contribution to the theory of delirium has not received
sufficient notice. In the Interpretation of Dreams, he pointed out that the
content of deliria is partly related to the individual’s experience; “even the
deliria of confusional states may have a meaning . . . they are unintelligible to

us owing to the gaps in them.” In the essay on Leonardo da Vinci, he pointed
out the similar mechanisms of dreaming and hallucinations; “a phantasy . . .
must have some meaning in the same way as any other psychical creation: a
dream, a vision or a delirium.” In this connection he quotes Radestock: “Both
in patients suffering from fever and in dreamers, memories arise from the
remote past, both sleeping and sick men recollect things which waking and
healthy men seem to have forgotten.” Freud also saw the working of the
mental apparatus, and that even in delirious states the unconscious never
overcomes the resistance of consciousness “so that the secret of the
childhood experiences is not betrayed even in the most confused delirium.”
As Lipowski has noted, the German psychiatrist Bonhoeffer classified
deliria, noting that specific etiologies could produce many types of delirium
reactions. Nonetheless there remained great terminological confusion, partly
relieved by the authoritative work of Engel and Romano. Delirium was

conceptualized as a syndrome of cerebral insufficiency, that could be
monitored by following the slowing of the electroencephalogram (EEG).
Hyperactivity, hallucinations, or agitation were not necessary for the
diagnosis. Delirium was defined as any acute, reversible syndrome of cerebral
insufficiency. Lipowski has introduced the concept of delirium as a
psychosomatic condition, in which both physical and psychological factors

interact causally. Psychological factors, such as sensory input, sleep
deprivation, the stress, setting and care of the medical illness, all were seen as
possible precipitating or intensifying factors in delirium etiology.
Classification
A number of related terms are used with different meaning to different

people. Delirium, which dynamically and historically should include all acute
brain syndromes, is used by many people to refer only to agitated
hallucinating patients. Confusion, metabolic encephalopathy, acute brain
syndrome, and psychosis associated with organic brain syndrome are,
conversely, sometimes applied only to the apathetic confused patient. The
issue is further complicated by the suggestion that the terms hyper- and
hypoactive delirium be used to make that distinction. However, this overlooks

the shifting and protean nature of the symptoms of delirium in any given
patient. These distinctions are quantitative, not qualitative. Delirium
represents a broad syndrome of disturbances in sensation, perception,
memory, thought, and judgment. It can run the gamut from a slight reduction
in alertness to coma, and indeed patients may pass through this sequence in
both directions, as their disease waxes and wanes.
In its mildest form it resembles alcohol intoxication, or hypnagogic or
hypnopompic phenomena, particularly in a strange place. It begins with a

mild clouding of perceptions, with a subjective lack of focus, blurring or
haziness. It is only with an effort that thought processes can be channeled
into logical and coherent patterns. Memory, especially for recent events,
becomes impaired. Speech and thinking become slowed, and the right answer
is obtained with delay. Perplexity, uncertainty, and vagueness are

communicated as the patient looks around searching for an answer. With
partial preservation of cerebral functioning, there may be moments of insight

into the perceptual, thought, and memory disturbances. Symbolic and
abstract thinking dwindle. Time disturbance appears with inability to give the
day of the week, hour of the day, or date. Place disorientation may occur, with
the hospital identified as home or as a branch of the hospital close to home.
Grasp, retention, and the capacity for attention are impaired. Patients become
distracted and fail to distinguish the relevant from the irrelevant.

Conversation becomes limited, with a tendency to short monosyllabic
phrases. Thought becomes disordered and fragmented with perseveration,
and an ultimate poverty of ideas. Drowsiness follows in many patients, while

others are restless and unable to sleep. Affect can be shallow or, in more
labile forms, irritation and agitation appear, with hypersensitivity to light and
noise. Headache may be present.
In the fully developed syndrome, the clouded sensorium and
disorientation proceed, and thinking may be so disconnected as to produce

incoherent speech. No matter how great the effort, reading becomes
impossible, and so may conversation. Progressive loss of motor control
appears with drooling, food spilling, poor food intake and hygiene, and
unkemptness. Ultimately, incontinence of urine and feces occur. This may
occur initially in dreams with ensuing shame, but in the end even the social
excretory conventions may be lost. Lack of contact with the environment may
be extreme, with total time and place disorientation and misidentification of

family members. Motor signs such as tremor, slurred speech, seizures,
increased autonomic activity appear, with fever, sweating, injected
conjunctivae, flushed countenance, rapid pulse, pilomotor responses, and
diarrhea. Patients may sleep only during the day when sensory cues are
sufficient to reorient and lessen anxiety, but night combines anxiety with
reduced sensory input, preventing sleep.
The fully developed syndrome is not merely the worsening of the mild
form but contains novel elements of the greatest scientific interest. It is the
appearance of hallucinations, initially reported as dreams, that raise major
questions. As Lipowski has noted, there is difficulty in estimating their
frequency, with a range of 39-73 percent. Visual hallucinations are generally

the most prominent, although the auditory modality is frequently involved,
and authors have commonly observed proprioceptive hallucinations in
postcardiotomy and tank respirator patients. Hallucinations are less marked

in the aged and in chronic disease. Lipowksi has raised three critical
questions with regard to the hallucinations: Why do they occur at all? Why
are they largely visual? How are they shaped by the ego’s conflicts?
West has provided a framework for answering these questions. His
analogy conveys the reciprocal relationship between reality and illusion . . . “a
man in his study standing at a closed glass window opposite the fireplace,
looking out at his garden in the sunset. He is absorbed by the view of the
outside world. He does not visualize the interior of the room in which he
stands. As it becomes darker outside, however, images of the objects in the
room behind him can be seen reflected dimly in the window glass. For a time
he may see either the garden (if he gazes into the distance) or the reflection of
the room’s interior (if he focuses on the glass a few inches from his face).
Night falls, but the fire still burns brightly in the fireplace and illuminates the
room. The watcher now sees in the glass a vivid reflection of the interior of
the room behind him, which appears to be outside the window. This illusion
becomes dimmer as the fire dies down, and finally, when it is dark both
outside and within, nothing more is seen. If the fire flares up from time to
time, the visions in the glass reappear.” For West, “perceptual release”
explains both the hallucinations of the delirious and the sleeper’s dream. For
both to occur, there must be a decrease in strength of the inhibiting forces

controlling release of recorded precepts, along with sufficient preservation of
arousal to permit the discharge of perception-bearing circuits. With relative
sensory deprivation during sleep, as well as in sensory restriction
experiments, and perhaps in delirium, residual awareness no longer

competes with current awareness, and the perceptual traces are released and
re-experienced, sometimes in rearranged form. This would also explain the

effect of sensory overload which “jams the circuits.” In sleep, environmental
awareness diminishes, yet the cortex is functioning sufficiently to allow for

discharge of memory, altered by the censorship of the weakened sleeping ego.
Optimal conditions for hallucinations (or hallucinogens) would be disturbed
sensory input while maintaining or enhancing arousal. Similarly, sub-
hallucinogenic drug doses in the presence of sleep deprivation may also
produce hallucinations.
By inference, it would appear that delirious hallucinations are primarily
visual, for the same reason that dreams are. It is likely there is a greater
amount of visual memory, of unusual intensity. It seems less likely that

nonspecific visual stimuli, produced within the visual pathway’s anatomy
provides the raw material, awaiting only secondary elaboration.
The visual hallucinations themselves vary widely in duration, vividness,
complexity, and relationship to other modalities. Particularly vivid, intense
hallucinations are seen in withdrawal syndromes, and we have also seen
them in postcardiotomy delirium.
Course
The course of delirium is characterized by fluctuation and variation,
often in the presence of apparently constant organic findings. In many

instances, this may be due to variations in emotional and environmental
factors, although unrecognized physiological changes in brain metabolism
may also occur.
Symptoms may last from moments to weeks, but rarely longer than a
month. Postcardiotomy delirium generally lasts several days. In the series by
Morse et al. on postoperative delirium over half of the patients recovered

within a week, and three-quarters eventually recovered completely.
Termination can also be by death or by passing into a chronic dementia.
Together with Frank, we have shown the absence of permanent organic
deficits in patients with the postcardiotomy syndrome. Obviously the
likelihood of persistent organic deficiencies are dependent on the nature of
the physical factors contributing to the delirium.
During the acute phase, with the savage physical assault on brain
function, various release phenomena appear. Unchecked id or sadistic

superego are no longer counterbalanced. Lack of inhibition, or depression
and paranoia can emerge. Once again, the more acute the syndrome, the more
disruptive it is to the defensive apparatus, and more primitive defenses

appear. Given overwhelming catastrophe there is a great tendency to blame
the self or others. In Risk, the author hallucinates that the surgeon has
operated on her to “get a brilliant article.” A frequent delusion is that the staff
is out to kill the patient, which is also a projection of the rage felt for being
forced to endure pain and suffering.
Obviously, the premorbid personality determines the quality of release
phenomena. Obsessive-compulsive personalities with emphasis on

performance may be hit hard by their inability to meet self-set standards, and
be terrified by weakly opposed aggressive and sexual impulses. Soiling may
produce extreme humiliation. Active personalities may react with outward
blame and heightened vigilance. For each patient, the unique blend of
premorbid personality, organic insult and clinical setting will shape the
content and even appearance of delirium.
Examination of the Delirious Patient
The skilled interviewer can often detect reduction in the level of
cognition during a routine history. Woven into such an interview can be

questions about dates of onset, admission, length of time in the hospital, vital
statistics etc., so that considerable information can be gained without
exposing the patient to a humiliating quiz in which he knows few of the
answers. The exposure of deficits may hinder further cooperation and foster
antagonistic attitudes. Arithmetic calculations are often used in less obvious
cases. The use of serial sevens and repetition of digits backward has been
scored by Katz et al. It has value in obtaining sequential state measures, but
fails in deliria characterized by relatively clear cognition, but with perceptual

aberrations or place disorientation. In severe cases, the month and year may
provide an easily obtainable barometer. In answering questions, the delirious
patient may not only make errors, but may respond slowly, utilize concrete
aids, like his fingers, or try to conceal his deficit by attacking the question.
Differential Diagnosis
Delirium must be suspected in any behavioral or emotional problem in a
patient who is seriously ill or exposed to sensory or movement restriction.

Dementia or chronic organic brain syndrome is usually ruled out by a history
of long-standing intellectual deficit, along with a relative absence of agitation,
affect, and hallucinations. However, dementia may only be diagnosed when

the underlying acute precipitant is treated and cognitive deficits persist. Quite
common is the worsening of a mild dementia by an acute organic illness or
stress to create a delirium, just as the added insult of sodium amytal may
precipitate severe confusion in a mildly organic patient.
At the other extreme, delirium must be distinguished from purely
functional illness. The EEG can often answer such a dilemma. Intravenous
sodium amytal, judiciously given, can also be helpful in the differential

diagnosis since the patient with delirium will get worse. In a patient with a
functional disorder, this etiology will become more apparent. This test should
be given with great care in situations where the patient’s physical condition
can be compromised by its use. Most difficult is the clinical differentiation
between retarded delirium and retarded depression. The depressed patient
may complain of memory loss related to his lack of interest, difficulty in
concentrating, and need for self-abuse. However, the mental status should
reveal the absence of confusion. The hallucinating schizophrenic tends to be
younger and have primarily auditory hallucinations. Once again, the
sensorium will be clear. Dissociative patients tend to not know who they are,
a great rarity in delirium. They generally also have a model for their
symptoms, a history of previous hysterical symptomatology, and are in a

stressful situation to which the delirium-like symptom is a compromise
solution.
Incidence
As Reding and Daniel have pointed out, delirium is frequently missed

because of inadequate mental status examination, failure to notice nurses’
notes, difficulties in distinguishing between normal aging and pathology, and
insufficient use of the EEG. They also cite an overemphasis on
psychodynamics. There is no doubt that nonpsychiatrists often miss the

diagnosis. Stated most baldly by Hoaken, “On surgical wards . . . the last thing
of interest . . . is the patient’s general behavior and mental state.” In view of
these problems of diagnosis, the true incidence of delirium can only be
estimated. Select groups, such as cardiac surgery patients, have a high

incidence, and the presence of large numbers of such patients can skew a
sample. Nonetheless, Skoog reported a 15 percent incidence in patients
admitted to a Swedish hospital. As in certain other studies, women had a

greater susceptibility. Foreigners were particularly vulnerable probably
because of lack of social and linguistic contact. In 1938, Cobb and McDermott
made the same observation of a high incidence in foreigners, some of whom
lacked obvious physical explanations. Even then, they suggested loneliness
and strangeness as possibly causal factors. Lipowski, in reviewing the German

literature, cites the estimate of Bleuler et al. that 30 percent of the 20-70 year
old population will, within their lifetime, sustain an episode of delirium, and
that 5-10 percent of medical patients in a general hospital suffer from it. The
rate is clearly higher for patients over sixty years, where it may approach 50
percent. One estimate is that one-sixth of psychiatric consultations in the
general hospital are requested for organic brain syndrome.
Brain Pathophysiology
Although toxic factors are not the whole story of delirium, consistent
brain pathophysiological problems have been demonstrated in metabolic
encephalopathies. The brain’s problems in oxidative metabolism can be
replicated at altitudes over 12,000 ft. and at blood sugar levels below 60 mg.
percent. Posner has summarized the pertinent neurophysiology. For reasons
that are not well understood, cerebral oxygen uptake declines in proportion
to the severity of the metabolic brain disease. The normal brain receives 55
ml. of blood per minute, about 15 percent of the resting cardiac output. If the
flow falls, more oxygen and glucose are initially extracted. But if the oxygen
tension of cerebral tissues falls below 4 mm. Hg, unconsciousness is
inevitable. There is no cerebral storage of oxygen and within only six seconds
of deprivation, coma occurs. A four-minute interruption of oxygen supply
almost always causes irreversible damage, and after fifteen minutes virtually
all nerve cells are dead. The brain is less demanding for glucose, its only
physiological substrate. One hundred g. of brain utilizes 5.5 mg. glucose per
minute, 85 percent of which reacts with oxygen. There is a reserve of 2 g. of

glucose to allow 90 minutes of metabolism without irreversible damage.
In addition, the brain requires enzymes and cofactors (vitamins and

electrolytes) to function. It is believed that metabolic derangements such as
vitamin deficiency, electrolyte imbalance, and exogenous and endogenous
poisons operate by inhibition of the cofactors. Nonetheless, the precise

mechanism of uremic and hepatic coma, two of the most common metabolic
poisonings, are not even known. Although diminished oxygen uptake is a
biochemical common denominator, there is no proven anatomic one.

Moreover, there is even disagreement as to which area of the brain is most
vulnerable to metabolic insult. The traditional view was that the most
primitive neural structures were best preserved, and the most recent
phylogenetic acquisitions least protected. In this sequence, the cortex is

affected initially, then subcortical structures. Pathological studies of anoxia
and hypoglycemia support this view, as do animal studies where cortical
electrical activity disappears first. A more recent theory holds that the brain
stem reticular formation is most vulnerable and that cortical neurons stop
functioning when no longer stimulated from below. In some animal studies,
electrical transmission through the reticular formation ceases while the

cortical neurons are still able to receive other afferent input. Clinically, it
would seem that the cortex is first attacked as decline in cortical function
preceded alteration of consciousness. Posner concludes that regional issues

such as energy needs, blood supply, etc., may determine the point of
maximum vulnerability.
Electroencephalographic Findings
The normal EEG has an 8-13 cycle per second (cps) base frequency. The
degree of slowing from this baseline parallels the degree of dysfunction. In
metabolic disease bilateral synchronous bursts of 1-3 cps are superimposed
on a 5-7 cps background. This slowing is an extremely consistent finding, and
monitoring it allows for an accurate reading of the clinical state. Slowing
parallels worsening and acceleration improvement. Change is more
important than absolute values; an initially high-frequency alpha may fall into
a normal range with delirium. The EEG is not specific to any single etiology,
but is affected by the intensity and duration of the metabolic problem. Recent
advances in computer technology have allowed the study of evoked
responses. Anticholinergic drug-induced delirium has been associated with
abolition of visual response after rhythm, resembling those of sleep. Itil found
anticholinergic hallucinogens to produce EEG’s with a marked increase of
slow waves with superimposed high-frequency fast activity. Fast beta waves
were related to an increase in hallucinations. Studies of the EEG during REM
sleep may shed further light on the electrical manifestations of image
formation.
Of great theoretical significance is the discovery that sensory restriction
can produce EEG changes. This material has been summarized by Schultz.
Heron was able to show progressive slowing of the EEG and
dysynchronization of the alpha rhythm persisting for hours after a sensory
restriction experiment. There were noticeable EEG changes during

hallucinatory periods. Zubek et al. found less alpha activity during
hallucinations, as well as an excess of theta activity especially over the
temporal lobes. Later he demonstrated a mean decrease in occipital lobe

frequency, albeit a highly variable one. This variability may be related to
differential susceptibility to sensory restriction. Moreover, Zubek and
Wilgosh showed occipital lobe slowing following immobilization in a coffin-
like box without sensory restriction. In this connection, it was also shown that
the EEG slowing due to sensory restriction could be diminished if exercise
was permitted. Immobilization alone could also produce intellectual and
perceptual impairments.
Metabolic Disturbances in Delirium
All diseases that can disturb the brain’s homeostasis can produce
delirium. There is little specificity to any etiologic agent. Specificity would

have to be associated with a selective rather than general effect on the brain.
Sedative or alcohol withdrawal syndromes which produce extreme agitation
and florid hallucinations may be such an instance. The intensity is also related
to their acute onset, while chronic debilitating illness leads to a quieter

syndrome. It should be borne in mind that organic factors often coexist with
one another in producing delirium, and that their effect is modified by
psychological and environmental factors. An outline of the protean types of

disorders that can contribute to delirium is given in the following list.
Organic Causal Factors in Delirium
I. Intrinsic central nervous system (CNS) disease
A. Tumor
1) Primary
2) Secondary
A. Infections
1) Encephalitis
2) Abscess
3) Meningitis
4) Neurosyphilis
5) Fungal and protozoan
B. Epilepsy
C. Ischemic
1) Diffuse or multifocal blood vessel obstruction
2) Large-vessel disease
a) Thrombosis
b) Embolism
3) Intravascular coagulation
a) Collagen disease
b) SBE (subacute bacterial endocarditis)
D. Hypertensive encephalopathy
E. CNS bleeding
1) Subarachnoid
2) Subdural hematoma
3) Bleeding diathesis
a) Purpura
b) Clotting disturbance
c) Leukemia
F. Degenerative
1) Senile
2) Presenile
3) Metabolic errors
4) Demyelinating
II. Non-CNS vascular disorders
A. Hypoxia due to pulmonary disease
B. Hypoxia due to cardiac disease
1) Congestive heart failure
2) Arrhythmia including cardiac arrest and Stokes-Adams
3) Shock as with myocardial infarction
4) Valvular disease as with aortic stenosis
C. Reduced peripheral resistance
D. Disorders of blood volume and viscosity
1) Polycythemia
2) Cryo- and macroglobulimemia
E. Anemias and hemoglobinopathies
1) Pernicious anemia
2) Carbon monoxide
3) Methemoglobinemia
III. Non-CNS organic disease
A. Liver
B. Kidney
C. Lung
IV. Endocrine hypo- or hyperfunction
A. Thyroid-myxedema, thyrotoxicosis
B. Parathyroid: hypo- and hyperfunction
C. Adrenal: Addison’s and Cushing’s, pheochromocytoma
D. Pancreas: diabetes, hypoglycemia
E. Pituitary hypofunction
V. Ionic or Acid-base Imbalance
A. Water intoxication or dehydration
B. Hyper- and hyponatremia
C. Hyper- and hypokalemia
D. Hyper- and hypocalcemia
E. Hyper- and hypomagnesomia
F. Acidosis, metabolic or respiratory
VI. Infections
A. Acute, such as: pneumonia, typhoid, malaria, acute rheumatic

fever
B. Chronic
VII. Environment
A. Low-oxygen hypoxia
B. Starvation hypoglycemia
C. Vitamin deficiencies: thiamin, niacin, pyridoxine, B12, folic acid
D. Heat and electricity
E. Radiation
VIII. Exogenous Poisons
A. Medications
1) Sedatives, barbiturates, and other hypnotics
2) Minor tranquilizers: diazepam, chlordiazepoxide
3) Phenothiazines
4) Opiates
5) Anticholinergics
6) Tricyclic antidepressants
7) Alcohol
8) Anticonvulsants
9) Digitalis
10) Quinidine
11) Salicylates
12) L-Dopa
13) Penicillin
14) Steroids
B. Poisons
1) Methyl alcohol
2) Ethylene glycol
3) Organic solvents
4) Heavy metals
5) Organophosphorus insecticides
IX. Withdrawal syndromes
A. Alcohol
B. Sedatives and hypnotics
In tropical countries, special emphasis must be placed on

trypanosomiasis and malaria as causes of delirium. They may produce either
gross or localized disturbances in the sensorium or seemingly functional
syndromes. Trypanosomiasis, with its insidious course, may particularly lead
to loss of interest in work, avoidance of friends, and cyclothymia, before
proceeding to confusion, lethargy, and somnolence. Falciparum malaria
infections produce a more acute syndrome. Parasitized red cells with greater
adhesiveness and reduced deformability block central nervous system

capillaries, until the lumens are obliterated by vast numbers of parasites
(Figure 2-1). Characteristic changes can then be seen in anoxic neurons
(Figure 2-2). Later changes, with peripheral hemorrhage, including necrosis,

demyelination, and gliosis are shown in Figure 2-3). There is a danger,
however, that an erroneous causal connection is made when malarial
parasites are found in the blood of a delirious patient. Other causes of

delirium must be excluded.
It should be underscored that failure to recognize and treat the physical

causes of acute delirium may result in permanent brain damage.
Unrecognized, and hence untreated myxedema and pernicious anemia are

particularly tragic examples of this. The diagnosis of pernicious anemia may
be especially difficult when folic acid treatment prevents the characteristic

hematological picture from emerging, also emphasizing the lack of correlation
between the anemia itself and cerebral symptoms. The latter may be
produced by endarteritis leading to anoxia (Figure 2-4) and accompanied by

demyelination (Figure 2-5 )
Figure 2-1.
(top) Case of cerebral malaria due to Plasmodium falciparum.
Photomicrographs from unstained frozen sections, 120 to 200 microns
thick. The malarial pigment, which is contained in the vessels, outlines the
vascular pattern. Cerebellar angioarchitecture (low magnification),
(center) Section from a cerebral area (low magnification), showing the
difference in the vascular pattern in the cortex (right part of the picture)
and in the white matter (left part). In the white matter it is possible to
recognize a small hemorrhagic area, represented by a group of
extravasated dots of pigment, (bottom) Section from a cortical area
(medium magnification), revealing that the coloration is due to the
granules of malarial pigment contained in the capillaries. (Courtesy of Dr.
Silvano Arieti and the Archives of Neurology and Psychiatry.)
Figure 2-2 .
(upper left) Case of cerebral malaria due to Plasmodium falciparum. Betz’s
cell, surrounded by a capillary loaded with parasites. Notice the
dissolution of tigroid substance in the cytoplasm of the nerve cell, (upper
right) Betz’s cells, showing retrograde (axonal) degeneration. The nucleus
is displaced, and the tigroid substance is dissolved in the center of the cell
but preserved at the periphery. Notice, also, the large number of parasites
in the neighboring capillaries, (bottom) Ganglion cell of the motor area,
showing acute swelling. Nissl stain, high magnification. (Courtesy of Dr.
Silvano Arieti and the Archives of Neurology and Psychiatry.)
Figure 2-3.
(top) Case of cerebral malaria due to Plasmodium falciparum. Formation of
a pseudogranuloma. In a small subcortical hemorrhage, the red cells have
almost completely disappeared from the center of the area (only a few are
left in radial positions) but are still numerous at the periphery. Mallory
stain, medium magnification, (center) The red cells have disappeared from
the peripheral area also. This area appears edematous and of loose
consistency and shows proliferation of glial cells. Note also a central
capillary loaded with parasites. Giemsa stain, medium magnification,
(bottom) The Pseudogranuloma is now almost formed. At the center one
sees in cross section a capillary loaded with parasites. A necrotic central
area is surrounded by a peripheral cuffing consisting predominantly of
glial cells. Nissl stain, medium magnification. (Courtesy of Dr. Silvano
Arieti and the Archives of Neurology and Psychiatry.)
Figure 2-4.
Figure 2-4.
(upper left) Progressive stages of endoarteritis in brain of patient suffering

from psychosis accompanying pernicious anemia. Vascular walls
moderately thickened, (lower left) More advanced stage. Vascular lumen
conspicuously reduced, (upper right) The lumen of the vessel is
considerably narrowed. Recanalization has already taken place, (lower
right) Cortical capillary, the lumen of which is completely occluded. Nissl
stain. (Courtesy of Drs. Armando Ferraro, Silvano Arieti, and W. H. English
and the Journal of Neuropathology and Experimental Neurology.)
Figure 2-5.
Figure 2-5.
(top) Case of psychosis accompanying pernicious anemia. Nissl stain.

Typical Lichtheim’s plaque consisting of a central degenerated area
surrounded by a crown of glial nuclei, (lower left) Plaque showing two
acellular areas, (lower right) Plaque showing an elongated acellular area
which probably follows the coruse of a vessel. (Courtesy of Drs. Armando
Ferraro, Silvano Arieti, and W. H. English and the Journal of
Neuropathology and Experimental Neurology.)
Roads to Hallucinations and Cognitive Dysfunction
The general hospital provides natural experiments in which the
following conditions, that can cause delirium, are combined.
Causes of Perceptual and Cognitive Impairment
I. Organic insult
II. Sensory monotony
III. Sensory overload
IV. Sleep and dream deprivation
V. Immobilization
VI. Overwhelming anxiety
Sensory deprivation is believed to be responsible for the hallucinations
of sailors, explorers, and perhaps even religious figures. Numerous studies
have demonstrated the frequent development of hallucinations, impairment

of time sense, and impaired perceptual-motor performance following sensory
monotony. It is most effective when combined with immobilization, as in
total-immersion experiments. Similarly, sensory bombardment via
immersion in a geodesic dome with psychedelic light and sound can also
produce cognitive impairment, particularly in field-dependent subjects.
Subjects deprived of sleeping and dreaming also develop cognitive

dysfunction, at times with hallucinations. Hallucinations of a purely functional
nature arise when massive anxiety requires the use of primitive mechanisms
of denial and projection. In this regard, Arieti’s concept of the expectant
attitude is relevant. The paranoid listens to the environment expecting to

hear his own critical self-appraisal.
As we shall see, there are situations in the general hospital highly

conducive to delirium production. Each of them will be examined in turn.
However, virtually all patients are subjected to some of the etiologic factors. A
physical disease is invariably present. Patients are separated from their

familiar environment, family, and even their clothes, and placed in single
rooms fostering monotony, or in busy wards leading to overstimulation.

Hearing aids or glasses are misplaced or removed for fear of loss. The same
may also be true of television sets and radios. Physical symptoms or the
strange environment may interfere with sleep. Sedatives that can cloud
consciousness are prescribed for sleep or tranquilization and given in larger
doses if not initially successful. Anxiety is rampant and suspiciousness

regarding medical care is always possible. Margolis, has focused on the
violations of patient’s privacy in the ICU. Processions of doctors, nurses, aides,
volunteers, equipment mechanics, floor scrubbers, relatives, and friends may
troop through. They see the patient at his worst, his weakness exposed.
In the laboratory, subdelirium levels of one factor combined with
subdelirium levels of another can produce delirium. Safer duplicated West’s
finding with anticholinergic hallucinogens and sleep deprivation. Half of a

hallucinogenic dose of scopolamine plus one sleepless night was equivalent to
a full hallucinogenic dose.
In 1936, while investigating the delirium associated with a course of five
to ten hyperthermia treatments, Ebaugh et al. discovered that 43 percent of
delirium patients had only a single episode, 80 percent of which occurred
during the first induction of fever. The inescapable conclusion is that the
delirium was fostered by the initial anxiety.
Special Syndromes
A number of syndromes are associated with a high incidence of

delirium. Since they are of great theoretical, as well as clinical significance,
they will be examined in detail.
Eye Surgery
With the former practice of patching both eyes after cataract surgery,
sudden visual deprivation was imposed. This produced a delirium referred to
as the “black patch psychosis” which illustrates the interaction of
environmental and organic factors. Jackson has reviewed the extensive
literature in this area over the last eighty years.
Cataract patients tend to be old and already suffering from some
chronic brain impairment. Retinal detachment patients are younger, but have
a more acute illness and greater restriction of postoperative movement. Both
groups have high levels of anxiety about the possibility of blindness. Colman
in 1894, first reported postoperative hallucinations. In 1900, Posey reported
twenty-four cases of delirium in elderly patients with patched eyes. “The
delirium began with mental restlessness and rapidly progressed to
hallucinations and ideas of persecution. Delirium developed during the
second day for eight patients; the third day for six; and the fourth day for
two.” This delayed response supports the idea that the restriction operates
gradually to contribute to the delirium. Moreover, the eye surgery, done

under local anesthesia, does not provide a fresh organic insult to the brain. In
1913 Parker reviewed the charts of a large series of cataract extractions.
Patients were described as “restless, maniacal, suspicious, uncontrollable, and

disoriented; getting out of bed; talking incoherently and removing their
patches” (maybe not so unwisely!). Once again the delirium began after a
latent interval from one to six days postoperatively, the same range as in most
postsurgical delirium. A report in 1917 by Brownell described the syndrome
as lasting a day or two.
Our understanding of etiology is enhanced by the dramatic discovery
that, despite the covering of both eyes, the delirium was more apt to begin
and/or worsen at night. Weisman and Hackett eloquently wrote “. . . night . . .
is the time when a hush falls on the ward, and auditory cues, which may have
been responsible for alerting and orienting the patient during the day are
replaced by silence with an occasional whispered conversation and the soft

sporadic sounds of the night. Under these circumstances . . .
misinterpretations may become delusions and anxiety may become panic.”
Added to this is the mystique of the night symbolizing danger and

vulnerability, and increasing the anxiety.
Coles and Linn suggest trial patching prior to surgery if it is absolutely
required. Delirium could be predicted when the EEG was abnormal and the
sodium amytal test positive. In high-risk patients, surgical techniques may
have to be modified, keeping in mind the patient’s likelihood of
noncooperation. Early mobilization and stimulation of the patient, as might

be obtained in a two- to four-bed room, were recommended. Ziskind et al
reported the highest delirium incidence in the non-English speaking, the deaf,
alcoholics, or those with obvious brain damage. Jackson noted the great
variability in insight, and that patches were most frequently removed by
patients at night. It seems clear that bilateral patching should be avoided and
that removal of patches may have dramatic therapeutic effects.
Respirator Delirium
The phenomena of respirator-induced delirium was described by
Holland and Coles in 1955 following an outbreak of poliomyelitis. Forty
percent of bulbar polio patients developed delirium beginning from one to

ten days after entering the respirator. Hallucinations and delusions were of a
pleasurable nature, frequently involving motion and travel. The emotional
stress was enormous. Patients feared that they would be unable to summon
help, since they could not close their tracheotomies should there be a power
failure or the plug be pulled accidentally. They faced the prospect of possibly
permanent paralysis or even death. As time in the tank progressed, patients
became depressed, finally showing hostility and anxiety with weaning from
the respirator. Disorientation and confusion were also noticed.
Mendelsohn and Foley provide an explanation of this syndrome. The
hallucinations occurred in a quasi-twilight state. They disappeared when the
patients’ limbs were manipulated or when someone spoke to them about
their real surroundings. They could not see their bodies, their vision was
restricted, hearing was impaired due to the repetitious motor sound, and
mobility was restricted by the paralysis and tank confinement.
Extending their clinical observations, seventeen normal control subjects

were put in the respirator. Only five could remain in it longer than thirty-six
hours. Eight sustained hallucinations and all were unable to concentrate or
judge time. Four had to terminate abruptly due to severe anxiety. Moreover,
the subjects were not febrile, and they knew they could get out, walk, and
breathe at any time.
Mendelsohn et al. structurally analyzed the hallucinations. In general,

hallucinations are wish-fulfilling or defensive. The latter tend to be auditory,
the former multisensory. They are facilitated by great anxiety and need in
schizophrenia, or in the nonschizophrenic subjected to enormous stress. The
polio patients’ hallucinations had both wish-fulfilling and defensive
characteristics. Movement motifs were enhanced by the vibration of the
pump motor. Hallucinations were extremely colorful, three dimensional, and
generally pleasant. They served the wish of being able to move again, yet
reality intruded to the extent that tank-type structures followed them along
as they anticipated their future lives.
The tank-respirator syndrome is now observed in patients with chronic
lung disease, such as kyphoscoliosis. It is also seen in neurological diseases,
especially if they combine paralysis with decreased sensation. Intermittent
removal from the tank, if possible, is recommended.
Cardiac Surgery
In 1964, Blachly, Egerton and Kornfeld et al. described a syndrome
occurring in the open heart recovery room (OHRR), three to five days
postoperatively. Logically, it was named postcardiotomy delirium. It often
began with illusions based on sounds created by the machinery in the room,
and with frequent proprioceptive distortions such as a rocking or floating

sensation. Patients would become briefly, or persistently, disoriented.
Delusions were common, sometimes with a frank paranoid flavor. One patient
thought a record player had been placed under her bed to torture her. She
also hallucinated the voices of absent family members. Like most patients, she
improved after transfer from the OHRR. Thirty-eight percent of Kornfeld
patients were adjudged delirious by chart review, and fully seventy percent of
those followed throughout the surgical experience had delirium symptoms.
Kornfeld confirmed Blachly’s finding that degree of preoperative illness
predisposed to delirium. Also confirmed was Blachly’s finding of a higher
incidence in double-valve replacement cases, and an association between

prolonged cardiopulmonary bypass time and delirium.
Kornfeld reasoned that the lucid interval of several days postoperatively
suggested that postoperative factors played a role in delirium causation.
Similarities were noted between the OHRR experience and sleep and sensory
deprivation studies. It was postulated that the intense anxiety the cardiac
surgery patient experienced might also play a part.
A number of recommendations were made to lessen delirium incidence
and severity. Uninterrupted sleep was to be encouraged. Individual rooms
were suggested to minimize patients waking each other or witnessing

anxiety-provoking emergencies. Less obtrusive monitoring equipment was
advocated to minimize sensory monotony and anxiety. Increased mobility
with early removal of wires and tubes was recommended. The monotonous
noise of oxygen, cooling, and air-conditioning apparatus was to be minimized.
Television sets, radios, clocks, and calendars were to be supplied to increase
stimuli and provide reality cueing.
A more detailed longitudinal study reported in 197030 of 142 survivors
showed a decrease in delirium incidence since the early report. Now only 24
percent experienced the delirium after a lucid interval, while 9 percent had
evidence of an organic mental syndrome upon awakening from anesthesia.
These latter patients were hypoactive and tended to lack florid
symptomatology. They tended to have severe organic illnesses.
The lucid interval delirium group was intensively studied. Organic
factors clearly played a role, since advanced age, and severity of pre- and
postoperative illness, and time on the cardiopulmonary bypass were all
correlated significantly with delirium.
An effort was made in the 1970s to understand the reduced incidence.

Decreased bypass time appeared to play a role, as within each operative
category reduction in incidence paralleled the varying reduction in bypass
time. It was also postulated that the adopted suggestions with regard to sleep
and environment, and the less panicky attitude of patients and staff might
also be responsible. Other investigators confirmed the role of social-
environmental factors in delirium incidence. Lazarus and Hagens studied two
groups undergoing open-heart surgery by the same surgeon at different

hospitals. In one hospital, modifications designed to lessen anxiety, sensory
monotony, and sleep deprivation halved the incidence of delirium. Layne and
Yudofsky reported that patients who did not express preoperative anxiety
had double the incidence of delirium of anxiety expressors. It seems clear that
pre- and postoperative emotional ventilation would play a prophylactic role.
This view was further confirmed when a member of our research team
reviewed the charts of patients seen by the research group and a comparable
group that had not been seen. The interviewed group had half the delirium
incidence of the unseen group.
The present authors have undertaken a detailed study of the personality
and psychological factors associated with postcardiotomy delirium. Organic
factors were once again found to be significantly related. A new finding, based
on statistically significant psychological test reports and suggestive
psychiatric ratings, was that patients characterized by dominance,
aggressivity, confidence, and an active orientation seemed more vulnerable to

delirium. It was reasoned that for such individuals, the passive, immobilized
patient role in the OHRR would be more stressful than it would be for more
passive patients. For the active group, the OHRR experience is an exact
opposite to their usual functioning and produces intense conflicts. Denying

anxiety, this group would be unable to benefit from preoperative
psychological ventilation which might reduce postoperative anger and
paranoia.
All these factors, it should be emphasized, complement rather than

conflict with organic risk factors. Other investigators have presented new
evidence confirming the importance of organic factors. Tufo has shown that
operative hypotension is associated with postoperative organicity. Kimball

has emphasized the significance of previous central nervous system insult.
Willner et al. have found organically based disturbance of analogy reasoning

predictive of delirium.
Our work has shown a high incidence of delirium, approaching 40
percent, in patients undergoing saphenous vein coronary artery bypass

surgery. This is believed to be related to relatively lengthy bypass times and
possibly the active-dominant character of the sample. These patients often
manifest the time urgency and aggressivity characteristically associated with
early onset of coronary disease.
General Surgery
The most straightforward study suggesting that psychological factors
play a role in general surgical delirium comes from two small hospitals in El
Dorado, Arkansas. The two hospitals have the same bed capacity and medical
staff, and accept random admissions. One of the ICUs is windowless, the other
has windows. Controlled factors were age, type of procedure, and
postoperative temperature. There were no differences between the two
groups. Yet the windowless ICU had a 40 percent delirium incidence as
compared with 18 percent in the windowed unit. Although it can be argued
that there is an unidentified causal difference, it would seem that a room
without windows during the critical immediate postoperative period is

deleterious.
Comprehensive information concerning general surgical delirium is
found in the work of Morse et al. Probably related to the excellent medical
and surgical care at the Mayo Clinic, the overall operative delirium rate was
only 0.5 percent. Sixty delirious patients, equally divided between retarded
and hyperactive forms were compared with a control group, matched for type
of operation, age, and sex. Twenty-two percent of the delirium group had
open-heart surgery, 18 percent hip or other fractures, 12 percent spinal
fusion, 10 percent colectomy; the remainder had miscellaneous surgery.
Delirium occurred from the third to the seventh day postoperatively.

Delusions were found in two-thirds of the cases. As would be expected, 55
percent of the delirium patients were over sixty. Age over sixty and duration
over one week were bad prognostic signs for recovery.
Abundant support was obtained for the general theory that organic,
social-environmental, and emotional factors combine to cause delirium. To be
sure, organic physical factors were extremely important. All parameters
studied were more likely to be abnormal in the delirium group, and the
following significantly so: abnormal EKG (electrocardiogram), albuminuria,

alkalosis, anemia, azotemia, hypochloremia, hypokalemia, hyponatremia, and
leukocytosis. The delirium group had significantly more cardiac failure,
cardiovascular disease, infection, drug or alcohol intoxication or withdrawal,

history of organic brain syndrome, preoperative disorientation, operative
procedure longer than four hours, emergency operation, postoperative

complications, and use of more than five drugs postoperatively. It should be
noted, however, that the abnormalities were not confined to the delirium
group.
Yet nonorganic factors also correlated significantly with delirium.
Morbid preoperative expectation was associated with a 33 percent delirium
incidence as compared with 3 percent not showing pessimism. Sensory
distortion, caused by visual disorders or partial deafness, was also much
more common in the delirium group, as was a history of more than two
previous operations. Denial of preoperative fear was associated with a lower
incidence of delirium.
Other, purely psychiatric factors were also significantly correlated with
delirium: a history of alcoholism or depression, a family history of psychosis,
functional GI (gastrointestinal) disturbance, insomnia, paranoid personality
or psychosis, history of previous postoperative psychosis, history of
psychiatric treatment, or retirement problems. Patients of the highest social
class seemed less susceptible to delirium. Clinical vignettes also supported

the psychobiological thesis. In one case, delirium cleared when a misplaced
hearing aid was found; in another, it worsened with a son’s departure.
Renal Disease
With the development of hemodialysis and transplantation surgery,
there has been a renewal of interest in the previously largely academic
question of neuropsychological disorders in end-stage renal failure.
Untreated, the mental changes show gradual onset and hence tend to less
dramatic manifestations. The usual sequence of events for chronic delirium is
followed. Difficulty in concentration and memory change appear associated
initially with normal or minimally changed EEG’s. This may long precede the
development of azotemia. Prodromal symptoms are followed by irritability,
labile affect, manifest disorientation and confusion, with delusions and

hallucinations. With the neurotoxic crumbling of the personality, dietary
indiscretions increase, creating a vicious cycle. Periods of lucidity decline and
torpor is common as myoclonus and fasciculations, asterixis and convulsions
develop. Lassitude passes into stupor and then coma, usually with heightened
muscle tone. Any improvement occurs in reverse order to the loss.
EEG changes parallel the clinical disorder, with slowing usually
accompanying BUN (blood urea nitrogen) levels over 60 mg. percent. Initially
there is slight slowing with a tendency to disorganization of alpha activity,

followed by progressive slowing and disorganization with paroxysms of
greater slowness, leading to diffuse slowing and spiking. Tyler claims that the
EEG is similar, but not identical to those of hepatic decompensation. Kiley and
Hines noted that wave frequency becomes slower before obvious electrolyte
changes. Some photic driving, as in a drug withdrawal syndrome, is seen

particularly during recovery phases, raising the provocative question of a
withdrawal syndrome to an unidentified toxin. Of course, no single electrolyte

correlates with EEG abnormalities, but rapid shifts in electrolytes cause
worsening of the EEG and the clinical state. Klinger reports photogenic
abnormal occipital sharp waves and Lossky-Nekhorocheff et al. showed
disappearance of the alpha rhythm and disturbance of the arresting reaction.
Complete records of abnormal slow waves preceded imminent death. Eighty
percent of irrational confused patients had abnormally slow frequencies, and

if 40 percent of the record is abnormally slow, psychological testing would
show cognitive impairment. It should be noted that frequently coexisting
diseases, such as anemia and hypertension, can also affect the EEG. Yet the
EEG can be used as an indicator for dialysis when there is slowing to less than
6 cps.
But is the treatment any better than the disease? The life of a dialysis
patient is dominated by conflicts about the value of staying alive. In the series
by Foster, Cohn et al. almost 50 percent of the dialysis patients made suicidal
threats. Interestingly, three of the four patients who made attempts
succumbed to their disease. Survival was related to physical factors, such as
low mean BUN, but also to Catholicism, the presence of parents, and
indifference to the fate of other dialysis patients.
Abram has greatly expanded our knowledge of the inner life of the
chronic dialysis patient. He classifies the uremic syndrome into the following
categories: asthenic, restless, hallucinating, schizophreniform, depressed,
manic, and paranoid. The asthenic category predominates. In a series of

thirty-eight patients, psychological testing revealed evidence of organicity in
all, with poor visual-motor coordination, and difficulty in nonverbal
abstraction and attention. Few patients had acute hyperactive episodes, and
when they did occur it was usually during the first episode of uremia, as in the
hyperthermia study, again suggesting multifactorial causation.
The initial adjustment to dialysis is euphoria as toxic apathy clears.
Anxiety appears at about the third to fifth dialyses, followed by depression as

the problems of the treatment become undeniable. Conflicts about
dependency and independence emerge and psychotherapy is frequently
indicated. From the third to the twelfth month the issue of whether life is
worth living becomes paramount. Viederman has well described these
problems. The patient has surrendered his autonomy, his clothes are
removed, privacy is denied, intake and elimination become subject to the

orders of others. There is no dietary freedom. Pain and exposure are
experienced two or three times a week for five to eight hours a day tied to a
machine. The dialysis bath comes to symbolize the womb and birth, and a
love-hate relationship develops with the machine. It becomes the frustrating
bad mother, breaking down frequently with ruptured coils and causing
weakness, cramps, and hypotension. Such experiences resonate with early
maternal encounters. The content of a delirium will clearly reflect this. One of
Viederman’s patients had the delusion she had been cured by God, and no
longer needed dialysis. Another had the somatic delusion of bodily
disintegration with holes in the skin.
According to Abram, life with the machine preoccupies the patient. He

becomes a compulsive gambler knowing the only roulette wheel in town is
rigged against him, but unable to stop using it. He fantasies or threatens to cut
his shunt, the weakest link, the umbilical cord to the machine. He frequently
imagines himself a Frankenstein and in his drawings sees himself as
increasingly resembling a dialyzer. He has become a semiartificial man, a
zombie, the living dead. In fantasy or delusion, mechanical monsters with
malevolent intent are after him. Even the nurses dream of the ubiquitous
machine and of being dialyzed. They develop psychosomatic illnesses and
there is a rapid staff turnover.
Intense relationships develop between patients and staff in this setting.
Male patients seeing themselves as castrated may exhibit themselves to the
nurses. Particularly where transplantation is considered, patients have great
difficulty in expressing anger to the staff for fear of being labelled

noncooperative and excluded from the hoped-for miracle surgery. In addition,
intense conflicts are experienced concerning family members who do or do
not offer their kidneys, and over assuming the identity of the donor.
Therefore, both the precipitation and content of any delirious episode must
be viewed in the widest possible context.
Hepatic Coma
The delirium associated with liver disease is in many ways similar to
that of uremia. In both, we witness a final chapter in a long process resulting

in a complex metabolic poisoning. Delirium in liver disease can be divided
into two groups, that of hepatic failure, and of portal shunting to the systemic
circulation.
The treatment of liver failure, despite the recent use of L-Dopa, leaves
much to be desired. There is no hepatic dialysis and symptoms tend to be

progressive. A prodromal syndrome is followed by impending coma, often
with asterixis (liver flap), and with characteristic, if not specific, EEG findings.
There are paroxysms of bilaterally symmetrical high-voltage delta waves 1½

—3 cps, along with relatively normal alpha waves.
Organic brain syndromes in patients with liver disease need not be

hepatic coma. Delirium can also be caused by anoxia from anemia following
gastrointestinal bleeding; central nervous system bleeding caused by a
clotting diathesis or head trauma, especially in the alcoholic; inadequately
metabolized sedatives or tranquilizers; and the effects of alcohol or its

withdrawal.
The differentiation between delirium tremens (DT) and hepatic coma is
particularly important since sedative-replacement therapy can be lethal for
the impending hepatic coma patient. The DT’s patient will characteristically
have abstained from alcohol one to three days before the appearance of
symptoms, be more alert, aggressive, and have more vivid hallucinations. His
tremor will be coarse and rhythmic. The chronic liver-disease patient, on the
other hand, is hypoactive, tends not to have intense hallucinations, and has an
irregular and flapping tremor.
Portal-systemic encephalopathy is the term applied to delirium caused
by portal shunting, which may be congenital or surgically acquired. It can be
produced with or without accompanying liver disease. Clinically it is similar

to impending hepatic coma, although at times there may be unique elements.
It has a chronic course with recurrent episodes of stupor or coma. Patients
may also manifest other neurological signs and symptoms as the illness
progresses. These may become irreversible. These patients can mistakenly be
thought to be taking excessive quantities of sedatives or tranquilizers. They
often suffer from headaches and the analgesics taken for their relief can be
inadequately metabolized, complicating the picture further. The drowsy

periods may follow meals with too much nitrogen content, since these
patients are particularly sensitive to nitrogenous substances. The rigorous
need for a protein-free intake may create psychological problems. This

syndrome has been attributed to the introduction of intestinal absorption
products directly into the systemic circulation. The blood ammonium is
usually raised, but it does not always correlate with the neurological state.
Burn Patients
The psychiatric aspects of extensive burn patients have been largely
ignored. Yet a third of the patients with significant burns may develop
delirium. Half of the delirium patients were hallucinating and thrashing, half
were somnolent. The extensiveness of the burn and its associated metabolic
derangements were obviously related to delirium causation. Premorbid
psychopathology was also implicated. It would seem that sensory restriction
may also play a role with limited mobility and impaired sensory input.
Certainly, massive anxiety would be mobilized by the traumatic event and the
threat of disfigurement and death.
Intensive Care Units
The ICU may reproduce many of the etiological factors in delirium. The
patients are quite sick and vulnerable, and even if delirium is not caused,
environmental factors may add to agitation, anxiety, and depression. The

cardiac care unit is similar in many ways to the OHRR. There are intravenous
(IV) catheters, electrocardiogram (EKG) cables, flashing EKG oscilloscopes
with bell alarms (with inevitable false alarms), and an omnipresent
defibrillator. A cardiac arrest brings a stampede of house officers. Parker and
Hodge have reported delirium in these units which they attribute to sensory
monotony. On the other hand, Hackett and Cassem did not find significant
psychopathology. It should be noted that the units vary greatly in

environment and personnel. In some converted units there is only curtain
separation, while newly constructed units have cubicles and concealed
monitoring equipment. The number of patients in a unit also varies. The
observation of death and complications in other patients can be particularly

distressing with predictable autonomic reactions, which could not come at a
worse time. Even patients who deny anxiety related to another patient’s
death would prefer to be in private rooms.
Caution should be used in applying the term ICU syndrome to delirium

in this setting. These patients are severely medically ill, or they would not be
there. They are also receiving complex medical regimens. Although we should
be aware of environmental factors, our nonpsychiatric colleagues must be

urged to explore all possible medical causes for delirium before invoking a
purely environmental explanation.
Departure from ICU’s can also be traumatic. It is frequently abrupt, and

viewed as a rejection with ensuing cardiovascular problems related to
increased catecholamine excretion. Symptoms akin to traumatic neurosis can

be produced which manifest themselves with delayed insomnia and
nightmares. Patients frequently are discharged from the units without
adequate recommendations to minimize over- and underactivity.
Treatment
The multifactorial causation of delirium requires a multifactorial
therapy. The role of psychic factors does not diminish in the slightest the need
for correction of underlying physical abnormalities, which may be brain- and
lifesaving. Delirium is a medical emergency; the brain cannot wait. Not only
should specific factors related to illnesses and medications be sought, but the
general physical condition of the patient, his hemoglobin level, hydration, and
nutrition must all be considered. Osier’s rule of 1892 still applies, “procure
sleep and support the strength.” The consulting psychiatrist often finds that
the patient with delirium has already been inappropriately treated with a
minor tranquilizer or barbiturate. Indeed, the most common recommendation
is the withdrawal of barbiturates or minor tranquilizers and substitution by
phenothiazines. Barbiturates and minor tranquilizers are only indicated in
withdrawal syndromes, and may worsen or precipitate a delirium. On the

other hand, chlorpromazine is particularly useful. It should be given 25 mgs.
intramuscularly, and repeated as needed. Usually 25 mg. IM (intramuscular),
or 50 to 100 mg. by mouth every four to six hours is sufficient. A standing

order, to be given when the patient is awake, is generally preferable to
awaiting severe symptoms. If excessive somnolence is produced, a less
sedating phenothiazine, such as thioridazine or trifluoperazine, can be
substituted for part or all of the dosage. The drugs have a potent
antipsychotic effect, and provide “chemical restraint” which is far superior to

physical. It may be necessary to assuage the undue fear internists and
surgeons have of these medications causing hepatitis and hypotension.
Generally the benefits far outweigh the risk. However, a greater risk is that
effective symptomatic treatment may dissuade the referring physician from
vigorously pursuing the etiology of the delirium once behavioral problems
have diminished.
Prevention and therapy should also include minimizing sleep
interruption and sensory restriction or overload. An overly sterile,

monotonous, instrument-laden hospital room provides a blank screen upon
which the patient can project his fantasies. Immobilization is also unnatural
and should be avoided. Familiar figures from the patient’s life should be
available to him as much as is feasible. Stays in OHRRs or ICUs should be as
brief as possible. The staff should be helped to provide a warm, trusting
relationship.
Psychotherapy visits should be brief and frequent. Recognizing the
precarious state of integration of these patients, efforts should be made at

support and ego enhancement, rather than at exposing deficits. Efforts should
be made to provide cueing, and to reduce the harsh criticisms of performance
failures. The psychiatrist must convey that he understands what the patient is
experiencing. Patients should be told that they have a reversible condition for
which there is appropriate treatment. They can be reassured that there is a

specific, usually correctable stress, and that they are not “going crazy.” They
should be encouraged to report unusual experiences to the staff.
Encouragement can be provided as recovery begins. After recovery, patients
should be given the opportunity to understand and integrate their experience.
Bibliography
Abram, H. S. “The Psychiatrist, the Treatment of Chronic Renal Failure and the Prolongation of
Life 1,” Am. J. Psychiatry, 124 (1968), 1351-1357.
_____. “The Prosthetic Man,” Compr. Psychiatry, 11 (1970), 475-481.
Adams, R. D. and M. Victor. “Delirium and Other Confusional States and Korsakoff’s Amnestic
Syndrome,” in M. W. Wintrobe et al., eds., Harrisons Textbook of Medicine, pp. 185-
193. New York: McGraw-Hill, 1970.
Andreasen, N. C., R. Noyes et al. “Management of Emotional Reactions in Seriously Burned

Adults,” N. Engl. J. Med., 286 (1972), 65-69.
Arieti, S. “Histopathologic Changes in Cerebral Malaria and Their Relation to Psychotic Sequels,”
Arch. Neurol. Psychiatry, 56 (1946), 79.
Blachly, P. H. and A. Starr. “Post-cardiotomy Delirium,” Am. J. Psychiatry, 121 (1964), 371-375.
Bleuler, M., J. Willi et al. Akute Psychische Begleiterscheinungen koerperlicher Krankheiten.

Stuttgart: Thieme, 1966.
Brownell, M. E. “Cataract Deliriums. A Complete Report of the Cases of Cataract Delirium
Occurring in the Ophthalmologic Clinic of the University of Michigan Between the
Years 1904 and 1917,” J. Mich. State Med. Assoc., 16 (1917), 282-286.
Cobb, S. and N. T. McDermott. “Clinic of Doctors Cobb and McDermott,” Med. Clin. North Am.,
(1938), 569-576.
Coles, R. S. and L. Linn. “Behavior Disturbances Related to Cataract Extraction,” Eye, Ear, Nose,
Throat Monthly, 35 (1956), 111-113.
Colman, W. S. “Hallucinations in the Sane, Associated with Local Organic Disease of the Sensory
Organs, etc.,” Br. Med. J., 1 (1894), 1015-1017.
Davidson, E. A. and P. Solomon. “The Differentiation of Delirium Tremens from Impending

Hepatic Coma and DT’s,” J. Ment. Sci., 104 (1958), 226-333.
Ebaugh, F. G., C. H. Barnacle et al. “Delirious Episodes Associated with Artificial Fever: A Study of
Two Hundred Cases,” Am. J. Psychiatry, 93 (1936), 191-217.
Egerton, N. and J. H. Kay. “Psychological Disturbances Associated with Open-Heart Surgery,” Br. J.
Psychiatry, 110 (1964), 433-439.
Engel, G. L. and J. Romano. “Delirium, a Syndrome of Cerebral Insufficiency,” J. Chronic Dis., 9

(1959), 260-277.
Evarts, E. V. “A Neurophysiologic Theory of Hallucinations,” in L. J. West, ed., Hallucinations, pp. 1-

14. New York: Grune & Stratton, 1962.
Ferraro, A., S. Arieti, and W. H. English. “Cerebral Changes in the Course of Pernicious Anemia and
Their Relationship to Psychic Symptoms,” J. Neuropathol. Exp. Neurol., 4 (1945),
217.
Fischer, J. E. and R. J. Baldessarini. “False Neurotransmitters and Hepatic Failure,” Lancet, 2

(1971), 75-79.
Foley, J. M., C. W. Watson et al. “Significance of EEG Changes in Hepatic Coma,” Trans. Am. Neurol.
Assoc., 75 (1950), 61.
Foster, F. G., G. L. Cohn et al. “Psychobiologic Factors and Individual Survival on Clinical Renal
Hemodialysis, a Two Year Follow-Up 1,” Psychosom. Med., 35, (1973), 64-82.
Frank, K. A., S. S. Heller et al. “Long-Term Effects of Open-Heart Surgery on Intellectual

Functioning,” J. Thorac. Cardiovasc. Surgery, 64 (1972), 811-815.
Frazier, J. G. The Golden Bough, abr. ed., New York: MacMillan, 1951.
Freud, S. (1897) “Letter to Fliess,” Number 69, in J. Strachey, ed., Standard Edition, Vol. 1, pp. 259-
260. London: Hogarth, 1966.
_____. (1900) The Interpretation of Dreams in J. Strachey, ed., Standard Edition, Vol.
London: Hogarth, 1953.
_____. (1910) “Leonardo da Vinci and a Memory of His Childhood,” in J. Strachey, ed., Standard
Edition, Vol. 11, pp. 63-137. London: Hogarth, 1957.
Gottschalk, C. A., J. L. Haer et al. “Effect of Sensory Overload on Psychological State Changes in
Social Alienation, Personal Disorganization and Cognitive-Intellectual Impairment,”
Arch. Gen. Psychiatry, 27 (1972), 451-457.
Hackett, T. P., N. H. Cassem et al. “The Coronary Care Unit, an Appraisal of Its Psychological
Hazards,” N. Engl. J. Med., 279 (1968), 1365-1370.
Hackett, T. P. and A. D. Weisman. “Psychiatric Management of Operative Syndromes II.

Psychodynamic Factors in Formulation and Management,” Psychosom. Med., 22
(1960), 356-372.
Hankoff, L. D. “Ancient Descriptions of Organic Brain Syndrome: the ‘Kordiakos’ of the Talmud,”
Am. J. Psychiatry, 129 (1972), 233-236.
Heller, S. S., K. A. Frank et al. “Psychiatric Complications of Open-Heart Surgery: a Re-
Examination,” N. Engl. J. Med., 283 (1970), 1015-1020.
Henry, D. W. and A. M. Mann. “Diagnosis and Treatment of Delirium,” J. Can. Med. Assoc., 93
(1965), 1156-1166.
Heron, W. “Cognitive and Physiological Effects of Perceptual Isolation,” in P. Solomon et al., eds.,
Sensory Deprivation. Cambridge, Mass.: Harvard University Press, 1961.
Hoaken, P. “Discussion of R. M. Morse, and E. M. Linin, ‘Anatomy of a Delirium’,” Am. J. Psychiatry,

128 (1971), 115.
Holland, J. C. and M. R. Coles. “Neuropsychiatric Aspects of Acute Poliomyelitis,” Am. J. Psychiatry,

114 (1957), 54-63.
Itil, T. and M. Fink. “Anticholinergic Drug-Induced Delirium, Experimental Modification,

Quantitative EEG and Behavioral Correlations,” J. New. Ment. Dis., 143 (1966), 492-
507.
Jackson, C. W., Jr. “Clinical Sensory Deprivation: a Review of Hospitalized Eye Surgery Patients,” in
J. P. Zubek, ed., Sensory Deprivation: Fifteen Years of Research. New York: Appleton-
Century-Crofts, 1969.
Johnson, M. H. “Drugs of Choice in Confusional States,” Med. Times, 100 (1972), 92-99.
Kaplan, D. “Emotional Reaction of Patients on Chronic Hemodialysis,” Psychosom. Med., 30 (1968),

521-533.
Katz, N. M., D. P. Agle et al. “Delirium in Surgical Patients under Intensive Care, Utility of Mental
Status Examination,” Arch. Surg., 104 (1972), 310-313.
Kiley, J. and O. Hines. “Electroencephalographic Evaluation of Uremia,” Arch. Intern. Med., 116
(1965), 67-73.
Kimball, C. P. “The Experience of Open-Heart Surgery III: Toward a Definition and Understanding
of Post-Cardiotomy Delirium,” Arch. Gen. Psychiatry, 27 (1972), 57-63.
Klein, R. F., V. S. Kliner et al. “Transfer from a Coronary Care Unit,” Arch. Intern. Med., 122 (1968),
104-108.
Klinger, M. “EEG Observations in Uremia,” Electroencephalogr. Clin. Neurophysiol., 6 (1954). 519.
Kolb, L. C. Modern Clinical Psychiatry. Philadelphia: Saunders, 1973.
Kornfeld, D. S. “Psychiatric Problems of an Intensive Care Unit,” Med. Clin. North Am., 55 (1971),
1353-1363.
_____. “Psychiatric Aspects of Liver Disease,” in A. Linder, ed., Emotional Factors in Gastrointestinal
Disease, pp. 166—181. Amsterdam: Excerpta Medica, 1974.
Kornfeld, D. S., S. Zimberg et al. “Psychiatric Complications of Open-Heart Surgery,” N. Engl. J.

Med., 273 (1965), 287-292.
Layne, O. L. and S. C. Yudofsky. “Post-Operative Psychosis in Cardiotomy Patients,” N. Engl. J. Med.,

284 (1971), 518-520.
Lazarus, H. R. and J. H. Hagens. “Prevention of Psychosis Following Open-Heart Surgery,” Am. J.

Psychiatry, 124 (1968), 1190-1195.
Lipowski, Z. J. “Delirium, Clouding of Consciousness and Confusion,” J. Nerv. Ment. Dis., 145
(1967), 227-255.
Lossky-Nekhorocheff, I., J. L. Lerique-Koechlin et al. “EEG dans les Anuries Aigues

Hyperazoteniques,” Rev. Neurol., 100 (1959), 317.
Mackenzie, R. Risk. New York: Viking, 1970.
Margolis, A. J. “Post-Operative Psychosis in the Intensive Care Unit,” Comp. Psychiatry, 8 (1967),
227-232.
Mendelsohn, J. and J. Foley. “An Abnormality of Mental Function Affecting Patients with
Poliomyelitis in a Tank-Type Respirator,” Trans. Am. Neurol. Assoc., 8 (1956), 134-
138.
Mendelsohn, J., P. Solomon et al. “Hallucinations in Poliomyelitis Patients During Treatment in a

Respirator,” J. Nerv. Ment. Dis., 12 (1958), 421-428.
Morse, R. M. “Post-Operative Delirium: A Syndrome of Multiple Causation,” Psychosomatics, 11

(1970), 164-168.
Morse, R. M. and E. M. Litin. “Post-Operative Delirium: a Study of Etiologic Factors,” Am. J.

Psychiatry, 126 (1969), 388-395.
_____. “Anatomy of a Delirium,” Am. J. Psychiatry, 128 (1971), 111-116.
Parker, D. L. and J. R. Hodge. “Delirium in a Coronary Care Unit,” JAMA, 20 (1967) 702-703.
Parker, W. R. “Post-Cataract Extraction Delirium,” JAMA, 61 (1913), 1174-1177.
Posey, W. C. “Mental Disturbances after Operations upon the Eye,” Ophthalmol. Rev., 19 (1900),
235-237.
Posner, J. B. “Delirium and Exogenous Metabolic Brain Disease,” in P. Beeson, and W. McDermott,
eds., Cecil and Loeb Textbook of Medicine, pp. 88-95. Philadelphia: Saunders, 1971.
Radestock, P. Schlaf und Traum. Leipzig: 1879.
Reding, G. R. and R. S. Daniels. “Organic Brain Syndromes in a General Hospital,” Am. J. Psychiatry,
120 (1964), 800-801.
Safer, D. J. “The Concomitant Effects of Mild Sleep Loss and an Anti-Cholinergic Drug,”
Psychopharmacologia, 17 (1970), 425-433.
Schultz, D. P. “Physiological Effects of Sensory Restriction—Electroencephalographic Changes,” in

D. P. Schultz, ed., Sensory Restriction, pp. 35—42. New York: Academic, 1965.
Shagass, C. “Electrophysiological Studies of Psychiatric Problems,” Can. Biol. Rev., 31 Suppl.
(1972), 77-95-
Sherlock, S., W. H. Summerskill, Jr. et al. “Portal—Systemic Encephalopathy,” Lancet, 2 (1954),

453-457.
Skoog, G. “The Course of Acute Confusional States,” Acta Psychiatr. Scandinavica, Suppl. 203
(1968), 29-32.
Tufo, H. M., A. M. Ostfeld et al. “Central Nervous System Dysfunction following Open-Heart
Surgery,” JAMA, 212 (1970), 1333-1340.
Tyler, H. R. “Neurologic Disorders in Renal Failure,” Am. J. Med., 44 (1968), 734-748.
Viederman, M. “Adaptive and Maladaptive Regression in Hemodialysis,” Psychiatry, 37 (1974),

68-77.
Weisman, A. D. and T. P. Hackett. “Psychosis after Eye Surgery,” N. Engl. J. Med., 258 (1968), 1284-
1289.
West, L. J. “A General Theory of Hallucinations and Dreams,” in L. J. West, ed., Hallucinations, pp.
275-291. New York: Grune & Stratton, 1962.
Willner, A. E., C. J. Rabiner et al. “Analogical Reasoning, Rheumatic Heart Disease and Post-
Operative Outcome in Patients Scheduled for Open-Heart Surgery.” Unpublished.
Wilson, L. M. “Intensive Care Delirium: The Effect of Outside Deprivation in a Windowless Unit,”
Arch. Intern. Med., 130 (1972), 225-226.
Ziskind, E. and H. Jones. “Observations on Mental Symptoms in Eye Patched Patients: Hypnagogic
Symptoms in Sensory Deprivation,” Am. J. Psychiatry, 116 (1960), 893-900.
Zubek, J. D. “Counteracting Effects of Physical Exercises Performed during Prolonged Perceptual

Deprivation,” Science, 142 (1963), 504-506.
_____. “Behavioral and EEG Changes after Fourteen Days of Perceptual Deprivation,” Psychonom.
Sci., 1 (1964), 57-58.
Zubek, J. P., D. Pushkar et al. “Perceptual Changes after Prolonged Sensory Isolation (Darkness
and Silence),” Can. J. Psychol., 15 (1961), 83-100.
Zubek, J. P. and L. Wilgosh. “Prolonged Immobilization of the Body: Changes in Performance and
in the Electroencephalogram,” Science, 140 (1963), 306-308.
Chapter 3
Aging and Psychiatric Diseases of Late Life
Ewald W. Busse
Terms and Definitions
Aging when applied to living organisms is used to identify changes that
take place gradually and end with death. Such changes may be a decline in
body efficiency, a change in structure, and a stoppage or reversal of growth.

Primary aging refers to biological processes that are apparently inborn and
inevitable detrimental changes which are time related but influenced by

stress, trauma, and environment. All people, animals, plants, as well as
nonliving matter become older, and all undergo identifiable changes with the
passage of time. Primary aging processes are not identical in all people, and
those that take place do not progress at the same rate. Secondary aging refers
to disabilities resulting from trauma and disease. The terms growth and
development usually represent biological processes which are the opposite of
aging. Living things must, of course, grow older; hence both growth and aging
can take place in the same living organisms at the same time.
The designation aged is often used arbitrarily to denote or define

persons who have achieved a certain chronological age within a given
environment. Utilizing chronological age to place a person in a group is a
great convenience for society, but the age of an individual does not reflect the
individual’s abilities. Furthermore, a person is considered old or aged at forty
in so-called underdeveloped nations, while in an industrialized or advanced
society, a person can live many more years before being considered aged.
Some scientists and scholars believe that the term aging is misleading
and prefer to use the term senescence to stand for the deterioration that
accompanies the passage of time. This term is, therefore, essentially the same
as primary aging. Senility, or senile changes, refers to what has been
previously described as secondary aging. The science of aging, called
gerontology, includes all of its aspects—biological, psychological, and
sociological. Geriatrics is a more restricted term applied to the biomedical

aspects of gerontology.
Expectation of life, that is, the average number of years of life remaining
to persons at a given age, is an estimate based upon the assumption that the
death rate in a single year or over some period of time will remain completely
unchanged in the future. Obviously any event that influences future death
rates alters the accuracy of the estimate called “life expectancy.” Life
expectancy at birth in the United States between 1900 and 1902 was as
follows: white males, 48.2 years; white females, 52.2 years. In 1968, the life
expectancy of American white males was 67.5 years, and of white females,
74.9 years. Nonwhite males had increased to 60.1 years, and non white
females to 67.5 years.
Negroes of all ages compose approximately 11 percent of the population
of the United States. However, because of the lower life expectancy, older
Negroes are underrepresented in both the total population and in the Negro
population.
In 1970, 9.9 percent of the United States’ citizens were 65 years of age
and over. This means that every tenth American is considered to be an older
American. In 1870, only 2.9 percent were 65 years and over. This shift in the
age distribution of our population is particularly significant to physicians and
psychiatrists. However, of equal if not greater importance to our society and
to psychiatry is the growing predominance of women. This is discussed

further in the section, The Older Population.
Longevity, the state of living considerably beyond the normal
expectation, is said to occur in identifiable groups of humans. A group of
people that have received particular public attention are the inhabitants of
Abkhasia in southern Russia. News media reports based upon articles by the
Soviet Russian scientist Basilevich, the American anthropologist Sula Benet,
and Alexander Leaf of Harvard University indicate that a significant number
of elderly individuals reach the age of 100 years or more. Although they show
age changes affecting the hair and skin, they reportedly have keen eyesight
and most have their own teeth. The latter is particularly remarkable when
one considers the loss of teeth in elderly Americans. The Abkhasians are
reported to be extremely active people who are slender and agile and
maintain physical cleanliness and neat clothing. They rarely marry before the
age of 30, and virginity for the bride is an absolute requirement. Yet sex is
considered good and pleasurable. Retirement is unknown and the status of
the aged in the community increases with age. Abkhasians themselves

attribute their longevity to their work patterns, sex, and dietary habits.
Although many individuals express the hope and belief that it is possible
to extend the life span, the hope of delaying aging focuses, for most
individuals, on the continuation of sexual vigor and reproductive capacity.
Perhaps the best known attempt to find prolonged youth is the medieval
search for the Fountain of Youth. It was taken seriously and was based upon a
science-fictionlike account written in the second century. Ponce de Leon’s
expedition in 1512 and his exploration of Florida were actually organized and
financed to specifically search for the Fountain of Youth. Rejuvenation efforts
have existed for centuries in the Near and Far East. Efforts to maintain and
restore youth were primarily rooted in the practice of gerocomy. Gerocomy is
the belief and practice that men absorb virtue and youth from women,
particularly young women. King David in the Old Testament believed it and
practiced it accordingly. In more recent times, Mahatma Gandhi practiced a
form by sleeping with his niece. According to Comfort this concept has some
support from modern experimental studies. Aged male rats respond

favorably when a young female rat is placed among them. Her presence and
activities greatly improve their condition and prolong their survival.
Theories of Aging
There is no unified theory of aging because of the complexity of the

interaction of biological, psychological, and sociological processes. A
discussion of social theories can be found in Vol. 6, Chap. 42 of this Handbook.
A brief and oversimplified review of the biological and psychological theories
of aging follows.
Biological Theories
There are three distinct biological components of the bodies of humans
and higher animals. Two of the components are cellular and one is
noncellular. One of the cellular components is made up of cells that are
capable of reproducing themselves throughout the animal or person’s life
span. Skin and white blood cells are examples of such cells that have the
capacity to reproduce. The second component is made up of those cells that
cannot reproduce and cannot be replaced. Such cells are the neurons of the
brain and of the nervous system. The third biological component is
noncellular; that is, it is the material that occupies the space between the
cells. It appears that aging is different in each of these components.
Consequently, many so-called aging processes have been described and

theories advanced. Some of these aging changes take place in at least two of
the components, but at this time none is applicable to all three components of
the body. One early biological explanation of aging rests on the assumption
that a living organism contains a fixed supply of energy not unlike that
contained within a coiled watch spring. When the spring of the watch is
unwound or the energy consumed, life ends (exhaustion theory). The
accumulation of harmful matter is another simple theory based upon the

increasing failure of the organism to dispose of waste products.
Deliberate biological programming is another explanation of aging and

death. The vital functions and the duration of the life of a cell are determined
by an intracellular memory stored in a DNA (dioxyribonucleic acid) controller

gene. Hayflick contends that dividing cells have a finite capacity for doing so.
He has demonstrated that human embryonic fibroblasts divide approximately
50 times and then die. Cells created at about age 20 years approximately
double 30 times, and cells acquired at a later age show a progressive decline
in their doubling capacities.
Another theory that has received considerable attention in the
laboratory relates to the reduction of life span of most organisms exposed to

ionizing radiation. Although radiation does produce disruption of many
functions, the changes and shortening of life resulting from radiation are
significantly different from those associated with the aging process. However,
aging and radiation effects do have some common features. For example, both
are accompanied by alterations in the structure of the gene transmitting DNA
molecule.
Another aging process that has received considerable laboratory
attention is the cross-linkage or eversion theory. The initial research was
directed towards collagen, the most abundant body protein found in the
noncellular component. One strand of the polypeptide that composes collagen

is gradually chemically linked with another, reducing the elasticity of the
material. Some investigators have claimed that cross-linkage occurs in other
proteins in the body, particularly those within cells.
Two interesting theories are the free-radical and the immunologic
theory of aging. Free radicals are highly reactive molecular fragments which
are ubiquitous in living substances and are produced by normal metabolic
processes, as well as exposure to ionizing radiation. Initiators of free radicals
include ozone, the allotropic form of oxygen, and hydrogen peroxide.
However, it is not known whether ozone is produced internally in the human
body. The introduction into the body of free-radical inhibitors has been
carried out with mice with some success. The existence of free radicals within
the body and their deleterious effects upon the central nervous system (CNS)
cannot be ignored. But it has yet to be demonstrated how to reduce the

deleterious effect without producing adverse side effects.
Wolford has given considerable attention to the immunologic theory of

aging. He believes that the phenomenon called autoimmunity is one of several
aging processes that may stem from a common “first cause” or single etiology.
There is little doubt that the immunologic processes in the advanced years of
life are considerably altered from that found in the young and middle-aged
adult and contribute to many of the disabilities that are present in late life.
It is conceivable that the autoimmune process is responsible for the loss

of brain cells in humans as well as in experimental animals.
Psychological Theories
Theories of aging emanating from psychologists and related behavioral
sciences are almost as numerous and diversified as those coming from the
biological scientists. Psychological theories of aging are often the extension of
personality and developmental theories into middle and late life. Erikson is
one of the few theorists who have acknowledged the state of late adulthood.
He holds that at this stage of life the status of ego integrity is of fundamental
importance. The basic conflict is between the acceptance of one’s life as useful
and successful versus a sense of despair and fear of death. Such personality
theories usually consider the innate human needs and forces that motivate
thought and behavior, and the modification of these biologically based
energies by the experience of living in a physical and social environment. In
early childhood, according to the theories of the development of personality,
the physiological changes of the growing child and the interaction with the
mother set the stage for basic personality characteristics and determine the
relationship between the existence of the individual and his environment.
There is no doubt that certain often unidentified characteristics are set early
in childhood. There is no escaping the fact that as humans pass through their
life experience they become increasingly different rather than similar. This
divergence in psychological and behavioral characteristics continues as a

response to the large array of possible learning and living experiences. The
increasing differences seems to continue until old age when it is possible that
the very aged return to greater similarity in certain characteristics, as they
share similar declines in biological functioning and socioeconomic
constraints.
Neugarten and his associates have attempted to explore patterns of
personality in middle and late life. They concluded that when 60-year olds are
compared to 40-year olds, the former see the environment as more complex
and dangerous. The older adult is less ready to contribute actively to society
and to influence persons in his environment; he moves from an outer to an
inner world orientation. In addition, older men seem to be more conscious
than younger men of their own “affiliative, nurturant, and sensual
prompting.” Older women become more self-accepting of their own
“aggressive and eccentric impulses.”
Much of the investigation concerned with psychological functioning in

the aged is directed towards cognitive function and learning. It is evident that
the decline in intellectual functioning does not affect all elderly people equally
and that some elderly people preserve their intelligence late in life. This
maintenance of psychological capabilities appears to be related to a number
of variables including general health, educational attainment, lifelong
patterns of learning, and economic conditions. Such studies give credence to a

so-called cybernetic or activity theory. The proponents of this theory
maintain, “To become functional early in life, neurons must be activated. To
retain their position of control, they must be reactivated repeatedly. We

believe that aging involves deterioration of neuronic control which proceeds
more rapidly if the cybernetic control systems are not used.” Thus the
cybernetic theory implies that previously established patterns of learning and
social activity are the determinants of patterns in late life.
The Older Population
In the United States there are approximately 20,000,000 men and

women aged 65 and over. The 1970 census showed that the older population
(i.e., 65 years and over) increased faster in the preceding ten-year period than
the remaining population,—an increase of 21.1 versus 12.5 percent. Of even

greater importance to the nursing home is the increase of those aged 75 and
over. This truly aged group (75+) increased by 37.1 percent. At least one in
every 11 persons in the United States is 65 or over. There is considerable
variation from sate to state in the percentage of 65-year-olds and over.

Florida ranks first with 14.5 percent. In 1900, 4.1 percent of the population of
the United States were in the older age group. By 1965 this figure had
increased to 9.4 percent. While the percentage has doubled, the actual
number of aged persons has increased six to seven-fold, i.e., from 3 to more
than 20 million.
At the turn of the century the difference in the number of elderly men
and women was not significant. Of particular importance to today’s society is
the growing predominance of women. Even though there are more boys than
girls born, the longer life expectancy for females results in a gradual shift in
percentages; therefore, after the age of 18 there are females for every 100
males in the total population. In the population 65 years and over, there are
138.5 females per 100 males. This proportion increases after age 75 to 156.2
females to every 100 males. The ever-growing number of widows and single
elderly women is presenting a very serious problem, as it is necessary to find
avenues of social participation which are rewarding to single elderly women
as opposed to married elderly men and women.
Retirement
Although age 65 is often used as the date for enforced retirement and
for the beginning of social security benefits, the assumption that most
individuals at age 65 experience a major change in their physical health and
mental efficiency is very misleading. Generally speaking, individuals between
65 and 75 are healthy and capable of living rewarding lives. From a health
statistical viewpoint, age 75 is a more important date than 65 because life
expectancy at age 75 is about nine years and it is then the health problems
increase significantly.
Persons 75 years or older are restricted in their activities because
illness confines them about 12 days more per year than those age 65 to 74.
The person in the older age group is in bed at least eight days more per year,
and is limited in general activity as the result of chronic conditions. Of
persons 75 and over, 23.7 percent are unable to carry on a major activity as
opposed to 9.7 percent of those between 65 and 74 years. Individuals of 75 or
over are often referred to as aged persons. This class comprises 8.1 percent of
the institutionalized, as opposed to 2 percent of those between 65 to 74 years.
There is no doubt that compulsory retirement and retirement because

of poor health account for many people leaving the labor force. However,
considering the persons who are compelled to retire because of employer
policy, there is no doubt that a significant percentage would be capable of
functioning for at least five to ten years past the retirement age. Compulsory
retirement plans are primarily associated with economic conditions and the
condition of the labor market rather than with the individual’s capability of
performing in some financially rewarding capacity.
Prejudice
Elderly people are the victims of widespread prejudice and bias.

Discrimination takes all forms, but one of the most difficult problems is the
fact that elderly people are ridiculed when they continue to strive for love and
affection, seek pleasure, and wish to maintain their self-esteem. This
widespread prejudice is the result of early acquired attitudes towards the

aged and can be attributed to a number of factors including socioeconomic
changes. Unfortunately, these prejudices are found not only in the lay public
but also in professional and volunteer workers who are products of the
society and therefore bring to their relationship with elderly people the
predetermined attitudes and patterns which are common in society. A British

scientist noting the extent of this prejudice has referred to it as
gerontophobia. If the elderly persons are to receive the care which they need
and deserve, it is important that these prejudices be eliminated, and their
previous contributions and present values and needs be recognized.
Physical and Mental Health
In the older population the close relationship between physical and
psychological state is particularly apparent. Chronic illnesses are prevalent
and their occurrence increases steadily with age. In earlier adulthood, that is,
up to 45 years of age, 45.3 percent of persons have one or more annoying
chronic condition. Fortunately these produce limitations of major activity in

only 7.4 percent. Between the ages of 45 and 64 chronic conditions are
present in 61.3 percent and limitations of activity in 18.3 percent. After age
65 chronic disorders increase to 78.7 percent and disability to 45.1 percent.
Those bedfast comprise 2.3 percent of the aged, while 6.1 percent are
confined to their rooms or living quarters. Of the remaining, 86.2 percent can
go out without difficulty, while 5.4 percent must exert considerable effort in
order to venture out from their confined environment. Obviously confined
persons are in danger of isolation and have difficulty maintaining social
activity, intellectual stimulation, and opportunities for learning. This
undoubtedly accounts in large measure for their decline in mental capacities.

The decline in intellectual and mental abilities have a clear relationship to
institutionalization in approximately 80 percent of the cases studied.
Need for Self-esteem
Self-esteem is a composite of innumerable self-ratings that are socially
influenced, but in a large measure constructed, measured, and valued by the
individual. Two components of self-esteem, which are often extremely

important to the elderly person, are his measure of whether he feels his life
has any value to himself and to others, and the more subtle but extremely
important measure of his capacity to deal successfully with physical disease
and trauma. Some individuals believe that they have resources that make it
possible for them to survive any period of illness successfully. However, there
are others who do not have this reserve strength and are completely at the
mercy of others to take care of them during an illness. Some individuals can
control this situation by economic resources, while others must be highly

dependent upon being liked and respected, and being considered sufficiently
worthwhile by others that they will be adequately cared for during their
illness. Chronic disability plays an important role in these measures of self-
esteem, since a disabled person may find it very difficult to feel that his life is
meaningful and justified and, in addition, may deplete his resources so that
his comfort and survival are tied to the goodwill of others.
Types of Mental Problems in the Aged Population
Health and service professionals working with elderly people refer to
the frequency of hypochondriacal and depressive reactions. Obviously, these
professionals are working with elderly who are in need of help whether it be
medical or socioeconomic. Therefore, in a cross-section of elderly people the
question arises, “How often does one encounter these reactions?” One of our
early studies indicated that 40 percent of elderly people were free of

psychological problems and another 54 percent were functioning well enough
to be classified as nonpsychotic even though they had various mental
symptoms. The remaining 6 percent were psychotic but functioning at a
socially acceptable level in the community and participated in our research.
Although it would be convenient for discussion purposes to indicate that the
psychoneurotic could clearly be separated into a distinguishable diagnostic

group, this was not actually the case. Thirty-three percent of all of the
subjects had mild to severe hypochondriasis. Of the approximately 11 percent
classified as severely psychoneurotic, depressive features and “intense body
concern,” that is, hypochondriasis, were major features of the psychoneurotic
reactions. Of interest are the group of psychotic elderly individuals who were
functioning in the community. What permits these individuals to function at a
socially acceptable level? The study includes a social-activity score, and this
does appear to be an important dimension. The neurotic group was markedly
less active in a social sense than the “normal” subjects. Thus the psychotics
approached the normal level of social activity. They were able to hold in check
and balance their psychotic thinking (which was detected by a psychiatric
examination) by maintaining a near-normal level of social activity.
The Use of Psychiatric Facilities
Kramer, et al. are responsible for most of the following information. In

1946, state, county, and private psychiatric hospitals accounted for 42
percent of all hospital beds in the United States. About 80 percent of the
mental beds were located in state and county mental hospitals. In 1969,
psychiatric beds had dropped to 31 percent of all hospital beds, but 80
percent of the mental hospital beds were still in state and county hospitals.
This happened despite the fact that 1400 general hospitals report routinely
admitting psychiatric patients and that over 2000 outpatient psychiatric
clinics were in operation. Studies of first admissions to public hospitals
continue to show that certain persons are more vulnerable to mental
disorders than others. These contributing factors hold regardless of age;
socioeconomic group; color; urban as compared to rural resident; and marital
status. Between 1946 and 1955, the number of first admissions being
returned to the community increased from 50 to 63 percent. However, for

those who remained in the hospital longer than one year the chances of ever
returning to the community decreased rapidly with increasing length of
hospitalization. Such patients are usually diagnosed as schizophrenics and

they have a high likelihood of growing old in the hospital. During this same
period, the public mental hospital continued to struggle with the problem of
providing medical and psychiatric care to large numbers of aged with brain
syndromes associated with senile brain disease and cerebral arteriosclerosis.
It does appear that between 1950 and 1968 there was either a
remarkable change in the number of mental disorders of the senium, or
alternatives for prolonged hospitalization were being developed, as there was
a decrease of 32.1 in the percentage of resident patients in public hospitals

with mental disorders of old age. Kramer also points out that there was a
sharp reduction in first admission for patients 65 years and over. Many state
hospital systems adopted policies that resulted in these reductions which, in
turn, led to an increased use of nursing homes and related facilities for aged
patients. As a consequence, between 1962 and 1965 the rate of first
admission for the age group 65 years and over dropped by 9.1 percent for
males, 11.5 percent for females; and 10.5 percent for both sexes combined.
Between 1965 and 1969, the corresponding decreases were 19 percent for
males, 43 percent for females, and 31 percent for both sexes combined.
Between 1946 and 1968, there was a rapid growth of outpatient
psychiatric clinics. Approximately 500 clinics were functioning in 1946. This

number expanded to almost 2000 by 1968. However, these facilities have had
an interesting distribution when one compares the age at termination of the
patients they served. These facilities have been used to a large extent by
children and adolescents under 18 years who account for about 33 percent of
the patient load. Adults in the age group 18 to 44 years account for another
51 percent; patients 45 to 54 years for 10 percent; 55 to 64, 4 percent; and 65
years and over only 2 percent. On the basis of population composition alone,
the aged are clearly under represented, as at that time they composed
approximately 9 percent of the population. In addition, day-care services
seemed to be playing a relatively minor role in the care of aged patients. Of

the estimated 11,000 admissions (nationwide basis) to day-care programs of
community mental health centers during 1969, only 2.6 percent, or 260
persons, were 65 years of age or older. Day activities of other types, such as
workshops, do exist for elderly people, but they are designed for prevention
rather than treatment, and serve the relatively normal aged. Although useful,
there are too few to have any substantial impact upon the health and
adjustment of the elderly.
Community mental health centers, as defined by the criteria necessary

for Federal funding, also do not appear to be carrying a proportionate load of
aged patients. As of 1969, only 4 percent of admissions were 65 years and
over. Psychiatric services in general hospitals are carrying a greater load, as

13 percent of the termination from these services were 65 years and older.
In the last 20 years the number of nursing homes in operation have
increased twentyfold and the number of beds over thirty times. Much of the
recent increase has been due to the impact of Medicaid and Medicare.
Among the institutionalized elderly individuals suffering from mental
illness, the distribution is approximately as follows: 51 percent are patients in

state and county mental hospitals; 43 percent are in nursing homes and
related facilities; 5 percent are occupants of Veterans Administration beds;

and 1 percent are in private mental hospitals. However, the percentage of
mentally ill aged in nursing homes is probably a minimum estimate, as

Kramer and his colleagues question the accuracy of the diagnosis submitted
from nursing homes. They believe that the actual number of mentally ill aged
in nursing homes has surpassed the number of mentally ill aged residents in
all other types of psychiatric inpatient facilities.
Depressive Episodes in the Elderly
Evidence indicates that depressive episodes increase in frequency and
depth in the advanced years of life. Elderly subjects are aware of these more
frequent and more annoying depressive periods, and they report that during
such episodes they feel discouraged, worried, and troubled and often see no
reason to continue their existence. However, only a small number admit

entertaining suicidal ideas, but a larger percentage state that during such
depressive episodes they would welcome a painless death. During such
periods, the elderly are more or less incapacitated, but they rarely seek
medical help. This type of reaction must be distinguished from the much
more serious psychotic depressive illness which is a common cause of
hospitalization.
The observation that elderly subjects were aware that they were
experiencing more frequent and more annoying depressive episodes is based
upon a study made some years ago and confirmed by more recent
longitudinal studies. Observations indicate that there is a difference in the

process leading to depressive episodes in the elderly as compared with the
middle-aged or young adults. Guilt and the turning inward of unconscious
impulses (interjection) that are unacceptable to the ego are common
mechanisms in the depressions of young adults. This is not the case with
elderly subjects. Depressive episodes can be readily linked with the loss of so-
called narcissistic supplies. The older subject becomes depressed when he
cannot find ways of gratifying his needs; that is, when social environmental
changes or the decreased efficiency of his body prevent him from meeting his
needs and reducing his tensions. He is likely to have a loss of self-esteem;

hence he feels depressed.
There is clear evidence that the frequency of depressive episodes is

influenced by the life situation. For example, three groups of subjects
reported mood disturbances occurring at least once a month and lasting from
a few hours to a few days. The highest number of subjects (48 percent)
reporting mood disturbances occurred in persons over the age of 60, unable
to work, attending an outpatient clinic for various physical disorders, and
suffering financial hardships. Depressive spells occurred in 44 percent who

were retired, in good health, and in acceptable financial condition. However,
only 25 percent of subjects continuing to work past the usual age of
retirement reported such experiences. Most of the subjects in the three

groups denied that they had experienced depressive spells of similar
frequency or duration earlier in life.
To fully appreciate the factors that are important to depressive episodes

in the elderly, particular attention must be given to attitudes toward chronic
disease, disability, and death. When studied longitudinally, the importance of

physical health as a determinant of depressive feelings becomes increasingly
evident. It appears that the aged person can tolerate the loss of love objects
and prestige better than a decline in health, as physical disability often
disrupts mobility and results in partial isolation. Hence the opportunities for
restoration of self-esteem are reduced.
Important factors that contribute to depressive feelings in elderly
persons are often conscious, as approximately 85 percent of elderly subjects

are able to identify the specific event or stimulus that precipitated the feelings
of depression. Therefore, many depressive episodes in the elderly are a
realistic grief response to a loss and not primarily influenced by unconscious
mechanisms. Hence the symptom is relieved when the actual loss or threat is
removed or compensated for.
Simon believes we need to know more about the crisis of bereavement
of widowhood not only in late life, but also in the middle years. There is
evidence that the death rate is increased among newly widowed persons for
several years at least. Generally, there are more women than men among
depressed persons in their fifties and sixties. After 65, it is about evenly
divided between women and men. Simon states that the bereaved constitute
a high-risk group that must be recognized and offered help.
Somewhat different statistics given in the Russian literature indicate
that after the age of 50, women are three to four times more likely than men
to develop depressions. However, when men become depressed, they are
more likely to be in the age group 50 to 59, while women are more likely to be
between 60 and 69 years of age. A smaller peak is reached for women who
have their first depressive episode before age 45.
As to premorbid personality traits, although a variety were common,
only 10 percent presented evidence of premorbid abnormalities which could

be considered pronounced psychopathology.
“Organically colored” depressions were identified in 13 percent of those
between the ages of 50 and 59; 8.3 percent between 60 and 69; and 28.7
percent after the age of 70. Before the age of 70, anxious-hypochondriacal and
anxious-delusional syndromes associated with the depressions were the most
common occurring in 31.5 and 26.7 percent, respectively.
Depression and Dementia
Depressive symptoms are not unusual in patients with organic brain
disease. The majority of clinical studies indicate that depressive symptoms

are more common in cerebral arteriosclerosis and cerebral vascular brain
disturbances than in senile dementia. One explanation is that insight is less
frequently observed in senile dementia.
Some years ago depression in the elderly was often considered
“prodromal depression” or the “neuroasthenic stage” of cerebral
arteriosclerosis or senile dementia. English investigators have demonstrated
that elderly depressives do not subsequently develop cerebral degeneration
any more than do elderly people in general.
Wang uses the term brain impairment to designate measures of loss of
brain function based on a number of laboratory procedures including EEG
(electroencephalogram), cerebral blood flow, cerebral metabolism, etc. The
degree of dementia is determined by psychological tests and/or clinical
measures of intellectual performance and emotional variations. Wang and
Busse point out that there is all too often a lack of correlation between these
two types of evaluations. Of particular concern are the discrepancies found in
patients with a precipitous decline observed clinically, but not paralleled by
evidence of rapid physiological brain changes. Careful consideration of

factors, such as general physical health, economic status, social environment,
and previous living habits, forces the clinician to concede that he is faced with
an illness of multiple etiology.
Pseudodementia
Depressed elderly patients occasionally present a clinical picture of
pseudodementia. According to Post, such patients appear to be severely
perplexed and disoriented, and have memory defects. They may show the
“syndrome of approximate answers.” Two observations help to exclude the
existence of true organic brain disease: (1) The history indicates a recent
abrupt onset of defective memory and judgment plus depressive symptoms;

(2) negativism is common; for example, the patient replies, “I don’t know,”
rather than confabulate as do many patients with brain impairment.
To summarize, for the latter part of the life span of most Americans—
particularly for those over the age of 65—life is replete with events that are
losses. In addition, the elderly person often does not have the socioeconomic
resources that would permit him or her to deal effectively with such losses.
The large number of elderly who do maintain a reasonable emotional balance
is evidence of the capacity of people to withstand stress, deprivation, pain,

and discomfort.
Hypochondriasis
Hypochondriasis is another common mental problem that is
encountered in elderly people. Hypochondriasis is ubiquitous but particularly
common in elderly people who seek help in a university clinic. It is generally

accepted that hypochondriasis is not a disease entity but a syndrome
consisting of an anxious preoccupation with the body or a portion of the body
which the patient believes is either diseased or not functioning properly.
Hypochondriasis may be part of a symptom pattern in a neurosis, a psychosis,
a psychophysiological reaction or a personality disturbance. Cross-sectional
and longitudinal studies have provided an opportunity to observe
hypochondriacal tendencies in elderly subjects residing in the community or

seeking medical help. Of elderly people in the community, 33 percent were
found to have varying degrees of hypochondriacal symptoms. A much greater
number showed what was called “high body concern,” because in many of
these cases the degree of concern was probably reality determined, that is,
organic disease actually existed and the complaints were not solely of
neurotic origin.
In the psychodyrmmics of hypochondriasis three major components are
recognized: (1) The patient’s interest may be withdrawn from other persons
or objects around him and be centered upon himself, his body, and its
functions; (2) the restrictions and discomforts produced by this psychic
illness may be utilized by the patient as punishment and partial atonement

for guilt resulting from feelings of hostility and a desire for revenge; and (3)
the symptom can be caused by a shift of anxiety from some specific area of
psychic conflict to a less threatening concern with bodily function. It has been
our observation that although the guilt mechanism is found in young

hypochondriacs, it is rarely encountered in older persons. The older person’s
high body concern is more likely to result from a withdrawal of his interests
in other persons or objects, and/or displacement of his anxiety.
Observations indicate that the frequency of persistent hypochondriacal

syndrome encountered in the patient population is not necessarily paralleled
in our community subjects. Studies showed that hypochondriacal episodes
were not infrequent in elderly persons who did not necessarily seek medical
help. The depressive element in the hypochondriacal reaction in community
subjects was easily recognized. For reasons previously mentioned, the
investigators preferred to rate “high body concern.” Other scales, based on
specific criteria, were used to rate the subjects in a number of areas of

functions and activities. The results of the entire medical (physical)
examination were summarized in terms of a five-point scale representing the
objective health status of the subject.
A subject’s health was considered to be medically good if there were no
symptoms of disease or, if the symptoms existed, the individual suffered no
more than 20 percent limitation of normal functioning. Subjects with

limitations of 20 percent or more were considered to be in poor health. The
subject was also given an opportunity to make a self-assessment of his health.
In this particular study a number of other observations were included as

important. Consideration was given to the IQ as determined by performance
on the WAIS (Wechsler Adult Intelligence Scale). The existence of excessive

preoccupation with health in the psychiatric examination was considered, as
well as a count of symptoms or complaints from the physical examination.
Morale was measured in terms of a Havighurst Attitude Scale, and the level of
activity was determined by an Activity Scale. Social placement factors were
also included in the study. Considered were age, sex, race, change in work
role, and socioeconomic status. Each subject had an opportunity by letter and
personal contact to be informed of his objective health status as evaluated by
the examining physicians.
The data from the original observations indicated that in 65 percent of
the subjects there was congruity between self-assessment and the medical
evaluation of health. Incongruity of self-assessment of health and medical
evaluation occurred almost without regard of the objective health status. Of
the subjects considered to be in good health, 31 percent were health

pessimists, and of those in poor health, 44 percent were optimists. Thus,
approximately one-third of elderly persons could not be relied upon to give
an accurate self-assessment of their physical health. Subjects whose health

was medically good and who had realistic self-appraisal were likely to be
older (that is, age 70 or above), to occupy a higher social status, and to
maintain a high level of social activity. In subjects of poor health, it appeared
that the younger was more likely to be pessimistic, while the older subject
used denial and maintained an optimistic view. There was also a sex
difference; pessimism was more characteristic of women, in spite of the fact
that the mortality rate favors the older woman. The pessimistic or
hypochondriacal person was likely to have low morale, to be poorly adjusted
to the environment, to report past and current periods of depression, and to
express feelings of neglect.
The persistent optimist uses his opportunity to pursue the busy life to
the point where he is too busy to recognize the appearance of physical
disease and disability. Consequently, the optimist is unlikely to have the
attention of a physician until the disease has become so serious that it cannot
be denied. At that point such a person often becomes seriously depressed and
requires support and skillful redirection to activities consistent with the
disability. The person using the mechanism of denial should not be seen as a
courageous person. A courageous person realistically appraises the situation,

determines the odds, accepts the challenge, and moves ahead.
Organic Brain Syndromes
The sequence of the disease discussed (disorders caused by or
associated with impairment of brain-tissue function) is essentially that found
in DSM II The Diagnostic and Statistical Manual of Mental Disorders. Under the
entry of organic brain syndrome are included all those diseases which result
in mental changes that can be attributed to diffuse or significant involvement
of brain-tissue function. The disease should be designated as either psychotic
or nonpsychotic, and the extent of the mental change whether it be mild,
moderate, or severe, should be identified. Furthermore, it is important to
distinguish acute from chronic brain disorders. The term acute is not used to
indicate a sudden onset of the disease, but implies reversibility. Both “acute”
and “chronic” are descriptive terms which are unrelated to etiology, as the
same causative agent can produce in one individual a temporary, that is,
acute, disorder, while in a second individual it may produce a chronic, that is,
permanent, disability.
The diagnosis of an acute brain disorder indicates that the patient is
expected to recover and that his physiological brain functioning will return to
normal. Unfortunately, particularly for the elderly patient, the experience of
an acute brain disorder often leaves the patient with a prolonged adverse
effect upon psychological functioning. The recovered elderly person is
seriously concerned that the brain disorder heralds the beginning of
intellectual decline and death. The anxiety and depression associated with the
recovery period from an acute organic brain reaction must be recognized and
relieved. Generally speaking, an acute brain disorder that occurs in older

persons is either a toxic or ischemic reaction. Recovery is dependent upon
elimination of the toxic substance and restoration of the brain to normal

metabolic functioning.
The criteria are limited to distinguish psychotic from nonpsychotic
reactions. DSM II [p. 31] describes patients as psychotic “when their mental
functioning is sufficiently impaired to interfere grossly with their capacity to
meet the ordinary demands of life.” The description of the nonpsychotic
organic brain syndrome is not extensive. It is mentioned that mild brain

damage often manifests itself by hyperactivity, short attention span, easy
detractibility, and impulsiveness. Conversely, sometimes the patient is
withdrawn, listless, perseverative, and unresponsive. It is also evident that
some symptoms, particularly in older individuals, are superimposed

responses to the mental changes that are the direct result of the organic brain
change.
According to the accepted diagnostic nomenclature, the word
“dementia” occurs in relationship to senile and presenile dementias that are

considered psychoses associated with organic brain syndromes.
Unfortunately, there is considerable discrepancy as to how clinicians and
investigators utilize the term dementia. Webster’s Third International

Dictionary defines dementia as “A condition of deteriorated mentality,
however caused; mental abnormality that is characterized by a marked

decline from the individual’s former intellectual level and often by emotional
apathy.” The 1969 edition of A Psychiatric Glossary defines dementia as “an

old term denoting madness or insanity; now used entirely to denote organic
loss of intellectual function.” John G. Allee’s version of Webster’s definitions
calls dementia “an incipient loss of reason.” This broadening of the definition
is the trend in medicine, as the term is being increasingly used to designate
any intellectual decline or organic cause, whether it be mild, moderate, or
severe. This possible conflict and confusion in the diagnostic terms should be
carefully considered by a psychiatrist, as the litigation of wills, testamentary
capacity, and competence frequently rest upon an accurate diagnosis and
description. The nonpsychotic nature of an early senile dementia should be

clearly stated.
Organic brain syndromes are likely to be accompanied by important

alterations in the person’s thinking and behavior. The so-called cognitive
functions which include comprehension, calculation, problem-solving,
learning, and judgment are impaired. Memory is spotty and orientation for
time, place, and person is faulty. Emotional responses are easily elicited and
are disproportionate or inappropriate to the stimulus. This basic clinical
picture characteristic of an organic brain disorder may be associated with a

wide variety of other symptoms. The type and severity of the symptoms are
not necessarily directly proportional to the extent of the physiological
disturbance, as they are often influenced by psychological patterns of long
standing and the particular psychological state of the patient at the time the
physiological disorder develops.
Dementia in Late Life
Several of the dementias that develop in the latter part of life appear at
least in some cases to be influenced by genetic factors. The evidence for
genetic transmission is strong in some dementias and less in others. Still, in
other diseases, the principle of “genetic heterogeneity” appears to operate,
which states that the phenotypic similarity, that is, the clinical manifestations
of the disease, may be produced by genotypically different conditions. Some
of the differences reported in various studies of heredity may be distorted by

the diagnostic criteria used.
Pratt reports on more than a dozen families in which a condition
developed that is identical with if not indistinguishable from Alzheimer’s
disease that is transmitted as a regularly manifested dominant trait. The
regular transmission of dementia differs from the common form of
Alzheimer’s disease, for a slight though definite tendency to familial
aggregation of the disorder is common. Furthermore, Pick’s disease, while

pathologically distinct, is clinically difficult to differentiate from Alzheimer’s
disease. However, Pick’s disease does appear to be associated with a

dominant autosomal mode of inheritance. The transmission of senile
dementia appears to be either a multifactorial or a dominant mode of
transmission. Close relatives of patients with senile dementia have a risk four
times that of the general population of developing the disease. Studies
conducted in Sweden have indicated that senile dementia is determined by a
single autosomal dominant gene carried by 12 percent of the general
population and reaching 40 percent manifestation at the age of 90 years. This
evidence indicates that senile dementia is qualitatively distinct from ordinary
senescence. It is also reasonable to assume that some specific enzyme or

other biochemical defect is the first cause of senile dementia. Alzheimer’s
disease, the most common of the presenile dementia, was not found in excess
within families of senile dementia, suggesting that it is in part determined by

factors that do not operate in senile dementia. Pratt concludes that the
evidence is more in keeping with a polygenic inheritance, with a shared
predisposition to both Alzheimer’s disease and senile dementia. As to
concordance rates in identical twins, senile dementia occurs in 43 percent
from monozygotic and 8 percent from dizygotic twins. If Alzheimer’s disease
affects one of a monozygotic pair, it is highly likely that the other will develop
the same manifestations of dementia.
Slow Virus and Dementia
The possibility that some of the dementias in late life can be attributed
to a slow virus cannot be disregarded. In 1968, Gibbs and his co-workers
reported the transmission of a disease from a patient diagnosed as having

Creutzfeldt-Jakob’s disease to a monkey. The following year the same
investigators reported successful transmission from man to monkey in six of
eight patients suffering from the same disorder, which is also known as
spongiform encephalopathy. Other investigators have reported the
observation of viruslike particles by electron microscope in patients with
spongiform encephalopathy. Familial instances of this disease have been

reported, but this may be the result of the transmission of the slow-acting
virus rather than the result of a genetically determined condition.
This discussion of differential diagnosis is primarily concerned with
senile dementia and the presenile dementias known as Alzheimer’s and as
Pick’s disease. Experienced clinicians have repeatedly found that there is no

reliable criteria to distinguish senile dementia from Alzheimer’s or from
Pick’s disease. There are clear-cut anatomical differences between Pick’s and
Alzheimer’s disease, but most pathologists doubt that any valid histological
distinction can be made between senile dementia and Alzheimer’s disease. To

further complicate the picture, there is in at least 20 percent of autopsy cases
a coexistence of senile and arteriosclerotic brain changes. Post does not agree
with the assertion that patients with Pick’s disease tend to repeat words or
brief phrases in a stereotyped manner and that they are less restless and
hyperkinetic than those with Alzheimer’s.
Both Alzheimer’s and Pick’s disease have an early date of onset. Hence
the age of the sick patient is often used as an important diagnostic criterion.
Some clinicians believe that senile dementia, in contrast to Alzheimer’s
disease, is accompanied by other evidence of exaggerated aging affecting the
entire body. Frequently there is a general wasting of muscles, shrinkage of

soft tissue, loss of elasticity of the skin, thinning and graying of the hair, and
easy fatigability. However, the fact that senile dementia has its onset
considerably later in life could explain why these aging symptoms are also
observed. Hence, they could be an aging phenomenon and not necessarily a

manifestation of the disease.
Alzheimer’s Disease
This illness was described by Louis Alzheimer in 1906. Its average onset
is the mid portion of the fifth decade of life. Occasionally, it begins in the
fourth decade of life. It is probably the most common of the presenile
dementias as it is found in 4 percent of the autopsies in a psychiatric
institution. Its sex distribution is in favor of females, the ratio being three to
two. The familial possibilities of this disorder have been discussed earlier (p.
79). Another clinical feature that may have importance is the recognition that
in spite of the loss of memory, illogical reasoning, etc., insight is often

preserved in patients with Alzheimer’s disease which results in a distressing
awareness of impending insanity. As the deterioration continues, speech

becomes seriously disturbed and involuntary movements of arms and legs
are frequently observed. The course of the disease is progressively
deteriorating with invariable fatal conclusions. The duration of the disease
varies from two to ten years and sometimes more. The average is usually
believed to be approximately four years. No specific treatment is known for

this disorder, and symptomatic environmental measures are the sole relief
that can be offered.
Pick’s Disease
Pick’s disease is generally characterized as a presenile dementia,

although it is doubtful that it is the result of the premature onset of an aging
process. The age of onset is very similar to that of Alzheimer’s disease. It most
frequently appears at approximately age 54, although occasionally it occurs
as early as the fortieth year of life. The recognition of this disease is attributed
to A. Pick, who lived in Prague and first published his work in 1802. Pick’s
original purpose was to illustrate the different types of aphasic
manifestations which can occur in senile brain diseases. It was really the
efforts of other scientists that established Pick’s disease as a distinct clinical
pathological entity. It is truly a rare disease, and the female ratio is two to
one. Again, the onset of aging is one of the primary distinguishing features of
Pick’s disease to senile dementia. Symptoms of focal cortical damage, usually
frontal or temporal in origin, are sometimes of help.

Pneumoencephalographic studies reveal the areas of localized atrophy. The
areas of most frequent involvement and their characteristic pathological
condition are described in Chapter 4.
Subtypes of senile dementia have been described by Ehrentheil. The
distinctions are often overlapping but include: (1) simple deterioration; (2)
the depressed and agitated type; (3) the delirious and confused type; (4) the
hyperactive type with motor restlessness and loquaciousness; and (5) the
paranoid type.
Experience indicates that approximately 50 percent of patients follow a

pattern of simple deterioration, with transient episodes of a wide variety of
reactions. However, a substantial number deteriorate without any dramatic
events accompanying the illness, and these people do not produce a serious
disturbance in the community. Hence they are kept in a protected
environment until they have reached an advanced stage of senile mental
deterioration. Of the disturbing types of reactions, the paranoid are probably
the most common and constitute 15 to 25 percent of the major manifestations

of this disorder.
Pathophysiology of Cerebral Vascular Disease
Cerebral vascular disease is often explained on the basis of vascular
insufficiency. Unfortunately, cerebral vascular insufficiency is not a
phenomenon that is amenable to direct observation. We are dependent upon
assuming its existence on the basis of other observations. Vascular
insufficiencies are believed to exist when it appears that the blood supply of
the brain is inadequate to meet its metabolic needs. It may be present
continuously, or occur intermittently when the blood flow falls below

acceptable levels, or it could occur if the metabolic activity of the brain
increased to a point that the normal supply was insufficient. There is a natural
tendency for a clinician to assume that the blood pressure is the primary
contributor to the presence or absence of vascular insufficiency. It must be
remembered that it is the cerebral blood flow, not the blood pressure, that is
the ultimate factor in determining the availability of oxygen to the brain.
Cerebral blood flow, usually expressed in ml. of blood per 100 g. of brain per
minute, is the result of two forces. Although blood pressure is important, it is
only one of several factors that must be considered in cerebral blood flow.
The first is the available pressure called the pressure head, that is, the
difference between the pressure on the arterial and that on the venous side.
The second factor is the cerebral vascular resistance. It is influenced by the
structure of the walls of the blood vessels, by the functional tone of the
vessels, the pressure on the vessels from without, that is, the intercranial
pressure, and the viscosity of the blood passing through the vessels. Cerebral
blood flow is clearly an extremely complicated phenomenon, as it is also
influenced by the metabolic demands of the brain. If the brain metabolism is
decreased, cerebral blood flow is also decreased. For this reason, it is often
extremely difficult to decide if a lowered cerebral blood flow may be
contributing to a decrease in brain metabolism, or is its result.
The caliber of the cerebral arteries is mainly determined by chemical
balance, especially by the concentration of carbon dioxide, CO2. It is the

partial CO2 pressure in the blood which normally determines the caliber of
the cerebral arteries. A rise in the CO2 pressure of the blood produces
cerebral vasodilatation. Interestingly, this takes place without simultaneous
systemic vasodilatation, so that the cerebral blood flow is increased until the
excess CO2 is removed. Although many pharmacological agents aimed at
improving the blood supply to the brain have been tried, most, if not all,
appear to be ineffective. This is because these pharmacological agents
produce systemic vasodilation which causes a fall in blood pressure which, in
turn, is compensated for by brain vascular changes so that the cerebral blood
flow remains unchanged. On the other hand, oxygen, doubtless, has an effect
upon the cerebral circulation acting as a vasoconstrictor. The inhalation of

100 percent oxygen produces a fall in cerebral blood flow of approximately
13 percent.
Episodic disturbances commonly referred to as transient ischemic
attacks are not infrequent in the older population. The majority of these
episodes are probably attributable to thrombi and emboli affecting areas
where restoration of collateral supply is possible. However, there is
increasing evidence that prolonged, marginal cerebral blood flow can produce
degenerative changes in the brain which lead to behavioral and intellectual
impairment.
Hyperbaric Therapy
In 1969, the Veterans Administration Hospital in Buffalo, New York,
reported that repeated exposures to hyperbaric oxygen (O2) may have a

positive effect on cognitive functioning in elderly patients for the diagnosis of
chronic brain syndrome. However, Goldfarb, et al. reported in 1970 that they
were unable to demonstrate this effect in a series of randomly selective
patients with “organic brain syndrome.” L. W. Thompson and his colleagues at
Duke University consider their results to be equivocal, but have shown some
positive changes in approximately 50 percent of their subjects.
The hyperbaric treatment program used by Thompson et al. consists of

thirty exposures to 2.5 atm. of absolute pressure, (the duration of each
exposure is 90 min.). The experimental group receives 100 percent oxygen
which provides alveolar oxygen (O2) tensions of approximately 1800 mm. Hg.
The control subjects breathe normal air at 1.3 atm. of pressure which
provides alveolar 02 tension levels slightly higher than air at one atmosphere.
Psychosis Associated with Other Cerebral Conditions
Cerebral Arteriosclerosis and Cerebral Vascular Disturbance
It is worthwhile again to caution the clinician to recognize that if the
mental disturbance is not of psychotic proportions, the condition is classified

under nonpsychotic organic brain syndrome with circulatory disturbance, not
with cerebral arteriosclerosis. This can be a cause of diagnostic confusion.
Furthermore, if the mental reactions result from such problems as cardiac
decompensation, it is necessary to include the underlying pathology as an

additional diagnosis. (See DSM II, p. 31 ).
Dementia associated with cerebral arteriosclerosis not infrequently

appears before the age of 70. The disease may appear in persons as young as
45 and can develop at any time in the late years of life. As all atherosclerotic
diseases, it is more common in males than in females (three times as common

in males than in females). Apparently female hormones do play a protective
role, and there are some clinicians who advocate the continuation of
supplemental estrogenic hormones in females for a number of reasons,
including the prevention of arteriosclerotic disease. Vascular pathology is not

only confined to the brain, but is usually found in other parts of the body. The
duration of the illness is difficult to determine, but the average appears to be
near 3.5 years.
Some clinicians indicate that more than 50 percent of cases with
cerebral arteriosclerosis demonstrate their first symptomatology by suddenly
developing a delirium manifested by confusion, incoherence, restlessness,
and not infrequently accompanied by hallucinations. However, this delirious
picture does subside and leaves the patient at a considerably reduced
functioning level from which he gradually declines further. As previously
noted, this gradual decline is first seen as defects of memory and then errors
in judgment. Some individuals become very irritable, aggressive, and
quarrelsome. In contrast with senile dementia, these patients are more likely
to have some insight into the fact that they are losing some of their
intellectual skills. Depression complicates the picture, and suicidal impulses

may produce a serious problem for the family and physician.
Changes of EEG in Late Life
Focal abnormalities of EEG, predominantly over the temporal areas of

the brain, and maximally on the left, have been repeatedly observed in 30 to
40 percent of apparently healthy elderly people. This finding was first
reported by Busse et al. in 1955. Since that date the observation of the
frequent occurrence of a left-temporal focus in old people has been reported

by other investigators. A study of healthy volunteers between the ages of 20
and 60 reveals that only 3 percent of normal adults under the age of 40 years
have temporal lobe EEG changes. This increases so that in the 20 years
between 40 and 60, 20 percent of the subjects show temporal lobe
irregularities. After age 60, the focal disturbance tends to be stabilized, as
very few elderly subjects studied longitudinally have developed a focus or

have shown an increase in the degree of abnormality once they have entered
the latter part of their life.
The exact origin of these foci as well as their significance is still not
clear. The localized EEG abnormality is usually episodic in nature and is
composed of high-voltage waves in the delta and theta range, occasionally

accompanied by focal short waves. The disturbance is found in the waking
record, is maximum in the drowsy state, and disappears in sleep. In 75 to 80
percent of the cases the abnormality is at a maximum or completely confined

to the left side of the brain. It is not related to handedness, and although it is
evidently episodic in nature, it is unrelated to seizures. There are indications
that these temporal foci commonly seen in normal senescence are associated
with a localized cerebral circulatory insufficiency.
Another common characteristic of EEG changes is the progressive
slowing of the dominant frequency involving the alpha frequency and the
appearance of slow waves in the theta or delta range. A slight slowing of the
alpha index is not pathognomonic for any particular brain disorder. However,
moderate to severe slowing is characteristically found in brain disorders
whether they are classified as degenerative or vascular in origin. Elderly
subjects in good health are found to have a mean occipital frequency which is
almost a full cycle slower than that found in healthy young adults.
Furthermore, about 7 percent of the EEG’s in the elderly subjects were

dominated by slow waves in the theta range, that is, 6 to 8 per second. Since a
good correlation has been demonstrated between EEG frequency and
cerebral oxygen consumption or blood flow, the slowing of the dominant
frequency in the majority of elderly people may indicate a depression of

cerebral metabolism.
The correlation between EEG changes with advancing age and reduced
intellectual functions indicates that, in residents of old age homes and other
institutions, alterations are related to measures of brain impairment.

Unfortunately, this correlation is not nearly as clear in subjects remaining in
the community. It is possible that those who live in the community are
actually adjusting at a borderline level and may be vulnerable to disruption in

functioning which would precipitate the appearance of organic brain disease.
The focal disturbances in senescent EEG’s have not been consistently

correlated with any particular psychological function or measure. However, a
review of our longitudinal studies indicates that the presence of a focus in the
left anterior temporal region is closely associated with a decline in verbal
abilities, while the diffuse slowing in the occipital rhythm is associated with a
decline in performance abilities. However, it is necessary to remember that
these findings may be influenced by such factors as levels of arousal,
medication, and innumerable other influences which require further study.
There appears to be a relationship between EEG frequency and blood
pressure, as the correlation between these two variables in healthy elderly

subjects is highly significant. Included in a study were also those individuals
with compensated heart disease, but who had significantly higher blood
pressure than those without heart disease. In these individuals with mild and
moderate hypertension, a somewhat faster EEG frequency is associated with

less evidence of brain disorder than in those individuals without heart
disease. All of these findings suggest that there is an impairment of cerebral
vascular autoregulation in many elderly subjects, and consequently the

cerebral blood flow has become more dependent upon the blood pressure. It
appears that moderate elevation of blood pressure in many individuals helps
to preserve the brain. However, sustained severe diastolic hypertension

(106+) is often associated with intellectual decline.
EEG’s taken of elderly subjects in their sleep reveal some very
important changes. Elderly subjects require a longer period to fall asleep and
their sleep is lighter. There are more frequent wakenings, and deep sleep
(stage 4) virtually disappears. These changes are considerably more

pronounced in persons with significant organic brain disease.
The Nursing Home
One of the most difficult tasks is the selection of a nursing home for a
chronically ill person, particularly if mentally impaired and advanced in age. If

one approaches such a complex task, it is essential not only to have guidelines
and standards for the services in a nursing home, but also one must evaluate
the patient so that the environment and activities selected are best suited to
meet his needs. For this purpose it is necessary to evaluate the extent of the
overt incapacities which reduce the individual’s capabilities for his own daily
personal care; for instance, the inability of a person to bathe and dress
without assistance, and the physical and mental capacity to be responsible for
mobility, either walking or through private or public conveyances.
Other changes occur in the later years which are not as easily
recognized and yet are very important to the total functioning of the
individual and for life satisfactions. For example, there may be a decline in a
person’s capacity to taste, smell, feel pain and temperature changes, to hear,
and to see. The process of senescence, or so-called normal aging, brings with
it a decline in the ability to hear certain high-frequency sounds and to
separate from a number of sounds those which are most meaningful. It also
affects the speed in which a person can adjust when moving from a dark to a
lighted room or vice versa. Also, the elderly person requires greater
illumination to work and to see such things as utensils and food. Such changes
require that the environment be structured to meet the needs of the elderly.
This environment is quite different from that which is best suited for the
health and adjustment of a younger person. The age changes mentioned
above appear relevant to the criteria used in selecting a nursing home.
What Is a Nursing Home?
Unfortunately, what is legally considered a nursing home may be
considerably different from one locality to another. A dimension was added to

the long-term health care of the elderly when the term “extended care” was
introduced by Public Law 89-97 amendments to the Social Security Act of
1965. Extended care and the extended-care facility conceived under Medicare
legislation are intended to be an extension of hospital care. It is meant to be
an active-treatment program aimed at restoring the patient to an acceptable
level of functioning within the community. The term “extended care” has
been, but should not be, confused with long-term care or continuing care. This
type of care involves patients who are unable to remain at home because they
cannot, physically or mentally, either independently or with assistance,
maintain a satisfactory adjustment. Generally speaking, such long-term
facilities are classified as nursing homes, but there are states such as New
York that permit one facility to offer both such services, that is, nursing-home
care and extended care. Obviously, extended care is oriented towards
rehabilitation, while nursing-home care is geared to maintaining life at a level
as satisfactory as possible. There is a financial differentiation, particularly
important as extended care can be financed by Medicare. The situation is
confused, since it is often difficult to distinguish between the patient’s need

for extended care and for nursing-home care. In determining eligibility, one of
the primary determinants is the prediction of the patient’s ability to regain
capacity to care for himself. Once it is determined that the patient requires
chronic or long-term institutional care, the patient is probably no longer
eligible for Medicare benefits, even though his health status may be such that
he requires constant attention. Long-term care is often provided in
proprietary nursing homes, in a few publicly sponsored chronic-disease
hospitals or homes for the aged and infirm, and in state mental institutions.
In selecting a long-term care facility, the advice of a knowledgeable
physician, though of value, may have limited use because of the complexity
and the fluidity of long-term facilities and programs. The physician, of course,
is interested in maintaining good communication with the nursing-home
administrator and the skilled health personnel on the staff. He is particularly
interested in ensuring that good records are kept so that he can evaluate the
health status of the patient and ensure his prescribed medication and
programs are accurately followed.
Administration
One of the most serious drawbacks in either a proprietary or public
nursing home is usually the remoteness of the director. The owner or the
director of a proprietary nursing home should be continually involved with
the services, as it is as easy to make the assumption that the home is
functioning very effectively because the purchasing systems, the accounting
methods, etc., are efficient. It is important to make certain that the
administrator does have the capacity to make judgments regarding policy

changes in patient care.
Nursing Home Location
Firm guidelines cannot be developed as to the urban, rural, or semirural

location of a nursing home. Regardless of where the home is located, there
should be sufficient stimuli in the environment to keep the person alert and
interested. An elderly person can be very lonely regardless of where the home
is located. Many approaches can be utilized to maximize the stimuli from the
environment. For example, in an air-conditioned nursing home, externally
located pickups transmit into the dining and living areas the familiar early
morning songs of birds. Such devices can be extended to a bird identification
by song or bird-watching activity which can add an important dimension to
living.
The nursing home cannot expect to function effectively as an isolated
unit. It must have intimate and continuing relationships with community
activity and resources. The administrator and personnel of the nursing home
must have good working relationships with church groups and any other
public or private groups or agencies that can be of value to the residents of

the home. Periodic visits and projects by such organizations as Girl Scouts
have proved to be of great value.
The Quality of Nursing Care
The personnel who come in day-to-day contact with the residents of a
nursing home include those associated with the so-called nursing service, the
food service, and other supporting service people. Employees associated with
the nursing service include registered nurses, practical nurses, nursing aides,
and attendants. All of these individuals offer what is called nursing care. It is
not merely the administration of drugs and the applications of treatment
techniques but an extremely demanding relationship with elderly people that

is necessary in order to make the older resident feel that he is understood,
that his needs are appreciated, and that his health and well-being are
important to those who come in contact with him. A chronically ill elderly
person is particularly aware of his high dependence upon nursing personnel,

as he can easily be deprived of many satisfactions if they become annoyed or
angry with him. Consequently, some patients try to be modest in their
requests, so that in the event they are in desperate need, nursing personnel
will adequately respond to their needs. Often an older person feels that he is
not being properly cared for but is afraid to express his displeasure because
he may antagonize the very ones who are responsible for his care.
Recent studies in Great Britain indicate that there is a serious

misconception regarding nursing by many nursing-home administrators.
They seem to believe that geriatric patients require less nursing skill and
fewer nurses than acute medical and surgical patients. Detailed records and
observations indicate that this is not true, particularly in homes which have
admitted or accumulated a large number of seriously ill people. The range of
diagnoses and treatment regimes is wide, requiring great knowledge and
skill, and many of the chronic illnesses are complicated by mental confusion
and the burden of fecal and urinary incontinence. Dr. Robin E. Irvien and Miss
B. J. Smith reported to the British Geriatric Society in London (Spring, 1970)
that many geriatric units require a very high nurse-patient ratio, a ratio of
one-to-one being the best.
Serious Illness
Although it is extremely important that the residents of a nursing home
have the services of a physician when required, it is obvious that many of the
complicated diagnostic procedures cannot possibly be carried out within a
nursing home. Therefore, transportation should be readily available for the
patient to be moved to the medical facility where diagnostic procedures can
be carried out, or to a hospital if necessary.
Food Service
The dietician and the administrator responsible for the preparation and
the serving of food to residents of nursing homes must be aware of the
physiological and pathological changes that accompany old age. The decline
in ability to taste and to smell are directly relevant to the dietary service. In
addition, the normal changes of aging require better lighting in order to
adequately see certain objects. The loss of teeth often makes it necessary for
the dietician to make foods attractive and distinctive without having them
appear as a pureed, undifferentiated mass.
The weak and unsteady hands of many elderly persons make it
embarrassing to attempt to cut food or to properly prepare it, such as the

buttering of bread and biscuits. Assistance in the preparation of food must be
done in an unobtrusive, helpful manner that is not embarrassing to the
patient. The plates must be deep, and some nursing homes prefer to use
compartment plates. Cups and glasses must be of adequate size, but not
heavy. The silverware, too, must be efficient but lightweight. The process of
eating is often a social event, and therefore it is essential that the persons can
sit comfortably, eat at a reasonable pace, and have an opportunity for
conversation after the meal. The chairs should be comfortable and the tables
large enough to permit adequate distances between the diners. It is important
that the consumption of food be observed so that adequate intake is assured

without forcing the elderly person as some people force children to eat all
that is placed before them.
There is no doubt that there is a continuing shortage of well-trained and
capable individuals in these service fields. Food service is no exception, and it
is unfortunate that many nursing homes are aware of deficiencies within their
food services but cannot find capable personnel, even though they are willing
to pay adequately. Consequently, it is often necessary for family and friends to
assist whenever possible and to make certain that food intake is pleasant and
adequate.
A number of investigators have found that the addition of beer and wine
to the routine of a nursing home or a chronic-care unit has proved to be

extremely effective toward improving patient morale. It is known that alcohol
is a sedative, but the availability and the addition of beer and wine have
increased conversation and social interaction. Certainly, people who have

been accustomed to such beverages throughout their life should not be
denied the opportunity to enjoy them in old age. Alcoholism or excessive

alcohol intake can be a problem at any age, but fortunately its consumption
can be carefully controlled in most nursing homes.
Activities
Visits to randomly selected nursing homes reveal that a large number of

patients appear to be withdrawn, unsociable, and virtually unreachable.
Purposeful mass activity has been found to be a very useful device in breaking
down this wall separating the elderly person from the world.
Physical Environment
Room arrangement, a roommate, ease of the residents’ movement in
their rooms and to recreational areas are all of utmost importance. The
nursing home should be a “home” in the true sense, offering security, comfort,
and stimulation. Residents in a nursing home should participate fully in

planning and carrying out social activities and have an opportunity to make
suggestions regarding not only the services rendered but the appearance and
structure of the environment. Lighting is of particular importance. Night
lights are necessary in many locations, as elderly people find it particularly

difficult to move around in the dark and cannot move from a well-lighted
room to a dark room without a lengthy delay in visual accommodation. With
advancing age there appears to be a rather capricious intolerance to changes

in temperature. It is important that the temperature of the building be held as
constant as possible so that the variation in how an elderly person responds
to the temperature can be individualized and handled by the addition of
wraps or the reduction in the number of clothes. The floor of a nursing home
should be level, avoiding even small steps. For example, bathroom floors
should not be raised requiring an older person to step up or down. Handrails
for assistance should be adjacent to commodes and bathtubs.
Nursing-Home Care Versus Hospitalization
In the 1970s, the proportion of older persons in mental hospitals has
increased steadily. At any given time, at least one of three beds in a public
mental hospital is occupied by a person 65 years or older. Approximately one-
third to one-half of the persons in the 65 or older age group in public mental
hospitals are admitted at an earlier age. However, the remaining one-half or
more were admitted at age 65 or older. Eighty-three percent of first-
admission older patients are diagnosed as having senile brain disease and/or
arteriosclerotic brain damage. The reliability of these clinical diagnoses has
been questioned and has been under study for many years. The coexistence of
senile and arteriosclerotic brain disease is not unusual and is discussed in
Chapter 4.
Nursing homes have become a major resource for the placement of aged
patients from state mental hospitals. Questions have been raised as to
whether these homes are appropriate for this type of patient. Investigators at
the Boston State Hospital conducted a one-year controlled study of sixteen
nursing homes housing approximately 14,000 patients. They found
institutional deprivation—physical, intellectual, or spiritual—to be a common

problem. Deprivation in nursing homes was found to be particularly related
to: (1) lack of stimulation; (2) lack of adequate walking space inside and
outside the homes; (3) lack of recreational and occupational therapy; (4) lack
of space for group socialization and activities; (5) lack of a common dining
room forcing patients to eat from trays in their rooms; (6) absence of
volunteer workers from the community; (7) separation of patients on
different floors, reducing the possibility of interaction; and (8) minimal

socialization between male and female patients. This study indicated that
regressive behavior can be the result of deprivation rather than organic
changes. Regressive behavior is manifested by withdrawal, seclusiveness,
uncooperativeness, incontinence, refusal to eat, loss of interest in personal

hygiene, loss of ability to perform self-care functions, and grossly
inappropriate social behavior. Some investigators believe that the nursing

supervisor is the key staff member in a nursing home. The type of person,
selected by the administrator and owner to be the nursing supervisor, is of

great importance. At least three types of nursing supervisors can be
identified. The permissive supervisor leads to an indifferent staff and anxious
patients. The dominant supervisor, although running a home that is a model
of efficiency and neatness, lowers the self-esteem of the staff and is likely to
disregard patients’ emotional needs. A staff-centered supervisor who shares
control of responsibility and planning with the staff is much more likely to
contribute to the effectiveness of the home program. A nursing supervisor
who has produced the best climate for the patient is desirable, but may not be
appreciated because some people prefer to have cleanliness and neatness
take priority over meeting emotional needs.
Bibliography
Aging. “Great Variations Found in State Aging Populations Patterns,” 204 (1971), 10-11.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-II).
Washington, D.C.: APA 1968.
_____. A Psychiatric Glossary, 3rd ed. Washington, D.C.: APA., 1969.
Benet, S. “Why They Live to Be 100 or Even Older in Abkhasia,” N.Y. Times Magazine, Dec. 26,
1971.
Brotman, H. E. Facts and Figures on Older Americans. The Older Population Revisited, Publication
182. Washington, D.C.: U.S.
Department of Health, Education, and Welfare, Administration on Aging, 1971.
Buckley, C. E. and F. C. Dorsey. “Serum Immunoglobulin Levels Throughout the Life-Span of

Healthy Man,” Ann. Intern. Med., 75 (1971), 673-682.
Bureau of the Census. Expectation of Life, Statistical Abstract of the United States, Life Table
Values No. 69, p. 53. Washington, D.C.: Bureau of the Census, 1971.
Busse, E. W. “Psychopathology,” in J. Birren, ed., Handbook of Aging and the Individual, pp. 364-
399. Chicago: University of Chicago Press, 1959.
_____. “Psychoneurotic Reactions and Defense Mechanisms in the Aged,” in P. H. Hoch and J. Zubin,
eds., Psychopathology of Aging, pp. 274-284. New York: Grune & Stratton, 1961.
_____. “The Mental Health of the Elderly,” Int. Ment. Health Res. Newsletter, 10 (1968), 13-16.
_____. “The Geriatric Patient and the Nursing Home,” N.C. Med. J., 33 (1972), 218-222.
_____. “Aging,” to be published in the World Book Encyclopedia, Chicago, 1975.
Busse, E. W., R. H. Barnes, A. J. Silverman et al. “Studies in the Processes of Aging. X: The Strengths
and Weaknesses of Psychic Functioning in the Aged,” Am. J. Psychiatry, 111 (1955),
896-901.
Busse, E. W., R. H. Dovenmuehle, and R. G. Brown. “Psychoneurotic Reactions of the Aged,”

Geriatrics, 15 (1960), 97-105.
Busse, E. W. and W. D. Obrist. “Significance of Focal Electroencephalographic Changes in the

Elderly,” Postgrad. Med., 34 (1963), 179-182.
_____. “Presenescent Electroencephalographic Changes in Normal Subjects,” J. Gerontol., 20 (1965),

315-320.
Comfort, A. Ageing: The Biology of Senescence. London: Routledge and Kegan Paul, 1964.
Davis, G. C., L. Thompson, and A. Heyman. “Hyperbaric Treatment in Dementia.” Paper presented
American Academy of Neurology, Boston, April 1973.
Department of Health, Education, and Welfare. Public Health Service Health Statistics, PHS Publ.
No. 580-536. Washington, D.C.: U.S. Govt. Print. Off., Oct. 1962.
Ehrenteil, O. “Differential Diagnosis of Organic Dementias in Affective Disorders in Aged

Persons,” Geriatrics, 12 (1957), 426.
Erikson, E. H. Identity and the Life Cycle. Psychological Issues Vol. 1, No. 1. New York:
International Universities Press, 1959.
_____. Gandhi’s Truth, pp. 21, 403-406. New York: Norton, 1969.
Gibbs, C. J., D. Gadjuske, D. Asher et al. “Creutzfeldt-Jakob Disease: Transmission to the

Chimpanzee,” Science, 161 (1968), 388-389.
Goldfarb, A. I., N. Hochstadt, and J. H. Jacobson. “Hyperbaric 0₂ Treatment of Organic Mental

Syndrome in Aged Persons,” Gerontologist, 10 (1970), 30.
Haase, G. R. “Diseases Presenting as Dementia,” in C. E. Wells, ed., Dementia, pp. 163-207.

Philadelphia: Davis, 1971.
Harman, D. “Free Radical Theory of Aging: Effect of Free Radical Reaction Inhibitors on the
Mortality Rate of Male LAF Mice,” J. Gerontol., 23 (1968), 476-482.
Hayflick, L. “Human Cells and Ageing,” Sci. Am., 218 (1968), 32-37.
Jacobs, E. A., P. M. Winter, and H. J. Albis. “Hyperoxygenation Effects on Cognitive Functioning in

the Aged,” N. Engl. J. Med., 281 (1969), 753-757.
Kahn, R. L., A. I. Goldfarb, M. Pollack et al. “The Relationship of Mental and Physical Status in
Institutionalized Aged Persons,” Am. J. Psychiatry, 117 (1960), 120-124.
Kramer, M., C. A. Taube, and R. W. Redick. Patterns of the Use of Psychiatric Facilities by the Aged—
Past, Present and Future, American Psychiatric Association Task Force on Aging.
Washington, D.C.: APA, June 1971.
Leaf, A. “Every Day is a Gift When You Are over 100,” Natl. Geogr. (Jan. 1973), 93-118.
Maddox, G. L. “Self-Assessment of Health Status,” J. Chron. Dis. 17 (1964), 449-460.
Marshall, J. The Management of Cerebral Vascular Disease. Boston: Little, Brown, 1965.
Neugarten, B. L. et al. Personality in Middle and Late Life, pp. 189—190. New York: Atherton,
1964.
Obrist, W. D. “Cerebral Physiology of the Aged: Influence of Circulatory Disorders,” in C. M. Gaitz,

ed., Aging and the Brain, pp. 117-133. New York: Plenum, 1972.
Post, F. The Clinical Psychiatry of Late Life. Oxford: Pergamon, 1965.
_____. The Significance of Affective Symptoms in Old Age, p. 10. Maudsley Monograph. London:
Oxford University Press, 1962.
Pratt, R. T. C. “The Genetics of Alzheimer’s Disease,” in G.E.W. Walstenholme and M. O’Connor,

eds., Alzheimer’s Disease and Related Conditions. London: A Ciba Foundation
Symposium, 1970.
Pryor, W. A. “Free Radicals of Biological Systems,” Sci. Am., 223 (1970), 70-83.
Shternberg, E. Y. and M. L. Rokhlina. “Depression in Old Age,” Zh. Nevropatol. Psikhiatr., 70

(1970), 1356-1364.
Simon, A. Background Paper, White House Conference on Aging. Washington, D.C.: U.S. Govt. Print.
Off., 1971.
Smith, K. U. and F. G. Smith. Cybernetic Principles of Learning and Education Design, p. 29. New
York: Holt, Rinehart, & Winston, 1965.
Strehler, B. L. “Genetic and Cellular Aspects of Life Span Prediction,” in E. Palmore and F. Jeffers,
eds., Prediction of Life Span, pp. 31-49. Lexington, Mass.: Heath, 1971.
Thompson, L. W. Effects of Hyberbaric Oxygenation on Psychological and Physiological Measures in

Elderly Patients with Dementia. Presented Gerontol. Soc., Miami, Nov. 1973.
Threatt, J., K. Nandy, and R. Fritz. “Brain Reactive Antibodies in Serum of Old Mice Demonstrated
by Immunofluorescence,” J. Gerontol., 26 (1971), 316-323.
Time, “The Old in the Country of the Young,” Aug. 3, 1970, pp. 49-54.
Wang, H. S. and E. W. Busse. “EEG of Healthy Old Persons—A Longitudinal Study. I. Dominant
Background Activity and Occipital Rhythm,” J. Gerontol., 23 (1969), 419-426.
_____. “Dementia in Old Age,” in C. E. Wells, ed., Dementia, pp. 152-161. Philadelphia: Davis, 1971.
Wang, H. S., W. D. Obrist, and E. W. Busse. “Neurophysiological Correlates of the Intellectual

Function of Elderly Persons Living in the Community,” Am. J. Psychiatry, 126
(1970), 1205-1212.
Wang, H. S., W. D. Obrist, C. Eisdorfer et al. “Heart Disease and Brain Impariment in Community
Aged Persons.” Presented 23rd Ann. Meet. Gerontol. Soc., Toronto, October 1970.
Wilkie, F. L. and C. Eisdorfer. “Intelligence and Blood Pressure in the Aged,” Science, 172 (1971),
959-962.
Wolford, R. L. The Immunological Theory of Aging. Copenhagen: Muksgaard, 1969.
Chapter 4
The Neuropathology Associated With The

Psychoses Of Aging
Armando Ferraro
Neuropathology of Cerebral Arteriosclerosis
To describe the pathologic changes in cerebral arteriosclerosis
accurately, it is necessary to separate the pathology of the large cerebral

blood vessels from that of the small blood vessels, arterioles, and capillaries.
In all the blood vessels involved, the ultimate result will be an obstruction to
the blood supply of a given area, thus resulting in softenings of variable
dimensions, or in the extravasation of blood leading to red softenings, or to

the rupture of a blood vessel leading to massive hemorrhages.
Before describing the pathology of the vascular changes, it may be well
to consider the fact that the clinical symptoms of cerebral arteriosclerosis are
related to the extent of the branching of the blood vessels participating in
brain-tissue damage caused by the softening or by the hemorrhage. Large
softenings or hemorrhages are evidently more apt to result in neurological
symptoms, whereas smaller softenings or blood extravasations are more apt
to result in mental symptoms. Furthermore, from a neurological standpoint,

the extent of the focal damage in the territory of the various blood vessels
involved will determine the extent of the neurological symptoms.
It is not my task to discuss the clinical neurological and psychiatric
aspects of cerebral arteriosclerosis, but it is not out of place here to mention
briefly that the brain is supplied by the superficial and deep branches of the
three main cerebral arteries, the anterior, the medial, and the posterior
cerebral arteries, which represent the offshoot of the anatomical branching of
the blood vessels participating in the formation of the circle of Willis. Very
briefly, the superficial territory of vascular irrigation of the anterior cerebral
artery covers in general the mesial surface of each cerebral hemisphere, that
of the middle cerebral artery covers their external surface, and that of the
posterior cerebral artery covers their basal surface. The neurological
symptoms which follow softenings or hemorrhages in the territory of the

superficial or deep branches of these arteries constitute the various clinical
pictures of hemiplegia, monoplegia of the upper or lower extremities,

hemianopsia, alexia, apraxia, aphasia and the like, according to the damaged
cerebral territory.
I see no need to report the details of the macroscopic appearance of the
brain damage in relation to the occlusion or rupture of each individual branch
of the three main cerebral arteries, and will limit myself to illustrating the
gross appearance of some of the focal softenings connected with the occlusion
of some of the branches of the anterior, middle, and posterior cerebral
arteries. Figure 4-1(a) illustrates the macroscopic appearance of a large area
of softening in the region supplied by the calloso-marginal branch of the

anterior cerebral artery; Fig. 4-1(b) the macroscopic appearance of a large
area of softening in the region supplied by the anterior-parietal artery, a
branch of the middle cerebral artery; and Fig. 4-1(c) the macroscopic
appearance of a large area of softening in the region supplied by two other

branches of the middle cerebral artery, the anterior temporal and the
temporo-occipital arteries. Figure 4-2 illustrates the macroscopic appearance
of a large bilateral area of softening in the region supplied by the parieto-

occipital artery, a surface branch of the posterior cerebral artery.
Figure 4-3 illustrates, better than any description, the sclerotic

appearance of some of the larger branches of both the anterior cerebral
artery (Figure 4-1(a)) and the middle cerebral artery (Figure 4-1(b)) which
discloses thickening of their walls, tortuosity, and nodosity. The pathologic

process involving the large cerebral blood vessels is generally designated as
“atherosclerosis” a process characterized by patches of yellowish material
deposited along the internal surface of the artery, but often visible from the
outside because of the translucency of the blood-vessel walls. These patches,
which impart a beady nodular appearance to the sclerotic vessels, result in
various degrees of narrowing of their lumen, because of their projecting

knobs under the intima layer of the vessel. Consequently the blood vessel
walls become irregularly dilated and at the same time lose their normal
elasticity. In addition to their local damaging effects, these changes evidently

contribute to the wider disturbance of the cerebral hemodynamic
equilibrium.
Figure 4-1.
(a) Macroscopic appearance of a large area of softening in the region
supplied by the callosomarginal artery, (b) Macroscopic appearance of a
large area of softening in the region supplied by the anterior parietal
artery, branch of the middle cerebral artery, (c) Macroscopic appearance
of a large area of softening in the region supplied by the anterior temporal
and the temporo-occipital arteries, branches of the middle cerebral artery.
Figure 4-2.
Figure 4-2.
Macroscopic appearance of a large bilateral area of softening in the region

supplied by the parieto-occipital artery, surface branch of the posterior
cerebral artery.
Figure 4-3.
(a) Macroscopic appearance of arteriosclerotic changes in branches of the
anterior cerebral artery, (b) Macroscopic appearance of arteriosclerotic
changes in branches of the middle cerebral artery. Note thickening,
tortuosity, and somewhat nodular appearance of the diseased blood
vessels.
Microscopically the focal yellowish thickenings of the large blood
vessels, also designated as “atheromas,” consist of fatty substances,
hyperplastic connective tissue, a thickened endothelial layer, and a thickened
internal elastic membrane. The lipids in the intima consist predominantly of
lipoproteins, cholesterol and its esters, 10 percent phospholipids and 30
percent natural fats. Hyaline and calcium deposits may also be found in the
midst of the atheromatous tissue undergoing necrosis. Figure 4-4 (a)

illustrates the fibrotic thickening of the walls of a sclerotic blood vessel and
their fatty degeneration, and Fig. 4-4(b) the lumen of a vessel reduced by
accumulated fat and elastic tissue, resulting from the splitting of its elastic
membrane.
The atheromatous changes of the large blood vessels in humans are,
with the exception of necrosis, quite similar to the changes produced
experimentally in rabbits, hens, cockerels, and dogs fed high cholesterol diets,
which result in a gradual shutting off of the blood circulation in the involved
area. However, this similarity of experimental pathology in humans and

animals, resulting from high cholesterol diet, applies only to blood vessels
outside the cerebral ones, inasmuch as, according to some investigators, the
latter do not seem to participate in the pathologic process as do the blood

vessels of other organs.
Figure 4-4.
Figure 4-4.
Microscopic atherosclerotic changes in a large blood vessel, (a) Fatty

degeneration and fibrotic thickening of the vessel walls, (b) Fatty
degeneration, splitting of the elastic membrane, and marked reduction of
the blood-vessel lumen.
Microscopic Changes in the Small Blood Vessels
In the small blood vessels the pathologic process has been designated
not as atherosclerosis but as “diffuse hypertrophic arteriosclerosis” by Evans,

Ophuls, and Moschkowitz, or “arterio-capillary” fibrosis by Gull and Sutton, or
“arteriolosclerosis” by Neuburger, Hall, and others. In the diffuse
hypertrophic type the early pathologic changes consist in the proliferation of

the endothelial lining cells of the intima, followed later by an increase in the
fibrous tissue and a delamination of the elastic membrane. In both small
arteries and arterioles, the process is a diffuse one which may lead not only to
a thickening of the media, but later to the hyaline degeneration of the entire
vessel wall. In this variety the increase in number of the cells of the intima,
and their concentric lamellation, produce what has been referred to as “an
onion-skin-like” appearance of the cross section of the vessel.
In the second variety of arteriosclerosis of the small blood vessels, the
“arteriolosclerosis,” Hall described as the outstanding feature the

hypertrophy of the muscular fibers of the media associated with increased
collagen, resulting in the thickening of the vessel wall with the exception of
the intima. A third variety is represented by “hyalinization” in which deposit
of hyaline material in the subintimal layer is the primary feature. Hyalinosis

may then extend gradually to the whole wall, leading at first to a decreased
contractility of the small blood vessel and ultimately to the reduction of its
lumen or even occlusion. According to Herburt, hyaline degeneration, a
frequent occurrence in cerebral arteriosclerosis, occurs when the arteriolar
lesion develops slowly, and such a change may be seen associated at first with
splitting, reduplication, and fragmentation of the internal elastic membrane.
Hyaline degeneration is, however, diffuse and prominent also in

cerebral hypertension. Without entering into the discussion of the general
relationship of hypertension to cerebral arteriosclerosis, the fact remains that
it is in association with severe hypertension that the most severe and diffuse
hyaline degeneration of the cerebral blood vessels has been reported and
related to imbibition of the blood vessel walls by protein substances due to
disturbed permeability of the vascular endothelium.
Anders and Eicke, reviewing their cases of hypertension, stress that the
occurrence of hyalinosis, which originates in the subendothelial layers, may
invade the whole wall of the vessel, protrude in its lumen and end in a global
fatty degeneration of the whole wall. They proposed for this condition the
term “arteriopathia hypertonica.” Rosenberg, in his studies of the blood
vessels in malignant hypertension, stresses however the point that a
thickening of all three layers of the small blood vessels with splitting of the
internal elastic membrane, and resulting reduction of the lumen of the blood
vessel, is as frequent an occurrence. Because of the difficulty of drawing a

distinct separation between hyaline degeneration, as an expression of
cerebral arteriosclerosis, and severe hyaline degeneration related only to
hypertension, one may consider general hyaline degeneration to be a variety
of arteriosclerosis fitting into the general picture of cerebral arteriosclerosis.
Figure 4-5 illustrates an advanced stage of hyaline degeneration in the midst

of other vascular changes in a case clinically and pathologically diagnosed as
cerebral arteriosclerosis.
Figure 4-5.
Marked hyaline degeneration of all the three layers of the walls of a blood
vessel.
A fourth variety of arteriosclerosis of the small blood vessels is the one

described by Scheinker, as “obliterative cerebral arteriosclerosis” found
particularly in older patients (sixty-eight to ninety-four years). He
differentiated this condition from the “diffuse hyperplastic variety” because in

obliterative cerebral arteriosclerosis, the pathologic changes are limited to
the intima in terms of a proliferation of the subendothelial connective tissue,
though accompanied by hyalinosis or of fatty degeneration of the vessel walls.
“Capillary fibrosis,” a special aspect of cerebral arteriosclerosis, has also
been considered as being related to other specific endogenous or exogenous
toxic or infectious diseases of the brain outside the field of cerebral
arteriosclerosis.
Microscopic Changes in the Brain Parenchyma
Those changes could be divided into two categories: the changes
following occlusion or rupture of large cerebral blood vessels, and the

changes which follow the involvement of small blood vessels. However, this
would repeat the basic description of the parenchymal change, which does
not differ in the two categories, as far as softenings and hemorrhages are
concerned, except in the severity and the extension of the lesions, the depth of
the damage, and the degree of the reparative process. It goes without saying,
that a large area of softening or hemorrhage is less apt to undergo repair
capable of reestablishing the functionality of the damaged tissue and its
continuity with the surrounding tissue.
Referring to a rather large area of softening of relatively recent
occurrence, the basic microscopic changes consist in the presence, in that
area, of a mixture of necrotic nervous tissue in the midst of which blood cells
may still be found. If the lesion is an older one, blood cells may be absent,
though residues of blood pigments may still be seen. If the softening is an
older one, the progressive removal of the necrotic tissue may result in the
formation of small or larger cavities in which remnants of the disintegrated

tissue may still be present, most of it having been removed by phagocytosis. A
certain amount of fluid may be present in such necrotic cavities. Figure 4-6
illustrates the microscopic appearance of such an area.
Figure 4-6.
Microscopic appearance of an area of softening which has resulted in two
cystic formations because of the inadequate process of repair. Note the
reparative activity of the astrocytes at the periphery of the cavities. Cajal’s
gold sublimate method for astrocytes.
Without reference to the size of the ischemic softening, I may briefly
state that an area of softening is characterized by a more or less complete
process of disorganization or destruction of the nervous parenchyma. The
destructive process involves all the neural elements, nerve cells, nerve fibers,
and glia cells, as well as the vascular and mesodermic elements of support.
Nerve cells undergoing all gradations of degenerative changes may be seen,
from the severe type of Nissl’s “liquefaction,” to the Spielmeyer “ischemic

type” of degeneration. Reparative activities soon take place. They begin with
the reaction of the microglia cells, which multiply, invade the degenerated
tissue, and disclose all stages of transformation into compound granular
corpuscles, intended to clear the disorganized areas from the remnants of

degenerated tissue (Figure 4-7). Concomitantly the mesodermic elements of
the nervous tissue, which constitute the blood vessel walls of the region,
begin to proliferate and gradually form a visible mesenchymal net.
Figure 4-7.
Figure 4-7.
Microscopic appearance of an area of softening disclosing the presence of a

large number of compound granular corpuscles. Nissl stain.
In the first stage of the process of repair, the mesenchymal reaction is
predominant. In a subsequent phase, the astrocytes participate very actively
in that process through their hyperplasia and hypertrophy leading gradually
also to the increased number of glia fibers, which, intermingling with the
connective tissue elements, form the ultimate scar tissue. In the final phase of
the process, the glia reaction is the dominant element, the scar tissue being
ultimately formed by a preponderance of glial fibers.
On the other hand, if the vascular occlusion has been a minor one, or of
a temporary nature as in the case of transitory vascular spasms, the structural
damage is much less intense. As a matter of fact, morphologic evidence of
parenchymal destruction may be lacking completely, if the spasm was of a
very short duration. Only if it lasts longer, will the blood deficiency result in
irreversible structural changes, and in the case of the cortex, in small patches
of the tissue, or in a more selective way in the involvement of individual nerve

cells of a given cortical area. This “neuronal or selective neurosis,” as Scholz
labeled it, is characterized mainly by the “ischemic type of degeneration” of

individual nerve cells. Their collective presence may result in the formation of
areas of different size and distribution in the midst of which bleaching of the
nerve cells constitutes the only indication of the ischemic damage. Figure 4-8
illustrates the low-power microscopic appearance of spotty areas of
bleaching in the brain cortex resulting from the paling of the nerve cells in the
affected areas. At times the ischemia of a cortical area determines a necrosis
of nerve cells along a certain well-defined cortical layer and is called “laminar
necrosis.” That transitory vasospasms may determine focal necrosis or
laminar necrosis has been documented by Neuburger in his cases of cardiac

arrest of no more than a few minutes.
Figure 4-8.
Microscopic appearance of spotty areas of cellular bleaching in the brain

cortex resulting from rarefaction, and paling of most of the nerve cells
which are undergoing an ischemic type of degeneration. Nissl stain.
Figure 4-9.
Figure 4-9.
Macroscopic appearance of a diffuse “granular atrophy” of the cerebral

cortex resulting from numerous cicatricial cortical retraction of the tissue.
In cases of “patchy neuronal necrosis,” the process of repair differs from

the one taking place in larger or smaller areas of typical softenings. The
reparative process in these cases is mainly one of glia repair, without
participation of the mesodermic tissue. Glial proliferation of astrocytes and

glial fibers represent the dominant elements in the resulting glia scars which
can be observed along the course of individual vessels (Alzheimer’s
Perivascular Gliosis). Whatever the nature of the scar tissue affecting the
cortex may be, the aggregation of several cicatricial areas may ultimately
result in the macroscopic appearance of what Spatz has described as

“Granular Atrophy of the Cortex.” Figure 4-9 illustrates the macroscopic
appearance of a diffuse “Granular Atrophy of the Cortex” resulting from
numerous minute cortical retractions due to scar tissue. The patchy type of
ischemia, as well as the laminar type of cortical degeneration, are evidently of
greater interest to the psychiatrist than to the neurologist, inasmuch as they
generally are not accompanied by appreciable neurological signs but are

more apt to result in mental symptoms.
Intracerebral hemorrhages may occur in both atherosclerosis of the

larger blood vessels and arteriosclerosis of the small vessels. They generally
are found more frequently in connection with atherosclerotic changes. They
may fill the ventricular cavities (Figure 4-10) or a cavity which they create by
compressing the surrounding tissue, so that the loss of brain tissue is only
apparent.
Figure 4-10.
Macroscopic appearance of a massive hemorrhage in the left lateral

ventricle.
In the past it was thought that massive hemorrhages in the brain were
primarily the result of a ruptured blood vessel related to high blood pressure,
or to a ruptured aneurysm. Later Rosenblath refuting, as most other
investigators did, the exclusive concept of Charcot, pointed to the coexistence
of advanced renal diseases in cases of cerebral hemorrhages. He advanced the
theory that under such circumstances an enzyme is elaborated, leading first
to autolysis of the brain tissue around the blood vessels, which as a point of
lowered resistance facilitates their rupture.
Westphal and Baer felt that cerebral hemorrhages arising from diseased
intracerebral arteries are the result of a progressive necrosis of the walls of
the blood vessels themselves, a condition which they termed “angio-necrosis.”
Globus and Strauss and, later on, experimentally, Globus and Epstein
established the fact that ischemic changes surrounding diseased blood vessels
are the important determinants of cerebral hemorrhages, especially if

associated with a concomitant increased blood pressure.
Smaller hemorrhages in cerebral arteriosclerosis may also assume the
form of what is termed “red softening” in which the disintegration of the

nervous tissue is more intimately related to extravasation of blood from
diseased vessels. In such instances, diapedesis seems to be the most
important mechanism, related however to the same prehemorrhagic

conditions of an altered perivascular tissue. Red softenings, which are
generally related to a more general cardiovascular deficiency, occur indeed
more frequently in connection with small arteriosclerotic vessels, as pointed
out by Wilson et al. and Neuburger. Vascular insufficiency may play a far
more important part in the pathogenesis of both softenings and hemorrhages

than does local vascular pathology. Loss of blood and myocardial and
circulatory failure may result in insufficient blood supply, resulting in a
slowing down of the local circulation which creates a prestasis or stasis
around the blood vessels, thus facilitating the development of white or red
softenings. Red softenings are generally localized in the more richly
vascularized gray matter where diapedetic hemorrhages take place not only
from capillaries, but also from small veins, thus pointing out the importance
also of the veinous circulation in the pathogenesis of hemorrhages.
Histopathogenesis of Cerebral Arteriosclerosis
Large Blood Vessels. Generally the accepted theories of atherosclerosis

of the larger cerebral blood vessels are the same as those which apply to the
other large blood vessels of the body. They stem mostly from the
experimental work of Ignatowski, Saltikow, Wesselkin, and Anitschkow, who
induced atherosclerosis in animals and related it to cholesterol deposits in

the blood vessel walls. However, in 1856, Virchow had already advanced the
theory that atherosclerosis was related to fatty imbibition of the blood vessel
walls, secondary to necrobiotic processes in the connective tissue cells and
ground substance of the intima, a theory later on accepted by Aschoff,
Ignatowski, Katz and Stamler, and most other investigators.
According to Wilens both intimal thickening and lipids deposits are
concomitant facts in atherosclerosis.
Klotz believes that an increase, between the endothelial cells, of the
ground substance which becomes hyaline-mucoid in character, precedes the
deposits of lipids in the intima.
Leary held that cholesterol-laden macrophages accumulate in the
Kupffer’s cells of the liver, and their analogues in the adrenals. These pass
into the blood and lymph stream, through the lining filter, and become
deposited in the intima of the arteries. From there they migrate through the
endothelial cells into the subintima.
Duguid held that cholesterol-laden macrophages accumulate in the
intima of the arteries and remain in place, but soon become incorporated
within the artery’s walls by the endothelium growing over the cell mass, and
give origin to intramural thrombi which may gradually increase in size.
Winternitz et al. feel that the greater vascularity of the blood vessel’s
walls, resulting from local deposits of fats or intramural thrombi, is an
important contributing factor to the production of atheromatous changes, a
thesis upheld by Geiringer’s findings.
Hueper contends that a film of fatty substances deposited on the surface

of the intima, because of altered colloid composition, interferes with the
proper oxidation metabolism of the intima, and results in changes which are
secondary to nutritional deficiency.
Small Blood Vessels. The histopathogenesis of the arteriosclerosis of
the small blood vessels may or may not have a direct relationship to the
atherosclerotic changes reported in the large blood vessels.
Are the hyperplastic changes of the small vessels an integral part of

atherosclerosis? It would be interesting, indeed, to investigate cases of
cerebral arteriosclerotic changes of the small blood vessels, and relate them
to the presence of severe or light atherosclerotic changes of the large arteries,
or more so, to the absence of such changes. Unfortunately the various

histopathogenetic theories of cerebral arteriosclerosis, mainly concerning
studies of the small blood vessels, have been advanced without any attempt
by their authors to correlate them with the pathology of the large blood
vessels.
Thus, Eros, studying the small cerebral blood vessels, with no reference
to the large ones, emphasized that the primary and most important
arteriosclerotic changes take place in the elastic tissue, especially in the

internal elastic membrane. All other degenerative changes, such as fatty and
mucoid degeneration, calcification, fibrous proliferation, and hyalinization,
are only secondary to the changes in the elastic tissue. In general he
distinguished two main types of the alterations of the elastic tissue: (1) the
hyperplastic degenerative type; and (2) the hypoplastic degenerative type.
The hyperplastic degenerative type is characterized by the initial
proliferation and splitting of the elastic membrane (Figure 4-11). As the
process advances, the elastic fibers gradually lose their individual outlines
and tend to fuse with each other, giving the membrane a thicker appearance.
While increased fibroblasts and collagenous fibers become more prominent,
they are subsequently followed by fat and calcium deposits and by

hyalinization and mucoid degeneration.
Figure 4-11.
Figure 4-11.
Hyperplastic type of cerebral arteriosclerosis; (a), (b), and (c) are pial
arteries; (d) is an intracerebral artery. Note the proliferation of the elastica
membrane, and the beginning degeneration of the hyperplastic tissue.
Weigert stain for elastic tissue. (Courtesy Dr. G. Eros and the J.
Neurophatol. Exp. Neurol.)
The hyperplastic degenerative type is characterized by either a very
slight tendency to proliferation of the elastic membrane, or none at all. In the
early stages the elastic membrane stains very poorly, loses its sharp outlines
and soon fades out (Figure 4-12). No split in the membrane occurs, and there
is only a slight tendency to fibrous proliferation of the intima proper. The
secondary degenerative changes start early, with fat appearing in the
loosened elastic membrane. Hyaline degeneration follows. Thrombosis is
much rarer.
Figure 4-12.
Atrophic type of cerebral arteriosclerosis. Note the atrophic appearance,

the thinning of the elastic membrane and the dilation of the blood vessel
lumen, and the degeneration of the blood vessel walls. (Courtesy Dr. G.
Eros and the J. Neurophatol. Exp. Neurol.)
Bruetsch makes a distinction between the histopathology of the large

blood vessels of the circle of Willis and the histopathology of the small
cerebral blood vessels. He does not however discuss the quantitative or
qualitative relationship of the two pathologic changes. He stated that the
lesions in the large cerebral arteries are predominantly fatty in type, owing to
an accumulation of cholesterol and lipids in the arterial walls. In the small
cerebral arteries, on the other hand, endothelial proliferation alone with
lipids deposits predominates, while in the smallest blood vessels, hyaline
degeneration often associated with endothelial and fibroblastic proliferation

is a frequent feature (Figure 4-13(a)). In both large and small blood vessels,
Bruetsch stressed the point that the fibroblastic proliferation is related to the
presence of what he calls “embryonic foci of cellular proliferation” in all the

involved blood vessels. These consist of a wall of loosely arranged cells, from
one to fifteen deep, of a variety of cellular elements (young fibroblasts,
lymphocytes, or Maximow’s undifferentiated mesenchymal cells) which may
erupt at any time and lead to further fibroblastic growth (Figure 4-13(b)).
Rapid proliferation of endothelial cells may entangle red cells and form an
occluding mass, although not a true thrombus. According to Altschul, the
endothelial cells which line the inner wall of the arteries of all sizes—large,
small, and even capillaries—are the progenitors of the foam cells found in the
midst of the arteriosclerotic changes, cells which morphologically resemble
closely mesenchimal or reticular cells if indeed they are not identical with
them. The intima of the larger arteries shows an additional feature not clearly
seen in the smallest vessels, namely thickening of the intima with consequent
narrowing of the lumen. Formation of foam cells and of the mesenchimal and
reticular cells must be considered together. The next stage of atheromatosis
in the larger vessels is the disintegration of the foam cells which help to form
the atheroma proper.
Figure 4-13.
(a) Small cortical artery. The lumen is filled with hyaline tissue. Toluidine
blue stain, (b) Small artery of the substantia nigra showing a focus of
embryonic cellular proliferation, sending a tongue of cytoplasma
containing minute hyperchromatic nuclei through the lumen. (Courtesy of
Dr. W. L. Bruetsch.)
Tuthill contends that arteriosclerosis is not a disease of primary fat
absorption. The first histopathological change is an increase in the height and
extension of the areas of split elastica, and collagen increase at the specific
sites of the branching of the large and of many small cerebral blood vessels.
These primary areas are present from birth, and may remain unchanged
through adult life. Deposits of fats and their absorption follow the primary
process of the splitting of the elastica and of the increase of the collagen
fibers. Hydrostatic changes at these levels of narrowing, related to the
changes in blood volume, constitute a contributing mechanical factor to the
genesis of arteriosclerosis.
Relationship between the Arteriosclerotic Changes and the Clinical Symptoms
The important aspect of the clinico-pathologic relationship, particularly
from the psychiatric standpoint, has been merely touched upon and by only a
few authors, though if properly developed it might furnish us with valuable
information. According to Eros, focal neurological symptoms were more
prevalent in cases of hyperplastic cerebral arteriosclerosis than in the
hypoplastic type. Out of twenty-six cases of the hypertrophic type of
arteriosclerosis, fifteen disclosed predominantly neurological focal
symptoms, whereas predominantly mental symptoms were present in
eighteen out of twenty-four cases of the hypoplastic type.
In the hypoplastic type the mental symptoms were usually much more
severe than in the hyperplastic. Delusions and hallucinations were more often
encountered in the hypoplastic type, while they were rather rare in the
hyperplastic. In the hyperplastic type the more severe mental symptoms
developed late in the course of the disease; at the beginning only irritability,
nervousness and emotional instability were predominant. In the hypoplastic

type, severe mental symptoms, often resembling schizophrenia, developed
rather early.
In the earlier stages therefore, according to Eros, some indications as to

the pathologic type of cerebral arteriosclerosis can be established on the basis
of the presence of focal symptoms and the severity and character of the
mental symptoms. In the later stages, when the damage of the parenchyma is
already far advanced and deterioration sets in, the clinico-pathological
distinction is difficult in the absence of focal neurological signs.
Physiopathology of Cerebral Arteriosclerosis
It has been assumed by most investigators that physiopathogenetic
mechanisms determining atherosclerosis in the large cerebral blood vessels
do not differ from the ones involved in atherosclerosis of the aorta, coronary
arteries, and other important blood vessels.
A very comprehensive review of the whole subject can be found in Katz

and Stamler’s book Experimental Atherosclerosis. These authors state that
cholesterol is primarily and not secondarily involved in experimental
atherogenesis. They feel that transintimal filtration from blood plasma is the
mechanism whereby lipids (lipoprotein complex) enter the arterial wall. They
also feel that the state of aggregation of cholesterol in plasma must be a key
factor influencing the extent and rate of transudation of lipids into the arterial
walls.
Although hypercholesterolemia is a factor in the production of the

disease, an important element is the ratio between the cholesterol content of
the blood and its phospholipids. The normal ratio in question is 0.8, i.e., 200
mg. of cholesterol per 100 to 250 cc. of phospholipids. The higher the ratio,
the higher the incidence of atherosclerosis, especially of the coronary arteries.

The lower the ratio, the more likely is the avoidance of atherosclerosis. Thus,
the more the phospholipids are increased, as compared to the total
cholesterol increase, the more protection exists against atherosclerosis.

Without any altered lipid metabolism, little or no atherosclerosis develops,
regardless of any other alterations of the arterial walls, including senescent
changes.
That cholesterolemia alone is not responsible for atherosclerosis is
indicated by the fact that hypercholesterolemia is not always found in
atherosclerosis. This is why Katz and Stamler state that it is not only the level
of cholesterol in the plasma that is important for atherogenesis, but also the
quantity of exogenous cholesterol the body must transport, turn over and
metabolize.
Further investigations on the relationship between cholesterol and
atherosclerosis, carried on by Gofman and his associates, established that in
man, a high concentration of plasma cholesterol bearing lipoproteins (Sf 10-
20) (Svedberg units of flotation) not directly correlated with the plasma total
cholesterol concentration is associated with atherosclerosis. The Sf 10-20
constitute the less dense components, isolated by ultracentrifugation. These
lipoproteins diminish on a restricted fat and cholesterol diet, even if no

decrease of total cholesterol concentration follows.
The cholesterol is generally bound to the beta-lipoproteins. The more

beta-lipoproteins, the more susceptibility to atherosclerosis. Kendall and
others feel, therefore, that atherosclerosis is the result of an elevated beta-
lipoprotein level, perhaps combined with other localizing factors.
Furthermore, individual situations as a result of which the plasma is unable to
hold a greater concentration of sterols in solution, may lead to the
precipitation of cholesterol in the blood stream.
Altered metabolism of lipids, so important in the production of
atherosclerosis, cannot be separated from its interplay with other factors of
exogenous or endogenous origin. Without entering into details, I will mention

some which may lead to the precipitation or aggravation of either
arteriosclerosis or atherosclerosis. They are: (1) hypervitaminosis; (2)
pyridoxine deficiency; (3) excessive vegetable proteins diet; (4)
adrenalinemia; (5) excessive adrenal steroids; (6) hypothyroidism; (7)

Diabetes mellitus; and (8) hypertension.
It has not yet been established whether the same physiopathologic
mechanism or precipitating factors in the production of atherosclerosis in the

large cerebral blood vessels apply also to the small and very small cerebral
blood vessels. On the whole, with the exception of a few attempts on a small
scale, very little attention has been paid to the more general problem of the
relationship of cerebral atherosclerosis to the lipid metabolism, and even less
attention to the relationship of that metabolism to the arteriosclerosis of the
small cerebral blood vessels. Investigations along such lines may furnish us
with valuable data on the significance of the pathological lesions of the small
blood vessels of the brain.
The various psychiatric hospitals all over the United States contain a
wealth of clinical and autopsy material waiting to be studied by a well-
organized team of research workers.
Beckenstein and Gold reported that in 1942 at the Brooklyn State
Hospital (New York) the number of deaths for arteriosclerosis and senile
psychoses was 703, that is, 77.5 percent of the total number of deaths in the
hospital for that same year. Out of these 703 deaths, 384 were cases of
psychoses associated with cerebral arteriosclerosis.
Constitution and Heredity
Several investigators have pointed out that a certain constitutional
physical makeup is more apt to be found among patients suffering from

arteriosclerosis and hypertension. Moschkowitz states that hypertensive
patients are generally soft-muscled individuals, pudgy, short-necked,

ungraceful, nonathletic, and overweight. Badia found that the
megalosplancnic type of Viola, or pycnic type of Kretschmer, discloses a
tendency to chronic changes in the blood vessels of the heart, to

hypertension, to precocious development of arteriosclerosis, and to cerebral
hemorrhages. This view is shared by Larimore and Fishberg.
From the point of view of heredity, it has often been reported that
siblings and parents of patients suffering from arteriosclerosis also disclose a
history of cardiovascular disease. I will only refer to Allbutt’s case of a patient
with hypertension, whose paternal ancestors for three generations had died
of apoplexy—a total of four generations.
Studies by Boas et al. of fifty families of arteriosclerotic patients whose
cholesterol values in the blood exceeded 300 mg. per 100 cc., revealed the
existence of abnormal cholesterol metabolism in 30 percent of all the families.
Within these, all or most of the siblings showed an elevation of serum
cholesterol. In addition, in nine of the fifty families, half of the examined
members exhibited hypercholesterolemia.
Studies by Weitz, Nador-Nikititis, Curtius and Korkhaus, and others on
the occurrence of arteriosclerosis, hypertension, and cerebral hemorrhages in
identical pair of twins reared in different environmental situations, support

the contention that heredity plays an important part in this type of vascular
pathology. Weitz feels that the predisposition to hypertension behaves in the
genetic sense as a Mendelian dominant character.
Differential Diagnosis from a Neuropathologic Standpoint
A few authors have been unwilling to accept a separation between

psychoses associated with arteriosclerosis and senile dementia (Tanzi and
Lugaro), basing their view on the assumption that arteriosclerosis and
senility are almost always associated. Meyer, discussing arteriosclerosis and
mental diseases, wrote that: “We have no means to speak of arteriosclerotic
insanity, but only of insanity of senile or prematurely senile involution. . . . the
real arteriosclerotic nature is only revealed by the course, and by the nervous
and collateral symptoms, of focalized or general arteriosclerosis.”
However, if one studies reports from clinical material, one does not
encounter such a constant combination of senile dementia and
arteriosclerosis. Simchowitz in a study of twenty-three cases of senile
dementia, found only eight in which well-developed arteriosclerosis was

present. Bonfiglio in a study of thirty-three cases of senile dementia, reported
only eight in which well-developed arteriosclerosis was present.
From a pathologic standpoint, one must not consider as characterizing

arteriosclerosis the mere presence, here and there, of small vessels disclosing
changes assignable to this condition. If this were the case, one should
diagnose as arteriosclerosis all sorts of mental disorders occurring in old age,

and also the changes found in the brain of mentally normal individuals who
die at an advanced age and whose vascular system shows occasional incipient
sclerosis.
One must also keep in mind the fact that senile changes of the small
blood vessels may lead ultimately to hyalinization and sclerosis of their walls.
A certain amount of overlapping of vascular pathology is therefore to be
expected. More characteristic of senile vascular changes are, according to
Baker, the splitting of the elastic membrane, a diminution of the muscular
elements, and fibrosis of the media, with increased collagenous substance.

Loss of elasticity, tortuosity, and dilatation of the blood vessels seem to occur
more frequently in senility. Furthermore, one finds numerous senile plaques
in senile psychoses, and also nerve cells disclosing the so-called Alzheimer’s
neurofibrillar disease—findings missing as a whole in cerebral
arteriosclerosis. In arteriosclerotic brains, senile plaques were found in only
one out of six cases by Simchowitz and in two out of nine cases by Bonfiglio.
Of additional assistance in the differential pathologic diagnosis between
senile and arteriosclerotic psychoses, is the frequent finding in

arteriosclerosis of vascular damage in the remainder of the cardiovascular
system and in the kidneys (cardiac hypertrophy, myocardial infarcts, passive
congestion of organs, and infarcts of the kidneys). Furthermore, the presence
of cerebral red or white softenings of various intensity and extension, and

involving well-known cerebral vascular territories, favors the diagnosis of
arteriosclerosis.
Neuropathology of Senile Psychoses
There is no direct correlation between cerebral pathological findings in
senile psychoses, and the development of mental symptoms. Contrary to
Simchowitz, who believed that senile dementia was merely an exaggeration of
the normal senium, Gellerstedt has shown that anatomically it is not a simple
quantitative difference which characterizes normal and pathological senium,
an opinion shared by Grünthal, Cerletti, Critchley, Bonfiglio, Rothschild, and
others. Moreover, in cases of pathological senility, there is a lack of

correlation between the severity of the cerebral structural change and the
severity of the intellectual impairment. Conversely, marked alterations are
occasionally found in the brains of old persons of normal mentality.
Therefore, tissue damage alone is not responsible for the onset of the
psychosis.
The following macroscopic and microscopic changes are in general
encountered in cases of senile psychoses:
Macroscopic Changes
Cranial Changes. The calvarium in old age is usually thicker than

normal, the density being generally uniform. Atrophy of the skull bones,
cranium, and face may be encountered much less frequently. Occasionally the
process of atrophy is localized particularly in the parietal region, and
hyperostosis of the inner table has been reported.
Brain. One of the general characteristics of the brain is a marked
shrinkage resulting from both atrophy and loss of lymphatic fluid. Instead of
an average weight between 1200 and 1400 g., weights of 1100 and 1000 g.
are often reported. Weights as low as 912 g. and 815 g. have been reported by
Grünthal and by Critchley.
Along with the shrinkage of the brain tissue, there follows a marked
difference of 23 to 24 percent, between the volume of the brain and the
volume capacity of the cranial cavity, instead of a normal difference of 12
percent. On the other hand, brains of normal old individuals may also
undergo marked shrinkage and loss in weight (1002 g. in a case reported by
Grünthal), whereas brains of severe cases of senile dementia may differ only
slightly from the normal average.
When shrinkage is present, as in most cases, the process is usually

generalized, although at times it is more prominent in the frontal area, and
the middle portion of the posterior area of the brain. The shrinkage of the
nervous tissue itself is reflected in the widening of the brain sulci and
thinning of the convolutions (Figure 4-14). As the result of a marked

shrinkage of the brain parenchyma, an internal hydrocephalus may develop.
Figure 4-14.
Figure 4-14.
Macroscopic aspect of a senile brain in which shrinkage is moderate. The

cerebral convolutions are thinned and the sulci are slightly widened.
The dura matter is almost always thickened and, in many cases,
adherent to the inner table of the skull. Longitudinal densification of that
covering may be seen following the course of the external blood vessels. The
pia is generally three to four or more times thicker than normal.
Subdural hematomas are occasionally found in from 8 to 9 percent of

the cases (Campbell) and Leri has reported occasional perforations of a thick
and edematous pia.
Microscopic Findings
The brain cortex generally discloses a reduction in size because of an
actual reduction in the volume of the nerve cells which appear smaller and
closer to each other, and because of an actual loss in their number.
In general, phylogenetically older parts of the cortex, such as the motor
areas, are less involved than are the parts developed later. The upper cellular
layers of the cortex, particularly the third one, show the greatest damage in
most cases, though not marked enough to disturb considerably the layering of
the cortical lamination. In some cases that lamination is, however, greatly
disturbed. In some areas the nerve cells still present may occasionally give
the impression of being even more numerous because of the shrinkage of
their interstitial tissue. In the same cortical convolutions, one may find areas
of marked shrinkage, i.e. volume reduction of most of the nerve cells and
marked disturbed lamination, near-by areas in which the cells are better
preserved, and the cytoarchitecture close to normal (Figures 4-15 to 4-18).
The pathological process which involves the individual nerve cells is
generally known as “shrinkage” of the nerve cell. Shrunken nerve cells, which
in the past were designated as “chronically diseased cells,” are seen scattered
in the various cortical areas. Most of the cells undergo a gradual process of
necrobiosis, which leads to their gradual disappearance. Remnant shadows of
such cells are dispersed here and there. Only occasionally, cells undergoing a
simple acute swelling, or conversely the “acute severe type of degeneration”
described by Nissl, are encountered. The shrinkage of the nerve cells which
results in their deeply stained appearance is the most frequent finding.
Among the preserved nerve cells, many disclose an increase in
pigmentation, particularly of the yellow type which may invade the whole of
the cellular body, and at times spread into some of its processes. The extreme
degree of such a change may lead to the “pigment atrophy” of the nerve cell, a
pathologic feature which seems to predilect the nerve cells of the inferior
olivary bodies, and at times the nerve cells of the dentate nucleus. In contrast
to the excessive pigmentation, a loss of the normal melanin pigment of the
cells of the substantia nigra has been reported by Stief, and by Grünthal. In
the basal ganglia, particularly in the striatum, a loss of the larger nerve cells
has been reported, and in the cerebellum the Purkinje nerve cells appear
diminished in size and in number.
Figure 4-15.
Figure 4-15.
Reduction in the number of nerve cells and considerable shrinkage of their

body, particularly in the inner cortical layers. Nissl stain.
Figure 4-16.
Figure 4-16.
Patchy area, in which nerve cells are reduced in number, and reduction in
the volume of the cell bodies is noticeable in the middle cortical layers.
Nissl stain.
Figure 4-17.
Marked reduction in the number of nerve cells in all of the cortical layers
and marked shrinkage in the cell body of the remaining ones. Nissl stain.
Figure 4-18.
Figure 4-18.
Uneven distribution of shrunken nerve cells and uneven reduction of their

number, mostly in the middle and outer layers. Nissl stain.
A special type of nerve-cell pathology first described by Simchowitz, the
so-called “granulo-vacuolar degeneration” has been reported in cases of
senile psychoses, particularly in the large pyramidal cells of the hippocampus,
though present also in other cortical areas (Piazza). The process consists in
the appearance of granules scattered in the cytoplasm of the nerve cells, each
granule being generally surrounded by a vacuole (Figure 4-19). According to
Simchowitz these granules do not contain fat tissue, a statement which is

contested by Piazza.
Another characteristic cellular change often found in senile dementia is
the so-called “Alzheimer neurofibrillar disease of the nerve cells,” a condition
first described by Alzheimer in a variety of ageing diseases of the brain, but
considered more closely related to that variety of presenile psychoses
designated Alzheimer’s disease. Within the nerve cells the neurofibrils
coalesce and condense, thus assuming various peculiar aspects such as

convolutions, spirals, loops, knots, and clumps within the cytoplasma (Figure
4-20), none of which are found in normal cells.
Figure 4-19.
Figure 4-19.
Nerve cells disclosing the granulo-vacuolar degeneration of Simchowitz;

granules surrounded by vacuoles in the midst of the cellular cytoplasm.
Nissl stain.
Figure 4-20.
Figure 4-20.
Various morphologic aspects of nerve cells disclosing the so-called

Alzheimer neurofibrillar disease. Silver carbonate impregnation method of
Del Rio Hortega.
These unusual formations, which have also been described as
surrounding certain nerve cells, have been considered by the majority of

investigators as resulting from degenerating neurofibrils within the nerve
cells. However, this point of view is not shared by Achucarro and Gayarre, Del
Rio Hortega, Lafora, or Divry, who have shown that the same changes occur in
the pericellular, the neuroglial, and the syncytial reticulum of Held, and even
in astrocytes, especially if undergoing ameboid degeneration, data which
seem to point to a wider physicochemical disturbance of the amyloid and
hyaline metabolism.
The association of Alzheimer’s neurofibrillar disease with the other
pathologic changes in the brain of senile psychotics occurs in 17 per cent of
the cases according to Simchowitz, but in less than 6 percent according to
Tiffany. On the other hand, according to Cerletti, Costantini, Fuller, Ley, and
Gellerstedt, neurofibrillar change has been found in a few nerve cells of the
brain of normal aged individuals.
Nerve cells showing the so-called Alzheimer’s fibrillar disease are now,
however, very numerous in senile dementia, and also in the presenile type of
psychosis designated “Alzheimer’s disease,” where Perusini first and Jervis
more recently, found that respectively one out of six and one out of two or
three cells disclosed that change.
The most striking microscopic pathological feature in the brain in cases
of senile psychosis is the presence of the so-called “senile plaques.” These

plaques were first described by Blocq and Marinesco, in a case of epilepsy in
1892, as neuroglia nodules; in 1898, Redlich called them miliary sclerosis,
and Fisher, in 1907, described them as “spherotrichia cerebri multiplex.” It
was Simchowitz who, in 1911, proposed the now generally accepted term of
“senile plaques.” They represent small areas of tissue degeneration, generally
of a roundish aspect, in the midst of which granular or filamentlike detritus is
recognizable in addition to other products of degeneration.
Senile plaques are scattered throughout the cortex from the frontal to
the occipital pole, as shown in Figures 4-21 to 4-23. The frontal lobes and the
Ammon’s horn seem to be seats of predilection. According to Tiffany, senile
plaques are found in the frontal, hippocampal, central, paracentral, occipital
convolutions, and basal ganglia in that order of frequency. Rothschild found
them in abundance in the amygdaloid nucleus, in small numbers in the
putamen and caudate nucleus, and less frequently in the thalamus and the
substantia nigra.
Figure 4-21.
Numerous senile plaques distributed in various cortical layers. Silver
carbonate impregnation method of Del Rio Hortega.
Figure 4-22.
High-power magnification of senile plaques, illustrating their grandular
and filamentous structure. Silver carbonate impregnation method of Del
Rio Hortega.
Figure 4-23.
High-power magnification of two senile plaques in the midst of which

reacting microglial cells are clearly visible. Silver carbonate impregnation
method of Del Rio Hortega.
According to Simchowitz, the number of plaques is the best index of the
severity of the senile process in the cortex. The more plaques, the more
severe is the process. Such a contention, although generally accepted, is
refuted by a few authors who feel that a pathological diagnosis of senile
dementia may be acceptable even in the absence of senile plaques.

Simchowitz and Perusini feel however, and I agree with them, that if a
detailed examination of the brain of a senile psychotic is undertaken, one will

never fail to find plaques, and their absence justifies a doubt as to the
diagnosis of senile dementia.
An important corollary to that statement concerns the presence of

plaques in normal senile brains. Such a question seems to have been disposed
of, because normal senile brains do show senile plaques, occasionally in
substantial numbers, and sometimes as many as in senile dementia.

Gellerstedt detected senile plaques in 84 percent of normal aged brains,
neurofibrillar alterations in 87 percent, and granulo-vacuolar degeneration in
40 percent. In each case, however, such findings were scarce, and at times
detectable only after very careful examination.
The senile plaques have been considered as deriving from various
individual structures of the nervous tissue. Some authors believe that they
originate from neuroglia elements; others consider them as derived from the
nerve cells. Still others assert that the disintegrated intercellular structure
and the neuroglia reticulum constitute the elements from which senile
plaques develop; Marinesco feels that they originate from deposits of

abnormal material.
In 1922, Ley first expressed the opinion that in the formation of the
senile plaques, microglia elements take part, a view later upheld by Verhaart,
and Urecchia and Elekes. My own investigation on the histogenesis of the

senile plaques has led me to conclude that senile plaques are formations that
indeed may originate not only from degenerating microglia cells, but also
from oligodendroglia cells and even directly from degenerating nerve cells
(see Figure 4-24). A detailed bibliography on the histogenesis of the senile
plaques may be found in my paper on this subject.
Figure 4-24.
Two Purkinje cells of the cerebellum undergoing individual degenerative

changes leading to the formation of senile plaques. Silver carbonate
impregnation method of Del Rio Hortega.
The histochemical process that governs the transformation of a cellular
element into a senile plaque is as yet somewhat obscure. All that can be said is
that it leads to the formation of a granular argyrophilic substance which

according to Divry represents a miliary hyalino-amyloidosis. The so-called
nucleus of the plaques, that is, its central portion, shows the staining
properties of an amyloid metachromatic substance which reacts in a brown-
reddish color to Lugol’s solution, which stains in red with Congo red, and
which above all is birefringent at polarized light.
Divry is also of the opinion that the so-called Alzheimer’s neurofibrillar
disease is the result of amyloid degeneration related to some colloidal
disruption, that is, of a flocculation of the fibrinoplastic cellular substance, a
process akin to syneresis. Morel and Wildi felt that the amyloid degeneration
in the plaques themselves, within the blood vessels or outside their walls, is
the result of an altered protein metabolism (paraproteinemia) associated

with impaired vascular permeability.
Free amyloid bodies are also frequently seen in senile dementia. They
are scattered in various cortical areas, in the white substance, in the

subependymal layer of the ventricular cavities, and more abundantly in the
external lamina of the Ammon’s horn. Various theories such as the
neurogenic, gliogenic, lymphogenic, hematogenic, and postmortem, have been

advanced for their histogenesis. After an investigation which Damon and I
carried out in this connection, we concluded that mostly microglial and
oligodendroglial elements contribute to the origin of said bodies, through an
amyloid degeneration of their cell bodies. Figure 4-25 illustrates amyloid

bodies impregnated by the silver carbonate method in the course of their
amyloid degeneration, and Figure 4-26 illustrates the genesis of amyloid
bodies from clusters of oligodendroglia cells, which still retain some of their
processes. An extensive literature on this subject is found in my publication
on this subject.
Figure 4-25.
Figure 4-25.
Numerous amyloid bodies diffusely distributed. Silver carbonate

impregnation method of Del Rio Hortega
Neuroglial Tissue
With the atrophic process, which involves not only the cortex but also
the white matter, there is a moderate neuroglia reaction of the progressive
type—astrocytic reaction—which if present, is found in the outer layers of

the cortex in the form of marginal gliosis. Hypertrophy of isolated astrocytes
is observed here and there in the white and gray matter, but much less
frequently an increase in their number (hyperplasia). Clasmatodendrosis of
the glial fibers as well as reticulocystic degeneration of the astrocyte bodies is
also found occasionally.
Deposits of free iron are common in the brain of aged people, localized
particularly in the perivascular spaces of either the cortex or the white
substance. A seat of predilection is generally the globus pallidus where free
deposits of iron seem to be found, independently from their immediate

relationship to the blood vessels. No specific relationship has been
established from the quantitative standpoint between iron deposits in normal
and pathological senility.
Myelin Sheaths and Nerve Fibers
In the brain cortex, the myelin sheaths do not seem to be substantially
involved, except for a slight diminution of the myelinated fibers in the
tangential layer, and a questionable diminution of fibers in the radiate and

supra-radiate layers. In the white matter, areas of patchy myelin rarefaction
may be observed.
The axis cylinders, corresponding to the areas of myelin involvement,
show occasional fragmentation, but nothing compared with that observed in
the midst of the senile plaques and in their immediate vicinity.
Blood Vessels
Cerletti first described in the senile atrophic tissue of the brain the
presence of vascular loops and vascular knots, resulting from the elongation
of the blood vessels which have lost their elasticity and which furthermore
have to adjust themselves to the narrower space offered by the shrunken
tissue. Aschoff reports ectasia of the blood vessels, widening of their lumen,
some increases of the internal elastic membrane and some twists in the
course of the blood vessels which he attributed to fibrosis of the muscular

elements.
Simchowitz described what he termed “simple senile changes” of the
small blood vessel: degenerative changes of the endothelial lining cells,
fibrosis of the media, and slight reactive proliferation of the adventitial cells.
According to Baker, in old age the internal elastic membrane discloses
fraying, and the muscular fibers of the media are replaced by connective
tissue which later may become hyalinized. Hyalinization may, according to

Binswanger and Schaxel, spread to the adventitia. In the course of that
process, the elastic fibers disappear first, followed by the muscular fibers of
the media. Collagenous tissue is ultimately found surrounding the arterioles
and the capillaries.
Figure 4-26.
Figure 4-26.
Oligodendroglial cells undergoing amyloid degeneration. Some of the cells

still disclose a few of their disintegrating processes. Silver carbonate
impregnation method of Del Rio Hortega.
In eight cases of arteriosclerosis associated with pronounced senile

changes, Eros reported that in seven of them, the blood vessels showed
hypoplastic degenerative changes of the elastic membrane. Recently Fisher

has reported, in cases of senile dementia, arteriosclerotic changes leading to
more or less marked occlusion of the internal carotid arteries. He feels that a
relationship may exist between these findings and the clinical picture
exhibited by these patients.
In cerebral blood vessels, Scholz has described a degenerative condition
of the media, occurring in very old people, which he termed Drusige
Entartung. This condition termed degenerescence grumeuse by Lafora,
consists on the infiltration of the media by a substance of homogeneous
appearance, which according to the latter, shows the staining properties of
the amyloid substance (Figures 4-27 and 4-28) and particularly of its
birefringence.
In the choroid plexus the most common findings are the proliferation of
the connective tissue, vacuolization and pigmentary degeneration of its
epithelial cells, and the presence of calcareous hyaline and psammomatous
bodies.
Figure 4-27.
Figure 4-27.
Amyloid degeneration within the walls of a blood vessel.
Figure 4-28.
Figure 4-28.
Birefringence of amyloid substance along the longitudinal course of a

blood vessel.
Spinal Cord
Its meninges are thickened and calcareous plaques may be seen
attached to the pia arachnoid. Ossification is only rarely found. The spinal
cord itself is generally shrunken and the myelin sheaths somewhat rarefied,
particularly in the posterior and lateral columns. Astrocytic proliferation may

be noticed around the blood vessels and in the areas of myelin involvement.
Accumulation of yellow pigment is often seen in the ganglion cells.
Occasionally “Alzheimer’s fibrillar disease” has been reported.
The blood vessels may show a combination of simple senile
degenerative and mild arteriosclerotic changes. Amyloid bodies generally
surrounding the blood vessels seem to be prominent along the spinal cord
septi and mostly in the zone entrance of the posterior roots.
Electroencephalographic Studies
Luce and Rothschild reported a slowing of the predominant rhythm in
their cases of senile psychoses, especially in those showing a more severe

intellectual impairment. Diffuse dysrhythmia of brain waves in senile
psychoses have been reported by Silverman, Busse, and Barnes. These
investigators found a correlation between diffuse dysrhythmias and

decreased facility to communicate, lower clarity of perception, increase in
concrete concept formations, and greatly reduced psychomotor speed. When
focal dysrhythmia was associated with diffuse abnormalities, organic

deterioration was clearly noted. McAdam and McClatchey felt that probably
an impaired cerebral blood flow was the important factor in the abnormal
electroencephalographic tracings. They too reported a high correlation
between slow rhythm activity and intellectual deterioration.
Neuropathology of Presenile Psychoses
Alzheimer’s Disease
It may be said in general that the same findings are reported in senile
dementia and in Alzheimer’s disease, a condition first described by Alzheimer

in 1907. Perusini in 1910 and in 1911 contributed substantially to its clinical
and pathological aspects, as a result of which the disease called Alzheimer’s
disease in Germany became known as Alzheimer-Perusini disease in Italy.
The atrophy of the brain tissue is more pronounced than in senile
dementia, the reduction in volume of the convolution and the widening of the
sulci being more marked (Figures 4-29 and 4-30). The process of atrophy,
generally involving most of the lobes, is occasionally more pronounced in
some of them—the frontal, temporal, parietal, or occipital. Circumscribed
atrophy in one lobe only is rare, and cases of this type may constitute variants
of Pick’s disease rather than genuine cases of Alzheimer’s disease.
Figure 4-29.
Figure 4-29.
Macroscopic appearance of the right cerebral hemisphere in a case of

Alzheimer’s disease. Note the widely distributed shrinkage of the cerebral
convolutions in most of the lobes and the markedly enlarged fissures and
sulci.
Figure 4-30.
Figure 4-30.
Macroscopic appearance of gross vertical sections of brain of Figure 4-29,

illustrating the cerebral atrophy and the widening of the sulci from the
frontal to the occipital pole and the dilatation of the lateral ventricles.
Histologically the process of atrophy is represented by a diffuse
disappearance of nerve cells and by a resulting disturbed cortical lamination.
No particular cortical layers are involved, the cellular atrophy being more
pronounced at times in the outer layers (Figure 4-31), at times in the middle
layers, (Figure 4-32), and at other times indiscriminately in all cortical layers
(Figure 4-33). On the whole, there seems to be no predilection for any special
cytoarchitectural field; cortical areas of more recent ontogenetical

development are as involved as are others of older organization. The involved
areas are irregular, and generally no clear-cut boundaries exist between
normal and pathological areas. Occasionally, though, a sharp boundary is
apparent between atrophic areas and the better preserved ones.
Figure 4-31.
Shrinkage and disappearance of nerve cells involving mostly the outer
cortical layers. Nissl stain.
Figure 4-32.
Shrinkage and disappearance of nerve cells involving predominantly the
middle cortical layers. Nissl stain.
Corresponding to the areas of cortical cellular atrophy, there occurs an
increase of glia cells. In the white matter, one finds also that increase which
may represent an actual numerical increase in the number of the glia cells, or
a relative one resulting from the shrinkage of the white substance. This glial
increase may constitute one of the differential features from the senile
psychoses, where gliosis, if present, rarely reaches an appreciable degree.

Occasionally, fibrillar gliosis may be seen in some of the areas of the white
substance, even though in those areas the myelin sheaths appear to be
preserved.
The most common individual type of the degenerative change of the
involved nerve cells is that of shrinkage, or pyknosis; these nerve cells appear
reduced in size, and deeply stained; their processes appear distorted and
tortuous. Their intracellular pigment is generally increased, particularly in
the lamina terminalis and the presubiculum of the Ammon’s horn. However,
one may also encounter a few nerve cells undergoing the severe acute type of
degeneration of Nissl, consisting in their swollen appearance, poverty of the
Nissl’s substance, a marked vacuolization and peripheral disintegration. At
times, a few nerve cells are encountered, undergoing the ischemic type of
cellular degeneration, particular in the vicinity of the blood vessels. Many

distorted shadows, remnants of nerve cells, are detected, giving the
impression that a slow progressive vascular mechanism contributes to the
atrophic process. Only occasionally has the granulo-vacuolar degeneration of
Simchowitz, frequently encountered in the senile psychoses, been reported in
Alzheimer’s disease.
Figure 4-33.
Shrinkage and disappearance of nerve cells involving, indiscriminately, all
cortical layers. Nissl stain.
A most characteristic change of the nerve cells is the so-called
Alzheimer’s neurofibrillar disease. Contrasting with senile dementia, this type
of cellular change has been reported by Lafora as being always present in
Alzheimer’s disease. Figure 4-34 illustrates various aspects of Alzheimer’s
neurofibrillar disease in individual cortical nerve cells. Occasionally, round
argyrophylic masses, resembling the inclusions described in Pick’s disease,

have been reported in the cytoplasm of a few cortical nerve cells.
A diagnosis of Alzheimer’s disease has been, however, considered

compatible with the absence in the nerve cells of the characteristic
neurofibrillar change, a statement contested by the majority of the
investigators. Indeed, if one considers the difficulty of establishing a
differential clinical diagnosis between senile dementia, Alzheimer’s disease
and Pick’s disease, one is justified in insisting—for a correct diagnosis of
Alzheimer’s disease—on the presence in the brain of the whole typical

pathology, including the Alzheimer’s neurofibrillar changes.
The proportion of the nerve cells showing Alzheimer’s neurofibrillar
change to normal cells is as high as 1 to 2, or 1 to 3. It is precisely the large

number of nerve cells disclosing that special intracellular change which
characterizes Alzheimer’s disease pathologically. There is, however, no
parallelism between the number of nerve cells so diseased and the cortical
atrophy, some severely atrophic areas lacking at times the presence of nerve
cells disclosing the neurofibrillar changes. Such changes are infrequent in the
basal ganglia (striatum and thalamus), but numerous in the Ammon’s horn,
particularly in the Sommer’s sector.
The pathogenesis of the Alzheimer neurofibrillar disease is a debated

question. Although the majority of the investigators still maintain that the
Alzheimer’s changes result from degenerated neurofibrils, others do not
share this view, having demonstrated that the same argyrophilic incrustation
of the neurofibrils in the cells are seen in the pericellular reticulum of the
nerve cells, in the neuroglia reticulum, in the sincytium of Held, in the
protoplasma of the cells of the choroid plexus, in the ependymal glio-
epithelial cells and even in the cytoplasm of astrocytes, especially of those
undergoing the so-called ameboid degeneration. These incrustations may,
therefore, originate not only from neurofibrils, but also from the thickening of
the spongioplasm of many other cells in the nervous tissue.
Alzheimer’s neurofibrillar disease, although generally essential for the
pathologic diagnosis of Alzheimer’s disease, is not pathognomonic of the
latter. It may be found in senile dementia, particularly of the presbyophrenic

variety. It has also been reported in other neuropsychiatric conditions, such
as chronic epidemic encephalitis, familiar spastic paralysis, amyotrophic
lateral sclerosis, disseminated sclerosis, involutional psychosis, Tay-Sachs

disease, and Pick’s disease. In all such conditions, the number of the nerve
cells showing Alzheimer’s changes is, however, very limited compared with
the large number of cells involved in Alzheimer’s disease. Furthermore, the
neurofibrillar disease reported in these various human conditions as well as
in some animals, may not be of the same nature as that reported in the
Alzheimer disease proper.
Figure 4-34.
High power view of Alzheimer’s neurofibrillary changes. Silver stain.
Senile Plaques
Senile plaques constitute an almost constant finding in Alzheimer’s

disease, rarely being absent in a typical case. According to Simchowitz, in
Alzheimer’s disease the plaques are dominant in the occipital and parietal
lobes, in contrast to their predominance in the frontal lobes in senile
dementia. In general, however, they are distributed throughout the cerebral
cortex, and more so in the subiculum of the Ammon’s horn, although they
have been reported in large number in the basal ganglia, the brain stem, and
the cerebellum. The more diffuse are the senile plaques and the more severe
and numerous the Alzheimer’s neurofibrillar changes, the more severe, in

general, are the clinical symptoms.
Blood Vessel Changes
Most of the vascular changes reported in senile psychoses are generally
found also in Alzheimer’s disease. The senile atrophic angiopathy (the
degenerative changes of the endothelial and aventitial cells of the blood
vessel walls) and the so-called “dysphoric angiopathy” (Drusige Entartung of
Scholz) have been reported in Alzheimer’s disease, although the latter seems
commoner in very old patients. The character of the histochemical alterations
in such angiopathy does not differ from those described by Divry in senile
psychosis, including the birefringence and the staining properties of the
material deposited in the walls of the small blood vessels, capillaries and
precapillaries and in their surrounding tissues, a material which possesses
the properties of the amyloid substance. Even in the senile plaques
themselves and in the argentophylic loops, spirals or baskets of the diseased
Alzheimer cells, the same substance was detected by Divry, thus pointing to a
general metabolic disorder of which Alzheimer’s disease of the brain may be a
local expression.
Pathogenesis of the Disease
The close relationship of Alzheimer’s disease to senile dementia, as first
described by Alzheimer, was soon accepted by Perusini, Bonfiglio, Frey, and
Fisher. Rheingold and Reichhardt consider the disease a variety of
presbiophrenia.
Runge considers Alzheimer’s disease a special form of senility,

occupying the same position among the senile psychoses that Lissauer’s
paralysis occupies in general paresis.
Hilpert, Rothschild and Kasanin, Malamud and Lowenberg, and
McMenemy and Pollack consider Alzheimer’s disease to be a syndrome which
is due to various exogenous or endogenous factors. Senility may be only one
of these factors.
Goodman recently advanced the theory that Alzheimer’s disease is

related to devitalized microglia cells which are unable to fulfill their supposed
trophic and nutritional functions. He related the devitalization to a
disturbance in the cerebral metabolism of the iron which appears increased

in practically all nerve cells.
Endocrine disturbances have also been thought to play a pathologic role

in cases where myxedema was found associated with that condition.
A common derivation for the senile and the presenile psychoses has
been advocated by Braunmuhl, on the basis of colloidal changes which are
common in senile and presenile states. In his opinion, aging of the brain is the
result of a change from a highly cellular colloid dispersion to a lesser one,
resulting in condensation and coagulation. This process of “protoplasma
hysteresis,” which may also occur in the presenile stages, does not differ from
the one occurring in senility proper under the influence of various
precipitating factors, which in Alzheimer’s disease may act with greater
intensity, thus leading to earlier and more extensive damage.
The vascular involvement, widely rejected in the past as a precipitating
factor in presenile psychoses, seems at present to be less reluctantly

accepted. Morel and Wildi emphasize the importance of the altered vascular
permeability. De Ajuriaguerra speaks of circulatory changes leading to

disturbed oxygen utilization, and Lafora speaks of cerebral vascular
pathoclisis. It is not, however, a matter of structural vascular damage,
inasmuch as this may be absent, but of altered functionality, which may be
transitory and recurrent (vasospasm). In Alzheimer’s disease, vasospasm may

constitute, indeed, a precipitating element which complicates the underlying
senile process, and therefore precipitates and aggravates its expression. This
contention is supported by the occurrence of nerve cell atrophy and gliosis,
which at times are detected along the longitudinal course of a blood vessel.
Furthermore the association of a mild arteriosclerosis with Alzheimer’s
disease has also been reported.
Von Bogaert summarized the relationship of the vascular permeability

to the presence of amyloid substance often reported in the brain in
Alzheimer’s disease. In his words: “In senile processes and therefore in
Alzheimer’s disease, an abnormal vascular permeability is found which allows

the production of complex substances, which in some cases possess the
attribute of the amyloid substance (amyloid angiopathy). If the deposit is
limited to the walls of the blood vessel, it is referred to as ‘congophilic
angiopathy;’ if it overflows into the adventitial space, welding it to the glio-

adventitial structure and even penetrating into the nervous parenchyma, it is
called ‘dishoric angiopathy.’ These discontinuous deposits tend to occur in
areas differing from those where hyalinosis occur—both substances are often
formed in the same brain, but in different parts. However, hyalinosis may be
closer than is generally thought to the congophilic material.” [p. 100] In his
opinion, cerebral amyloid angiopathy is a sign of a more general humoral

disturbance and of local tissue changes, which characterize “normal
involution,” but which become more pronounced in pathological senility and
presenility.
Relationship of Alzheimer’s Disease

to the So-called “Juvenile Type”
The occurrence of Alzheimer’s disease in early periods of life has
created doubts as to the classification of the disease as a presenile psychosis.
Similar doubts resulted also because of the occurrence of the disease in very
old age. For the latter, a delayed pathological senility, triggered by delaying
precipitating factors, may explain the occurrence of Alzheimer’s disease in the
course of advanced senium, and may preserve its relationship to it.
Concerning the so-called cases of “juvenile Alzheimer’s disease,” a
critical review of some of these cases, undertaken by Jervis and Soltz, brought
out the following conclusions: Four of the ten cases reviewed 84 and 85,155
disclosed insufficient pathological evidence and atypical clinical
manifestations and therefore did not justify the original diagnosis of “juvenile
Alzheimer’s disease.” In three other cases although the pathology was
characteristic, the clinical symptoms were atypical enough to exclude them
from Alzheimer’s disease. The four remaining cases were typical from both
the clinical and pathological standpoint. These cases occurred late in the
fourth decade of life, instead of the fifth, in which presenile psychosis is more
common. Jervis and Soltz concluded that this margin is evidently too narrow
and insufficient to justify the differentiation of a nosological variety of a
“juvenile type of Alzheimer’s disease.”
Also the “juvenile familial cases” disclosing a dominant genetic trait,

described by von Bogaert et al. and Worster-Drought et al., do not seem to
belong to Alzheimer’s disease. The paucity of the cerebral changes
characteristic of that disease, the mental picture lacking the typical
impairment of trans-cortical associative functions, and the presence of
outstanding pyramidal, cerebellar, or extra-pyramidal neurological

symptoms, indicate a closer relationship of these cases to heredode-
generative diseases (spastic spinal paralysis, hereditary ataxia, hereditary
chorea) than to Alzheimer’s disease.
Genetic Factors
Some cases have been described in support of a direct genetic
hereditary link, although serious doubts have been expressed as to their
correct clinical diagnosis. Other cases of Alzheimer’s disease show more of an
indirect hereditary link, inasmuch as, in the same family, cases of senile
dementia, schizophrenia, feeblemindedness, or alcoholism have been
reported. Studying genetically and clinically sixty-nine cases of Alzheimer’s
disease, the Sjogrens et al., reported three secondary cases in three families
among the parents of the patients, and three secondary cases among the
siblings. The authors point out the possibility of a multifactorial inheritance in
Alzheimer’s disease, including genetic factors determining premature

pathologic aging.
Pick’s Disease
Pick’s disease is an endogenous disease occurring in the presenile
period of life, and is characterized clinically by a state of dementia, in addition
to which, because of a primary circumscribed atrophy of the cerebral
hemispheres, certain focal symptoms develop. This atrophy is the result of a
slowly progressing degenerative process, lacking the character of
inflammation or necrosis, and therefore disclosing no appreciable product of
the disintegration of the involved tissue. Although Pick, who first described
this condition, considered it related to the senile psychoses, other
investigators feel that the disease is an entity to be classified among the
heredode-generative processes.
The macroscopic appearance of the brain in Pick’s disease reveals the
presence of a circumscribed lobar atrophy, which is expressed in terms of
shrinkage more or less pronounced, of the involved lobes, the marked
shrinkage of the individual convolutions (knife-blade appearance) and the

broad widening of the cortical sulci.
Figure 4-35.
(a) Lateral view of a brain showing the atrophy, circumscribed mainly to
the frontal and temporal lobes, (b) Medial aspect of the same brain. Note
the well-preserved paracentral lobule.
The cerebral atrophy is generally circumscribed and localized in the
orbitofrontal and temporal lobes. It is generally symmetrical but more
pronounced over the left hemisphere. Frontotemporal-parietal localization is

also encountered. Lobar atrophy limited exclusively to the occipital
convolutions lacks postmortem pathological confirmation. In the frontal
lobes, the frontal poles are more frequently involved. In the temporal lobes,
the convolutions T₂ and T₃ are more frequently involved. The two posterior
thirds of convolution T₁ are generally preserved. In the parietal lobe, the
gyrus supramarginalis is mostly affected.
According to Spatz, the most resistant cortical areas to the process of
atrophy are the occipital convolutions, especially the calcarine area, the
central convolutions, the paracentral lobule, the more dorsal portions of the
frontal lobes, near the interhemispheric fissure, the temporal convolutions of

Heschl, the caudal portion of the first temporal convolution and the Ammon’s
horn.
Spatz also reports the presence of primary foci from where the atrophic
process initiates, diffusing later to the surrounding tissue. One of these
primary foci is to be found in the mediocaudal portion of the orbital lobes

(gyrus rectus); a second focus he reported in the insula, a third in the fronto-
opercular region, a fourth in the opercular portion of the precentral
convolution, and a fifth in the frontal pole.
It is difficult to evaluate the report of Bonfiglio who described a case of

Pick’s disease with atrophy limited solely to the basal ganglia, or the one of
Verhaart, where the predominance of the atrophy was in a cerebellar lobe.
Figure 4-35(a) illustrates the macroscopic aspect of the brain in a case
of Pick’s disease, disclosing a dominant fronto-temporal atrophy. The third
frontal, the first temporal, and the pre- and postcentral convolutions are well
preserved. The Figure 4-35(b) illustrates the atrophy in the medial aspect of
the same brain hemisphere. The frontal lobe is markedly atrophic, whereas
the paracentral lobule is well preserved.
Figure 4-36.
Figure 4-36.
Pneumoencephalogram showing a large amount of air over the frontal

lobes and the enlargement of the lateral ventricle.
Microscopic Changes
The meninges appear thicker because of a more or less pronounced

increase in the connective tissue. The main parenchymatous changes consist
of a slow progressive process of atrophy of the neurons without appreciable

disintegration or necrosis of the nervous tissue, but accompanied by
hyperplasia of the glia fibers, and to a lesser degree of the astrocytes
themselves.
Spatz, Onari, and Bagh found the atrophy to be systemic, initiating at the
distal end of the neuron, and progressing centripetally toward the nerve cell.
The intensity and the diffusion of the involvement of the neurons determine
the intensity of the shrinkage of the gray and white matter and of the
subsequent dilatation of the cerebral ventricles.
Corresponding to the marked lobar atrophy, the encephalogram reveals
a collection of air in the corresponding portion of the ventricular cavities.
Figure 4-36 illustrates the pneumoencephalographic findings related to the
marked frontal atrophy in the case illustrated in Figure 4-35.
The degenerative process of the cortical nerve cells leads to their
gradual rarefaction and complete disappearance. This process has no definite

predilection, being at times more pronounced in certain cortical layers, and at
others involving all of them. In certain cases the cellular atrophy from the
outer layers of the cortex invades the middle layers (Figure 4-37); in others it
is limited to the external layers; in still others it is more pronounced in the
inner layers. In others it may unevenly involve most of the cortical layers
(Figure 4-38). The boundaries between better-preserved areas and areas of

major involvement are, at times, sharply demarcated while at others they
fade gradually into well-preserved areas. At other times the disappearance of
the nerve cells is patchy, and may be seen to follow the longitudinal course of
a blood vessel (Figure 4-39).
The predominant type of the cellular involvement is the simple
shrinkage of the cell body, with increased pigmentation so that it gradually
becomes very pyknotic. Occasionally, however, vacuolation of its cytoplasm is
observed, as well as the more specific type of granulo-vacuolar degeneration
described by Simchowitz. In a few areas, the ischemic type of cellular
degeneration described by Spielmeyer may also be encountered. Occasionally
some of the degenerating nerve cells show increased content of fat products.
But the most characteristic aspects of nerve cell degeneration are two
special ones which have been considered by some investigators as
characteristic of Pick’s disease. One type consists in the so-called “cellular
swelling” (Blähung of Alzheimer) (Figure 4-40). Since the cytoplasm of these
nerve cells has lost most of its Nissl’s substance, these swollen cells appear
poorly stained except for a thin peripheral chromatine band of the cytoplasm
itself or of its nucleus. The nucleus, either swollen or distorted and pyknotic,
is excentrically located. This type of cellular lesion seems to have a
predilection for the less severely atrophic cortical areas, and recalls the type
of cellular reaction described by Meyer in various mental diseases as “central
neuritis.”
Figure 4-37.
Extreme diminution of nerve cells and remnants of others, mostly in the
outer cortical layers and extending into the middle layers.
Figure 4-38.
Unevenly distributed nerve cells undergoing atrophy leading to cellular

rarefaction in all the cortical layers.
Figure 4-39.
Figure 4-39.
Patchy areas of cellular atrophy and rarefaction of nerve cells along the
longitudinal course of some blood vessels. Nissl stain.
Figure 4-40.
Figure 4-40.
Nerve cells of the first temporal convolution undergoing the characteristic

swelling (Blähung). Nissl stain.
The other characteristic type of nerve cell change consists in the
presence in the nerve cells of intracellular argyrophylic roundish inclusions,
particularly numerous in the Ammon’s horn. They are known as “cytoplasmic
inclusions of Alzheimer” (Figure 4-41). These roundish bodies, which may
displace the nucleus, possess metachromatic staining properties in addition

to being argyrophylics. Though they do not stain with Congo Red, or show the
optic birefringence of the amyloid substance, Divry considers them to be the
expression of colloidal condensation, an early stage of amyloid degeneration.
It is worthy of notice that nerve cells with cytoplasmic inclusions are
found at times in large number in the areas where the atrophic changes are of
a very moderate degree.
Myelin Sheaths
Involvement of axis cylinders and myelin sheaths varies from area to
area, disclosing various aspects of early swelling, of fragmentation, and of
granular disintegration accompanied by various degrees of demyelination.

The demyelination may extend to the corpus callosum, while in the white
substance it spares most of the so-called arcuate fibers. The sheaths of the
optic nerves seem also better respected.
Figure 4-41.
Figure 4-41.
Characteristic argentophilic inclusions in the nerve cells of the Sommer

sector of the Ammon’s horn. Cajal silver stain.
Figure 4-42.
Figure 4-42.
(a) Typical hypertrophy and hyperplasia of astrocytes, (b) Astrocytes

undergoing degeneration (clasmatodendrosis). Cajal’s gold-sublimate
method.
Glial Reaction
The glial reaction in Pick’s disease, as opposed to senile psychoses or
Alzheimer’s disease, is a major component of the histopathological process. At
times there is a definite increase in the number of astrocytes and their related
number of glia fibers, plainly visible with the Cajal method of gold sublimate
impregnation. In the midst of such a glial astrocytic hyperplasia, hypertrophic
cells are found disclosing at higher power, evident signs of
clasmatodendrosis. Figure 4-42(a) illustrates an area of glia hypertrophy, and
Figure 4-42(b) shows cells undergoing swelling and fragmentation of their
processes (clasmatodenrosis). Oligodendroglia cells appear individually
normal, but they give the impression of being abnormally numerous in the
white matter. This is presumably related to the shrinkage of the white matter
and does not necessarily represent an absolute numerical increase. As
already mentioned in the definition of the disease, there are little or no fatty
degeneration products in the atrophic areas, either free in the tissue or

embedded in the microglia cells.
A common finding in relation to the reaction of the glia reaction in the

areas disclosing a severe demyelinating process (Figure 4-43(a)) is the
presence of an outstanding glial fibrosis (Figure 4-43(b)). Another impressive
change is the very marked increase in the number of glial nuclei, detectable
by the staining method, in the midst of some atrophic areas. Particularly
interesting is the great increase of those nuclei which I have reported in a
typical case, along the course of various small branches of small blood vessels
which appear to be surrounded by a heavy collection of glial nuclei (Figure 4-

44). Such a marked reaction surrounding the blood vessels seems to indicate
the participation of a vascular factor in the pathogenesis of the disease.
Figure 4-43.
Figure 4-43.
Section of the temporal lobe illustrating the correlation between (a)

demyelination (Spielmeyer’s method for myelin sheaths) and (b) fibro-glia
proliferation on the same area (Holzer’s stain for gliafibers).
Blood Vessels
The blood vessels appear, at times, as if increased in number, though
that appearance may be related to the shrinkage of the surrounding nervous
parenchyma. Changes in individual blood vessels may run the gamut from a
slight thickening of the adventitia, to minor proliferative changes of the lining
endothelial cells, thus leading to an occasional slight endarteritis. Hyaline
degeneration of small blood vessels has also been reported.
Iron Pigments and Other Changes
Increased iron pigment is generally found in the gray and white matter,
either free in the tissue or embedded in the glia or nerve cells, more so at the
boundaries between cortex and the white substance, and more so in the
severely atrophic areas.
The participation of the basal ganglia and of the substantia nigra, in the
pathologic process, thus leading to the development of extra-pyramidal
symptoms, has been emphasized by Ferraro and Jervis, and confirmed

recently by Spatz. The latter stated that: “Our concept that extrapyramidal
symptoms do not occur in Pick’s disease must be revised.” The atrophy
reported in various nuclei of the thalamus has been interpreted by Simma, as

related to both a primary cellular atrophy of some of the thalamic nuclei, and
to a secondary one resulting from the damage of the corresponding cortical
areas where the thalamic fibers end.
Senile plaques and Alzheimer’s neurofibrillar disease, although
occasionally reported, do not constitute a necessary pathologic component of

the structural damage in Pick’s disease.
Figure 4-44.
Small branches of a cerebral blood vessel, in the white matter, surrounded

by a very marked increase of glia nuclei which outline the vascular course
in an atrophic area.
An attempt by Neumann to describe two different types of Pick’s disease
needs confirmation. The author feels that in one group there is a marked focal
cortical devastation, with loss of nerve cells and axis cylinders. Demyelination
and reactive gliosis parallel each other in severity. In the second group there
is a widespread gliosis of the subcortex, out of proportion to the
demyelination of these areas. Damage of cortical structures is less

pronounced. Neumann suggests that these two types may have a different
etiology.
Nosologic Position of Pick’s Disease
and Its Pathogenesis
That Pick’s disease should be classified among the presenile psychoses,
and thus related to senile psychoses, seems to be the opinion of a group of
investigators. They believe that not only does the disease share some clinical
features with Alzheimer’s disease, but also that some of the characteristics of
the circumscribed atrophy are similar pathologically to those of the more

diffuse atrophy described in Alzheimer’s disease. Furthermore, they feel that
in cases of senile dementia there has been occasionally found a predominance
of the senile atrophic process in one or more lobes. In addition, in Pick’s
disease, the same predominance of the cortical cellular atrophy in certain
outer, middle, or inner layers, just as in senile psychoses and particularly in
Alzheimer’s disease, constitutes one more relationship between Pick’s disease
and the senile psychoses as maintained by Pick, Fisher, Altmann, and
Spielmeyer.
Another group of investigators led by Spatz, Onari, and Bagh, considers

Pick’s disease to be a member of the large group of progressive
heredodegenerative systemic cerebral and spinal atrophies. They consider
Pick’s disease the result of a localized, premature cerebral senescence. The

localized atrophy begins at the distal end of the neurons in the white
substance, and progresses as a retrograde degeneration towards the nerve
cells of origin, thus explaining the pathologic aspect of the swelling of the
cortical nerve cells. This theory, which is an offshoot of Gower’s concept of
abiotrophy, implies that certain functional units are more apt to become
diseased because of impaired congenital vitality.
This theory receives support from those who state that in Pick’s disease
only certain cytoarchitectural areas are involved, that the third layer of the
cortex is the predominantly diseased, or that younger ontogenetical systems

or associated areas, more recently myelinated, are the ones primarily
involved. Neuropathologic investigations do not always support this theory.
Regions comparatively younger, such as Broca’s area and the temporal gyri of
Heschl, have been often reported spared, whereas regions phylogenetically
older, such as the gyri hippocampi and the Ammon’s horn, have been severely
involved. Furthermore, involvement of regions corresponding to the

associative areas of Flechsig, or to the third cortical layer, is not a constant
finding. Finally the involvement of subcortical gray structures, a finding
invoked in support of the theory that the disease is heredodegenerative in

nature, might not be a primary involvement as maintained, but a secondary
one, resulting at least in part from the atrophy of the corresponding cortical
areas.
On the other hand, cases of Pick’s disease in which genetic factors play a
role, are undoubtedly on record. Sjogren et al., in eighteen cases of Pick’s

disease confirmed by autopsy, have reported the occurrence in three families
of three secondary cases among the parents, and in another family, one
secondary case among the siblings. They feel that in Pick’s disease the
hypothesis of a major dominant gene, with modifying genes, appears
somewhat acceptable. The report of Sanders et al., of a family in which

seventeen members were apparently affected by the disease in the course of
four generations, and the report of Malamud and Waggoner, of another family
with fifteen affected members in four generations, also support the Mendelian
dominant character of the disease.
However, the fact that in Pick’s disease, and to a lesser extent in
Alzheimer’s disease, the initial pathological involvement centers around the
neurons (nerve cells and nerve fibers) with subsequent glial reaction, but no
appreciable mesodermic involvement, seems to favor the concept of a close

relationship between pathologic senility and presenility. If one considers that
this same pathologic process of progressive atrophy affects all organs in the
course of senility, one is tempted to see, in the general metabolic changes

related to senility, the common pathogenic factor in the etiology of both senile
and presenile psychoses. Genetic factors may, however, govern the premature
development of the aging process as well as the structural makeup of the
brain as a whole, or of certain portions of it.
This concept of a genetic premature senescence should not however

diminish the importance of various exogenous factors—toxic, infectious, or
endocrine—which have been considered by some investigators as the
pathogenetic mechanisms in senility and presenility. These exogenous
environmental, and endogenous metabolic or endocrine or vascular factors
are apt to accelerate the inherited process of aging. That a precipitating

vascular factor may play an important part in determining some of the
localized structural changes in Pick’s disease has been hypothesized by
several investigators, among whom are Schenk, De Ajuriaguerra, and La-fora.
The latter refers also to the possibility of anoxia resulting from circulatory
impairment, dependent on gradual occlusion of the internal carotid artery, as
reported by Miller-Fisher. However structural vascular structural changes are
not essential in order to precipitate presenile changes. As Jervis and Ferraro

already reported in 1936, some of their findings, particularly in the white
matter, were very suggestive of functional vasomotor imbalance, perhaps a
vasospasm occurring repeatedly and followed in the long run by structural
damage, i.e., nerve cell atrophy and their replacement by perivascular gliosis.
Why repeated transitory angiospasms should affect only certain areas of the
brain, remains to be investigated. Lafora speaks of vascular pathoclisis as

playing a role in senile and presenile dementias.
Bibliography
Achucarro, N. and M. Gayarre. “Contribution al estudio de la Neuroglia en la corteza de la

dementia senil y su participation en la alteration celular de Alzheimer,” Trab. Lab.
Invest. Biolog. Cajal, 12 (1914), 67.
Adlesberg, D., L. E. Schaeffer, and R. Dritsch. “Adrenal Cortex and Lipid Metabolism; Effects of
Cortisone and ACTH on Serum Lipids in Man,” Proc. Soc. Exp. Biol. Med., 74 (1950),
877.
Allbutt, C. Quoted by A. M. Fishberg, in Hypertension and Nephritis. Philadelphia: Lea & Febiger,
1939.
Altmann, E. “Ueber die Umschriebene Gehirnatrophie des Spaeteren Alters,” Zentralbl. Neurol.
Psychiat., 83 (1923), 60.
Altschul, R. “Histologic Analysis of Arteriosclerosis,” Arch. Pathol., 38 (1944), 305-
Altschul, R., F. Hoffer, and J. D. Stephen. “Influence of Nicotinic Acid and Serum Cholesterol in
Man,” Arch. Bio-chem., 54 (1955), 588.
Alzheimer, A. “Ueber Eigenartige Erkrankung der Hirnrinden,” Allg. Z. Psychiatr., 1907.
Anders, H. E., and N. J. Eicke. “Ueber Veranderungen an Gehirngefassen bei Hypertonie,” Z. Ges.
Neurol. Psychiatr., 167 (1939). 562.
Anitschkow, N. “Experimental Arteriosclerosis in Animals,” n E. V. Cowdry, ed., Arteriosclerosis.

Macmillan: New York 1933.
Anitschkow, N. and S. Shalatow. “Ueber Experimentelle Cholesterinsteatosis und ihre Bedeutung

fur die Entstehung Einiger Pathologisher Prozesse,” Zentralbl. Allg. Path., 34
(1913), 1.
Aschoff, L. “Ueber Arteriosklerose,” Z. Ges. Neurol. Psychiatr., 167 (1939), 214.
Badia Brandia, M. “El Factor herencia en la etiologia de la hipertonia essential,” Rev. Med.
Barcelona, 12 (1930), 3.
Bagh, K. von. “Klinische und Pathologisch Anatomische Studien an 30 Faellen von Umschriebener
Atrophie der Grosshirnrinde (Picksche Krankheit),” Ann. Med. Int. Fennicae (1946).
Baker, A. B. “Structure of the Small Cerebral Arteries and Their Change with Age,” Am. J. Pathol,
13 (1937), 453.
Barrett, A. M. “A Case of Alzheimer’s Disease with Unusual Neurological Disturbances,” J. Nerv.

Ment. Dis., 40 (1913), 361.
Beckenstein, N. and L. Gold. “Problems of Senile Arteriosclerotic Mental Patients; A Review of 200
Cases,” Psychiatr. Q., 19 (1945), 398.
Binswanger, O. and J. Schaxel. “Beitraege zur Normalen und Pathologischen Anatomie der Arterie
des Gehirns,” Arch. Psychiatr., 58 (1917), 141.
Bleuler, E. Textbook of Psychiatry. New York: Macmillan, 1924.
Blocq, P. and G. Marinesco. “Sur les lesions et la pathogenie de l’epilepsie dite essentielle,” Sem.
Med., 12 (1892), 445.
Boas, E., A. Parets, and D. Adlersberg. “Hereditary Disturbance of Cholesterol Metabolism; A

Factor in the Genesis of Atherosclerosis,” Am. Heart J., 352, 611.
Bogaert, L. Von. “Cerebral Amyloid Angiopathy and Alzheimer’s Disease,” in G. E. W.

Wolstenholme and M. O’Connor, eds., Alzheimer’s Disease and Related Conditions, p.
95. A Ciba Foundation Symposium. London: Churchill, 1970.
Bogaert, L. Von and I. Bertrand. “Pathologic Changes of Senile Type in Charcot Disease,” Arch.
Neurol. Psychiatry, 16 (1926), 263.
Bogaert, L. Von, M. Maere, and T. De Smedt. “Sur les Formes familiales precoces de la maladie
d’Alzheimer,” Monatsschr. Psychiatr. Neurol., 102 (1940), 249.
Bonfiglio, F. L’Anatomia patologica delle psicosi dell’eta senile,” Riv. Sperim. Freniatria, 45 (1921),
219.
Bonfiglio, G. “Die Umschriebene Atrophy der Basalganglien,” Z. Ges. Neurol. Psychiatr., 106 (1937),
306.
_____. “LYstopatologia delle psicosi dell’ eta senile e presenile,” Proc. 1st Int. Congr. Neuropathol.,
Vol. II. Turin: Rosenberg & Sellier, 1952.
Braunmuhl, A. von. “Zur Histopathologie der Umschriebenen Grosshirnrindenatrophie,” Arch.

Pathol. Anat. 270 (1928), 448.
Braunmuhl, A. von and K. Leonhard. “Ueber ein Schwesternpaar mit Pickscher
Kranheit,” Z. Ges. Neurol Psychiatr., 150 (1934), 209.
Bruetsch, W. L. “Arterioscelerotic Occlusion of Cerebral Arteries; Mechanism and Therapeutic

Considerations,” Circulation, 11 (1955), 900.
_____. “The Importance of Endothelial and Fibroblastic Cell Proliferation in Arteriosclerotic

Occlusion of Cerebral Arteries,” J. Neuropathol. Exp. Neurol., 14 (1955), 348.
Campbell, A. W. “The Morbid Changes in the Cerebro-Spinal Nervous System of the Aged Insane,”
J. Ment. Sci., 40 (1894), 638.
Cardona, F. “Sulla atrofia cerebrale circoscritta di Pick,” Riv. Patol. Nerv. Ment., 67 (1936), 7.
Cerletti, U. “Nodi, treccie e grovigli vasali nel cervello senile,” Rend. Accad. Naz. Lincei, (1909).
_____. “Una revisione del problema della degenerazione cosi detta senile,” Atti. Soc. Lombarda Sci.
Med. Biol., 14 (1925), 2.
Costantini, F. “Un senile normale 105 Anni,” Riv. Sperim. Freniatria, 37 (1911), 510.
Critchley, M. “Discussion on Presenile Psychoses,” Proc. R. Soc. Med., 31 (1928), 1443.
_____. “The Neurology of Old Age,” Lancet 1 (1931), 1221.
Curtius, F. and G. Korkhaus. “Klinische Zwillingstudien,” Z. Ges. Anat., 15 (1930), 229.
Daley, R. M., H. E. Ungerleider, and R. E. Gubner. “Prognosis in Hypertension,” JAMA, 121 (1943),
383.
De Ajuriaguerra, J. “Discussion on the Pathology of Senility,” Proc. 1st Int. Congr. Neuropathol., Vol.
2. Turin: Rosenberg & Sellier, 1952.
Del Rio Hortega, P. “Sobre la Formaciones fibrilares del Epitelio Ependimario,” Mem. R. Soc. Esp.
Histo. Nat., 15, 1929.
_____. “Sobre la verdadera signification de las cellulas neuroglixas llamada amiboides,” Bol. Soc.
Biol., 1918. “Sobre las Formaciones fibrilares del epitelio ependimario,” Mem. R.
Soc. Esp. Hist. Nat., 15, 1929.
Divry, P. “La pathochimie generale et cellulaire des processus seniles et preseniles,” Proc. 1st Int.
Congr. Neuropathol, Vol. 2. Turin: Rosenberg and Sellier, 1952.
Duguid, J. B. “Pathogenesis of Atherosclerosis,” Lancet, 257 (1949), 925.
Eros, G. “Observations on Cerebral Arteriosclerosis,” J. Neuropathol. Exp. Neurol., 10 (1951), 237.
Evans, G. “The Nature of Arteriosclerosis,” Br. Med. J., 1 (1923), 454.
Fenyes, I. “Alzheimersche Fibrillenveraen-derungen im Himstammeiner in 28 Jaehrigen

Postencephalitischen,” Arch. Psychiatry, 96 (1932), 700.
Ferraro, A. “The Origin and Formation of Senile Plaques,” Arch. Neurol. Psychiatry, 25 (1931),
1042.
Ferraro, A. and L. A. Damon. “The Histogenesis of the Amyloid Bodies in the Central Nervous
System,” Arch. Neurol. Psychiatry, 12 (1931), 229,
Ferraro, A. and G. Jervis. “Pick’s Disease,” Arch. Neurol. Psychiatry, 36 (1936), 739.
Fishberg, A. M. Hypertension and Nephritis, 4th ed. Philadelphia: Lea & Febiger, 1958.
Fisher, O. “Die Histopathologie der Presbiophrenie,” Allg. Z. Psychiatr., 45 (1908), 500.
_____. “Ein Weiterer Beitrage zur Klinik und Pathologie der Presbiophrenie,” Z. Ges. Neurol.
Psychiatr., 27 (1913), 397.
Fluegel, F. E. “Quelques recherches anatomiques sur la degenerescence senile de la moelle

epiniere,” Rev. Neurol., 34, 618.
French, J. E. “Atherosclerosis,” in H. Florey, ed., General Pathology, 2nd ed. Philadelphia: Saunders,
1958.
Frey, E. “Beitrage zur Klinik und Pathologische Anatomie der Alzheimerschen Krankheit,” Z. Ges.
Neurol. Psychiatr., 27 (1913). 397-
Fuller, S. “Alzheimer’s Disease; (Senium Praecox),” J. Nerv. Ment. Dis., 39 (1912), 440.
Gans, A. “Betrachtungen ueber Art und Ausbreitung des Krankhaften Processes in Einem Fall von
Pickscher Atrophie des Stirnhirns,” Z. Ges. Neurol. Psychiatr., 80 (1923), 10.
_____. “Falle von Pickscher Atrophie des Stirnhim,” Zentralbl. Neurol., 33 (1923), 516.
Geiringer, E. “Intimal Vascularization and Atherosclerosis,” J. Pathol. Bacteriol., 631 (1951), 201.
Gellerstedt, N. “Zur Kenntniss der Himveranderungen bei der Normalen Alter-dissolution,”

Inaugural Dissertation, Upsala University, 1933.
Globus, J. H. and J. A. Epstein. “Massive Cerebral Hemorrhage; Spontaneous and Experimentally

Induced,” Proc. 1st Int. Congr. Neuropathol., Vol. 1. Turin: Rosenberg & Sellier, 1952.
Globus, J. H. and I. Strauss. “Massive Cerebral Hemorrhage,” Arch. Neurol. Psychiatry, 18 (1925),
215.
Gofman, J. W., F. Lindgren, H. Elliot et al. “The Role of Lipids and Lipoproteins in Arteriosclerosis,”
Science, 111 (1950), 166.
Goodman, L. “Alzheimer’s Disease; A Clinico-Pathological Analysis of Twenty-three Cases,” J. Nerv.

Ment. Dis., 118 (1953), 97.
Grunthal, E. “Klinish-Anatomisch Vergleichende Untersuchungen ueber den Greisenblodsinn,” Z.
Ges. Neurol. Psychiatr., 3 (1927), 763.
_____. “Ueber Erblichkeit der Pickschen Krankheit,” Z. Ges. Neurol. Psychiatr., 136, 464.
Grunthal, E. and O. Wegnert. “Nachweis von Erblichheit der Alzheimerschen Krankheit,”

Monatsschr. Psychiatr. Neurol., 101 (1939), 8.
Gull, W. and H. Sutton. “Arterio-Capillary Fibrosis,” Med. Chirurg. Trans. 55 (1872), 273.
Hall, M. H. “The Blood and Lymphatic Vessels,” in W. Anderson, ed., Pathology, 3rd ed. St. Louis:
Mosby, 1957.
Herburt, P. A. Pathology. Philadelphia: Lea & Febiger, 1955.
Hilpert, P. “Zur Klinik und Histopathologie der Alzheimershen Krankheiten,” Archiv. Psychiatr., 76
(1926), 379.
Hueper, W. C. “Arteriosclerosis,” Arch. Pathol, 38 (1944). 162; 39 (1945). 51.
Ignatowski, A. “Ueber die Wirkung des Tierischen Eiweisses auf die Aorta und die
Parenchymatosen Organe der Kaninchen,” Arch. Pathol, Anat., 198 (1909), 245.
James, G. W. B. Quoted by L. Bini in Le Demenze Presenili. Rome: Edizioni Italiane, 1948.
Jervis, G. A. “Alzheimer’s Disease,” Psychiatr. Q., 11 (1937), 5.
_____. “The Presenile Dementias,” in O. J. Kaplan, ed., Mental Disorders in Later Life, p. 262.
Stanford: Stanford University Press, 1956.
Jervis, J. and S. Soltz. “Alzheimer’s Disease; The So-Called Juvenile Type,” Am. J. Psychiatry, 99
(1936), 39.
Katz, L. N. and J. Stamler. Experimental Atherosclerosis, Springfield, 111.: Charles C. Thomas,

1953.
Kehrer, F. “Die Psychoses des Um-und Rückbildungs Alters,” Z. Ges. Neurol. Psychiatr., 167 (1939).
35.
Kendall, F. E. “Aging and Atherosclerosis,” Bull. N.Y. Acad. Med., 32 (1956), 517.
Klotz, O. “Compensatory Hyperplasia of the Intima,” J. Exp. Med., 12 (1910), 707.
Kraepelin, E. Lehrbuch der Psychiatrie. Leipzig: Barth, 1912.
Lafora, G. R. “Zur Frage des Normalen und Pathologische Senium,” Z. Ges. Neurol. Psychiatr., 13
(1912), 460.
_____. “Valorisation critique des decouvertes histopathologiques de la senilite,” Proc. 1st Int. Congr.
Neuropathol., Vol. 2. Turin: Rosenberg & Sellier, 1952.
Larimore, J. W. “A Study of Blood Pressure in Relation to Types of Bodily Habitus,” Arch. Intern.
Med., 31 (1923), 567.
Leary, T. “The Genesis of Atherosclerosis,” Arch. Pathol., 32 (1941), 507.
Leri, A. “Le cerveau senile,” These, Universite de Lille, 1906.
Lewy, F. “Primare und Sekundare Involutive Veranderungen des Gehims,” Krankheitsforsch., 1

(1925), 164. go. Ley, R. Etude anatomique de la senilite. Brussels: Livre Jubilaire de
la Societe Beige de Neurologie, 1932.
Liebow, I. M. and H. K. Hellerstein. “Cardiac Complications of Diabetes Mellitus,” Am. J. Med., 7

(1949), 660.
Lowenberg, K. and D. Rothschild. “Alzheimer’s Disease; Its Occurrence on the Basis of a Variety of
Etiologic Factors,” Amer. J. Psychiatry, 99 (1931), 289.
Lowenberg, K. and R. W. Waggoner. “Familial Organic Psychosis (Alzheimer’s Type),” Arch.

Neurol. Psychiatry, 31 (1934), 737.
Luce, R. E. and D. Rothschild. “The Correlation of Encephalographic and Clinical Observations in
Psychiatric Patients over 65,” J. Gerontol., 8 (1953), 167.
Luthy, F. “Ueber Einige Bemerkenswerte Falle von Multipler Sklerose,” Z. Ges. Neurol Psychiatr.,
130 (1930), 219.
Me Adam, W. and W. T. McClatchey. “The Electroencephalogram in Aged Patients,” J. Ment. Sci., 98

(1952), 711.
McMenemey, W. H. and E. Pollack. “Presenile Diseases of the Central Nervous System,” Arch.
Neurol. Psychiatr., 45, 683.
Malamud, N. and R. W. Waggoner. “Genealogic and Clinico-Pathologic Study of Pick’s Disease,”

Arch. Neurol. Psychiatr., 50 (1943), 288.
Malamud, W. and K. Lowenberg. “Alzheimer’s Disease,” Arch. Neurol. Psychiatr., 21:805, 1929.
Marinesco, G. “Contribution a l’etude anatomo-clinique et a la pathogenie de la forme tardive de

lldiotie Amaurotique,” Bull. Acad. Med. Roumaine, 9 (1925), 119.
Meyer, A. “On Parenchymatous Systemic Degeneration Mainly in the Central Nervous System,”
Brain, 92 (1901).
_____. “Arteriosclerosis and Mental Diseases,” Trans. Med. Soc. New York, 1903.
Miller-Fisher, C. “Discussion on Senility,” Proc. 1st Int. Congr. Neuropathol., Vol. 2. Turin:
Rosenberg & Sellier, 1952.
Morel, F. and E. Wildi. “General and Cellular Pathochemistry of Senile and Presenile Alterations of
the Brain,” Proc. 1st Int. Congr. Neuropathol, Vol 2. Turin: Rosenberg & Sellier, 1952.
Moschkowitz, E. Vascular Scleroses. New York: Oxford, 1942.
_____. “Hyperplastic Arteriosclerosis versus Atherosclerosis,” JAMA, 143 (1950), 861.
Moyano, A. “Dementia Presenile; Pick y Alzheimer,” Arch. Argent. Neurol., 7 (1932), 231.
Nador-Nikititis, E. de. “Sur l’etiologie de l’hypertension arterielle essentielle,” Arch. Mai. Coeur., 18
(1925), 582.
Neuburger, K. T. “Arteriosclerosis,” in O. Bumke, ed., Handbuch der Geisteskrankheiten, p. 570.

Berlin: Springer, 1930.
_____. “Summary and Critical Evaluation of Neuropathology of Vascular Diseases,” Proc. 1st Int.
Congr. Neuropathol. Vol. 1. Turin: Rosenberg & Sellier, 1952.
Neumann, M. A. “Pick’s Disease,” J. Neuropathol. Exp. Neurol. 8 (1949), 255.
Onari, K. V. and H. Spatz. “Anatomische Beitrage zur Lehre von der Picksche Krankheit,” Z. Ges.
Neurol. Psychiatr., 101 (1926), 470.
Ophuls, W. “The Pathogenesis of Arteriosclerosis,” in E. V. Crowdry, ed., Arteriosclerosis. New

York: Macmillan, 1933.
Perusini, G. “Ueber Klinische und Histologische Eigenartige Psychische Erkrankungen des

Spaetern Lebensalters,” in F. Nissl and A. Alzheimer, eds., Histologische und
Histopathologische Arbeiten ueber die Grosshirnrinde mit Besonderer
Beruechksichtigung der Pathologischen Anatomie der Geisteskrankheiten, Vol. 3, p.
297. Jena: Fischer, 1910.
Piazza, U. “Contributoalio studio del nosografismo e del reperto istopatologico delle

presbiofrenie,” Riv. Ital. Neurol. Psych., 5 (1912), 193-
Pick, A. “Senile Hirnatrophie als Grundlage von Herderscheinungen,” Wien. Klin. Wochenschr., 14
(1901), 403.
_____. “Ueber einen Symptomcomplex der Dementia Senilis durch Umschriebene Hirnatrophie,”
Monatschr. Psychiatr. Neurol., 19 (1906), 97.
Redlich, E. “Ueber Miliare Sklerose der Himrinde bei Sender Atrophie,” Jahrb. Psychiatr. Neurol.,
17 (1898), 208.
Reichardt, M. Quoted by L. Bini in La Demenze Presenili. Rome: Edizioni Italiane, 1948.
Rheingold, J. “Ueber Presbiophrenie Sprachstorungen,” Z. Ges. Neurol. Psychiatr., 76 (1922), 220.
Rinehart, J. F. and L. D. Greenberg. “Arteriosclerotic Lesions in Pyridoxin Deficient Monkeys,” Am.

J. Pathol., 25 (1949), 481.
Rosenberg, E. F. “The Brain in Malignant Hypertension,” Arch. Intern. Med., 651 (1940), 544.
Rosenblath, E. “Ueber die Entstehung der Hirnblutung bei dem Schlaganfall,” Dtsch. Z. Nervenh.,
61 (1918), 10.
Rothschild, D. “Senile Psychoses and Psychoses with Cerebral Arteriosclerosis,” in O. Kaplan, ed.,
Mental Disorders in Later Life, p. 289. Stanford: Stanford University Press, 1956.
Rothschild, D. and J. Kasanin. “Clinico-Pathologic Study of Alzheimer’s Disease,” Archiv. Neurol.

Psychiatr., 36 (1936), 293.
Ruczika, V. “Beitraege zum Studium der Protoplasma-Histeretischen Vorgaenge,” Arch. Mikr.

Anat., 101 (1924), 459.
Runge, W. “Die Geistesstorungen des Greisenalters,” in O. Bumke, ed., Handbook der

Geisteskrankheiten, Vol. 8. Berlin: Springer, 1930.
Saltikow, S. “Die Experimentelle erzeugten Arterienveranderungen,” Zentralbl Allg. Pathol. Anat.,

19 (1908), 321.
Sanders, J., V. W. Schenk, and P. van Veen. “A Family with Pick’s Disease,” J. Nerv. Ment. Dis., 92
(1940), 684.
Schaffer, K. “Zur Normalen und Pathologischen Fibrillenbau der Kleinhirnrinde,” Z. Ges. Neurol.
Psychiatr., 16 (1926), 263.
Scheinker, I. M. “Obliterative Cerebral Arteriosclerosis, A Characteristic Vascular Syndrome,” Am.

J. Pathol., 22 (1908), 321.
Schenk, V. W. D. “Maladie de Pick; Etude Anatomo-Clinique de 8 Cas,” Ann. Med. Psychol, 109
(1951), 574.
Schnitzler, J. G. “Zur Abgrenzung der Sogennanten Alzheimersche Krankheit,” Z. Ges. Neurol.

Psychiatr., 7 (1911), 34.
Scholz, W. “Die Drusige Entartung der Hirnarterien und Capillaren,” Z. Ges. Neurol. Psychiatr., 162
(1938), 694.
_____. “Les Necroses parenchymateuses electives par hypoxemie et oligemie et leur expression
topistique,” Proc. 1st Int. Congr. Neuropathol. Turin: Rosenberg & Sellier, 1952.
Schottky, J. “Ueber Praesenile Verblodung,” Z. Ges. Neurol. Psychiatr., 140, 133.
Silverman, A. M., E. W. Busse, and R. H. Barnes. “Studies in the Process of Aging;

Electroencephalographic Findings in 400 Elderly Subjects,” Electroencephalogr.
Clin. Neurophysiol., 7 (1955), 67.
Simchowitz, T. “Histologische Studienueber die Senile Demenz,” Histol. Histopathol. Arb. Nissl. 4
(1910), 268.
Simma, K. “Die Subcorticalen Veranderungen bei Pickscher Krankheit,” Monatschr. Psychiatr.

Neurol., 123 (1952), 205.
Sjogren, T. M., H. Sjogren, and A. G. H. Lindgren. “Morbus Alzheimer and Morbus Pick; A Genetic
Clinical and Patho-Anatomical Study,” Acta. Psychiatr. Scand. 82-1 (Suppl.), 1952.
Spatz, H. “Ueber die Systematischen Atrophien,” Arch. Psychiatr., 108 (1937), 1.
_____. “Pathologisch Anatomie der Kreislaufstorungen des Gehirn,” Z. Ges. Neurol. Psychiatr., 167
(1939). 301.
_____. “La Maladie de Pick et la senescence cerebrale prematuree localisee,” Proc. 1st Int. Congr.
Neuropathol., Vol. 2. Turin: Rosenberg & Sellier, 1952.
Spielmeyer, W. “Ueber die Alterserkrankungen des Zentralnervensystem,” Dsch. Med.
Wochenschr., (1911).
Stief, A. “Beitrage zur Histologie der senilen Demenz,” Z. Ges. Neurol. Psychiatr., 91 (1924), 579.
Tanzi, E. and E. Lugaro. “Trattato delle malattie mentali,” Soci. Editricie Milanese. Milan, 1916.
Tiffany, W. J. “The Occurrence of Miliary Plaques in Senile Brains,” Am. J. Insan., 70 (1913-14),
739.
Tuthill, C. R. “Cerebral Arteries in Relation to Arteriosclerosis,” Arch. Pathol., 16 (1933), 453.
Urecchia, C. T. and C. Danetz. “Quelques Considerations sur la maladie d’Alzheimer,” Encephale,

19 (1924), 382.
Urecchia, C. T. and N. Elekes. “Contribution a l’etude des plaques seniles,” Bull. Acad. Nat. Med., 94
(1925), 795.
Verhaart, W. J. C. “On the Development of Senile Plaques in Alzheimer’s Disease and Other Senile
Cerebral Diseases,” Acta. Psychiatr. et Neurol., 4 (1929), 339.
_____. “Over die Ziekte van Pick,” Med. Tijasch Geneesk, 74 (1930), 586.
Virchow, R. Die Cellularpathologie in ihrer Begrundung auf physiologischer und pathologischer

Gewebelehre. Frankfurt: Meidinger 1858.
Vogt, C. “Die Picksche Atrophie als Beispiel fur die Eunomische Form der Schichtenpatholise,” J.
Psychol. Neurol., 36, (), 124.
Weimann, W. “Ueber eine Atypische Presenile Verblodung,” Z. Ges. Neurol. Psychiatr., 23 (1921),
355.
Weitz, W. “Studien an Einetigen Zwillingen,” Z. Klin. Med., 101 (1925), 115.
Wesselkin, N. W. “Ueber die Ablagerung von Fettartigen Stoffen in den Organen,” Arch. Pathol.
Anat., 212 (1913), 225.
Westphal, K. and R. Baer. “Ueber die Entstehung des Schlaganfalles Pathologischanatomische

Untersuchungen zur Frage der Enstehung des Schlaganfalles,” Dsch. Arch. Klin.
Med., 151 (1926), 1.1.59.
Wilens, S. L. “The Nature of Diffuse Intimal Thickening,” Am. J. Path., 272 (1950), 825.
Wilson, G., C. Rupp, and H. E. Riggs. “Factors Influencing the Development of Cerebral Vascular
Accidents,” JAMA, 145 (1951), 1227.
Winternitz, M. C., R. M. Thomas, and P. M. Le Compte. The Biology of Arteriosclerosis, Springfield,

Ill.: Charles C. Thomas, 1938.
Worster-Drought, C., J. Greenfield, and W. McMenemey. “A Form of Presenile Dementia with

Spastic Paralysis,” Brain, 63 (1940), 237.
Chapter 5
Neurosyphilitic Conditions:
General Paralysis, General Paresis, Dementia
Paralytica
Walter L. Bruetsch
Haslam, an apothecary at Bethlem Hospital in London, is usually
credited with having given the first description of general paralysis in 1798.
In 1793, however, Chiarugi, the “Italian Pinel,” had described some
presumably genuine cases.
Haslam’s thesis consisted of a report of twenty-nine consecutive cases

of insanity which came to autopsy. Of the twenty-nine patients, four may
conceivably have been cases of dementia paralytica. The credit for having
described this disease is based chiefly on one report—that of a man, forty-two

years of age. The mental illness had come on suddenly, while he was working
in a garden. He believed himself to be the king of Denmark and at other times
the king of France. He also professed to be the master of all dead and living
languages and claimed that he had come to England with William the
Conqueror. Later, he developed apoplectic phenomena. His speech was
inarticulate. He became demented, bedridden, and emaciated, and his
buttocks ulcerated. Eighteen months after the onset, he died. Postmortem

examination revealed opaque and thickened meninges and enlarged
ventricles. It is fair to say that Haslam unknowingly described in this report a
typical case of general paralysis.
In the upsurge of syphilis during the Napoleonic wars, many former
soldiers developed general paralysis, and French psychiatrists deserve credit
for the elucidation of the disorder. Esquirol, in 1814, directed attention to the
slurred speech accompanying it. In 1822 Bayle, a young physician at the
insane asylum of Charenton in the suburbs of Paris, was the first to recognize
general paralysis as a disease entity with characteristic symptoms and
distinctive brain changes. The importance of this contribution lies in the fact
that, for the first time, a group of patients whose disease could be recognized
both clinically and anatomically as a distinct entity had been separated from
the general run of mental cases.
In 1826 the French psychiatrist Calmeil referred to the disease as

paralysie generate des alienes (the general paralysis of the insane). To this
day, the term has been retained with slight variations in most countries.
Calmeil explained why he coined this term: The French clinicians were
impressed by the fact that no other mental disease culminated so frequently
in “general paralysis” of all the mental and physical faculties. In the advanced
stage, the patients developed a generalized weakness of the entire muscular
system. They became unable to move about and finally became bedfast. On
the other hand, in the institutions there were many other cases of insanity
with similar abnormal behavior and dementia, yet in spite of being there for
twenty and more years, the patients did not develop this kind of general
weakness.
Etiology
There was much speculation as to the etiology of the disease. Calmeil
only once referred to syphilis in the anamnesis of a known debauchee, saying
only that he did not know whether this patient had a venereal disease and
whether he had been treated with mercury. For many years, it did not enter
the minds of psychiatrists that a “skin disease” could also be responsible for a
mental disease. Most earlier authors believed that occupations in life which
involved hardships, both mental and physical, favored the onset of the illness.
As late as 1877, von Krafft-Ebing gave the following etiologic possibilities:
heredity, dissipation (Bacchus and Venus), smoking of ten to twenty Virginia
cigars, excessive heat and cold, trauma to the head, exhaustive efforts to make
a living, weak nerves, and fright. Among women the menopause was given as
the most important factor because the onset of general paralysis was frequent
between the ages of forty and fifty. Strikingly, von Krafft-Ebing in 1877 did
not mention syphilis among the possible causes, although Esmarch and Jessen
had published their now famous paper on syphilis and insanity in 1857.
At about the same time, 1860, the Danish physician Steenberg also saw
such a connection. In his doctoral thesis entitled, “Syphilitic Brain Disease,”
Steenberg reviewed the hitherto assumed causes of dementia paralytica, such
as heredity, psychic causes, overwork, and alcoholism. He showed that
separately and collectively they were insufficient to explain dementia

paralytica, but that, by assuming syphilis as the etiologic factor, a solution as
to the cause of this disease was at hand. In 1874 Jespersen, among others, on
the basis of a large amount of data, furnished the evidence that general
paralysis resulted from syphilis.
At the International Medical Congress in Copenhagen in 1884, where
the question of syphilis in dementia paralytica was discussed, there occurred

one of the last important disputes concerning the etiology of general
paralysis. The Danish physicians were outspoken in their assertion that
dementia paralytica was a result of syphilis. Mobius (Leipzig) shared this

view. Bajenoff (Moscow) discussed Maudsley’s (London) absolute rejection of
the theory of the syphilogenic origin of the condition. He himself was

skeptical. Magnan (Paris) mentioned that at the mental hospital of St. Anne in
Paris, where 300 general paralytics were admitted annually, only thirty to
forty syphilitics were found among the cases of dementia paralytica. He again
emphasized the role of alcohol. In France almost no one, with the exception of
Fournier, believed at that time that there was a connection between general
paralysis and syphilis. Shortly before the turn of the century, in 1898, no less
an authority than Virchow, in a discussion before the Berlin Medical Society,
vehemently denied the syphilitic etiology of general paralysis, tabes dorsalis,
tabetic optic atrophy, and aortic aneurysm.
At this stage, the trend of investigation shifted from the clinic to the
laboratory. With the introduction of the newer methods of staining,
histopathologic studies on the brain cortex of the mentally ill received a new
impetus. In 1904 Nissl and Alzheimer gave a detailed description of the

microscopic changes in the brain of general paralytic patients, which were
uniform in all instances, including those without a history of syphilis.
Furthermore, the Wassermann test, which had been devised about this time
(1906), gave a positive reaction in blood and spinal fluid. Schaudinn, in 1905,
had discovered the organism of syphilis, but, owing to technical difficulties, it

was not until 1913 that Noguchi and Moore were able to demonstrate
spirochetes in the brain of general paralytics. The demonstration of

Treponema pallidum in the cerebral cortex closed the chain of evidence
concerning the syphilitic nature of the disease.
Frequency
Throughout the world, until the advent of penicillin, general paralysis
was responsible for a high proportion of the admissions to mental

institutions. Of the patients admitted to state hospitals for mental disease in
the United States, between 5 and 15 percent were so afflicted. In the mental
hospital Dalldorf, in Berlin, the admission rate of both men and women
paralytics in the period from 1892 to 1902 varied between 22 and 32 percent
of the total admissions. In 1930 the number of general paralytics admitted to
the Tokyo Insane Hospital constituted 30.7 percent. In Batavia (former Dutch
East Indies), one third of all Asiatic patients admitted to the psychiatric pision
of the General Hospital suffered from neurosyphilis. At the Central State
Hospital of Indianapolis, from 1927 to 1931, the admission rate due to
general paralysis varied between 20.5 and 24.7 percent. By 1947 the figure
had dropped to 12.2 percent, and in 1970 it had dwindled to less than 1
percent.
Most general paralytic patients now in mental institutions of the United
States are carryovers from the previous decades of high-admission rates.

They are patients who were treated with malaria or penicillin but in whom
residual organic defects prevented a return to the community.
In a group of 241 patients with various types of neurosyphilis, there
were twelve cases of general paralysis.
Clinical Features
The clinical picture of general paralysis consists of a progressive

deterioration, leading to a complete undermining of the whole mental and
physical personality. It always terminates fatally if not properly treated.
The symptomatology is varied, and general paralysis may produce any

psychiatric syndrome, such as manic-like phases, severe depressions,
schizophrenic symptoms, and, in the initial stage, a psychoneurosis.
The incubation period averages fifteen years, the lower limit being three
years and the upper range approximately forty years.
Mental Symptoms
The most outstanding feature of general paralysis is the progressive
destruction of all mental functions. The central symptom of the disease is the
dementia, around which are grouped a variety of accessory psychiatric and

neurologic manifestations.
The onset of the mental disorder is often difficult to ascertain. The
history, as given by the patient, concerning the earliest symptoms is usually
worthless. Of greater importance are the observations of close relatives, but
even the patient’s wife may fail to see the significance of the earliest changes,
such as misplacing various articles and repeating the same story several
times. One patient, an ardent card player, would sit up all night playing cards,
and at other times would shuffle a deck of cards endlessly without playing.
Memory soon becomes affected. Recent events cannot be remembered,

while remote happenings may still be recounted with accuracy. The patient
forgets that he has just eaten his dinner, and he is confused about the time of
day. Although the patient may do some minor erratic things, his personality
may remain intact for a considerable length of time, and routine duties may
be carried out remarkably well.
A disturbance of affect may set in relatively early. The patients become

apathetic and dull, and remain unimpressed by tragedies that may strike their
families. Sometimes, the incipient stage is characterized by anxiety and
emotional instability. The appearance of euphoria is most characteristic. This
feeling of well-being is difficult to differentiate from the peculiar stage of

happiness in the manic phase of a manic-depressive psychosis. It may be a
component of the loss of judgment.
With the advance of the illness, irritability, loss of memory, and
slovenliness become more obvious. At this stage, gross mental abnormalities
may suddenly appear. I knew a patient who drove at high speed through a red
light, killing a pedestrian. When he was arrested, he did not comprehend the
seriousness of the charge and told police in an excited manner that he was
King Herod. Some patients commit sudden acts of violence. One patient at a
public health center, where he was receiving weekly injections of

tryparsamide, took the door of the waiting room off the hinges and tore the
linoleum from the floor. A bartender entered his competitor’s business place
and, with an ax, hacked the furniture to pieces. Sometimes patients will do
odd and silly things, such as going to the grocery store and walking away
without paying the bill. One patient tried to buy a Buick automobile in a five-
and-ten-cent store. A merchant created confusion in a bank, where he insisted
on cashing a check for $25,000 without having funds on deposit. One patient
forced his wife into the car and drove her to the local mental hospital, saying
that she was insane. Another patient came home with a six-foot maple tree
and tried to plant it on the windowsill.
Such acts are the result of gross loss of judgment, which is one of the
basic symptoms of the disease and from which some of the delusions
originate. Delusions, however, are not always present in the clinical picture.
Some patients live merely in childlike contentment, manifesting boastful
tendencies throughout the course of the disease. The content of the delusions
is usually related to the educational background and to the news of the day. In
the 1920s, when Henry Ford was in the limelight, many patients imagined
themselves to be Henry Ford. At about the same time, the Prince of Wales,
then a bachelor, visited the United States. An unmarried woman with general
paralysis told me that she was engaged to marry the Prince. In 1933, when
prohibition ended, one patient boasted of drinking several gallons of whisky a
day. During World War II, a grandiose paralytic told medical students during
a lecture that he was a pe-bomber pilot and that he had just returned from the
battle of the Coral Sea, during which he had sunk several Japanese battleships
and a dozen cruisers. His plane had had both wings shot off, but he returned
safely to his base. Other patients during the war period claimed to own
aircraft carriers and battleships. The records of the grandiose delusions often
give a panorama of the historic and social background of a nation. In France
the patients used to be Napoleon, in Germany they were the Kaiser, in Czarist
Russia they were czars and grand dukes. But in Soviet Russia they are great
engineers or inventors. Grandiose delusions, as a rule, are transitory and

disappear easily, even without treatment. On the other hand, in a few malaria-
treated patients, exalted delusions persisted for years, although the serology
had reverted to normal.
As the psychosis progresses, the mental deterioration becomes the

outstanding symptom, and the original symptomatology recedes to the
background. In the terminal stage the deterioration is profound. There is no
other mental disease in which dementia is so complete. At this time there are
often wild outbursts of destructiveness, and the strongest sedation is
necessary to control the patient. The most absurd things may happen. One
patient drove a pencil deep into the root of his tongue, “trying to dig out a bug
which was under his molar teeth.” Frequently, one observes prolonged
grinding of the teeth which is almost pathognomonic of the disease. Finally,
the patients become bedridden and develop a “general paralysis” of all the
intellectual and physical functions. Bedsores over hips and buttocks may
develop, which even the utmost care cannot prevent. In other instances,
spasticity sets in, causing flexed extremities, and subsequent contractures of
legs and arms. Following penicillin treatment, the physical condition of the
patient is better maintained despite dementia, and distressing states such as
these here described are now rarely seen.
Psychiatric Syndromes
How frequently the various syndromes occur is difficult to estimate,
because they cannot be sharply differentiated and often merge into one
another. Bostroem’s figures, listed in Table 5-1, are possibly the most reliable.
Table 5-1
SYNDROME PERCENT
Simple dementia 34.0
Euphoric dementia 29.0
Expansive type 10.0
Hypomanic form 0.5
Depressive form 7.0
Delirious and confusional state 11.0
Motor excitement 5.5
Schizophrenic syndrome 3.0
The Simple and Euphoric Dementias
The most common type of general paralysis is the gradually
deteriorating form. A slowly advancing dementia occurs without delusions
and excitement. Impairment of judgment, memory defects, and lack of insight
are the principal symptoms. In half of the cases, the dementia is colored by a
euphoric state.
The Expansive and Depressed Forms
The usual textbook picture of general paralysis represents the

expansive type with delusions of grandeur. The exalted mood, the absurd
delusions of wealth and power, and the happy, cheerful frame of mind make
the diagnosis easy.
The depressed type may start with an attack of extreme worry lasting
for months before other symptoms appear. The picture may resemble an
agitated depression in middle life or an involutional melancholia. One of my
patients believed that he was going to die and prayed in a loud voice for long
periods of time. A fifty-year-old preacher threatened to chop off his head as a

sacrifice for the sins which he had committed. Occasionally there are
successful suicide attempts. The taking of poison was the first symptom of
disease in one instance; in another, a patient jumped out of a third-floor

hospital window.
The Schizophrenic Syndrome
About 3 percent of the cases of general paralysis present the
schizophrenic form. From South America a much higher rate has been
reported. Some patients in this group present paranoid delusions as the only
outstanding clinical manifestation. One patient told me that people were
reading her thoughts; another accused relatives and physicians of trying to

poison him to collect his insurance. A laborer brought a revolver to the
factory and shot a fellow worker, imagining that the latter held a grudge
against him. Paranoid delusions occurring in general paralysis may be as
fleeting and temporary as the grandiose delusions, and often disappear
following therapy. Instances with the psychopathology characteristic of
schizophrenia have been reported by the most experienced psychiatrists.
Bumke tells of a case with negativism from the pre-Wasserman days. For one
year this patient was considered a catatonic schizophrenic, until he suddenly
died of paralytic convulsions.
Hallucinations occur in about 6 percent of cases. Auditory and visual
hallucinations are most common, but olfactory hallucinations have also been
observed. At times, it is difficult to say whether one is dealing with true
hallucinations or with confabulation. Hechst, in a histologic study of the
schizophrenic type of general paralysis, came to the conclusion that
schizophrenic symptoms are not associated with any particular localization of

the paralytic brain process.
The Senile Form
Until Nissl’s and Alzheimer’s histopathologic studies, senile general
paralysis was in the main unrecognized, being diagnosed as senile or
arteriosclerotic psychosis. In the aged, the disease is particularly difficult to

diagnose without a spinal fluid examination. In most cases, argyrophil
plaques in the brain are absent, but senile alterations are occasionally added
to the paralytic process. Contrary to prevailing opinion, excellent therapeutic
successes have been obtained in old age.
The Taboparalytic Form
In the taboparalytic form there is a combination of general paralysis and
tabes dorsalis (Figure 5-1). Some clinicians are willing to make a diagnosis of
taboparalysis only if, in addition to the absent patellar reflexes, there is an

ataxic gait or other tabetic symptoms, such as root pains, crises, etc. Absent
knee jerks without other symptoms of tabes are common, and these cases are
not different from those of the usual general paralytic patient.
Figure 5-1.
Spinal cord in taboparalysis. There is a degeneration of the posterior

columns. Weil’s myelin sheath stain.
Lissauer’s General Paralysis
In 1901, Lissauer called attention to an atypical type of general
paralysis, characterized by epileptiform and apoplectiform attacks, followed
by signs of a localizing nature, such as hemiplegia, aphasia, apraxia, or
hemianopsia. Lissauer’s general paralysis is rare. At autopsy, there is extreme
atrophy of an entire cerebral region, or of a group of convolutions, which far
exceeds the generalized cortical atrophy of the brain in the average case.
Prepsychotic Personality
Most authors agree that, in general paralysis, the premorbid personality
influences the clinical picture. The cerebral process seems to serve as a
release for personality trends, intensifying innate tendencies. If an inpidual
with a cyclothymic constitution develops general paralysis, he will frequently
show a manic or depressive reaction. If he has euphoric tendencies, he will
become expansive and excited. Likewise, schizoid personalities are prone to
show schizophrenic states. This relation, however, is not an absolute one. In

some instances the clinical picture corresponds only slightly to the premorbid
personality, and in others not at all.
Physical Signs
The important neurologic symptoms of general paralysis are the speech
defect, pupillary abnormalities, handwriting disorders, changes in the tendon
reflexes, convulsions, and apoplectic phenomena.
In the incipient stage no physical signs may be present, and a most

careful neurologic examination, including psychologic testing and
electroencephalogram, may give no clue as to the organic nature of the illness.
But an examination of the cerebrospinal fluid will, even at this early stage,
reveal a typical “paretic” formula. In some instances, the nervous

manifestations were attributed to stressful life experiences until, weeks later,
more obvious symptoms became manifest or the spinal fluid was examined.
On the other hand, the disease may begin with a sudden convulsion, a
transient hemiplegia, or an aphasia preceding mental changes by several
months.
The disorder of speech is so typical that a correct diagnosis can often be
made as the patient talks. The disturbed articulation is manifested as
hesitation and later as slurring. The speech defect used to be the main
symptom on which the psychiatrists of the nineteenth century depended for

diagnosis. If this particular speech involvement was present in an insane
patient, he was considered incurable. It can often be recognized during
conversation. Otherwise, test phrases such as “Methodist Episcopal Church,”

“army reorganization,” “national hospital for the epileptics,” and others have
to be employed to reveal the disturbance. Later, the patient is unable to form

sentences, and in the terminal stage, the speech is completely unintelligible. It
should be added that cerebral arteriosclerosis with bulbar symptoms may
cause a similar speech impediment.
The pupillary changes consist of irregularity of outline, inequality of
size, and impairment (diminution or absence) of the light and convergence
reflexes. Normal pupils are present in 5-10 percent of cases, but toward the
end of the illness almost all untreated paralytics have pupillary abnormalities.
Following penicillin treatment, there is, at times, an improvement in the
pupillary reactions. Of greatest importance is the Argyll Robertson pupil. The
frequency of this sign depends on the stage of the disease. It is infrequent in
incipient general paralysis; in the advanced stage, it is present in about 50
percent of cases. Pupils which are fixed to both light and accommodation are
less frequent. The diagnostic value of absolute fixation of the pupils is not as
great as that of the Argyll Robertson sign; the former may be observed in
various other diseases, for example, cerebral arteriosclerosis, multiple
sclerosis, or alcoholism.
Handwriting disturbance is manifested by misspelled words, omissions,
misplacements, and repetitions of letters and syllables (Figure 5-2). Almost
never does the patient recognize the mistakes. Occasionally, the outstanding
feature of the handwriting disorder is the tremor. In the advanced stage,
there is agraphia, the patient being unable to draw more than a few wavering
lines. The handwriting is normal in 10 percent of patients.
Figure 5-2.
Sample of handwriting in general paralysis. The patient was asked to write

Central State Hospital, Indianapolis, Indiana, and the date, which was June
28, 1952.
Junius and Arndt reported on knee jerks in 992 untreated cases; patellar
reflexes were normal in 16 percent, increased in 54 percent, and diminished
or absent in 30 percent. The abdominal reflexes are occasionally absent; less
frequently, the cremasteric reflexes are wanting.
A fine or coarse rapid tremor particularly of the extended fingers,

tongue, and labial muscles is often present. The face becomes expressionless
and devoid of normal mimic motions. There is flattening and smoothing out of
the nasolabial folds.
The most important motor disturbances are convulsions and apoplectic
phenomena. They appear in any stage of the disease and are present in 35-65
percent of cases. Psychomotor attacks or epileptic equivalents occur,
manifested by sudden periods of excitement, extreme violence, and impulsive
shouting, sodes. In successfully treated patients, the Some patients have died
during these epi-convulsions, as a rule, cease entirely. Occasionally, however,
the seizures persist indefinitely, despite disappearance of all other symptoms.

In a few otherwise completely recovered cases, convulsions made their
appearance for the first time a few months or several years after malaria or
penicillin therapy.
Syphilitic Optic Atrophy
In about 2 percent of general paralysis there is complete or nearly
complete blindness owing to optic atrophy. If special attention is paid to the
early stages of this complication, partial optic atrophy can be recognized in

about one third of the cases (Figure 5-3). The early signs consist of field
defects, and somewhat later of pallor of the optic disks, reduction of visual
acuity, and difficulties in distinguishing colors.
Syphilitic optic atrophy is due to a chronic inflammatory process,
followed by a slow degeneration of the nerve fibers. Infiltrations, composed of
plasma cells and lymphocytes, extend from the periphery along the septa
toward the interior of the optic nerves, first producing marginal
degeneration. This manifests itself in a concentric and slowly advancing
narrowing of the visual fields.
Figure 5-3.
Figure 5-3.
Partial syphilitic optic atrophy in general paralysis. The optic nerve reveals a
large marginal area of demyelination. There was two-grade paleness of the
optic disk and an irregular contraction of the visual field. (Courtesy of
Charles C. Thomas, Publisher.)
Involvement of the Aorta
The most important and frequent extracerebral lesion of general

paralysis is syphilitic aortitis, having been observed at autopsy in 33-56
percent of cases. Most instances are clinically asymptomatic, with the

exception of the aortic aneurysm and aortic valve incompetency. In the
author’s own findings, a slight or moderate widening of the aortic arch, as
revealed in X-rays, was present in 7 per cent. An insufficiency of the aortic
valve was diagnosed by auscultation in 2 percent.
Laboratory Findings1
Cerebrospinal Fluid
The abnormalities of cerebrospinal fluid consist of an increase of cells,
elevation of the total protein, increase in globulin, a first-zone colloidal gold

curve (paretic curve), and a strongly positive Wassermann reaction. The
blood Wassermann and Kahn tests are positive in 95 percent.
There are patients in whom only a complete spinal fluid examination
permits a differential diagnosis between general paralysis and other
psychiatric conditions. Negative spinal fluid in an untreated (but not in a
treated) patient precludes the diagnosis of general paralysis.
Electroencephalogram
In untreated patients, abnormal or borderline tracings are observed in

from 55-81 percent. In general paralysis or in any other type of neurosyphilis,
there is no characteristic electroencephalographic pattern. The more
abnormal the electroencephalogram, the greater is the likelihood of a history
of convulsions. The incidence of abnormal electroencephalograms, in cases of

general paralysis with seizures, is 91 percent, as compared to 44 percent in
those without convulsions.
Following successful therapy, an improvement in the
electroencephalographic tracings has been reported in most instances. In the
interpretation of an electroencephalogram the existence of organic
alterations may be revealed, but an occasional absence of
electroencephalographic abnormality does not exclude the presence of a
cerebral lesion.
Pneumoencephalogram
Pneumoencephalography is not a delicate diagnostic method because of
the limitations in the recognition of minor cortical atrophies. It is of little
auxiliary value in the diagnosis of early general paralysis. In advanced cases

there is dilatation of the ventricular system and of the subarachnoid spaces.
Pathology
Gross Changes
The macroscopic findings in general paralysis consist of cloudy and
thickened meninges, atrophy of the cerebral convolutions (Figure 5-4),

enlargement of the ventricles, and granular ependymitis. In incipient cases
there may be almost no gross changes in the brain. The turbidity of the
meninges is the result of a chronic syphilitic meningitis. Minor degrees of
atrophy of the cerebral convolutions are difficult to discern. The decrease of
weight due to the atrophic process may amount to 100 g., or more, although it
is not rare to find brains with normal or even increased weight.
Figure 5-4.
Brain in general paralysis. Marked atrophy of the cerebral convolutions. The

sulci are gaping.
Microscopic Changes
The main histologic feature of general paralysis is a syphilitic
meningoencephalitis. The meninges are infiltrated with plasma cells and

lymphocytes (Figure 5-5). In the cortex, and to a lesser degree in the white
matter, there is perivascular infiltration (Figure 5-6). Some of the infiltrating

cells in the vessel walls and the rod cells of Nissl, when stained by the
Turnbull blue method, reveal blue pigment granules. This pigment represents
the so-called “iron of general paralysis.” In the capillaries, multiplication of
endothelial cells takes place, causing capillary obstruction. Moreover, there is
new formation of capillary buds and of small blood vessels, most of which
never become normally functional blood channels. These newly formed

vessels pierce the parenchymatous tissue. They contribute to the subtle
disorganization of the cortex and thus become an important factor in the
causation of the ensuing dementia. Another alteration of the mesodermal

tissue is the formation of rod cells, the Stabchenzellen of Nissl. The rod cells
are derivatives of Hortega’s microglial cells, which assume the form of
enlarged rod-shaped cellular elements. And finally, there is a diminution of
the perivascular clasmatocytes (histiocytes), only seen on supravital study.
Figure 5-5.
Figure 5-5.
General paralysis. Syphilitic meningitis. The meninges are infiltrated with

plasma cells and lymphocytes. Toluidine blue stain
Figure 5-6.
Figure 5-6.
Perivascular infiltration of a cortical vessel in general paralysis. Toluidine

blue stain.
The scarcity of the phagocytic elements in the general paralytic brain is
linked to the question as to why only a small number (3-5 percent) of all
untreated syphilitics develop general paralysis. Clasmatocytes are generally
identified with antibody formation and with local tissue immunity.
The ganglion cells show all degrees of changes, the majority of diseased
nerve cells exhibiting the chronic type of cell degeneration. But normal-
appearing neurons are found lying next to markedly degenerated forms. The
myelin sheaths and the axis cylinders, as well as the neuroglia reveal minor
alterations. Cajal gave an excellent review of the glial changes in general
paralysis.
The summation of the histopathologic changes in both the mesodermal

and the ectodermal tissue leads to a disturbed cytoarchitecture of the cortex,
in which the normal arrangement of the cell layers is lost (Figure 5-7).
Figure 5-7.
Disturbed cytoarchitecture of brain cortex in general paralysis. The normal
arrangement of cell layers is lost, and the ganglion cells show all degrees of
degeneration. Perivascular infiltration is pronounced. Toluidine blue stain.
Spirochetes in the Brain
In brains of untreated patients, spirochetes in great numbers may be
present (Figure 8). In other brains a few or no organisms can be found,
despite time-consuming search in many tissue blocks. In his famous 1913
studies, Noguchi, and all others after him, succeeded in finding Treponema
pallidum in approximately one fourth of the cases. The high percentage of
negative results is explained by a possible cyclic decrease, and by an increase

in the number of organisms. During the phasic decrease, spirochetes rarely
attain such numbers as to put themselves within easy reach of microscopic
search. Treponema pallidum has a preference for the gray matter. In the white
matter and in the meninges they are rare, if not completely absent.
Figure 5-8.
General paralysis. Spirochetes in cerebral cortex. Dieterle stain.
Treatment
After the syphilitic etiology of general paralysis had been established,
antisyphilitic treatment with arsphenamine (salvarsan), bismuth, and
mercury compounds was tried, but without success.
Malaria Therapy
For many years it had been recognized that mental patients improved
occasionally after an intercurrent febrile disease, such as typhoid fever,

malaria, erysipelas, and tuberculosis. In 1887, Wagner-Jauregg proposed the
idea of intentionally inducing a febrile disease for therapeutic purposes. He
selected first the streptococcus of erysipelas, but this proved unsatisfactory. A
simple fever-producing agent became available in 1890 with Koch’s

tuberculin. Wagner-Jauregg used tuberculin at first in all types of psychiatric
patients. After observing improvement mainly among general paralytics, he
concentrated on that mental disorder. Later, he used typhoid vaccines.
During World War I, a soldier who had contracted malaria on the Balkan
Front was admitted by mistake to the psychiatric clinic of the University of
Vienna. Wagner-Jauregg, then head of the clinic, seized this opportunity, and
on June 14, 1917, inoculated three general paralytic patients with the blood
from this soldier. This marked the beginning of malaria therapy. The first
favorable reports of this mode of treatment were received with skepticism,
but psychiatrists in Europe soon hailed the discovery. In 1927 Wagner-
Jauregg was awarded the Nobel prize for this achievement.
Malaria therapy consisted of inoculating a general paralytic patient with

1-3 cc. of Plasmodium vivax (tertian) malaria blood, obtained from another
patient who was undergoing this treatment. The patient was permitted to
have eight to twelve malarial paroxysms with daily temperature elevations
ranging from 103 to 105° F. Malaria fever was then terminated with quinine.
Penicillin Therapy
In 1943, when Mahoney and co-workers suggested that penicillin had
treponemicidal action, the National Research Council furnished the expensive

new drug to a few psychiatrists (Dattner, Ebaugh, Solomon, and Bruetsch) for
evaluation in the treatment of general paralysis. It soon became apparent that
penicillin in the amount of 10 million units was equal to malaria therapy and
would surpass it if given in still higher total dosage. Although Treponema
pallidum was extraordinarily sensitive to penicillin, it was possible to show

that 10 million units were not sufficient because spirochetes persisted in
some brains. A minimum of 15-20 million units was recommended for
maximal results in general paralysis.
Malaria therapy produced full recoveries in 35 percent of unselected
patients. Penicillin, in the total dosage of 10 million units, raised the recovery
figure to 50 percent.
Latin-American investigators by using a combination of penicillins
which maintain various levels of blood concentration, raised the recovery rate
to 83 percent. The schedule consists of three injections of 2.4 million units of
benzathine penicillin G (1.2 million units into each buttock) on the first, fifth,
and ninth days, plus twenty injections of 500,000 units of procaine penicillin,
administered every twelve hours. The total dosage is 17,200,000 units, given
within ten days.
The disappearance of mental symptoms may begin during therapy, or it

may be delayed for several weeks or months. Within six to twelve months
there will be an improvement in the nonspecific tests of the spinal fluid (cell
count, globulin, total protein, and the colloidal gold reaction). But the
Wassermann tests of blood and spinal fluid may not become negative for ten
years or longer. Persistence of positive serologic tests for syphilis, or
progression of clinical symptoms, does not necessarily mean a continuation of
infection. Treatment for the sole purpose of obtaining seronegativity is

usually futile.
The favorable effect of penicillin is also reflected in the brain tissue.
There is a reduction and final disappearance of the round cell infiltrations, of
Nissl’s rod cells, and of the iron pigment.
The action of penicillin is on the syphilitic organisms themselves.
Malaria therapy, on the other hand, stimulates the defensive powers of the
host by activation of the reticuloendothelial cells (clasmatocytes, histiocytes).
There is convincing evidence that penicillin alone is capable of curing
general paralysis. Where it fails, malaria therapy will also probably fail.
To sum up, penicillin in the treatment of general paralysis is highly
efficacious in large dosage. It is inexpensive and practically without risk, and

the treatment is of short duration.
Retreatment
If the patient has received a minimum of 15 million units of penicillin,
retreatment is usually not necessary. If there is no improvement after three
months, another course of penicillin may be given, for the penicillin might
have been absorbed poorly from the muscle depots.
Penicillin Sensitivity2
Penicillin allergy is now the most common of all drug allergies and the
most frequent cause of anaphylactic shock in man. In cases with a clear-cut

penicillin allergy, penicillin should not be used. When the history of penicillin
allergy is less clear-cut, consideration may be given to penicillin skin testing
or hemagglutination tests. Skin tests using nanogram amounts of penicilloyl
polylysine and penicillin from the vial detect many, but not all, cases of
penicillin allergy. Fatalities due to intradermal testing are extremely rare, but
have been reported. Intradermal tests should be followed by intramuscular
tests using minute amounts of penicillin. All penicillin allergy testing should
be done in the hospital with resuscitation equipment at the bedside,

experienced medical personnel, and a large-bore intravenous drip running.
Symptoms of anaphylaxis to penicillin include vertigo, nausea, flushing,
pruritis, dyspnea, and abdominal pain. At the first sign, 0.5 cc. at 1/1000
epinephrine and 50 mg. Benadryl should be given IM, and an intravenous drip
with large needle started. If severe dyspnea or hypotension occurs,
intravenous vasopressors, air way, and assisted respiration will be necessary.
One complication of antibiotic treatment of syphilis is the Jarisch-
Herxheimer reaction. The reaction is presumed to be a response to antigens

released from killed spirochetes. Fever appears within twelve hours of the
onset of treatment and lasts up to 48 hours. Temperatures of 102° F are not
rare and 104° F has been recorded. Aspirin and skin cooling measures may be
used for treatment. In neurosyphilis, convulsions and increased agitation may
appear. The patient must be sedated and restrained if necessary. Treatment
should be continued with no change in the original schedule.
If penicillin cannot be used, tetracycline is the drug of choice. The drug
should be given orally in pided doses of 2 g. per day for thirty to forty days for
neurosyphilis. Follow-up spinal fluid analysis should be performed more
frequently (at 1, 3, 6, and 24 months after treatment would be adequate for
the usual case). Erythromycin is the drug of third choice. It should be given
orally in the estolate form (Ilosone) in the same doses as tetracycline. Liver
function must be monitored as hepatotoxicity has been reported with

erythromycin estolate. Other forms of erythromycin are not absorbed from
the gastrointestinal tract well enough to be used. Cephalothin is probably a
good alternative to penicillin in the treatment of neurosyphilis. However, a
significant number of people allergic to penicillin are also allergic to

cephalothin, and treatment schedules for neurosyphilis have not been
clinically evaluated.
Psychotherapy
After successful treatment with penicillin, the patient becomes a well-
adjusted personality without any psychotherapy whatsoever. If treatment
with antibiotics should fail, psychotherapy will not benefit the patient either.
After the patient has gained insight, the problem should be frankly
discussed with him and his relatives. Specific instructions as to medical

checkups and the avoidance of hazardous occupations should be provided.
Work around dangerous machines and the driving of trucks and buses should
be prohibited, because a former general paralytic patient is never entirely
safe from a seizure, although he may have been free of mental symptoms for
years.
The Fully Recovered Patient
The intelligence in this group shows no deviation from previous levels,
and full working capacity is restored. This is true not only of the simpler
occupations, such as farming, but also of the professions. Kauders reported a
general paralytic patient who was treated in 1920 with therapeutic malaria
and, twenty-seven years later, at the age of eighty, enjoyed full mental and
physical health, being active as the manager of a circus.
The Partially Recovered Patient
In some cases the premorbid intellectual and emotional status cannot
be restored. These patients require permanent institutional care. They
constitute the bulk of the general paralytic patients who are at present in
mental institutions. For example, hospitalization for approximately 5000
veterans of World War I, who developed insanity due to syphilis, has now
been provided by the Veterans Administration. In most of these patients, the

delusions and the bizarre behavior have disappeared; they now represent all
stages of mental deterioration. In some instances, cyclothymic manifestations
have come into prominence, and others exhibit a schizophrenic picture with
mannerisms and oddities which in no way can be differentiated from the
classical type of schizophrenia. Since in some of these cases the spinal fluid
abnormalities have reverted to normal and the pupillary reactions also have
become normal, there are no longer clinical signs in the conventional sense of
an organic psychosis.
Some authors attributed the new clinical picture to a concomitant
affective or schizophrenic disorder. The post-treatment psychiatric
syndromes in general paralysis are complex exogenous reactions resulting
from residual alterations of the brain cortex, which are so subtle that they do
not reveal themselves with present methods of neurohistology.
Patients with residual brain damage at times have periods of acute
agitation and require treatment with tranquilizing drugs.
A paranoid-hallucinatory syndrome develops in a few patients during or

after malaria or penicillin treatment. Electroshock therapy is of benefit in this
condition.
Psychosis with Meningovascular Neurosyphilis
The term “meningovascular neurosyphilis” embraces syphilitic
processes in the meninges and vessels of the brain. In contrast to general
paralysis, which is always fatal if not treated, meningovascular syphilis
frequently shows clinical and serologic improvement even without treatment.
The important anatomic feature is cerebral softening due to endarteritic

occlusion of cerebral arteries. The common clinical manifestation is apoplexy
resulting in a hemiplegia, which at times is associated with an aphasia. The
hemiplegia often improves rapidly, without any therapy, and to a far greater
degree than might be expected from the initial symptoms.
The focal lesions are sometimes associated with acute psychic
disturbances, in which periods of confusion and delirious states are

conspicuous. Clouding of consciousness develops in some patients, with
complete disorientation of several months’ duration. This may be followed by

a rather sudden return to an almost normal mentality. In other instances,
various degrees of emotional apathy or dementia may follow the stroke.
Slight pupillary changes are frequently the only residual neurological signs.
Figure 5-9.
Figure 5-9.
Syphilitic occlusion of artery in brain of patient with meningovascular

neurosyphilis. Hematoxylin-eosin stain.
The chronic mental disorders with meningovascular syphilis do not
show any characteristic content and may resemble any psychotic state.
Patients with gumma of the brain usually present mental symptoms, but
a gummatous new growth is now a great rarity.
Figure 5-10.
Figure 5-10.
Meningovascular neurosyphilis. Large area of softening involving right

internal capsule. Stroke at age of forty-one. The patient was hemiplegic and
aphasic for the remainder of his life.
Laboratory Findings
Cerebrospinal Fluid Reactions
In the fluid, the cell count may vary between 5 and 500 cells per cubic
mm. In half of the cases, the cell count is normal. The protein content ranges
from normal values to 500 mg. per 100 cc. In a typical case, the colloidal gold
reaction shows a mid-zone curve, but a first-zone (paretic) curve is
occasionally present. The Wassermann reaction in the spinal fluid is positive
in two thirds of the cases, and in the blood in 80 percent. Occasionally, a
positive Wassermann reaction of the blood or of the spinal fluid is the only
abnormality.
Electroencephalogram
Patients with recent vascular accidents have a higher percentage of
abnormalities in the electroencephalogram than those with old lesions. In
some patients with an old hemiplegia, the electroencephalogram is normal.
Therapy
In the treatment of meningovascular syphilis, a course of penicillin
consisting of 10 million units is usually sufficient.
The So-called “Tabetic Psychosis” Other Than Taboparalysis
In an occasional instance of tabes dorsalis, a psychotic state occurs,
resulting from syphilitic endarteritis of the small cortical vessels. In 10

percent of tabes, general paralysis (taboparalysis) used to develop. This
tragedy can now be prevented by penicillin therapy.
Psychosis with Congenital Neurosyphilis
Juvenile General Paralysis
This form of general paralysis constituted 1.6-1.8 percent of all cases
admitted to mental institutions. In the great majority of cases, the illness

begins around the age of fourteen or fifteen. In 10 percent the onset is before
the sixth year of life, and in 3.6 percent mental symptoms begin after the
twentieth year.
There are minor clinical variations from the adult form. Mental
retardation, which is present in about 40 percent, becomes apparent soon
after birth and is often associated with retarded physical development.
Convulsions prior to the onset of juvenile general paralysis occur in one third
of the cases, simulating idiopathic epilepsy. Optic atrophy is more frequent

than in the adult form.
The psychiatric syndromes are less clear-cut, with the exception of the
dementing type. A schizophrenic picture with mutism, catatonic behavior,
and negativism has been observed. One of my patients, a well-developed and
intelligent seventeen-year-old Negro girl, without the physical stigmata of
congenital syphilis and with normal pupillary reactions, was considered a
catatonic schizophrenic, until a routine spinal fluid examination revealed
findings characteristic of general paralysis. Following penicillin therapy there

was complete recovery.
Stigmata of congenital syphilis are present in 75 percent and consist of
Hutchinson’s teeth (Figure 5-11), residue of previous interstitial keratitis, and
nerve deafness, listed according to their importance.
Figure 5-11.
Figure 5-11.
Juvenile (congenital) general paralysis. Hutchinson’s teeth. Note notching of

median incisors.
The anatomic changes in the brain are generally the same as in the adult
type.
Juvenile Meningovascular Neurosyphilis
This type of congenital neurosyphilis is more frequent than juvenile
general paralysis, but its diagnosis is infinitely more difficult because of the
uncharacteristic clinical and serologic findings. Symptoms may be present at
the time of birth or may make their appearance in infancy, puberty, or even
later in life.
Whenever congenital syphilis involves the central nervous system, it
may cause arrest or deterioration of the intellectual development of the child.
Behavior disorders are occasionally observed in this type of cerebral
involvement, which is usually stationary in nature. The abnormal behavior
ranges from lying, stealing, and attacks of rage to impulsive acts. Irritability,
restlessness, and depressive phases are often present. Two thirds of these
problem children rate below average in intelligence, some being feeble-

minded and others are borderline cases of mental deficiency. The remaining
children possess normal intelligence. Psychotic episodes may occur,
associated with temporary confusion, periodic hallucinations, and
pseudodementia.
Penicillin treatment shows particularly favorable results in progressive
cases. In stationary cases with positive serologic reactions, therapy has a
prophylactic effect in forestalling a new flare-up of the disease in later years.
Bibliography
Alexander, M. and J. Titeca. “L’Épilepsie post-malariathérapique,” J. Beige Neurol. Psychiatr., 36

(1936), 354.
Alpers, B. J. “Gumma of the Brain,” Am. J. Syph., 23 (1939), 233.
Alzheimer, A. “Histologische Studien zur Differentialdiagnose der Progressiven Paralyse,” in A.

Alzheimer, and F. Nissl, eds., Histologische und Histopathologische Arheiten über die
Grosshirnrinde, mit Besonderer Berücksichtigung der Pathologischen Anatomie der
Geisteskrankheiten, Vol. 1, p. 18. Jena: Fischer, 1905-1913.
Arieti, S. “General Paresis in Senility; Critical Review of the Literature and Clinico-Pathologic
Report of Six Cases,” Am. J. Psychiatry, 101 (1945), 585.
Bayle, A. L. J. Recherches sur l’arachnitis chronique, la gastrite et la gastro-entérite chronique, et la

goutte, considérées comme causes de l’alienation mentale. Paris: Didot le Jeune,
1822.
Benda, C. E. “Syphilis in Serum Negative Feebleminded Children; A Histologic Study in

Meningoencephalitis Syphilitica and in the Nissl-Alzheimer Endarteritis,” Am. J.
Psychiatry, 96 (1940), 1295.
Borges Fortes, A. “Tratamento da Paralisia General pela Penicilina, Arq. Bras. Neuriat. Psiquiatr.,
51 (1956), 23. Penicilina e demência paralítica, O Hospital, Rio de Janeiro,
November, 1956, pp. 645-673.
Bostroem, A. “Die Luespsychosen,” in O. Bumke, ed., Handbuch der Geisteskrankheiten, Vol. 8,

Spez. Teil 4, pp. 70-146. Berlin: Springer, 1930.
_____. “Die progressive Paralyse (Klinik),” in O. Bumke, ed., Handbuch der Geisteskrankheiten, Vol.
8, Spez. Teil 4, p. 248. Berlin: Springer, 1930.
Bruetsch, W. L. “Activation of the Mesenchyme with Therapeutic Malaria,” J. Nerv. Ment. Dis., 76
(1932), 209.
_____. “The Histopathology of Therapeutic (Tertian) Malaria,” Am. J. Psychiatry, 12, (1949) 19.
_____. “Penicillin or Malaria Therapy in the Treatment of General Paralysis? (A Clinico-Anatomic

Study),” Dis. Nerv. Syst., 10 (1949), 368.
_____. “Why Malaria Cures General Paralysis,” J. Indiana State Med. Assoc., 42 (1949), 211.
_____. “Penicillin Therapy of Cardiovascular Syphilis with Large Total Dosage; Its Rationale Based
on Histologic Studies,” Am. J. Syph., 35 (1951), 252.
_____. Syphilitic Optic Atrophy, pp. 6, 57, 78. Springfield, Ill.: Charles C. Thomas, 1953.
_____. “Neurosyphilis: Symptomatology and Pathology,” in A. B. Baker, ed., Clinical Neurology, Vol.
2, pp. 799-845. New York: Hoeber, 1955.
Bumke, O. Lehrhuch der Geisteskrankheiten, p. 386. München: Bergmann, 1936.
Cajal, S. R. “Neuroglia of the Cerebrum and Cerebellum in Progressive Paralysis with Technical
Observations on the Silver Impregnation of Pathologic Nervous Tissue,” Z. Ges.
Neurol. Psychiatr., 100 (1926), 738.
Callaway, J. L., H. Löwenbach, R. O. Noojin et al. “Electroencephalographic Findings in Central

Nervous System Syphilis Before and After Treatment with Penicillin,” JAMA, 129
(1945), 938.
Calmeil, L. F. De la Paralysie considérée chez les aliénés. Paris: Bailliere, 1826.
Dattner, B. “Zur Frage der Paranoid-Halluzinatorischen Paralysen,” Wien. Med. Wochnschr., 87

(1937), 278.
_____. “Treatment of Neurosyphilis with Penicillin Alone at Bellevue Hospital,” Am. J. Syph. Gonor.
Ven. Dis., 32 (1948), 399.
Dayton, N. A. “Degree of Mental Deficiency Resulting from Congenital Syphilis,” JAMA, 87 (1926),
907.
DeWeck, A. L. in M. Samter et al., eds., Immunological Diseases, 2nd ed., p. 433. Boston: Little
Brown, 1971.
Ebaugh, F. G., H. H. Dixon, H. E. Kiene et al. “Encephalographic Studies in General Paresis,” Am. J.
Psychiatry, 10 (1931), 737.
Epstein, S. H. and H. C. Solomon. “The Effect of Treatment on the Mental Level of Patients with
General Paresis,” Am. J. Psychiatry, 95 (1939), 1181.
Esmarch, F. and W. Jessen. “Syphilis und Geistesstörung,” Allg. Ztschr. Psychiatr., 14 (1857), 20.
Esquirol, E. “Démence,” in Dictionaire des sciences médicales, Vol. 8, p. 283. Paris: Panckoucke,
1814.
Ferguson, F. R. and M. Critchley. “A Clinical Study of Congenital Neurosyphilis,” Br. J. Child. Dis., 26
(1929), 163.
_____. “A Clinical Study of Congenital Neurosyphilis. Part II. Congenital Tabes, Tabo-paresis and
General Paralysis,” Br. J. Child. Dis., 27 (1930), 1.
Finley, K. H., A. S. Rose, and H. C. Solomon. “Electroencephalographic Studies on Neurosyphilis,”

Arch. Neurol. Psychiatry, 47 (1942), 718.
Forster, E. and E. Tomasczewski. “Nachweis von Lebenden Spirochäten im Gehirm von

Paralytikem,” Dtsch. Med. Wochnschr., 39 (1913), 1237.
Gianascol, A. J., G. D. Weickhardt, and M. A. Neumann. “Penicillin Treatment of General Paresis; A

Clinicoanatomic Study,” Am. J. Syph., 38 (1954), 251.
Gjestland, T. “The Oslo Study of Untreated Syphilis; An Epidemiologic Investigation of the Natural
Course of the Syphilitic Infection Based upon a Re-study of the Boeck-Bruusgaard
Material,” Acta Derm. Venereal., Suppl. 34, 35 (1955), 1.
Gougerot, H. “Les Reliquats cicatriciels de la syphilis viscérale. Épilepsie résiduelle après guérison
de la paralysie générale progressive,” Paris Med., 1 (1929), 209.
Grant, A. R. and H. T. Kirkland. “Spirochaetes in the Brain in General Paralysis,” J. Ment. Sci., 73
(1927), 595.
Greenblatt, M. and S. Levin. “Factors Affecting the Electroencephalogram of Patients with

Neurosyphilis,” Am. J. Psychiatry, 102 (1945), 40.
Gross, S. W., A. Stein, and P. G. Myerson. “Surgical Treatment of Gummas of the Brain,” Am. J. Surg.,
58 (1942), 78.
Haslam, J. Observations on Insanity: with Practical Remarks on the Disease and an Account of the
Morbid Appearances on Dissection. London: Rivington, 1798.
Hayes, R. H. and I. Werbner. “Chlorpromazine in the Treatment of Symptomatically Refractory

Conditions in General Paretics,” Dis. Nerv. Syst., 17 (1956), 48.
Hechst, B. “Histopathologische Untersuchungen bei der Schizophrenen Form der Progressiven

Paralyse,” Arch. Psychiatr., 102 (1934), 25.
Hooshmand, H., M. R. Escobar, and S. W. Kopf. “Neurosyphilis: A Study of 241 Patients,” JAMA, 219
(1972), 726-729.
Idsoe, O., T. Guthe, R. P. Willcox et al. “Nature and Extent of Penicillin Side Reactions with
Particular References to 151 Fatalities from Anaphylactic Shock,” Bull. WHO., 38
(1968), 159.
Jahnel, F. “Die Spirochaeten bei der Paralyse,” in O. Bumke, ed., Handbuch der Geisteskrankheiten,
Vol. 11, pp. 498-538. Berlin: Springer, 1930.
Junius, P. and M. Arndt. “Beiträge zur Statistik, Aetiologie, Symptomatologie und pathologischen
Anatomie der progressiven Paralyse,” Arch. Psychiatr., 44 (1908), 249.
Kauders, O. “Zur Klinik, Theorie und Geschichte der Malariabehandlung,” Wien. Z. Nervenheilkd., 1
(1947), 47.
Kraepelin, E. “General Paresis,” Nerv. & Ment. Dis. Monogr., No. 14. New York: Nerv. & Ment. Dis.
Publ. Co., 1913.
Krafft-Ebing, von, R. “Zur Kenntnis des Paralytischen Irreseins beim Weiblichen Geschlecht,”
Arch. Psychiatr., 7 (1877), 182.
Lissauer, H., and E. Storch. “Uber einige Fälle Atypischer Progressiver Paralyse,” Monatsschr.
Psychiatr. Neurol., 9 (1901), 401.
Löwenberg, K. “Syphilis of the Central Nervous System and of the Aorta,” Klin. Wochnschr., 3
(1924), 531.
Lucas and Price. “Cooperative Evaluation and Treatment for Early Syphilis,” Br. J. Vener. Dis., 43
(1967), 244-248.
Lurie, L. A., J. V. Greenbaum, and E. B. Brandes. “Syphilis as a Factor in Behavior Disorders of

Children,” Urol. Cutan. Rev., 45 (1941), 108.
McCartney, J. L. “The Psychopathic Hospitals of Japan,” J. Nerv. Ment. Dis., 71 (1930), 640.
Mahoney, J. F., R. C. Arnold, and A. Harris. “Penicillin Treatment of Early Syphilis; Preliminary
Report,” Ven. Dis. Inform., 24 (1943), 355; Am. J. Public Health, 33 (1943), 1387.
Menninger, W. C. Juvenile Paresis. Baltimore: Williams & Wilkins, 1936.
Merritt, H. H., M. Moore, and H. C. Solomon. “The Iron Reaction in Paretic Neurosyphilis,” Am. J.
Syph., 17 (1933), 387.
Merritt, H. H. and M. Springlova. “Lissauer’s Dementia Paralytica; A Clinical and Pathologic

Study,” Arch. Neurol. if Psychiatry, 27 (1932), 987.
Neel, A. V. and I. Ostenfeld. “Contribution to History of Dementia Paralytica with Special

Reference to Contributions of Scandinavian, Particularly Danish Scientists,” Acta
Nicol, W. D. “General Paralysis of the Insane,” Br. J. Vener. Dis., 32 (1956), 9.
Nissl, F. “Zur Histopathologie der Paralytischen Rindenerkrankung,” in A. Alzheimer, and F. Nissl,

eds., Histologische und Histopathologische Arheiten über die Grosshirnrinde, mit
Besonderer Berücksichtigung der Pathologischen Anatomie der Geisteskrankheiten,
Vol. 1, p. 315. Jena: Fischer, 1905-1913.
Noguchi, H. “Additional Studies on the Presence of Spirochaeta Pallida in General Paralysis and
Tabes Dorsalis,” J. Cutan. Dis., 31 (1913), 543.
Noguchi, H. and J. W. Moore. “A Demonstration of Treponema Pallidum in the Brain in Cases of

General Paralysis,” J. Exp. Med., 17 (1913), 232.
Orlando, R. and M. Arndt. Paralisis General. Estado Actual y Problemas, pp. 101, 179. Buenos Aires:
Lopez & Etchegoyen, 1945.
_____. “La atrofia óptica en la neurosífilis,” Neuropsiquiatría, 1 (1950), 110.
Page, J. “Mental Disease in Russia,” Am. J. Psychiatry, 94 (1938), 859.
Rothschild, D. “Dementia Paralytica Accompanied by Manic-Depressive and Schizophrenic

Psychoses; the Significance of Their Co-existence,” Am. J. Psychiatry, 96 (1940),
1043.
Schulte, H. “Klinischer Beitrag zur Kenntnis der Kongenitalluischen Störungen des

Zentralnervensystems,” Z. Ges. Neurol. Psychiatr., 169 (1940), 250.
Sparling, F. “Diagnosis and Treatment of Syphilis,” N. Engl. J. Med., 284 (1971), 642-657.
Taggart, S. R., S. B. Russell, and E. V. Price. “Report of Syphilis Follow-up Program Among
Veterans After World War II,”J. Chron. Dis., 4 (1956), 579.
Thomas, E. W. “Current Status of Therapy in Syphilis,” JAMA, 162 (1956), 1536.
Van Wulfften Palthe, P. M. “Syphilis des Nervensystems bei Asiaten in Niederländisch-Indien

(Java und Sumatra),” Acta Psychiatr. Neurol., 12 (1937), 207.
Virchow, R. “In Discussion of: Tabische Sehnerven Atrophie, Tabes, Progressive Paralyse und
Aneurysma der Aorta,” Berl. Klin. Wochnschr., 35 (1898), 691.
Volland, W. “Ueber das ‘Paralyseeisen’ und die Eisenablagerungen bei Mesaortitis Syphilitica
unter Besonderer Berücksichtigung ihrer Herkunft und Spezifität
(Histopathologische und Humoralpathologische Untersuchungen),” Arch. Path.
Anat., 309 (1942), 145.
Wagner-Jauregg, J. and W. L. Bruetsch. “The History of the Malaria Treatment of General

Paralysis,” Am. J. Psychiatry, 102 (1946), 577.
Warrell, D. A. “Physiologic Changes during the Jarisch-Herxheimer Reaction in Early Syphilis,”
Am. J. Med., 284 (1971), 642-657.
Wong, Y. T. and H. Packer. “Penicillin Versus Penicillin-Malaria in the Treatment of Dementia

Paralytica,” Am. J. Syph., Gonor. Ven. Dis., 32 (1948), 212.
Notes
1 Sparling’s article can be consulted for further details of laboratory findings in the diagnosis and
treatment of syphilis.
2 We are indebted to William T. Bachmann for editorial advice and help in revising this section on
penicillin sensitivity.
Chapter 6
Postencephalitic States Or Conditions
Henry Brill
Postencephalitic States or Conditions
Various acute encephalitic syndromes have long been recognized but
postencephalitic states, as they are now understood, did not emerge as
important until the 1916-1930 epidemic of encephalitis lethargica which

showed that such a disease could do vast damage and that medicine was quite
unprepared to cope with viral encephalitis. This experience had a profound

impact on medical thinking and left great concern that this disease or even a
more devastating one might break out again. This fear has now abated, but
recent advances in general virology indicate that the concern was not without
foundation. In an article entitled “Viruses may Surprise Us” Sabin is quoted as
saying that new syndromes may be caused by familiar viruses, by new ones,
or by new antigenic variants as in the case of influenza. He feels that more
study needs to be directed toward pre- and postnatal viral infections in
congenital defects. The potential scope of this problem is seen in his
statement that “The viruses of the human heritage which maintain
themselves in nature by passing from one human being to another, now
number about 200—the vast majority identified during the last 10 years.” He
states, “In addition, studies mostly of recent years have revealed at least 200
distinct viruses in the arthropod-borne group.”
It is clear that we live more intimately with the world of viruses than
was previously realized and many of them are now known to attack the
central nervous system. The resulting syndromes are described as meningitis,

meningo-encephalitis, and encephalomyelitis, according to the pathology
which tends to predominate, but there is a continuum among these
pathological forms and mixed states are common.
Most of these infections, such as herpes simplex, Japanese B
encephalitis, and St. Louis encephalitis, do not become chronic, and they leave
residual central nervous system damage in only a minority of cases. Such

damage can be severe and may be focal and/or diffuse, but it is not
progressive. The acute infection may be marked by a well-defined febrile
episode associated with the usual cerebral signs such as stiff neck, stupor,
coma, convulsions, and myoclonia, but at least in some postencephalitic states
there may be no such history. One can only speculate what part such
infections may play in the total psychiatric scene. So far we know only about
cases where the damage is severe or the clinical syndrome is specific. It
remains to be seen whether viral infections can also cause minor degrees of
damage which lead to conduct disorders, hyperkinesis of children, and other
syndromes now gathered under the controversial rubric of minimal brain

dysfunction (MBD). For a time, the experience with Von Economo’s
encephalitis suggested that this was a distinct possibility, but most
authorities now seem to reject this view.
To some extent, the question has been reopened by the discovery of
chronic virus infections of the central nervous system, especially that of Kuru
and slow measles in man, as well as scrapie and visna in animals (see p. 163).
In addition it has been shown that viruses may multiply within
morphologically intact neurons and produce disease through dysfunction of

these neurons. What may be the psychiatric significance of these data remains
for future research to decide, but it is now certain that encephalitis lethargica
is not the only chronic progressive viral infection of the brain.
Classification and Nomenclature
Terminology in this field makes use of anatomical, clinical, and

etiological names but is actually controlled by usage. Thus the so called
postencephalitic states following Von Economo’s disease are, in fact, chronic
encephalitic states, with pathological evidence of continued active
inflammation alongside evidence of previous destruction. They were
designated as postencephalitic because historically they were observed after
acute infections and long before the chronic nature of the infection was fully
understood; the term has now been established by usage. Usage has also
decreed that the major postencephalitic and chronic encephalitic states,
which were known before Von Economo’s disease was discovered, should
continue to be described separately under their old designations, and this
includes such entities as rheumatic chorea, paresis, and rabies, as well as

infantile cerebral palsy. On the other hand, the postencephalitic and chronic
encephalitic disorders which were recognized after Von Economo’s
encephalitis tend to be classed with the postencephalitic states.
This is true even though postencephalitic residuals were recognized

well before Von Economo’s time. Oppenheim, as quoted by Mayer, noted
already in 1900 that such damage could be left after measles, scarlet fever,
pneumonia, erysipelas, whooping cough, and mumps, and after the

hemorrhagic encephalitis of influenza. These syndromes must, however, have
been considered neurological rather than psychiatric because the prestigious

Tuke’s Dictionary of Psychological Medicine in 1892 does not even list a
category of encephalitis. It describes “inflammation of the brain” but only

under the heading of “delirium.” The Dictionary even mentions mental
disorders following influenza but does not appear to relate them to brain
damage.
Advance has been spectacular since the days of Oppenheim and even
Von Economo, but many uncertainties still remain, and we still have no fully
established system of classification of the syndromes now recognized as
encephalitic or postencephalitic.
Some of the disorders are classified by their vectors as in the case of
arthopod-borne viruses (arbo viruses); others are classified on the basis of
pathology (hemorrhagic encephalitis); some by the distribution of pathology

(leukoencephalitis), still others by geographical titles (Japanese B., Australian
X, Russian summer encephalitis), and some by the host species (fox
encephalitis, equine encephalitis). Finally, the classification by pathological

syndrome is also of a multiple nature and may be based on the distribution of
the reaction (leukoencephalitis), the location of the pathology as in
encephalomyelitis, or the nature of response (inclusion body encephalitis).
As the etiological agents are identified, descriptive terms are becoming

more specific, or are being displaced by terms derived from the etiological
agent such as “encephalitis due to slow measles virus.” Even an etiological

classification must at this time, however, remain incomplete because the
classification of the viruses themselves is still a matter of vigorous debate.
Distinctions among the various forms of encephalitis and
postencephalitic states, other than the Von Economo type, still remain of
limited clinical importance, and a simple account of the major forms seems
adequate for most purposes since they represent essentially chronic, static,
nonspecific organic brain syndromes. Nevertheless, the clinician cannot
ignore even the acute reactions, if only because he must usually diagnose the
postencephalitic states retrospectively and on the basis of clinical history and

hospital records of the initial infection.
Encephalitis Lethargica (Von Economo’s Disease)
History
In 1917 Von Economo described what seemed to be a new epidemic

disease which he called encephalitis lethargica. During the next few years this
disorder took on pandemic proportions and involved tens of thousands of

victims leaving an estimated one third of them with permanent, progressive,
bizarre neuropsychiatric residuals. Decades of research have failed to resolve
the mystery of the origin of this disorder or its mode of transmission. The
etiological agent is presumed to be a virus, but it has not been isolated nor
have specific immune bodies been identified, even though a considerable
number of cases still survive with what appears to be a chronic active
encephalitic process.
The original outbreak overlapped the 1919 pandemic of influenza and
for a long time these two disorders were confused with each other, but they
are now considered to be entirely separate.
During the epidemic and for some time thereafter scientific interest was
intense, and it was hoped that this strange new disease would be a sort of a
medical Rosetta Stone which would provide neurophysiological equivalents
of somatic events and vice versa. Many challenging questions were raised
because of the close association of a well-defined neuropathology with
classical functional disorders such as compulsive obsessive states, hysterical
neuroses, and psychoses with severe conduct disorders, all of them
intertwined with neurological and neurovegetative changes. Contemporary
observers were firmly convinced that they were observing not simple release
phenomena but specific reactions to the damage caused by encephalitis. For a
time the issues which had been raised seemed to have good hopes of
resolution, but research results were minimal, and scientific interest finally
faded. It was not until the development of the major tranquilizers and the
subsequent introduction of L-Dopa that such hopes were revived.
Epidemiology
The epidemiology of encephalitis lethargica has now receded into
medical history. The disease may have been endemic in Eastern Europe, and
Neal quotes papers to that effect, but the first well-documented scientific
report deals with the 1916-1917 epidemic which soon became pandemic and
persisted for at least a dozen years as a disease of winter months. It involved
persons of all ages, but mainly between ten and thirty. Direct transmission
was not shown to be a factor, and the incubation period appeared to run from
several days to two weeks. The total number of victims is unknown, although
in Britain the peak of the outbreak was reached with 5036 cases reported in
1924. In New York 1247 cases were admitted to mental hospitals between
1919 and 1939. Wilson states that mental signs remained in over half the
cases who had them during the acute phase and were seen in about a third of
all survivors below the age of sixteen. Other authorities estimate that about a
third of all the victims died, while another third suffered the progressive
disorder and only a third recovered. Many of those subsequently disabled
could give no history of an acute attack.
The subsequent course of the epidemic was no less mysterious than its
origin. By 1930 it had apparently run its course, although sporadic cases were
reported for the next decade or more and some authors were still reporting
occasional cases in the 1960s. The Lancet published such a paper and raised
serious questions editorially as to the diagnosis, but still was moved to ask: “If
the infection has not vanished, does it perhaps lurk under other guise . . . and
is recrudescence still a possibility?” This unanswered question still haunts the
subject.
Pathology
The acute lesion is nonpurulent and non-hemorrhagic, which

distinguishes it from the bacterial infections and influenza, respectively. It is
located in the gray matter of the brain and the cord, which separates it from
various types of leukoencephalitis (measles, mumps, vaccina). Inflammatory

perivascular reaction is usually severe, and microscopic foci are widely
disseminated, particularly in the cortex (Figure 6-1), basal ganglia (Figure 6-
2), hypothalamus, and periaqueductal gray matter of the brain stem. The
substantia nigra is especially damaged (Figure 6-3), and this damage remains
a hallmark of the disease. In chronic cases the usual residuals of old
inflammation are found, particularly in the basal ganglia and mesencephalon,

but in addition, even after many years, new areas of active inflammation are
to be seen in the same general distribution. The pathological findings are

highly variable as to intensity and distribution, which is in striking contrast to
the relative uniformity of the clinical typology.
Etiology and Pathogenesis
The etiology has always been assumed to be a filterable virus, even
though no inclusion bodies have been described, no virus isolated, and no
specific immune bodies identified.
Figure 6-1.
Cerebrum: White matter disclosing a blood vessel with enlarged perivascular

space containing an inflammatory exudate (some macrophages are filled
with yellowish or greenish pigmentation). Nissl stain; medium-power
magnification.
Originally, theories as to pathogenesis revolved about the location of the

neuropathology and the nature of the underlying psychopathology of the
individual. It is perhaps a measure of the state of medical thinking at that time

that social issues received no attention. The neuropathology did indeed
indicate that the central gray was important for psychic functioning, and the
damage to the basal ganglia and substantia nigra was correlated with the
Parkinsonian syndrome. Nevertheless, the available explanations were never
adequate to account for the complex pattern of this disorder. Theories based
on psychodynamics and personality studies were equally unsatisfying, and
indeed most authors opposed the idea that this postencephalitic syndrome
was simply a release phenomenon and an expression of underlying
personality. As Rosner said, “The tragic feature is personality change, not
personality exaggeration.” A new chapter in the understanding of the

pathogenesis of this disorder was opened in the early 1950s, and some of the
mystery was dispelled when it was found that full doses of the tranquilizing
agents of the phenothiazine and Rauwolfia series can reproduce many of the
features of the chronic encephalitic syndrome in a quantitatively controllable,

reversible, and nonprogressive form. Such symptoms include Parkinsonian
rigidity, masked facies, tremor, salivation, and on occasion even oculogyric
crises, dystonia, torsion spasm, and akathesia. Use of these tranquilizers may
also precipitate emotional complications, especially depression, restlessness,
and tension, all of which are seen in the postencephalitic syndrome. One can
even see some parallel between the reusable stupor of acute encephalitis and
that produced by heavy phenothiazine dosage.
Figure 6-2.
(top) An area in the globus pallidus revealing the presence of a perivascular
inflammatory reaction. Nissl stain; low-power magnification.
(bottom) Perivascular inflammatory exudate showing predominance of

lymphocytes. Nissl stain; medium-power magnification.
The significance of the curious parallelism between the tranquilizer-

induced reactions and those resulting from lethargic encephalitis has since
been further clarified by observations of the action of another drug, L-Dopa.
This drug was originally developed on the basis of a hypothesis that the
Parkinsonian symptoms were related to the observed depletion of brain
dopamine, especially in the basal ganglia and
Figure 6-3.
(top) Substantia nigra of an adult (control case), (bottom) Depigmentation
and pronounced loss of neurons in the substantia nigra in a postencephalitic
Parkinsonian syndrome. Nissl stain; medium-power magnification.
substantia nigra. Dopamine itself proved ineffective, but L-Dopa, which
is converted to dopamine in the brain, proved to be of value. It is thought to
act as a neurotransmitter of inhibitory impulses, and counterbalances the

central acetylcholine which is excitatory. A lack of dopamine appears to
release an overaction of acetylcholine, and this imbalance is thought to be a
fundamental cause of Parkinson’s syndrome. It is of great theoretical interest
that the new drug can itself initiate a wide variety of dose-dependent
reversible psychiatric and neurological symptoms, because this gives further
evidence that dopamine is indeed important in psychic as well as neurological
functioning. All this has again directed major scientific attention to a study of
the Parkinsonian syndrome, but this time it is at the level of molecular

biology.
Psychiatric Symptoms
Perhaps the most difficult aspect of this singular disease to describe is
the psychiatric symptomatology. To those who know the cases, chronic
encephalitis has a high degree of specificity and a quality which can hardly be
mistaken, but it is virtually impossible to identify and completely separate the

components of the diagnosis. The physician’s impression is constellative,
global, and composed of a blend of psychiatric, neurological, and vegetative
symptoms and signs, no one of which is specific in isolation from the others.
The psychiatric symptoms are not typically organic in nature, since memory
and intellect are not impaired, and when they occur in the absence of other
findings, there is nothing to distinguish this disorder from personality

disorder, neurosis, hypochondriasis, or functional psychosis. Many
postencephalitics were indeed treated under other diagnoses during their
pre-Parkinsonian phase and correctly classified only as neurological
symptoms emerged, often an event of chagrin and surprise for the

psychiatrist.
Wilson comments that “despite variations the generic picture is
curiously precise, but none the less cumbersome to define.” This holds true of
the psychiatric as well as the neurological aspects and, indeed, any separation
between the two must be, to a large extent, artificial, since even the grossest
postencephalitic Parkinsonian syndrome has functional components, while
tics and characteristic compulsive and phobic symptoms are found so

regularly associated with the disorder that it is hard to escape the conclusion
that some organic factor underlies both. The view that symptoms are
determined by both organic and dynamic factors as stated by Schilder seems
entirely tenable. We will now consider some of the commoner

postencephalitic subsyndromes.
Conduct Disorder
Especially in children, even before the onset of gross neurological
symptoms, severe conduct disorder was a frequent sequel, beginning
immediately after the acute infection or after a delay of months. Among the
characteristics of the children, particularly the group aged three to ten years,
were a marked destructiveness and impulsiveness, with a tendency to carry
primitive impulses into headlong action. Children who had previously
behaved normally, would he, steal, destroy property, set fire, and commit
sexual offenses, without thought of punishment. The motivation was even less
comprehensible and less subject to immediate control than in the so-called
psychopathies, but the capacity for real remorse was strikingly well retained.
A characteristic instability of emotion, coupled with disinhibition of action,

led to serious aggressions, usually against others, but occasionally against the
patient himself, resulting in gruesome self-mutilations. Institutionalization of
these cases was imperative and led to the development of some of the early
units for inpatient care of emotionally disturbed children, notably the one at
Kings Park State Hospital in New York, in 1924.
In adults, conduct disorder was also a serious problem, although not to
the same degree as in children. Yet the results were a serious problem, and a
famous virologist whose father was a victim of this disease once commented
to me that it had changed him from a well-known academician into “an
animal.” Like the children, adults would express deep remorse and retained
the capacity for self-criticism of their behavior, which seemed to have a
compulsive quality. There was often a marked discrepancy between the good
intellectual capacity and the primitive behavior. Such a patient was a “master
of what he said” but, in his compulsive action, was a “slave of what he did.” In
the mental hospital these patients were known for their impulsive behavior
and occasional aggressiveness, even though they usually made good
emotional contact and could discuss things quite clearly. Lethargic

encephalitis is described as being able to cause convulsive disorder in
children; in very young patients mental deficiency is also a possible outcome.
Cases of conduct disorder due to Von Economo’s disease are now no
longer seen. They were usually at their worst before the onset of obvious
neurological symptoms, and the behavior problems gradually disappeared as

the neurological disability advanced. In addition, of course, childhood cases
have long since ceased to appear.
Schizophrenic-like Reactions
Reactions similar to schizophrenia have been described, but true
schizophrenia is quite unusual, and, on closer examination, these are seen to

be pseudoschizophrenias. The emotional reaction is shallow and often dull
and apathetic, but it is still postencephalitic and not schizophrenic. Delusions
of reference and hallucinations may occur, but they are superficial and lacking
in schizophrenic symbolism. Certain of the motor rigidities of encephalitis
lethargica sometimes bear a superficial resemblance to catatonia, and various
paranoid reactions, especially of transitory nature, also occur. Paranoid
hallucinatory and delusional syndromes are sometimes due to atropine-type
medications but are usually a part of the postencephalitic picture. They are
distinguished from schizophrenia by the absence of the usual schizophrenic
disorders of emotion and thought and the lack of autism. Actually, the
postencephalitic patient tends to manifest strong dependency needs, and this

leads to a clinging relationship which is quite the opposite of schizophrenic
withdrawal, and his ability to discuss and control his problems is also
different in quality from that seen in schizophrenia. This aspect of the chronic
encephalitic reaction is well described by Schilder.
Depression
A strong tendency to depression is reflected in the characteristic
whining voice, clinging manner, and dependent and complaining attitude.
Depression often centers about the physical symptoms, and is hard to

distinguish from hypochondriasis. Self-accusations and delusions of guilt may
take the form of a monotonous plaint whose pattern is perhaps so strongly
colored by the facies, the voice, and the bradykinesis and bradyphrenia that it
seems different from ordinary depressions. The pleading, demanding, and
impatient clinging resembles what one sometimes encounters in epileptics.
The content tends to be of an organic depressive nature. Euphoria is
described but is relatively unusual.
In a review of 201 cases of postencephalitic Parkinsonism, Neal found
pathological depression listed nine times, psychotic depression eight times,
and hypomania eight times, but depression of the pattern described above is
far more frequent.
Hypochondriasis
Patients may complain of almost all forms of physical discomfort. These
include pains, burning, tension, restless feelings, shooting sensations, and

dead feelings, as well as hypochondriacal concern about heart, lungs,
stomach, etc. Verbal productions are often marked by a compulsive quality
and are full of expressions of frustration, impatience, and discomfort, but

these are difficult to evaluate since the disease attacks neural elements
throughout the central nervous system; often the patients leave the
impression that they may be suffering from something akin to central pain.
The response to placebo is striking and could well shake the confidence
of the strongest organicist; no patients are more suggestible or more readily

pacified for a short time by a new therapy. Yet they are equally suggestible
with respect to some of the gross neurological symptoms and can even be
brought to suppress the Parkinsonian tremors for brief periods of time. In
this connection they seem to be manifesting an organically determined
disorder of volition.
Eye Findings
Among the most common complaints are those centered about the eyes.
The patients seem to be trying to verbalize some indescribable sense of
discomfort, and indeed, their eyes often appear congested and uncomfortable.
Some of this must be laid to loss of eye blink and the long periods of rigid
stare with resultant fatigue and discomfort in the muscles and periocular
tissues, but the oculogyric crisis as yet remains without full explanation of
either functional or organic type. It is now reproduceable chemically with
some of the phenothiazines and with L-Dopa. In postencephalitics it is
strongly associated with other psychiatric symptoms such as forced thinking

and stereotyped ideas or a compulsive preoccupation with the eyes of others.
Attacks may be periodic and fairly regular but are usually irregular. They may
be controlled for a time by an effort of will, but the patients do not consider
the attacks as subject to volition since they complain, “My eyes turn up,” and
not “I have to turn my eyes up.” The usual direction of gaze is upward, but
variants include forced gaze in other directions and combinations with

postural distortions. Attacks may last from minutes to hours and may be
interrupted only by falling asleep.
Other ocular complaints include burning, blurred vision, photophobia,
shooting pains, macropsia, micropsia, and visual distortion. Here too one can
identify functional components, but disorder of the visual neurological
apparatus is extensive, and these patients also suffer from various
opthalmoplegias, often with diplopia, and show pupillary anomalies and
accommodation difficulties. The staring, unblinking expression and masklike
greasy facies may suggest the diagnosis at first glance.
Work Capacity
Loss of work capacity is sometimes given little emphasis in psychiatric
descriptions, perhaps because it is not obvious in the examining room, and it

often seems to be assumed that this impairment is, somehow, secondary to
other factors. However, in a number of neuropsychiatric disorders and
especially in the postencephalitic state, as well as in other conditions with

brain damage, impairment of work capacity can be a leading symptom and a
disability of its own, not strongly correlated with other signs or symptoms
and highly resistant to therapy. As yet little studied, except in relation to

vocational and other types of rehabilitation, this problem is prominent and
persistent in postencephalitics, may antedate gross neuropsychiatric findings,
and quite commonly continues after they are brought under control by
medication; it may be related to the chronic sense of fatigue often described
and to slowness of thinking or bradyphrenia.
Neurological and Vegetative Symptoms
Parkinsonism is by far the commonest finding. This is characterized by

masking of the face, loss of blink, and in the extremities a characteristic
rhythmical tremor, rigidity, and loss of associated reflexes. It is less frequent
in children and has a marked tendency to progress. Onset is characteristically

insidious, local and asymmetrical; it spreads gradually to other parts of the
body, becoming more intense and more general, until the fully developed
syndrome is present. The motor disability, even when severe, may be briefly
reversible, sometimes in a spectacular manner. The author once saw a

severely incapacitated former boxer, who had been annoyed for days by a
fellow patient, suddenly recapture his motor capacity with great effect, and
then lapse again into a full Parkinsonian state. On command, such patients
can regularly suspend their tremor for a short time, and catch a ball or carry
out some other brief coordinated task, but despite pride in their performance,
they do not initiate it themselves. The moment they relax, the rigidity and
rhythmical tremor take over again. Gait is characteristic and diagnostic.
Associated movements of the arms and trunk are impaired or lost. The arms
do not swing, and in the fully developed syndrome the body is carried “en
bloc.” In addition, there are almost always bizarre changes and motor
distortions. The patient leans conspicuously, usually forward but sometimes
backward or to the side; he sidles, or shuffles along with some typical oddity
of movement; often it looks like a tic blended into the walk. Among the
variants are propulsive gait, a tendency to lean forward and walk always
faster in a half run which may not stop till the patient reaches a point of
support, or retropulsion—-a similar tendency to walk or run backward. The
usual postencephalitic compulsive quality characterizes these symptoms too.
Rigidity is of cogwheel type and asymmetrical. Tics and mannerisms of
many kinds are seen, among them torticollis, facial grimaces, and movements
difficult to distinguish from torsion spasms. The tremor, which is a rhythmical
rest tremor, ceases only during sleep; it is most often seen in the upper
extremities but may involve other parts, especially the legs, jaw, and tongue,
in various combinations. Among the rarer syndromes are cataplexies and
myasthenoid disturbances as well as chorealike movements. All of these bear
the stamp of the basic disease.
The speech of the well-developed case is highly characteristic, and the
many varieties have a common denominator. The voice is monotonous, nasal
and somewhat singsong, and often trails off into nothingness, as does the
writing, because spasm increases as the activity progresses. Frequently
observed is palilalia, a needless repetition of words or phrases. Sometimes

dysarthria is prominent, and sometimes bradykinesis; often, refuge is taken in
a few hastily spoken words, followed by staring silence.
Hypersalivation is the most prominent of the purely vegetative findings

and, combined with the masking and stiffness of the face and lips, often leads
to drooling. Among the wide variety of other neurovegetative disturbances
are seborrhea of the face, irregularity of respiration often of bizarre form,
marked adiposity (sometimes with polydipsia and polyuria), disturbances of

appetite and of sleep, lability of temperature control, excess perspiration, and
pupillary irregularities.
Course
The chronic syndrome may follow the initial infection immediately or
after a latent period which may last for many years. Once neurological
symptoms have been established, the usual course is irregularly progressive
although static cases have been described. Pregnancy, trauma, infection, or

other stress can produce exacerbations. A majority of the cases now seen in
ordinary clinic and hospital practice give no history of acute encephalitis,

although sometimes a story of illness with diplopia or hypersomnia can be
elicited. In this respect the sequence is analogous to that of paresis.
Diagnosis rests on the neurological and neurovegetative findings and
the history of progression. This disorder is distinguished from Parkinsons
disease by the asymmetry and irregularity of the symptoms and the bizarre
additional elements. The postencephalitic form is also to be distinguished
from the many nonprogressive types of Parkinsonian syndrome. None of
these has the vegetative findings or the typical encephalitic disturbances of
gait, station, and behavior. Poisoning by carbon monoxide or manganese,

cerebral trauma, and Wilson’s disease may also produce basal ganglion
symptoms, and these are similarly differentiated. Parkinsonism due to
medication may combine with a neurological disability of other origin to
produce puzzling syndromes, but the matter becomes clear when medication
is withdrawn.
In the case of a child with pure behavior disorder, diagnosis poses a
more difficult problem, and in the absence of at least minor specific

progressive neurological findings, or of a known outbreak it would seem that
the diagnosis of encephalitis lethargica should not be made.
Treatment
Treatment of the chronic encephalitic syndrome remains symptomatic.
Medication, regimen, psychotherapy, and psychosurgery are all used, and

effects in the psychic, somatic, and social spheres reinforce each other.
Medication
The pharmacological therapies are, in general, used according to
schedules which call for titrating drugs against symptoms, the end point
being a satisfactory effect, or symptoms of toxic overdose, whichever comes
first, and often the two are not far apart. The topic is so complex as to forbid a
complete review of all drugs in this paper, but drug-induced Parkinsonism

has made this type of treatment commonplace, and there are many excellent
descriptions; one example is Chap. 72 in the 1971 AMA Drug Evaluations.
Three general classes of drugs are now available, the anticholinergic,
the antihistamines, and the newer drugs levodopa and amantidine. The
anticholinergic drugs tend to lose their effectiveness with continued

administration, and for this reason a fairly complex pharmacy is necessary,
but shifts from one to another medication should not be made abruptly. The
anticholinergic group produces atropinelike side effects and one must watch
for such complications as prostatism, glaucoma, and serious loss of

accommodation for near vision. Temperature control may also be impaired,
and this is doubly important because it appears that this function is already
weakened by the encephailitis, and deaths from heat stroke can occur.
Fortunately, the newer anticholinergics have far less peripheral effect than
the original drugs which they have now virtually replaced. The older drugs
include atropine itself, scopolamine, hyoscyamine, stramonium, and
bellabulgara. In addition, the amphetamines once had considerable vogue.
The anticholinergic drugs in current use are synthetic and include

trihexyphenedyl HCl (Artane, Pipanol, Tremin HCl), biperiden (Akineton),
cycrimine HCl (Pagitane) and procyclidine HCl (Kemadrin).
The antihistamine-type drugs are of weaker action, have fewer side
effects and are used chiefly to potentiate the effects of the anticholinergics or
for patients who cannot tolerate the more potent drugs. They include
diphenhydramine HCl (Benadryl), chlor-phenoxamine HCl (Phenoxene), and

orphen-adrine HCl (Disipal). Benztropine mesylate (Cogentin) is described as
intermediate between the anticholinergics and the antihistaminics in
therapeutic potency and side reactions.
Both L-Dopa and amantidine appear to be effective in postencephalitic
Parkinsonism and seem to represent a distinct advance in practice as well as

theory. L-Dopa (levodopa) influences all the symptoms, akinesia, ridigity, and
tremor being benefited in that order. Toxic effects are frequent and include
mental symptoms and various types of involuntary movement. It appears that
in the present state of knowledge, L-Dopa is best reserved to treat the

exacerbations of the postencephalitic state and to give relief in the intractable
cases. Amantidine is also effective but far less dramatic. It has milder side
effects, is additive to the anticholinergic drugs and does not appear to
establish tolerance. Where, for any reason, the anticholinergic drugs are
withdrawn, the process should be gradual to avoid serious aggravation of
symptoms.
Regimen
All authors acknowledge that the general management of the patient is
important. Adequate nutrition, regular exercise within the limits of the
patient’s capacity, maintenance of interest and activity, moderate recreational

interests and hobbies, physiotherapy, vocational training, and rehabilitation
where indicated, are all important elements. On the other hand, overstress is
harmful, and excess fatigue is to be avoided. Alcohol is usually poorly
tolerated and is not advised. Above all, an optimistic constructive attitude on

the part of the physician is crucial.
Psychotherapy
Complex psychotherapeutic techniques have been described by various

authors, but I am inclined to agree with Bosner quoted by Neal, that “effective
psychotherapy in chronic encephalitis still demands a rather primitive
dependence on rapport between patient and doctor.” While there are
limitations, the psychotherapeutic modalities which are available should be
tried. Used in conjunction with the drug therapy and regimen, they can
produce marked amelioration of an otherwise intolerable existence.
Neurosurgery
Neurosurgery has been reserved for far advanced intractable cases of

postencephalitic Parkinsonism. Destructive lesions of the globus pallidus, the
thalamus, the subthalamic region, and even the internal capsule have all been
reported as producing desirable results. When successful, these procedures
improve both rigidity and tremor on the opposite side of the body, with
corresponding general improvement of symptoms. Bilateral operations are
common. Among the earlier operations were cortical excisions to control
tremor and rigidity, and nerve sections for torticollis.
Other Postencephalitic States
The spectacular experience with encephalitis lethargica focused medical

attention on encephalitis as a cause of neuropsychiatric disorders, and within
a few years a number of new entities were identified. The first was St. Louis
encephalitis described in 1933. Others include Japanese B encephalitis,
Australian X disease, and Murray Valley encephalitis.
The late 1960s have seen spectacular advances in virology due to such
technical improvements as new methods of virus culture, the use of the
electron microscope for identification, and the development of new
immunological techniques, such as immunofluorescent staining methods. As a
result the number of identified viruses has greatly increased and various
types of viral encephalitis are being diagnosed and reported routinely. They
remain, however, more important from the point of view of public health than
from that of psychiatry, because in most types the acute attack generally ends
in complete recovery, although death rates are sometimes high. When
residuals do occur they are nonspecific and nonprogressive, and their

treatment belongs to that of the organic syndromes. Certain rare types of
chronic progressive encephalitis have, however, been identified and because
of this fact and because the various forms of encephalitis do represent a
variety of central nervous system pathology, these viral infections do have

some psychiatric interest. A brief discussion of several of the more important
types of viral encephalitis is presented here. For a more exhaustive account of
the virology, the reader is referred to the comprehensive report by Whitty et

al.
Encephalitis Due to Arbo Viruses

(Arthropod-Borne)
These include St. Louis, Japanese B, equine, and California encephalitis,
and Colorado tick fever, some sixty types in all. They vary widely as to
morbidity and mortality; recovery with severe sequelae is not unusual. The
residual defect is nonspecific and therapy is that of the focal and diffuse
syndromes which follow. Many of these disorders occur in epidemic form.
Hemorrhagic Encephalitis
Hemorrhagic encephalitis has been known for at least 200 years. It may
complicate many types of infection but is most frequently associated with
influenza. Recovery with serious damage is reported even in the older
literature. The lesion is nonprogressive, nonspecific, focal and/or diffuse, and
the treatment of these postencephalitic states is that of the chronic brain

syndrome which follows.
Postinfectious Encephalitis
(Leukoencephalitis)
Postinfectious encephalitis is a variety occasionally seen after many
viral infections, especially the exanthems, and the statement is often made
that within recent years such reactions have become more frequent.
After infection with such viruses as varicella, variola, measles, mumps,
vaccina, or after rabies vaccination, acute demyelinating encephalomyelitis

may develop very rapidly. This is primarily in the white matter and tends to
center about the venous system. The nature of the reaction remains obscure;
it is not considered to be due to a direct attack of the virus on the nervous
tissue but probably represents an immunologic allergic mechanism similar to
that of experimental allergic encephalomyelitis. The location of the offending
virus, the site of autoimmune body formation, and the nature of the reaction
remain to be explored. Thrombosis of small vessels and areas of necrosis and
hemorrhage are found. When recovery occurs, it is usually complete, but

there may be severe residuals with hemiplegia, convulsions, mental defect,
and behavior disorder. Such syndromes may be also due to vascular lesions of
unknown mechanism which can complicate a wide variety of systemic

infections in children.
Other Types
Among the types left to be discussed, the slow, latent, or chronic types
are especially interesting. The demonstration of “slow” measles virus as an
etiological agent in encephalitis of children is of great theoretical importance
even though the condition is relatively rare. This virus attacks the
parenchyma directly, invades the cells and replicates within them and is thus
quite different in mechanism from the encephalitis which is generally caused
by the exanthems. It is of insidious onset, and generally progresses with
increasing cerebral symptoms such as mental deterioration and myoclonus to
a fatal outcome within a year. Measles can also cause the usual
leukoencephalitis like that following other exanthems.
Amantidine has been reported as checking the spread of slow measles
encephalitis, which is now thought to include several disorders previously
known under such names as subacute sclerosing panencephalitis (SSPE)
(Pette Dohring), subacute sclerosing leukoencephalitis (Van Bogaert), and
Dawson’s inclusion body encephalitis. Another form of slow virus infection
known as Kuru is found only in New Guinea among the Fore people where it
appears to be of relatively recent origin. It takes the course of a fatal

degenerative cerebellar disease, but it has been shown to be transmittable to
chimpanzees. Other forms of chronic virus encephalitis have been identified
in humans and in animals (Cytomegalus virus, fetal rubella, visna and scrapie
in sheep, mumps in hamsters, etc. So far as is known today, such disorders are
rare in humans, but the potential implications of these discoveries is obvious.
Another important recently discovered viral encephalitis is that due to
herpes simplex. Now considered to be the commonest cause of nonepidemic

encephalitis, it often leaves severe neuropsychiatric residuals. It does not
belong to the “slow virus” group.
Finally, one may note that virus infections of the central nervous system
may be not only latent or chronic, but they may also not be demonstrable by
ordinary neuropathological techniques. Such viruses may produce disease by
causing dysfunction in morphologically intact but infected neurons.
What such findings may mean for neuropsychiatric practice remains to
be seen. At the very least, the door has been opened to diagnosis, prevention,
and even treatment of some relatively rare obscure diseases which till now
were thought to be degenerative. The preponderance of evidence today
seems to be against assigning a significant role to the virus infection with
respect to major psychiatric problems such as the highly controversial MBD.
But virus infections have surprised us before, and as Sabin has pointed out,
they may do so again. The scene for such a surprise may have been set by the
laboratory demonstrations of chronic latent virus infection of the central
nervous system. For this we find clinical support in the observation that
clinical symptoms of viral encephalitis may break out when

immunosuppressant drugs are used.
It is to be expected that we shall hear much more on these issues in the
near future. It does not seem likely that interest in the viral forms of
encephalitis will again be lost as happened after the 1916-1930 epidemic.
Bibliography
American Medical Association, Council on Drugs. AM A Drug Evaluations, 1st ed. Chicago: Am.
Med. Assoc., 1971.
Brody, J. A., W. Henle, and H. Koprowski. Chronic Infections, Neuropathic Agents (China), and Other
Slow Virus Infections. New York: Springer Verlag, 1967.
Calne, D. B., G. M. Sterne, D. R. Laurence et al. “L-Dopa in Post Encephalitic Parkinsonism,” Lancet,
1 (1969), 744-747.
De Jong, R., ed. Yearbook of Neurology Psychiatry and Neurosurgery, 1967-68, footnote p. 64.
Chicago: Yearbook Medical Publishers, 1968.
Gaydusek, D. C., C. J. Gibbs, Jr., and N. Alpers. “Experimental Transmission of Kuru-Like Syndrome
to Chimpanzees,” Nature, 209 (1966), 794-796.
Haslam, R. H. A., M. P. McQuillan, and D. B. Clark. “Amantidine Therapy in Subacute Sclerosing

Panencephalitis,” Neurology, 19 (1969), 1080-1086.
Hughes, R. C., J. G. Polgar, and D. Weight-man. “Levodopa in Parkinsonism: The Effects of

Withdrawal of Anticholinergic Drugs,” Br. Med. J., 2 (1971), 487-491.
Hunter, R. and M. Jones. “Acute Lethargic-Type Encephalitis,” Lancet, 2 (1966), 1023-1024.
Johnson, R. T. “Chronic Infections Neuropathic Agents: Possible Mechanisms of Pathogenesis,”

Curr. Top. Microbiol. Immunol., 40 (1967), 3-8.
----. “Neurologic Diseases Associated with Viral Infections,” Postgrad. Med., 48 (1971), 158-163. n.
Johnson, R. T. and K. P. Johnson. “Slow and Chronic Vims Infections of the Central
Nervous System,” in F. Plum, ed., Recent Advances in Neurology, pp. 33-78.
Philadelphia: Davis, 1969.
Journal of the American Medical Association, unsigned editorial. “St. Louis Encephalitis,” 193
(1965), 150-151.
----. “Current Viruses May Surprise Us,” 197 (1968), 49-50.
Krayenbuhl, H., K. Akert, K. Hartman et al. “Study of Anatomico-Clinical Correlation in Patients

Operated on for Parkinsonism,” Neurochirurgie, 10 (1964), 397-412.
Lancet, unsigned editorial. “Encephalitis of a Lethargica Type in a Mental Hospital,” 2 (1966),

1014-1015.
Malzberg, B. “Age of First Admissions with Encephalitis Lethargica,” Psychiatr. Q., 3 (1929), 244.
Marshall, W. J. S. “Herpes Encephalitis Treated with Intravenous Idoxuridane and External

Decompression,” Lancet, 2 (1970), 579-580.
Martin, J. P. “Globus Pallidus in Post Encephalitic Parkinsonism,” J. Neurol. Sci. 2 (1965), 344-365.
Martin, W. E. “Tyrosine Hydroxylase Deficiency, a Unifying Concept of Parkinsonism,” Lancet, 1

(1971), 1050-1051.
Mayer, E. E., ed. Oppenheim s Diseases of the Nervous System. Philadelphia: Lippincott, 1900.
Neal, J. B., ed. Encephalitis: A Clinical Study. New York: Grune & Stratton, 1942.
Parkes, J. D., K. J. Zilka, P. Marsden et al. “Amantidine Dosage in Treatment of Parkinson’s

Disease,” Lancet, 1 (1970), 1130—1130-1133
Richter, R. W. and S. Sadatomo. “Neurologic Sequelae of Japanese B Encephalitis,” Neurology, 11

(1961), 553-559.
Schilder, P. (1953) Brain and Personality, reprinted. New York: International Universities Press,
1969.
Tuke, D. H. Dictionary of Psychological Medicine. Philadelphia: Blakiston, 1892.
Wilson, S. A. K. Neurology, Vol. 1. Baltimore: Williams & Wilkins, 1940.
Waltz, J. M., M. Riklan, S. Stellar et al. “Cryothalamectomy for Parkinson’s Disease: Statistical
Analysis,” Neurology, 16 (1966), 994-1002.
Whitty, C. W. M., J. T. Hughes, and F. O. MacCallum, eds., Virus Diseases and the Central Nervous
System. London: Oxford University Press, 1969.
Wildy, P., ed. Classification and Nomenclature of Viruses. Vol. 5. Monograph of Virology. First
Report of the Int. Comm. on Nomenclature of Viruses. Basel: Karger, 1971.
Chapter 7
Head Injury
Kenneth Tuerk, Irving Fish and Joseph Ransohoff
The increasing incidence of serious head injuries in the United States is

a byproduct of the rapid pace of urban life, as well as of the increasing use of
high-speed transportation. Precise statistics are not available but the
estimates are staggering. It is well known that accidents are by far the leading
cause of death under the age of thirty, over 100,000 annually in the United
States. Approximately 50,000 deaths occur each year as a result of automobile

accidents, and of these, it is estimated that 60 percent of the victims (or
30,000) died directly as a result of head injury. Vehicular accidents account
for about 3 million head injuries yearly, 750,000 concussions, 150,000 skull
fractures and 150,000 significant brain injuries (Figures 7-1 and 7-2).
Improved facilities, better understanding of the pathology of head
trauma, and advancements in therapy have led to more successful treatment.
Mortality has decreased, but as increasing numbers of patients are saved, the
morbidity rate has increased. Not all patients are fortunate enough to recover
without neurological sequelae.
Evaluation of a posttraumatic patient can be quite complex. Certain
deficits, such as hemiparesis, and hemianopsia are obviously of an organic
nature. Subtle mental changes may be either organic or functional, or
represent a combination of both factors. At times, the symptoms may be only

those of mild mental changes, such as irritability or forgetfulness, with or
without such vague symptoms as headache and light-headedness. The skills
of both the neurologist and psychiatrist may be taxed in evaluating and
treating these patients with the ultimate goal of rehabilitation and return to a
normal, productive position in society.
In evaluating the head injury patient, the examining physician should be
aware of the possibility of preexisting disease of the central nervous system
which may not come to light until an episode of trauma brings it to the
patient’s or the physician’s attention. A slowly developing homonymous

hemianopsia may go totally unnoticed by the patient, for example, until such
time as he is involved in an auto accident when the other vehicle approaches
from his “blind side.” Similarly, the patient with developing cerebellar ataxia
may not be conscious of his gait disturbance until a fall. Subsequently he may
date all of his difficulties to that dramatic episode.
Similarly, in evaluating the patient for possible mental changes after
head trauma, one must not only determine that trauma actually occurred, but
also that it was significant, and that there was a cause-and-effect relationship
between the trauma and the symptoms.
Figure 7—1.
The brain of a thirty-year old male in a traffic accident. The dura is reflected
from the left hemisphere to show a subdural hematoma. In the rolandic
operculum there is contusion of the brain with subpial bloody discoloration
of the cortex. Below in the temporal lobe there are contusion and laceration
of the brain. The cut in the occipital lobe is an autopsy artifact. (Courtesy of
Dr. Paul I. Yakolev, Warren Anatomical Museum, Harvard University.)
Figure 7—2.
Figure 7—2.
The brain of a middle-aged man who suffered a head injury in an automobile

accident several years prior to his death. He showed both intellectual and
social deterioration and died in a state hospital. The frontal lobes show old
traumatic destruction of convolutions, with atrophy and scarring of the
brain. The pia-arachnoid is stripped off from the right hemisphere to show
extensive corticomeningeal adhesions over the areas of the old cerebral
trauma. (Courtesy of Dr. Paul I. Yakolev, Warren Anatomical Museum,
Harvard University.)
Significant Head Trauma
Significant head trauma is generally thought to be that which is followed
either by alteration in the state of consciousness, focal neurological signs, or a
skull fracture. Although the patient may appear absolutely normal in all
respects, any of these conditions are grounds for hospitalization for at least a
twenty-four-hour observation period.
In arriving at these criteria, one must remember that while injuries to
the soft tissues of the head are not of neurological significance per se, they do
afford some indication of the forces applied to the head during the trauma,
and can serve to alert us to the possibility of underlying brain damage. During
the twenty-four-hour period of observation, evidence of acute intracranial
changes generally appears. We must remember, however, that while these
guidelines are helpful, it is certainly possible for delayed deterioration to
occur after a period of observation, as in the incidence of chronic subdural
hematoma, and can even occur without meeting any of the above criteria for
admission to the hospital for observation. Figures 7-3 to 7-5 show various
stages of brain damage after cerebral trauma.
Trauma, severe enough to cause alteration or loss of consciousness, is

obviously significant. Indeed, the severity of the brain injury can be correlated
with the length of time the patient remains unconscious. Loss of
consciousness for a few seconds to an hour may be empirically classified as

mild, one to twenty-four hours as severe. This, however, is a rough guide and
does not mean that a patient who was unconscious for only a few seconds (or
not at all) cannot develop dangerous complications.
Figure 7-3.
Cerebral Trauma. Contusion; two days old. Cortex. Hemorrhagic extravasate

in the right lower corner of the field; hyperemia; perivascular infiltration
(“cuffing”) with inflammatory cells. Cresyl violet stain (X 80). (Courtesy of Dr.
Paul I. Yakolev, Warren Anatomical Museum, Harvard University.)
Patients with a history of unconsciousness often have a period of pre-
and posttraumatic amnesia. Pretraumatic amnesia is defined as the time
interval from the last moment remembered before injury to the time of injury.
Posttraumatic amnesia is defined as the time interval from the moment of
injury to the time when the patient remembers awakening. Again, a rough
correlation can frequently be made between the severity of the intracranial
injury, the length of unconsciousness and the extent of pre- and
posttraumatic amnesia.
Following head injury, the patient may be seen in either the acute or
chronic stage. Although most patients will not be seen by a psychiatrist until
the chronic stage, a brief discussion of the acutely injured patient is important
to an understanding of the posttraumatic psychiatric sequelae.
Concussion
The definition and implications of the term “concussion” have
undergone much change since the description of Wilfred Trotter in 1925. He

felt that it was an “essentially transient state due to head injury which is of
instantaneous onset, manifest widespread symptoms of purely paralytic kind,
does not as such comprise any evidence of structural cerebral injury and is
always followed by amnesia for the actual moment of the accident.”
Figure 7-4.
Figure 7-4.
Cerebral Trauma. Contusion; six days old. Cortex. Intense proliferation of

new capillaries; patchy areas of nerve-cell loss; beginning organization of
the damaged tissue into future scar. Cresyl violet stain (X 80). (Courtesy of
Dr. Paul I. Yakolev, Warren Anatomical Museum, Harvard University.)
Some authors have included those patients who are dazed and
confused, as well as those who have actually lost consciousness. Clinically, a
concussion with loss of consciousness is accompanied by flaccidity, abnormal

brain stem reflexes, bradycardia, and apnea. If this state is prolonged, death
may ensue, and autopsy may show few or no structural changes. These
phenomena can be explained in only two ways: widespread simultaneous
neural dysfunction or focal dysfunction in areas concerned with levels of
consciousness, as well as respiratory and cardiac reflexes.
It has been shown by French and Magoun that destruction of the
reticular formation can produce coma. It has also been shown by Foltz and
Schmidt that, following concussion in monkeys, evoked potentials from
peripheral stimulation are abolished in the reticular formation but not in
other ascending pathways. Finally, electrical action in the brain decreases
markedly in many areas after concussion, but the most marked depression
almost always occurs in the medial reticular formation. These physiological

data, with marked dysfunction of the reticular formation, seem adequate to
explain the clinical events during and after a concussion.
A search for a structural pathological explanation is still in progress. It is
felt, at least by some schools of neuropathology, that structural alterations do
occur at the time of concussion and include changes in neurons as well as
axons. However, cause and effect have not been proved and these changes
may be concomitant rather than causative. Indeed, it seems difficult to explain

the phenomenon of concussion as anything other than brain-stem
dysfunction and the absence of significant lesions is not surprising, as

structural changes in this area are rarely compatible with survival. In any
case, the term concussion comprises a convenient clinical category for the
multitude of patients who have a head injury, a brief alteration in the state of
consciousness and complete return to neurological normalcy after a relatively
short period of time.
Figure 7-5.
Cerebral Trauma. Contusion; several weeks old. Cortex. Organized scar;

proliferation of mesodermal and neuroglial cicatricail tissue; the scar tissue
is relatively avascular. Hematoxylin and eosin stain (X 40). (Courtesy of Dr.
Paul I. Yakolev, Warren Anatomical Museum, Harvard University.)
Posttraumatic Syndrome
The arguments pro and con structural damage take on real significance
in the consideration of the posttraumatic syndrome. This entity is defined as
headaches, a feeling of unsteadiness, at times true vertigo, and mental

changes. These symptoms may occur alone or in combination, and they may
or may not be associated with other more objective neurological signs. They
may occur following minimal trauma as well as after a more severe injury.
However, the degree of injury does not necessarily correlate with the severity
of the posttraumatic syndrome. Headache is the most prominent symptom
and is a complaint of most patients in the postconcussion state. Giddiness
and/or vertigo are about equally frequent, being present in approximately 50
percent of patients. True vertigo usually indicates pathology and, when

associated with postural nystagmus, is objective evidence of damage to the
vestibular system. Finally, the many mental symptoms which occur are the
most difficult to characterize. Although a mild organic mental syndrome may,
indeed, be present, normal results on formal testing are the rule. The usual
complaints are nervousness, irritability, impaired memory, and difficulty in
concentration.
Although Russell found a slightly higher incidence of this syndrome in
more severely injured patients, there is truly no consistent relationship

between the severity of postconcussion state and the extent of the injury. A
mildly dazed patient may be disabled for years, while a comatose patient may
recover without developing this syndrome. Taylor argues convincingly for an

organic etiology, expressing the opinion that this syndrome is present in the
majority of patients following head injury and, if this is a functional disorder,

then the majority of all postconcussion patients have disabling functional
disorders. On the other hand, it is quite clear that there is a high incidence of
this syndrome in industrial as opposed to recreational accidents, and a higher
incidence of occupational incapacitation in cases involved in compensation or
litigation actions. These facts, however, may be due to secondary gain rather
than being related to the organic or functional aspects of the syndrome. In the
follow-up study after the Korean War, 60 percent of the patients with long-
term persistence of posttraumatic syndromes (four to six years) were

competing as well as or better than before the injury. Brenner et al.,
Symmons, and Miller, have all concluded that symptoms which persist for a
long period of time are at least in part due to a significant functional overlay.
Many investigators have felt that secondary gain plays an important role in
the persistence of symptoms and that when financial matters are settled, the
syndrome will subside. Two long-term follow-up studies, however, do not
bear this out and in addition, the incidence of persistent and disabling
symptoms is significantly higher in patients over the age of fifty. This suggests
that this syndrome cannot be totally accounted for on a functional basis. It

would seem likely, in conclusion, that an organic substrate of a vasomotor
nature affecting brain-stem functions plays an important part in the

posttraumatic state. It also seems clear that there are non-organic functional
factors affecting those individuals in whom the syndrome persists for months
or years.
Mental Changes Associated with Structural Injury
Patients with gross structural damage may have either contusions,
lacerations, or hematomas. The hematomas may be either epidural, subdural,
intracerebral or, commonly, combinations thereof. Brain swelling (cerebral
edema) occurs in a high percentage of instances in association with these
lesions and accounts for a significant degree of their morbidity and mortality.
Neurological and neurosurgical evaluations are imperative and dictate the
immediate medical or surgical treatment. The condition of the patient and his
mental state will be determined by the extent of the injury to the brain, the
intracerebral location of the injury and, finally, the degree of increased
intracranial pressure.
Increased intracranial pressure will be relieved by either medical
decompression with mannitol and/or steroids, or by surgical decompression.
Early symptoms of increased intracranial pressure may include headache and

increasing drowsiness, as well as progressive focal neurological deficits.
Once the pressure is controlled, the patient’s clinical status will be a
function of the extent and location of the intracerebral damage. Whether the
insult be a contusion, laceration or hematoma, the degree of dysfunction
should be maximal soon after the injury. At this point, the cerebral
dysfunction is a result of: (1) dead and dying cells; (2) injured cells and
connections which are not functioning, but will recover and function again;
and (3) cells which are not functioning well because of pressure from either
edematous brain or hematoma. Recovery begins soon after injury, as the
edema subsides and the repair processes ensue. The final result, assuming
optimal recovery, will depend on the amount of unavoidable damage which
was sustained at the time of injury. Thus, whether the patient is first seen
while comatose, lethargic, or normal, he should remain stable or improve.

Any further significant deterioration in the clinical status heralds the onset of
a new pathological process other than the original trauma. This may be a
systemic problem such as hypoxia or sepsis, or a neurological one such as
seizures, meningitis, or hydrocephalus. In any case, one should be alerted to

possible deterioration in a patient who was stable or improving. The cause is
often treatable and the deterioration reversible.
In addition to the extent of the injury, the mental status can also be
determined by the location of the lesion. A very small lesion, strategically

placed in the brain stem, produces a greater deficit than a much larger lesion
in one of the “silent” areas of the brain. Other focal lesions may produce a
neurological deficit, such as hemiparesis or hemianopsia, without any change

in mental status.
Although contusions, lacerations, and hematomas may occur at any site,
the anterior temporal lobes and the frontal lobes are most common, owing to
the sharp bony prominence of the sphenoid ridge and the roof of the orbits.
Focal Injury
There are two areas of focal injury of particular interest to the
psychiatrist. The first is the area of the dominant hemisphere, where a lesion
may produce disturbances in comprehension manifest by some degree of
aphasia, either expressive or receptive. See Chapter 11, entitled “Aphasia,” for
a detailed description of these symptoms. When severe, there is no question
about the diagnosis and its organic substrate. However, a minimal degree of
receptive dysfunction following recuperation from a head injury may bring

the patient to the attention of a psychiatrist. The presenting complaint may be
“personality change” or “inability to function as before” the injury. Awareness
of the condition and appropriate examination will demonstrate the true
etiology and the simple “personality change” may become a focal deficit in
expression or understanding or both.
The second area of focal lesions, which may require psychiatric
consultation, are the frontal and anterior temporal lobes, particularly when
the orbital and medial portions are injured. As noted before, the frontal and
temporal lobes are preferred sites for injury in head trauma. The first, and
perhaps still one of the best, descriptions of such a patient is that of Phineas T.
Gage, who, in 1848, was injured with a crowbar in the left frontal lobe. He
recovered and lived for many years, but underwent an extreme change in
personality and behavior which was followed and reported by his physician.
Other reports have since appeared, but most of the information on the effects
of frontal lobe ablation has come from patients on whom it was surgically
performed for therapeutic reasons. This technique was first employed by
Moniz in 1936. The patients with frontal lobe ablation are characterized by
apathy and lack of foresight. Their affect is flat, anxiety is reduced, and there
is a lack of concern for the consequences of their actions, both verbal and
physical. This leads to inappropriate behavior, tactlessness, and a lack of
concern for environment and personal appearance.
Extensive testing has been performed on patients before and after
ablation. Speech is particularly affected. There is a significant reduction in

spontaneous speech. Verbal response to questions is delayed and reduced to
phrases and short sentences. Intelligence tests are difficult to evaluate. They
show definite reduction in verbal scores. Performance scores are about the
same and may actually improve after frontal-lobe ablations. There is
decreased facility for abstract thinking. However, part of the reduction in
scores may be attributed to damages in personality.
Organic Mental Syndrome (OMS)
The most common and disabling change in mental status after severe
head injury is an organic mental syndrome. This is a condition resulting from
any of a number of organic pathological processes, whether traumatic or not.
The syndrome thus is a final common pathway of many organic diseases, one
of which is trauma and its sequelae.
The hallmarks of the syndrome are dementia and loss of recent

memory. In its mildest form, there are subtle changes in personality such as
increased instability, decreased attention span, reduction in capacity for
abstract thinking and, out of proportion to all other signs, a decrease in recent
memory and recall. If the organic mental syndrome is more severe, an

outright dementia may occur with disorientation, lack of personal care,
incontinence, and severe lability of affect. The mood may be either manic or
depressed but this is governed to some extent by the pre-morbid personality.
Focal neurological deficits may or may not be present. However, attempts to
correlate the OMS with a specific localization of brain injury have failed. It is
best correlated with diffuse, bilateral cerebral dysfunction. The first and most
common etiology of an OMS following head injury is diffuse, bilateral brain
damage as a result of the trauma and secondary edema.
As his state of consciousness improves, the patient may pass through a

stage of traumatic delirium characterized by excessive motor activity and
confusion. He may scream, try to climb out of bed, and alternate between
periods of spontaneous but inappropriate speech and sleep. Sedation and

restraints may be necessary to prevent the patient from inflicting further
injury upon himself.
Finally, continuing on the path of recovery, the patient manifests a
severe organic mental syndrome which gradually becomes milder and finally
disappears.
Depending on the severity of the injury, patients may pass through
these stages in a few minutes, days, or months. Generally, the more severe the
injury, the longer the period of unconsciousness and the more extended and
gradual the recovery period. After very brief concussions, there may only be a
few minutes of confusion before return to normal, and all these stages may
not be evident.
Unfortunately, not all patients recover. Those with a severe deficit may
be considered for institutionalization. Those with a milder deficit may be

discharged from the hospital only to arouse anxiety in the family by even
moderate changes in their behavior and personality. This may create havoc
within the family unit.
The first step in the evaluation of such patients is to confirm the

diagnosis of organic mental syndrome, i.e., dementia and loss of recent
memory. At times, psychometric evaluation may be helpful in establishing the
diagnosis. In cases of a posttraumatic organic mental syndrome, the crucial
questions to be asked are whether the process is the end result of the
traumatic event, whether further recovery will occur and, finally, whether the
arrest in recovery is the result of some intervening, superimposed disease or
complication. These patients are often young and ambulatory with a long life
expectancy. Therefore, particularly as the rate of recovery of mental function
is decreasing or when the condition has stabilized, the physician must be
absolutely sure that nothing further can be done to advance recovery before
offering a final diagnosis and prognosis to the patients and their families.
Chronic Subdural Hematoma
A chronic subdural hematoma usually manifests itself by increased
intracranial pressure and progressive focal neurological deficit. At times, and

particularly in an injured brain, a progressive organic mental syndrome may
be the earliest sign. If not corrected, this progression may continue until the
patient becomes progressively obtunded and, finally, comatose. Headache,
although usually present, may easily be overlooked. Focal neurological signs
may not be present until late and papilledema may be present in 25 percent
of cases. Skull X-ray may show the pineal gland to be shifted off the midline.
Brain scan will be positive in 90 percent of cases. Lumbar puncture may show
xanthochromia and increased protein in 50 percent of cases. Lumbar
pressure is usually elevated, but a normal pressure does not exclude the
diagnosis of hematoma. Echogram may show a shift of the midline structures,
and cerebral angiography is diagnostic.
Early diagnosis and treatment is quite gratifying, with most patients
returning to their previous neurological status. However, the diagnosis may
be missed in a slowly deteriorating patient until coma and herniation ensue.
Emergency surgery at this time, while often successful, does not always carry
the same favorable prognosis.
Communicating Hydrocephalus
Another complicating condition, which may produce an organic mental

syndrome, is a secondary communicating hydrocephalus. It has been known
for some time that head trauma with bloody CSF (cerebrospinal fluid) may
produce a subacute hydrocephalus in the weeks following the injury. Moritz
and Wartman, in 1938, discussed three cases with postmortem changes of
arachnoiditis. In 1956, Foltz and Ward reported the successful treatment of
hydrocephalus after subarachnoid hemorrhage of diverse etiologies,
including trauma. In their cases, onset was between the second and tenth
week after the hemorrhage. The important factor in all of these cases appears
to be the arachnoidal reaction to the blood in the spinal fluid, producing an
obstruction to the normal flow of fluid in the subarachnoid space. The
obstruction is usually at the level of the tentorium but may, at times, be over
the cerebral convexity. This obstruction results in communicating
hydrocephalus with its attendant large ventricles and signs of diffuse cerebral
dysfunction. Although this was once thought to be a rare occurrence, studies
have shown that some degree of hydrocephalus, although not always
clinically significant, is quite common after head injury with bloody CSF.
The clinical course of posttraumatic hydrocephalus may vary. In its
mildest state the diagnosis may be an incidental finding when contrast

studies are performed for other reasons. In other cases, there may be a mild
organic mental syndrome or deterioration of a previously improving
neurological state. After a few weeks, the mechanisms of production and
resorption of spinal fluid equilibrate and the process may resolve

spontaneously. Finally, in its most severe expression, the hydrocephalus is
progressive and relentless, causing not only a plateau of mental recovery, but
retrogression, leading at times to severe obtundation. Neurological and

neurosurgical consultations are imperative as the situation may become
reversible after a shunting procedure.
In 1965, Adams et al. reported the syndrome of “normal-pressure

hydrocephalus” (occult hydrocephalus, low-pressure hydrocephalus). These
patients present with a progressive OMS, unsteady gait, urinary incontinence,
and normal pressure on lumbar puncture. There is nothing particularly

characteristic about the OMS but the gait disturbance is quite unusual. It is
somewhat broad based and unsteady, although no cerebellar signs are

present. There appears to be some difficulty with the initiation of walking
movements and some patients have stated that “it feels as if my feet are glued
to the floor.” This has been characterized as “a magnetic gait.” Onset of these
symptoms may be months and even years after the injury. Skull X-ray and
lumbar puncture are normal. Definitive diagnostic tools are RISA (radioactive
iodinated serum albumin) cisternogram and pneumoencephalogram. In the
former, the I salt-free albumin is injected via lumbar puncture. Normally, the
follow-up brain scans show activity in the basal cisterns in four hours. By
twenty-four hours, there is diffuse activity over the cerebral convexities and
sagittal sinus. In occult hydrocephalus, the activity enters the lateral
ventricles within six hours and, even at the end of forty-eight hours, there is
no activity over the convexities. The pneumoencephalogram shows enlarged

ventricles with little or no air in the supratentorial subarachnoid space,
indicating a block of the CSF pathways at the level of the tentorium. This
condition must be differentiated from hydrocephalus ex-vacuo, i.e., cerebral
atrophy. In this situation, the RISA scan is normal and, although the ventricles
are large as a result of atrophy, air does pass over the convexities and
demonstrates widened sulci and atrophic gyri. Although there are two
contrary reports, most observers feel that shunting is of no value in these
patients, as the hydrocephalus is secondary to atrophy, in contrast to the

results of shunting in patients with obstructive hydrocephalus secondary to
trauma.
In addition to trauma, other etiologies accounting for occult
hydrocephalus include subarachnoid hemorrhage, meningitis, and
intracranial surgery. The idiopathic cases are thought to be due to
unrecognized or forgotten trauma or infection. The few pathologic studies
performed have confirmed the presence of adhesions at the base of the brain.
Posttraumatic Epilepsy
Posttraumatic epilepsy is a disorder which, at first, may appear to be

functional but is, on close examination, an organic sequela of head injury. The
incidence is quite low in closed head injuries, whether or not the patient has
been unconscious. However, when the dura is penetrated, the incidence rises
to about 50 percent.
Posttraumatic seizures can be divided into two groups, depending on

whether the onset is early or late. Of the patients who develop seizures, about
10-15 percent have their ictus within one month, often within the first forty-
eight hours after injury. These seizures are secondary to an irritative process
set off by cerebral contusion, laceration, or edema. The prognosis is good and
after appropriate therapy, the seizures usually subside. Although the long-
term prognosis is good, maintenance anticonvulsant therapy should be
initiated and a baseline EEG (electroencephalogram) obtained. Therapy may

be discontinued after two years if the EEG has reverted to normal.
About 85 percent of patients with posttraumatic epilepsy have a
delayed onset. Of those who develop seizures, 50 percent do so within six
months and 75 percent in two years. Because of the high incidence of
posttraumatic seizures in penetrating wounds and the social stigmata
accompanying these seizures, we feel that all such patients should be placed
on prophylactic anticonvulsant therapy for at least two years. The medication
may then be discontinued if the EEG is normal. The prognosis of all types of
posttraumatic seizures is good.
The seizure itself, with its period of relative hypoxia and postictal
confusion may interrupt the convalescence of the head-injured patient,
particularly if repeated. Focal neurological deficits may become more
pronounced postictally and, with lesions of the dominant hemisphere,
aphasia may become exaggerated.
Approximately 80 percent of posttraumatic seizures have a focal
component. At times, the seizure arising from a temporal lobe focus consists
entirely of psychomotor phenomena. These patients, more than others, may
be brought to psychiatric attention. The dreamy state, periods of amnesia,

episodes of deja-vu and sudden emotional outbursts may easily be mistaken
for a functional disorder.
Boxing Encephalopathy
Boxing encephalopathy (chronic progressive traumatic encephalopathy
of boxing) has been associated with the injuries received in the ring. The
disease is characterized by a progressive OMS with both pyramidal and
extrapyramidal signs. Symptoms do not usually occur until fifteen to twenty-
five years after the onset of the boxing career. Only a few pathological
examinations have been performed and these show atrophy with widespread
areas of gliosis. The etiology is contested. It was long felt to be secondary to

repeated trauma with each episode causing a bit more permanent damage.
This hypothesis is contradicted by the fact that symptoms may not begin until
long after retirement and are then progressive. Alcoholism has been invoked
as a possible etiology but retrospective studies have shown that a significant

number of these patients are not alcoholic. The exact etiology remains to be
clarified. It may simply be that the repeated episodes of trauma leave only a
marginal reserve. As these patients become older, they develop an OMS at an

early age.
Head Trauma in Children
If the incidence of head trauma is high in adulthood, it is virtually 100
percent in childhood, multiple minor head injuries being a frequent

occurrence in this age group. Approximately 200,000 children each year have
head trauma severe enough for them to be hospitalized. About 5-10 percent
of these exhibit neurologic findings at the time of admission.
The differences in the sequelae of head trauma in children as compared

to adults, is related to two main factors: (1) The state of closure of the sutures
of the skull at the time of injury, and (2) The state of development of the brain
at the time of injury.
Sutures
At birth the sutures of the skull are not closed. This allows for the
growth of the skull to accommodate the enlarging brain comfortably, without
increasing the pressure within the cranium. The period of the most rapid
postnatal brain growth is the first six months of life. At about six to nine
months, the sutures begin to fuse. The anterior fontanelle is the last to close at
about eighteen months of age. Fusion between the bones of the skull
gradually becomes more firm over several years.
The nonfused or partially fused skull of the infant and young child is
apparently better able to absorb the energy transmitted to it by external
forces, molding or distorting with the blow, and protecting the underlying
brain. The young brain with its higher water content is also better able to
tolerate external forces than the older, more solid adult brain. Every summer
we see in our large-city hospital emergency rooms innumerable instances of
survival following falls from open windows four or five floors above the
street. This is another evidence for the tolerance of the infant to head trauma.
Thus, the dynamics of increased intracranial pressure are different in

early childhood than in adulthood, and the younger the child, the greater the
difference. It was mentioned previously that brain dysfunction following head
trauma is caused by (1) direct injury to the brain, e.g., laceration or contusion;
(2) by edema; and (3) by increased intracranial pressure secondary to edema
or blood which may be intracerebral or extracerebral (subdural or epidural
hematoma). Increased intracranial pressure in adults causes downward
herniation in the cerebrum through the tentorium, causing pressure on the

brain stem which results in disturbances of consciousness, cranial-nerve
dysfunction and abnormalities in cardiovascular and respiratory function.
This threatens life and must be treated immediately by decompression as

mentioned previously. Otherwise permanent brain-stem dysfunction can
result, although the brain stem may not have been injured directly. In young
children, with an open fontanelle and sutures that are not closed,
supratentorial blood or edema causes enlargement of the skull and

accommodation of the increased contents which result from the injury.
Consequently, the brain has less of a tendency to “herniate down” into the
brain stem. However, this can occasionally take place if the sudden increase in
intracranial volume exceeds the expansion capacity of the skull. Obviously,
the older the child, the more the dynamics approach those of adults, and
therefore, the more danger of injury secondary to herniation.
Hydrocephalus may follow head trauma because of obstruction of the
extraventricular spinal fluid pathways along the base of the brain. This results
in an enlarged head and pressure on the white matter surrounding the

ventricles. Treatment consists of shunting the fluid from the ventricles into
another body cavity such as the atrium of the heart, the peritoneum, or the
pleural space.
If subdural hematomas are very large, they may also cause enlargement
of the head and pressure on the gray matter of the cerebrum. If the subdurals
are small, they may resorb on their own without causing pressure sequelae.
Sometimes repeated paracentesis of the subdural fluid is enough to prevent
signs and symptoms. If the subdurals are very large, shunting of the fluid into
another body cavity may be required.
Brain Development
The second major factor which differentiates the prognosis and
sequelae of head trauma in children from adulthood is the state of

development of the brain at the time of injury. The newborn brain has fewer
cells, less myelin, and a less well developed dendritic system than that of
adults. The immature injured brain is able to compensate better. It is said to
have more plasticity. Intact parts of the brain can “take over” an injured or
destroyed area’s function. For example, in an adult, an injury to the dominant
hemisphere in the speech centers results in aphasia. In children under two
this never happens, and even up to the age of five, “compensation” by the
opposite side is frequently complete or almost complete. As the patient gets
older, the ability to compensate decreases.
All of this means that a child with a brain injury secondary to head
trauma has a far better chance for complete or satisfactory recovery than an
adult with a comparable head injury. Also, the younger the child, the better
the chances of satisfactory mental and motor recovery. Unfortunately, this
does not mean that every child recovers satisfactorily from a head injury.
Approximately 5-10 percent of childhood head injuries, which result in

hospitalization, are severe. About 30 percent of children with severe head
injury who survive, remain with neurological and/or mental dysfunction.
The most accurate gauge as to whether a child will remain with a brain
dysfunction is the same as that with adults, namely the longer the
posttraumatic amnesia (PTA), the more likely the chance for a permanent
deficit. However, at every phase of recovery, the degree is much better in

childhood.
Richardson studied ten children who were comatose from seven to
forty-seven days after head injury. The PTA varied between twenty-five and
sixty-five days. Only one patient was so incapacitated that he could not care
for himself. Six others had motor or movement abnormalities. All had some
intellectual and behavioral changes. Improvement in these patients continued
for up to four years after the head injury.
An interesting study of patients who suffered less severe head trauma
and were evaluated an average of ten years later, was performed by Dencker
in Sweden. These patients were twins, and the twin was used as control. She
failed to find any significant differences in intellectual, personality, EEG, or
performance between the “head injured” and the control groups.
Sequelae of Head Trauma in Childhood
The common neurologic and psychologic sequelae of head trauma may

be listed in six categories.
Motor and Movement Disorders
Focal damage in the pyramidal system gives rise to spastic hemiplegia
or hemiparesis. If the lesion is bilateral, quadraparesis results. If the lesion
involves the postcentral gyrus, sensory abnormalities result. Sensory
impairment is usually incomplete. Destruction of the extrapyramidal system,
such as the lenticular nuclei, may result in choreiform or athetoid movements,

tremors, and rigidity.
Posttraumatic Syndrome
The posttraumatic syndrome, seen so extensively in adults, occurs in
only about 1-6 percent of children following head injury. In children,
headaches predominate, with giddiness and aesthenia being quite rare. The
vast majority of patients with this syndrome have a self-limited course,
usually lasting less than six months. The very few cases which persist beyond
six months are usually early adolescents or preadolescents. The etiology and
pathogenesis of this syndrome is discussed earlier in this chapter (p. 171).
Posttraumatic Epilepsy
Posttraumatic epilepsy occurs in about 10 percent of children. The
lesions are usually located in the medial portion of the temporal lobe, the
posterior frontal, or the anterior parietal lobes. Those children who suffer a
seizure at the time of or very shortly after a head injury are not more likely to
have posttraumatic epilepsy. Even an EEG which shows epileptiform activity
soon after injury is an unreliable prognosticator, for over a period of several

weeks the epileptiform activity gradually disappears. If permanent seizures
occur, it is generally within the first two years after the acute head injury.
Minimal Cerebral
Dysfunction Syndrome
Although many patients recover full motor and sensory functions, they
may remain with signs and symptoms of minimal cerebral dysfunction. These
include hyperactivity, easy distractibility, short attention span, visual motor-

perception deficits, cognitive dysfunction, clumsiness, spatial disorientation,
and learning disability. This syndrome is discussed fully in Chapter 8. Suffice
it to say here that head injury is occasionally etiologic in this syndrome.

Caution must be shown in ascribing head trauma as the etiology in too many
patients with minimal cerebral dysfunction. Almost every child has had a
significant bump on the head at one time or another. This does not mean that
the etiology of the minimal cerebral dysfunction is necessarily related to the

head trauma.
Mental Retardation
Mental retardation resulting from head injury is a result of diffuse brain
injury. Generally, the more extensive the injury, the more severe the
retardation. There are usually associated motor and/or movement disorders

associated with the mental retardation secondary to head trauma. In these
patients the head injury is usually severe and the PTA prolonged.
Personality Changes
Occasionally children have profound changes in personality that are
beyond those which fit into the category of minimal cerebral dysfunction. In
addition to hyperactivity and short attention span they become aggressive,
destructive, lacking in judgment, and emotionally extremely labile. This can
be severely incapacitating to the child and his family. These children usually
respond poorly to psychotherapy and medication. It may or may not be
associated with motor dysfunction.
Natural History of Children Suffering Head Trauma
As mentioned previously, most children who suffer head trauma do not

show any adverse sequelae. When evaluating the patient who has deficits
(neurologic, intellectual, or behavioral), we must keep in mind the fact that
recovery can take place for a period of up to four years after the injury. This
means that we must not “give up” on a patient early or because he has severe
deficits soon after head trauma. For example, passive exercises to prevent
contractures should be continued. Educational and environmental

manipulation should be instituted when necessary. There should be frequent
reassessment because gradual improvement is the rule and what may have
been appropriate educational placement at the time of initial evaluation may
be inappropriate six or eight months later.
Finally, evaluation of therapy must be assessed in the light of the
spontaneous improvement. Heroic claims have been made for several
elaborate modes of therapy. They must be assessed with the natural history
of spontaneous improvement of head injuries in children in mind.
Bibliography
Adams, R. D. “Further Observations on Normal Pressure Hydrocephalus,” Proc. R. Soc. Med., 59

(1966), 1135-1140.
Adams, R. D., C. M. Fisher, S. Hakim et al.
“Symptomatic Occult Hydrocephalus with ‘Normal’ Cerebrospinal Fluid Pressure: a Treatable

Syndrome,” N. Engl. J. Med., 273 (1965). 117-126.
Barber, H. O. “Postural Nystagmus, Especially after Head Injury,” Laryngoscope, 74 (1964), 891-
944.
Brenner, C., A. P. Friedman, H. H. Merritt et al. “Post-Traumatic Headache,” J. Neurosurg., 1 (1944),

379-391.
Caverness, W. F. “Onset and Cessation of Fits Following Craniocerebral Trauma,” J. Neurosurg., 20

(1963), 570-583.
_____. “Post-Traumatic Sequelae,” in W. F. Caverness and A. E. Walker, eds., Head Injury Conference
Proceedings, pp. 209-219. Philadelphia: Lippincott, 1966.
Courville, C. B. Commotio Cerebir. Los Angeles: San Lucas Press, 1953.
Critchley, M. “Medical Aspects of Boxing, Particularly from a Neurological Standpoint,” Br. Med. J.,
1 (1957), 359.
Crown, S. “Psychological Changes Following Prefrontal Lobotomy. A Review,” J. Ment. Sci., 97
(1951), 49-83-
Dencker, S. J. “Closed Head Injury in Twins,” Arch. Gen. Psychiatry, 2 (1960), 569.
DeVivo, D. C. and P. R. Dodge. “Diagnosis and Management of Head Injury,” Pediatrics, 48 (1971),
129.
Foltz, E. L. and R. P. Schmidt. “The Role of the Reticular Formation in the Coma of Head Injury,” J.
Neurosurg., 13 (1956), 145-154.
Foltz, E. L. and A. J. Ward, Jr. “Communicating Hydrocephalus from Subarachnoid Bleeding,”J.

Neurosurg., 13 (1963), 546-566.
Freeman, W. and J. W. Watts. Psychosurgery, 2nd ed. Springfield, Ill.: Charles Thomas, 1950.
French, J. D., and H. W. Magoun. “Effects of Chronic Lesions in the Cephalic Brain Stem of
Monkeys,” Arch. Neurol. Psychiatry, 68 (1952), 591-604.
Friedman, A. P., C. Brenner, and Denny-Brown, “Post-Traumatic Vertigo and Dizziness,” J.

Neurosurg., 2 (1945); 36-46.
Gordon, N. “Post-Traumatic Vertigo with Special Reference to Postural Nystagmus,” Lancet, 1

(1954), 1126.
Heinz, E. R., D. O. Davis, and H. R. Karp. “Abnormal Isotope Cisternography in Symptomatic Occult
Hydrocephalus. A Correlative Isotope Neuroradiology Study in 130 Subjects,”
Radiology, 95 (1970), 105-120.
Johnson, J. “Organic Psychosyndrome Due to Boxing,” Br. J. Psychiatry, 115 (1969), 45-53.
Kilberg, J. K. “Head Injury in Automobile Accidents,” in W. F. Caverness and A. E. Walker, eds.,

Head Injury Conference Proceedings, pp. 27-36. Philadelphia: Lippincott, 1966.
Lindenberg, R. “Trauma of Meninges and Brain,” in J. Minckles, ed., Pathology of the Nervous
System, Vol. 2, pp. 1705-1765. New York: McGraw-Hill, 1971.
Mealey, J., Jr. Pediatric Head Injuries. Springfield, Ill.: Charles C. Thomas, 1968.
Miller, H. “Accident Neurosis,” Br. Med. J., 1 (1961), 919, 992.
Moniz, E. “Essai d’un Traitment Chirurgical de Certaines Psychoses,” Bull. Acad. Med. Paris, 115
(1936), 385-392.
Moritz, A. R. and W. B. Wartman. “Post-Traumatic Internal Hydrocephalus,” Am. J. Med. Sci., 195
(1938), 65-70.
Ojeman, R. G., C. M. Fisher, R. D. Adams et al. “Further Experiences with the Syndrome of ‘Normal’
Pressure Hydrocephalus,” J. Neurosurg., 31 (1969), 279-294.
Petrie, A. Personality and the Frontal Lobes, Philadelphia: Blakiston, 1952.
Phillips, G. “Traumatic Epilepsy after Closed Head Injury,” J. Neurol. Neurosurg. Psychiatry, 17
(1954), 1-10.
Rabe, E. F., R. E. Flynn, and P. R. Dodge. “Subdural Collections of Fluid in Infants and Children,”
Neurology, 18 (1968), 559.
Richardson, F. “Some Effects of Severe Head Injury. A Follow-up Study of Children and
Adolescents after Protracted Coma,” Dev. Med. Child Neurol., 5 (1963), 471.
Russell, W. R. “The After Effects of Head Injury,” Trans. Med. Chir. Soc. Edinburgh, 113 (1933-
1934), 129-144.
Russell, W. R. and A. Smith. “Post-traumatic Amnesia in Closed Head Injury,” Arch. Neurol., 5
(1961), 4-17.
Salmon, J. H. “Senile and Presenile Dementia. Ventriculoatrial Shunt for Symptomatic Treatment,”
Geriatrics, 24 (1969), 67-72.
Salmon, J. H. and J. L. Armitage. “Symptomatic Treatment of Hydrocephalus Ex-vacuo.
Ventriculoatrial Shunt for Degenerative Brain Disease,” Neurology, 18 (1969),
1223-1226.
Spillane, J. D. Five Boxers, Br. Med. J., 2 (1962), 1205-1210.
Steegman, A. T. “Dr. Harlow’s Famous Case. The Impossible Accident of P. T. Gage,” Surgery, 52
(1962), 952-958.
Stritch, S. J. “Shearing of the Nerve Fibers as a Cause of Brain Damage in Head Injury. A
Pathological Study of 20 Cases,” Lancet, 2 (1961), 443-448.
Symonds, C. P. “Concussion and Contusion of the Brain and their Sequelae,” in S. Brock, ed.,
Injuries of the Brain and Spinal Cord and Their Coverings, 4th ed., pp. 69-117.
Baltimore: Williams & Wilkins, 1960.
_____.“Concussion and Its Sequelae,” Lancet, 1 (1962), 1-5.
Symonds, C. P. and W. R. Russell. “Accidental Head Injuries: Prognosis in Service Patients,” Lancet,
1 (1943), 7-14.
Taylor, A. R. “Post-Concussional Sequelae. Br. Med. ]., 3 (1967), 67-71.
Trotter, W. “On Certain Minor Injuries of the Brain,” Lancet, 1 (1924), 933-939.
Vital Statistics of the United States, Vol. 2, Mortality, Washington, D.C.: Nat. Center for Health
Statistics, 1967.
Walker, A. E. Post-Traumatic Epilepsy. Springfield Ill.: Charles C. Thomas, 1949.
Chapter 8
Functional Disturbances In Brain Damage
Kurt Goldstein
Our knowledge of functional disturbances in brain damage is based on

the patient’s symptoms. Symptoms are modifications of behavior in various
performance fields. If one considers the symptoms as directly dependent
upon damage of the brain matter in various regions and as directly related to
defects in different performance fields, one can draw some conclusions about
the relationship between a disturbance of a particular performance and a

specific brain damage. Although the results thus reached are useful for
practical purposes, we learn little of how a lesion modifies the specific
function, and of the origin of the symptoms.
First of all, the pathological-anatomical picture seldom indicates the

degree of functional disturbance produced by the injury, since this depends
primarily upon the extent and intensity of the injury—factors which cannot
be correctly determined even by careful microscopic investigation.
Furthermore, the difficulty is increased by the fact that the kind of damage—
such as hemorrhage, tumor, inflammation, or intoxication—has a different
effect on the functional disturbance.
The question of the relationship between the symptom and the
disturbance of the brain matter’s function is by no means as simple as has
often been thought; indeed, one can say it has become increasingly
problematical. The main difficulty consists in determining which of the
observed phenomena are actually directly related to the defect of the brain—
a question which is, as yet, far from clear. Increasingly, we have learned that,
when we refer to disturbance of performance caused by a brain lesion, we
must consider not only the disturbed performance but all the observable
modifications of the patient’s behavior. We know from Jackson’s distinction

between different groups of sequelae of brain damage (see p. 183), that this is
a very difficult task. When one further realizes that, in a brain lesion, the
symptoms can differ because of various conditions of the whole organism,

and that they may become understandable only as phenomena depending
also upon the organism’s general condition, it is doubtful whether one can
speak of symptoms as caused by brain lesion alone, or whether one can do so
only in an abstract, theoretical consideration of the facts.
As clinicians, we cannot be satisfied with merely theoretical

interpretations of the symptomatology—interpretations based not on clinical
experience but derived from studies in normal physiology and psychology—
as has frequently been tried in the past. We have to try to reach a better
understanding of the functional disturbances in brain damage by taking into
consideration all that we observe about the patient, his whole behavior at a
given moment, especially its deviation from the norm. This is what I consider
to be my task in this presentation.
The material available for this procedure is so vast that to discuss a
considerable part of it here would be impossible. I shall therefore try to show,
by use of typical examples of symptom complexes, which factors must be
considered for an understanding of the structure of symptoms in brain
damage, thus enabling the reader to apply our results to other symptom
complexes.
Previous Views Regarding Brain Damage
Until recently, the symptoms observed in damage of the brain cortex
were considered to be expressions of a loss of so-called “images,” the
aftereffects of previous experiences deposited in different circumscribed
regions of the brain cortex, according to the different performance fields. It

was also postulated that the symptoms could not result exclusively from the
effect of these circumscribed defects—that additional factors must be
involved; only thus could the variations, the alternation between normal and
abnormal reactions of the patient in seemingly the same task, be understood.
These other modifying factors were considered to be “general mental
capacities” such as attention, memory, interest, and emotions. The additional
factors were brought more or less into relationship to localized or general

brain functions. The influence of the atomistic theory of brain function was so
great that one overlooked the fact that, by introducing these general
functions, nothing was gained. As a matter of fact, closer observation showed
that these “general functions” varied in the same way as did the single
performance. Attention, for instance, may seem to be sometimes grossly
disturbed, and yet the same patient, under other conditions, may appear
attentive or even abnormally so (see Goldstein, p. 249). Thus we found

ourselves in the same situation as before when we tried to understand the
variations of the phenomena by assuming the influence of such general
functions.
Today it is hardly understandable that the solution to the problem was

not discovered earlier, namely: to consider the symptoms not only in relation
to the dysfunction of limited parts of the brain but in relation to the individual
in whom they appear; in other words, to consider them as performances of
the sick individual. The concentration of study not on the single symptom but
on the behavior of the total personality of the patient, during examination and
in everyday life, made it more and more evident that the symptoms could
only be correctly evaluated if one considered them in relation to the condition
of the total psychophysical personality. This instigated an intensive study of
each single symptom in relation to the behavior of the total patient at a given
moment, which, in turn, became the point of departure for the concept of the
so-called organismic approach to psychopathology in general (see in regard
to this, Goldstein). It is this organismic approach which is the basis for this
presentation.
The new approach was not the result of a new theoretical concept but
the outcome of better observation and investigation. Closer scrutiny led to the
concept that the symptoms are consequences of the sick organism’s struggle
with the demands of the tasks confronting it; in other words, symptoms are
forms of behavior by which the individual tries, in spite of his defect, to come
to terms in the best way with the outer and inner world. The approach grew
out of the necessities of neuropsychiatric practice, out of the task of retraining
a great number of young men with brain injuries and different mental defects
with which we were confronted during and after World War I, and out of the
recognition that the psychopathological theories prevailing at that time, and
the methods of training based on them, were insufficient to fulfill the task.
There was an urgent need to find a more successful interpretation of the

phenomena, particularly so because the subjects with whom we were dealing
could not any more be considered as interesting objects for theoretical
studies, as was often the case in psychopathology in earlier times. The
disastrous condition of the young men confronted us with a strong challenge
to help them in every way possible. The approach became particularly
promising after the analysis of the symptomatology of a great number of

patients with various brain injuries had revealed another point of view in the
consideration of organismic life in general and of man’s in particular, namely:
that the basic motivation of the living being is to realize its own nature; that
is, to realize all its capacities to the highest degree possible in a given
situation. By applying this viewpoint, many seemingly contradictory
symptoms became understandable, and much better results of retraining
were achieved.
The structure of the organismic approach will become clearer when we

consider individual symptoms in brain damage. We shall see, then, that
phenomena which were once considered to be different, isolated defects
appear now to be simply different expressions of the same brain damage

under different conditions of the whole organism.
Before entering into the subject, I want to make a few general remarks
about the period in which the organismic approach originated and the place
of this new approach within the ideas of that time. It was related to the new
“holistic” orientation in physiology and medicine in general, which finds its

expression in such a saying as, “There is no sickness—there are only sick
human beings.” I refer in this connection to a congress held in 1932 under the
topic Einheitsbestrebungen in der Medizin,’’ where men famous in anatomy,
physiology, and different fields of medicine came together to discuss this
question with great enthusiasm.
While the new approach brought deeper insight into the function of the
organism and a better understanding of pathological phenomena, it

confronted us with a number of new methodological problems. When one
considers each symptom as dependent on the condition of the entire
organism, great difficulty arises in determining the relationship of a symptom
to the specific brain damage. This particular problem had been seriously
considered fifty years before by the famous English neurologist and
psychopathologist, John Hughlings Jackson, who reached a general point of

view in psychopathology to which ours bears much similarity.
Jackson, as an outgrowth of his experiences with aphasic patients,
emphasized that psychopathological phenomena can be understood only if

one gives up the theory of images, and he stopped considering disturbances
of images in brain defects as causes of symptoms. He believed that, in order to
understand psychopathological phenomena, one has to begin by analyzing the

modification—due to its damage—of the function of the brain, and by
considering the different symptoms of aphasic patients as expressions of a

disintegration of the brain matter; expressions of a lowering of the function of
the brain to a level where automatic and emotional reactions still are
possible, while the highest function, the propositional symbolic function, is
more or less lost.
Jackson’s ideas were so far ahead of his time that he found little
approval. In the famous discussion between him and the French neurologist,
Broca, at the British Association for the Advancement of Science in London in

1868 in which both men defended their contradictory theories about the
function of the brain, Broca emerged as victor; afterward, Jackson had little
influence on the work in psychopathology. Although some great men in the
field at that time, A. Pick, C. von Monakow, Adolf Meyer, and others, stressed
Jackson’s great significance, referred to his ideas, and used them in their
work, he was nearly forgotten for a long time. He had to be newly discovered.
This rediscovery occurred during the period referred to previously when
clinical practice demanded better procedures for helping brain-injured
soldiers in England. It was the English neurologist, Henry Head, who based
his treatments on Jackson’s ideas and demonstrated their fruitfulness for
understanding much of the aphasic symptomatology and for its treatment. A

little earlier, other unbiased studies by Storch, Heilbronner, Pierre Marie,
Lotmar, Boumann, Gruenbaum, Woerkom, and K. Goldstein, influenced more

or less by Jackson, gave different new interpretations of psychopathological
phenomena which can be considered as precursory to the organismic
approach.
By stressing the organismic approach as the best one for an

understanding of the symptoms in brain damage, I do not want to imply that
this approach has found full acceptance. Although a considerable amount of
psycho-pathological research is more or less influenced by it, certain men

prominent in the field are strongly opposed to it, for example, in this country,
Nielson and some others.
Adherents to the older “classic” theory, founded on associationism and

the assumption of isolated, circumscribed disturbances, base their opposition
primarily on the argument that the new approach is too general and does not
therefore do justice to the problem of localization, and, even more important

in respect to the problem with which we are dealing here, to the great variety
of modifications of performance of the brain-damaged patient.
As to the opposition concerning the problem of localization, I would like
to point to various papers of my own, particularly the presentation of the

subject in the German Handbuch der normalen und pathologischen Physiologie.
There I have shown that this problem is by no means neglected by the new
approach; moreover, that the approach put it on a more realistic basis, so that
many mistakes originating from the old concept can be avoided.
Proof that the new approach emphasizes the great variety of symptoms
and the problem of understanding them will become apparent when we now
discuss the symptomatology of patients with severe damage of the brain
cortex.
Effect of Impairment of the Abstract

Attitude Owing to Brain Damage
I shall not start with a description of patients with defects in special
performance fields, such as speech, motility, vision, sensation, etc., but with
patients who show disturbances in all these fields in such a way that some
performances in each field are impaired and even lost, while others seem
relatively well preserved. This clinical picture occurs particularly in severe
lesions of the frontal lobes or in diffuse damage of the brain cortex by injury
or intoxication, in general paresis, etc. It can be shown that the complex and
outwardly very inconsistent symptomatology of the patient can be

understood as an effect of the damage to a special mental capacity which we
call the abstract attitude. Before going into this matter, it seems necessary to
make some remarks concerning the concept of the human mind which
underlies this interpretation.
The normal individual displays two kinds of attitudes toward the world
—the concrete one and the abstract one. In the concrete one we are given
over passively and bound to the immediate experience of the very things or
situations in their uniqueness. Our thinking and acting are determined by the
immediate claims made by the particular aspect of the object or situation. For
instance, we act concretely when we enter a dark room and turn on the light
switch. If, however, we refrain from turning the switch, reflecting that we
might awaken someone asleep in the room, then we are acting abstractly. We
transcend the immediately given aspect of sense impressions, we detach
ourselves from the latter, and consider the situation from a conceptual point
of view, reacting accordingly. The abstract attitude corresponds
approximately to what Henry Head has called—in relation to speech —
symbolic behavior.
The healthy individual is able to shift voluntarily from one attitude to

the other, according to the demands of the situation. Some tasks can be
performed only by virtue of the one, some only by virtue of the other attitude.
For the beginning of any activity, the abstract attitude is a presupposition.

During activity, the concrete attitude is often dominant, but, should the course
of action be interfered with or disrupted, abstraction is required to correct

such disturbances and to continue the activity properly.
Patients with impairment of abstract attitude may not appear to deviate
grossly from normals in everyday behavior, because many routine tasks do

not require the abstract attitude once these tasks have been set going. During
observation of the patient in a variety of situations, however, it becomes
evident that he does not react like a normal individual; he appears more
stereotyped and reserved. He seems to lack initiative and spontaneity. Tasks
which demand choice or shifting particularly reveal the defect.
From analysis of the behavior of a great number of such patients in
various everyday and test situations, we have compiled a list of modes of

behavior in which the performances are disturbed owing to impairment of
the abstract attitude.
The patient fails if he has:
1. to assume a definite mental set;
2. to give an account to himself for acts and for thoughts;
3. to shift reflectively from one aspect of a situation to another;
4. to keep in mind various aspects of a task or of any presentation

simultaneously;
5. to grasp the essential of a given whole, that is, break it up into

pieces, isolate them, and synthesize them;
6. to abstract common properties reflectively;
7. to perform concepts, symbols, to understand them;
8. voluntarily to evoke previous experiences, for example images;
9. to assume the attitude toward the “merely possible;” and
10. to detach the ego from the outer world or from inner experiences.
It has often been said that the defect of the patients consists of an
inability to cope with new situations, but that they are able to proceed in an
abstract way as far as old experiences are concerned. The fact, however, is
that patients fail equally in familiar situations and in new ones, if the
situations demand the abstract attitude. On the other hand, they can cope
with new tasks successfully, but they can do so only as long as these do not
require the abstract attitude. Indeed, patients are more likely to fail in new
situations rather than in old ones because the former frequently demand new
sets, in other words, the abstract attitude.
The analysis of many patients’ failures in different tasks has shown that
a great number of symptoms are explainable as the result of this one defect
and that in the same way the variations of the patients’ reactions in
apparently the same task can be so explained. If the patient seems to be

successful at one time and fails at another, this seeming inconsistency is
resolved when we realize that the tasks which appear equal to us may (as a
result of the disturbance of this function) not be at all the same for the
patient. The following example may illustrate this. If we present to the patient
an angle built of two little sticks, with the opening downward, and ask him to
copy the presentation after it is removed, he produces the angle correctly. If

we present the same angle with the opening upward, the patient, after the
angle is removed, is not able to produce it. For us, the angles are not different;
for him, they are not only different, they have nothing in common. He says
that the one (with the opening downward) appears to him like a roof; the
other structure does not mean anything to him. His correct response was
determined by the fact that the first structure appeared to him as something
which corresponds to concrete experience; he failed with the second

structure because this was not the case, because he could not assume the
abstract attitude which is necessary to fulfill this task.
This is one of numerous examples which definitely show not only that
the patient can react only to (for him) concrete conditions, but also how
careful we should be in our interpretation, since the task set before the
patient may to him appear totally different from the way it appears to us.
A few further examples from different performance fields may illustrate
the failures due to impairment of abstract attitude. Just as the patient cannot
deal with figures when they do not represent concrete objects, he fails further
when he is confronted with ideas, thoughts, and feelings when their handling
presupposes abstract attitude. He is unable to shift from reciting one series

(for instance, numbers) to another (days of the week), because active shifting
is impossible for him. He can follow or even take part in a conversation about
a familiar topic or a given situation, but if he has to shift to another topic—
even one equally familiar—he is at a complete loss. He may be able to read a
word and, at another time, spell it, but when asked first to read and
immediately afterward to spell, he is unable to do so. The patient’s speech in
everyday life may not show much deviation from the norm. He may in certain
situations have a great number of relevant words at his disposal; this is the
case when the words belong concretely to the situation. He will fail
concerning the same words, however, when the situation demands that he
consider their meaning. His words fit only definite concrete situations. He
cannot understand that the same word can have different meanings. In
respect to learning, he has the greatest difficulty in rote learning and very
quickly forgets what he has learned. The same difficulty exists in the behavior
of the patient with regard to practical activities, such as handicraft and labor.
(Concerning the symptomatology of such patients, see.)
I would like further to mention two important general points. The first
is that loss of abstract capacity cannot be regained by retraining. Only

improvement of the brain damage may more or less restore the impaired
capacity. The second point is that there are different degrees of abstract
behavior, depending on the extent of conceptional complexity which the
performance in question involves. Thus the patient may be able to fulfill some
performances which need abstract consideration. The highest degree of
abstract behavior is required for the conscious and volitional act of forming
generalized concepts or for thinking in terms of a principle and its
subordinate acts and verbalizing these acts. Similar abstract behavior is the
act of consciously and volitionally directing and controlling every phase of a
performance and of accounting for it verbally.
A lower degree of abstraction is necessary in volitionally planning an act
or series of acts without distinct awareness of or self-accounting for every
phase of its further course. In some performance, as in intelligent behavior in

everyday life, only the directional act is usually abstract, and the ensuing
performance follows a concrete plan. Here the patient may be successful until
difficulties arise. He may fail when the required shift demands the abstract,
anticipatory deliberation. It is apparent that only careful analysis of each
performance in respect to the degree of abstraction required for execution
will allow us to decide whether or not the patient is disturbed. The decision is
easiest if some tests which have been constructed for this purpose are used.
We are inclined to believe with Jackson that the abstract capacity, the
symbol function, being the expression of the most complex function of the
brain, suffers first in damage to the brain cortex, while isolated lesions in the
motor and sensory areas show only damage of the concrete performance
“instrumentalities” (see p. 188). Not infrequently, the symptomatology
consists of a mixture of damage to both parts, although the damage may not
necessarily be equal in both. Thus we can get very complex clinical pictures.
The opponents to the organismic approach stressed that it took into
consideration only symptoms belonging to the higher level, the abstract
attitude. This criticism may appear to be justified, since some authors
mentioned only these disturbances in aphasic patients, because they

considered aphasia an expression of a damage of symbolic function or
“intelligence.” This holds true, for example, for Pierre Marie, Ludwig
Binswanger, and Kronfeld and Sternberg. It is, from the organismic approach,
not at all appropriate, however, to omit the symptoms belonging to defects in
the lower-level function, the so-called motor and sensory instrumentalities,
which are necessary for realization of the symbolic function in the

performances of the organism. The very complex picture which aphasia
represents, in which motor and sensory disturbances of letters, words, and
other features of language not dependent on the defect of the symbolic

function are often so completely mixed with those which are dependent on it,
gives all the more reason to study carefully the structure of all abnormal
phenomena. Otherwise, one cannot reach a correct conclusion as to the origin
of the clinical symptoms. This is all the more necessary since defects in the
instrumentalities secondarily influence the use of the symbolic function. Only
by analysis of all symptoms can one clarify what is primarily due to the latter.
Indeed, even Jackson showed insufficient interest in the effects of
disturbances of the “instrumentalities,” in the destruction of single words and
letters, in the disturbances of grammar, of the finding of words, and of
sentence formation which are related to dedifferentiation of the function of

the motor and sensory apparatuses.
The problem of the relationship between the disturbances in damage of
the instrumentalities of language (the instrumentalities belonging to the
concrete forms of behavior, see Goldstein, p. 163) and those due to damage of
the symbolic function interests us, particularly, because clarity concerning

this relationship is essential for correct evaluation of the symptoms not only
in aphasia but in all performance fields.
Jackson did not sufficiently evaluate the disturbances of the
instrumentalities, because he considered the separation between the higher
and lower functions of the brain cortex to be too absolute. There is no doubt
that the processes in the higher and lower levels of the brain are, to some
extent, associated; both belong to the “mental apparatus.” The organismic
approach assumes that any damage which concerns one part of an apparatus
changes the function of the rest of the apparatus as well; the “parts” can be
considered as only artificially separated “parts” of a whole. This is the case in
the connection between the lower- and higher-level functions of the brain
cortex. Under normal conditions all performances are determined by a
working together of both functions as a unit. Under certain conditions,
performances come into the fore which are related to the one level; under
other conditions, those which are related to the other level. Such a
preponderance of behavior related to one level exists if this level is important

for the self-realization of the individual in a particular situation. Thus, for
instance, if an individual is thinking with concentration, the concrete world is
more or less forgotten; it is, so to speak, in the background (see p. 109). The
opposite holds true when an individual is totally involved in concrete

behavior. The various abnormal performances correspond to the different
ways in which the union of the two functions is impaired.
Jackson speaks of a disintegration from the voluntary to the automatic-
emotional level. He goes so far in his separation of the two levels that he
assumes, concerning language, that the lower-level activities are related to
the “inferior” hemisphere, the right one, while the symbolic function is
connected with the “superior” left hemisphere, an assumption which is not in

accord with the newer concept of localization. Indeed, Jackson has stressed, in
general, the modification of the function of one apparatus owing to damage of

another one connected with the first one. On this concept is based his
distinction of positive and negative symptoms; the negative ones are an

expression of the direct damage of an apparatus, the positive ones the effect
of the modification of the function of an apparatus due to another one to
which it is related. But he did not come, in my opinion, to a correct conclusion
regarding the function of the lower-level apparatus separated from the
function of the higher one in disintegration of brain function. He assumed that
defects in the higher level did not alter the behavior related to the lower level,
in so far as the lower level continues to remain “integrated.” We assume, too,
that impairment of abstract attitude is an effect of a dedifferentiation of brain
function, a reduction of the most complicated function to a simpler one;

however, this does not imply that the undamaged lower-level apparatus
remains unmodified in its way of functioning. Phenomena belonging to the
lower level do not remain fully integrated, and the preserved automatic and
emotional performances of the patient do not simply represent the effect of
the lower-level function as it existed before. It is not enough to say that the
function of the brain is reduced from a level corresponding to the voluntary

activities to a lower one corresponding to emotional and automatic
performances. The character of this reduction, of this modification of the

brain function, has to be considered if one wants to understand behavior on
the lower level in all its details. Neither the automatic nor the emotional
reactions of patients with impairment of abstract attitude appear, on closer
investigation, “normal.”
The Automatisms in Damage of the Higher Level of Brain Function
The automatic reactions in damage of the higher level of the brain
function show definite deviations from the norm. They do not come so easily
into action. Conditions in the outer world or within the individual, which
usually instigate them, must now be present in a very “adequate” way; in even
small deviations from the familiar conditions, the learned automatisms do not
occur. So, for instance, it is not enough to ask the patient to utter the (very
automatized) series of numbers; the first numbers often have to be presented

orally; only then is the patient able to speak the rest of the series correctly. If
the patient is interrupted at any point in the procedure, he will not be able to
continue, as a normal person would. These and many other phenomena not
only show that the automatisms also are functionally modified in damage to
the higher level, but also point to the fact that the automatisms are normally
closely related to the higher level, more closely than one usually assumes.
The observable modifications of the automatic reactions are not fully

explainable by the assumption of a lack of the influence of the higher-level
function; only when one considers them as a change in the normal

relationship between the figure and ground in the unit they represent can
they be understood. Every process in a stimulated area is accompanied by a
definite excitation in the part of the organism not directly stimulated. We call
the excitation in the stimulated area the figure and the excitation in the rest of
the organism the ground. All performances of the organism, as well as all
experiences, are so organized. Figure and ground are intimately
interconnected; to every figure belongs a definite ground. The phenomena
corresponding to either one can be properly evaluated only by considering
the other as well. What is meant by figure and ground is most obvious in
visual experiences; however, all other experiences and performances, such as
motor reactions, speaking, thinking, feeling, etc., are organized in a similar
way. To this organization of the performances correspond equal

organizations of the physiological processes in the nervous system.
All damage to the nervous system, especially brain damage, disturbs the
figure-ground organization in general or in a part which belongs to a definite
performance field. The sharp differentiation of figure from ground suffers,
including a general leveling or intermingling of the phenomena belonging to

figure and background. This can, at times, be carried to the point of inversion,
so that what normally is figure becomes ground, and vice versa. We expect a
definite figure as reaction to a definite stimulation, but the patient may

respond according to the background. This change of the normal figure-
ground organization is the basis of a great number of symptoms in damage of
the nervous system and in neuroses and psychoses. It is clear that reactions in
isolated parts will be deprived of the influences of the normal figure-ground

organization which goes on within them, and that they will thus be changed,
particularly in respect to their contents. Normal figure-ground organization
is, like all performances, dependent upon processes belonging to the higher
level as well as to those within the realm of the instrumentalities. It is
determined by previous experience, by memory. Furthermore, one has to
consider that figure-ground organization in one field is related to the figure-

ground organization which the whole organism represents.
In all performances the whole unit is in action. According to the
significance of one or the other part for the performance, this part is in the
foreground, but the performance is correct only if it occurs in correct
relationship to the background which the other part represents—which

changes according to the demands of a definite task. If the lower-level
function is somewhat separated from the higher-level function, this will come
to the fore in modifications of the automatisms, according to the significance

of the higher-level function in preserving the relationship of the two levels for
definite tasks of the organism—in some tasks more, in others less. Thus the
patient’s difficulty in starting an automatic series shows that, for the setting in
motion of an automatism, some higher-level function (I would say some
abstract attitude) is necessary. What has taken place following disintegration
of the brain function is a damage of the normal figure-ground relationships
between the two levels, which may be observed in variations of the automatic
activities under various conditions of the whole organism, by which the
figure-ground relationship is determined. Normally, this figure-ground
relationship exists which makes possible the fulfillment of the task to which
the organism is exposed. After damage to the higher level function, the figure-
ground organizations are disturbed—the most complicated ones more than
the simpler ones. This shows that the automatisms are, in general, effective,
but they are not normal, being modified by the disturbance of the more
complicated figure-ground configurations in the disintegration of the brain
function involved.
This interpretation of the automatic performances in disintegration of
the brain function corresponds to the general explanation of the automatisms

and reflexes, to concrete behavior in general, which I have given on another
occasion (see Chap. 5). I tried to show that these phenomena are not the
effect of isolated processes in the organism but represent figures in

organizations of the whole organism which differ from those in normal
performances only in the special form of the organization.
There is another factor which brings us further understanding of the

modification of the behavior in damage of abstraction: the influence of
isolation of the lower level in its function. The change of the function of one
part of a unit owing to its separation from another part cannot be considered
alone as the effect of a lack of influence of one on the other. The effect of
isolation itself modifies the function of the separated part. Consideration of

this factor has proved to be of the greatest significance for understanding
many symptoms in pathology. It has shown that the modification follows
definite laws which are equally discernible in each performance field which is
in a state of isolation. The modification by isolation concerns particularly the
dynamics of the processes. We shall consider them in more detail later, when
we take up symptoms which are the effect of direct damage to the
instrumentalities (see p. 195).
Emotional Reactions in Disintegration of the Brain Function
For Jackson, the paradigm of the lower-level function was emotional,

interjectional speech which is usually fully preserved in damage to the higher
level, the symbolic function. Concerning this preservation of emotional,
interjectional speech, we are confronted with a more difficult problem than in
the automatisms—owing to the uncertainty of opinion about the nature of

emotions. Jackson was inclined to consider emotional reactions as belonging
to the same category of behavior as the automatisms, and thus to consider the
preservation of both in disintegration of brain function as equal phenomena.
It is doubtful whether it is justified to put the two groups of phenomena

under the same heading. Normally, they show a number of differences,
particularly a different relationship to the total personality and to the
symbolic function. Automatic phenomena represent part processes of the

voluntary activities and are dependent on them. They always occur under the
direction of the latter or under the direction of outer-world influences.
Emotional reactions are not voluntarily produced, but their connection with
the abstract attitude differs essentially from the connection of the automatic
activities with the latter. The emotional activities have something in common
with the abstract activities in that both represent attempts of the personality
to come to terms with the world, that both are emanations of a definite
attitude toward the world. The emotional attitude differs from the abstract
attitude, however, in that this coming together of personality and world is
more immediate, more in relation to the existence of the individual, while the
abstract attitude guarantees the organization of an ordered world separated
from the individual. Because of this close connection to the existence of the
individual, emotions play a particular role in all forms of self-realization and
occur in concomitance with, and not in dependence on, the voluntary

activities. One has often assumed that emotions are simply disturbing
phenomena. This is most certainly wrong. I would like to refer in this respect
to newer research published by Leeper and K. Goldstein. Success and failure
in all performances are accompanied by definite emotions. Which kind of

emotion arises depends on the implications of the situation with regard to the
individual’s way of realizing his nature in a particular case. The correct

emotions—that is, those which help to achieve self-realization—are of great
significance for executing correct performances.
The emotions are complex phenomena; they consist of inner
experiences which are not conscious in the usual sense of the word, but of
which we are well aware (see in regard to this Goldstein, p. 34). They consist
further of activities by which they are “actualized”—movements of the face
and body, the so-called expressive movements of different kind; of linguistic
utterances such as interjections, sounds, words, and sentences which are
brought to the fore in characteristic intonations; and finally of physiological

processes in the vegetative nervous system.
What has been called emotional language represents the linguistic part
of the motor activities (instrumentalities) belonging to emotions. The
activities in emotions—and so also the linguistic phenomena—are based on
innate mechanisms acquired in experiences related to the world in general,
and most particularly in relation to other human beings. These motor
phenomena correspond to the other automatisms in so far as they are

concrete activities and come to the fore in emotional situations, as the
automatisms do in voluntary activities.
From this aspect it seems incorrect to speak of emotional language; it

would at least be less prejudiced to speak of linguistic means, linguistic
instrumentalities for realizing the emotional attitude which a situation
provokes. They represent special linguistic phenomena, but they are not
different in principle from those instrumentalities which are used in abstract
attitude. Emotional language is a special, not a more primitive, form of
language. The emotional attitude is not a more primitive attitude than the
abstract one; it differs from it by another kind of relationship to the total
personality, a closer one. It seems appropriate to assume that the greater

significance of emotions for the existence of the personality in the world
makes the substrata underlying them more resistant to damage of the brain
function. It is for this reason that they are better preserved than those
substrata underlying the symbolic attitude.
From our discussion it seems that we are not justified in considering
that emotional reactions are equal to automatisms. We have mentioned that
the automatisms show modifications in impairment of abstraction. Does that
impairment not find expression also in differences between the emotional

reactions of the patient as compared to those of normal individuals? I think it
does. Clarification of this point seems to me important for a better
understanding of the abnormally frequent occurrence of emotional reactions

and their modifications in patients.
Considering the facts, we must stress the following: Emotional
phenomena usually are more predominant in patients with impairment of

abstraction than in normal people. Most probably the reason for this is that
the world of the patient, owing to impairment of abstract attitude, is not

organized normally and so makes many normal reactions impossible. The
patient, when urged to react, tries to do what he is able to do, and he is most
able to produce emotional reactions, and therefore also emotional language.
The emotional activities, however, occur not only more frequently than
normally but they are modified as well. They show the characteristics of
isolation (see p. 194); the isolation is due to the lack of the normal relatedness
to the reactions in the abstract world, by the impairment of the latter.
Thus we come to the following result: Preservation of the emotional
language is an expression of the preservation of emotional reactions; in
individuals with disintegration of the brain function, it is not—as is the case in
preservation of the automatisms—a direct effect of an inferior brain function
coming to the fore. Preservation of emotional reaction represents the
maintenance of this attitude of man toward the world, which, in normal man,
exists alongside the abstract attitude. Because the emotional attitude is more
closely related to the personality and more important for its self-realization, it
shows greater resistance toward damage of the brain function and thus may
remain undisturbed when the abstract attitude is disturbed. The emotional
instrumentalities are preserved in the same way as are the instrumentalities

in general in impairment of abstract behavior. This shows in the possibility of
using them in concrete behavior. The odd preservation of emotional language

does not present a special problem. Whether a patient is able to produce
language or not depends on the attitude under which such language is
demanded in a given situation, that is, whether the abstract one or the
emotional fits the situation. If the latter is the case, the patient will bring out
words; in the former case, he will not. This could be demonstrated by a great
number of examples which show that the patient is able to utter a word in an
emotional attitude but is not able to do so voluntarily, that is, in the abstract
attitude, even immediately afterward. One particularly instructive example
concerning a patient of Jackson may illustrate this. The patient responded to

the demand to say “no” by saying, “I cannot say ‘no.’ ” He was not able,
however, to repeat the word “no.” The speaking of the word “no” in the
sentence is not a voluntary act but belongs to the patient’s concrete reactions.
The repetition of the word “no” presupposes the voluntary attitude (see ref. p.
71) which he could not assume, therefore he was unable to say the word on
demand. From a superficial aspect this would seem to be a contradiction,

since the patient was able to say the word “no” with great emphasis when
asked to do something which he could not do, that is, when in an emotional
attitude. This seeming contradiction is resolved when we realize that the
words appear to be the same but actually are not the same, since they
represent totally different reactions of the whole organism. The patient was
able to utter the word only when the situation induced him to take an
emotional attitude. It is obvious that wrong interpretations of the patient’s
capacities can easily occur if this difference in attitude is not taken into
consideration.
I would like to mention, in the latter respect, another very instructive
example: it concerns the difficulty in finding words, particularly names of
even the most common objects. This is a very frequent symptom of aphasic
patients. No matter how similar, on face value, failures of the patients may
appear in respect to the finding of words, the defects can be due to a defect of
an entirely different function. In one kind of patient, the inability to name is
an expression of an impairment of abstraction; in another, it is a sequela of a

defect in the instrumentalities of language, a memory defect. The patients of
the first kind have not lost the words but are not able to utter them in naming,
because naming, as analysis has revealed, presupposes the abstract attitude.
The other kind of patients, with difficulty in finding the name, have no defect
in abstract attitude, but their instrumentalities of language are damaged, and
therefore they cannot find the words. Only when one considers the whole
picture which the patients present does the difference of the origin of the
symptom become apparent. As long as one pays attention only to the effective
reaction, as has often been done—in this case the difficulty in naming objects
—the underlying damage of the brain function may appear the same. This
fallacy occurs particularly if one records the results of examination by the
plus and minus method and considers the answers only in respect to success
or failure. This conclusion from the effective answer, without analysis of the
way in which the patient came to the answer, the “fallacy of effect,” is the
cause of many mistakes in the interpretation of psychopathological
phenomena and in the building of theories. It shows up particularly in failures
of retraining when the interpretation was wrong.
Similar observations, as we have mentioned, can be made not only
concerning the language of the patients but in regard to other motor activities
which belong to emotional situations. An example may illustrate this: The

patient was asked to behave as he would in a situation in which he became
angry with some one and was menacing him. He was not able to do so. When
we demonstrated such behavior to him, he began to laugh, apparently
perplexed, not quite sure what was meant. He was not able to perform the
action on demand. But, observed in a situation in which he actually got angry,
he behaved instantaneously like a normal individual as shown by the
expression of his face, the action of his fists, etc. This example points to the
important difference which often exists between the patient’s behavior
during special examination and during everyday life. Observation under the
latter condition, so often neglected, deserves the greatest attention.
Symptoms Due to Direct Damage of the Instrumentalities
Up to now, our description of symptoms in damage of the brain cortex
was concerned with effects due to disintegration of the brain function from
the higher-level function to the lower one. We have discussed symptoms

caused by impairment of the higher-level function, the abstract attitude, and
have discussed the effect of the impairment of the abstract attitude on the
lower-level function, the motor and sensory activities, the so-called
instrumentalities, by which the higher-level function is actualized.
At this point we shall consider symptoms which are the effect of direct
damage to the instrumentalities. We have to restrict ourselves here to a
survey of the different ways in which damage of the function of the brain,
concentrated in definite regions, is revealed in modifications of normal
behavior. From this point of view, we have to classify the symptoms into two
main groups.
Symptoms which Represent Direct Sequelae of Damage to the Substratum of a

Definite Region
These sequelae rarely take the form of complete loss of a performance;
more commonly, the performances affected undergo modifications. Such

modifications can be considered as a result of a systematic disintegration of
the concerned function. Structurally, this disintegration invariably exhibits
the same features, regardless of the region involved, be it the spinal cord or
the subcortical apparatus, and regardless of whether it concerns reflexes,

motility, sensation, speech, thinking, or feeling. A particularly important
consequence of this dedifferentiation is impairment of abstract attitude and
abnormal concreteness of behavior, about which we have spoken before.
All direct damage causes a rise of the threshold and a retardation of
excitation. The receptivity of the patient is reduced in the involved sense
organ. It takes him much longer to react. This manifests itself in the fact that
patients may succeed perfectly in a task when they are given a sufficiently
long time of exposure but fail in the same task when given only brief
exposure, for example, when examined by the tachistoscope. (The
tachistoscope is an instrument which allows exposure in different short

lengths of time.) Pathology consists of a slowing down of the physiological
process.
The patient may perceive when the stimulus is strong enough and
presented long enough, but he may cease to see it after a certain time, in spite
of continued stimulation. Later, the sensation may appear again; it seems that
the threshold changes during stimulation. This is also true in stimulation of
normal individuals, but it is far more apparent in brain damage.
When excitation takes place despite obstacles, it spreads abnormally
and remains effective an excessively long time. This is due to disturbance of
the process of “equalization” by which the effect of the stimulation is

regulated (see Goldstein, p. 113). Examples here are phenomena such as tonic
innervation, repetition of the same movements, reiteration in reflexes
(clonus), etc. A word grasped with great difficulty by an aphasic patient sticks,
perseverates, and influences subsequent performances.
Another characteristic effect of the damage is the fact that performances
are determined to a much greater extent than normally by stimulating
influences, external or internal. We call this abnormal stimulus
responsiveness.
Symptoms Due to a Separation of an Undamaged Area from a Damaged One
By such separation or, better, “isolation,” the function of the undamaged

area, and thus the performance, is modified in a definite way. The pathology
can consist in an isolation of parts of the unit which the organism as a whole
presents and an isolation of the subunits corresponding to definite
performance fields. Isolation can occur in gross anatomical separation or in

functional separation; it can also occur in psychological conditions.
It seems useful to give here a brief summary of the functional changes
caused by isolation (see Goldstein, p. 133). The reaction appears modified in

the following ways:
1. The effect of an adequate “stimulus” is abnormally strong.
2. The effect of an adequate stimulus is of abnormal duration.
3. The reaction is abnormally influenced by inadequate stimuli,

external or internal. It is abnormally “stimulus bound.”
4. The individual is forced to react. He appears to be easily fixated
when his reaction to the present stimulus is completely
successful. If his reaction, however, is not fully successful, he
seems to be forced to react to another present stimulus. If,
now, the correct reaction takes place, fixation will set in; if
the correct reaction does not take place, the patient will
again be forced to react to still another stimulus, etc. Thus he
may appear very distracted. The patient seems to be driven
to achieve an “adequate” reaction by which the entrance of
“catastrophe” is eliminated (p. 197). Fixation and
distractibility appear so as the two results of the same defect
under different conditions.
5. As a result of loss of the normal influence of the rest of the

organism on the activity in the isolated part, the reaction
appears to be lacking special contents. It appears, or actually
is, more “primitive” because it lacks properties belonging to
the “nature” of the individual. The degree of primitivity and
diminished appropriateness depends on the place and extent
of the isolation, on how large a part of the whole organism is
excluded from cooperating in the reaction (see p. 148 ff.).
6. Isolation distorts the normal figure-ground organization which is of

essential importance for the outcome of any normal reaction.
All the factors mentioned above are responsible for occurrences of
abnormal performances, and all of them have to be considered in the
evaluation of any one symptom in damage of the brain cortex.
Symptoms Representing the Reaction of the Individual to the Defect
So far, we have discussed symptoms in brain damage only in their
relation to defects of structure and function of the brain. Our results were still
somewhat unsatisfactory, particularly in regard to understanding the
variability of the symptoms. We must try, therefore, to go a step further, to
regard the phenomena not only in their relation to the damage of structure
and function but in their relation to the reaction of the individual and of the
whole organism to the defect. Such a step corresponds to the procedure of the
organismic approach and often leads to a better understanding of the
patient’s behavior.
Systematic investigation of the patient’s general condition while he is
able to fulfill a task and when he is unable to do so reveals another fallacy,
which consists of only recording the effect of failure or success in the

performance. One observes, particularly in patients with impairment of
abstract attitude, that the patient, unable to fulfill a simple, seemingly
unimportant task, may be completely changed in his total appearance. The

same man who, shortly before, looked animated, calm, in good mood, well
poised, collected, and cooperative, while successfully fulfilling a task, appears
now to change color, to be agitated; he starts to fumble and becomes
unfriendly, evasive, even aggressive. This overt behavior is very reminiscent

of that of a person in a state of anxiety. The relationship of this general
condition to the capacity of fulfilling a task becomes particularly evident from
the fact that such a general condition can be experimentally produced, in
some patients, by presenting them with a task which we know they will not
be able to perform.
We call the state of the patient, when he is successful, an ordered
condition; the state in a situation of failure, a disordered or catastrophic

condition. In the latter condition the patient is incapable of performing tasks
in which he is usually successful, which he is able to do very well when in the
“ordered” condition. Such failure lasts for shorter or longer periods of time.
One observes frequent catastrophic conditions, particularly in patients with
impairment of abstract capacity. Since an individual with such impairment is
unable to account to himself for what he is doing or experiencing we assume

that he is not aware of his failure; as a matter of fact, he is unable to say, when
questioned about it, whether or not he has been confronted with something
frightening. Hence we come to the conclusion that the catastrophic condition

is not a conscious reaction to the failure but, rather, belongs intrinsically to
the objective situation of the organism in failure.
Even the smallest failure may have this effect on these patients, since
they are unable to decide which failure might be dangerous for them and
which might not. They are, so to speak, always endangered whenever their
reaction is not adequate. Thus any objective failure can bring the organism
into disorder, into catastrophe, into anxiety.
I cannot, in this presentation, discuss the consequences of our

description of these phenomena for a theory of anxiety (see Chap. 7). Here,
we are interested only in the symptoms which these patients show, owing to
the occurrence of anxiety, which are not directly related to the damage of the
brain. If we do not pay attention to this, we may be deceived about the

patient’s brain defect and may consider symptoms as being related to it, when
actually they are not. Consideration of the phenomenon of catastrophe
explains the variability of symptoms under similar conditions.
One factor which is apt to modify the symptomatology considerably is
the development of protective mechanisms by which the occurrence of
catastrophes is eliminated or at least reduced. It is easy to understand that all
patients, when they do not essentially improve, have the greatest desire to get
rid of the anxiety, for otherwise they are prevented from using even their
preserved capacities and thus from coming, at least partially, to a state of self-
realization.
We realize that patients with even severe brain damage and impairment
of abstraction show, after a certain time, a diminution of the disordered
behavior, of catastrophic conditions and anxiety, and yet, examination reveals
no change whatever in the damage to their mental capacities. In such cases
this can occur only if the patient is no longer exposed to tasks he cannot cope
with, or is able to take the failure without reacting with catastrophe.
Concerning the first point, observation of his behavior in everyday life reveals
that he lives apparently in a modified environment, an environment from
which far fewer tasks arise which might lead to catastrophes. How does such
modification of environment take place? Observation shows that the patient
is withdrawn from the world around him so that a number of stimuli,
including dangerous ones, do not arise. He avoids company. He is as much as

possible doing something which he is able to do well. What he is doing may
not have any particular significance for him, but concentration on activities
which are possible for him makes him relatively impervious to dreaded
stimulation. Particularly interesting is his excessive orderliness in all

respects. Everything in the surrounding world has a definite place. Similarly,
he is very meticulous in his behavior as to time, whereby the determination
as to when he should do something is related to events and to activities of his

which always occur at the same time, or to a definite position of the hands of a
clock. This orderliness enables him to prevent too frequent catastrophes.
Another interesting protective mechanism is unawareness of the defect.
We observe this particularly in patients with impairment of abstract attitude,
but also in patients who are incapacitated in a special performance field

without mental damage, for instance, in severe hemiplegia. This symptom,
called Anton’s symptom, described first by Anton in 1899, occurs particularly
when the incapacitation is total (see p. 38), so severe that the patient is not
able to use the disturbed capacity at all. The symptom may not take place if
the defect is partial and if the patient is able to use the capacity at least to a
certain degree, for example, if he can move his paralyzed leg somewhat. This
protective mechanism has been described as denial, a procedure which would
demand a somewhat conscious activity. I do not think that such an

interpretation is correct. Certainly, it can be rejected as far as it applies to
patients with impairment of the abstract attitude, who are, owing to this
defect, unable to do anything voluntarily. Whether the phenomenon becomes
more understandable if one ascribes to it unconscious influences is doubtful. I
think it is sufficient to consider it as an effect of a new organization of the
behavior of the organism, which, though not directly related to the defect,
occurs from the organism’s tendency to realize the capacities which it has, in
pathology those which are preserved. Within this new organization the effect
of the disturbance does not become apparent. This would make it
understandable that the patient is not only unaware of the defect, but that the
defect is so arranged in his behavior, without his knowledge, that the
disturbance does not show.
It is not the disagreeable experience of the failure itself which produces
the new organization. This becomes evident when lack of awareness or other
protective mechanisms disappear under the influence of the physician. As
transference develops between patient and physician—when, for example,
under the influence of the physician the patient learns to bear his
disturbances and learns through his own experience that, by bearing them,
his general contact with the world is improved—then he is more able to
realize himself without the shelter of the protective mechanisms. With this
added security, he is able to give up his safeguards. Indeed, the more the
abstract capacity which makes such deliberation possible is preserved, the
more is this the case.
We consider the organization of protective mechanisms as an
expression of the attempt of the organism to come to terms with the demands
made on it, in such a way that self-realization is guaranteed as much as

possible. I would like to stress that these passively originating, protective
mechanisms occur not only when the abstract attitude is impaired but also if
it is by circumstances diminished, as, for example, in severe anxiety in normal

individuals.
There is another way to eliminate danger to self-realization which is
produced more actively by conscious interference. One should distinguish

these mechanisms, which occur particularly in neuroses, from the passively
originating protective mechanisms by terming them differently—by calling

them defense mechanisms.
In view of these facts, we should be very cautious in the interpretation
of symptoms; the possibility that some phenomena observed in the patient
might not be the effect of a damage but of a protective mechanism always has
to be considered. This concerns also the absence of symptoms by “denial,”
which might be expected in a special damage of the brain.
Somatic symptoms, resulting from defects of the nervous system, can
also bring the patient into general disorder. Here also, we observe after a
certain time, a modification of behavior by which, even when the original
damage is neither eliminated nor improved it is no longer effective. For
instance, a patient may, after damage to one hemisphere of the cerebellum,
suffer from disequilibrium, falling, deviations in walking, etc., and from
different disturbances in general, subjectively and objectively, and so may be
hindered subjectively or objectively in his self-realization. After a certain time
the general disturbances improve, without improvement of the pathological

condition (which special examination shows existent as before).
Concomitantly with the general improvement, however, we see that a

deviation of the body has occurred, which seems to bring about a new
equilibrium, a better general condition, and thus a better possibility for self-
realization. The patient, however, is not aware of his deviation.
That this general improvement is related to the deviation becomes

apparent by the fact that improvement disappears immediately when one
tries to eliminate the deviation; in other words, such action brings the patient
into the previous condition, into catastrophe. We say that the deviation
represents the individual’s new, preferred condition (see p. 340). The
following few remarks may explain what is meant by this. If we consider an

organism by the usual atomistic method as composed of parts, members, and
organs which can be used in very different ways, and if we then look at the
organism in its natural behavior, we find that many kinds of behavior which,
on the basis of the first consideration can be conceived of as possible, are

actually not realized. Instead, only a definite selective range of behavior can
be observed. Normally, each performance is executed only in a definite or, as
we say, preferred manner. Observation of the whole organism in a situation

where one performance field—be it motility, perception, language, etc.—
shows preferred behavior reveals that all other performance fields exhibit
preferred behavior as well. In the above case we say that the organism is in an
ordered condition; it performs all its activities in the best way; it can use all
its capacities in coming to terms with the demands of the outer world; it has a
definite constant visual acuity, an erect position of the body, is able to speak
and to act according to its nature, that is, is able to realize itself in the best
way.
The organism always tries to achieve such ordered behavior in spite of
its defect. It can be reached only through modification of the behavior in the
damaged performance field by finding a new preferred behavior which goes
along with a somewhat modified but preferred behavior all over. This must be
considered in our evaluation of deviations; we have to distinguish those
which are the expression of the defect from those which are an expression of
the new, preferred behavior; that is, from those which are means to guarantee
the new order. This distinction demands careful study of the influence of the
deviation on the behavior of the whole organism, that is, whether or not it is
accompanied by order or disorder of the latter. A symptom belonging to a
preferred condition is characterized by the fact that any voluntary change of
the new preferred behavior brings the organism into general disorder and
that it returns involuntarily to that very behavior. So, for instance, should the
head be in a tilted position, any attempt to bring it to the normal erect state
produces not only general disorder, but the head returns involuntarily to the
new preferred condition, in this case a tilted position.
What we have described here concerning the effect of a cerebellar

damage can be observed in damage of each performance field in the change of
the direction of the performances toward a new preferred order. This new
preferred condition can be achieved in two different ways. One way consists
of yielding, giving in to the defect; the other, of building a counteracting

mechanism by which the effect due to an abnormal condition is compensated.
These two ways of eliminating the danger to self-realization do not present
equal effects. By the first, the normal functioning is, in principle, unchanged. It
is the more “natural” procedure; it occurs more automatically, scarcely
demands voluntary activity on the part of the individual, and therefore brings
greater security. By the second way the normal form of functioning in the
particular apparatus is changed. It is a more volitional type of behavior; it is
not as secure, leads more readily to fluctuation, and admits greater
possibilities for catastrophic reactions. Whether one or the other way of

adapting to the irreparable defect occurs depends on which offers the best
possibility for self-realization under the given conditions. If this is guaranteed
by the first procedure, it will occur, since it is the more secure procedure; if,
however, this is not possible, then the second way of adaptation occurs.
The significance of the preferred condition for the best performance

must be considered most carefully in all therapy, even if that condition
deviates from the “normal.” Any attempt to bring the patient into the
“normal” condition may make all treatment meaningless and inane. The
similarity of this situation in organically disturbed patients and in neurotics is
theoretically of the greatest interest. Unfortunately, we cannot even touch
this point here.
We mentioned before that the symptomatology of a patient with brain
damage can become more difficult to understand in direct relation to the

defect because of a factor other than the protective mechanisms. This factor is
the development of the relation between the physician and the patient. If this
relationship is good, the patient will no longer become afraid so easily and the
occurrence of catastrophes may be diminished; thus, many defects may come
to the fore which the patient concealed simply by not reacting because he was
afraid to let them appear. The development of a kind of transference between
the patient and the physician is of the greatest significance for a correct
examination, for finding the defects related to the damage, for evaluation of
the symptoms, and, not least, for execution of correct therapy. This
development of transference in organic patients has not had the attention it
deserves. In this respect I would like to refer the reader to my article about
organismic therapy.
The Nature of “Distorted” Performances and

Their Interpretation as Symbolic Phenomena
The discussion of the protective mechanisms, particularly their
consideration as new preferred behavior, has some bearing on the

understanding of phenomena which are usually called compensational or
distortive. When we observe such phenomena, the question of whether we
are actually dealing with pathology always arises. I have in mind particularly
some reactions, unusual as to form and content, of aphasic, apraxic, agnostic
patients. What does the material which the patient brings to the fore
represent? Sometimes it certainly is the expression of disturbances in the
field of the instrumentalities. Sometimes, however, one gets the impression
that the material corresponds to activities and experiences which have played
a particular role in the premorbid life of the personality, and which are now
released, so to speak, through pathology. From this point of view such

material has been considered as of particular significance for the study of the
deeper level of the patient’s personality. It seems to me important that we
look at these phenomena a little more carefully than is usually done. They
deserve attention not only in relation to their interpretative value as
symptoms but from a more general point of view as well. They have
suggested an interpretation as “symbolic” phenomena, which, in my opinion,
is mostly wrong. The error originated because their relationship to the total
condition and behavior of the patient was not fully considered.
Some utterances of aphasics, also of such whose symbolic function was
generally disturbed, can easily give the impression of symbolic phenomena
and often have been interpreted as such. I think they can be understood in
various other ways as well which are not in contradiction to the existing basic
defect, the defect of the symbolic function. Some are so-called “physiognomic
phenomena” and represent normal reactions which occur in a special
concrete and not symbolic attitude of the individual. This is easily overlooked
because these phenomena are not well known. In our culture particularly,
they play a small part in everyday life and are not familiar except in the
experience of artists. In normal life they are, so to speak, embedded in our
realistic everyday attitude toward the world, and they come to the fore only
in special situations. We do not have sufficient studies of the physiognomic
behavior of our patients, but I feel justified in assuming, from my experience,

that this behavior differs from normal physiognomic experiences which are
related somewhat to the symbolic attitude. This relation is lacking in the
physiognomic experiences of the patients. They appear particularly when the

attitude of abstraction is diminished by pathology, and especially in patients
with a premorbid inclination for the physiognomic attitude toward the world.
Such utterances should not be considered as symbolic. For these patients, a
shifting from the physiognomic attitude to the more usual attitude, which, for
normal individuals is easy, becomes almost impossible. Their aspect is, so to
say, fixated due to “isolation.”
Other utterances are more difficult to evaluate and frequently give rise
to symbolic interpretations. They are outstanding in the sense that they

consist of poetic, symbolic, or even newly coined words; they may appear to
be utterances of particularly intelligent, cultured, and erudite personalities. I
have often observed such “quasi-symbolic” phenomena in aphasic patients. In
a recent paper, W. Riese has stressed the occurrence of such phenomena. He

has considered them as means “evidently to compensate the naming defect of
the patients.” The patients’ neologisms “impress the listener by their
descriptive and figurative power.” The language of one of his patients, “a
highly educated scientist and humanitarian” before his sickness, became
“after a brief initial period of complete loss of speech, formal, solemn,
poetical, dramatic, pathetic and ‘Shakespearean,’ frequently using

quotations.” He continues: “What the brain injury brought to the fore was that
element in his nature which disease could not destroy, but rather released”
and “I reached the conclusion that disease may occasionally reveal though in
a distorted fashion what is great and noble in man’s nature.” p. 11
It is true that such utterances and behavior may occur in patients with
brain defects. I have noted that disease may emphasize the premorbid
character of the patient, especially in the way the patient now bears the defect
and in what way the untouched part of the personality helps him to overcome
his failures. Whether in a patient with impairment of the abstract attitude an
interpretation such as W. Riese suggests is justified, I would doubt. In such
cases, I think, we are dealing with phenomena of “quasi-high” value, and I

assume that the patient Riese describes belonged to that group. Closer
consideration may show that the phenomena represent material which
previously belonged to the behavior of a high-level personality, which
appears now in the form of protective mechanisms and has lost their previous
meaning for the particular individual. These utterances represent the
undamaged remnants of the instrumentalities of speaking and thinking,
which prevail now because the adequate activities due to the impairment of
abstraction are impossible. The previous particular way of speaking, the
previous rhythm and preference for poetic, dramatic, pathetic expression of
the personality are preserved, but this material no longer is an expression of

the attitude to which it originally belonged, the attitude which is lost through
damage to the brain. Some abnormalities which these utterances show, and
which Riese has carefully reported, reveal that we are no longer dealing with
utterances prompted by the premorbid personality of the patient. They reveal
“no planning, no effort, they occur passively, apparently without intent.” In all
this, they show the characteristics of isolated automatisms. The rapidity and
fluence with which they are uttered (which Riese mentions, and which I have
often observed on such occasions) may be even better described as being
“thrust out.” I think that the patient utters the words in this manner because
he wants to get rid as quickly as possible of the distress in which he finds
himself when he cannot react correctly but feels forced to do so. As one of my
patients said: “If one is asked, one has to answer,” and he brought out
something which occurred passively in him by association of previous

knowledge to the task he had to fulfill now. He said definitely that he did not
know and could not say how it entered his mind, but that he was forced to
utter it.
Such examples definitely point to the fact that these utterances are not
related to the present personality. Certainly, their prominence is an indicator
that we are confronted with experiences which the individual has had before,
and therefore his utterances may reveal the premorbid character of the
personality, but we cannot assume that they represent the old personality as
released by pathology. In any case, we must be careful to see whether we are
justified in so doing or whether these utterances do not belong to “quasi-
high” behavior.
I have discussed these phenomena in some detail because I consider it
important for the psychiatrist to be fully aware of this problem. We meet the
same problem and the same wrong interpretation in the evaluation of
utterances of schizophrenics, which have often been considered as symbolic,
as expressions of deep insight into the essential things of human life, which
disease has revealed. Here too, I do not want to deny that the particular
premorbid personality of the schizophrenic patient may become apparent in
some of his behavior. This is understandable, because we assume that the

patient is not totally modified in the typical schizophrenic manner but is
partially normal, or, better, in some respects normal. (Federn has stressed
this particularly.) Thus he may show normal and even high-level personality
behavior under some conditions, but I would deny that this particular high-
level behavior is related to the schizophrenic condition. We shall understand
the behavior of the patient only when we distinguish sharply between high-
level behavior and “quasi” reactions which only appear to be of high-level
nature. That the latter occur in schizophrenics is to be expected, particularly
when we assume that the patient’s behavior is frequently abnormally
concrete.
We know, since Vigotski’s investigation, that thinking in concepts is

disturbed in schizophrenic patients, at least in some groups of such patients.
This was confirmed by the work of Hanfmann, Kasanin, Bolles and Goldstein,
and others. Storch was already doubtful whether one is justified in
considering schizophrenic behavior as symbolic. Beck has stressed, on the

basis of his Rorschach studies on schizophrenics, that it is an error to assume
that the schizophrenic gives the world “a form and outline which the healthier
do not see,” that he has “a greater power or superior ability to transmute his
experience into something richer.” The author wonders “whether the general
belief in the schizophrenic profuse fantasy life is not due to confusing
distortion with fantasy.” He adds: “Fantasy actually involves a creating of

something totally new. . . . The schizophrenics’ misconstructions take on
fantastic form. But this is still not fantasy. It is inaccuracy. . . . Not having the
power to apprehend the presented real world is what chiefly distinguishes
the schizophrenic’s percepts and his thinking.”
I have come to the conclusion that in schizophrenia we are dealing not

with an organic defect of abstraction but with a nonuse of abstraction which
concerns only a definite part of the world, and that this is an effect of the
anxiety which the schizophrenic experienced in early youth in relation to his
personal environment. This nonuse of abstraction is a protective mechanism
against the danger of catastrophe and anxiety.
The fact that the origin of the abnormal concreteness in schizophrenics
differs from the origin of such concreteness in organic patients becomes

apparent in certain essential differences of the symptomatology. This can be
seen, for instance, in the frequent appearances of physiognomic experiences.
The schizophrenic’s utterances sometimes yield “symbolic” interpretations
but are often revealed, by analysis, to be only pseudo-symbolic phenomena.
Such phenomena are here particularly suited to appear as symbolic, since the
distortion of behavior brings out much of the instrumentalities belonging to

the preschizophrenic condition of the patient where the symbolic attitude
plays a more or less important role in the thinking of the patient. Further
attention must be paid to the fact that schizophrenics often build complex
mechanisms to cover their ideas, feelings, etc., which may easily appear to be
of a high-level function, owing to their complexity, but which prove to be only

complex associations built on a very concrete basis. This is often difficult to
unveil, because the schizophrenic has not only passively originating

protective mechanisms, like the organic patient, but also has defense
mechanisms, which he produces intentionally, that may give the impression
of higher-level function and sometimes may be also an expression of it. The
picture of schizophrenic behavior is so complex that its origin may be
understood only by a very detailed analysis. In this analysis the distinction
between real symbolic and “quasi,” pseudo-symbolic behavior has to be taken

very seriously.
The So-called General Mental Functions as Origin of Definite Symptoms
I stressed, in the beginning of my presentation, that in the interpretation
of symptoms a distinction has often been made between defects in a special

performance field and defects of so-called general functions, and that this
distinction is not justified since the general functions appear changed in the
same manner as do the specific performances. There is not enough space here
to give detailed proof of the correctness of my statement, but I would like to
make a few remarks about the changes in these general functions, particularly
those which are related to the personality change of the patient owing to
impairment of abstract attitude. I have chosen these because analysis of this
dependence may be especially useful for psychiatrists.
First, there is the problem of memory. Under certain circumstances the

faculty for reproducing facts acquired previously may be about normal in
patients with impairment of abstract attitude. Things learned in school, for
example, may be recalled very well, but that is the case only in certain
situations. The situation must be suited to the reawakening of old
impressions. If the required answer demands an abstract attitude on the part
of the patient, he may be unable to recollect. Therefore he fails in many
intelligence tests which seem very simple to a normal person, and may be
amazingly successful in others which appear complicated to us, namely in
those which can be executed without the abstract attitude. He is able to learn
new facts and to keep them in mind, but he can learn them only in a Concrete
situation and can reproduce them only in the same situation in which he has
learned them. Because intentional recollection of experiences acquired in
infancy requires an abstract attitude of the adult in relation to the situation at
that time, and the events in infancy were not experienced abstractively, the
patient is unable to recall experiences of infancy, but we can observe that
aftereffects of such experiences appear passively, at times, in his behavior. He
is incapable of recollecting when asked to recall things which have nothing to
do with the given situation. He can recall only when he is able to regard the
present situation in such a way that facts from the past belong to it. Repeated
observation in many different situations demonstrates clearly that such

memory failures are not caused by an impairment of memory content. The
patient has the material in his memory, but he is not able to use it freely. He
can use it only in connection with a definite concrete situation.
We arrive at the same results in testing attention. At one time the
patient appears inattentive and distracted; at other times, he is attentive,
even abnormally so. The patient’s attention is usually weak in special
examinations, particularly so at the beginning, when he has not as yet become
aware of the approach to the whole situation, something he can get only
through concrete activity. When he has done so, has entered the situation
concretely, his attention is usually satisfactory, and he may even appear
abnormally attentive, because under such circumstances he might often be

totally untouched by other stimuli from the environment to which normal
persons would unfailingly react. In other situations he will seem to be very
distracted, as, for instance, in those which demand a change of approach. He
seems distracted because he is incapable of making a choice. Consequently, it
is not correct to speak of a change in attention in such patients in terms of
plus or minus. The state of the patient’s attention is but part of his total
behavior and is to be understood only in connection with it.
Another important problem is judgment as to the patients’ emotional

experiences. Usually, the patients are considered emotionally dull, and often
they appear so, but it would be incorrect simply to say that they are suffering
from a diminution of emotions. The same patient can be dull under some
conditions and very excited under others. This can be explained when we
consider the patient’s emotional behavior in relation to his entire behavior in
a given situation. When he does not react emotionally in an adequate way,
investigation may reveal that he has not grasped the situation in such a way
that emotion could arise. The patient may have grasped only one part of the
situation—the part which can be grasped concretely—and this part may not
give any reason for an emotional reaction. His emotional reaction appears to
us inappropriate because we grasp the whole situation to which the
emotional character is attached, while he reacts only to a part of it. This
connection between emotions and total behavior becomes understandable

when we consider that emotions are not simply related to definite
experiences but are, as I have stressed before (see p. 190), inherent aspects of
all behavior, are part and parcel of behavior. No behavior is without emotion,
and what we call lack of emotion is a deviation from normal emotions
corresponding to the deviation of behavior in general. From this point of
view, the following modifications of reactions, which are of particular interest

in respect to the problem of emotions in general, are interesting: We
frequently see that a patient reacts either not at all or in an abnormally quick
manner. The latter occurs particularly when the patient believes he has the
correct answer to a problem. Although this quick behavior might seem to be

simply an effect of a change in the time factor of his reactivity, it is actually the
effect of an emotional factor. To some extent, the patients are always in

danger of coming into catastrophic conditions, and the quick response is an
effect of their tension, of which they want to rid themselves by all means.
They are forced to release tension because they cannot handle it and cannot
bear it. To bear tension presupposes deliberation, considering the future, etc.,
all of which is related to abstraction. The difference in behavior between
these patients and normal people throws light on the nature of the trend to
release tension. The patients must, so to speak, follow the “pleasure
principle.” They must, owing to their abnormal concreteness, react to the
stimulus in a way which brings release. The trend to release tension thus
appears as an expression of pathology, as an effect of a protective mechanism

to prevent catastrophic conditions. The ability to speed up an activity or part
of it, when this corresponds to the requirements of the task, belongs to
normal behavior, but in the same way as the capacity to bear tension and
even to enjoy it at times, when it is necessary to fulfill a particular task. In

contrast to this, patients with impairment of abstraction are only able to
experience the pleasure of release of tension. They never appear to enjoy
anything, a fact which is often clearly revealed by the expression of their

faces. This becomes understandable when we are aware of the fact that in any
kind of joy immediate reality is transcended, that joy is a phenomenon which
presupposes the abstract attitude and especially the category of possibility.

Thus brain-injured patients who are impaired in this attitude cannot feel joy.
Experience with brain-injured patients teaches us that we have to distinguish
between pleasure through release of tension and the active feeling of
enjoyment and freedom so characteristic of joy. Pleasure through release of

tension is the passive feeling of being freed from distress, and therefore this
feeling lasts, in normals, only until a new situation stimulates new activity.
Joy, on the other hand, is something we try to extend, something which
admits the possibility of infinite continuation.
The two emotions of joy and pleasure play essentially different roles in
regard to self-realization. They belong to different performances or different

parts of a performance. Pleasure may be a necessary state of respite, but it is a
phenomenon of standstill. It is akin to death. It separates us from the world
and the other individuals in it; it is equilibrium, quietness. In joy there is
disequilibrium. But this disequilibrium is productive, leading toward fruitful
activity and a particular kind of self-realization. This difference in the
significance of the two emotional states for the normal person and the brain-
injured patient is an expression of the essentially different behavior of the
latter and of the different world in which he lives.
The drive toward release of tension is one of the causes for the strange
behavior of brain-injured patients in friendship and love situations. The lack
of the experience of future forces them to look for close relationships to other
people and to maintain such relationships at all costs. At the same time, close
relationships are terminated suddenly should their maintenance necessitate
some bearing of tension, that is, should any difficulties arise in the
relationship. The following example is illustrative: One of my patients, Mr. A.,

was for years a close friend of another patient, Mr. X. One day Mr. X. went to a
movie with another man. Mr. X. had invited Mr. A. to go along with them, but
the latter did not want to go, since he had seen the picture before. When Mr.
X. returned, my patient was in a state of great excitement and refused to
speak to Mr. X. He could not be quieted by any explanation. He was told that
his friend had not meant to offend him and that his friendship had not
changed, but these explanations made no impression at all. From that time on,
Mr. A. was the enemy of his old friend, Mr. X. He was aware only of the fact
that his friend had been companion to another man, and he felt himself
slighted. The experience had produced great tension in him. He regarded his
friend as the cause of that tension and reacted to him in a way which is
readily understandable in terms of his inability to bear tension and to put

himself in the place of someone else.
Another patient never seemed to be concerned about his family. He
never spoke of his wife or children and was unresponsive when we
questioned him about them. When we suggested to him that he should write
to his family, he was utterly indifferent. He appeared to lack all feelings in this
respect. At times, according to an established practice, he visited his family in

another town and stayed there for several days. We learned that while he was
at home he conducted himself as any man would in the bosom of his family.
He was kind and affectionate to his wife and children, and interested in their
affairs in so far as his abilities would permit. Upon his return to the hospital
from such a visit, he would, when asked about his family, smile in an
embarrassed way and give evasive answers; he seemed utterly estranged
from his home situation. Unquestionably, the peculiar behavior of this man
was not actually an effect of deterioration of his character on the emotional

and moral side; his behavior was the result, rather, of the fact that, owing to
his impairment of abstraction, he could not summon up the home situation
when he was not actually there, and therefore he could not show adequate
feeling and behavior. Lack of active imagination, which is so apparent in this
example, makes such patients incapable of experiencing any expectation for
the future. Active imagination depends on the abstract capacity.
This lack is apparent, for instance, in the behavior of a male patient
toward a woman whom he later married. When he was with her, he seemed
to behave in a friendly, affectionate way and to be very fond of the girl. But
when he was separated from her, he did not care about her at all; he would
not seek her out and certainly did not desire to have a love relationship with
her. When he was questioned, his answers indicated that he did not even
understand what sexual desire meant. He could not imagine any sexual
situation and did not understand pictures which showed such situations.
When he met the girl again, however, when she spoke to him, he was
immediately able to enter into the previous relationship. He was as
affectionate as before. When she induced him to go to bed with her, embraced
him and put his penis into her vagina, he performed an apparently normal act
of sexual intercourse, with satisfaction for both. She had the feeling that he
loved her. She became pregnant, and they married. The above case also
reveals the great significance of speech and voice for any relationship,
particularly when other possibilities are destroyed by the defect of the brain
function, as was the case here.
Some other so-called general factors which are often mentioned as
obstacles to examining such patients consist of fatigue and perseveration.
Here, also, observation shows that these phenomena are not always present
in the same way, that they change according to the situation, as do all
performances. Observation of our patients shows that fatigue is not a simple
function of the duration of continuous performance but depends to a high

degree upon whether or not the performance in question is within or
somewhat above the capacity level of the patient. Thus a paradoxical situation
may occur, where fatigue decreases as the activity continues. This happens,
for instance, when a later task is “easy” to perform while the earlier tasks
could be executed only with difficulty. Another point is the fact that fatigue
does not express itself simply as a slowing down of performance but,
especially at the beginning, as a fluctuation of performance (Goldstein, p.

260). Subjectively, the individual feels not only incapacitation but also
discomfort, uncertainty, and distress. The phenomena occurring in fatigue
show great similarity to those observed in catastrophic conditions and seem
to be closely related to them. Patients with severe brain damage tire easily
because many normal tasks represent difficult ones for them, thus producing
distress. While fatigue in difficult tasks may thus be understandable, we may

ask whether the same point of view is appropriate to explain the fact that
fatigue occurs also in continuous work consisting of a task which is within the
limits of the individual’s capacity. I think that is the case. Continuation means
consumption of energy which deteriorates the function of the substratum, so
that a task which was previously easy to perform may be changed into a
difficult one; therefore, mere continuation may produce catastrophe and
fatigue. This becomes evident by the fact that fatigue does not set in as early
when the task is varied. Boredom and interest influence the fatigue rate. This
must be considered particularly in testing situations. If, after we recognize the

onset of fatigue, we should change the task, the patient may then perform
without fatigue and may do so better, both subjectively and objectively. This
is particularly true if the succeeding task is within the capacities of the
individual, and if the change does not demand a voluntary shifting on the part
of the individual, which, as we have mentioned previously, is an especially
difficult problem for many brain-injured patients. Automatized performances

may be continued for a long time without the patient showing and
experiencing fatigue. We frequently observe, however, severe breakdowns
after excellent performances. This suggests that the symptoms of fatigue are
not only signs of catastrophe but also indications of imminent catastrophe—
warnings, which, thoroughly considered, may help to prevent the latter.
Patients with a mental defect which appears in a lack of planning and
foresight are particularly prone to fatigue, since they do not recognize the
protective danger signals and thus become abnormally tired.
Perseveration is a frequent phenomenon in brain damage. I am inclined
to assume that it is a secondary phenomenon due to incapacitation in some
performances, and a means to avoid catastrophe occurring under such
conditions. Perseveration occurs particularly when the patient is forced to
fulfill tasks with which he is unable to cope. For instance, a patient who has
difficulty with arithmetic may be able to answer promptly at long as he has to
solve problems which are within his capacity. The moment he is given a
problem which he is unable to fulfill, he may either be thrown into a
catastrophic state and not react at all, or he may repeat the last correct result
or a part of it, that is, he perseverates. If he is then given an example,
however, which he is able to solve, he may again answer correctly, and all
perseveration will disappear. The same patient may show perseveration
under some conditions and distractibility under others, so that it becomes
evident that we are not dealing with a primary defect of rigidity. As we have
explained previously, the sick organism tries to react as well as possible to the
task set before him. Confronted with assignments which he cannot fulfill, he
tries to react to that part of the task in which he is able to succeed by means of
his remaining capacity, and he sticks to that rigidly, because thus he can best
avoid catastrophe. But under certain conditions he becomes aware that he
has not fulfilled the task correctly. Then he gives up the first reaction, I think,
because continuing it does not help in overcoming distress. He tries again and
may become attached to another part of the situation to which he is able to
react, but again may feel that he is not performing the task demanded. Thus
he appears abnormally distractible. Neither rigidity, perseveration, nor
distractibility is a defect per se; they are phenomena coming to the fore under
special conditions which can be defined. They can be avoided—at least to a
certain degree—by the same means by which abnormal fatigue can be
avoided, because ultimately they originate from the same cause.
Some Remarks Concerning the Method of Examination
I would like to conclude with some remarks concerning the method of
examination which follows the rules prescribed by the organismic approach.
From our discussion it is evident that only a method can be successful which
takes the relationship of each performance of the patient, each success and
each failure, to the whole behavior of the patient and the whole organism into
consideration, and which particularly keeps in mind that a performance can
be evaluated correctly only in respect to the trend of the organism for self-
realization. The organismic approach by no means overlooks the significance
of the study of details, correct reactions and failures, of the quantitative
deviations from the average and the influence of previous capacities of the
individual patient; it uses all available quantitative methods and applies

statistics to the evaluation. But one should be aware that statistics can be
really helpful only when we are confronted with quantitatively different
material, and that, in the symptomatology of brain cortex damage,

particularly those which are of interest for the psychiatrist, we are mostly
dealing with qualitative deviations from the norm. Statistically valid results,
therefore, are not too important for the increase of our knowledge of what
pathology did to the patient and what we can learn from pathological findings
for understanding normal behavior.
According to our evaluation of the significance of abstract attitude for all
performances, the capacity of abstraction should be tested in the beginning of
any examination. Whether the abstract attitude is impaired and how much it
is impaired can be evaluated by observing the patient under the conditions of
various modes of behavior which can be correctly executed only in this
attitude. Some tests have been constructed which allow one to judge the
patient’s capacity in an easier and more correct way. The tests differ as to
whether the material used is language or the execution of some performances
—matching, sorting, making choices, etc. The results with the first group of
tests are sometimes difficult to establish because of the ambiguity of language
and because they are not always simple to apply when the patients are
suffering from language defects. The advantage of the other group of tests is
not only that they do not use language but also that they are so organized that
judgment can be based directly on the results of the behavior of the subject in
the test.
As an example of the first group of tests, the Proverb-and-Phrases tests
by Hadlich, John Benjamin may be mentioned; as an example of the other
group, the Vigotski test should be mentioned, particularly in the presentation

by Hanfmann and Kasanin; further mention should be made of the various
performance tests of Goldstein and Gelb, Goldstein and Scheerer, Weigl, and
others. (See also the papers by Von Domarus, Beck, Cameron, and Angyal, and
the psychological monograph by Goldstein and Scheerer.)
The use of various tests in examining the same patient is recommended,
since each test differs somewhat as to its applicability and definiteness in

determining the impairment of abstraction and as to its ability to characterize
the various forms of abnormal concreteness. The technique of the Goldstein-
Gelb-Scheerer tests enables one, by the use of various materials and by the
application of various specified subtests besides the main test, to determine
whether or not a patient can assume the abstract attitude, to measure

somewhat the degree of the impairment, and to find out the specific type of
concreteness to which the patient is confined. This proved to be particularly
helpful in distinguishing between the defect in organic patients and in
schizophrenics.
Bibliography
Angyal, A. “Disturbances Thinking in Schizophrenia,” in J. S. Kasanin, ed., Language and Thought

in Schizophrenia. Berkeley: Univ. California Press, 1944.
Anton, “Fehlende Selbstwahrnehmung des Defekts,” Arch. Psychiatr., 32 (1899).
Beck, S. J. “Errors in Perception and Fantasy in Schizophrenia,” in J. S. Kasanin, ed., Language and
Thought in Schizophrenia. Berkeley: Univ. California Press, 1944.
Benjamin, J. “A Method for Distinguishing and Evaluating Formal Thinking Disorders in

Schizophrenia,” in J. S. Kasanin, ed., Language and Thought in Schizophrenia.
Berkeley: Univ. California Press, 1944.
Bolles, M. and K. Goldstein. “A Study of Impairment of Abstract Behavior in Schizophrenic

Patients,” Psychiatr. Q., 12 (1938), 42.
Boumann, L. and A. A. Gruenbaum. “Experimentell Psychologische Untersuchungen zur Aphasie,”

Z. Ges. Neurol. Psychiatr., (1925), 96.
Brugsch, T., ed. Einheitsbestrebungen in der Medizin. Leipzig: Steinkopf, 1933.
Cameron, N. “Experimental Analysis of Schizophrenic Thinking,” in J. S. Kasanin, ed., Language

and Thought in Schizophrenia. Berkeley: Univ. California Press, 1944.
Critchley, M. The Parietal Lobe. London: Arnold, 1953.
Domarus, E., von. “The Specific Laws in Logic in Schizophrenia,” in J. S. Kasanin, ed., Language and
Thought in Schizophrenia. Berkeley: Univ. California Press, 1944.
Goldstein, K. Aftereffects of Brain Injuries in War. New York: Grune & Stratton, 1942.
----. “The Concept of Transference in the Treatment of Organic and Functional Nervous Disease,”
Acta Psychother., 2 (3/4) (1954), 334.
----. “The Effect of Brain Damage on the Personality,” Psychiatry, 15(3) (1952), 245.
----. “On Emotions,” J. Psychol., 31 (1951). 37.
----.Language and Language Disturbances. New York: Grune & Stratton, 1948.
----.“Die Lokalisation in der Grosshimrinde,” Handbuch der Normalen und Pathologischen

Physiologie, Vol. 10, pp. 600-842. Berlin: Springer, 1927.
----.“The Modification of Behavior Consequent to Cerebral Lesions,” Psychiatr. Q., 10 (1936), 586.
----. “Naming and Pseudonaming.” Word., 2(1) (1946), 1.
----.The Organism. New York: American Book, 1939.
----.“Physiological Aspects of Convalescence and Rehabilitation Following Certain Nervous

System Injuries,” Symposium, K. Ancel, ed. Federation Proceedings, 1944.
----.“The Significance of the Frontal Lobes for Mental Performance,” J. Neurol. Psychopathol., 17
(1936), 27.
----.“Das Symptom, seine Entstehung und Bedeutung,” Arch. Psychiatr. Neurol., 6 (1925), 84.
----.“Then Two Ways of Adjustment of the Organism to Cerebral Defects.” J. Mt. Sinai Hosp., 9
(1942), 4.
Goldstein, K. and A. Gelb. “Ueber Farbennamenamnesie,” Psychol. Forsch., 6 (1924), 127.
Goldstein, K. and M. Scheerer. “Abstract and Concrete Behavior,” Psychol. Monograph, 53 (1941),
239.
Goldstein, K. and J. Steinfeld. “The Condition of Sexual Behavior by Visual Agnosia,” Bull. Forest
Lawn Series, 1 (1942), 37-
Goldstein, K. “The Organismic Approach,” in S. Arieti, ed., American Handbook of Psychiatry, Vol. 2,
1st ed., pp. 770-797. New York: Basic Books, 1959.
Hanfmann, E. and J. Kasanin. “A Method for the Study of Schizophrenia,” Arch. Neurol. Psychiatr.,
41 (1939), 568.
Head, H. Aphasia and Kindred Disorders of Speech. New York: Macmillan, 1926.
Heilbronner, K. “Die Aphasischen, Aphasischen und Agnostischen Storungen,” Handbuch der

Neurologie, Springer, Berlin, 1919.
Jackson, J. H. “Croonian Lectures on the Evolution and Dissolution of the Nervous System,” Lancet
(1884), 535, 649, 739.
Kasanin, J. S., ed. Language and Thought in Schizophrenia, Collected Papers. Berkeley: Univ.
California Press, 1944.
Kronfeld, A. and E. Sternberg. “Der Gedankliche Aufbau der Klassischer Aphasiedehre, etc.,”
Psychol. Medizin, Vol. 2. Stuttgart: Enke.
Leeper, R. W. “A Motivational Theory of Emotion, etc.,” Psychol. Rev., 55 (1948), 5.
Lotmar, F. “Zur Kenntnis der erschwerten Wortfindung, etc.,” Schweiz. Arch. Neurol. Psychiatr., 5
(1919), 206.
Marie, P. “Revision de la question de l’aphasie,” Semaine Medicale, 1906.
Nielson, T. M. Agnosia, Apraxia, Aphasia, New York: Hoeber, 1947.
Riese, W. “Hughlings Jackson’s Doctrine of Aphasia and Its Significance Today.” J. Nerv. Ment. Dis.,
122(1) (1955), 1.
Schachtel, E. G. “On Memory and Childhood Amnesia,” Psychiatry, 10 (1947), 1.
Storch. A. The Primitive Archaic Forms of Inner Experiences and Thought in Schizophrenia. Nerv. &
Ment. Dis. Monog. No. New York: Nerv. and Ment. Dis. Publ. Co., 1934.
Vigotski, I. “Thought in Schizophrenia,” Arch. Neurol. Psychiatr., 31 (1934), 1063.
Weigl, E. “On the Psychology of So-called Processes of Abstraction,” J. Abnorm. Soc. Psychol., 36
(1941), 3-
Werner, H., Comparative Psychology of Mental Development, p. 59. New York: Harper, 1940.
Woerkom, W. von. “Ueber Stoerung im Denken bei Aphasie-Patienten,” Monats-schr. Psychiatr.

Neurol., (1925), 59.
Chapter 9
Psychiatric Conditions Associated With Focal

Lesions Of The Central Nervous System1
D. Frank Benson and Norman Geschwind
Introduction
Traditionally, focal pathology which involves the central nervous
system has been the concern of the neurologist and neurosurgeon. It has long
been realized, however, that focal pathology can produce a great variety of
behavioral changes, some of which may directly involve the psychiatrist and
are the subject of this chapter.
Most abnormalities of behavior caused by focal brain disease involve
malfunction of major motor and sensory systems and produce little difficulty
in diagnosis. Some behavioral manifestations, however, such as those
involving the so-called higher functions, e.g., aphasia, memory loss, and
attention, are sometimes not readily recognized and categorized. In addition,
there is a group of behavioral disturbances produced by focal brain damage
which are distinctly psychiatric in nature. The latter include such
manifestations as aggressive behavior, compulsiveness, severe anxiety,
euphoria, depression, paranoia, and others. This chapter will present some of
the disturbances of the higher functions and psychiatric disorders produced
by focal lesions. Admixture of symptoms is common and represents a
considerable challenge to the diagnostician, particularly when one realizes
that many of the individual signs or symptoms seen with neurological disease
also occur frequently in functional disorders.
Not all types of psychiatric symptomatology occur as the result of brain
lesions, but the variety observed is extensive. Rejection of the possibility of
organic causation because the clinical picture is, for example, typically
schizophrenic, is unjustified. Furthermore, one should not automatically
assume that psychiatric disorder is only indirectly related to an organic cause.
Focal lesions often produce characteristic psychiatric disorders. For example,

right hemisphere symptomatology is distinctly different from that of a
temporal-lobe epilepsy, and Broca’s and Wernicke’s aphasics consistently

show different emotional behavior.
It should be remembered that brain lesions causing psychiatric disorder
may do so without producing any significant disturbance of cognitive

function. The extensive literature on frontal lobotomy demonstrates that,
despite dramatic changes in behavior, changes in cognitive function are not
prominent. Failure of psychological test batteries to show signs of
“organicity” does not exclude organic causation for psychiatric
symptomatology.
The reader may well decide that the differential diagnosis between
organic and functional disorder can be extremely difficult; we would agree.

While organic causes of psychiatric complaints are less common than
functional, their recognition is important both for theoretical reasons and
because they open additional and specific therapeutic possibilities.
Certain general rules may be helpful. Hallucinations in childhood are far
more suggestive of organic causation than when they occur in early adult life.
A marked change in personality beyond the age of forty always suggests the
possibility of organic disease. Meticulous history-taking may be needed to
bring this out, however. If a change in personality occurs insidiously over
several years, striking abnormalities may remain unnoticed by the family.

Also, many people have a bias towards perceiving the personalities of their
close associates as continuous. Thus the woman who has just been beaten by
her husband may insist that there has been no change in his personality, yet
admit, on direct questioning, that he had never struck her during the first ten
years of their marriage.
One must be wary of sweeping statements such as: “Aggressiveness is
characteristic of organic disease of the brain.” The symptom of
aggressiveness, in fact, differs sharply in organic disorders. Temporal-lobe
epileptics often give elaborate justifications for aggressive behavior based on
strongly held moral positions; the same sort of justification would be
extremely unusual in a patient with a frontal lesion who had been aggressive.
Of course, much aggressive behavior, particularly in the young, has no

demonstrable pathology in the brain.
Finally, we must comment on the word “depression” which presents
difficulties because of its ambiguous use. At present, it is used both as a
diagnosis and as a description of behavior. Even when employed to describe
behavior, the usage is ambiguous. The statement that a patient is “depressed”
may mean that he is agitated, tearful, guilt-ridden, and suicidal. It may also
mean that the patient is apathetic and suffers a psychomotor retardation.

While psychomotor retardation may be the cardinal sign of a late-life
depression, it is also a characteristic of many organic behavioral disorders.

The apathetic, depressed appearance of many cases of organic brain disorder
merely reflects a shallowness of emotional expression. Agitated depression,
on the other hand, is rare as an organic symptom and a psychogenic

depressive illness almost never occurs in patients with severe organic brain
disorder. The term “depressed” should therefore be avoided as a description
of behavior and replaced by more precise descriptive terms.
Etiologic Factors
In general, the symptomatology produced by focal pathology of the
central nervous system (CNS) depends on the anatomic locus of the lesion as
well as the specific variety of pathology. The most frequent forms of focal
pathology underlying behavioral symptoms are intracerebral space-
occupying lesions, cerebrovascular disease, and trauma. Some manifestations
of inflammatory disease, particularly abscess or granuloma, may produce

focal symptomatology, but many varieties of central nervous system (CNS)
disease (the degenerative, demyelinating, toxic-metabolic, developmental,
and most inflammatory disorders) cause widespread CNS pathology (see

chapter 3 for additional details). Even these disorders, however, often
produce focal disturbances.
Most cerebrovascular and traumatic insults to the brain occur acutely,
and the history suggests the probable source of behavioral changes. Many
behavioral symptoms, however, do not occur immediately and differentiation
from symptoms produced by a reaction to the diseased state may prove

difficult. Premorbid personality structure is often retained but individual
personality traits may become either exaggerated or damped. Changes in
behavioral responses (mood, affect, interpersonal relations) which occur late
after acute brain damage may not be manifestations of the original pathology.
Additional organic disturbance or purely psychogenic reactions may underlie
such changes. Both states are potentially correctable but all too frequently
insufficient attention is given to these patients; the clinician tends to accept

the original insult as the source of the late behavioral developments.
Space occupying lesions offer much greater diagnostic difficulty. The

onset is usually insidious, often with vague behavioral changes, and the
classic signs of CNS involvement frequently appear late. As emphasized by
Mayer-Gross et al., the absence of organic clinical features does not exclude
the possibility of organic disease; indeed, apparently functional disturbances
are often the earliest manifestations of brain tumor. Many psychiatrists have
had the sobering experience of misdiagnosing and offering psychotherapy to

a patient subsequently proved to have a brain tumor. Abnormal behavior
patterns which appear unrelated to present stress, personal or familial
background, genetic processes or other positive indications of functional

disorder should always arouse suspicion, particularly in the older patient.
Several inflammatory diseases may appear only, or primarily, as focal
processes and produce behavioral symptomatology. For instance rabies, a

virus infection, involving the hypothalamus and hippocampus, usually
produces depression, anxiety, and apprehension initially, then advances to

terrifying delusions and ideas of reference. Only later do physical signs, such
as pharyngeal spasms, occur. Encephalitis caused by herpes simplex infection
usually centers in one or both temporal lobes. Early symptoms may include
disorientation, memory loss, and aimless wandering. Bizarre ideation and
inappropriate actions may occur before delirium, fever, severe headache, and
diminished state of consciousness announce the presence of encephalitis.
Most often the course of herpes encephalitis is fairly rapid and dramatic, but
if slow and/or partial in development, it may offer a severe challenge for
diagnosis. Intracerebral granulomas and abscesses often present the general

signs of space-occupying lesions but, if the onset is insidious, strongly
resemble deteriorating functional disturbances. Hypochondriasis,
psychomotor retardation including apathy, cognitive deterioration, and loose

thought associations may be the presenting signs.
Subcortical Syndromes
One of the striking advances of the past two decades in the
understanding of cerebral mechanisms concerns the effects, both facilitatory
and inhibitory, of various subcortical structures. Most dramatic was the

demonstration by Moruzzi and Magoun of the effect that lesions of the
brainstem reticular substance had on sleep and consciousness. In the cat,
destructive lesions of the midbrain reticular substance produced a state of

somnolence, both clinical and electrical (EEG). The animal would respond to
sensory stimuli (noise and touch) and could move all limbs but remained
asleep. In contrast, an animal with lesions involving the major motor and
sensory pathways of the midbrain, but sparing the reticular substance,
retained a normal ability to awaken. It is suggested that this central reticular

core, through connections with many subcortical neural structures, acts to
modulate and modify cerebral activity. The functions attributed to this system
include the initiation and maintenance of wakefulness, the orienting reflex

and the focus of attention, many sensory control processes including
habituation and external inhibition, conditional learning, memory functions,
and the management of internal inhibition including light and deep sleep.
Another system, essentially antagonistic to the reticular system, has
been demonstrated. This is usually called the nonspecific thalamocortical

projection system, but involves, anatomically, many subcortical centres
including medullary and other brainstem centers, the caudate nucleus,
hypothalamic and limbic structures, portions of the thalamus and selected

areas of cortex. Identification of these two phylogenetically ancient and
interlocking systems, both of which constantly modify cerebral activity, has
allowed fuller understanding of complex mental symptomatology. In general,
behavioral responses result from a composite of internal and external stimuli

set against both of these internal regulating mechanisms. Many behavior
modifiers, particularly drugs and the toxic states, are best understood as
involving these subcortical systems. These behavior modifiers, while
primarily affecting a single system, usually have a widespread (thus nonfocal
or multifocal) distribution; there are, however, several focal disorders which
produce major behavioral alterations by involvement of these subcortical

systems and which will now be discussed.
Consciousness
Modifications of the state of consciousness may be produced by focal
lesions involving specific subcortical areas. Thus the unconscious states,
coma, stupor, and lethargy, produced by head injury, are often ascribed to
focal involvement of the mesencephalic reticular substance. At times gross

pathology (i.e., hemorrhage, infarction, edema, or laceration) is present in the
upper brainstem of patients who have suffered prolonged coma; other cases,
however, show only minimal evidence of pathology, e.g., demyelination or
lymphocytic clusters. Often there is no pathological remnant, even in cases

which suffered moderately prolonged unconsciousness. Other varieties of
focal pathology may also affect this area and produce changes in the state of
consciousness. Thus tumors, aneurysms, hemorrhages, and infectious
processes (encephalitis ) which involve the upper brainstem often produce a

diminution of alertness.
Attention
Two clinically distinguishable varieties of attention abnormality can be
ascribed to disorders in the subcortical alerting system. One is the type
occurring in drug-intoxication states, head injury, increased intracranial
pressure, etc., associated with the diminished state of alertness described
above. These patients can be alerted but their attention rapidly wanes and
they drift back into a somnolent state (accurately described as “drifting
attention”). In these cases the “background” state of alertness is impaired

while “phasic” alerting is relatively unaffected. This disturbance of attention
usually indicates pathological involvement of the midbrain or thalamic
portion of the reticular activating system.
In the second variety of attention disturbance the patient appears fully
alert but has great difficulty maintaining attention on the immediate task
(called “wandering attention” ). While this patient is alert and attempts to be
cooperative, his attention is distracted by almost any external stimulus. A

coherent mental evaluation is extremely difficult because of this
unpredictable irregularity of attention. Wandering attention may result from

either focal or widespread CNS disease; if present, focal pathology is usually
located higher in the neuraxis than that which produces the drifting attention
state. Subfrontal tumors, CNS lues, and some tumors of the limbic system are
characterized by this inability to inhibit external stimuli. Clinically similar
defects of attention may be seen in the severely depressed patient (internal
distracting stimuli) and the acute schizophrenic with grossly disturbed
thought processing (distracted by either internal or external stimuli).
Thus when a patient with a behavioral problem manifests a disturbance
of attention, the examiner should suspect pathology involving the two
complex, subcortical neural systems which modify cerebral activity, the

reticular activating system and the nonspecific thalamo-cortical projection
system.
Akinetic Mutism
Akinetic mutism has been defined as a state of limited responsiveness to

the environment in the absence of gross alteration of sensory-motor
mechanisms. Two varieties are recognized, a hyperpathic type (coma vigil)
and an apathetic type (somnolent mutism). In the former variety there is a

state of alert or vigilant coma in which the patient lies immobile but appears
alert since there is free movement of the eyes in following visual stimuli. If
stimulated sufficiently, this patient may become restless or even agitated and
may even say a few words but soon settles back to a state of extreme inertia.
In the second variety the patient is also immobile but with eyes closed. Only
strong stimuli produce movement, including eye opening; vertical gaze palsy
or even total ophthalmoplegia, including loss of pupillary light reflex, is

usually present. After stimulation, this patient rapidly subsides into the
lethargic state, so that this is an apathetic or somnolent variety of akinetic
mutism.
The two varieties of akinetic mutism reflect separate neuroanatomical
loci. In the apathetic type the lesion, as would be expected, involves the
junction area of the mesencephalon and diencephalon and produces both a
state of lethargy and occulomotor disturbances. The vigilant variety occurs

with pathology higher in the neuraxis, usually involving the postero-medial
and inferior aspects of the frontal (septal area) or the hypothalamus. Both
varieties involve portions of the reticular activating and/or the diffuse
thalamic projection systems. Many varieties of pathology may produce
akinetic mutism, including tumor, granuloma, abscess, encephalitis,
hemorrhage, trauma, vascular infarction, angioma, and occult hydrocephalus.

Thus this specific behavioral disturbance is dependent on the location, not the
nature of the pathology.
Limbic System Syndromes
Since Papez’s postulation that portions of the rhinencephalon (limbic
system) were important for emotion, there has been an increasing emphasis
on the role played by these phylogenetically ancient structures in behavior.
For the present discussion the limbic system includes the hippocampus and
hippocampal gyrus, the temporal pole, amygdala, fornix, hypothalamus, septal
nuclei, certain thalamic nuclei (anterior, dorso-medial and intralaminar),
cingulate gyrus, and parts of the orbital frontal cortex. The functions of these
structures have been extensively reviewed and need not be listed here. Many
behavioral syndromes may result from disease involving the limbic system. It
should be noted that most disorders which affect the limbic system also affect
other structures. Since, anatomically the limbic system is spread through
much of the brain it is often involved along with contiguous, nonlimbic
structures. This combination of behavioral features produces a complex

clinical picture. Focal involvement of limbic function does occur, however,
and can produce striking behavioral pictures. When one considers the “four
F’s” of the limbic system, feeding, fighting, fleeing, and the undertaking of
mating activity, it is obvious that disorders of the limbic system will often
come to the attention of the psychiatrist.
Emotional Disturbance
There has long been awareness that structural brain disorder could
cause emotional disturbance and, since Papez, many investigators have
considered damage to the limbic system as particularly important. Others
have noted that pathology outside the actual limbic system may produce
severe behavior disorder which they attribute to limbic release or dis-
inhibition. Many of the emotional disturbances produced by damage to the
limbic system are similar to those seen in “functional” disorders.
In 1937 Kluver and Bucy demonstrated that bilateral anterior temporal-

lobe resection produces a striking behavioral change in the monkey.
Abnormalities included psychic blindness, abnormal tameness,
hypersexuality, strong oral tendencies and hypermetamorphopsia, the

tendency to shift attention frequently. Their work implied that bilateral
limbic destruction (or release) could produce striking behavioral
abnormality. Very few human cases which fit, this description have been
reported. The authors once cared for a university professor, severely injured
in an auto accident, who was found at operation to have severe bilateral
anterior temporal contusions. Necrotic tissue was removed from the anterior
temporal regions on both sides. During recovery there was a phase, lasting
over a month, in which he was fully conscious, and had no demonstrable
paresis, primary sensory loss or visual field defect. He did not appear to
understand language and spoke only a mumbled jargon. He apparently

recognized no one (not even old friends) and could not, or would not, name
objects placed in front of him or in his hand. He ate voraciously and showed a
tendency to place everything in his mouth, even such things as the tea bags
from his tray. He made sexual advances indiscriminately but otherwise had a
flat affect. There was an almost constant shifting of attention and if restrained
he would become agitated, only to calm down immediately if his attention
was diverted. We believed he fulfilled the clinical criteria for the KIuver-Bucy
syndrome at that time. He eventually made considerable recovery. Most
reported cases of the human Kluver-Bucy syndrome show some, but not all, of
the features reported in the original animal experiments.
Flattening of affect (placidity) has also been reported, in tumors and

vascular disorders of the limbic system, particularly involving the anterior
midline structures (septal area and hypothalamus). The affective change may
vary from a mild indifference to a total akinetic mute state (see above).
Malamud, in his description of psychiatric symptoms produced by tumors

involving the limbic system, described seven cases with anterior midline
pathology, who showed affective changes (flattening, depression, manic
outbursts, or instability) and who were originally diagnosed as either

schizophrenic or neurotic. Severe depressive symptomatology including
withdrawal, negativism, apathy, and even suicide attempts, has also been
reported with limbic pathology. Many of the objective findings of depression,

are, however, also produced by bilateral brain pathology (see below, frontal
lobes). As already noted, psychomotor retardation can be produced in many
ways and deserves careful evaluation.
Agitated, aggressive, impulsive, and assaultive behavior have also been
ascribed to pathological involvement of the limbic system. Most of these

reports suggest a relationship between violent behavior and temporal-lobe
disorder, specifically seizures, and will be discussed under Temporal Lobe
Syndromes.
Vegetative Disturbances
Pathology involving the limbic system can produce abnormalities in
vegetative or endocrine function. When these symptoms are combined with
the emotional disturbances described above, the resulting syndrome can
readily be mistaken for psychosomatic or neurotic disturbance. Severe

anorexia, clinically identical to anorexia nervosa, has been described
frequently with hypothalamic disease including tumors. The opposite, i.e.,
hyperphagia, associated with outbursts of rage, polydipsia, polyuria, and
slowly progressive dementia has been reported in a patient with a tiny tumor
of the hypothalamus. Diabetes insipidus is a well known disorder resulting
from pathology involving the anterior portion of the pituitary; it can be
differentiated from “compulsive water drinking” only by carefully performed

water loading tests. Amenorrhea, impotence, sterility, and loss of libido are
reported with limbic pathology, particularly that affecting the midline
structures. Conversely, hypersexual behavior has been reported following
midline encephalitis and abnormal sexual behavior has been reported in

cases with seizures arising from temporal-lobe foci.
Memory Disturbances
Another major neuropsychiatric aspect of limbic-system disease
concerns memory. In the past two decades a fairly clear-cut clinical-
anatomical correlation has been demonstrated for memory defects. Excellent
reviews of this work are available and only a synopsis will be presented here.
Many terms have been used to describe memory functions.

Unfortunately, the usage of these terms in the literature has not been
consistent. In general the functions called memory may be divided into three
distinct categories: immediate recall (also called registration, short-term
memory, immediate memory, minute memory, auditory attention); recent
memory (consolidation, short-term memory, intermediate-term memory,
ability to acquire new knowledge, learning, putting to memory); and remote
memory (retrieval, long-term memory, store of information, ability to retrieve
old knowledge). Note that “short-term memory” has been and still is used to
refer to two different types of memory function, an unfortunate source of

additional confusion. Clinical and pathological findings clearly demonstrate
that one variety, i.e., recent memory or the ability to acquire new knowledge,
depends upon intactness of limbic structures. The classic example of
disordered recent memory is Korsakoff’s psychosis incidental to thiamine
deficiency (see Chapter 15). Similar mental pictures may occur after head
trauma (posttraumatic amnesia), cerebrovascular disease, cerebral surgery,
and, in a modified state, electroconvulsive shock therapy.
Korsakoff’s psychosis is often called the amnestic-confabulatory
syndrome to emphasize its two most conspicuous features. The amnesia has
distinct clinical characteristics. There is excellent (sometimes supernormal)
ability to attend to auditory stimuli, and tests such as digit span are usually
normal. In contrast, newly learned material cannot be retained for even a few
minutes. Thus the doctor’s name is forgotten within minutes and there is
disorientation as to time and place because the patient cannot “remember.”

The ability to retrieve old learned material is relatively preserved, but
evaluation reveals a period of retrograde amnesia. Most often this period is at
least several years before onset; often there are gross lacunae in memories
for many additional years. The best retained memories are either those that
are oldest and most overlearned (language, toilet training, feeding, dressing
and grooming activities, and early life experiences) or those concerning
emotionally significant occurrences (operations, death of a loved one, etc.).
Confabulation, often noted as the second major symptom of Korsakoff’s
psychosis, is not a constant feature and is not necessary for the diagnosis, but,
when present, is remarkable. The patient answers all questions, often with
bizarre responses. Thus, when asked where he is, he will offer an incorrect
address or place name; if asked when he last saw the examiner he will give a
response, again incorrect and often apparently bizarre; when asked the day
and date he hesitates, then responds incorrectly; if asked what he did the
previous day he often describes a job, a trip, a visit, or some other activity in
considerable but incorrect detail. Careful study of confabulatory responses
usually reveals that they represent material from the patient’s past. Barbizet
has described the confabulatory state as one in which the patient cannot
remember that he cannot remember; when asked a question he will offer the
best answer available to him, something from his store of old, overlearned
memories. Confabulations, then, represent old information offered in answer

to a new question.
Recovery from Korsakoff’s psychosis is variable, but at least some

degree of improvement is usual. The first sign of recovery is realization that
something is wrong with the memory. As this concept grows, the amount of
confabulation decreases and within two to three months of onset, almost all
patients with Korsakoff’s psychosis cease confabulating. Some patients make
considerable recovery, sufficient to allow them to return home and even to
undertake a simple job. Others, however, fail to recover, and must remain in
custodial care. In general, the disability in acquiring new knowledge, as
characterized by Korsakoff’s psychosis, is accompanied by a striking
personality change which usually includes passivity, indifference, apathy, and
contentment. In the later stages of the illness, although apathy usually

persists, some of the patients do express concern about their disorder and
may even show episodes of anger.
Nutritional Korsakoff’s psychosis is based on thiamine deficiency
secondary to alcoholism or severe malnutrition. The onset is usually acute,
with restlessness, confusion, and often an occulomotor abnormality signifying
Wernicke’s encephalopathy. With prompt treatment (thiamine by injection)
the occulomotor disturbance can be corrected. The stage of acute alcohol
withdrawal is passed in a few more days. Only then (usually five to ten days
after onset) can the presence of Korsakoff’s psychosis be ascertained with

certainty.
There are many reports on the neuropathology of Korsakoff’s psychosis
and all agree that bilateral pathology in the mammillary bodies (posterior
hypothalamus) is almost always present. A recent study, based on fifty-three
cases, claims that degenerative changes in the dorsal medial nucleus of the
thalamus were more important in the pathogenesis of memory disorder than
those in the mammillary bodies.
Posttraumatic amnesia (PTA) is even more common than Korsakoff s
psychosis but is usually accompanied by so many other signs and symptoms
that the memory loss is often not clearly demonstrated. Pure posttraumatic
amnesia and Korsakoff’s psychosis present similar clinical pictures. Complete
recovery, however, is much more likely after traumatic memory loss. During
periods of PTA the patient exhibits a long retrograde amnesia amounting to at

least several years; if the PTA clears this retrograde amnesia shrinks and
becomes very short, often involving only a few seconds preceding the head
trauma. From this it would appear that the same structures that are necessary
for learning new material are also necessary for retrieval of recently learned
material. As head injury produces widespread effects, it is difficult to localise

precisely the pathology responsible for PTA. Most investigators agree,
however, that the temporal lobes, particularly the hippocampal regions, are
the most likely sites of pathology underlying traumatic memory disturbance.
Clinical pictures similar to Korsakoff’s psychosis have been reported
following cerebrovascular disease. In these cases bilateral posterior cerebral
artery obstruction which produced infarction of the medial aspects of both
the temporal and occipital lobes has been demonstrated. Unilateral infarction
of the left hippocampal region may produce a memory loss similar to that of
Korsakoff s psychosis except that it clears in a few months.
Brain tumor with bilateral medial temporal involvement can cause an
amnesic state. Similarly, colloid cysts of the third ventricle and other tumors
involving the walls of the hypothalamus can produce an amnestic state. In
these cases obstruction of CSF (cerebrospinal fluid) flow producing a
hydrocephalus must be considered, but in some reported cases with memory

loss this complication has been adequately ruled out.
Typical Korsakoff-like states may occur after temporal-lobe surgery.
Scoville reports this finding after bilateral temporal-lobe resection, and a
number of surgeons have reported memory loss after unilateral temporal-
lobe resection. In the latter, subsequent study usually demonstrated
significant pathology in the unoperated temporal lobe. There are reports of
amnestic state following bilateral surgical sectioning of the fornix or bilateral

fornix infarction but most neurosurgeons quote other works suggesting that
there are no residua of bilateral fornix section.
Thus a severe memory disorder (inability to learn new material plus
inability to retrieve recently learned material) appears after bilateral injury to
central limbic-system structures (hippocampal region and mammillary

bodies, possibly the dorsal-medial nucleus of the thalamus and the fornix).
When this memory loss, with its strong element of disorientation, is
combined with the emotional and vegetative disorders mentioned earlier, the
resulting clinical picture, presents many features commonly seen by the
psychiatrist.
Syndromes of Unilateral Hemispheric Involvement
The cerebral hemispheres, comparatively massive in size, are the most
striking anatomical feature of the human nervous system. These structures

comprise a vast area of enfolded cortex with underlying white matter
pathways and subcortical nuclear centers. The two hemispheres have often
been considered mirror images of each other, but recent investigations have
demonstrated significant asymmetries. Certain behavioral tasks are
dependent upon the function, solely or primarily, of only one of the two
hemispheres. Language is the prime example of a strongly lateralized cerebral

function (dominance), but some other behavioral tasks are, to a greater or
lesser degree, also hemisphere-specific. While knowledge of these lateralized
functions and of the significance of the interhemispheric connections remains
incomplete, knowledge of the recognized hemisphere-specific syndromes is

important to the student of behavior.
The dramatic loss of language following left hemisphere damage and the
common preference for the right hand in skilled activities has emphasized the
importance of the left hemisphere. This hemisphere is often called the

dominant or major hemisphere and some investigators have considered that
the right hemisphere acts only as a reserve, an area of cortex which performs
only elementary activities but has the potential to take over many of the
“higher” functions subserved by the left hemisphere. The possibility that the
right hemisphere is also dominant for specific functions has been promoted
by the study of constructional disturbances following right hemisphere
pathology. Recent studies of behavior following temporal lobectomy and

callosal separation have further demonstrated the functional importance of
each of the hemispheres and the great importance of interhemispheric
cooperation in carrying out complex behavioral tasks.
Left Hemisphere
The loss of language (aphasia) following focal damage to the left

hemisphere and the absence of language problems following a similarly
placed lesion in the right hemisphere are the most striking manifestations of
lateralization of cortical function. Language function is frequently correlated

with handedness and the two have been carefully studied. Aphasia, the loss of
language function, is the best studied of the lateralized hemisphere
disabilities and will be reviewed below (and in Chapter 11). For most humans
the left hemisphere appears essential for verbal tasks including speech,
comprehension of speech, reading, and writing. The ability to name or
describe a function is also specific for the left hemisphere. Studies of the
syndromes of corpus callosum separation, first described by Liepmann
demonstrate this clearly. Patients who have suffered separation of the corpus
callosum neither name nor describe the function of objects placed in their left
hand (when blindfolded) but can select the correct objects from a group
(using the left hand). Recognition and memory of the palpated object is
performed by the right hemisphere but translation into words is not. In

contrast, objects placed in the right hand are immediately named and fully
described. Somewhat analogous results are present after left-temporal
lobectomy; there is a drop in verbal memory, both in comparison to
premorbid scores and to the abilities of individuals who have undergone right
temporal lobectomy. Tests of callosally sectioned patients have suggested the
presence of some reading capability in the right hemisphere, but the reading
level is rudimentary when compared to the function performed by the left
hemisphere. Writing is also a strongly lateralized left-hemisphere function.
Callosally disconnected patients can write legible sentences with the right
hand but either cannot write (except for copying) or write aphasically with
the left hand.
Many skilled motor activities appear to be under left-hemisphere
control. Actions performed to verbal command are directly dependent upon
left-hemisphere function, but even imitation of movements is often difficult

for patients who have suffered left-hemisphere damage. This asymmetry of
motor function comprises most of the findings referred to as apraxia.
Thus we see that focal damage in the left hemisphere may result in
many symptoms related to language or motor control; this includes many of
the varieties of aphasia, alexia, agraphia and apraxia. Left-hemisphere
damage may be present without any of these symptoms, but their presence
strongly suggests left-hemisphere involvement.
Right Hemisphere
Several comparatively rare behavioral abnormalities, e.g., dressing
difficulty and prosopagnosia are traditionally linked to right hemisphere
damage and several other disturbances, such as constructional difficulty and
unilateral neglect, are frequently reported after right-hemisphere damage.
Some investigators suggest a single common factor, a disturbance of visual-
spatial orientation and recent studies demonstrate that this function is more
disturbed following right than left hemisphere damage; visual-motor

difficulties are however not confined to rightsided damage.
Constructional disturbance (often called constructional apraxia)
denotes a difficulty in drawing, copying, or manipulating spatial patterns or
designs. Both right and left hemisphere focal damage are capable of
producing constructional disturbance, but most authorities agree that the
disturbance is greater in right hemisphere pathology. Problems in
construction are seen in a high proportion of cases with structural brain

lesions, and studies show that the disability demonstrated in constructional
tasks correlates with both the specific demands of a given test and the locus
of pathology. In general the properties of constructional ability which deal
with execution (e.g., drawing, manipulation) are more affected by left-
hemisphere damage, while the properties dealing with visual-spatial

orientation and recall are more affected by right-hemisphere damage.
Unfortunately almost all of the standard tests (Bender-Gestalt, Benton three-
dimensional figures, etc.) combine both types of task and therefore act as
screening tests. The presence of significant constructional disturbance
strongly suggests an organic basis for a behavioral problem, and if
constructional disturbance is the only significant neurological abnormality

noted, a right-hemisphere locus should be suspected.
Prosopagnosia is a state in which there is difficulty in recognizing faces
of individuals who are well known to the sufferer. At the extreme, even the
patient’s own face cannot be recognized in a mirror and male-female
distinction is dependent upon clothing or other nonphysiognomic features.

Several investigators have suggested that facial recognition depends on
subtle visual distinctions and consider that prosopagnosia represents a mild
variety, almost a forme fruste, of visual agnosia. A number of recent studies

have demonstrated that patients with right-hemisphere pathology have
greater difficulty in distinguishing facial features than those with left-
hemisphere damage. None of their subjects, however, had true

prosopagnosia. Prosopagnosia is rare but it is almost always reported in
patients who have other evidence suggesting right-hemisphere pathology.
Recently Tzavaras et al. reviewed all cases of true prosopagnosia with
postmortem reports in the literature and found that each had bilateral
pathology, suggesting that this disorder results, not from right-hemisphere
damage alone, but from bilateral involvement of specific areas. This would
explain the great rarity of prosopagnosia despite the common occurrence of
right hemisphere pathology.
Dressing disturbance (apraxia) was first described in 1941 and has
been described frequently since then. Two varieties have been distinguished.
One is dependent upon unilateral neglect in which the patient adequately

grooms one side of the face and body while totally ignoring the other. The
second resembles a visual-spatial disturbance; when given an article of
clothing the patient is unable to orient it correctly in space and, while
attempting this, hopelessly tangles the article of clothing. The first variety,
like other examples of unilateral neglect, is more commonly, but not
exclusively, associated with right-hemisphere damage; the visual-spatial type
occurs in patients with severe right or bilateral posterior cerebral

involvement.
Musical ability, at least that portion dealing with melody, rhythm, and
inflection, appears to be a function of the right hemisphere. There are a

number of cases of “amusia” recorded in the literature, some with right-
hemisphere damage, others with left. A recent investigation by Bogen and
Gordon showed that after injection of sodium amytal into the left carotid
artery, the patients could hum a melody but could not sing the words. After
right sided injection the opposite happened, i.e., good ability to recite the
words but without a recognizable melody.
Unilateral neglect is a fairly common expression of cerebral damage and
frequently manifests itself through rather complex behavioral
symptomatology. While neglect can occur after damage in either hemisphere,
it is most frequent when the site of pathology is on the right. All behavioral
symptoms to be mentioned here can occur following left brain damage, but
are more common or severe with right-hemisphere involvement.
A great number of variations of unilateral neglect are recognized (see
Critchley for detailed classification), dependent on specific combinations of
behavioral abnormality.
These variations can be considered points on a spectrum, not sharply
distinct clinical entities, but to be understood they must be separated. For this
purpose a simple classification will suffice:
1. Inattention to
2. Unconcern about
} illness, blindness, paralysis, etc.
3. Unawareness of
4. Denial of
The first and third categories indicate degrees of neglect, most often
involving one side only, and are self-descriptive. Unawareness is a more
severe degree of unilateral neglect and often indicates the presence of some
degree of clouding of the sensorium. While the demonstration of inattention
often demands some special examination technique (such as double
simultaneous stimulation), simple observation of the patient with
unawareness will show considerable decrease in use of the involved side or
limb. When confronted, these patients admit that they have the difficulty
demonstrated and also admit concern about the disabled state. They do not
express concern, however, unless prompted, and attempt their routine
activities as though they had no disability. The patient manifesting unconcern,
on the other hand, shows evidence of inattention and/or unawareness

coupled with an indifference for the disability. He also admits to the disability
when confronted, but shows an inappropriate, flat, or facetious reaction. The
final variety, in which there is overt denial of the illness, is the most severe.
The patient will deny such obvious disabilities as unilateral paralysis or

blindness, insisting that he can walk or run, or attempting to describe an
unseen panorama in front of him. He often employs vague excuses for not
performing the requested task (e.g., “I’ve been ill recently,” “I don’t have my
spectacles here,” “The light in this room seems very poor,” etc.). The
symptoms are bizarre and these patients always show some disturbance of
mental status. This denial of illness must be differentiated from psychogenic

denial, the strongly motivated attempt to downgrade the severity of an illness
or situation (see below).
Each variety of unilateral neglect may involve impairment of any
sensory or motor function. Denial and unawareness may also involve purely
mental tasks (i.e., denial or unawareness of aphasia, memory loss, intellectual
deterioration, etc.). Denny-Brown et al. suggested an asymmetry of finely
balanced hemispheric functions (amorphosynthesis) as the underlying factor

in unilateral neglect. They postulated that a system attuned, through years of
practice, to respond equally to balanced sensory stimuli reaching each
hemisphere will respond most to the stronger signals arriving in the normal
hemisphere and will neglect the weaker signals arriving in the damaged
hemisphere. Amorphosynthesis appears to offer a basis (anatomically and
functionally) for the common occurrence of inattention and unawareness
after unilateral cortical damage. The greater prevalence of right- than left-
hemisphere damage as the source of unilateral inattention, however,
demands additional explanation. The possibility that there is a specific center

for modulation (awareness) of this balance has been suggested. Damage to
such a center, then, could weaken the ability to recognize unilateral

inequalities. This intriguing hypothesis, however, remains totally
unsubstantiated and additional factors must be considered.
Active denial of disease cannot be explained simply on the basis of
amorphosynthesis. For instance, Anton’s Syndrome, the denial of blindness,

almost invariably occurs in the context of bilateral visual loss. Even the classic
denial of hemiplegia (anosognosia of Babinski) appears to go beyond a mere
inequality of stimuli reaching the cortex. This disorder occurs much more
frequently in cases of left hemiplegia, and there is a tendency to treat
anosognosia as a symptom of right-hemisphere (parietal) disorder. This
doctrine has been questioned. Weinstein, who has made extensive studies of
the disorder, suggests that anosognosia is motivated, i.e., the patient shows
evidence of awareness of the disability which he is denying. As evidence he
cites the dying patient, denying illness, but revealing that he recognizes the
situation by describing the hospital as “a slaughter-house” or as a final rest
home. He also cites the frequent occurrence of reduplication of place, where
the patient names the hospital correctly but locates it much closer to his own
home town. Weinstein records many patients who suffer anosognosia but do
not have right hemisphere disease. While his own material did contain more
left than right hemiplegias, we would agree that it is appropriate to consider

other aspects of behavior when analyzing denial of illness.
The emotional behavior demonstrated in the milder disturbance,

unconcern, is worthy of note. These patients exhibit shallow emotional
reactions, often have a mildly euphoric affect, tend to flare up with outbursts
of anger which recede rapidly. Often they are facetious and show
inappropriate social behavior. In short, they resemble patients with frontal-

lobe pathology (see below) and their unconcern about a unilateral
neurological disability could be considered a combination of “frontal
lobishness” and amorphosynthesis.
Another possible consideration would be that a disorder of memory had

been added to the specific neurological loss. Patients may deny disease
because they cannot remember that they have any difficulty. Indeed, this
mechanism does occur in some cases of denial and, when carefully sought,
significant recent memory loss is present in many cases of denial associated
with organic brain disease. There can be little doubt that disorder of memory
is a frequent and important component of anosognosia, but there are cases in
which it does not seem to be playing a role.
Another theory that has been advanced to explain the greater frequency
of denial or unconcern with right rather than left hemisphere lesions is that
right-hemisphere lesions produce a change in emotional responsiveness.
Proponents of this view note the apathy, facetiousness, and mild euphoria of
many left hemiplegics (right-hemisphere damage), contrasting this with the
sadness and despair of many right-hemiplegic patients. If correct, this view

would suggest right-hemisphere dominance for some aspects of emotion. The
strongest evidence for this view is the very difference in the emotional
responses of right and left hemiplegics. Evidence advanced from other types
of data to support this concept is still controversial. Some investigators assert
that right unilateral ECT (electroconvulsive therapy) is more effective than

left in the treatment of depression; this is not substantiated in other reports.
Some observers report that after left-carotid amytal injection patients show a
right hemiplegia, aphasia, and weeping, while after right-carotid injection
they are said to show left hemiplegia and euphoria, but others deny finding
these results in their material. The patient composition of the various series
may have been different, and this issue must remain open. Certainly, if a
unilateral difference in emotional response does exist it would play a
significant role in the response to neurologic disability.
A final possibility to be considered is the presence of a purely
psychological source of the denial. Certainly psychogenic denial does exist
(the repressions, sublimations, etc., of psychodynamics) and sometimes
produces a denial of perfectly obvious illness. There are significant
differentiating points, however, and the type of denial should always be

ascertained. The organic variety of denial occurs only in the face of brain
disease complicated by impairment of mental functioning; the functional
variety, in contrast, occurs without evidence of coarse brain disease and in a

clear mental state. The psychogenic type of denial is usually intellectualized,
rationalized, and presented in a quasi-logical manner; in contrast, the denial

of the brain-injured patient tends to be crude and concrete.
In summary, organic brain disorders exist in which the presence of
disease is neglected or denied. These cases frequently show an inequality of

basic sensori-motor function and, in the more severe syndrome of denial of
disease, this inequality is complicated by a change in the mental picture,
either a facetious, euphoric “frontal-lobe” type of behavior or a loss of recent
memory.
Language Syndromes—Aphasia
Much more is known about abnormal language function than any of the
other disorders of behavior produced by focal brain damage. Generally
termed “aphasia,” this subject has been intensively studied for over a century;
unfortunately there are still many unsolved problems and a great deal of
disagreement exists. When fully developed, aphasia usually presents little
diagnostic difficulty and indicates focal brain disease. In more subtle forms,
however, aphasia may prove difficult to recognize and is easily mistaken for a
functional psychiatric disease. Also, several of the varieties of aphasia

produce specific behavior patterns which merit psychiatric concern. A short
review of aphasia will help in recognition of these problems.
Aphasia can be defined most simply as a loss or impairment of language
caused by brain damage. This definition presupposes that normal language
had once been present and excludes pure speech disturbance (i.e., bulbar
palsy, Parkinsonian dysarthria, scanning speech, etc.). For the vast majority of
people the function of language is performed almost exclusively by one
hemisphere, the left, a factor of obvious significance in the study of focal brain
disease. Specifically, over 99 percent of right-handed people have language
dominance in the left hemisphere. The picture is not so clear for the left-
handed but increasing evidence suggests that some language function in each
hemisphere is most common. The presence of aphasia indicates left-

hemisphere pathology in at least 95 percent of cases, regardless of
handedness.
Further evaluation of the phenomenon of aphasia is dependent upon the
classification of the varieties. Dozens of classifications of aphasia are
currently in use, based on clinical, anatomical, neurological, psychological,
linguistic, and even philosophical considerations. Careful evaluation
demonstrates that the same or at least highly similar symptoms appear in
many of the classifications, although under different names. The following list
presents the classification developed at the Boston Veterans Administration
Hospital, which is a modification of several of the nineteenth-century
continental classifications and is based on personal evaluation, by the

authors, of over 1500 aphasics; it presents this classification of the aphasias
as well as some significant related disorders.
Clinical Varieties of Aphasia
A. Aphasia with repetition disturbance
1. Broca’s aphasia
2. Wernicke’s aphasia
3. Conduction aphasia
B. Aphasia without repetition disturbance
1. Isolation of the speech area
2. Transcortical motor aphasia
3. Transcortical sensory aphasia
4. Anomic aphasia
C. Disturbances primarily affecting reading and writing
1. Alexia with agraphia
D. Total aphasia
1. Global aphasia
E. Syndromes with disturbance of a single language modality
1. Aphemia
2. Pure word deafness
3. Alexia without agraphia
Two of the most popular simple classifications of aphasia deserve
comment, if only to reject them. First, the popular expressive-receptive
classification of Weisenburg and McBride has serious shortcomings. Almost
all aphasics have difficulty with language expression but there are important
differences in the type of expressive disorder which this classification
overlooks. The equally popular motor-sensory dichotomy, originally
proposed in 1874 by Wernicke, is unsuitable because, in great part, the

original, specific meanings of these terms have been lost. Most often they are
equated to the unsatisfactory expressive-receptive dichotomy. If these terms
are to be used, the examiner must recognize that many forms of disordered
expression are not “motor” disturbances.
Aphasia may be usefully subdivided into aphasia with normal repetition
and aphasia with abnormal repetition. The latter category includes the classic
varieties, Broca’s and Wernicke’s aphasias and a third distinct variety,
conduction aphasia. Each variety will be described briefly and correlated with
the usual anatomic locus of the causative lesion.
Broca’s Aphasia
Originally described in 1861 by Broca and subsequently described
under many different names (motor aphasia, cortical dysarthria, verbal
aphasia, efferent kinetic aphasia), this variety of language disturbance has a
fairly consistent symptom picture. Conversational speech is nonfluent
(dysarthric, sparse, dysprosodic, effortful, of short-phrase length, and
consisting mainly of meaning-rich words); comprehension of spoken
language is essentially normal; both repetition and naming ability are
disturbed but are often better than spontaneous speech. Writing is almost
always abnormal, whereas reading comprehension is often preserved. The
causative lesion almost invariably involves the posterior-inferior portion of
the third frontal convolution (Broca’s area). Most patients with Broca’s
aphasia also have a right hemiplegia, and apraxia (the sympathetic dyspraxia
of Liepmann) often affects the left limbs.
Wernicke’s Aphasia
A second variety of aphasia, first described in 1874 by Wernicke
presents a strikingly different clinical picture. Conversational speech is
distinctly fluent (well articulated, presented rapidly with normal melody and
phrase length) but is often contaminated by word-finding pauses and

paraphasias. The term “paraphasia” designates substitutions within language.
This may involve phonemes (literal paraphasia) or words (verbal paraphasia
) or may consist of completely incorrect utterances (neologisms). When
multiple paraphasias are combined with a rapid output, the production

becomes incomprehensible and is sometimes called “jargon aphasia.” Since
“jargon aphasia” may also be used to designate other types of disordered
speech, one must be careful about its use. The verbal content of the output in
Wernicke’s aphasia is strongly biased toward relational, grammatical, and
filler words and phrases; it is deficient in the meaningful nouns noted in
Broca’s aphasia. Other characteristics include severe disturbance of both

comprehension and repetition of spoken language, inability to read or write,
and usually a difficulty in word finding (naming). The causative lesion usually
involves the posterior-superior portion of the first temporal gyrus. Often

there are no overt neurologic signs (such as paralysis, sensory loss, or
hemianopia) except for the language disturbance and, on the basis of his
rapid, bizarre speech and poor comprehension, the patient may be
misdiagnosed as confused or psychotic.
Conduction Aphasia
Originally characterized by Wernicke and eventually confirmed by a
number of European neurologists, this variety still has not been accepted by
many investigators. Much recent work including our own gives strong
support to its existence and importance. Clinically these cases show fluent
speech, often contaminated by paraphasia, with good comprehension but
seriously disturbed repetition. Naming is disturbed, as is writing. Quite

frequently reading comprehension is maintained, even though reading aloud
is impossible. Paresis is minimal or absent, but cortical sensory loss on the
right side of the body is often present. Classically, the causative lesion was
described as lying deep in the white matter of the supramarginal gyrus, thus
involving the arcuate fasciculus and acting to separate the temporo-parietal
language area from the frontal language area. Individual cases of conduction
aphasia, however, have been reported in which the significant pathology was
a total destruction of the left first temporal gyrus; in other words, in some
cases the picture of conduction aphasia rather than Wernicke’s aphasia

occurs with lesions in this site. Two different anatomical locations of
pathology apparently can produce the same clinical syndrome.
The second group of aphasias, those in which repetition is normal, are
more difficult to diagnose, and patients with these disorders are frequently
referred to the psychiatrist for behavioral investigation. While most often the
result of focal brain disease, some of these syndromes can also derive from
more widespread dysfunction, particularly degenerative or toxic-metabolic
disorders, and, when seen in mild form, offer considerable diagnostic

difficulty.
Isolation of the Speech Area
This striking clinical syndrome has only been reported a few times in
pure form but is not infrequent in less complete form. The patient with the
isolation syndrome does not speak unless spoken to, and then repeats almost
slavishly what has been said by the examiner (echolalia). There is no
demonstrable comprehension of spoken or written language, no ability to
write or name objects, but, in contrast, great ability to repeat even long and
complex sentences, nonsense material, and foreign phrases. Usually these

patients can complete stock phrases, e.g., grass is; red, white and. A severe
degree of primary neurological disability is usually present and, in fact,
almost the only useful function retained by these patients is the ability to
repeat. The pathology has, in general, been caused by severe anoxia which has
selectively involved the vascular border zone between the middle cerebral
and anterior and posterior cerebral tributaries. This pathology spares the
immediate perisylvian area but involves large areas of cortex in the frontal,
temporal, and parietal lobes.
Transcortical Motor Aphasia
In this disorder the patient is nonfluent in conversational speech

(except for a striking ability to echo), comprehends well, and repeats
normally. Naming, reading, and writing are usually disturbed. Hemiplegia is
present in most cases. The language output may resemble that of Broca’s
aphasia but is better described as a reluctance to speak. The comparative ease

and clarity of repetition is all the more remarkable in contrast. The causative
lesion involves the frontal association cortex anterior and/or superior to
Broca’s area, the frontal portion of the border zone.
Transcortical Sensory Aphasia
In pure from this disorder is rather uncommon, but it occurs fairly often
in incomplete form and is often misdiagnosed. The patient speaks fluently but
incoherently. He often repeats the examiner’s questions (echolalia) but then
produces totally unrelated answers. These answers, however, consist of real

words, phrases, and sentences with proper intonation. Testing of
comprehension shows remarkable disturbance, often a total inability to
understand. Alexia and agraphia are present, in addition to a severe naming
disturbance. Repetition is dramatically intact. These patients may have

cortical sensory disturbance and/or homonymous hemianopsia but often
have no paresis. The causative lesion involves the dominant parietal cortex,
specifically the parietal border zone and/or the posterior temporal cortex.
Anomic Aphasia
Disturbances of word finding are certainly the most common finding in
aphasia, and vary from mild to gross in degree. In the purest form, called
anomic aphasia, conversational speech is fluent and somewhat paraphasic,
and comprehension of spoken language may be slightly disturbed but is
usually adequate, and repetition is perfectly normal. Testing demonstrates
some difficulty in word finding and writing, and often (but not always) some
disturbance in reading. Usually there is no evidence of elementary
neurological disorder. The clinical picture of anomic aphasia may be the
result of focal vascular pathology in the posterior portion of the border zone
area. A similar aphasic picture is often a prominent feature of biparietal
degenerative disorders such as Alzheimer’s Disease, and also appears in toxic
or metabolic encephalopathy or raised intracranial pressure. Anomic aphasia
also occurs in the recovery stage of many varieties of aphasia. Anomic

aphasia, then, is seen frequently but, by itself, does not indicate a specific
cerebral focus or particular etiology.
The clinical picture of any case of aphasia depends not only on the areas
involved but also on the degree of involvement, the degree of language

dominance, and differences in individual language development.
Nevertheless, most cases of aphasia can readily be placed in this classification
and the site of the underlying focal lesion can be localized with a high degree
of accuracy. Table 9-1 gives an outline of the primary differentiating findings
of the major types of aphasia.
Table 9-1. Clinical Aspects of Aphasia

SPONTANEOUS COMPREHENSION REPETITION NAMING READING WRITING
SPEECH
Broca’s NF + — ± aloud — —
aphasia comp. +
Wernicke’s F — — ± — —
aphasia
Conduction F + — ± aloud — —
aphasia comp. +
Global NF — — — — —
aphasia
Isolation NF — + — — —
syndrome
Transcortical NF + + — aloud — —
motor comp. +
Transcortical F — + — — —
sensory
Anomic F + + — + —
aphasia
Legend: NF = non fluent; F = fluent; + = normal or mildly affected; — = severely affected; ± = variable
degree of involvement.
Several other varieties of aphasia deserve comment. Global aphasia
refers to significant disturbance of comprehension with grossly nonfluent

speech, usually caused by a large lesion in the sylvian region involving nearly
all of the speech regions. Pure word deafness denotes a “pure” disturbance of
auditory language comprehension; the patient understands written but not
spoken language. Speaking and writing are essentially normal. Aphemia

denotes a “pure” disturbance of spoken language, the patient retaining
language comprehension and the ability to write. Alexia without agraphia
denotes loss of the ability to read with no other language loss. These entities
sometimes occur in “pure” form but, not infrequently, they are seen with only
slight admixture of other disorders.
Psychiatric Features of Aphasia
Having considered briefly the clinical-anatomical outline of the aphasias
recorded above, let us now turn to the behavioral features which may bring
the patient to the attention of the psychiatrist. First we will note the problems
that lead to diagnostic errors, then the specific reactions seen in aphasic
individuals which demand psychiatric management.
Anomic Aphasia
Even a mild difficulty with word-finding (naming on visual or tactile
confrontation, manufacturing word lists), suggests organic brain disease and
warrants investigation of this possibility. In view of the large number of

people using drugs, the possibility of toxic sources of anomia is important. It
should be noted that a disproportionate degree of difficulty in writing
(agraphia) is almost always present in patients with clinically significant toxic
or metabolic disorders.
Word Salad
For many years psychiatrists have described a severe disorganization of
spoken and written language which occurs in degenerated schizophrenics,
called “word salad” at its most extreme. It is generally recognized that
improved treatment of the schizophrenic has made this disorder uncommon,
but the diagnosis is still made occasionally. It has been our experience that
every case of “word salad” which we have been asked to evaluate in ten years
has had a demonstrable Wernicke’s aphasia or, rarely, transcortical sensory
aphasia with significant comprehension loss and marked neologistic
paraphasia. A specific organic basis has always been demonstrable. Thus,
before accepting the diagnosis of word salad on the basis of schizophrenia,

patients should be carefully evaluated for evidence of aphasia. There should
be little difficulty in making this distinction. Word salad is traditionally a
disorder of the chronic, backward schizophrenic. Acute onset of fluent

language output filled with paraphasic errors in a previously healthy
individual in middle or late life almost invariably indicates the presence of
aphasia. Even in the patient with well-established chronic schizophrenic
disorder, the acute onset of “word salad” should suggest aphasia. The greatest
problem occurs in the long-term patient who has been misusing language for
many years. Even in this patient, language disorder should be considered and
evaluated; there are instances of fluent aphasics misdiagnosed and treated for
years as psychotic.
Paranoid Reaction
Among the many recognized sources of paranoid reaction, the
psychiatrist should also be aware of the aphasias, particularly those with
severe comprehension disturbance (Wernicke’s aphasia, pure word deafness
and transcortical sensory aphasia). These patients often ask the examiner to
speak more clearly (they hear but cannot understand) and do not realize that
they are speaking gibberish. They may believe that those around them are
discussing them, possibly in a special code which they hear but cannot
understand. They develop severe frustrations and suspicions because their
questions or statements go unheeded. A very large number of patients
suffering auditory comprehension disability in marked degree show some
degree of paranoia (similar to the paranoia which occurs in some cases of

long-standing deafness). Their suspicion may be so extreme that the patient
becomes a danger to the hospital staff, his family, other patients,
acquaintances, or himself. The majority of patients from our aphasia section

needing seclusion care have suffered a paranoid reaction, complicating an
aphasia with severe comprehension difficulty.
Depression, Frustration, and the Catastrophic Reaction
In aphasia, as in all organic brain disease, the diagnosis of depressed
affective state may be difficult. Many patients with organic brain disease,
particularly those with anterior involvement, show a blunting of affect,

psychomotor retardation, and diminished interest in their surroundings. Yet,
when specifically questioned, they do not express depressive feelings. These
objective signs of depression are commonly noted after frontal (see below)
and certain subcortical (e.g., Parkinsonism) lesions but the appearance of
apathy is not accompanied by a depressed affective state. Nonetheless, true

depression can occur in aphasic patients, and is particularly common in
Broca’s aphasia. In contrast, the patient with a severe aphasia from a
posterior lesion rarely exhibits depression; in fact, these patients often fail to
recognize their problem and appear euphoric or unconcerned. We believe

that the depressive reaction seen in Broca’s aphasia is usually a normal
response to his disability. The lack of concern of the patient with the posterior
lesion, on the other hand, is abnormal and depends on the specific clinical
qualities produced by a specifically located brain lesion.
Frustration is seen most frequently in the aphasic with an anterior
lesion. While frustration can be unpleasant for the patient and a hindrance to
therapy, it is actually a favourable prognostic sign; the patient shows that he

cares, is more likely to make an effort, and is therefore a better candidate for
therapy. Goldstein described an extreme degree of frustration in aphasia

under the term “catastrophic reaction.” In this state the degree of frustration
was overwhelming, leading to emotional breakdown with a combination of

weeping, withdrawal, and anger. The catastrophic reaction is very rare and if
the aphasic patient is handled with sympathy, frustration need not interfere
with either evaluation or therapy.
In general, understanding, sympathy, and encouragement on the part of

the examiner or therapist can overcome most of the complications of
frustration in aphasia. This level of “supportive psychotherapy” is an integral
part of the management of almost all victims of aphasia. Affective illness, on

the other hand, is often difficult to manage and demands considerable
attention. In our experience the depressed aphasic patient has not responded
well to treatment with antidepressant drugs and we have been reluctant to
use ECT on individuals who have recently suffered a major brain injury.
Intensive supportive measures, preferably by someone experienced in
communicating with aphasic patients, is usually helpful. We have found that a
trained speech therapist, working under the guidance of a psychiatrist, is

more useful than either alone or both working with the patient
independently. Additional support can be gained by including these patients
in a small group with others receiving aphasia therapy. Group therapy not
only offers support and a relationship with others suffering a similar
disability, but also offers practice in communication in a less stressful
environment.
Frontal-Lobe Syndromes
The frontal lobes are the largest divisions of the cortex, and with the
Rolandic and sylvian fissures and the sagittal sulcus as boundaries, are also
the best demarcated. The frontal lobes, however, are far from homogeneous.
At least four distinct subdivisions, based on thalamic connections, can be
specified, i.e., Rolandic, sylvian, limbic-temporal, and frontal proper, and

distinct neurological symptomatology has been suggested for each. In many
cases, however, an admixture of symptoms referable to these four divisions is
seen. In addition, frontal signs are often mixed with signs resulting from
damage to other parts of the brain. Despite this common overlap of

symptomatology, a clinical picture suggestive of frontal-lobe involvement has
been recognized for many years.
Many of the changes produced by frontal-lobe pathology are
neurological, (paralysis, aphasia, etc.). In addition, involvement of frontal

association cortex can produce a transient total unresponsiveness to visual
stimuli in the opposite field, a transient sensory loss (inattention), and
occulomotor disturbance; some authors have even attributed a memory

defect to frontal lesions. Frontal pathology produces distinct changes in
behavior and personality, often referred to as the “frontal-lobe syndrome.”

The literature contains many descriptions of frontal-lobe syndromes, with
variations based on the type of pathological material evaluated or on the

orientation of the investigator. To evaluate this we will briefly review reports
of frontal head injury, of psychosurgery, and of brain tumors, with several
other neurological disorders which primarily affect the frontal lobes.
Head Injury
Behavioral changes following frontal-lobe injury have been reported for

over one hundred years. In 1868 Harlow described his patient Phineas Gage,
a previously neat, upright, and capable foreman, who sustained an injury in
which a crowbar traversed the left frontal lobe. Following injury the patient
was described as irresponsible, vacillating, and incapable of carrying out
sequential activities. Many similar case studies have followed, one of the most
notable being the patient of Brickner who underwent bilateral frontal-lobe
resection for treatment of a parasagittal meningioma. In addition to

individual case studies, there are many group studies of patients with frontal-
lobe war injuries. Feuchtwanger studied patients with frontal gunshot

wounds and described changes in mood and attitude, including facetiousness,
euphoria, irritability and apathy, defective attention, tactlessness and

inability to plan ahead. Kleist" separated convexity lesions (motor and
intellectual abnormalities) and orbital lesions (emotional disturbances), a
division confirmed by others. A third locale, called the basal area but actually
indicating midline inferior frontal structures, has also been suggested as the
source of specific symptomatology. In general, these studies agreed that
convexity lesions were characterized by a lack of drive, disinhibition,
indifference, lack of productive thinking, euphoria, and incapacity to make a
decision. Patients with orbital lesions were said to have normal intelligence
on formal testing but severe personality changes; they were aggressive,
disinhibited, demanding, interfering, and lacking in perseverance, with

increased sexual libido and potency and proneness to criminal offences. With
involvement of the basal area (hypothalamus and orbital frontal region)
marked sluggishness and apathy were described, along with a disturbance of

the fundamental drives such as appetite, thirst, and sleep.
While these studies suggest that differentiation of the psychiatric

picture may be based on the site of focal injury, this division is somewhat
artificial. Most head injuries are not well localized, and a broader definition of
the frontal-lobe syndrome is needed. In a recent British review of head injury

cases Lishman included under the term “frontal lobe syndrome” all patients
with one or more of the following psychic symptoms in severe degree: (1)
euphoria; (2) lack of judgment, reliability, or foresight; (3) disinhibition; and

(4) facile or childish behavior. To this list many investigators would want to
add apathy, the loss of drive.
Psychosurgery
Psychosurgery, the attempt to control abnormal behavior through

surgical attack on the brain, has produced a great deal of information on the
functions of the frontal lobes. While there has been some disagreement in
reported results, due in part to variation in the surgical procedure, there has
been much agreement on the behavioral outcome of frontal lobectomy and
leucotomy, cingulotomy, and orbital undercutting. Greenblatt and Solomon

reviewed much of the pertinent literature and their own extensive experience
up to 1956 and outlined four principal behavioral consequences of bilateral
frontal lobotomy:
1. Reduced drive demonstrated by
a. apathy, laziness, lack of initiative and spontaneity, and general

contentment;
b. decrease in suspicion, hostility, aggressiveness, violence,

delusions, and fantasy.
2. Reduced self-concern demonstrated by
a. decreased self-consciousness, less preoccupation with self, less

sensitivity to criticism.
3. More immediate outward behavior demonstrated by
a. less withdrawn, more notice of external activity;
b. more outspoken, lack of tact, less concern for the future.
4. Superficial, shallow affective state
a. quicker to become angry, but bear no grudge;
b. general euphoria.
These behavioral changes are noticeably similar to the changes noted
after severe frontal-lobe injury and can be said to characterize the “frontal-
lobe syndrome.”
Cerebral Tumor
A third source of study material, of more concern to the practicing
psychiatrist, consists of tumors involving the frontal lobes. Onset is usually
insidious and behavioral abnormalities often appear first, prompting early
psychiatric evaluation. At first behavior may be poorly restrained and
tactless, with decreased concern for family members and a mood of fatuous
jocularity (Witzelsucht). The patient may become boastful or grandiose, but
initiative is decreased; work quality deteriorates along with decreasing
attentiveness and concern, and finally a state of apathy and indifference

replaces the previous euphoria. Socially unacceptable disinhibition such as
urinating in public, carelessness in dressing, or inappropriate sexual

approach may occur. By this late stage there is often other evidence to
suggest neurological disorder such as seizures, unilateral paresis, visual

disturbance, headache, or aphasia. These findings may, however, first suggest
psychiatric disorder. In a review of 250 cases operated on for frontal-lobe
seizure foci, Rasmussen noted six varieties of aura. Three were clearly
neurological with combinations of unconsciousness, adversive turning, and
generalized grand-mal seizures, but the other three consisted of behavioral
symptoms. These included: (a) a vague epigastric sensation, i.e., a rising
feeling beginning in the abdomen; (b) vague, poorly described sensations

which involved the entire body, usually called “restlessness,” “flush,”
“heaviness,” etc.; and (c) sudden alterations in thought process, a forced
thinking. The latter was described by the patients as “forced to think about
something,” “my thoughts suddenly became fixed,” or “loss of thought
control.” The first sign of aphasia in frontal tumor is almost always a loss of
word-finding ability (anomia), producing a rambling, circumlocutory speech
pattern, difficult to recognize as aphasic. Thus, tumors of the frontal lobe

often mimic psychiatric disorder and offer a formidable diagnostic problem
for the psychiatrist.
Syphilis
Before the advent of penicillin, general paralysis of the insane (GPI) was
one of the commonest forms of organic brain disease, affecting first, and
usually most severely, the frontal lobes (see Chapter 5). Now a rare disorder,
GPI still deserves consideration in the differential diagnosis of dementia,
especially in the middle-aged. A considerable variation in the onset and
course has been reported; usually the onset is insidious with change of
temperament and personality occurring before notable intellectual loss. Most
often (in about two-thirds of cases) there is a gradual deterioration into a
simple or euphoric dementia, characterized by impaired judgement, defective

memory, and lack of insight. A much smaller group (about 10 percent)
develop the classic expansiveness with a happy, exalted mood and delusions
of superb health, fabulous sexual prowess, masterful artistic capabilities, or

superhuman strength. Differentiation from true mania is necessary but
usually easy; the GPI victim is childlike and naive and the presence of
underlying dementia is often readily demonstrated. The opposite state,
serious depression, occurs almost as frequently in the early stages of GPI,
with hypochondriacal and nihilistic delusions and even suicide attempts.
Again the presence of dementia and a shallow, blunted affective state help to
differentiate GPI from true depression. Once suspected, the diagnosis of GPI is
readily confirmed by neurological examination and laboratory studies. The

outstanding success and comparative safety of penicillin therapy makes it
virtually mandatory that any case with reasonable suspicion of GPI receive a
full therapeutic course (12-16 million units in divided doses). Many such
patients are restored to full mental health (up to 80 percent of cases treated
early;) others are left with a stable residual brain damage, usually a dementia
with major frontal-lobe features.
Huntington’s Chorea
A more generalized disorder of the CNS which often produces major
frontal-lobe disturbance is Huntington’s chorea (see Chapter 17). The earliest

manifestations are usually psychiatric, with insidious but progressive
personality deterioration, showing either of two pictures, i.e., irritability,
morose discontent, and oversensitivity or apathy and social disinhibition. The

further progression to chorea and dementia is uneven; some patients have
severe movement disorder and little dementia, while others show the
opposite. Severe personality deterioration, however, invariably occurs and
may precede either state by many years. A distinctive feature of the dementia
of Huntington’s chorea is the relative preservation in most cases of new
learning ability in the face of severe intellectual dysfunction and marked
distractibility.
Normal Pressure Hydrocephalus
Normal pressure hydrocephalus (NPH), a frequently reversible disorder
of cerebrospinal fluid circulation, produces a dementia which features

marked frontal-lobe symptomatology. Of the three cardinal symptoms of
NPH, gait disturbance, incontinence, and dementia, the first two and at least
part of the third appear to result from frontal-lobe dysfunction. In this

disorder there is a tremendous overall increase in size of the ventricular
system, but with the greatest enlargement demonstrable in the frontal horns.
Diagnosis, by intrathecal radioisotope study, air encephalogram, or both can
be followed by shunting, most often a ventriculoatrial bypass, which often
produces a dramatic improvement in the entire picture.
Presenile Dementia
Of the presenile dementias (see Chapter 3), Pick’s disease is

characterized by early and marked changes in the frontal lobe in contrast to
the early biparietal involvement of Alzheimer’s disease. Pick’s disease is well
described as a “sloppy” dementia with crude, coarse social behavior,
incontinence, and apathy. Alzheimer’s disease can, in most cases, be termed a

“neat” dementia featuring a remarkable preservation of social graces
overlying a severe disturbance of cognitive functions. In late stages, with

increased involvement of the frontal cortex, Alzheimer patients also develop a
“sloppy” dementia. Occasionally, a patient with Alzheimer’s disease shows

early frontal signs and may be differentiated from patients with Pick’s disease
only by the greater intellectual disturbances.
Pseudobulbar States
A variable mixture of signs and symptoms is contained in the syndrome
usually referred to as pseudobulbar palsy. The prefix “pseudo-” is used to
indicate that bilateral upper motor neuron paresis is producing a false
impression of lower brainstem (bulbar) pathology. Thus a flattened,
expressionless face, lack of eye blinking, hoarseness, dysphagia, and drooling
are common. In addition, there is often but not always evidence of bilateral
upper motor neuron paresis of the limbs; incontinence, apathy, and
disinterest are common but are not essential parts of the picture. The most
characteristic finding is a disturbance in the control of behavior, correctly
termed a “lability of emotional expression.” These patients laugh or cry

excessively, usually in response to an appropriate but trivial stimulus. In
some cases an initial laughing expression can be seen to change slowly to
unhappiness and then to agony. While the initial response may be

appropriate to the stimulus, the degree of response is not; if asked, the patient
will deny experiencing the degree of happiness or sadness that he is
expressing and often feels distress because of his inability to control the
response.
Recognition of the pseudobulbar state can help the psychiatrist avoid
several misdiagnoses. The presence of an expressionless facies in a patient

who manifests outbursts of severe weeping in response to appropriate but
mild stimuli can easily lead to the diagnosis of a depressive reaction. The
pseudobulbar state does not respond well to the present antidepressive drugs
and ECT is quite likely to harm an already damaged brain further. The proper
diagnosis can be made simply by noting the marked difference between the
subjective and the objective expression of emotion, and the presence of
bilateral motor involvement.
The drooling and expressionless patient who has outbursts of excessive
laughing or crying is easily considered to be demented. It is true that many

patients with pseudobulbar state do suffer intellectual deterioration but in
some disorders, amyotrophic lateral sclerosis for instance, signs of the
pseudobulbar state may coexist with an entirely intact intellect. Even cases of
psuedobulbar palsy secondary to bilateral vascular disease may have

considerable retention of intellect. The lability of emotional expression seen
in the pseudobulbar state should be considered an example of disinhibition,
not of intellectual impairment.
In summary, the behavioral symptomatology of frontal-lobe pathology
is varied but can be characterized by: (1) some degree of poor judgment or
foresight; (2) superficial or shallow affective state; (3) disinhibition; and (4)
reduced drive and self-concern. When some combination of these findings is
noted in a behavioral evaluation, organic pathology involving the frontal
lobes should be suspected.
Temporal-Lobe Syndromes
The temporal lobe, like the frontal lobe, has long been considered to
have a symptomatology of its own but the anatomical demarcation of the
temporal lobe is less exact. The sylvian fissure does separate the temporal
lobe from the frontal and anterior parietal lobes, but the posterior boundary
of the temporal lobe is indistinct. The supramarginal and angular gyri and the
temporal-occipital junction are all transitional areas, both anatomically and
functionally. Williams suggested three discrete functional areas for the

temporal lobe: (1) special sensory, i.e., primarily auditory but also containing
cortical centers for taste, smell, and equilibrium; (2) association, i.e., not only
auditory but also visual and possibly some somesthetic association areas
which occupy much of the lateral surface of the temporal lobe; and (3)
visceral, i.e., the medial and inferior aspects of the temporal lobe contain
major structures of the phylogenetically ancient limbic lobe (hippocampus,
amygdala, fornix, uncus, hippocampal gyrus). Pathology in the temporal lobe

usually involves several of these areas simultaneously, producing a varied
symptomatology. Many of the symptoms produced by temporal-lobe
dysfunction have already been discussed (aphasia, memory loss, limbic

disorders) but one aspect of great significance for the psychiatrist remains,
the behavioral abnormalities associated with temporal-lobe seizures.
Temporal-Lobe Seizures
It is generally accepted that the temporal lobe contains the most
epileptogenic tissue in the brain, but only in recent years has the full
implication of temporal-lobe seizures been realized. Many varieties of motor
seizures from short absences to full grand-mal convulsions are the result of
temporal foci. Associated in some cases with seizures discharge, but often
appearing to occur independently, are many varieties of aura, ictal
manifestations and postictal activities which are behavioral acts. The

following list outlines these symptoms.
Ictal Symptoms of Psychomotor Epilepsy
I. Sensory symptoms
A. External: Olfactory, auditory, visual, somesthetic sensations
B. Visceral: oropharyngeal, esophageal, abdominal sensations,

etc. (i.e., nausea, palpitations, hunger, heat, cold, need to
urinate, etc.)
II. Mental symptoms
A. Consciousness: varies from fully normal to totally lost
B. Perceptual:
1) Illusions: micropsia, macropsia, metamorphasia, deja vu,

jamais vu, depersonalization, etc.
2) Hallucinations: complex, dynamic, dreamlike
C. Ideational: thought-blocking or interfering thoughts
D. Temporal: time stands still (or rushes by)
E. Affective: fear, depression, pleasant, unpleasant, anger
III. Motor signs
A. Somatic:
1) Simple: clonic contractions, unilateral or bilateral

hypertonic: primarily axial, posturings
2) Complex: orienting and investigatory actions; ambulation

or flight; response to stimuli (scratching, putting hand to
face, clearing throat, etc.); confusional state gestures:
palpation of body part, rearrangement of clothes,
manipulation of objects, occupational activities
B. Vegetative signs:
1) Respiratory: apnea, polypnea
2) Digestive: mastication, salivation, borborygmi
3) Vasomotor: paleness, flushing
4) Pupillary: usually mydriasis
C. Speech disorders:
1) Aphasia (indicative of left-temporal focus)
2) Speech automatism (indicative of right temporal focus)
This classification was originally presented by Gastaut from a study of

several thousand temporal-lobe seizure patients. Several modifications have
been made based on subsequent studies. Unfortunately, this list can only offer
an outline of the many behavioral disturbances that occur; it cannot provide
the detailed clinical description that each variety deserves. For this the reader
is referred to clinical studies. Some aspects of temporal-lobe-seizure behavior
have, however, received considerable attention in recent years and deserve to
be discussed here.
The motor manifestations of temporal-lobe discharge may be extremely

limited, often consisting of only a few seconds of absence, and are easily
mistaken for the thought-blocking of a schizophrenic or a neurotic. Motor
activity, such as movement of the jaw, mastication, licking of the lips, eye
blinking, or the rhythmic jerking of a finger may be observed. A glassy-eyed,

vacant stare and a total amnesia for the period of absence are common. Often,
however, the patient resumes activity or conversation immediately after the
short episode and continues as though nothing had happened. Thus, even an
experienced observer may be unaware that he has witnessed an epileptic
seizure.
Abnormalities of perception are frequent manifestations of temporal-

lobe seizure. Micropsia or macropsia (changes in the size of objects seen)
should always suggest temporal or temporal-occipital pathology. “Deja vu” is
a feeling that an episode occurring now has occurred in exactly the same
fashion in the past (re-experience, familiarity). Efron has suggested that this
phenomenon is due to a delay in the callosal transfer of sensory impulses
from the nondominant hemisphere to the dominant hemisphere. The delay
could produce a repeated conscious experiencing of the single stimulus and

thus a strong sense of familiarity. Deja vu is experienced by almost everyone
at some time but, if a frequent complaint, temporal-lobe pathology should be
suspected. It is more common with right-hemisphere than left-hemisphere
disease.
The presence of an emotion, mood, or feeling tone as part of a
psychomotor seizure has received attention. Williams studied all descriptions

of the emotional content reported as part of a convulsive episode by several
thousand patients. Only one hundred of them described emotional
experiences and only four states were noted (fear, depression, pleasantness,
unpleasantness). Other observers have confirmed this limited variety of ictal
emotionality. Fear is reported most often (well over half in several series) and
a report of paroxysmal unexplained feelings of fear should suggest the
possibility of psychomotor seizures.
Serafetinides and Falconer studied speech disturbances reported by one

hundred patients treated surgically for temporal-lobe seizures, and found
significant disturbance in sixty-seven. Dysphasic manifestations (inability to
produce or comprehend speech) were associated with left-temporal lesions
almost exclusively. Speech automatisms (recurrent utterances), on the other

hand, occurred most often in cases with right-temporal-lobe pathology. The
patients producing speech automatisms were always unaware (amnesic),
while those with dysphasia were usually aware of their language difficulties.
Aggressive, violent behavior either ictal, postictal or interictal has
recently received emphasis as part of the temporal-lobe seizure pattern. Mark
et al. speak of a “dyscontrol syndrome” and outline four major symptoms: (1)
unrestrained and senseless brutality (particularly wife- or child-beating); (2)
manic behavior after limited alcoholic intake (pathological intoxication); (3)
sexual assault; and (4) repeated serious traffic accidents. In addition to these
symptoms they look for speech or reading defects, visual field defects,
memory impairment, seizures, hallucinations “or other indications of
schizophrenia,” gross sleep disturbances, and episodic mood disturbances.

Any combination warrants investigation by EEG and pneumoencephalogram;
demonstration of a focal abnormality in the temporal lobe in either would be

considered confirmation of psychomotor seizures as the source of behavioral
dyscontrol. Mark et al. have recorded a number of carefully investigated cases
and their hypothesis has received additional support from other cases. Other
investigators, however, have disagreed; the role of temporal lobe seizures in
violent behavior remains unsettled (see below).
A number of careful studies have demonstrated that at least one type of
serious interictal behavior disturbance may occur in patients with temporal-

lobe-seizure disorder. This has been called a schizophrenia-like state and,
indeed, is often indistinguishable from schizophrenia. In this condition there
are frequent delusions—both primary and secondary—and hallucinations,
mainly auditory, but occasionally mixed with visual, gustatory, or olfactory
references. Paranoid states are common, as well as catatonic states and
repetitive, stereotyped, ritualistic activities. Affective responses, however, are

usually preserved; this preservation of affect and the ability to establish
rapport are the major clinical points which differentiate the schizophrenia
states from “true” schizophrenia. Pond found no deterioration to a

hebephrenic state in the schizophrenia-like group, although partial mental
and social incapacity was the longterm outlook. The quasi-schizophrenia state
often appears at a time when the seizures decrease or are brought under
control, usually many years after the onset of seizures. In the majority (80
percent in Slater’s series) there is evidence of temporal-lobe pathology as the
source of the seizure focus.
In addition to the schizophrenic-like state, many authors suggest that
other aspects of interictal behavior may be altered in patients with temporal-
lobe seizures. Personality deterioration, dementing states, and paroxysmal
mood changes are frequently reported. Many investigators state that
psychomotor epilepsy produces behavior changes which are “clinically
indistinguishable from purely psychiatric disorders” (Gibbs). Some feel that
impulsiveness and aggressive behavior are common interictal phenomena

and use this point to urge earlier and more radical treatment of temporal-lobe
epilepsy.
The presence of psychiatric abnormalities in the interictal phase of
psychomotor epilepsy, however, is not universally accepted. Guerrant et al.
reviewed the literature comparing the behavior of psychomotor and other
seizure patients and found an absence of careful documentation. They then
analyzed the psychiatric status of thirty-two psychomotor epileptics, twenty-

six idiopathic grand-mal patients and twenty-six patients with chronic
medical illness not involving the brain, utilizing both psychiatric and
psychological evaluations. They found no differences in the incidence of
psychiatric abnormality in any of the three groups, and concluded that
psychomotor epilepsy did not produce a specific personality derangement.

Their conclusion is seriously weakened, however, by the fact that over 90
percent of all three groups, including their “normal” control group, had
psychiatric abnormality, and by their own finding that “psychotic”
abnormalities were more common in the temporal-lobe group, while
“neurotic” abnormalities were more frequent in the medical controls. Stevens
performed a similar study comparing psychomotor and grand-mal-seizure

patients and found the incidence of psychiatric abnormality approximately
equal in the two types, with a much lower incidence in focal nontemporal
epileptics. She noted, however, that the prevalent psychiatric disabilities in

the psychomotor group included “schizophrenia, mood disturbance, anxiety,
and withdrawal” while the grand-mal group showed apathy and mental
slowing. Also, the psychomotor patients decompensated psychiatrically when
they became seizure free whereas the grand-mal group decompensated in the
face of more frequent seizures. Most recently Mignone et al. analyzed the
results of psychological tests given to seizure patients at the NIH and found
no significant difference in Minnesota Multiphasic Personality Inventory
(MMPI) profiles between psychomotor and nonpsychomotor epileptics. The

profiles of both groups, however, were different from normal controls. There
would appear to be an increased incidence of behavioral abnormality in

patients with psychomotor seizures when compared to normal subjects;
whether this behavioral abnormality differs either quantitatively or

qualitatively from that of grand-mal epileptics remains unsettled.
The diagnosis of temporal-lobe disorder as the cause of bizarre or
paroxysmal behavior depends on a healthy degree of suspicion on the part of
the examiner. History of a major seizure occurring at any time of life in a
patient with bizarre behavioral problems should arouse suspicion.
Confirmation by laboratory studies is not always easy to obtain. Not only

routine EEGs but one or more specialized studies such as sleep- or metrazol-
activated tracings utilizing special leads (sphenoidal or nasopharyngeal)
should be used. The presence of a temporal-spike focus, either unilateral or

bilateral, would confirm a suspected temporal-lobe-seizure diagnosis. Air
encephalography is often abnormal in patients with temporal-lobe-seizure
disorder. This is a hospital procedure with distinct though transient
morbidity, and is usually reserved for patients considered for surgery or
where the presence of a tumor is suspected.
Treatment of temporal-lobe-seizure disorder is neither easy nor certain.
Anticonvulsants, usually in large doses, are sometimes effective. Mysoline,
Dilantin, and phenobarbital are most frequently recommended. Control of

interictal symptoms may be aided by use of tranquilizers such as the
phenothiazines, Valium or Librium. Successful control has occasionally been
reported with other anticonvulsants; bromides, Phenurone, or Mesantoin
have all been used but toxicity limits their use to exceptional cases under the
closest supervision.
Surgery has proved beneficial in carefully selected cases of temporal-
lobe seizures. If the focus for the seizure discharge is localized in one
temporal lobe, removal of that lobe often produces improved seizure control,
improved personality, and even improved intelligence. Temporal-lobe
amputation, however, is known to affect memory; verbal memory is

disturbed if the left side is removed, and nonverbal memory by right-
temporal amputation. The degree of memory loss, however, is mild and
usually not significant to the patient. Bilateral temporal-lobe amputation, on
the other hand, produces a severe memory disturbance resembling

Korsakoff’s psychosis. Similar memory loss has occasionally been reported
after unilateral amputation. In this situation, pathology involving the other
temporal lobe has been either demonstrated or conjectured. Temporal-lobe

amputation does not appear to alter the schizophrenic-like behavior in most
cases. Most investigators agree that surgery has a limited place at present in
the treatment of seizures but has been successful in selected cases, and with
improving techniques—particularly specific stereotaxic procedures—may

play an important role in the future.
Parietal- and Occipital-Lobe Syndromes
The primary function of these posterior hemispheric areas is the
reception and integration of extrinsic sensory stimuli. Somesthetic

information first reaches the cortex in the post-Rolandic area, and visual
stimuli are initially channelled to the calcarine cortex of the occipital lobe.
Surrounding both of these areas of primary sensory cortex are large areas of
sensory association cortex. In addition, a fairly large area of cortex at the
temporo parieto-occipital junction, the angular gyrus, appears to act as a

secondary association area, receiving and processing stimuli from visual,
somesthetic, and auditory association areas. It is in this area that cross-modal
associations (from one sensory sphere to another) are thought to occur. Much
of the clinical symptomatology of these two areas consists of demonstrable
sensory deficit (e.g., decreased position sense, astereognosis, visual field
defect) but some of the symptomatology can mimic psychiatric disturbance.
Intelligence
Damage to the parietal lobe, particularly the angular gyrus, which

disrupts second-order associations, may affect certain aspects of intelligence.
Involvement of the left angular gyrus usually produces a severe aphasia with
constructional disturbance, right-left disturbance, acalculia, and other
disturbances to be discussed; but despite these specific disturbances other
aspects of intelligence may not be affected. With bilateral parietal
involvement, however, severe intellectual deterioration is noted. Alzheimer’s

disease usually starts with biparietal deterioration; depression of intelligence
is an early clinical feature. Analysis of findings, however, demonstrates that
specific abnormalities are notable (i.e., anomia, constructional disability,
memory disturbance); it does not appear appropriate to consider the parietal
lobes as centers for some overall faculty of “intelligence.”
Body Image
Through the sensory channels entering the brain (vision, cutaneous
sensibility, proprioceptive impulses, labyrinthine inputs, etc.) we are

consciously aware of our own bodies, their component parts, and their
constantly changing position in space. This complex function may be referred
to as “body image” or “body scheme” and is subject to a number of disorders
(see Chapter 33). The most prominent disorders of body image are those
producing neglect, unawareness, or even denial of a part of one’s body, and
have been discussed in the section on right-hemisphere disorders. While

many reports link these disorders to parietal defects, other studies suggest
that lesions elsewhere may also be implicated. Amorphosynthesis, the

inequality of perceptual rivalry discussed earlier, usually indicates parietal or
occipital locus of causative lesion.
The Gerstmann syndrome is often cited as an example of disturbance of
body image. As originally defined, this syndrome consisted of four
components: finger agnosia, right-left disorientation, acalculia, and agraphia.

To this complex Schilder added a fifth component, constructional disturbance.
There was general agreement that the Gerstmann syndrome indicated
dominant (usually left) parietal pathology. Recent studies have questioned
the syndrome as lacking in intersymptom correlation, but there is still general
agreement that the combination of all four of the originally listed components
strongly suggests dominant parietal dysfunction. The fifth component,
constructional disturbance (see earlier discussion), while not soley produced
by parietal dysfunction is very severe, with biparietal pathology; this is often
one of the earliest signs of a dementing process beginning with parietal

degeneration.
Neuropsychological investigation of brain-injured individuals has
demonstrated that parietal damage, far more than damage in other areas,
produces a disturbance of topographical orientation. Both route-finding and

maze-learning were abnormal in many cases with parietal damage, but
neither difficulty was related to defect in one hemisphere preferentially. The
patient who tells of getting lost on the streets or is unable to find his way
about the ward should be suspected of parietal disturbance. This deficit has
been termed topographagnosia and may be investigated clinically by asking

the patient to draw or locate significant features on a map of his state,
country, home, or the hospital ward.
Visual Hallucinations
Most of the signs and symptoms produced by focal pathology in the
occipital lobe are obviously neurological or ophthalmologic and are rarely
considered functional. An exception, however, must be made for visual
hallucinations. There are many varieties of visual hallucination, some
associated with psychiatric disorders (e.g., schizophrenia) and some with
obvious organic pathology (e.g., temporal or occipital tumor). Some occur in
special stress situations without obvious alteration of nervous tissue (e.g.,

black-patch psychosis, the hallucinations of sensory deprivation) and some
are the product of a transient functional alteration (e.g., a migraine aura).
Visual hallucinations may occur in many nonfocal brain diseases such as
delirium tremens, drug intoxications, febrile states, and encephalitis (see

chapters 1 and 2). Often, however, the etiologic causation is not clear when
hallucinosis is first investigated and a short review of some focal CNS lesion-
producing hallucinations is indicated.
Tumors are well known as a source of visual hallucinations. In 1889
Jackson and Beevor reported well-formed visual hallucinations in a case with

a tumor involving the tip of the right temporal lobe. The next year Henschen
reported a case of visual hallucinosis in a patient with an irritative lesion of
the occipital lobe. Most subsequent reports have confirmed the importance of
the temporo-occipital axis in cases of visual hallucinations caused by tumor.
There is also a relationship between the nature of the hallucinatory
experience and the location of the tumor. With occipital involvement the
visual imagery is often brightly colored, diffuse, and formless, usually
involving only one half of the visual field. The images are described as floating
stars, zig-zags, spots, or fire. When the tumor is more anterior, the
hallucinatory images tend to be well formed and are sometimes accompanied
by auditory hallucinations. Familiar individuals or objects, often in
meaningful activity, have been reported in the visual hallucinations of

temporal-lobe tumor cases. Formed hallucinations may also occur in occipital
lesions, particularly if the right hemisphere is involved.
Not all visual hallucinations due to structural lesions involve cortical
structures, however. There are reports of visual hallucinations occurring in
patients subsequently proved to have pathology which involves the

subcortical visual pathways. In some the hallucinations consisted of poorly
formed images, colored and in motion; in others the images were complex,
with recognizable figures and faces. The latter occurred almost exclusively in
patients who became recently blind and persisted after the onset of blindness.
Another type of visual hallucination, reported only rarely but likely to
cause diagnostic confusion, is peduncular hallucinosis. Most patients with this

disorder are elderly and are usually described as being mildly confused; some
complain of giddiness or vertigo, and blindness or severe diminution of vision

is usually reported. The hallucinations tend to be persistent and well formed,
frequently Lilliputian (little people, miniature animals, etc.), often brightly
colored, and usually in rapid movement. The affective response to these
hallucinations is often one of pleasure; the patients are interested in and
amused by the hallucinatory experience. Only rarely does the hallucination

produce distress or alarm. In the cases first reported, vascular pathology
involving the mesencephalon was reported. More recently “peduncular
hallucinosis” has been reported with mass lesions in the interpeduncular
fossa (pituitary or hypothalamic tumors). The disturbance of vision may be

due to pressure on the optic tracts, but may also be secondary to bilateral
obstruction of the posterior cerebral arteries producing ischemia in the
calcarine region, or to other as yet unexplained mesencephalic mechanisms.
Focal causes of hallucinosis are exceptional; most individuals suffering

hallucinations have a demonstrable toxic-metabolic or functional source. If
the patient reports depression of visual acuity along with the hallucinosis,
however, a focal disturbance should be sought.
Brain Tumors
Of all focal neurological disorders producing psychiatric

symptomatology, the most perturbing to psychiatrists is the brain tumor. As
so cogently stated by Pool and Correll: “There is a pathetic, poignant
ineffectiveness about doing psychotherapy in the hope of exorcising an
expanding brain tumor. We have become so enchanted with emotional factors
in the production of symptoms that we sometimes forget organic
components.”
Brain tumor is not common in psychiatric practice and its rarity allows
the physician to overlook this possibility when seeing a patient with clear-cut
behavioral symptomatology. Hard statistics on the frequency of brain tumor

in psychiatric practice are not available; several studies report the occurrence
of brain tumor as ranging between 0.3 and 0.6 percent of new patients in
general psychiatric practices. Mental hospitals report that brain tumor is
present in between 1.5 and 4.0 percent of their autopsies.
The classic signs and symptoms of brain tumor, i.e., headache, vomiting,
and papilledema often occur too late to be helpful. Most earlier abnormalities
such as seizures, hemiparesis, visual field defect, etc., indicate neurological
disorder and patients with these findings are usually seen by neurologists or
neurosurgeons. Many brain tumors do not produce elementary neurological

findings initially, however, and may produce psychiatric symptomatology. In
fact, most individuals with tumors seen by the psychiatrist have no
elementary neurological signs or symptoms. The question of why the patient

with a brain tumor is so often seen by the psychiatrist has been explored and
the following suggested:
1. Behavioral changes may be the only initial finding, but the organic
nature of these symptoms may not be obvious.
2. A brain tumor may occur in a functionally psychotic individual.
3. The patient may develop functional symptoms secondary to a

misdiagnosis and/or mismanagement of the unrecognized
brain tumor.
4. The patient may develop functional symptoms secondary to

subjective awareness of decreased function caused by brain
tumor.
As the psychiatric symptomatology of the brain-tumor patient may be
identical to that arising from psychogenic causes, psychiatrists must remain
alert for other suspicious symptomatology. A persistent and increasing

headache should always be considered suspicious. Most signs of increased
intracranial pressure, however, occur late, often too late for optimal
treatment. The most helpful symptomatology depends upon focal

disturbances produced by the tumor, a subject already discussed in this
chapter. While tumors producing motor, sensory, visual, or extraocular
symptoms, seizures, etc., eventually become obvious, tumors occupying a so-
called “silent area”—e.g., the anterior frontal, or posterior parietal regions of

either hemisphere, or the right temporal lobe—do not. Psychiatric
symptomatology may be the major abnormality.
While a high level of suspicion is the one indispensable tool for
diagnosing brain tumors, one simple test may help. Reproduction (copying) of
line drawings, including both two dimensional figures (square, daisy, clock,
etc.) and three-dimensional figures (cube, house, etc.), are requested, and
judgment is made concerning the quality of the reproduction. Poor
reproductions may result from unilateral neglect, messiness of lines,
alteration of angles, loss of the third dimension, disturbance of either internal

or external configuration, etc. Normal adults copy line drawings adequately as
do persons with psychogenic disorders, but pathology in either hemisphere
involving frontal, parietal, or occipital tissue usually causes difficulty in
producing copies. If there is uncertainty about the drawing ability,

standardized psychological tests such as the Bender-Gestalt may be employed
for confirmation. Almost any type of organic brain disorder including
degenerative dementia, head injury, meningitis, etc., will produce

abnormality. In contrast, most psychogenic disorders do not cause
abnormalities and the tests are valuable as screening measures. While
abnormal drawings do not specify location or type of pathology, poor ability

to reproduce drawings should be looked upon with considerable suspicion.
Note, however, that significant lesions of the temporal lobes may not cause
any drawing problems.
Laboratory studies can be of help in diagnosing brain tumor, but they
are only of value when the presence of brain tumor is suspected.
At present, both the electroencephalogram and the radioisotope brain

scan offer non-traumatic evaluation for brain tumor and the new
computerized axial tomograph (CAT) appears to perform this function even
better. If these tests give equivocal or nondiagnostic results, additional testing

may be necessary. Lumbar puncture is useful, elevated pressure or elevated
protein being suggestive of brain tumor. Arteriography and
pneumoencephalography are used frequently and are often mandatory in the
full investigation for brain tumor. Each of the last three tests carries a small
but real risk for the patient and should be performed under the supervision of
a neurologist or neurosurgeon. Negative results are not necessarily useful.
There are many reports of negative diagnostic tests in patients subsequently

proved to have a tumor.
As the brain is contained in a fixed structure, anything that takes up
space acts as a tumor. The list of brain tumors, therefore, is extensive. The
tumor most likely to produce psychtetric symptomatology is the meningioma
because it grows slowly, often originates in silent areas and can become very
large before producing recognizable neurological symptomatology. Similarly,

slow growing members of the glioma family (oligodendroglioma and low-
grade astrocytoma) often cause difficulty for the psychiatrist. Subfrontal

tumors such as craniopharyngioma and supracellar cyst frequently present
with psychiatric symptomatology. Rapidly growing gliomas, dependent upon
their location, can also lead to behavioral changes. Hematoma, particularly
chronic subdural hematoma of the elderly, and abscess often produce
psychiatric symptomatology. Actually, almost anything which occupies space

inside the skull can produce psychiatric findings and be mistaken for
psychogenic disease. A strong level of suspicion remains the most valuable
clinical tool available for this treacherous diagnostic problem.
Bibliography
Adams, R. D., C. M. Fisher, S. Hakim et al. “Symptomatic Occult Hydrocephalus with ‘Normal’
Cerebrospinalfluid Pressure: a Treatable Syndrome,” N. Engl. J. Med., 273 (1965).
117-126.
Angel, R. W. and D. F. Benson. “Normal Air Encephalogram in Patients with Tumor of the Brain,”
Neurology, 9 (1959), 426-429.
Arrigoni, G. and E. De Renzi. “Constructional Apraxia and Hemispheric Locus of Lesion,” Cortex, 1
(1964), 170-197.
Barbizet, J. “Defect of Memorizing of Hippocampal-Mammillary Origin,” J. Neurol. Neurosurg.

Psychiatry, 26 (1963), 127-135.
----. Human Memory and Its Pathology. San Francisco: Freeman, 1970.
Benson, D. F. and M. I. Barton. “Disturbances in Constructional Apraxia,” Cortex, 6 (1970), 19-46.
Benson, D. F. and N. Geschwind. Shrinking Retrograde Amnesia. J. Neurol. Neurosurg. Psychiatry,

30 (1967), 457-461.
----. “Cerebral Dominance and Its Disturbances,” Pediatr. Clin. North Am., 15 (1968), 759-769-
----. “Aphasia and Related Cortical Disturbances,” in A. B. Baker and L. H. Baker, eds., Clinical
Neurology, pp. 1-26. New York: Harper & Row, 1971.
Benson, D. F., M. LeMay, D. H. Patten et al. “Diagnosis of Normal-Pressure Hydrocephalus,” N.

Engl. J. Med., 283 (1970), 609-615.
Benson, D. F. and D. H. Patten. “The Use of Radioactive Isotopes in the Localization of Aphasia-
Producing Lesions,” Cortex, 3 (1967), 258-271.
Benson, D. F., W. Sheremata, R. Bouchard et al. “Conduction Aphasia,” Arch. Neurol., 28 (1973),
339-346.
Benton, A. L. “The Fiction of the ‘Gerstmann Syndrome’,” Neurol. Neurosurg. Psychiatry, 24 (1961),
176-181.
----. “Constructional Apraxia and Minor Hemisphere,” Confm. Neurol., 29 (1967), 1-16.
Benton, A. L. and M. W. Van Allen. “Impairment in Facial Recognition in Patients with Cerebral
Disease,” Cortex, 4 (1969), 344-358.
Bleuler, E. Dementia Praecox. Trans, by J. Zinkin. New York: International Universities Press,
1950.
Bloch, S. “Etiological Aspects of the Schizophrenia-like Psychosis of Temporal Lobe Epilepsy,”

Med. J. Aust., 1 (1969), 451-455.
Bogen, J. E. “The Other Side of the Brain II: An Appositional Mind,” Bull. Los Angeles Neurol. Soc.,
34 (1969), 135-162.
Bogen, J. E. and H. W. Gordon. “Musical Tests for Functional Lateralization with Intracarotid
Amobarbital,” Nature, 230 (1971), 524-525.
Bornstein, B. “Prosopagnosia,” in L. Halpern, ed., Problems of Dynamic Neurology, pp. 283-318.
Jerusalem: Jerusalem Post Press, 1963.
Brain, W. R. “Visual Disorientation with Special Reference to Lesions of the Right Cerebral
Hemisphere,” Brain, 64 (1941), 244-272.
Brickner, R. M. The Intellectual Functions of the Frontal Lobes. New York: Macmillan, 1936.
Brion, S., C. Pragier, R. Guerin et al. “Korsakoff Syndrome Due to Bilateral Softening of Fornix,”
Rev. Neurol. Paris, 120 (1969), 225-262.
Broca, P. “Remarques sur le siege de la faculte du langage articule, suivis d’une observation
d’aphemie,” Bull. Soc. Anat. Paris (1861), 330-357.
Bruetsch, W. L. “Neurosyphilitic Conditions,” in S. Arieti, ed., American Handbook of Psychiatry,

Vol. 2, 1st ed., pp. 1003-1021. New York: Basic Books, 1959.
Butters, N. and B. A. Brody. “The Role of the Left Parietal Lobe in the Mediation of Intra- and
Cross-Modal Associations,” Cortex, 4 (1968), 328-343.
Cairns, H. and W. H. Mosberg, Jr. “Colloid Cyst of the Third Ventricle,” Surg. Gynecol. Obstet., 92
(1951), 545-570.
Cogan, D. Personal communication.
Cole, M. and O. L. Zangwill. “Deja Vu in Temporal Lobe Epilepsy,” J. Neurol. Neurosurg. Psychiatry,
26 (1963), 37-38.
Costello, C. G., G. P. Belton, J. C. Abra et al. “The Amnesic and Therapeutic Effects of Bilateral and
Unilateral ECT,” Br. J. Psychiatry, 116, (1970), 69-78.
Critchley, M. “Neurological Aspects of Visual and Auditory Hallucinations,” Br. J. Med., 2 (1939),
634-659.
----. The Varietal Lobes. London: Arnold, 1953.
Crosby, E. C., E. Humphrey, and E. W. Lauer. Correlative Neuroanatomy of the Nervous System. New
York: Macmillan 1962.
Currier, R. D., S. C. Little, J. F. Suess et al. “Sexual Seizures,” Arch. Neurol., 25 (1971), 260-264.
Dee, H. L. “Visuoconstructive and Visuoperceptive Deficit in Patients with Unilateral Cerebral

Lesions,” Neuropsychologia, 8 (1970), 305-314.
DeJong, R. N., H. H. Itabashi, and J. R. Olson. “Memory Loss Due to Hippocampal Lesions, Report of
a Case,” Arch. Neurol., 20 (1969), 339-348-
Dempsey, E. M. and R. S. Morrison. “The Electrical Activity of a Thalamo-Cortical Relay System,”

Am. J. Psychol., 138 (1943), 283-296.
Denny-Brown, D. “The Frontal Lobes and Their Functions,” in A. Feiling, ed.,
Modern Trends in Neurology, pp. 13-89. New York: Hoeber, 1951.
Denny-Brown, D. and B. Q. Banker. “Amorphosynthesis from Left Parietal Lesion,” Arch. Neurol.,
71 (1954), 302-313.
Denny-Brown, D., J. S. Meyer, and S. Horenstein. “The Significance of Perceptual Rivalry Resulting
from Parietal Lesion,” Brain, 75 (1952), 29-471.
DeRenzi, E. and H. Spinnler. “Facial Recognition in Brain Damaged Patients,” Neurology, 16

(1966), 145-152.
Dincman, J ,F. and G. W. Thorn. “Diseases of the Neurohypophysis,” in M. W. Wintrobe et al., eds.,
Harrison’s Principles of Internal Medicine, 6th ed., pp. 435-443. New York: McGraw-
Hill, 1970.
Dott, N. M. “Hypothalamus—Surgical Aspects,” in The Hypothalamus. London: Oliver and Boyd,

1938.
Efron, R. “Temporal Perception, Aphasia and Deja Vu,” Brain, 86 (1963), 403-424.
Ervin, F., A. W. Epstein, and H. E. King. “Behavior of Epileptic and Non-Epileptic Patients with
‘Temporal Spikes’,” Arch. Neurol. Psychiatry, 74 (1955), 488-497.
Falconer, M. A. “Significance of Surgery for Temporal Lobe Epilepsy in Childhood and

Adolescence,” J. Neurosurg., 33 (1964), 233-252.
Falconer, M. A., E. A. Serafetinides, and J. A. Corsellis. “Etiology and Pathogenesis of Temporal

Lobe Epilepsy,” Arch. Neurol., 10 (1964), 233-248.
Faust, C. “Die Psychischen Storungen nach Hirntraumen,” in H. W. Gruhnle, ed., Psychiatrie der
Gegenwart, Band 2, pp. 552-645. Berlin: Springer, 1960.
Feuchtwanger, E. Die Funktionen des Stirnhirns. Berlin: Springer, 1923.
----. Amusie. Berlin: Springer, 1930.
Flor-Henry, P. “Schizophrenic-like Reactions and Affective Psychoses Associated with Temporal

Lobe Epilepsy: Etiological Factors,” Am. J. Psychiatry, 126 (1969), 400-403.
----. “Psychosis and Temporal Lobe Epilepsy,” Epilepsia, 10 (1969), 363-395.
Fredericks, J. A. M. “Disorders of the Body Schema,” in P. G. Winken and G. W. Bruynm eds.,

Handbook of Clinical Neurology, Vol. 4, pp. 207-240. Amsterdam: North-Holland,
1969.
Freedman, A. M. and H. I. Kaplan. Comprehensive Text Book of Psychiatry. Baltimore: Williams &
Wilkins, 1967.
Freeman, W. and J. W. Watts. Psychosurgery. Springfield, Ill.: Charles C. Thomas, 1942.
French, J. D. “Brain Lesions Associated with Prolonged Unconsciousness,” Arch. Neurol.

Psychiatry, 68 (1952), 727-740.
Friedman, H. M. and N. Allen. “Chronic Effects of Complete Limbic Lobe Destruction in Man,”
Neurology, 19 (1969), 679-690.
Gastaut, H. “So-called ‘Psychomotor’ and ‘Temporal’ Epilepsy,” Epilepsia (3rd ser., 2 (1953), 59-
99.
Gazzaniga, M. S., J. E. Bogen, and R. W. Sperry. “Some Functional Effects of Sectioning the Cerebral
Commissures in Man,” Proc. Natl. Acad. Sci. USA, 48 (1962), 1765-1769.
Gazzaniga, M. S. and R. W. Sperry. “Language after Section of the Cerebral Commissures,” Brain,
90 (1967), 131-148.
Gerstmann, J. “Fingeragnosie und Isolierte Agraphie, ein Neues Syndrom,” Z. Ges. Neurol.
Psychiatr, 108 (1927), 152-177.
Geschwind, N. “The Development of the Brain and the Evolution of Language,” in I. J. M. Stuart,
ed., Monograph Series on Languages and Linguistics, No. 17, report of the 15th
Annual Round Table Meeting on Linguistic and Language Studies, April 1964, pp.
155-169. Washington: Georgetown University Press, 1964.
---- . “Disconnexion Syndromes in Animals and Man,” Brain, 88 (1965), 237-294, 585-644.
----. “The Apraxias,” in E. W. Straus and R. M. Griffith, eds., Proceedings of the Second Lexington
VAH Conference on Will and Action, pp. 91-102. Pittsburgh: Duquesne University
Press, 1967.
Geschwind, N. and M. Fusillo. “Color Naming Defects in Association with Alexia,” Arch. Neurol., 15
(1966), 137-146.
Geschwind, N. and M. Kaplan. “A Human Cerebral Disconnection Syndrome,” Neurology, 12

(1962), 675-685.
Geschwind, N. and W. Levitsky. “Human Brain: Left-Right Asymmetry in Temporal Speech

Region,” Science, 161 (1968), 186-187.
Geschwind, N., F. A. Quadfasel, and J. Segarra. “Isolation of the Speech Area,” Neuropsychologia, 6
(1968), 327-340.
Gibbs, E. L., F. A. Gibbs, and B. Fuster. “Psychomotor Epilepsy,” Arch. Neurol. Psychiatry, 60
(1948), 331-339.
Gibbs, F. A. “Ictal and Non-Ictal Psychiatric Disorders in Temporal Lobe Epilepsy,” J. Nerv. Ment.
Dis., 113 (1951), 522-528.
Gibbs, F. A. and E. L. Gibbs. “Psychiatric Implications of Discharging Temporal Lobe Lesions,”

Trans. Am. Neurol. Assoc., 73 (1978), 133-137.
Glaser, G. H. and H. J. Pincus. “Limbic Encephalitis,” J. Nerv. Ment. Dis., 149 (1969), 59-67.
Gloning, I., K. Gloning, C. Haub et al. “Comparison of Verbal Behavior in Right-Handed and Non
Right-Handed Patients with Anatomically Verified Lesion of One Hemisphere,”
Cortex, 5 (1969), 43-52.
Goldstein, K. Language and Language Disturbances. New York: Grune & Stratton, 1948.
Goodglass, H. and F. Quadfasel. “Language Laterality in Left Handed Aphasics,” Brain, 77 (1954),
521-548.
Greenblatt, M. and H. C. Solomon. “Studies of Lobotomy,” in The Brain and Human Behavior, pp.
19-34. Proceedings of the Association for Research in Nervous and Mental Diseases
(ARNMD), Dec. 7 and 8, 1956. New York: Hafner, 1966.
Grinker, R. and A. Sahs. Neurology, 6th ed. Springfield, Ill.: Charles C. Thomas, 1966.
Guerrant, J., W. N. Anderson, A. Fischer et al. Personality in Epilepsy. Springfield, Ill: Charles C.
Thomas, 1962.
Halliday, A. M., K. Davison, M. W. Browne et al. “A Comparison of the Effects on Depression and
Memory of Bilateral ECT and Unilateral ECT to the Dominant and Non-Dominant
Hemispheres,” Br. J. Psychiatry, 114 (1968), 997-1012.
Harlow, J. “Recovery from the Passage of an Iron Bar Through the Head,” Publ. Mass. Med. Soc., 2,
1868.
Hecaen, H. “Clinical Symptomatology in Right and Left Hemisphere Lesions,” in V. B. Mountcastle,
ed., Interhemispheric Relations and Cerebral Dominance, pp. 215-243. Baltimore:
Johns Hopkins, 1962.
Hecaen, H. and J. de Ajuriaguerra. Meconnaissances et Hallucinations Corporelles. Paris: Mason,

1952.
Hecaen, H. and G. Assal. “A Comparison of Constructive Deficits Following Right and Left
Hemispheric Lesions,” Neuropsychologia, 8 (1970), 289-303.
Hecaen, H., M. B. Dell, and A. Roger. “L’Aphasie de conduction,” L’Encepliale, 2 (1955). 170-195’
Hecaen, H. and J. Sauget. “Cerebral Dominance in Left-Handed Subjects,” Cortex, 7 (1971), 19-48.
Hecaen, H. and A. Tzavaras. “Etude Neuropsychologique des Troubles de la Reconnaissance des

Visages Humains,” Bull. Psychol, 276 (1968-9), 754-762.
Heimburger, R. F., W. Demyer, and R. M. Reitan. “Implications of Gerstmann’s Syndrome,” J.

Neurol. Neurosurg. Psychiatry, 27 (1967), 52-57.
Henschen, S. E. Klinische und anatomische Beitrage zur Pathologie des Gehirns. Uppsala: Almquist
and Wilsell, 1890.
Hill, D. “The Schizophrenia-like Psychoses of Epilepsy,” (Discussion) Proc. Roy. Soc. 55 (1962),
315-316.
Hobbs, G. E. “Brain Tumors Simulating Psychiatric Disease,” Can. Med. J., 88 (1963), 186-188.
Hooshmand, H. and B. W. Brawley. “Temporal Lobe Seizures and Exhibitionism,” Neurology, 19

(1970), 1119-1124.
Jackson, J. H. Selected Writings, Vol. 2, J. Taylor, ed. London: Hodder and Stoughton, 1932.
Jackson, J. H. and C. Beevor. “Case of Tumor of the Right Temporal Sphenoidal Lobe Bearing on
the Localization of the Sense of Smell and the Interpretation of a Particular Variety
of Epilepsy,” Brain, 12 (1889), 346-357.
Johnson, J. “Sexual Impotence and the Limbic System,” Br. J. Psychol., 111 (1965), 300-303.
Kennard, M. “Alterations in Response to Visual Stimuli Following Lesions of the Frontal Lobe in
Monkeys,” Arch. Neurol. Psychiatry, 41 (1939), 1153-1165.
Kim, C., D. R. Bonnett, and T. S. Roberts. “Primary Amenorrhea Secondary to Non-Communicating

Hydrocephalus,” Neurology, 19 (1969), 533-535-
Kimura, D. “Right Temporal Lobe Damage,” Arch. Neurol., 8 (1963), 264-271.
Kinsbourne, M. “The Minor Cerebral Hemisphere as a Source of Aphasic Speech,” Arch. Neurol., 25
(1971), 302-306.
Kleist, K. Gehirnpathologie. Leipzig: Barth, 1934.
Kluver, H. and P. C. Bucy. “Psychic Blindness and Other Symptoms Following Bilateral Temporal
Lobectomy in Rhesus Monkeys,” Am. J. Physiol., 119 (1937), 352-353.
Kretschmer, E. “Die Orbitalhirnund Zwischenhimsyndrome nach Schadelbasis Frakturen,” Allg. Z.

Psychiatry, 124 (1949). 358-360.
LeMay, M. and P. F. J. New. “Radiological Diagnosis of Occult Normal-Pressure Hydrocephalus,”

Radiology, 96 (1970), 347-358.
Lhermitte, J. Les Hallucinations. Paris: G. Doin & Cie., 1951.
Liepmann, H. Das Krankheitsbild der Apraxie (‘Motorischen Asymbolie'). Berlin: Karger, 1900.
---- . “Das Krankheitsbild der Apraxie,” Monatsschr. Psychiatr. Neurol., 17 (1905), 289-311.
Lishman, W. A. “Brain Damage in Relation to Psychiatric Disability after Head Injury,” Br. J.
Psychiatry, 114 (1968), 373-410.
Luria, A. R., K. H. Pribram, and E. D. Homskaya. “An Experimental Analysis of the Behavioral
Disturbance Produced by a Left Frontal Arachnoidal Endothelioma,”
Neuropsychologia, 2 (1964), 257-280.
McFie, J., M. F. Piercy, and O. L. Zangwill. “Visual-Spatial Agnosia,” Brain, 73(1950), 167-190. log.
McFie, J. and O. L. Zangwill. “Visual Constructive Disabilities Associated with Lesions of the Left
Cerebral Hemisphere,” Brain, 83 (1960), 243-260.
MacRae, D. “Isolated Fear, A Temporal Lobe Aura,” Neurology, 4 (1954), 497-505.
MacRae, D., C. L. Branch, and B. Milner. “The Occipital Horns and Cerebral Dominance,” Neurology,
18 (1968), 95-98.
MacLean, P. D. “Psychomatic Disease and the Visceral Brain,” Psychosom. Med., 11 (1949); 338-
353.
---- . “The Limbic System and its Hippocampal Formation, J. Neurosurg., 11 (1954). 29-44.
---- . “The Limbic System (Visceral Brain) in Relation to Central Gray and Reticulum of the Brain
Stem,” Psychosom. Med., 17 (1955), 355-366.
----. “Contrasting Functions of Limbic and Neocortical Systems of the Brain and their Relevance to
Psychophysiological Aspects of Medicine,” Am. J. Med., 25 (1958), 611-626.
Magoun, H. W. The Waking Brain. Springfield, Ill.: Charles C. Thomas, 1963.
Malamud, N. “Psychiatric Symptoms and the Limbic Lobe,” Bull. Los Angeles Neurol. Soc., 22
(1957), 131-139.
---- . Atlas of Neuropathology. Berkeley: University of California Press, 1957.
---- . “Psychiatric Disorder with Intracranial Tumor of Limbic System,” Arch. Neurol., 17 (1967),
113-123.
Margerison, J. H. and J. A. N. Corsellis. “Epilepsy and the Temporal Lobes: A Clinical,
Electroencephalographic and Neuropathological Study of the Brain in Epilepsy,
with Particular Reference to the Temporal Lobes,” Brain, 89 (1966), 499-530.
Mark, V. H., W. H. Sweet, F. R. Ervin et al. “Brain Disease and Violent Behavior,” presented at the
Society for the Advancement of Behavioral Therapy (in conjunction with the Am.
Psychiatric Assoc.), Sept. 3, 1967, Washington, D.C.
Mayer-Gross, W., E. Slater, and M. Roth. Clinical Psychiatry, 3rd ed., London: Bailliere, 1969.
Michael, R. P. and J. L. Gibbons. “Some Inter-Relationships between the Endocrine System and
Neuropsychiatry,” Int. Rev. Neurobiol., 5 (1963), 243.
Mignone, R. J., E. F. Donnelly, and P. Sadowsky. “Psychomotor and Non-Psychomotor Epileptics,”

Epilepsia, 11 (1970), 345-359.
Milner, B., and W. Penfield. “The Effect of Hippocampal Lesions on Recent Memory,” Trans. Am.
Neurol. Assoc., 80 (1955), 42-48.
Milner, B. “Visual Recognition and Recall After Right Temporal Lobe Excision in Man,”
Moruzzi, G. and H. W. Magoun. “Brain Stem Reticular Formation and Activation of the EEG,”
Electroencephalogr. Clin. Neurophysiol., 1 (1949), 455-473.
Mulder, D. W. and D. Daly. “Psychiatric Symptoms Associated with Lesions of Temporal Lobe,”
JAMA, 150 (1952), 173-176.
Nahor, A. and D. F. Benson. “A Screening Test for Organic Brain Disease in Emergency Psychiatric
Evaluation,” Behav. Psychiatry, 2 (1970), 23-26.
Nielson, J. M. Agnosia, Apraxia and Aphasia: Their Value in Cerebral Localization. New York:
Hafner, 1936.
Papez, J. W. “A Proposed Mechanism of Emotion,” Arch. Neurol. Psychiatry, 38 (1937), 725-743.
Paterson, A. and O. L. Zangwill. “Disorders of Visual Space Perception Associated with Lesions of
the Right Cerebral Hemisphere,” Brain, 67 (1944), 331-358.
Patten, D. H. and D. F. Benson. “Diagnosis of Normal-Pressure Hydrocephalus by RISA

Cisternography,” J. Nucl. Med., 9 (1968), 457-461.
Peters, U. H. “Pseudo-psychopathic Emotion Syndrome of Temporal Lobe Epileptic,” Nervenarzt,

40 (1969), 75—82.
Piercy, M. and V. O. G. Smyth. “Right Hemisphere Dominance for Certain Non-Verbal Intellectual
Skills,” Brain, 85 (1962), 775-790.
----. “The Effects of Cerebral Lesions on Intellectual Function: A Review of Current Research
Trends,” Br. J. Psychiatry, 110 (1964), 310-352.
Pilleri, G. “The Kluver-Bucy Syndrome in Man,” Psychiatry Neurol., 152 (1967), 65-103.
Poeck, K. “Pathophysiology of Emotional Disorders Associated with Brain Damage,” in P. J. Vinken

and G. W. Bruyn, eds., Handbook of Clinical Neurology. Vol. 3, pp. 343-367.
Amsterdam: North-Holland, 1969.
Poeck, K. and B. Orgass. “Gerstmann’s Syndrome and Aphasia,” Cortex, 2 (1966), 421-437.
Poeck, K. and G. Pilleri. “Release of Hypersexual Behavior Due to Lesion in the Limbic System,”
Acta. Neurol. Scand., 41 (1965), 233-244.
Pond, D. A. “The Schizophrenia-like Psychoses of Epilepsy,” Proc. R. Soc. Med., 55 (1962), 316.
Pool, J. L. and J. W. Correll. “Psychiatric Symptoms Masking Brain Tumor,” J. Med. Soc. N.J., 33
(1958), 4-9.
Rasmussen, T. “Surgical Therapy of Frontal Lobe Epilepsy,” Epilepsia, 4 (1963), 181-198.
Reeves, A. G. and F. Plum. “Hyperphagia, Rage and Dementia Accompanying a Ventromedial

Hypothalamic Neoplasm,” Arch. Neurol., 20 (1969), 616-624.
Remington, F. B. and S. L. Rubert. “Why Patients with Brain Tumors Come to a Psychiatric
Hospital: A Thirty Year Survey,” Am. J. Psychiatry, 119 (1962), 256-257.
Roberts, L. “The Relationship of Cerebral Dominance to Hand, Auditory and Ophthalmic

Preference,” in P. J. Vinken and G. W. Bruyn, eds., Handbook of Clinical Neurology,
Vol. 4, pp. 312-326. Amsterdam: North-Holland, 1969.
Rozanski, J. “Peduncular Hallucinosis Following Vertebral Angiography,” Neurology, 2 (1952),

341-349.
Schilder, P. “Fingeragnosie, Fingerapraxie, Fingeraphasie,” Nervenarzt, 4 (1931), 625-629.
Scoville, W. B. “The Limbic Lobe in Man,” J. Neurosurg., 11 (1954), 64-66.
Scoville, W. B. and B. Milner. “Loss of Recent Memory after Bilateral Hippocampal Lesions,” J.
Segarra, J. M. “Cerebral Vascular Disease and Behavior. I. The Syndrome of the Mesencephalic
Artery,” Arch. Neurol., 23 (1970), 408-418.
Semmes, J., S. Weinstein, L. Ghent et al. “Correlates of Impaired Orientation in Personal and
Extrapersonal Space,” Brain, 86 (1963), 747-772.
Serafetinides, E. A. and M. A. Falconer. “The Effects of Temporal Lobectomy in Epileptic Patients

with Psychosis,” J. Ment. Sci., 108 (1962), 584-593.
----. “Some Observations of Memory Impairment After Temporal Lobectomy for Epilepsy,” J.
----. “Speech Disturbances in Temporal Lobe Seizures. A Study of 100 Epileptic Patients
Submitted to Anterior Temporal Lobectomy,” Brain, 86 (1963), 333-346.
Shearer, M. L. and S. M. Finch. “Periodic Organic Psychosis Associated with Recurrent Herpes
Simplex,” N. Engl. J. Med., 271 (1964), 494-497.
Slater, E., A. W. Beard, and E. Glithero. “The Schizophrenia-like Psychoses of Epilepsy,” Br. J.
Psychiatry, 109 (1963), 95-150.
Smith, R. A., D. B. Gelles, and J. J. Vanderhagen. “Subcortical Visual Hallucinations,” Cortex, 7

(1971), 162-168.
Smith, R. A. and W. A. Smith. “Loss of Recent Memory as a Sign of Focal Temporal Lobe Disorder,”
J. Neurosurg., 24 (1966), 91-95.
Spillane, J. D. “Nervous and Mental Disorders in Cushing’s Syndrome,” Brain, 74 (1951), 72-94.
Stevens, J. R. “Psychiatric Implications of Psychomotor Epilepsy,” Arch. Gen. Psychiatry, 14 (1966),

461-471.
Stritch, S. J. “The Pathology of Brain Damage Due to Blunt Head Injuries,” in A. E. Walker and W. F.
Caveness, eds., The Late Effect of Head Injury, pp. 501-526. Springfield, Ill.: Charles
C. Thomas, 1969.
Subirana, A. “The Relationship Between Handedness and Language Function,” Int. J. Neurol., 4
(1964), 215-234.
Sweet, W. H., F. Ervin, and V. Mark. “The Relationship of Violent Behavior to Focal Cerebral
Disease,” in S. Garattini, and E. B. Sigg, eds., Aggressive Behavior, PP. 336-352.
Proceedings of the Symposium on the Biology of Aggressive Behavior, Milan, May
1968. Amsterdam: Excerpta Medica, 1969.
Sweet, W. H., G. A. Talland, and F. R. Ervin. “Loss of Recent Memory Following Section of the
Fornix,” Trans. Am. Neurol. Assoc., 84 (1959), 76-82.
Sykes, M. K. and R. F. Tredgold. “Restricted Orbital Undercutting,” Br. J. Psychiatry, 110 (1964),
609-640.
Talland, G. A. Deranged Memory: A Psychonomic Study of the Amnesic Syndrome. New York:
Academic, 1965.
Taveras, J. M. “Low-Pressure Hydrocephalus in Neuro-Ophthalmology,” in J. L. Smith, ed.,
Symposium of the University of Miami and the Bascom Palmer Eye Institute, Vol. 4,
pp. 239-309. St. Louis: Mosby, 1968.
Taylor, D. C. “Aggression and Epilepsy,” J. Psychosom. Res., 13 (1969), 229-236.
Terzian, H. and G. Dalle-Ore. “Syndrome of Klüver-Bucy Reproduced in Man by Bilateral Removal

of the Temporal Lobes,” Neurology, 5 (1955), 373-381.
Thomas, E. W. “Current Status of Therapy in Syphilis,” JAMA, 162 (1956), 1536-1539.
Tow, P. MacD. and C. W. M. Whitty. “Personality Changes After Operations on the Cingulate Gyrus
in Man,” J. Neurol. Neurosurg. Psychiatry, 16 (1953), 186-193.
Tzavaras, A., H. Hecaen, and H. LeBras. Le Probleme de la Specificite du Deficit de la

reconnaissance du visage humain lors des lesions hemispheriques unilaterales,”
Ullman, M. Behavioral Changes in Patients Following Strokes. Springfield: Charles C. Thomas,

1962.
Victor, M., R. D. Adams, and G. H. Collins. The Wernicke-Korsakoff Syndrome. Philadelphia: Davis,
1971.
Victor, M., J. Angevine, E. Mancall et al. “Memory Loss with Lesions of Hippocampal Formation,”
Arch. Neurol., 5 (1961), 244-263.
Walch, R. “Uber die Aufgaben der Himverletztenheime nach dem Bundesversorgungsgesetz,” in E.

Renwald, ed., Das Hirntrauma, pp. 461-468. Stuttgart: Thieme, 1956.
Walker, A. E. “Recent Memory Impairment in Unilateral Temporal Lesions,” Arch. Neurol., 78

(1957). 543-552-
Walshe, F. G. and W. F. Hoyt. Clinical Neuro-Ophthalmology, 3rd ed. Baltimore: Williams & Wilkins,
1969.
Warrington, E. K. “Constructional Apraxia,” in P. J. Vinken and G. W. Bruyn, eds., Handbook of
Clinical Neurology, Vol. 4, pp. 67-83. Amsterdam: North-Holland, 1969.
Weinstein, E. A. and M. Cole. “Concepts of Anosognosia,” in L. Halpern, ed., Problems of Dynamic

Neurology, pp. 254-273. Jerusalem: Jerusalem, 1963.
Weinstein, E. A. and R. L. Kahn. Denial of Illness: Symbolic and Physiologic Aspects. Springfield, Ill.:
Charles C. Thomas, 1955.
Weisenburg, T. S. and K. E. McBride. Aphasia. New York: Hafner, 1964.
Welch, K. and P. Stuteville. “Experimental Production of Unilateral Neglect in Monkeys,” Brain, 81

(1958), 341-347.
Wernicke, C. Der aphasiche Symptomen-complex. Breslau: Franck & Weigert, 1874.
Wertheim, N. and M. I. Botez. “Receptive Amusia: A Clinical Analysis,” Brain, 84 (1961), 19-30.
White, L. E. and R. F. Hain. “Anorexia in Association with a Destructive Lesion in the

Hypothalamus,” Arch. Pathol., 68 (1959), 275-281.
Whitty, C. W. M. and O. L. Zangwill. Amnesia. New York: Appleton-Century-Crofts, 1966.
Williams, D. “The Structure of Emotions Reflected in Epileptic Experiences,” Brain, 79 (1956), 29-
67.
----. “The Temporal Lobe and Epilepsy,” in D. Williams, ed., Modern Trends in Neurology, 2nd ser.
pp. 338-352. London: Butterworth, 1957.
Williams, M. and J. Pennybacker. “Memory Disturbances in Third Ventricle Tumors,” J. Neurol.

Neurosurg. Psychiatry, 17 (1954), 115-123.
Yakovlev, P. I. and P. Rakic. “Patterns of Decussation of Bulbar Pyramids and Distribution of

Pyramidal Tracts on Two Sides of the Spinal Cord,” Trans. Am. Neurol. Assoc., 91
(1966), 366-367.
Zangwill, O. L. “Intellectual Status in Aphasia,” in P. J. Vinken and G. W. Bruyn, eds., Handbook of
Clinical Neurology, Vol. 4, pp. 105-111. Amsterdam: North-Holland, 1969.
Notes
1The work reported here was supported in part by Grant NS-06209 of the National Institute of
Neurological Diseases and Stroke.
Chapter 10
The Neural Organization Of Language: Aphasia

And Neuropsychiatry1
Jason W. Brown
. . . the thought which only seemed naked was but pleading for the clothes
it wore to become visible, while the words lurking afar were not empty
shells as they seemed, but were only waiting for the thought they already
concealed to set them aflame and in motion.
—Vladimir Nabokov
The History of Aphasia
From Gall to Wernicke
Although there are references to speech loss from cerebral lesions
dating as far back as the Hippocratic Corpus of 400 B.C., the modern era is
usually taken to begin with the phrenology of Franz Joseph Gall in the early
19th century. His work had far-reaching implications, but for the still unborn
field of aphasia research it signaled a shift in attention away from the holistic
approach which was current at the time to the possibility of a cerebral
localization of speech. Gall reasoned specifically from a single instance in
which large eyes and a prodigious verbal memory happened to occur in the
same individual, a childhood acquaintance, that speech was a function of the

frontal lobes. The French neurologist Bouillaud was so impressed by this
assertion that he offered an award of 500 Frs. to anyone who could disprove
it. Bouillaud also wrote an historically important paper in which he

distinguished between the sign function of speech and its articulatory
apparatus (i.e., between internal and external speech), and on the basis of a
few cases argued that the “legislative organ of speech” resided in the anterior
(frontal) lobes of the brain.
Paul Broca, a student under Bouillaud at Bicêtre Hospital, could not fail
to be influenced by the exciting debate stimulated by these ideas. An
opportunity to settle the issue finally occurred when a fifty-one-year old
patient with excellent comprehension but almost complete loss of speech was
admitted to the ward. The postmortem examination, from which date one can
ascribe the beginnings of the science of aphasia, demonstrated, as predicted
by Bouillaud, a large Sylvian lesion in the left hemisphere, the center of which
was in the third, and partly the second, frontal convolution. Broca conceived
the speech loss, aphemia, to be a kind of ataxia of those movements which
served for the articulation of words. In subsequent papers he defined the
“motor speech area” as consisting of the posterior part of the third or inferior
frontal convolution (F3), and by 1865 sufficient data had been collected to
suggest a possible relationship, in right handers, to the left hemisphere. It is of

interest that the term “aphemia,” chosen by Broca for this disorder, was
criticized by Trousseau on the grounds that it connoted infamy (i.e.,
unspeakableness ), rather than lack of speech. Gradually it has become

customary to use the term “aphasia” for loss of speech and writing, and
“aphemia” for loss of speech alone.
Certainly it can be said that at that time the various approaches to the
problem of aphasia had not yet hardened into the distinct schools of thought
that so characterized later work in the field. While Broca is often represented
as the earliest “localizer,” an impartial reading of his papers gives a very
different impression. For example, his treatment of “aphemia” as a return to a
childhood stage in speech development foreshadows modem accounts of

agrammatism and phonemic disintegration. Moreover, Broca stressed that
aphemia was a type of motor speech disorder, and distinguished it, as had
Bouillaud before him, from the true language disturbance of verbal amnesia.
Hughlings Jackson was generally sympathetic to Broca’s work, though
he disapproved of the distinction between articulation and word memory,

these being just different aspects of the capacity to produce words. Following
J. G. F. Baillarger, Jackson stressed the common dissociation between
voluntary and involuntary performances in motor aphasia, and suggested a
special relation of the latter to minor hemisphere. In later writings Jackson
emphasized that the aphasic, though speechless, was not wordless, and that
aphasia consisted not of a loss of speech but a loss of the ability to
“propositionize,” defining a proposition as a relation of words such as to make
one new meaning. Perhaps Jackson’s chief contribution to aphasia theory, and
particularly to what was later to become psychoanalytic theory, was his

evolutionary account of levels of function. According to this view, successively
higher levels of functional organization were laid down in the course of
encephalization, each new level suppressing and having a degree less

automatization than that which came before. This conception had a clear
impact on Freud’s early thinking and without doubt figured prominently in
the topographic theory and the account of repression.
The ontogenetic interpretation of Broca, and the phylogenetic account

of Jackson, were destined to survive but a short time in neuropsychology. In
1874 Carl Wernicke, after six months on an aphasia service, published his
monograph Der aphasische Symptomenkomplex. Following T. Meynert’s
demonstration of the central terminations of the auditory nerve, Wernicke

argued that destruction of the sound images of words, laid down adjacent to
the acoustic projection zone in the posterior part of the superior temporal
convolution (T₁), should result in an inability to understand or repeat speech.
Since patients with impaired speech comprehension appeared to recognize
objects, and could express some needs by mimicry, the concepts
corresponding to these sounds images were thought to be intact. Thus, three

forms of aphasia could be distinguished: (1) motor or Broca’s aphasia; (2)
sensory aphasia (with destruction of the auditory sound images); and (3)
verbal amnesia, due to involvement of the posterior concept field

(Begriffsfeld). Moreover, Wernicke also commented that a lesion between the
“sensory” and “motor” zones should produce a condition in which
comprehension was preserved, speech was intelligible though paraphasic,
and repetition was selectively impaired. This latter disorder, described on a
theoretical basis only, was termed conduction aphasia, (Leitungsaphasie).
The simple diagrams which Wernicke employed to illustrate these aphasic

disorders (Figure 10-1) lead to the brain maps of L. Lichtheim and others,
achieving in the latter part of the 19th century an almost baroque complexity,
as in the ornate but wholly imaginary diagram of Charcot (Figure 10-2).
Figure 10-1.
Figure 10-1.
Diagrams from Wernicke representing hypothetical sensori-motor centres

and conducting pathways
Figure 10-2.
Figure 10-2.
Charcot’s illustration of mechanisms involved between hearing the sound of

a bell, and producing the word “bell” in speech and writing. (Reprinted with
the permission of Butterworth & Company.)
The association theory of Wernicke, in providing a reductionistic
alternative to the genetic accounts of Broca and Jackson, had an enormous
appeal at the time and continued to dominate thinking until the critique of
Pierre Marie in 1906. However, the Wemicke-Lichtheim model was
challenged in one short but important monograph.
The Contribution of Freud to Aphasia
In 1891, when Freud’s modest study of aphasia first appeared, the
school of Wernicke was the most influential in Europe. It is only against this
background that one can sense the daring—indeed, revolutionary—flavor of
Freud’s work.2 The book is chiefly concerned with a refutation of the

localizationist (centers and pathways) model in favor of a concept of a unitary
cortical speech zone:
Our concept of the organization of the central apparatus of speech is that

of a continuous cortical region occupying the space between the
terminations of the optic and acoustic nerves and of the areas of the
cranial and certain peripheral motor nerves in the left hemisphere. . . . We
have refused to localize the psychic elements of the speech process in
specified areas within this region . . . (and) the speech centres are, in our
view, parts of the cortex which may claim a pathological but no special
physiological significance, [p. 67]
In relation to this speech zone, language was built up through a process
of psychological association (Figure 10-3). Accordingly:
From the psychological point of view the “word” is the functional unit of
speech; it is a complex concept constituted of auditory, visual and kin-
aesthetic elements, [p. 73]
Figure 10-3.
Schema of the formation of a word concept, from Freud.
It follows that:
. . . all aphasias originate in interruption of associations, i.e., of conduction.

Aphasia through destruction or lesion of a centre is to us no more and no
less than aphasia through lesion of those association fibres which meet in
that nodal point called a centre, [pp. 67-68]
On this basis Freud attempted a reclassification of the aphasias, an
attempt far from successful, for even he had to confess that:
I am well aware that the considerations set out in this book must leave a
feeling of dissatisfaction in the reader’s mind. I have endeavored to
demolish a convenient and attractive theory of the aphasias, and having
succeeded in this, I have been able to put into its place something less
obvious and less complete, [p. 104]
The reader does sense, however, that the work on aphasia served to
liberate Freud’s thinking from the anatomically bound dogmas of the time,
and encouraged him to proceed into psychological speculation without the
gnawing feeling that anatomy—at least the anatomy of the day—must always
have the last word. There is, moreover, much in this monograph which
presaged his later formulations. Specifically, one notes the application of the
Jacksonian concept of dissolution to the pathology of learned associations;

there is the importance given to the “word” as the final segment in thought
production, signaling the prominent position later to be given to verbalization
in the psychoanalytic method; there is a suggestion that the analysis of
paraphasic errors may have played a part in his later concept of “slips-of-the-
tongue;” and chiefly, to my mind, there is the central idea that if
neuropsychological symptoms could result from a breakdown in learned
associations, psychological symptomatology might result from the formation

of pathological associations.
A Search for New Formulations
Whereas Freud’s lucid and meticulous criticism of the classical school
fell on deaf ears, Pierre Marie’s aggressive paper of 1906 came like a
bombshell. The very subtitle of this paper “La troisieme circonvolution
frontale gauche ne joue aucun role special dans la fonction du langage,” was
an indication of Marie’s extreme dissatisfaction with the excessively
localizationist approach to aphasic disorders. Marie held that the expressive
defect in motor “aphasia” was actually an anarthria due to involvement of the
zone of the lenticular nucleus (Figure 10-4). Wernicke’s, or true, aphasia was
a kind of intellectual defect resulting from a posterior lesion. A combination of
anarthria and the comprehension defect of true aphasia was responsible for
“Broca’s aphasia.”
Figure 10-4.
A lesion of the quadrilateral space of Marie, lying between the anterior (a)
and posterior (b) extent of the lenticular nucleus, produces an anarthria,
while a lesion at I, involving the lenticular zone and also interrupting
temporoparietal fibers, accounts for true aphasia.
At the same time that Marie was attempting to rid neurology of its
aphasia brain maps, as naive as they were numerous, another and more
constructive trend was under way. The point of view was beginning to
emerge that language was not a piecemeal assembly of smaller units but
rather a productive activity within a cognitive matrix. The influence of

Humboldt was still present in the developing science of linguistics, and this,
combined with the hierarchic theory of Jackson and the mental structuralism
of the Wurzburg school, came together in Arnold Pick’s new concept of the
aphasias.
For Pick the aphasias were disruptions at sequential stages in the
realization of speech out of thought. He described four stages in the transition

of thought to speech: an early stage (1) in which thought is formulated with
increasing clarity out of memory in such a way that its partial contents are
combined to a type of schematic or structural whole; the second stage (2),

that of structural thought, is prior to linguistic formulation; there is a
preparation toward a predicative arrangement, and elements of tone, tempo,
and grammar come into play; the next stage (3), that of the sentence pattern,
develops under the influence of an emotional factor, and leads to the

automatic choice of words. There is a correspondence between Pick’s account
of intuitive (1) and structural (2) thought, and the Bewusstseinslage and
Bewusstheit of the Wurzburg school, as well as with the (later) “sphere” and
“concept” of Paul Schilder. Moreover, the possibility that language issued out
of a prefigurative ideational stage embedded in a spatial attitude leads to the

concept of spatial defects in the semantic aphasia of Head (see p. 257), as well
as the more recent notion that the memory trace may be integrated in the
space-coordinate system. Pick’s work has been discussed in recent
publications by Spreen and Brown.
In England, Head, who was familiar with Pick’s writings, attempted to
incorporate them with personal observations of aphasic patients. His
classification of verbal, syntactic, nominal, and semantic aphasia represents
an advance only in the postulation of the final of these forms, semantic

aphasia. Even here, however, the effort to bring this disputed “deep-level”
aphasia into relation with disorders of spatial-constructional thought tended
to weaken the force of Head’s argument.
The two other major figures of the time, Karl Kleist and Kurt Goldstein,
were unable to resolve their dynamic psychological point of view with a
localizationist mentality. Kleist, for example, attempted to translate Pick’s

classification into an extreme form of (myeloarchitectonic) cortical
localization. While there is much of value in Kleist’s work, a cursory glance at

his pathological specimens is enough to dissuade even the most sympathetic
reader from too ready an acceptance of his anatomical theories. On the other
hand, Goldstein did not even attempt to superimpose his view of the
psychology of language on a pathological anatomy, but wisely elected to treat
the psychological and pathological aspects separately. With regard to the

former, his contribution has to be measured by the exhaustive scholarship
which was brought to bear on every phase of his work, the Gestalt
orientation, and emphasis on organismic factors. The cognitive basis of
language was always in the foreground of his work. Perhaps the one concept
for which he is best known is the distinction of “abstract” and “concrete”
behavior. However, most workers now recognize that disorders which were
attributed to alteration of the abstract attitude, e.g., anomia, occur without

such alteration, while concrete thinking occurs in the absence of true anomia.
For this reason, a classification of aphasia based on the concept of
“abstraction” and “concreteness” does not have wide appeal. According to
Goldstein, anomia (anomic or amnesic aphasia) was a disorder of thought

(i.e., of abstraction), while Broca’s aphasia was chiefly a defect of the final
stages of word production. Central (conduction) aphasia was a disturbance

between the two, at the transition of thought to speech, viz., a defect of “inner
speech.” To some extent this classification recalls the microgenetic account of

Pick, though Goldstein’s pathological descriptions, and his interpretations of
the pathological anatomy, did not deviate greatly from the original views of
his teacher, Wernicke.
In addition to this line of study, which was fundamentally a continuation
of certain trends in the early German school of aphasia, there were also
during this time several other noteworthy contributions. Weisenberg and
McBride introduced American readers to the historical debate surrounding
various issues in the field, and provided a healthy—even if somewhat
vacuous—alternative to the rigid classifications then available. Johannes
Nielsen was for many years one of the principle authorities on aphasia in the
United States. His work, like that of Kleist, was characterized by erudition and
a dynamic point of view not readily apparent on superficial reading. Penfield
and Roberts gave valuable descriptions on the effects of stimulation of speech
cortex in waking subjects, and argued, chiefly from negative extirpations, that
thalamo-cortical connections played a central role in the anatomical
organization of language. Some of these traditions have been carried on in
England, by Brain and Critchley among others. In Germany, the Gestalt

approach has been furthered by the work of Bay and Conrad, and in France
the best known authors are Alajouanine, Lhermitte and coworkers, and
Hecaen.
Status of the Field
There are two major orientations in modern aphasia research, both of
which have grown out of the classical tradition: the argument from the
psychological point of view, and the argument from the point of view of
anatomy.
Psychological Accounts of Aphasia
A great number of distinct theories fall into this category. Of these, one
of the more progressive is the current attempt to bring linguistic description
into relation with aphasic symptomatology. Psycholinguists have shown

increasing interest in aphasic language and the term neurolinguistics is often
taken as a designation of this new synthetic approach.
One of the earliest attempts in this direction was Jakobson’s study of

aphasic breakdown and correspondences with language acquisition in the
child. More recently, utilizing Luria’s classification and the distinction implicit
in this system of posterior spatial (simultaneous) and anterior temporal

(successive) processes, two major categories of aphasic disturbance have
been distinguished, a similarity disorder, characterized by an inability to
select and identify, and a contiguity disorder, characterized by an inability to

combine and integrate.
There have also been attempts to demonstrate correspondences

between aphasic language and expectations of distinctive feature theory.
Especially important in this regard are studies by Blumstein and Lecours and
Lhermitte. The transformational grammar of Chomsky has been tested
against aphasic language in studies by Weigl and Bierwisch. In this respect,
the reader is referred to studies by Goodglass, and Zurif on agrammatism;
Green, Kreindler, and Kertesz on jargonaphasia; and Marshall and Newcombe,
and Rinnert and Whitaker on semantic paraphasia. A review of work in

psycholinguistics and aphasia was published in 1973.
The term “neurolinguistics” appears to have been introduced by Henri
Hecaen, who has also developed a linguistic typology of the aphasias.
Accordingly, three major aphasic groups, expressive, amnesic, and sensory,
are distinguished. Within the expressive group, there are three forms: (1) an
impairment of phonemic realization (motor aphasia); (2) an impairment of
syntactic realization (agrammatism ); and (3) an impairment of programming
at the level of the phrase (conduction aphasia). Amnesic aphasia is a

selectional disorder, often linked to other aphasic forms. Within the group of
sensory aphasia, three elements can be isolated: word deafness, impaired
verbal comprehension, and a disorganization of attention. These elements
often occur together in varying degree, and determine the pattern of

expressive language.
The classification of Luria is a departure from standard works chiefly in

the functional approach toward each aphasic syndrome, and not in the
description of the symptom complex per se. The following six forms are
distinguished: (1) sensory aphasia, in which the expressive pattern is
attributed to impaired phonemic discrimination; (2) acoustic-amnestic
aphasia, which differs from the above chiefly in the improved repetition; (3)
afferent and (4) efferent motor aphasia, which incorporate distinct aspects of
Broca’s aphasia; (5) semantic aphasia, which seems to include amnestic
aphasia, and is similar to Head’s account; and (6) dynamic aphasia, with
reduced spontaneity of speech, similar to a mild transcortical motor aphasia.
However, objections can be raised against this classification on several

counts. For example, the impairment of phonemic discrimination, central to
the sensory forms, is tested chiefly through productive systems; phonemic
discrimination is an extremely resistant ability in a wide range of aphasic

patients with disturbed speech comprehension; evidence for the kin-aesthetic
basis and postcentral localization of afferent aphasia is wanting; dynamic
aphasia seems to merge with the reduced speech picture of dements and
various types of partial mutism. Moreover, as suggested by the syndrome

designations, there is assumed to be a specific functional impairment in each
disorder, i.e., in verbal memory, acoustic sensation, the evidence for which is
at best controversial. Finally, the pathological account of primary and
secondary cortical “analysers” in relation to these disorders does not take us

very far beyond classical speculations regarding a similar role for primary
(projection) and secondary (association) cortex. Nonetheless, Luria’s work is
extremely valuable for the ingenious testing methods and careful clinical
observation, the thorough study of individual cases and the application of an
experimental approach to traditional “bedside” technique. From the point of
view of theory, the major contribution is the concept of aphasia as a
disturbance in cognitive function. Thus, speaking of language organization,
Luria has written that the system of semantic codes “possesses a complex
hierarchical structure. It begins with the system of words, behind each of
which there stands not only a unitary image, but a complex system of
generalizations of those things which the word signifies.” Similarly,
perception is studied not as a simple receptive function but as an active
process, comparable to speech and motility. Perception involves “. .. the
recognition of the dominant signs of an object, the creation of a series of

visual hypotheses or alternatives, the choice of the most probable of these
hypotheses, and the final determination of the required image . . .” The reader
will note that this sequence is identical to other descriptions of stages in the
course of problem-solving behavior, i.e., thinking.
Eberhard Bay has also viewed aphasia as a disturbance in concept

formation. However, Bay’s model is incomplete and to a degree expedient,
and exception can be taken to many interpretations, e.g., the account of
agrammatism as an economy of effort or the explanation of paraphasia as

secondary to lack of speech awareness and logorrhea.
Klaus Conrad conceives aphasia as an arrest or interruption in the
microgenesis of cognition. An aphasia is a pregestalt (Vorgestalt) stage in the
process of language formation. Conrad has distinguished four levels of
pathophysiological change which, from the highest to the lowest are,
respectively, Strukturwandel, Gestaltwandel, Funktionswandel, and

Formivandel. Pathology induces a change in functional level, not a loss of
function. The reduced level then determines the symptomatology. However
appealing this approach, the discussion of aphasia is not altogether
successful, for a general theory of regression does not account for the
diversity of aphasic symptoms. Conrad has also helped to clarify the problem
of “severity” in hierarchical systems. In Conrad’s view, the lower (i.e., word
close) the lesion, the more severe, but more restricted, the local effect, while
higher (i.e., thought close) defects produce a slight impairment in more
widespread functions, and involve more of the patient’s native personality.
Anatomical Theories of Aphasia
Psychological studies of aphasia have not yet succeeded in the
formulation of a unitary theory of these disorders, nor are such theories
commonly attempted. However, caution has not been the most distinguishing
characteristic of the anatomical school. Although there continue to be minor

disputes over the specific role in language of one or another anatomical
structure, the basic approach, on which there is, regrettably, essential
agreement, has remained unchanged for a century after Wernicke’s
monograph. The position has been summarized by Geschwind.
According to this view (Figure 10-5) speech is perceived by way of (left)
Wernicke’s area, and from there conveyed to “Parietal association” cortex for
comprehension. Language is presumed to be formed in some way in the

posterior part of the brain and passed forward to Broca’s area for articulation.
Repetition is accomplished through a cortical reflex circuit, comprising
Wernicke’s area, Broca’s area, and the fasciculus arcuatus between, though
this pathway is not usually specified as that underlying the postero-anterior

flow (development) of spontaneous speech. The aphasias represent
disruptions of these processes (actually, the processes are inferred from their
pathology to be localized to these areas). Thus, a lesion of left posterior

superior temporal gyrus is said to produce Wernicke’s (sensory, receptive,
jargon) aphasia, lesion of the posterior inferior frontal gyrus, Broca’s (motor,
expressive, anarthric) aphasia, and lesion of the fasciculus arcuatus,

conduction (central, repetition) aphasia.
Figure 10-5.
Figure 10-5.
A contemporary diagram of speech cortex, illustrating structures which are

presumed to be involved in the production of aphasia, i.e., Broca’s area in
motor aphasia, Wernicke’s area in jargonaphasia, angular gyrus in anomia,
and arcuate fasciculus in “conduction” aphasia. (From “Language and the
Brain,” by N. Geschwind. Copyright c 1972 by Scientific American, Inc. All
rights reserved.)
Anomia (amnestic, nominal aphasia) is due to lesion of parietal cortex
(angular gyrus), but does not have the strong localizing features of the other
syndromes. The transcortical aphasias occur with selective preservation of

the primary speech zone. Disorders of reading, writing, and praxis are aligned
with this anatomical account through interpretations based on the effects of
lesion of the corpus callosum. For example, the syndrome of “pure alexia” or
word blindness is explained through the destruction of the left occipital
cortex and the splenium of corpus callosum, which produces a state in which
the patient presumably can see written words in the intact left visual field but
is unable to read because of interruption of callosal fibers conveying the
perception of these words to “speech cortex” for language analysis (Figure
10-6).
Figure 10-6.
Figure 10-6.
According to the classical account of pure alexia, a lesion of left occipital

cortex and splenium of corpus callosum results in an interruption in the flow
of visual information to left speech cortex, while lesion of angular gyrus leads
to alexia with agraphia. This condition, however, can be explained on a
perceptual basis through a reduced functional level in right occipital lobe.
This classical account of aphasia has been reinforced through findings in
patients undergoing complete surgical section of the corpus callosum as a
form of treatment for epileptic seizures. Two recent reviews by Dirnond and
Gazzaniga are available. Following this operation, patients demonstrate a
relative inability to name objects tactually with the left hand, or read material
presented tachistoscopically to the left visual field, nor can they carry out to
command skilled actions with the (distal) left extremities. However, patients
are able to identify the tactual or visual object or word by selecting it (the
appropriate object) from an assortment, if this is done nonverbally and with
the left hand. This has led to the conclusion that right-hemispheric contents
are isolated from dominant left-hemispheric, and that, to some extent, one
can speak of a separate consciousness in each hemisphere. Evidence for a left-
hemispheric priority in verbal tasks, and a right-hemispheric priority on
visual-spatial performance, has given rise to speculations regarding different

forms of thought in each hemisphere. Such considerations range from the
improbable (Figure 10-7) to the absurd. The wide interest in studies of this
type, and the readiness with which many students accept the simple
interpretations offered, suggests that we are at the beginning of a wave of
neophrenology that could lead to a long unproductive period in
neuropsychology.
Comment. There is no question but that the introduction of linguistic
concepts and methods has had a profound effect on research in aphasia. In
particular, interest in transformational grammar, and experimental studies
stimulated by this model, have helped to bring about a considerably more
dynamic approach to the problems of aphasia than has characterized the field
in the past. There is also increasing dissatisfaction with previous theories of
aphasia. This includes those on the one hand in which some common element
is isolated from the symptomatology and then employed to explain all the
other symptoms, e.g., as has occurred in regard to “abstract attitude,” Gestalt
formation, etc., as well as, at the other extreme, accounts in which a specific
(disordered) function is proposed for each element of the symptom complex,
e.g., as in stimulus response or association theories of aphasia.
Figure 10-7.
A more extreme representation of left and right hemispheric functional
asymmetry. (From “Perception in the Absence of the Neocortical
Commissures,” in D. A. Hamburg, K. Pribram, and A. Stunkard, eds.
Perception and Its Disorders. New York: Williams & Wilkins. Reprinted with
the permission of the publisher and the Association for Research in Nervous
and Mental Disease.)
Psychological models of aphasia must, it would seem, conform to the
constraints imposed by pathological correlations of aphasic syndromes. The
pathology of aphasia is neither obvious nor random but is a subtle clue to the
anatomy and organization of normal language. Both language production and
the anatomical structure by which it is supported develop in an orderly way.
In pathology, the change in language and the change in structure are
inseparable and equally lawful. Structure is not a rigid skeleton on which

function is superimposed, but is an organic form created by the continuous
flow of process. Seen in this light, the combined study of aphasic language and
of its correlated brain pathology appears to be the most trustworthy guide to
an understanding of the structure of real language.
Typology of Aphasia
Introduction
Language develops through a formative or microgenetic process as a
component of cognition. There are several more or less arbitrary stages in
this process, though normally we are aware of only the final product. In
various states, for example during sleep or hypnagogy, one may see these
earlier, otherwise concealed (i.e., traversed), levels appearing as pathological
speech forms. Generally this is a transient phenomenon. However, with
structural brain lesion the “earlier” stage, the aphasic syndrome, may become
the final speech product and this product may persist indefinitely as a
relatively stable form. Each type of aphasia, therefore, can be conceived as a
preliminary level in normal language which pathology has brought to the fore.
Moreover, at each of these levels, the “pathological” language form, the

aphasia, also points to a corresponding level in cognitive development. Thus
we may study an aphasia both from the point of view of language, as a
manifestation of a prefigurative stage in the normal process, and from the

point of view of cognition, as exhibiting features characteristic of whatever
cognitive stage happens to be realized in the momentary language level.
When we look at aphasia from this standpoint, questions arise
concerning some of the most basic aspects of brain study. For example, the
view that an aphasic syndrome is the result of a combination of two or more

discrete defects must be treated with great caution. Wernicke’s aphasia is not
word deafness plus verbal paraphasia plus anosognosia plus euphoria, but
rather is a defect in cognition at some level where processes underlying these

disorders (rather, achievements) are coextensive. The aphasic syndrome
represents a molar level to which the patient has been reduced and is not a
compilation of disorganized functions.
This, in turn, has implications for our understanding of severity. Within
the posterior or fluent aphasias, for example, it would be misleading to speak

of a severe jargon or a mild paraphasia. This ignores the change in the
qualitative aspects of the jargon, or the paraphasia. When semantic jargon
deteriorates it may become neologistic; when verbal paraphasia deteriorates
it may approach semantic jargon. The central point is that an alteration of one
element in the disorder, say in comprehension or in repetition, will always be

accompanied by a change in other elements as well. If there is sufficient
change the result is a new syndrome and not just a more severe manifestation
of the original condition. We may say that severity in a microgenetic system
always entails a difference of kind as well as degree.
In the classification that follows, the aphasias are arranged in such a
way as to reflect the sequence of stages in normal language production
(Figure 10-8). This sequence unfolds on an axis between a semantic or
selectional process and a stage of phonemic encoding. The precursors of the

words, the forms or clusters of the utterance-to-be, emerge through a
semantic operation by means of which the developing utterance is shaped in
the direction of the final performance. At this stage, there is a “noun priority”
in the entry of lexical items into the forming sentence pattern. A transition
then occurs from the ordered abstract-sentence frame to the phonemic

representatives of the constituent words in preparation for articulation. At
this stage, the small (function) words are introduced. In the course of this
process both a referential (i.e., nominative) and an expositional (i.e.,
discursive ) orientation can be discerned, a discovery which has helped to
clarify some of the complex interrelationships between these forms.
Figure 10-8.
The aphasias can be aligned in a transitional series corresponding to the

sequence of stages in normal language production. These relationships are
especially evident in the course of recovery or deterioration. In pathological
states the arrows are to be considered bidirectional. A distinction is made as
to whether there is preferential involvement in referential or expositional
speech (partial aphasic forms) or both (major syndromes). Neologistic
jargon is not depicted but represents involvement of both the semantic and
phonemic levels.
Apart from its linguistic character, each of the aphasias incorporates
aspects of a corresponding level in cognition. A change in awareness or in
affect, the presence or absence of delusional or hallucinatory phenomena,
these are not additions to the clinical picture but have an inner bond with the
aphasic form. These alterations in cognition will be briefly noted in the
description of each syndrome and more fully discussed in the final section.
Reference will be made to the pathological “locus” of each type of aphasia,
reserving a more thoroughgoing discussion for the following section.
Description of the Aphasias
Semantic Disorders
Semantic Jargon. This is basically a disorder of word meaning that

involves both naming and conversational speech in the presence of moderate
loss of oral comprehension. The disorder is associated with a lesion of the
posterior-middle and superior-temporal gyrus (posterior T₂ and T₁), often

bilaterally. In older patients the lesion is more commonly unilateral and on
the left side. Semantic jargon is one form of Wernicke’s (receptive, sensory)
aphasia. Such patients produce good words and sentences, but with defective
meaning. An example from Alajouanine et al. is a patient who described a fork
as "... a need for a schedule” or another who defined a spoon as “. . . how many
schemes on your throat.” Another patient, asked about his poor vision, said
“My wires don’t hire right.” A case of Kreindler et al. replied to a question
about his health with: “I felt worse because I can no longer keep in mind from
the mind of the minds to keep me from mind and up to the ear which can be
to find among ourselves.” A patient of Heilbronner responded to a similar
question with “Yes, I think that I am now so safe than now much with others
to some extent directly.” Occasionally, neologisms are present which may lead
to strikingly bizarre utterances. Thus an aphasic physician, asked if he was a
doctor, said “Me? Yes sir. I’m a male demaploze on my own. I still know my
tubaboys what for I have that’s gone hell and some of them go.”
Speech production is fluent, there is no word search, in spite of
incorrect choices, and vocabulary use is fairly good, at times even pretentious.
There is semantic or verbal paraphasia on tests of naming and repetition. This
refers to a substitution of one word for another, e.g., “table” for “chair.”
However, in semantic jargon the link between the substitution and the target
word is often not so clear as in the “in-class” substitution of this example.
Rather, a patient might call a chair an “engine,” or an “Argentina.” The term
semantic paraphasia can be used for this latter type of substitution, and verbal
paraphasia for categorical substitution.
Comprehension is moderately impaired, though ordinarily some
understanding is possible, while reading aloud and writing show alterations

parallel with speech. About 20 percent of such patients are hemiparetic, the
rest often ambulatory and with few or no “hard” neurological findings. In such
patients, a distinction from psychotic language or thought disorder is
frequently difficult. This is particularly so in view of the fact that there is
commonly a euphoric, even manic, mood elevation or aggressivity, and
auditory hallucinations may occur during the course. A paranoid state is not
uncommon, and may make speech therapy difficult or impossible. Patients
tend to be logorrheic, and show partial or complete absence of awareness of
their defective speech. However, they usually reject jargon spoken by the
examiner, and resist efforts at correction of their own speech. The awareness
of speech content, as with all other elements of the syndrome, may change
from moment to moment. Awareness appears to be inversely related to the
semantic “distance” of the utterance from its presumed goal.
This stage of unintelligible semantic jargon may resolve in one of two

directions, to involvement of expositional speech with intact naming, or
involvement of referential speech (naming) with preserved conversation. The
former is termed “semantic aphasia,” the latter (pure) “semantic paraphasia.”

Both of these disorders occur with bilateral temporal-lobe pathology.
Semantic Aphasia. This disorder was first described by Head as an
interruption at a prelinguistic phase in the thought-speech transition.

Patients demonstrated a want of recognition of the full significance of words
and phrases apart from their verbal meaning. There was a failure to
comprehend the final aim or goal of an action and an inability to clearly
formulate a general conception of what was heard, read or seen in a picture,
although many of the details were enumerated. Memory and intelligence
were relatively intact, counting was possible, but calculations were impaired
and there was a failure to understand jokes, games, and puzzles. In Head’s
descriptions the recorded statements and short letters of his cases do not
always convey to the reader the full flavor of the defect as emphasized in the
commentary. Nor did his spatial tests clearly illustrate the specific nature of
the disorder. However, most of his cases demonstrated some grammatical

disturbance. Thus one patient wrote: “Just a few lines to let you know that I
am getting on all right and I shall will be home again. I must tell you that
Uncle George and Aunt Ann cane (came) and see me yesterday and more so
Bob Higgins so I am very Lucky for getting friends.” On another occasion, this
patient remarked, “I was worked for . . .” Another patient wrote: “. . . one could
spend one’s time in a more profitably . . .” and another said: “If I pay too much
attention I get wrong with what I’ve got to do.” Another patient said: “My son
is just home from Ireland. He is a flying man. Takes the ship about to carry the
police to give information, to carry the letters of the police.”
More recent studies show that in semantic aphasia there is a
disturbance of contextual meaning, through which utterances of skewed

meaning are produced. The disorder is especially prominent in proverb, story,
or picture interpretation. Consider this example of a patient’s written
description of his speech (patient’s capitals and punctuation).
Speech that could be found as a Type of speed I believe. I possible mood of

my own maybe because of misunderstanding. Possibly because of my own
thought In a certain way. a friend of mine told myself. I had a “cast Iron
Fact” especially during a conversation, [p. 45]
The disorder is apparent in speech and writing. Speech is fluent and
somewhat logorrheic, and may have a confabulatory flavor (see below).
Comprehension may be quite good, while naming, reading aloud, and

repetition are intact. Spatial-constructional difficulty may or may not be
present, and the neurological examination can be normal except for the
aphasia. Patients tend to be euphoric with partial insight into their disability.
Paranoia and hallucination are not prominent features, but too few cases have
been described to be more precise on this point.
Semantic Paraphasia. In this disorder which has been (incorrectly)

termed “nonaphasic misnaming,” conversational speech is fairly well
preserved but errors occur on tests of object naming. These take the form of
“associative” responses, e.g., a pipe is called a smoker, glasses a telescope. The

pretentious and facetious quality of the paraphasia appears when a doctor is
called a butcher or a syringe a hydrometer to measure fluids. The paraphasia
affects about 10-15 percent of names produced, depending upon test item.
Although the object-naming difficulty may follow a word-frequency
distribution, this not true for the paraphasic response.
The disorder usually occurs in the context of diffuse disease,
drowsiness, or confusion. Speech is fluent, at times logorrheic, but not clearly

aphasic. Comprehension is good and repetition is preserved. Patients show
euphoria, reduced speech awareness, and/or denial. There is a similarity with
certain Korsakoff patients who may also show semantic paraphasia restricted
to naming tasks, as in the Korsakoff patient who referred to the examiner as
“Herman Joseph Prince Macaroni.”
Mechanism of the Semantic Disorders. Three disorders of semantic

origin have been described: (1) semantic aphasia, when context (expositional
speech) is primarily affected; (2) semantic paraphasia, with disturbance in
referential speech; and (3) semantic jargon, when both reference and context
are involved. The fact that the first and second forms occur independently
indicates that neither is a partial expression of the other, though semantic
jargon may be taken as a combination of the two. The mechanism which
accounts for the disorder is similar in both the expositional and referential
forms. In semantic aphasia the speaker is unable to use the verb or predicate
of the forming utterance as a free unit to which the subject and object only
partially relate. A combination of any two of these elements (e.g., subject and
verb, or verb and object) tends to determine the third. The direction of this
pressure is not invariably subject → verb → object, but is often the reverse. All
lexical items may be affected, and it may be difficult to determine which
element of the phrase is defective (if content words, paraphasia; if function
words, paragrammatism). In the above example, “speech that could be found .
..” acceptable bondings occur between individual words (speech that, that
could, could be found) but not between the initial and latter segments of the
phrase. The disorder has a close relation to schizophrenic speech. Consider an
example from the study of paralogic by von Domarus, quoted by Arieti:
Certain Indians (A) / are / swift (x)

Stags (B) / are / swift (x)
∴ Certain Indians (A) are stags (B)
Here, A ≅ x becomes A = x
B ≅ x becomes B = x
A ≅ x ≅B becomes A = x = B
This is quite similar to what occurs in semantic aphasia. In the following
example from a Cloze test an aphasic patient was required to insert words
deleted from a test phrase. The patient’s solution is in brackets. Test phrase is
“The baby—something that he had—done before.” [p. 49]
A. x. B.
The baby [was] something
that he had [been] done before
Here A ≅ x and x ≅ B becomes A = B
The inserted word agrees with those in its immediate surround (e.g.,
baby was, was something; had been, been done) and a partial fit is accepted as
satisfactory. Responses to proverb tests show identical errors, the patient
generally interpreting one component of the proverb partially and then
attempting to consolidate it obliquely to the other components.
In semantic aphasia the noun phrase tends to become stabilized at the
expense of its predicative relationships. Context is adapted to subject. One

might say that the noun phrase conditions the predicate rather than being
contained within, or defined by, it. This has a determining effect upon
utterances in which topics are developed within understood contexts. In
semantic paraphasia (see below), misnamings show the influence of implicit

contexts derived from the examiner’s knowledge of the object to be named.
However, predicative or contextual function is otherwise adequate and acts to
normalize noun production in conversational speech.
In semantic paraphasia there is an identification of two otherwise
disparate subjects (e.g., “doctor” and “butcher”) on the basis of one or two
shared attributes (e.g., white coat, cutting, etc.). Consider the following
example:
Task Presented object A Shared predicate C Paraphasic response B
Naming bedpan stool, sitting, etc. “piano stool”
Mechanism
A ≅ B
B ≅ C
∴ A = C
Related Disorders. Similar language disturbances have been noted in
schizophrenic patients. For example, the utterance “A boy threw a stone at me

to make an understanding between myself and the purpose of wrongdoing.”
is similar in structure to that of semantic aphasia, while Arieti’s example of
word salad, “The house burnt the cow horrendendously always,” is very close
to semantic jargon. The disorder of semantic paraphasia is recalled in the
“associative” misnamings of schizophrenic patients, as in “le song” for bird, “le
kiss” for mouth. Similarities between schizophrenic and aphasic speech have
also been discussed by Schilder, Critchley, and Alajouanine. Arieti has given a
full and lucid discussion of the problem of schizophrenic language, and has
demonstrated the central position of paralogical thinking.
Kleist commented that paralogia was a confabulation within the verbal
sphere. This concept is probably identical with the “confabulation d’origine

verbale” of catatonic patients. If paralogia is a kind of “verbal” confabulation,
it may be asked to what extent this relates to the confabulation of Korsakoffs
syndrome and related confusional states. Language of this type has been
described in Korsakoff’s syndrome, as in the response of a patient to the

proverb Safety First, “It’s rather a lateral term which means it could apply to a
host of things. A road for one thing.” Victor has commented that aphasic
errors are common during the confusional prelude of the amnestic syndrome.
It is likely that an inner bond exists between the semantic aphasic

complex and confabulation. Confabulation is no more the “filling in of a gap in
memory” than is paraphasia a compensation for a memory loss. In
confabulation there is substitution of a semantic field, in semantic paraphasia,
there is substitution within the semantic field. The two speech forms reflect
the microgenetic level of disruption and are not unrelated psychological
deficits. In this respect it is of interest that patients with semantic jargon have
often been described as having features of the Korsakoff syndrome.

Moreover, the possibility that an inner relationship exists between amnestic
confabulation and schizophrenic paramnesia has not received sufficient
attention.
Nominal Disorders
The developing linguistic form, having more or less successfully

traversed the semantic or selectional stage, proceeds toward the “abstract
representation” of the (correct) lexical item. Disorders at this level are,
therefore, characterized by improved control of word-meaning but inability
to evoke the intended word. As with the preceding stage, anomia is not a
single entity but is rather a series of (pathological) speech forms which point
to one or another segment or phase of the process of language production. A
disturbance at this stage may occur to some extent independently in
referential speech (as in anomia proper, i.e., word-finding difficulty) and in
expositional speech (so-called empty speech of anomia, circumlocution).
Verbal paraphasia occurs as well, and is to be distinguished from semantic

paraphasia, with which it has generally been equated, on the basis of the “in-
class” substitutions (“shaver” for razor, “green” for red). Verbal paraphasia is
to be conceived as an intermediate stage between semantic paraphasia and

anomia proper.
Background. The concept of verbal amnesia as a defect in the mental

evocation of words was an early development in aphasia study. As a
distinction was drawn between internal and external speech, verbal amnesia,
as a disturbance of the internal phase of language, came to be set against

motor aphasia, which was a disturbance of the external phase. This early view
gave way to a division of anomia into specific visual, auditory, tactile, and
motoric forms, and for a time the concept of a pure anomia regardless of
sensory modality was abandoned (see Pitres, for a review of the historical
period). The modern conception of anomia dates from the papers of Kurt
Goldstein.
According to Goldstein, the difficulty in naming objects derived from an
inability to assume an “abstract attitude” with regard to the item being tested.
Words which could not be produced as names, or which could be produced
but not brought into relation with the object designated, appeared
spontaneously in conversation. This indicated that word memory was
preserved. Thus it must be the conditions under which the word is evoked
that are altered, viz., a loss of the ability to apply words as symbols for
objects, i.e., as word concepts. This difficulty became even more apparent if
the patient was asked to sort objects according to various attributes such as
color, size, or shape. The inability to give the name of a single object reflected
a disturbance of the word concept of that object, and this disturbance was
exaggerated by the requirement that diverse objects be categorized according
to shared attributes.
Goldstein’s description of amnesic aphasia (anomia) achieved wider

acceptance than his psychological account. It was pointed out that abstraction
was frequently impaired in the absence of anomia, and that anomia occurred
with categorical behavior that was not strikingly abnormal, or if so, no

different from that seen in other aphasic syndromes. Also to be included in
this period are works by Heilbronner and Lotmar, particularly as concerns

verbal paraphasia. Lotmar especially discussed the spheric nature of word
substitution, and attempted to show how apparently random substitutions

occurred through intermediate links.
Recent studies have shown that word frequency is an important factor
in the anomic defect. It has been shown in normal subjects, in dysphasics, and
in patients with organic dementia, that word-finding difficulty relates to the
vocabulary frequency of the target item, i.e., the object or action to be named.
In a study deriving from this work, A. Wingfield, cited by Oldfield,

demonstrated that perceptual identification does not show the same
frequency dependency as does object naming. This led Oldfield to propose a
two-stage model of naming, an initial stage of perceptual identification and a
second stage of word finding, only the latter of which is dependent on word
frequency. There is some evidence that the specific anomias (e.g., “visual” or
“tactile” anomia), and true or aphasic anomia relate to involvement at each of
these respective stages.
Verbal Paraphasia. This disorder refers to a stage where the lexical

item, the word, has realized (been selected to the point of) a categorical
approximation, e.g., “shaver” for razor, “green” for red. There is some ability
to self-correct, i.e., some awareness of speech error, but this may differ from
one moment to the next, depending on the nature of the substitution.
Although the difficulty in naming may have a relationship to the vocabulary

frequency of the target word, i.e., patients having more difficulty with rare
than common words, the paraphasic errors do not appear to show this effect.
Thus, patients may say “spectacles” for glasses, or “fuchsia” for red. While this
form of language is often admixed with other anomic features (see below),
the absence of verbal paraphasia in anomia proper should not be interpreted
as a reluctance to speak or a more careful search for words. Verbal
paraphasia is not a reflection of personality type; rather it reflects a cognitive
level around which the “personality” is organized. Features of this cognitive

level include some degree of euphoria, a more active, though not logorrheic,
speech flow than in anomia, and partial awareness of the disorder.
Anomic Aphasia (anomia, amnesic or nominal aphasia). Patients of this
type have difficulty in word finding which affects nouns preferentially.
Typically, such patients can point to the correct object when it is named, can
repeat the object name, and can select the correct name from a group,
although they are unable to name the object directly. This is true for “visual
naming,” as well as naming through other perceptual modes, e.g., touching the
object, hearing the sound of the object, etc. Patients are also unable to name
from a description or definition of the object, e.g., “what do you use to sweep
the floor?” The word-finding difficulty may be akin to the common

phenomenon of word lapse or the forgetting of a name or place in the speech
flow. Not uncommon is the incipient “tip-of-the-tongue” nature of the needed
word. Patients may be able to give the initial letter of the target word or the
number of syllables, and can use the test object appropriately. These features
suggest that word meaning is relatively well preserved and that some
“skeleton” or abstract frame of the intended word is available. The disorder
may be limited to referential speech, or may appear in conversation with
circumlocution and emptiness of speech. The true anomic who does not
produce verbal paraphasias has a more acute awareness of his difficulty and
may show frustration and catastrophic reactions.
The difficulty in word finding tends to occur in the following direction:

nouns → verbs → grammatical (function) words. Abstract nouns may be more
difficult than concrete nouns. When the disorder involves both referential and
expositional speech, a “nonfluent” state can result. Such patients have greatly
reduced speech with only a starter phrase or a stereotypy available, such as

“Well I . . .” or “It’s a . . .” Speech tends to be limited to small grammatical
words and simple verbs. This condition can be distinguished from anterior
nonfluency (i.e., Broca’s aphasia) by the reciprocal order of word loss. In the
anomic, the small verbs and function words are the last, not the first, to
disappear.
Word-finding difficulty occurs in various organic and nonorganic states.

Anomia and circumlocution have been described in schizophrenia. Chapman
has emphasized that schizophrenic patients “have a true difficulty in word
finding, although it tends to be episodic in occurrence and very similar to the

paroxysmal dysphasia which occurs in temporal lobe epilepsy.” Anomic
errors are also common in fatigue and distraction, and in sleep and
transitional utterance.
Anomia tends to be associated with either unilateral or diffuse lesions.
In anomia and in verbal paraphasia, lesions may occur outside the classical
speech areas. The more severe “nonfluent” anomia occurs with unilateral
(left) temporo-parietal lesion. Lesions of the posterior middle-temporal gyrus
(T₂) and its continuation to angular gyrus appear to be highly correlated with
this form. The more fluent the anomia, the more likely is diffuse pathology or
lesion outside the speech area.
Anomia occurs in dementia, increased intracranial pressure,
postanaesthetic or confusional states, as well as with subcortical or thalamic
lesion, where it is most likely due to a referred effect on cortex.
Comment on the Semantic and Anomic Disorders. The various

disorders which have thus far been discussed can be aligned in a series which
retraces the microgenetic development of normal language. The sequence of

semantic jargon, through associative and then categorical substitution to true
anomia, corresponds to stages in the normal productive process. Within the
semantic “segment,” the progression is through systems or fields of word
meaning of wide “psychological distance.” These lead to more narrow

“associative” responses which represent an intermediate stage between
semantic jargon and correct word selection. Anomia points to a stage where
the correct word has been all but selected but cannot yet be fully realized in
speech. The anomic stage corresponds to the emergence of the correct lexical
item preparatory to phonemic encoding.
In addition to this linguistic change, there is an evolution of other

aspects of cognition. Thus, in semantic jargon there is euphoria, at times
mania, often with a paranoid trend. There is logorrhea and a lack of
awareness of speech error. This picture gives way in semantic aphasia and
semantic paraphasia, to a mitigation of logorrhea and euphoria, with patchy

but still incomplete awareness of difficulty. This continues into verbal
paraphasia where incorrect words (e.g., “table” for chair) can often be
rejected. There is a transition from active, but not logorrheic, speech to
hesitancy, and finally to an inability to speak at all. The transition from one
state to another occurs pari passu with increasing awareness of speech
errors, improved self-correction, and step-by-step transformation from one

affective and behavioral form to another.
Phonemic Disorders
These disorders point to a stage in the production of language where

the intended word, having been properly selected, does not achieve correct
phonemic realization. According to whether the defect is expressed primarily

in referential or expositional speech, we can distinguish, respectively,
phonemic paraphasia and phonemic aphasia. Ordinarily these are included
together in the syndrome of central or conduction aphasia.
Background. The phonemic disorders were originally defined on an
anatomic basis by Wernicke without regard to the qualitative aspects of the
speech of such patients. The disturbed function of repetition was gradually
singled out as central to the syndrome and attributed to damage to a pathway
between the posterior and anterior speech areas (see Brown for further
discussion). Kurt Goldstein argued against an interruption of a conducting
pathway in favor of a more dynamic interpretation. Goldstein believed the

condition represented an impairment at the thought-speech transition, and
termed it “central” aphasia, placing emphasis on the paraphasia as reflecting a
disturbance of inner speech. Goldstein’s comments regarding a possible
relationship between anomic aphasia and central (phonemic) aphasia are

worth quoting in full:
A combination of amnesic aphasia with symptoms of central aphasia is

frequent. There arises the question of whether we are dealing with an
accidental combination due to similar locality of the underlying lesion, or
whether there is an inner relationship between both defects. As little as we
are able to say now, the latter possibility is worth pondering in respect to
the closeness of the phenomenon of inner speech to the nonspeech mental
process, [pp. 277-278]
Phonemic Paraphasia. In this disorder, the disturbance chiefly affects
nouns and is apparent on tests of object naming. Spontaneous speech is often
quite good with few or rare paraphasias. Patients make errors of the type:
“cable” for table, or “predident” for president. Repetition may be involved in a
similar manner. Comprehension may be quite good. Such patients are usually
classified as mild “conduction” aphasics or resolving “motor” aphasics.
Phonemic Aphasia (central, conduction aphasia). When conversational
speech shows a picture of fluent phonemic paraphasia with phonemic errors
on naming and repetition tasks and good comprehension, the diagnosis of
phonemic aphasia is in order. There is a close resemblance to phonemic

paraphasia, the distinction resting on the improved speech and defective
naming and repetition of the former, and the more impaired spontaneous
speech of the latter, where naming may be relatively well preserved and
repetition is involved at the phrase, rather than single-word, level. This
disorder may be present at the start and may appear in the course of a
deteriorating anomia and as a stage in the recovery of a neologistic jargon

(see below). An example of such speech is that of a patient who, when asked
where she lived, said: “I have been spa staying with a friend of mine but I do
hate to imp impose on her. I want to pay my own way. Do they have some sort
of chart where you can take this tee tee . . .” When phonemic aphasia develops
out of a neologistic jargon (q.v.), speech is more active with some neologism
and comprehension is less well preserved. Such a patient described his
speech difficulty as: “Well it’s very hard to because I don’t know what it would
my pi why what’s wrong with it, but I can’t food, it’s food and rood to read the
way I used to do all right off . ”
The disturbance is equally present in naming and repetition and in a
manner generally comparable to conversational speech. This is particularly
evident when phonemic aphasia appears in the deterioration of an anomia.
Thus, if an anomic patient is asked to name an ashtray, the word is not
produced but can be repeated. In the regression of the anomia, the patient
will first fail to cue with the initial sound of the word, i.e., when the examiner
says “ash . . . ,” but will still repeat the word “ashtray.” At a later stage failure
will occur in spite of a strong phonemic cue, e.g., “ashtr . . . ,” in which all but
the final syllable of the word is given, but the word “ashtray” can still be
repeated. Ultimately a stage is reached where the patient can neither cue nor
repeat. At this point the patient is a phonemic (conduction) aphasic. In this

example we can see that the disorder of repetition is only a failure to name
given the whole word as a cue. The transition from the anomic, who repeats
the word but fails to name with a cue up to the penultimate syllable, and the
phonemic aphasic who fails given a cue including the final syllable (i.e., on
repetition) establishes a functional continuity between these two disorders.
There is a different speech form in these patients since the phonemic aphasic
has achieved a linguistic level beyond that of the anomic. There is also a
heightened awareness of speech content. Circumlocution has given way to
deficient production, frustration to selfcorrection.
With regard to anatomical correlation, the evidence suggests that
dominant posterior-superior temporal gyrus and its “parietal continuation”
as supramarginal gyrus are chiefly involved. Cases with a lesion of angular
gyrus have been reported, as well as instances in younger patients with a
lesion limited to the left Wernicke’s area.
Phonemic aphasia is uncommon in non-organic states, but phonemic

errors may occur in speech during fatigue or distraction. An example of such
errors in normal sleep utterance is the following: “David, I day (?say) David . .
. that’s you that day dated day dravid Dave dravid about 25 or 30 noked
naked day dreams.” The “clang association” is more prominent than is

generally seen in phonemic aphasia, although clang errors are prominent in
neologist jargon (see below).
The Problem of Neologism
Aphasic jargon with neologism is a disturbance altogether different

from semantic jargon, although both disorders are often treated as different
manifestations of Wernicke’s aphasia. As in the semantic, nominal, and

phonemic disorders, there may be two expressions of the defect, in referential
speech, as neologistic paraphasia, and in both referential and expositional

speech, as neologistic jargon.
Neologistic Paraphasia. In this disorder, speech is generally
comprehensible with occasional neologism, often in the context of fluent
phonemic paraphasias. The neologism appears especially when a highly

specific response is demanded, e.g., on proverb interpretation, and under the
conditions of naming. An example is the following, from a patient who was
questioned about his work: . . it was my job as a convince, a confoser, not
confoler but almost the same as a man who was commersed.” Another patient
described her accident in this way, “So when I passed drive I told him let me
drive. I had go so he let me go, so I went, wen in and went in on the semidore.”
The neologism primarily affects content words with relative sparing of the
small grammatical words. The disorder is probably closely allied to phonemic
aphasia and paraphasia, the neologism at times appearing as a phonemic
error severe enough to render the word unintelligible.
Neologistic Jargon. This disorder refers to speech so pervaded by

neologism that it is no longer intelligible. The neologisms may range from
wordlike products to a series of clang contaminations. Thus, one patient
responded to the idiom “swell-headed” with the interpretation, “She is selfice
on purpiten,” while at another time, asked about her speech problem, she
said: “Because no one gotta scotta gowan thwa thirst gell gerst derund gystrol
that’s all.” A progression may be seen from fluent, logorrheic neologistic
speech with few clang associations, to reiteration of certain neologisms and

perseverations on the basis of sound similarity to clang association so intense
that it seems to determine the jargon output, e.g., “Then he graf, so I’ll graf,
I’m giving ink, no, gefergen, in pane, I can’t grasp, I haven’t grob the grabben,
I’m going to the glimmeril let me go.”
In such patients, comprehension is severely impaired. Naming and
repetition are characterized by neologistic responses, e.g., “galeefs” for comb,

“errendear” for yellow. There is a lack of awareness of speech errors, and
patients will gesture actively, seemingly convinced that they are
communicating something to the examiner. There is heightened affectivity,
often with euphoria and exaggerated expression. It is of interest that patients

will appear to accept their own jargon if it is recorded and played back to
them, but will reject the same (transcribed) jargon if it is spoken to them by
an examiner.
The pathological location of the lesion is in the dominant posterior
superior temporal region. There is evidence that the lesion incorporates both
Wernicke’s area proper and supramarginal gyrus.
In schizophrenia, neologisms are more often of the “portmanteau” type,
either as fusions of separate words, e.g., “mondteufel,” “cage-weather juice,”

“snowhousehold,” or assimilations of otherwise recognizable components of
separate words, e.g., “enduration” for endure plus concentration. These forms
can perhaps be explained along the lines suggested for semantic paraphasia.
Occasionally, unintelligible utterances may occur, e.g., “I have seen you but
your words alworthen” (Question: What does alworthen mean?) “Ashers
guiding the circumfrax.” (see Bleuler for other examples). In schizophasic
jargon, one may encounter utterances of the type: “Ulrass Asia peru arull
pelhuss Pisa anuell pelli.” Similar types of jargon may be seen in transitional
states, e.g., “amarande es tifiercia,” and sleep speech, e.g., “she shad hero sher
sher sheril shaw takes part . . . ” A form of aphasic jargon referred to as
undifferentiated or phonemic jargon may resemble such utterances, e.g., “Eh

oh malaty, eh favllity, abelabla tay kare abelabla tay to po sta here, aberdar
yesteday (?yesterday)
Interpretation of Neologistic Jargon. Although the place of neologistic
jargon in the aphasias is uncertain, there is evidence that, at least in the most
florid cases, it may represent a combination of semantic jargon and phonemic

aphasia. In such cases, semantic paraphasias would be produced which would
not achieve correct phonemic realization, the result being a phonemic
distortion superimposed on a semantic paraphasia. This is consistent with the
fact that neologistic jargon tends to improve to either semantic jargon or

phonemic aphasia. Thus, if the semantic disorder clears, the patient is left
with a phonemic defect, while clearing of the phonemic disorder would reveal
the underlying semantic disturbance. In other (milder) cases, however, the

neologism probably consists of a normal underlying word frame which is
distorted to the point of unintelligibility by phonemic paraphasia. In addition,
there are certainly many instances, as illustrated above, where the neologism
is a result of clang associations and/or word fusions.
Anarthric Aphasia
Included in this group are disorders at the final stage in speech
production, disturbances affecting expositional speech primarily—as in
agrammatism—and disturbances affecting both referential and expositional
speech, anarthric or Broca’s aphasia. While these disorders are considered as

if they were impairments at a stage in advance of that involved in phonemic
aphasia, viz., at the terminal grammatization and articulation, it may well be
that they represent alterations in a motoric or action system organized, not in

sequence, but in parallel with posterior linguistic structures.
Background. The historic period (discussed on pp. 243-244) during

which the symptomatology and pathological correlative features of Broca’s
aphasia were worked out, gave way to a series of analytic studies which
began with investigations of agrammatism. Isserlin and Pick noted a
gradation in Broca’s aphasia from mild hesitation and stammering in speech,

through agrammatism to a stage of near muteness. The agrammatic stage,
characterized by a predominance of nouns and verbs (especially infinitives),
lack of prefixes and suffixes, and pronoun confusion closely resembled an
early stage of childhood speech.
More recently, Alajouanine has made important contributions to our
understanding of stereotypies and speech awareness in the Broca’s aphasic.

Following the approach and classification of Hughlings Jackson, Alajouanine
has emphasized the automatic nature of the stereotypy and the lack of
awareness which accompanies it, and he has distinguished four stages

through which the stereotypy resolves. There is an initial stage of
modification in which, through intonational adjustments, the stereotypy
comes to express a wide variety of emotional states; then a stage of checking
the stereotypy which signals the patient’s first awareness of the utterance,
followed by a transitional period in which other expressions, automatic or
not, come to accompany the original, but now impersistent stereotypy; finally,
there is abolition of the stereotypy with gradual return of speech into an

agrammatic phase.
Sabouraud et al. have characterized the fundamental defect in Broca’s
aphasia as an inability at different levels to pass from one complete utterance

to another. This results from a loss of contrasting features in the expression;
i.e. those oppositions which provide for lexical definition are conserved while
contextual contrast is lost. Luria has distinguished two forms of frontal

aphasia, a kinetic or efferent motor aphasia, and a kinesthetic or afferent
motor aphasia. He argues that these two independent conditions constitute
what is usually called Broca’s aphasia.
Agrammatism (telegrammatism). This disorder is characterized by

relatively good use of nouns or substantives and a loss of the small function
or grammatical words. This is especially prominent in conversational speech,
but is generally present in repetition, reading aloud and writing as well. The
disturbance may be present from the start, as in the so-called one-word or

holophrastic sentence, e.g., the patient saying “water” or “glass, water”
instead of “May I have a glass of water?” This may improve to more typical
agrammatic speech:
My uh mother died uh, me uh, fifteen uh, oh I guess six months my mother
pass away . . . my brother in uh Baltimore an stay all night an ’en I lef’ for
Florida, Mammi Beach, an uh, an uh, anen uh, Mammi Beach an stay all
night and back again. Hitch hike.
With continued improvement this leads to a stage of relatively good

speech with loss of inflections, restriction of verbs to the infinitive or present
tense and an absence of unstressed grammatical words. Agrammatism has
been considered a kind of speech economy, an articulatory defect primarily

affecting grammatical words, and a true grammatical deficit. In our view the
problem may be considered a deficiency in phonemic realization affecting
grammatical words primarily. Since there is a graded entry of nouns, verbs
and function words into the forming sentence, i.e., leading from an initial
noun priority to the final grammatization, there is preservation of these
content words which have already achieved a stage of phonemic encoding.
For this reason it is the still developing function words, and particularly the
late-added inflections, which are preferentially involved. This helps to explain
why the order of word loss in agrammatism (grammatical words → verbs →

nouns) is reciprocal to that of anomia (nouns → verbs → grammatical words).
In the latter, the nouns are the first to appear and are therefore the first to be
lost, whereas in agrammatism the nouns have completed their development

and are therefore the most resistant.
Agrammatism is the commonest form of aphasia in dextrals with right

hemispheric lesions and is probably more common in aphasic lefthanders
regardless of side of lesion. In such patients, language organization is similar
in some respects to that of children in whom, next to muteness, agrammatism

is the most common aphasic form. It is also of interest that agrammatism has
been described in catatonic schizophrenia, though it is by no means common
in this disorder. The pathological localization of agrammatism is presumably
the same as for anarthric aphasia.
Anarthric Aphasia (Broca’s, motor, expressive aphasia). In this form
the usual picture is one of nearly total speech loss, often with no verbalization
apart from a stereotypy or automatism. Comprehension may be well
preserved but other speech performances are about equally impaired. At
times, naming and repetition may be slightly better than conversational
speech Such patients may improve to phonemic paraphasia or to
agrammatism, depending on whether the content words or the terminal
grammatization is chiefly affected. Less commonly there is recovery to

dysarthria with abolition of the stereotypy and the gradual return of labored
but nonaphasic speech.
In addition, the majority of patients are hemiplegic, and most have facial
and leftsided apraxia. Writing is impaired to the same extent as speech. In
cases where writing is markedly superior to speech, a diagnosis of “pure”
motor aphasia may be considered, although the existence of this form is now
held in some doubt. The term “nonfluency” is often used in relation to such
patients. This concept includes a number of disturbances, however, such as

dysprosody, dysarthria, agrammatism, and short “phrase length,” so that
unless the precise characteristics of the nonfluent condition are specified, the
concept itself is of little value. Patients with anarthric aphasia tend also to be
somewhat apathetic and passive in their behavior. Some writers have
commented on the loss of volition or will (Willenlosigkeit), an attitude which

is, in fact, more common than the frustration or despair often identified with
this disorder. At times, one may see apathy give way to euphoric elation or
labile crying during the stereotypic utterance. Awareness of the difficulty may
change from moment to moment in relation to the dominant speech form, i.e.,
volitional or automatic speech.
Although there has been much controversy over the exact borders of
Broca’s area, there is general agreement on the central importance of the
posterior part of the inferior or third frontal convolution (F3). Goldstein cited
evidence for a more extended speech zone, involving the precentral

operculum and mechanisms in this latter area for movement of the mouth,
tongue and larynx.
Comment. In the preceding discussion, the major aphasic disorders

have been reviewed from the point of view of a model of normal language
production. Accordingly, the aphasias represent disruptions of (actually, a
coming-to-the-fore of) earlier or prefigurative stages in the formative process.

It now remains to bring the transcortical aphasias and the so-called isolation
syndrome into relation with this model.
“Transcortical” Aphasia
Background. This group of disorders comprises three major forms,
transcortical motor aphasia (TMA), transcortical sensory aphasia (TSA), and
combined transcortical aphasia (CTA) or “isolation” syndrome. Common to all

forms is the occurrence of good (echolalic) repetition. In respect of the above
forms, this occurs in the context of impaired speech, impaired
comprehension, or impairment of both speech and comprehension.
Historically the concept of a speech area separated from other portions of the
cortex was first suggested by Huebner in 1889, on the basis of a single case
with loss of speech and comprehension, but relatively good writing, both
spontaneous and to dictation, reading aloud and repetition. The brain showed
two principal lesions (Figure 10-9), softening around the posterior part of T₁,
presumably interrupting connections between Wernicke’s area and the
parietal-concept field, and a small area of softening in F3 considered (in my
view, incorrectly) to be of no importance.
Figure 10-9.
Heubner’s drawing of the major lesions in a case of echolalia with markedly

reduced speech and comprehension (combined transcortical aphasia,
“isolation syndrome” ).
Subsequently, cases of echolalia with temporal-lobe atrophy were
described by Pick and Liepmann. The chief clinical feature of these and all
subsequent cases is echolalia. This is characterized not simply by the ability
to repeat but by compulsive and automatic repetition.
The echo response is a brief, precise and often explosive utterance

which differs from the approximations of childhood imitation. Echolalia is not
a parrotlike reflex function. There is often “personalization” of the content,
e.g., the patient asked “How are you?” echoes “How am I?” Moreover, it
invariably has a social character, the response occurring only when the
patient is addressed. There is also a completion effect," patients finishing
incomplete rhymes or phrases, e.g., “ham and . . . (eggs).” Patients may also
correct in the echo an incorrect grammatical form in the presentation.
In dementia, echolalia occurs with widespread but predominantly

temporal-lobe atrophy. In aphasic states, there may be partial lesion of either
anterior (TMA) or posterior (TSA) speech areas, or both (CTA) (see Figure
10-10). Echolalia may result from a predominantly posterior lesion assumed
to interrupt parietal associations when there is diffuse atrophy or a smaller

anterior lesion; or there may be a large infarct in the center of the dominant
Sylvian speech zone." Geschwind et al. have described a demented echolalic
with diffuse pathology sparing the Sylvian speech area. These authors argued
that the intact portion of cortex and intervening arcuate fasciculus mediated
the echolalic repetition, speech initiation and comprehension having been
lost as a result of destruction of the remainder of the cortex. Echolalia is a
symptom in a variety of late-stage dementias. It occurs in schizophrenia and
mental deficiency. In the latter, it may represent the furthermost stage of

language acquisition.
Figure 10-10 .
A personal case of combined transcortical aphasia (CTA). There is a large

cystic infarct in the left posterior inferior frontal region, destroying much of
Broca’s area and extending subcortically to involve the region of traversal of
the arcuate fasciculus. There is another area of superficial softening in
posterior middle temporal gyrus. The pathology of CTA is a partial lesion of
the anterior and posterior speech zone, bringing about a reduced functional
level in performances supported or mediated by these areas.
Interpretation of Echolalia. In aphasic states it is not uncommon to
have echolalia at the level of single words or very short phrases. This may
occur in phonemic and in jargon aphasia, and is a partial expression of the
more pronounced echo response seen in the so-called transcortical aphasia.
In the motor form of transcortical aphasia, echolalia stands out against a
background of reduced spontaneous speech. The pathology of this disorder is
incompletely understood, but often there is a partial involvement of Broca’s

area. In transcortical sensory aphasia, there is a more automatic echo
response appearing in the context of reduced comprehension. In this disorder
the pathology appears to be the subtotal involvement of Wernicke’s area. The
isolation syndrome may correctly be conceived as a combined (motor and

sensory) transcortical aphasia.
The anatomical limits of Broca’s and Wernicke’s areas are defined on an
arbitrary basis so that it is unclear how a pathological lesion can be said to

“surround” or lie on the periphery of these areas.
It is more likely that there is a partial lesion of either the anterior or the
posterior speech zone, or both, and that this pathology brings about a
deterioration or regression of function within those damaged areas. There is
evidence for such partial lesions in all cases described, not only in the two
focal cases but in a variety of diffuse atrophies as well.
The need for a more dynamic account of this disorder is emphasized by
cases such as that of Stengel (and one of my own cases) where CTA occurs
with destruction of the entire (left) Sylvian area. To say that the echo
response derives from the opposite hemisphere is not to solve the problem
but only to transfer it to the other side, for it is impossible to say whether the
echo response reflects the degree to which the left hemisphere has been
reduced or the highest level of which the right hemisphere is capable. Both
arguments, in fact, amount to the same thing, since echolalia, like every other
aphasic syndrome, is determined by the combined performance of both
residual left and intact right hemispheric capacity. This concept of a linguistic
regression induced by partial (or complete) damage to both of the (left)

cortical speech zones, and of the resultant symptom, echolalia, as an
achievement of the combined action of both hemispheres, helps to bring this
disorder into relation with other conditions, e.g., dementia or mental

retardation, where echolalia occurs, respectively, as a final stage in
deterioration or as an endpoint in development.
The Neural Organization of Language
In historical writings on aphasia, it was generally maintained that the

localization of a specific function could be inferred from an impairment of
that function with focal pathology, that a lesion of a specific area gave rise to a
symptom through disruption of the normal mechanism localized in, or
mediated by, the area in question. Gradually, however, it has become clear
that the anatomical structure which mediates language and cognition is as
dynamic as the psychological systems which it supports. The “centers” of

traditional aphasiology may rather be considered as levels by means of which
language is carried one stage further. Similarly, the conducting pathways of
the classical theory are not to be conceived as channels for the association of
ideas, to link up perceptions to movements, or written words to spoken
sounds, but are more likely concerned with temporal interrelationships
between various levels in the cognitive structure. The nature of the
anatomical organization underlying language production can best be
understood through a consideration of the process of cerebral dominance or
lateralization.
Dominance
Although estimates differ, it is generally assumed that about 85 percent
of the population is right-handed, and of these nearly all have left-
hemispheric dominance for language. Among left-handers, there is a slightly
greater tendency for left-hemispheric language dominance than right. In a

large group of unselected patients there is about an 80 percent chance of
developing some degree of aphasia with a left-hemispheric lesion regardless
of handedness, and conversely, if one looks at an unselected population of
right and left handed aphasics, about 95 percent have a left-hemispheric
lesion. Furthermore, studies by Brown and Wilson, suggest that hemispheric
dominance for speech may be independent to an extent from hemispheric

dominance for praxis, and that degree of speech lateralization may be
inversely related to the priority of the opposite (usually right) hemisphere in
spatial performance. Among the procedures currently being used to study

hemispheric dominance are selective intracarotid amytal injection, dichotic
listening and unilateral ECT (electro-convulsive therapy).
Lateralization and the Formation of the Speech Area
Hemispheric dominance or lateralization for language is not a state
which is achieved at a certain time, say by age five, ten, or twenty, but is
rather a process which, in a normal brain, may continue throughout life.
Moreover, there is fundamentally no difference between lateralization and

“localization.” Rather they are different aspects or phases of a unitary process.
The initial phase, interhemispheric specification (lateralization), leads to a
diffuse language organization in the left hemisphere. This is followed by a
second phase of intrahemispheric specification (“localization”) in which

progressive differentiation occurs within the wider speech zone of that (the
dominant) hemisphere.
If we examine the effects of a lesion of left Wernicke’s area (posterior
T₁), we discover that the form of aphasia produced by this lesion differs
according to the age of the patient. Such a lesion in a five-year-old child
produces a “motor” type of aphasia, with mutism or agrammatism. In a ten-
year-old child, one sees an anomic aphasia, while at that same age and on into
middle life, a phonemic (conduction or central) aphasia may result. Finally, in
late life, this lesion produces a jargonaphasia. Thus, four different types of
aphasia can occur with the same lesion, depending on the age of the patient.
At the very least this is persuasive evidence against a naive function
localization.
Our knowledge that the process of inter- and intrahemispheric language
specification takes place during the life span helps to account for this
phenomenon. In the young child, an initial diffuse left-hemispheric language
organization accounts for the fact that a lesion of frontal, parietal, or temporal
lobe (including Wernicke’s area) produces a “motor” form of aphasia.
Subsequently, within this wider area a new region will emerge (Figure 10-
11(a)), a lesion of which (incorporating Wernicke’s area) produces an anomic
aphasia. Gradually into middle life, a still smaller region is differentiated
within the previous zone, a lesion of which (again, including Wernicke’s area)
produces phonemic paraphasia and phonemic aphasia (Figure 10-11(b)).
Finally in late life there is gradual differentiation of a still smaller zone
(Wernicke’s area proper), lesion of which produces jargonaphasia (Figure 10-
11 (c)). Consistent with this is the fact that jargonaphasia is unusual in young
adults where it generally requires bilateral lesions, possibly of limbic
structures. The central point is that a two-phase developmental sequence,

lateralization followed by intrahemispheric specification, creates a dynamic
emergent structure which then supports the process of language production.
At each stage in this process, involvement of the residual area of each

preceding stratum produces the form of aphasia identified with that stratum
when it represented the dominant level in ontogenesis.
Figure 10—11.
An illustration of zones of core differentiation in the posterior language area.

The angular (Ang.) and supramarginal (Supr.) gyri, and Wernicke’s area
(Wern.) represent ontogenetic levels in an evolving structural form, and are
not the discrete anatomical loci of traditional cortical morphology.
Moreover, these strata are not to be conceived solely as neocortical
differentiations, but as representatives of more widely distributed levels in
cerebral phylogenesis. Further, the levels correspond to the three major
sequential stages of language production which have been revealed in the
study of the posterior aphasias:
Phonemic (specialized neocortical) asymmetric, localized
Nominal (neocortical) unilateral but poorly localized
Semantic (limbic) bilateral
The semantic disorders are associated either with bilateral temporal
lesions or unilateral (left) temporal lesion in the presence of mild generalized
involvement. There is evidence in such disorders of bilateral limbic system

lesion or involvement of the cortical representatives of limbic structures. The
nominal disorders (anomia and verbal paraphasia) occur with either diffuse
or focal involvement of neocortex; however, focal lesions cannot be

accurately localized, and anomia can also result from subcortical lesion,
probably through a referred effect on generalized neocortex. The phonemic
disorders are strictly associated with asymmetric focal lesions. Neologistic

jargon is also asymmetric and focal, as it concerns, either directly or in
combination, a disruption at the phonemic level. This morphogenetic

progression from a limbic, through a generalized-neocortical to a specialized
(asymmetric) neocortical level provides a dynamic, emergent structure
mediating corresponding stages in the microgenesis of language and
cognition.
There is a close relationship between this ontogenetic process which
builds up the speech area, and the process of encephalization. In fact, the
asymmetric structure of the speech area is a continuation of a similar trend in

phylogeny. In this respect, the old theory of encephalization as a series of
levels of progressively higher functional organization has been reexamined
by Sanides, who has demonstrated that brain expansion occurs through a
process of “core differentiation.” According to Sanides, in the phylogeny of

neocortex “. . . ever new waves of growth and differentiation evolved, and
each time a new cortex developed as a core, displacing the previous core to a
ringlike structure.” There is a striking correspondence between this account

and the description of differentiation within the posterior, and by implication,
the anterior speech areas in the course of maturation. Sanides has also
demonstrated that the “association” or “integration” cortex in man is not, as

traditionally believed, the “highest” region of the brain, but precedes the
“primary” or “projection” cortex in evolution. This is consistent with the idea
that lesions of “integration” cortex produce, as in anomia, a disorder micro-
genetically prior to disorders produced by lesion of “primary” cortex and

immediate surround, e.g. phonemic aphasia and neologistic jargon. It is likely,
therefore, that asymmetric neocortical organization, i.e., hemispheric
specification for language, represents an ontogenetic solution to a
phylogenetic problem, that of size limitations imposed upon an expanding
brain in the course of evolution.
There have also been important recent findings with regard to cortico-
cortical connections. There is evidence (in subhuman primates) that the

frontal “integration” cortex receives projections from the various “sensory”
cortices and that it is in relation to limbic system by way of cingulate gyrus
and lateral temporal lobe, and to thalamus via nu. dorsomedialis. Similarly,
the temporo-parietal “integration” cortex receives short fiber connections

from the various “sensory” cortices, and is also in relation to the limbic
system via lateral temporal cortex and cingulate gyrus, and to the thalamus
by way of lateralis posterior and pulvinar. Moreover, there are connections

between parietal lobe and frontal granular cortex. These facts suggest that in
primates, anterior and posterior “integration” cortices, i.e., regions
homologous to the corresponding speech zones in man, are organized in a

similar if not parallel fashion. Both areas are in relation to the parasensory
cortices, both connect to medial and lateral limbic structures and have
comparable thalamic representations.
These findings are of significance with regard to the problem of the
relationship between the posterior and anterior speech areas. While it is

generally believed that language is formed posteriorly and somehow
conveyed, by way of the thalamus, insula or association pathways, to Broca’s
area for motor speech, there is, in fact, little evidence for this view. Rather, it
may well be that a simultaneous realization occurs out of a common deep
structure into the final linguistic and motoric components of the language act.
Comment. The neural organization of language is characterized by an
evolving structural form which is built up during the course of life by a

continuous two-stage process, that of inter- and intrahemispheric
specification. The process through which the language structure develops,
moreover, is only a prolongation into ontogeny of an identical trend in
phylogenesis. This genetic approach to the problem of language organization
can recapture the dynamic element which is ignored by older static concepts
of “centers” and conducting pathways.
The term microgenesis has been proposed for the continuous formative
activity which underlies cognition. It is implicit that the process of
microgenesis recapitulates the sequence of phylo- and ontogenetic forms. The

described series of evolutionary and developmental levels supports this
process of cognitive formation. Language, that is, the series of levels through
which language develops, may be thought of as a final ontogenetic

“sensorimotor” differentiation within the neocortical ground supporting
cognition up to a prelinguistic phase.
General Aspects of Aphasia
Denial
Denial or lack of awareness of disease is a common manifestation in
both organic and functional disorders. The first description was by von
Monakow in 1885 in respect to two cases of cortical blindness, while the term
anosognosia, often applied to this phenomenon, was coined by Babinski for
lack of awareness of hemiparesis. Lack of awareness is also characteristic of
several aphasic forms, e.g., jargon, stereotypy, and echo responses. In general,
three types of denial are recognized: (1) partial or complete unawareness of a
deficit; (2) explicit denial of the deficit, or, in the case of hemiplegic denial, of
the very existence of the hemiparetic limbs; and (3) denial associated with
distortions, hallucinations, or other illusory phenomena referrable to the
impaired body zone (e.g., phantom or reduplicated limbs, visual
hallucination). The view that denial is a reaction of the personality as a whole
to the disorder is contradicted by the selective nature of the symptom. Thus,

patients with left hemiplegia may deny weakness in the arm but admit to
weakness in the leg. This occurs when there is a return of threshold sensory
or motor function in the lower extremity while the arm remains fully
paralyzed. Similarly, there may be catastrophic depression over subtotal

cortical blindness with persistent denial of a hemiplegia. One patient with a
left hemiplegia and previous amputation of the first two fingers of the left
hand was able to correctly explain why he could not move his amputated
fingers, but when asked to move the other (paralyzed) fingers of the same
hand, he refused to admit the paralysis. In a case of cortical blindness, there
was denial for the totally blind right visual field and awareness of visual loss
on the left side where only minimal vision remained (motion and light
perception). Thus, denial may spare a less recent disorder, may involve one of
two (usually the more severely involved) hemiparetic limbs, and may spare
deficient performances referrable to the same body zone, depending on the
reason for the deficiency.
In patients with denial there is commonly some degree of
disorientation, recent memory loss, and a confabulatory trend. There appears
to be a relationship between the severity of the perceptual deficit and the

confabulation. Cases of denial with fair visual or somaesthetic perception
have a marked Korsakoff syndrome, whereas the more severe the perceptual
impairment, the less prominent the Korsakoff and confusional state. This
inner bond between the severity of the perceptual disturbance and the
occurrence of confabulation is an important clue toward an understanding of
the mechanism of denial.
Those forms of language accompanied by deficient insight, the
stereotypy, the echo response, and certain types of jargon are not isolated
problems but are part of a continuous series across the spectrum of linguistic
change. A transition has been demonstrated between the stereotypic and the
volitional utterance (see p. 265). Patients who recover from a Broca’s aphasia
do not recall the stereotypic content, but may painfully recollect their initial
attempts to produce their own name. In echolalia, there is commonly an

inverse relation between the fidelity of the repetition and the degree to which
it is understood. Such patients may show echolalia for nonsense words or a
foreign language, and paraphasic repetition for their mother tongue. In some
patients, a transition occurs between the echo and normal repetition. This
takes place over four stages: (1) initial brief latency, explosive echo responses
accompanied by euphoria or labile emotionality, and lack of awareness for
the echoed content; (2) echolike responses with surprise or uncertainty

(partial awareness) of the performance; (3) repetitions with paraphasia,
especially phonemic paraphasia, with moderate awareness, and efforts at
self-correction; and (4) complete failure of an anomic type, with acute self-
awareness, frustration, and at times catastrophic reactions. These forms of

repetition may coexist and alternate in a single patient, just as the Broca’s
aphasic may have concurrent stereotypy and volitional speech. In each

instance, awareness can only be described in terms of a momentary state, as a
part of a general attitude bound up with an utterance in the process of

formation.
Affective Changes in Aphasia
It has long been recognized that aphasic patients tend to show different
affective features according to the nature of their language disorder. Schilder
wondered whether the apathy and/or depression of Broca’s aphasia and the
euphoria of Wernicke’s aphasia were intrinsic to the speech disturbance
rather than a secondary reaction. A study of linguistic change in aphasia
suggests that the affective picture is indeed an inner component, not
something “added on” to the language disturbance. Moreover, the affective

state is not specific to the “syndrome” but to the cognitive level, or speech
content manifesting that level, which is in the foreground at the precise
moment during which the affect is displayed. This helps to account for the
fluctuation in affective state that occurs in aphasic patients, since this is

correlated with a similar fluctuation in the linguistic-cognitive level.
In general, the semantic disorders are characterized by varying degrees
of euphoria and excitement. In anomia, there is an improved awareness of the

speech disorder, frustration, and some degree of self-correction and
censorship. In phonemic aphasia, there is a more acute insight into the speech
content, with improved self-correction. Marked alterations in affect are
usually not apparent. In Broca’s aphasia, there is apathy, dullness, and some
depression. Frustration and catastrophic reaction are not as common in this

group as in anomia. Patients with neologistic jargon may be euphoric and
excited. At times there is a definite paranoid trend, though systematized
delusions are unusual. Paranoia may also occur in semantic jargon but is less
common. In the rare disorder of word deafness, a condition characterized by
impaired speech perception despite good hearing and nonaphasic speech, the
presentation is almost invariably characterized by an acute psychosis with

marked paranoid ideation and auditory hallucination. Many of these patients
are initially hospitalized on a psychiatric service until diagnosis becomes
clear. The etiology of paranoia in aphasia is uncertain, though there are at

least three possible explanations: (1) it might reflect a lesion of temporal lobe
independent of the aphasia; (2) it might relate to impaired speech perception
and in that respect would be comparable to the “paranoia of the deaf”; or (3)
it might have an inner relationship with the language form of the aphasia.
Hallucination
Hallucination does occur in aphasia, chiefly, if not exclusively, with the
temporal-lobe disorders, word deafness and (less commonly) jargon. In the

former, auditory hallucination tends to appear at the onset, while in jargon it
may intervene after several days. These hallucinations may consist of noises,
single words, or sentences, e.g. the patient of Ziegler who heard such phrases
as “Carl, we’re going this way” and “It will be all right.” As in other perceptual
spheres, e.g., vision or somaesthesis, there is a relation between the density of
the perceptual deficit and the likelihood of hallucination. In organic disease,
hallucination often points to a lesion of the cortical projection zone of the
hallucinated modality.
In schizophrenic patients, there is impaired comprehension during a
bout of auditory hallucination. This has been attributed to inattention or
distraction. Yet a similar phenomenon occurs in organic cases, where the

hallucination seems to “fill the void” created by the loss of the perceptual
channel. In general, there is a striking similarity between functional and
organic hallucination. The fact that in the former there may be a higher
incidence of auditory than visual content, or that organic hallucination is less

systematized, may reflect, respectively, only fortuitous anatomical factors
(e.g., the rarity of a focal lesion restricted to auditory cortex) and duration, i.e.
that systematization requires a more prolonged hallucinatory state than is

generally seen in organic conditions. In fact, in some instances where
hallucination may persist for several years, e.g., in “peduncular hallucinosis,”
patients may develop a hallucinatory psychosis with marked organization

and systematization of the hallucinatory ideation. One difference between
organic and functional cases in this respect may be the fact that the former do
not show the same degree of fear or panic at the onset of the hallucinatory
state; in fact, some organic patients appear to be entertained by their

hallucinations. Certainly, this seems to be true for some cases of organic visual
hallucination, but probably does not hold for auditory hallucination.
Toward a Unitary Model of
Organic and Functional Disorders
Every symptom in an aphasic disorder points to a level in cognition. The
change in affect or in awareness, the occurrence of delusional or hallucinatory
states, the appearance of concrete or paralogical thinking, these are not, so to

say, outside the aphasia but are a reflection of that cognitive level of which
the aphasic speech form is one element.
A study of the aphasias suggests that the pattern of symptom formation

is identical in organic and functional disorders. An aphasia represents a
disruption in, i.e., a coming-to-the-fore of, higher levels in the linguistic
component of cognition. Agnosia and apraxia are parallel disorders in the

spheres of perception and action. The asymmetric organization of these
“higher” levels accounts for their special relationship to organic, i.e.,
unilateral, pathology. In functional states, the picture also corresponds to a
“coming-to-the-fore,” but of lower levels in cognition. Symptoms may appear
preferentially in the affective, motoric, perceptual, or linguistic components of
cognition. Similar symptoms can be produced by organic lesions, if bilateral

and precisely localized.
An approach to the aphasias, as well as to all psychopathological

disorders, from the point of view of cognition can reveal this inner bond
between organic and functional change.
Bibliography
Alajouanine, T. “Verbal Realization in Aphasia,” Brain, 79 (1956), 1-28.
----. L’Aphasie et le Langage Pathologique. Paris: Bailliere, 1968.
Alajouanine, T., O. Sabouraud, and de Ribaucourt. “Le Jargon des aphasiques,” J. Psychol., 45
(1952), 158-180, 293-329.
Arieti, S. Interpretation of Schizophrenia, 1st ed., New York: Brunner, 1955; 2nd ed., New York:
Basic Books, 1974.
Avakian-Whitaker, H. “On Echolalia.” Paper presented at the Academy of Aphasia. Rochester,

1972.
Babinski, J. “Contribution a l’étude des troubles mentaux dans l’hémiplégie organique cérébrale
(Anosognosie),” Rev. Neurol. (Paris), 27 (1914), 845-848.
Barton, M., M. Maruszewski, and D. Urrea. “Variation of Stimulus Context and Its Effects on Word-
Finding Ability in Aphasics,” Cortex, 5 (1969), 351-365.
Bay, E. “Aphasia and Non-verbal Disorders of Language,” Brain, 85 (1962), 411-426.
----. “Present Concepts of Aphasia,” Geriatrics, 19 (1964), 319-331.
Benton, A. and R. Joynt. “Early Descriptions of Aphasia,” Arch. Neurol., 3 (1960), 205-222.
Binswanger, L. Sigmund Freud: Reminiscences of a Friendship. New York: Grune & Stratton, 1957.
Bleuler, E. Dementia Praecox. New York: International Universities Press, 1950.
Blumstein, S. “Phonological Aspects of Aphasic Speech,” in C. Gribble, ed., Studies Presented to

Professor R. Jakobson by His Students, pp. 39-43. Cambridge: Slavica, 1970.
Bogen, J. “The Other Side of the Brain,” Bull. Los Angeles Neurol. Soc., 34 (1970), 73-105, 135-162.
Bouillaud, J. “Réchèrches cliniques propres à demontier que la perte de la parole, etc., Arch. Gen.
Méd., 8 (1825), 25-45.
Brain, R. Speech Disorders. London: Butterworths, 1961.
Broca, P. “Remarques sur le siège de la faculté du langage articulé,” Bull Soc. Anat., 36 (1861),
330-357.
----. “Nouvelle observation d’aphémie produite par une lésion de la moitié postérieure des
deuxième et troisième circonvolutions frontales,” Bull. Soc. Anat., 36 (1861), 398-
407.
----. “Localisation des fonctions cérébrales siège du langage articulé,” Bull Soc. Anthropol., 4
(1863), 200-204.
----. “Sur le Siège de la faculté du langage articulé,” Bull. Soc. Anthropol., 6 (1865), 377-393.
Brown, J. “Hemispheric Specialization and the Corpus Callosum,” in C. Gunderson, ed., Present
Concepts in Internal Medicine. San Francisco: Publ. Letterman Hospital, 1969.
----. Aphasia, Apraxia and Agnosia: Clinical and Theoretical Aspects. Springfield, Ill.: Charles C.
Thomas, 1972.
----. “Introduction,” in: A. Pick, Aphasia. (English translation), Springfield, Ill.: Charles C. Thomas,
1973.
----. “Language, Cognition and the Thalamus,” Confin. Neurol., 36 (1974), 33-60.
----. “The Neural Organization of Language,” Brain Lang., 1 (1975), in press.
----. “The Problem of Repetition,” Cortex (1975-76) in press.
Brown, J. and J. Jaffe. “Hypothesis on Cerebral Dominance,” Neuropsychologia, (1975), 107-110.
Brown, J. and F. Wilson. “Crossed Aphasia in a Dextral,” Neurology, 23 (1973), 23-30.
Cameron, N. “Experimental Analysis of Schizophrenic Thinking,” in J. Kasanin, ed., Language and
Thought in Schizophrenia, pp. 50-64. New York: Norton, 1964.
Chapman, J. “The Early Symptoms of Schizophrenia, “Br. J. Psychiatry, 112 (1966), 225-251.
Charcot, J.M. “Des Variétés de l’aphasie,” Prog. Méd., 11 (1883), 487-488, 521-523.
Chomsky, N. Syntactic Structures. The Hague: Mouton, 1957.
----. Aspects of the Theory of Syntax. Cambridge: M.I.T. Press, 1965.
Conrad, K. “Strukturanalysen hirnpathologische Fälle, I: Uber Struktur und Gestaltwandel.” Dtsch.

Z. Nervenheilk., 158 (1947), 344-371.
Critchley, M. Aphasiology and other Aspects of Language. London: Arnold, 1970.
Dimond, S. The Double Brain. Edinburgh: Churchill Livingstone, 1972.
Domarus, von E. “The Specific Laws of Logic in Schizophrenia,” in J. Kasanin, ed., Language and
Thought in Schizophrenia, pp. 104-114. New York: Norton, 1964.
Freud, S. On Aphasia. Translated by Stengel. New York: International Universities Press, 1953.
Froeschels, E. “A Peculiar Intermediary State between Waking and Sleep,” J. Clin. Psychopathol., 7
(1946), 825-833.
Gall, F. and C. Spurzheim. Anatomie et Physiologie du Système Nerveux en Général et du Cerveau en

Particulier. Paris: Schoell, 1810-1819.
Gazzaniga, M. The Bisected Brain. New York: Appleton-Century-Crofts, 1970.
Geschwind, N. “The Paradoxical Position of Kurt Goldstein in the History of Aphasia,” Cortex, 1
(1964), 214-224.
----. “Language and the Brain,” Sci. Am., 226 (1972), 76-83.
Geschwind, N., F. Quadfasel and J. Segarra. “Isolation of the Speech Area,” Neuropsychologia, 6
(1968), 327-340.
Goldstein, K. Die Transkortikalen Aphasien. Jena: Fischer, 1915.
----. “Das Wesen der amnestischen Aphasie,” Schweiz. Arch. Neurol. Psychiatr., 15 (1924), 163-175.
----. “The Significance of Psychological Research in Schizophrenia,” J. Nerv. Ment. Dis., 97 (1943),
261-279.
----. Language and Language Disturbances. New York: Grune & Stratton, 1948.
Goodglass, H. “Redefining the Concept of Agrammatism in Aphasia,” Proc. 12th Int. Speech Voice
Ther. Conf., Padua, 1962, pp. 108-116.
----. “Studies on the Grammar of Aphasics,” in S. Rosenberg and J. Kaplan, eds., Developments in
Applied Psycholinguistic Research. New York: Macmillan, 1968.
Goodglass, H. and S. Blumstein. Psycholinguistics and Aphasia. Baltimore: The Johns Hopkins
University Press, 1973.
Green, E. “Phonological and Grammatical Aspects of Jargon in an Aphasic Patient,” Lang. Speech,
12 (1969), 103-118.
Head, H. Aphasia and Kindred Disorders of Speech. New York: Macmillan, 1926.
Hecaen, H. and J. Dubois. La Naissance de la Neuropsychologie du Langage. Paris: Flammarion,

1969.
Hecaen, H., J. Dubois, and P. Marcie. “Critères Neurolinguistiques d’une Classification des
Aphasies,” Acta Neurol. Psychiatr. Belg., 67 (1967), 959-987.
Heilbronner, K. Zur Symptomatologie der Aphasie. Archiv. Psychiatr. Nervenheilk., 43 (1908), 234-
298.
Heubner, O. “Über Aphasie,” Schmidt’s Jahrb., 224 (1889). 220-222.
Howes, D. “Application of the Word-Frequency Concept to Aphasia,” in A. V. S. De Reuck and M.

O’Connor, eds., Disorders of Language. London: Churchill, 1964.
Isserlin, M. “Aphasie,” in O. Bumke and O. Foerster, eds., Handbuch der Neurologie, Vol. 6, pp. 627-
806. Berlin: Springer, 1936.
Jackson, H. Selected Writings of John Hughlings Jackson, Vol. 2, J. Taylor, ed., London: Hodder &
Stoughton, 1932.
Jakobson, R. “Towards a Linguistic Typology of Aphasic Impairments,” in A. V. S. De Reuck and M.

O’Connor, eds., Disorders of Language. London: Churchill, 1964.
----. Child Language, Aphasia and Phonological Universals. The Hague: Mouton, 1968.
Jakobson, R. and M. Halle. Fundamentals of Language. The Hague: Mouton, 1956.
Jones, E. and T. Powell. “An Anatomical Study of Converging Sensory Pathways Within the
Cerebral Cortex of the Monkey,” Brain, 93 (1970), 793-820.
Kertesz, A. “A Linguistic Analysis of Fluent Aphasia,” Brain Lang., 1 (1974), 43-62.
Kertesz, A. and F. Benson. “Neologistic Jargon,” Cortex, 6 (1970) 362-386.
----. “The Classification of Schizophrenia,” J. Ment. Sci., 103 (1957), 443-463.
----. Sensory Aphasia and Amusia. Oxford: Pergamon, 1962.
Kreindler, A., C. Calavrezo, and L. Mihăilescu. “Linguistic Analysis of One Case of Jargon Aphasia,”
Rev. Roumaine Neurol., 8 (1971), 209-228.
Lashley, K. “The Problem of Serial Order in Behavior,” in L. Jefress, ed., Cerebral Mechanisms in
Behavior (Hixon Symposium), pp. 112-136. New York: Wiley, 1951.
Lecours, A. and F. Lhermitte. “Phonemic Paraphasias: Linguistic Structures and Tentative

Hypotheses,” Cortex,. 5 (1969), 193-228.
Lhermitte, F. “Sémiologie de l’aphasie,” Rev. Praticien, 15 (1965), 2255-2292.
Liepmann, H. “Ein Fall von Echolalie,” Neurol Zentralbl., (1900), 389-399.
Lotmar, F. “Zur Kenntnis der erschwerten Wortfindung und ihrer Bedeutung für das Denken des
Aphasischen,” Schweiz. Arch. Neurol. Psychiatr., 5 (1919), 206-239.
Luria, A. Higher Cortical Functions in Man. New York: Basic Books, 1966.
Marie, P. “Révision de la question de l’aphasie,” Sem. Méd., 21 (1906), 241-247, 493-500, 565-571.
Marshall, J. and F. Newcombe. “Syntactic and Semantic Errors in Paralexia,” Neuropsychologia, 6

(1966), 169-176.
Monakow, C. von. “Experimentelle und Pathologische-anatomische Untersuchungen über die

Beziehungen der sogennanten Sehsphare zu den infrakortikalen Opticuscentren
und zum N. Opticus,” Arch. Psychiatr., 16 (1885), 151-199.
Morsier, G. de. “Les Hallucinations,” Rev. Otoneurophtalmol., 16 (1938), 241-352.
Nielsen, J. Agnosia, Apraxia, Aphasia. New York: Hafner, 1965.
Oldfield, R. “Things, Words and the Brain,” Q. J. Exp. Psychol., 18 (1966), 340-353.
Pandya, D. and H. Kuypers. “Cortico-Cortical Connections in the Rhesus Monkey,” Brain Res., 13
(1969), 13-36.
Pandya, D. and F. Sanides. “Architectonic Parcellation of the Temporal Operculum in Rhesus

Monkey and Its Projection Pattern,” Z. Anat. Entwickl. Gesch., 139 (1973), 127-161.
Penfield, W. and L. Roberts. Speech and Brain Mechanisms. Princeton: University Press, 1959.
Petras, J. “Connections of the Parietal Lobe,” J. Psychiatr. Res., 8 (1971), 189-201.
Pick, A. Beiträge zur Pathologie und pathologischen Anatomie des Centralnerven-systems. Berlin:
Karger, 1898.
----. Die agrammatischen Sprachstorungen. Berlin: Springer, 1913.
----. Aphasia. Translated by J. Brown. Springfield, Ill.: Charles C. Thomas, 1973.
Pitres, A. “L’Aphasie amnésique et ses variétés cliniques,” L’Echo Med., 24 (1898), 276-281, 289-
294, 301-306, 313-317. 325-332, 337-342, 351-352, 373-378, 385-390, 397-405,
409-425, 433-437.
Riese, W. “The Early History of Aphasia,” Bull. Hist. Med., 21 (1947), 322-334.
Rinnert, C. and H. Whitaker. “Semantic Confusions by Aphasic Patients,” Cortex, 9 (1973), 56-81.
Rochford, G. and M. Williams. “Studies in the Development and Breakdown of the Use of Names,”
J. Neurol. Neurosurg. Psychiatr., 25 (1962), 228-233.
Sabouraud, O., J. Gagnepain, and A. Sabouraud. “Vers une Approche linguistique des problèmes de
l’aphasie (II). L’Aphasie de Broca,” Rev. Neuropsychiatr. l’Ouest., 2 (1963), 3-38.
Sanides, F. “Functional Architecture of Motor and Sensory Cortices in the Light of a New Concept
of Neocortex Evolution,” in C. Noback and W. Montagna, eds., The Primate Brain, p.
183. New York: Appleton-Century-Crofts, 1970.
Schilder, P. and N. Sugar. “Zur Lehre von den schizophrenen Sprachstörungen,” Z. Neurol
Psychiatr., 104 (1926), 689-714.
Sperry, R. “Perception in the Absence of the Neocortical Commissures,” in D. A. Hamburg, K.

Pribram, and A. Stunkard, eds., Perception and Its Disorders, Vol. 28, pp. 123-138.
Association for Research in Nervous and Mental Disease. New York: Williams &
Wilkins, 1970.
Spreen, O. “Psycholinguistic Aspects of Aphasia,” J. Speech Hear. Res., 11 (1968), 467-480.
----. “Psycholinguistics and Aphasia: The Contribution of Arnold Pick,” in H. Goodglass and S.
Blumstein, eds., Psycholinguistics and Aphasia, pp. 141-170. Baltimore: The Johns
Hopkins University Press, 1973.
Stengel, E. “A Clinical and Psychological Study of Echo-Reactions,” J. Ment. Sci., 93 (1947), 598-
612.
Stengel, E. and G. Steele. “Unawareness of Physical Disability (Anosognosia),” J. Ment. Sci., 92

(1946). 379-388.
Trousseau, A. “De l’Aphasie, maladie décrite récemment sous le nom impropre d’aphémie,” Gaz.
Hopitaux, 37 (1864).
Victor, M. Personal communication to author, 1973.
Victor, M., Adams, R., and G. Collins. The Wernicke-Korsakoff Syndrome. Philadelphia: Davis, 1971.
Weigl, E. and M. Bierwisch. “Neuropsychology and Linguistics: Topics of Common Research,”

Found. Lang., 6 (1970), 1-18.
Weinstein, E. and N. Keller. “Linguistic Patterns of Misnaming in Brain Injury,” Neuropsychologia,

1 (1964), 79-90.
Weinstein, E., O. Lyerly, M. Cole et al., “Meaning in Jargon Aphasia,” Cortex, 2 (1966), 165-187.
Weisenburg, T. and K. E. McBride. (1935) Aphasia: A Clinical and Psychological Study; reprinted.
New York: Hafner, 1964.
Wernicke, C. Der aphasische Symptomenkomplex. Breslau: Cohn and Weigart, 1874.
Young, R. Mind, Brain and Adaptation in the Nineteenth Century, Oxford: Clarendon, 1970.
Ziegler, D. “Word Deafness and Wernicke’s Aphasia,” Arch. Neurol. Psychiatry, 67 (1952), 323-
331.
Zurif, E. Paper presented at International Neuropsychology Society, Boston, 1974.
Notes
1 Supported in part through a grant from the Foundations’ Fund for Research in Psychiatry.
2 Years later Freud was to write to Binswanger that Wernicke was ". . . an interesting example of the
poverty of scientific thought. He was a brain anatomist and could not help dissecting the
soul as he had the brain."
Chapter 11
Aphasia:
Behavioral Aspects1
J.P. Mohr and Murray Sidman
Introduction
The subject matter of aphasia encompasses a spectrum ranging from
the practical assessment of an acutely brain injured patient to the abstract
theory of language. Since definitions of aphasia vary with the approach to the
subject matter, descriptions adequate for one purpose are often
inappropriate for another. This chapter is oriented toward the behavioral
features of aphasia deficits.
Any understanding of aphasia requires consideration of the roles played

by individual variables in the performance profile observed in a given patient
at a given time. In roughly descending order of importance, these variables
include the methods used to delineate the deficit, the site of the brain injury,
the patient’s age and handedness, the rapidity of onset, duration, causative
agent, the size of the brain injury, and coexisting motor and sensory deficits.
Singly, and in combination, they can account for many seemingly
contradictory or only loosely comparable features of different cases of

aphasia.
A theoretical structure is helpful, but not a prerequisite in approaching

the subject of aphasia. The spectrum of traditional and current theories of
aphasia can be accommodated within the following elementary summary. At
the lowest level of complexity, the basic instrumentalities subserving
discrimination, replication, and production of verbal stimuli, the phonologic
aspects of language, are considered to require the proper functioning of the
cortical surface and subcortical white matter structures grouped around the
Sylvian fissure of the left cerebrum. Auditory inputs from the brain stem pass
via white matter pathways to the primary auditory cortex (Heschl’s
transverse gyri) located in the superior temporal lobe at the posterior region
of the Sylvian fissure. Vocal outputs are controlled by the primary motor
cortex (Rolandic fissure), subserving movements of the oropharynx, larynx,

and respiratory apparatus. Control of the individual movements, transitions
of movements, and melodic sequences involved in speaking aloud is exerted

via the adjacent premotor cortex in the inferior frontal region (Broca’s area).
Fiber pathways in the arcuate fasciculus, deep to the insula, may link the
auditory and vocal motor regions to permit repeating aloud from dictation. At
a level of greater complexity, organization and comprehension of
conversational speech, especially its semantic and syntactic aspects, are
traditionally thought to reflect activity of the inferior parietal and posterior

temporal regions adjacent to the auditory cortex, the combination usually
referred to as Wernicke’s area. Combined lexic and graphic activity is also
thought to involve inferior parietal activity, especially those portions

adjoining the more posteriorly situated occipital lobe, whose main function
involves processing of visual inputs. The most complex, abstract, and
theoretical levels of language activity are considered to involve preverbal
thought, i.e., the formulation of the basic message to be conveyed; posterior
and deep temporal-lobe functions may underlie these processes, the
documentation for which remains theoretical and introspective at best.
Two main variations of the foregoing underlie most writings in the field
of aphasia, even though they are not always explicitly stated. In the first
variation, brain mechanisms underlying language behavior are seen to reflect
the interaction of relatively autonomous cerebral regions, i.e., auditory, visual,
and motor. Constellations of individual findings (syndromes), which
constitute clinical aphasia, reflect focal brain injuries (lesions) of varying

origin, involving the cortical surface “centers” or the white matter pathways,
separately or in various combinations. In the second variation, only one
cerebral region, situated in the posterior portion of the Sylvian fissure, is
crucial for language behavior. The cerebral regions serving sensory input and
motor output are seen functionally as essentially centripetal or centrifugal,
respectively, to this central zone. Syndrome analysis is directed toward

discovering evidence of deficits thought to reflect damage to the central
language mechanism, irrespective of the input or output channels involved in
the behavior being tested. Such deficits are considered aphasic, while
involvements reflecting only damage to the centrifugal or the centripetal
functions are not.
The basic theoretical formulations outlined above have served as the
foundation for most of the many different viewpoints toward aphasia. It is all
the more unfortunate, in view of the enormous amount of study given the
subject, that basic ambiguities still prevent a clear understanding of the
subject.
Testing for Aphasia
The major aphasic syndromes were originally described from clinical
observations. Although ingenious tests were often used in assessing the

classic cases, the data now available are in most cases summary notes which
reflect the investigator’s interpretation of the behavior more than they do the
actual behavior itself. The subsequent development of methods for analyzing
behavior has resulted in a continual updating of the components of individual
aphasic syndromes, with some divergence from previous interpretations.
Much of the controversy in the field of aphasia stems from clinical
differences among patients with apparently similar lesions. Much of this
variability reflects the selection of the aphasic population to be tested, the
actual tests administered, and the methods of test administration.
Case Selection
A variety of approaches has been used in the selection of cases.
Historically, the report of a single case or a few cases showing virtually

identical findings, has set the precedent still favored by many investigators.
Reports of one, or of a limited number of cases, generally include anatomic
findings proved by autopsy, and involve intensive study for varying periods of
time, and/or show singular or unique findings bearing on aphasia theory, all
encompassed in a readably brief account. Taken together, fewer than one

hundred such cases have contributed the majority of the data upon which the
major current ideas on aphasia depend. Yet even these intensively studied
single cases have undergone only a limited number of tests. It has been
argued that such cases are so rare and unusual that they are not
representative of the field of aphasia in general. This contention has been

countered by the point that the combined factors of anatomy and pathologic
processes in naturally occurring illness usually result in brain injuries whose
location and extent encompass so many important regions simultaneously
that most cases are too complex to permit a detailed analysis. The rare case of
sharply specifiable deficits is of value as the exception that helps clarify the
rules.
Another approach to case selection has been to study a large group

sharing in common some major variables, such as site of lesion, etiology, age,
etc. War injuries are a prototype of this approach. These studies provide
corroboration for the individual case reports. They suffer from the statistical
summary approach in which details of individual cases can get lost in group
averages.
In yet another approach, the purpose has been to screen an unselected
population using a single test or series of tests. Separation of the case
material in the groups is then based on the responses made by individuals.
Such collections of cases seem to show the most general, and least specific,
findings. Critics contend that the nonspecificity of the findings reflects the
inclusion of cases differing widely in type, whose individual differences
disappear when the data are averaged together. Supporters point to the need
to establish an approach to deficit profile without dependence on these
traditional criteria, so as to permit some validation of the traditional means of

classifying cases.
Test Methods
The authors believe that the methodology used to approach a case of
aphasia is basic to all other considerations, since it provides the data from
which the theories should be derived. Accordingly, test methodology will be
discussed before taking up the analysis of aphasia.
In his monograph on aphasia in 1874, Wernicke noted a tendency for
patients to seize upon any kind of cues available to them when they
experienced difficulties with the tests designed to assess their language

behavior. Although he recorded this observation—that patients may use any
of a number of possible means to approach a task—in his early monograph on
aphasia, deliberate specification of individual parameters in aphasia testing

has received intensive attention only in recent years. As late as 1966
proposals could still be found calling for standardization of the stimulus,
response, and other variables involved in aphasia testing.
At the present time, since major research centers tend to maintain and
use their own methods, data from different centers are often not strictly
comparable. Ambiguities and differences in the observation of aphasic

behavior are a paramount source of disagreement, and a review of the major
methods used to evaluate aphasia patients seems justified.
Behavioral
Although all aphasia tests are behavioral, few investigators explicitly
and systematically use the principles and techniques that stem from objective
behavioral science. We have, therefore, used the term “behavioral” to
characterize our own approach.
With some oversimplification, we can specify three major classes of
behavioral variables which may interact with physiological processes to
govern a person’s interaction with his environment. First, all behavior,
including that exhibited in aphasia tests, is governed by its consequences.

Rather than depend solely on a patient’s presumed motivation to do well in
our tests, we provide explicit positive reinforcement, i.e., to encourage correct
responses. Behavioral deficits, aphasic or other, may result from the
breakdown of the controlling relation between behavior and its

consequences, and the terms, “motivational” or “reinforcement deficit,” are
often applied. Little is known about such clinical deficits in humans; it need
only be said here that a patient is likely to exhibit no consistent behavior if

presumed reinforcers in the test situation are ineffective, and any conclusions
about aphasia will be untenable in such patients.
A second class of variables is subsumed in the term, “stimulus control.”
Appropriate behavior occurs in response to stimuli which set the occasion for
reinforcement, as determined by a person’s behavioral history. When we
observe that a particular stimulus occasions a response, and that its absence
fails to do so, we have a controlling relation between stimulus and response.
An example of the complexity involved in stimulus control is the relation
between traffic lights and a driver’s behavior. We have achieved considerable

initial support for the notion that many aphasic deficits represent
breakdowns of stimulus control; for example the controlling relation between
printed words and oral naming (speech deficit), between pictures and written
naming (writing deficit), or the nonverbal selection of appropriate pictures in
response to printed words (reading comprehension).
The third class of variables may be termed “instructional.” These
include the constant stimuli of the test environment, the test procedures
themselves, and the specific instructions given to the patient about what he is
expected to do. Clearly, a patient who is not sensitive to instructional factors
will exhibit test behavior that is unrelated to the purposes of the tests. Like
motivational deficits, instructional deficits invalidate any conclusions specific
to aphasia. Since aphasia, by its very nature, represents a communication

disorder, instructional deficit is often difficult to circumvent in aphasia
evaluation. The problem can be overcome by appropriate use of effective
reinforcers, which function nonverbally to inform the patient when he is

performing as requested.
Controls for reinforcement and instructional deficits are built into the
procedures of the tests, which are, themselves, oriented toward the analysis
of stimulus-control deficits characteristic of aphasia. The sequence of tests,
furthermore, has been designed to reveal intact forms of stimulus control,
thereby reducing the number of factors that must be considered to play a role
in the patient’s deficit. The tests themselves simply required the patient to
name orally, write, or match (select from a number of alternatives) visual,

auditory, or palpated test stimuli, such as single letters, three-letter picturable
nouns and their pictures, color names and their colors, digit names and their
digits, and manipulable objects. These tests demonstrate the control exerted
by each stimulus (visual, auditory, or palpated) over each type of response

(oral, naming, writing, and matching). The test battery yields a stimulus-
control matrix in which stimulus (input) channels, response (output)
channels, and controlling stimulus-response or stimulus-stimulus relations

can be evaluated.
Such systematic behavioral evaluation has revealed six large groups of

patients, five of which have not yet been extensively studied. The first group
includes patients whose deficit is so mild as to escape detection by simple
tests. These cases are frequently considered normal on initial brief bedside
examinations. It remains to be seen whether more complex materials, at the
sentence, paragraph, and syntactical level, will reveal deficit constellations
similar to those shown in other patients tested with the simpler materials.
The second two groups are at the other end of the scale, and completely
new test procedures will be required to study them effectively. The most
severe deficits are those in which reinforcement is inadequate to maintain
behavior, thereby precluding the delineation of a deficit profile. The few such
patients we have tested have been those with medially placed frontal lesions
exhibiting symptoms of hydrocephalus, clinical states of delirium, and
dementia. This is a potentially fruitful area for the application of Pavlovian
conditioning techniques. Also untestable by the present methods are patients

with deficient instructional control, for their test behavior is completely
unrelated to our test materials and procedures. These patients include a
number of cases exhibiting the bedside syndrome of central, or Wernicke’s,

aphasia. Instructional deficits can be differentiated from reinforcement
deficits only if reinforcement can be shown to be effective in some other kind
of test, such as a less demanding visual or auditory discrimination, in which

the need for instructional control is minimal.
The fourth and fifth groups are those who show deficient input
(stimulus)33 or output (response) channels. These two groups include the

vast majority of cases labelled in a brief bedside examination as showing
“agnosia,” “pure” word blindness, deafness, mutism, etc. Input deficit reveals
itself when a particular type of stimulus fails consistently to control any type
of response. Output deficit reveals itself when a particular type of response
consistently fails to occur in the presence of any stimulus. The functions of the
input and output channels are assessed by identity tests. These involve a
response which is physically identical to the test stimulus. For example,

repeating dictated words aloud, copying printed words, and choosing from
among a visually presented set of words one which is typed and spelled
exactly like the test stimulus, are all examples of responses which are
physically identical to the test stimulus. These identity tests require no

previous experience with the stimuli and serve principally to test the
adequacy of stimulus discrimination and response production in the input
and output channels used for testing.
Once these identity tests have shown the adequacy of the input and
output channels, those channels and stimuli found adequate can then be used
to explore the specificity of stimulus control in “nonidentity” tasks. In these
tests, the response required is not physically identical to the test stimulus.
Examples include spoken responses to visual stimuli, written response to
dictated stimuli, selection of choices (matching) in which, for example, the

test stimuli are pictures, and the comparison stimuli are words.
The sixth group of patients, with intact input and output channels,
display differential relational deficits between otherwise normally

functioning stimulus and response systems. This group, which includes the
vast majority of patients whose conventional clinical bedside evaluation
reveals clear evidence of aphasic disorder, has revealed a number of deficit
profiles. Some include classical syndromes, some appear to be previously
undescribed, and some are mainly of methodological and interpretive interest

(see references 23, 24, 33, 34, 43, and 44).
Other investigators have independently devised methods similar in

principle to our behavioral model. The principle of using common
manipulable object stimuli presented separately in visual, auditory, and
palpated form for separate spoken and written naming responses began with
Head’s six objects. It was popularized in the United States, was increased to
twenty objects, is found in modified form as a basis for a currently popular
aphasia test battery, and, in reduced form, is present as a subtest in many

other aphasia test batteries. Extensive use has been made of the matching-to-
sample paradigm as a means of “facilitating” correct responses on verbal tests
requiring spoken or written responses where errors appeared.
Similar procedures have seen extensive use in production examinations
of inter- and intramodality performances in cases of surgical sections of the
corpus callosum.
Traditional Test Batteries
Another major approach to delineation of aphasic deficits involves the
presentation of a wide variety of individual tests, each designed to assess a
given aspect of behavior, without deliberate continuity of stimulus material,
input and response channels, or reinforcement across the spectrum of tests.
Each test in the subgroups is constructed to stand individually and have its
own validity. The performance profile that results for a given patient is
compared with that obtained in normals and in other aphasic patients.
The corpus of tests included in these traditional batteries appears to
have arisen from the large variety of individual tests created by previous
aphasiologists, to which modifications have steadily been added. Credit is
given to Weisenburg and McBride for the first systematic use of standard
clinical psychological tests, including IQ tests, in the evaluation of aphasia.
Several major groups of investigators have developed and validated
systematically constructed batteries of individual and separate tests to an

impressive level of complexity and reliability.
Many of these test batteries contain an almost panoramic array of
individual tests, covering virtually every theoretical aspect of speech function.

Under circumstances of increasing complexity in succeeding trials, the subject
may be asked to: name visually displayed manipulable objects, pictures,
colors, forms, pictures reduced in size, numbers, letters, printed words,

printed sentences; recognize sounds such as clapping made by the examiner;
point to body parts on command; name a manipulable object placed unseen in
either hand; indicate which one of several visually displayed printed words
corresponds most closely to dictated sentences; point to the one of several
visually presented words which matches the answer to a visually presented

question after dictated paragraphs have been read to the subject; silently
read printed questions and point to the visually presented words which
answer the question; silently read paragraphs and answer printed questions
by pointing to the correct printed alternative; count from one to twenty;

name the alphabet from A to Z, the days of the week, the months of the year;
write numbers, letters, words, and sentences to dictation; answer visually
presented or dictated sentences in the form of questions by speaking aloud or

writing the answers spontaneously; perform various computations on paper;
press buttons which ring a bell or buzzer to indicate which among several
alternatives is the principle that underlies a variety of pictures; place unseen
objects into unseen holes conforming to the same shape; indicate which
tapped rhythm matches the one originally presented; select the printed
speech sounds dominant in the spoken form of visually presented words; tap
with the index finger of each hand as rapidly as possible; reset a moving clock
after it has completed ten cycles; speak aloud the word which is opposite in
meaning to that spoken by the examiner or presented visually by the
examiner; match spoken words to the correct one of several visually
presented words which differ from one another in minor spelling or in
similarities of sound or meaning; read a complicated paragraph silently and
draw a line through a given letter each time it occurs in the paragraph; copy
on paper complex visually presented forms; sort colors according to a
previously dictated underlying principle; draw a man; find a figure hidden in
a larger visually displayed figure; assemble blocks and other components to
match visually displayed models; trace through a visually presented maze;
recall a dictated short sentence after the passage of a short period of time;
interpret proverbs dictated by the examiner; sing familiar songs; explain the
difference between a father’s brother and a brother’s father, name items
missing in a picture which are ordinarily expected to be present; describe the
absurdity in a picture deliberately drawn to show an incongruous situation;

take up a number of complex bodily positions demonstrated by the examiner
seated facing the patient; name pictures presented as line drawings
overlapping one another, up to four or five or a greater number of individual

line drawings; indicate the direction the arrow should move in a drawing
demonstrating a series of levers connected together with an arrow at one end
and a handle at the other end; repeat from dictation a long series of
complicated and closely related sound sequences; spell words forward and
backwards; supply captions for complicated pictures. . . . The individual tests
detailed above in simple descriptive form by no means encompass the vast
spectrum available.
The brief enumeration of tests available in traditional test batteries
points up a commonly noted problem with the utilization of many of these
tests: the patient must show by behavior that instructions on the tasks have
been sufficient before the examiner is free to conclude or undertake analysis
as to reasons for failure. As a consequence, these tests are of value chiefly in
demonstrating that the patient is capable of accomplishing them correctly.
Reasons for failure can only rarely be analyzed on an individual test basis.
Instead, the analyses of the syndromes delineated by these test batteries
depend principally upon a comparison of the overall test scores among
patients of differing focal brain injury and/or common etiology for their
validity and for their value in assessing a deficit in aphasia. As a tool for
analyzing the individual deficits or the range of deficits, there is so little
deliberate continuity of test stimulus material, or input, or response channels
utilized for such testing, as to make the individual tests virtually

noncomparable with one another.
However critical our remarks may be concerning the analytic

shortcomings of the tests, their value in predicting site and type of brain
injury has been empirically validated. The question of which tests are critical,
and why, and their relations to language or other behavioral processes have
yet to be clarified.
Theory-Corroborating Tests
A number of individual tests used and popularized by famous
investigators were designed to demonstrate a particular point concerning the
nature of aphasia, or to corroborate particular theories. Like many of the
individual tests in the traditional test batteries, these theory-corroborating
tests frequently are of greatest clinical value in demonstrating that the patient
is capable of the tested performance, thereby indicating that the individual
parameter which the test allegedly assesses is intact. The extent to which the
data provided by the aphasic patient corroborate the test originator’s views
on aphasia is now mainly only a subject of historical interest.
These tests include the well-known three-paper test of Marie: The
patient is presented with a piece of paper on which the examiner, in his own
handwriting, has written an instruction to the effect that, “When you have
finished reading this page, tear the page into three parts. Give one to me.
Throw a second on the floor. Put the third in your pocket.” The capacity of the
intact patient to translate *he examiner’s handwriting style and follow this
three-step command goes a long way towards settling any issue regarding the
presence of aphasia. Goldstein proposed another variety of tests to assess
impairment in “abstract attitude.” In these tests, the patients were asked to
select from among a variety of stimuli the one which did not match the
remainder of the group in terms of some functional principle, or to name the
overall categorical word which would best describe the functional class of
which the demonstrated materials were members, for example, tools. As a
later development, Luria has devised a variety of tests of increasing
complexity which utilize essentially Pavlovian methods, but which have not
yet been popularized in the West.
Analysis of Aphasia
Despite its clinical frequency and the relatively large number of
investigations into its properties, aphasia has proved a difficult subject for
study. Definitions of terms remain unagreed upon even at the present time.
The use of familiar but poorly defined eponyms, such as Broca’s aphasia, to
characterize clinical syndromes makes it frequently impossible to determine
whether an aspect of aphasic behavior that emerges from detailed analysis is

actually a component of the syndrome. Everyday clinical cases regularly
provide more exceptions than do illustrations of the rules predicted by the
all-encompassing theories of aphasia.
Despite its limitations, the behavioral approach to aphasia provides
quantitative assessment of a variety of responses to a range of stimulus
materials; it determines the state of individual input and output channels as a

prerequisite for the identification of deficient input-output relations; it
follows the evolution of syndromes over time; and its data are available for
interpretation by any theories. It provided the nucleus of the material
detailed below for the analysis of aphasia.
General Properties of Aphasia
Cases of aphasia share many general features of behavior with normal

subjects, especially when the latter are tired or tested under difficult
conditions. Reinforcement that is inadequate to maintain behavior in the face
of frequent errors commonly leads to breakdown of the control exerted by
the test procedures. This state of affairs is revealed in a number of ways. The
patient may simply stop responding. He may perseverate previously correct
responses, even though these responses are complex, i.e., writing whole
words. At times, long delays occur before he responds. He complains of being
tired or uncomfortable; lame excuses of poor vision, inadequate education,
unfamiliarity with the tests, etc., are common. Occasionally, outbursts of
anger occur, with the patient scattering the test stimuli around, rising and
leaving the test site, turning away, or even assaulting the examiner. Control
over the patient’s behavior can usually be reestablished by changing to a task
he can easily accomplish, increasing the reinforcement, slowing the rate of
testing, and similar devices. The patient’s ability to return to the task, and
perform reliably over a long test session, suggests that “fatigue,” traditionally
considered a major variable in aphasia, is a reflection of the test procedures.
Signs of fatigue are mostly evident when the patient is having difficulty with
the test.
The errors occurring when the test situation maintains adequate

control over the patient’s behavior take three main forms, which are also
common with normal subjects. Repetition of a previous response or portion
thereof (perseveration) is common. In many instances, a correct response

given previously is repeated on a subsequent trial when the patient is having
trouble with the test. At times, the source of this repetitious response
(perseveration) is less clear. Many nonperseverative errors, such as literal or
verbal errors, also show evidence of control exerted by the test situation.
Literal errors approximate the desired response along some physical
parameter, and take the form of similar sounds (“tog” for “dog”) or shapes
(“d” for “b”), etc. The response may bear so little physical resemblance to the
one desired as to be characterized as neologism or jargon. Verbal errors share
some functional class with the desired response; “cow” for “dog,” “green” for
“orange,” and occasionally, “grass” for “green.” At levels more complex than
words, errors may appear in word sequence or sentence structure (semantic
errors); grammatical construction may become simplified (agrammatism);
the patient may accept as correct familiar sequences of words into which the
examiner has deliberately substituted unexpected words or even neologisms;

other forms of errors may occur which become more and more difficult to
separate from performances which characterize normal people deficient in
education.
As patients and normal cases are retested over extended periods of

time, general improvements in performance occur (see references 17, 23, 24,
33, 35, and 44). In oral and written naming, verbal paraphasic errors continue
but are increasingly represented by names within the test set and
decreasingly by names not in the test set. Even the patients’ spontaneous
responses gradually become restricted to words that are involved in the test
itself. Presentation of the first letter or two letters of short words frequently
used in the tests are sufficient for the experienced patient to respond
correctly; introduction of novel stimulus materials prompts a dramatic
reduction in the rate of performance and an increase in errors. Repeated
testing with stimuli previously found difficult is associated with considerable

evidence of patient dissatisfaction as soon as the first trial occurs,
demonstrating his learned familiarity with the components of the test. In
addition to gradual learning, some of the improvements are sudden, even

after long periods of poor performance on a given test, and appear to
represent newly discovered abilities, whose origins remain obscure. In most
instances, however, the performance improves in a slow but steady fashion.
A dichotomy in performance between identity and nonidentity tests
also characterizes aphasic and normal cases. Scores on tests for which
identity responses are available equal or exceed those tests for which these
responses are not available (nonidentity). Identity tests (see the section on
test methods, p. 281) must be subdivided into first- and second-order
identities for this rule to hold. In first-order identity tests, the patient need
only indicate the physical identity of the same stimulus presented twice in the
same modality. For example, a patient points to the blue color identical to the
blue test stimulus, palpates a skeleton key exactly as he palpated the same
key just before, nods when he hears the same word heard earlier as the test
stimulus, etc. In second-order identity tests, the patient is required to cross a

modality or to produce a response which takes a physical form identical to
the test stimulus. Examples include repeating from dictation, copying on
paper from sight or touch, and matching palpated manipulable objects to

visual manipulable objects. Such tests, although they do not involve actual
physical identities, can nevertheless be done correctly by normal subjects
even if they have had no previous experience with the stimuli. No exception
occurs to the rule that first-order identity performances equal or exceed

nonidentity performances on equivalent tests, but an occasional deficit in
performance of second-order identity tests may occur in aphasic patients

when the equivalent nonidentity test is intact. For example, when presented
with a series of dictated letters spelling a word, the patient may succeed in
pronouncing the word at a time when he experiences difficulty repeating the
sequence of individual letters. In general, however, both first- and second-
order identity tests are accomplished successfully at times when the
nonidentity forms of the test are not.
When identity tests are done poorly, input or output deficits must be
suspected. When identity tests are done well, poor performances on
nonidentity tests reveal relational disorders, i.e., responses are deficient only
in relation to certain stimuli, or stimulus control is deficient only when

certain responses are called for. Relational disorders, i.e., impaired
performance on tests in which the correctly spoken, written, or matching-to-
sample response requires previous experience with the test stimulus, prove
to be critical components of syndromes that have classically emphasized
input or output deficits, and may be taken to define the most interesting
aspects, at least, of aphasia.
Syndromes with Greatest Emphasis on Output Channel Deficits
Vocal Output Channel and General Relational Disorder
Behavioral studies of cases which initially appear to typify the clinical

bedside syndrome of total aphasia, and later are consistent with Broca’s
aphasia, have corroborated traditional features, but, in addition, have
revealed a number of findings hitherto undescribed in these syndromes.

These new findings prompt a reconsideration of the anatomical mechanisms
and explanations.
The deficit profile has four main components. A double deficit is found
in oral naming; first, the patient is mute and produces no vocal responses on
either identity or nonidentity tests. Later, the mutism clears away, as
indicated by satisfactory oral naming in identity tests of repeating from
dictation. From that point on, the second disorder, a relational deficit, is
revealed: impaired performance in nonidentity oral naming tests. In contrast
with oral naming, the performance on identity tests of written naming and
matching-to-sample are intact from the beginning. Later, when oral-naming
identity performance becomes adequate, so that anarthria can no longer
account for poor scores on nonidentity oral naming tests, nonidentity written
and oral naming can be compared in response to the same stimuli. At this
point, the third deficit component appears, i.e., superiority of nonidentity
written naming over nonidentity oral naming. The fourth component is
demonstrated in all response forms and stimulus materials in nonidentity

tests, namely, performance on tests involving the sounds of words exceeds
performance on tests involving the sounds of single letters. This component is
demonstrated by better scores in matching and writing of dictated words

than of single letters, and better scores in the oral naming of visually
presented words than of single letters. By contrast, most wholly visual tests
are performed satisfactorily for both materials: The patient can match
dissimilarly shaped upper- with lower-case letters having a name in common

(i.e., E—e), and even can match scrambled words with pictures. Interestingly,
one test ostensibly involving wholly visual functions, matching visual letters
with homonymous visual words that do not contain the letter (c—sea, q—
cue, i—eye), is done poorly. The time required for the delineation of each of
the main features of the syndrome varies from a few weeks to several years in
individual cases.
The initial mutism is severe. Only a few noises are made in forced
exhalation. With time, vocalization emerges to testable levels. It shows
elements of dyspraxia, revealed by improper setting of the oropharynx, and
impaired coordination of respiration with vocalization, resulting in lack of
smooth speech melody i.e., dysprosody. Despite traditional emphasis on the
attributes of the vocal response, performance on the identity tasks in
repeating from dictation follows the expected patterns of exceeding that of
the nonidentity tasks of producing the same names in response to
appropriate visual, palpated, or even nonverbal sound stimuli.
The duration of the mutism is variable. In a few right-handed cases, the
deficit ameliorates in a dramatically brief period—days to one or a few weeks.
Such rapid amelioration in a right-handed patient with left inferior frontal

infarction has been considered a sign of superficial involvement of a cortical
surface. The intact intrahemispherical pathways (arcuate fasciculus) through
which the central language zone (Wernicke’s) is considered to relate to the

ipsilateral inferior frontal region (Broca’s area), and thence transcallosally to
the nondominant inferior frontal region, have traditionally been presumed
sufficient to permit the nondominant inferior frontal region to mediate the
vocal responses and permit the “recovery.” Recently, right-handed cases have
been followed through this period of dramatically rapid amelioration of vocal

speech deficit. Detailed autopsy evidence showed major damage to the
dominant inferior frontal region, including the pathways considered
necessary to mediate “recovery.” Traditional formulations do not explain
these cases, and alternative pathways, as yet undelineated, must be

considered. The findings suggest the need for revision of current notions of
cerebral “dominance” for speech, and indicate that the degree to which the
inferior frontal regions share the mediation of vocal speech is only poorly
understood.
The superiority of written over oral naming, when identity responses
for both are intact, calls into question some notions of how writing behavior
is mediated. Most classic and many modern accounts indicate that the deficit
in written naming is a reflection of that in oral naming, and is at least as
severe, usually more so. Accounts of aphasic deficits consider that writing
reflects two components. In the first component, the morphology of the
individual letters and digits is believed to depend on a direct pathway from

visual to motor regions which guide hand movements. Until recently, no
theory has challenged the classic notion that the second component, the
verbal content of the writing, depends upon pathways which pass through
Broca’s area, and presumably utilize it as a way station: “one speaks as one
writes.” The only quantitative study of this important subject, revealing a
superiority of nonidentity written naming over nonidentity oral naming when

both were adequate on identity tests, challenges this classical interpretation.
The independence of written and oral naming suggests a new view, which
does not assume an obligatory relation between written and oral naming
based on a unitary brain mechanism. Instead, the coexistence of superficially
similar deficits in written and oral naming may merely reflect anatomical
proximity of the two regions subserving these separate motor responses,
favoring their common involvement by a single pathological lesion. Such
anatomic proximity implies no functional interdependence between the two
areas.
The more severe deficit with letter rather than with word sounds,
common to written and oral naming, appears also in matching-to-sample

behavior. The emphasis in traditional formulations, which envisioned the two
naming deficits as reflecting correlated output disorders, can be properly
shifted to include all forms of behavior. As a result, the deficit can be
considered central to the input and output channels, per se. It must be
pointed out, however, in anticipation of the following section on central
aphasia, that the deficit profile in which nonidentity tasks show better scores
with words than letters is opposite to that commonly found in cases
conforming to traditional criteria for central aphasia. Instead, this
disproportionate deficit in nonidentity tasks involving the sounds of letters
appears unique to this syndrome.
Explanation of the data requires still further revision of accounts of both

Broca’s and total aphasia. Classical writings have explained the syndrome of
total aphasia as a combination of Broca’s and Wernicke’s (central) aphasia.
The syndrome outlined above, although it conforms to classical clinical
bedside criteria for total aphasia, is not explainable as a simple combination

of Broca’s and central aphasia. In addition, the complexity of the satisfactory
responses in many nonidentity tasks suggests that the term, “total aphasia,” is
misleading. The deficit appears highly specific to certain verbal tasks, with
disproportionately better performances on others of seemingly similar or
greater difficulty.
Definitions of Broca’s aphasia have given greatest attention to the

disorder in oral speech, with emphasis on the dyspraxic, dysprosodic,
dysgrammatic components; on the issue of coexisting dyspraxias for nonvocal
movements involving the same oropharyngeal musculature; on the

coexistence of facial, lingual, and palatal paresis; on the issue of cerebral
dominance; and on the exact location and depth of the lesion. Scanty
information exists on the writing deficit, which is usually explained on the
basis of the presumed dependence of verbal content on vocal speech, implicit
or explicit. Broca’s two cases appear to have had principally disorders of
vocalization. Unsettling reference, however, has always been made to mild or
moderate impairments in “comprehension,” which occur in tests of silent

reading and in performance of multistep dictated or printed commands.
Ingenious tests with normals, in which the tongue has been restrained, have
shown impairments in reading, implicating vocal speech deficit as a partial
explanation for the otherwise unaccountable deficits in comprehension in

Broca’s aphasia. Such explanations, however, do not account for the
deficiencies in response to auditory dictated commands. Another approach
has been anatomical, suggesting that clinically unsuspected posterior

extension of the lesion has occurred along the postcentral and parietal
operculum, accounting for the minor central aphasia impairments. As
emphasized above, however, the behavioral deficit in response to dictated
stimuli in this syndrome is not typical of central aphasia. Finally, little or no

qualitative differences separate the vocal and graphic behavior in total and
Broca’s aphasia.
The ambiguities surrounding the definition of Broca’s aphasia have not
been clarified over the years. Considering the great similarity between later
cases of the traditional bedside syndrome of total aphasia, the uncertain
status of “comprehension” in cases of Broca’s aphasia, the anatomic problems
surrounding the extent of the lesion in autopsied cases, and the wide
variation in the course of the deficit, one might ask whether actual deficit
features or mere historical precedent substantiate the syndrome of Broca’s
aphasia. The present authors suspect that the understandable desire to honor
Broca’s efforts at anatomicopathologic correlation serve as the chief basis for
continued recognition of a separate syndrome referred to as Broca’s aphasia.
Further analysis of the syndrome of which the classical Broca’s and total
aphasia appear to be elements may be expected to modify views concerning
the function of the anterior Sylvian operculum and the cerebral organization
of language.
Disproportionate Literal Paraphasia
In this syndrome, errors appear in both identity and nonidentity oral
naming tasks, but not in equivalent tasks involving matching-to-sample.
Although this syndrome is classified as both an identity and nonidentity
output disorder of oral naming, the patient shows none of the mutism
characteristically observed in the syndrome described above. Instead,
vocalizations occur readily, but are equally erroneous on identity and
nonidentity tasks. For example, repeating aloud, reading from text, and oral
naming of visual, auditory, or palpated stimuli show similar scores with
similar errors. In contrast to the deficit in oral naming, tasks not involving a
spoken response, such as matching-to-sample, are done extremely well, and
written naming is often quite satisfactory. The patient’s exasperation and
efforts at self-correction of his oral naming errors attest to his ready
awareness of the deficit. The patient’s errors include a disproportionate
number of literal paraphasias, involving close anatomic approximations of the

oropharyngeal positions required to produce the correct responses in each of
the articulatory classes from lip to pharynx position. Errors increase with the
rate of speech and with the proximity of the oropharyngeal settings required
to produce the sequences of syllables.
In Wernicke’s original scheme, the term “conduction aphasia” was
proposed for the syndrome, which could be considered to reflect interruption
of the pathways from the “sensory” (Wernicke’s) speech region to the “motor”
(Broca’s) regions. As originally constructed, the syndrome contained three

elements. First, comprehension would be intact, since Wernicke’s region was
preserved. Second, the motor elements of speech (articulation, prosody)
would be intact, reflecting the spared motor-speech regions. Third, content of

speech would be paraphasic, as tested by spontaneous speech, reading aloud,
and repeating from dictation. This third feature, the only real deficit to be
found, was the expected result of the pathologic interruption of pathways
linking Wernicke’s region to the motor (Broca’s) speech region. It is

important to stress that the deficit was to take the form of paraphasic oral
speech. Only the motor elements—articulation and speech melody—were
considered to be normal, indicating that the deficit in speech does not merely
reflect involvement of the inferior frontal (Broca’s) region.
Cases frequently appear clinically which exhibit paraphasic, normally
articulated, and normally melodic speech, with superficially intact
comprehension, and are considered to satisfy the criteria for conduction

aphasia. In most such cases, however, deficits in comprehension can readily
be brought out by testing silent reading or matching-to-sample, which do not
involve oral speech. These cases are more frequently better reclassified as
examples of mild central (Wernicke’s) aphasia.
The search for cases defined by the more stringent criterion of no
demonstrable deficit in comprehension, has yielded few cases of conduction

aphasia. Awareness of this interesting syndrome has increased only in the
1960s, but most reports are in the early literature. Presumably, their rarity
reflects the greater likelihood that pathologic injuries to the fiber pathways
connecting the Wernicke and Broca regions would not be as discrete as

required. Instead, the injury is more likely to involve larger areas, and result
in more traditional syndromes of central, motor, or total aphasia.
Even fewer cases satisfying the clinical criteria have provided autopsy
data. Meager though these data are they pose a problem in interpretation by
classic theory, which predicts that the main lesion should lie in the pathways
linking the auditory with the motor-speech regions. Attempts to identify
these pathways have focused on the arcuate fasciculus, a white matter bundle
which appears to pass between the posterior superior temporal plane
(Wernicke’s region) and the inferior frontal region (Broca’s region), and
satisfies the gross anatomic requirements. Autopsy cases of “conduction”

aphasia, however, have shown cortical surface infarction, apparently of
embolic origin, without necessary involvement of the more deeply situated
arcuate fasciculus. To date, no cases have been reported that show pure
involvement of the arcuate fasciculus. The clinical setting for such a lesion
occurs occasionally in putamenal hemorrhage, in which the hemorrhagic
mass is limited to the posterior lateral putamen and the immediate
surrounding area, which includes the arcuate fasciculus. In the one such case
that has come to light, the clinical syndrome was more of a central than a
conduction aphasia.
Luria has described a syndrome of afferent motor aphasia. In contrast
with the usual form of motor aphasia, which he has referred to as “efferent,”
literal paraphasic errors in oral speech are attributable to anatomic settings

of the oral apparatus that are imprecise but closely approximating those
required. The lesion is presumed to lie in the postcentral region, interfering
with sensory kinesthetic feedback from the oral cavity. The clinical findings
agree with those delineated by behavioral methodology, adhering closely to
classically defined conduction aphasia, but pointing clearly to mechanisms
different in principle from those proposed classically.
The extent to which literal and verbal paraphasias occur independently
of one another, as well as the basic deficit(s) reflected by literal paraphasia,
remain important unclarified issues. Literal paraphasias that prove

principally to reflect oropharyngeal anatomic approximations point to
sensory and/or motor Rolandic deficits. Traditionally, by contrast, literal
paraphasias are considered to take the form of homonyms of the desired
response, and to reflect auditory input deficits. Verbal paraphasias, by

contrast, are traditionally thought of as synonyms. However, few studies
specify the relative frequency of each type. Furthermore, literal and verbal
paraphasias are considered to occur together with such regularity as to

suggest some mechanism in common, yet even fewer studies document the
frequency with which they occur in the same case, especially a case with
autopsy material. As a result, the theories on either form of paraphasia are

largely speculative.
General Relational Disorders
A surprising proportion of cases tested by behavioral methods show
deficits only on nonidentity tasks. No deficits are found for a given test
stimulus on identity tests of repeating the stimulus from dictation, copying at
sight, or matching the stimulus to its exact duplicate in the same modality.
These intact performances permit the assertion that sensory discrimination
and response production are adequate for these stimulus materials, and
preclude an explanation of the impairments that is based on deficient input
and output channels.
Although deficit profiles observed on nonidentity tests across the

various stimulus materials take several forms, one in particular typifies that
predicted by traditional formulations of central, or true, aphasia. This profile
shows a similar deficit in response to each of the classes of test stimuli. For
example, in response to the same stimuli, whether they are single letters,
words, pictures, color names, colors, digit names, digits, or manipulable
objects, scores on nonidentity tasks of matching-to-sample exceed those for
oral naming, which exceed those for written naming. Improvement occurs
gradually with time and more or less equally with all types of test stimuli. At
any point in time, errors may occur in response to any individual stimulus,
but no individual stimulus reliably sets the stage for an error each time it is
presented.
The traditional formulation of the true or central deficit in aphasia
involves disruption of a supramodal function whose normal role is to relate

physically dissimilar stimuli which are verbally equivalent. This function was
held to be accomplished by the “concept center.” Wernicke, among others,
considered this function actually to be performed by the portion of the brain
outside those pathways subserving the instrumentalities of language.
Wernicke argued that the initial acquisition of language is probably an
auditory experience. Learning to speak aloud would involve auditory
modulation of vocal efforts. Reading aloud would involve acquisition of an
auditory-visual link between sounds and graphic stimuli, establishing

pathways which would then permit instructions to the vocal apparatus for
reading aloud utilizing the auditory region as an intermediate. A similar link
would modulate graphic motor behavior. Lesions of the auditory region and
connections would be expected to disrupt these relations.
The added assumption was that these separate behaviors permanently
depend upon the auditory region. This dependence would account for the
overall deficit in the utilization of the instrumentalities of language in lesions
affecting the auditory region and related pathways.
Wernicke was careful to separate the essentially servile performances

utilizing the instrumentality of language from the more abstract and poorly
understood aspects of brain function involving “concepts.” Diagrammatically,

his scheme showed pathways from the ear to the superior temporal lobe
serving auditory speech discrimination; pathways from the superior temporal
lobe to the inferior frontal region serving to convey the instructions for
vocalization to the motor region; pathways from the inferior frontal region to
the brain stem serving to innervate the bulbar apparatus to produce speech
sounds; pathways from the superior temporal lobe to the occipital region
linking auditory with visual functions to subserve reading. None of these
pathways necessarily serves “understanding” or “central language function.”

Instead, pathways from the superior temporal lobe to the remainder of the
brain were considered to permit the auditory experiences, and those visual
and palpated sensory experiences translated into auditory equivalences, to

arouse associations in the remainder of the brain which provide “meaning” to
the stimuli. Similarly, pathways outside the main speech zone were
considered to converge upon the motor speech regions (Broca’s area) to
permit “meaning” to be given to vocal utterances. Without challenging the

notions in principle, Dejerine added the angular gyrus as a word center,
whose supramodal function was to relate auditory and visual lexical stimuli
as verbal equivalents, and to guide the motor regions for graphic responses.
Recent arguments have modernized the proposal of the angular gyrus as
exerting a supramodal function relating physically dissimilar but verbally
equivalent stimuli. Others have proposed essentially similar translatory

functions for the inferior parietal regions, of which the angular gyrus is a
component. These views argue that integration, or morphosynthesis, is the
basic function to be expected of the inferior parietal region, since its anatomic
position lies between the main primary sensory receiving areas in the
cerebral cortex.
Emphasis on this region as central to language function helps
encompass many aspects of behavior in such cases. The patients exhibit a
remarkable unawareness of the extent, the time, even the existence, of their
deficit. Both literal and verbal errors (especially verbal) occur in all forms of
language usage, in tasks involving comprehension, and in language
formulation, with scarcely a pause for correction. Oral speech tends to contain
far more words than expected or required for efficient communication. The
term “logorrhea,” also referred to as augmentation and press of speech,
denotes the tremendous barrage of vocalizations that frequently
characterizes these cases of central aphasia. In addition, efforts to instruct the
patient to modify his response for different tests frequently are unsuccessful;
they are often met with perseveration of previous responses or principles of
response, even though the tests have changed. Particularly frustrating to the
examiner is the frequent tendency of patients to respond to commands only
by acknowledging that a command was given; efforts to vary the command by

adding, “please,” “I would like you to . . .,” etc., are frequently met by a reply
like “O.K., I will,” but with no actual performance. Even more suggestive of a
unitary deficit is the all pervasive nature of the deficit in language usage,
which appears in tests involving spoken, written, and matching-to-sample
responses.
Despite the many indices favoring these all-encompassing views of
language function, a series of findings, both anatomic and behavioral, remain
unaccounted for. Anatomically, an occasional case whose deficit profile
suggests the traditional syndrome of total aphasia is shown at autopsy to
have a lesion wholly confined to the dominant temporal lobe. The temporal-
lobe mutism in these cases contrasts sharply with the logorrhea usually
characterizing such lesions. While temporal-lobe mutism suggests that the

posterior Sylvian regions exert the major controlling function over the output
of the inferior frontal region, such findings pose the difficult problem of
explaining opposite observations by the same anatomic lesion. Suggestions
that the more commonly observed logorrhea represents a release effect in

which the inferior frontal region “runs on unchecked,” seem less tenable in
view of the existence of temporal-lobe mutism. Another suggestion is that
logorrhea may represent a functional sign of decreased awareness by the

patient of the extent of his deficit.
Another major anatomic question remains on how limited a lesion may

produce the syndrome. Autopsies commonly show infarction which varies
considerably from case to case, spreading over variable distances from the
superior temporal plane to the parietal, occipital, and temporal regions. There
are only a few well-studied cases of focal lesions confined to the superior
temporal plane. As a consequence of the wide differences in the
neuropathologic basis for the clinical syndrome, there is considerable
variation in what different authors accept as the anatomical boundaries of
Wernicke’s area. For some, the area is considered to be confined strictly to
the superior temporal plane just posterior to Heschl’s transverse auditory

gyri, and ending before or at the inferior parietal lobules posteriorly and the
second temporal convolution inferiorly. Other authors consider that the
region is simply the large posterior Sylvian territory, encompassing all the
previously mentioned areas and extending as far back as the anterior
occipital region. This lack of universal agreement as to the extent of
Wernicke’s area has led to considerable ambiguity in the components of the
individual syndrome.
Behavioral findings provide yet another series of problems for unitary

views of language function, as well as the opportunity to test a number of
predictions implicit in traditional theses. As alluded to above under Vocal
Output Channel, demonstration of opposite relational deficits in test scores

with words and single letters between cases clinically classified as total
aphasia or as central aphasia, respectively, leads to the realization that the
relational deficit in total aphasia is not identical to that in central aphasia, and
forces the abandonment of the assumption that a common deficit profile

encompasses all relational performances in cases of aphasia. However, the
coexistence of the severe output channel deficit in oral naming in total
aphasia dilutes the significance of the findings somewhat, since other large
differences separate the two types of cases.
The demonstration of differential deficits among patients who show
only relational deficits further dispels notions of a unitary hierarchical deficit
profile in aphasia. For example, some cases perform better in nonidentity

tasks involving matching than in oral naming, and better in oral than in
written naming, while others show a superiority of nonidentity oral naming
over both matching-to-sample and written naming for a given class of
stimulus materials. With different classes of stimulus materials, exceptions

have been documented in which scores in nonidentity tasks with one material
exceed those in another with one patient, while the opposite hierarchy of
scores with these materials is seen in another patient.
Evidence of still greater complexity in relational deficit profiles is
provided by examples of different deficits with different materials in the same
patient. One patient, for example, experienced more difficulty in naming

(reading) visual picture names than in naming the pictures; with colors and
color names, however, the opposite was true—he had more trouble naming
colors than visual color names.
Evolution of the deficit profiles across time also reveals a number of
surprising changes. A smooth evolution sometimes occurs, all scores rising
uniformly and gradually to approximate satisfactory levels. In a number of
cases, however, improvements occur gradually in one or more test stimulus
materials, input, or response channels, leaving others essentially unchanged
or improving at a much slower rate. As a consequence of these unequal
changes, the later profile is quite different from that predicted by the initial
assessments. Autopsied cases present anatomic findings for which a decision
has to be made regarding the behavioral correlation. Failure of investigators
to follow these evolutions has probably contributed significantly to

interpretive problems in retrospective reviews of clinical anatomical studies.
One byproduct of the systematic behavioral approach is the opportunity

to assess predictions of deficit profiles based on traditional syndrome
formulation. The behavior presumed to be involved in spelling, in particular,
proved of interest. The steps involved in pronouncing words in response to

dictated spelled words, or conversely, in spelling aloud in response to
dictated words, have been held to require, first, the “mental” transfer of
auditory to visual images, and then the “reading” aloud of these mental
images as words or sequences of single letters. These views are the basis for
explaining the impaired performance on spelling tasks by patients with the
syndrome of dyslexia and dysgraphia. Destruction of the angular gyrus, held
responsible for the mental transformations, would be expected to result in

spelling deficits. By transforming the presumed mental operations into
observable behavior, it was possible to test these predictions, and to find
them unsupported by data. Patients who could pronounce dictated spelled
words, and spell dictated pronounced words were, nevertheless, deficient in
writing the dictated spelled words, that is to say, in explicitly demonstrating

transformation of the auditory stimuli to their visual graphic equivalents. Nor
could they read visually presented words aloud, the second presumed
component of the mental task. Thus, explicit behavioral analysis revealed

patients who could perform both spelling tasks, yet were unable to perform
the tasks whose “mental” accomplishment was supposed to make spelling
possible. Verifiable behavioral alternatives to such mentalistic mechanisms
appear warranted if we are to avoid the postulation of plausible-sounding
anatomic correlations to explain nonexistent behavioral processes, or vice
versa.
The problems posed above for unitary notions of aphasia remain
unsolved; the behavioral data are not as yet sufficient in scope to supplant
traditional formulations in their entirety. Perhaps the major value of the
behavioral observations at present is to call attention to the usefulness of the
methodology. By delineating individual components of the deficit profile,
some understanding of the hierarchies of relevant variables can be achieved.

Behavioral studies also suggest that one should approach aphasia by
emphasizing techniques which are most likely to reveal behavior that is still
available to the patient, rather than design tests to promote errors. It may
even become feasible to measure the deficits in aphasia by the lengths the
examiner must go to provide a setting for the patient to accomplish the
desired behavior. By placing the burden on the examiner to find the patient’s
capacities, deficits reflecting artifacts of the test situation would be reduced,
and emphasis would shift to the delineation of variables which permit the
patient to acquire new behavior, and perhaps mitigate his aphasia.
Approach to a Clinical Case of Aphasia
The concern of the clinician approaching a case of aphasia is to clarify
the syndrome presented sufficiently to make judgments on the likely
anatomic regions affected and on the etiology of the brain injury.
The clinical situations where assessment of aphasia is needed generally
fall into four large groups. (1) The patient appears intact and the question
arises whether there is any deficit in interpersonal communication at all.
Examples include patients who have suffered traumatic head injury, are
recovering from suspected encephalitis, or are in the early stages of
suspected brain tumor or degenerative brain disease; (2) The patient is

grossly aphasic. The approach in such a case involves the attempt to establish
what positive behavior, of any kind, is available to the patient, so as to assess
what regions of the brain can be inferred to have survived. Examples include
patients suffering massive traumatic head injury, devastating strokes, serious
encephalitis, and the like; (3) Aphasia may form an important part of the
clinical picture and analysis of the positive and negative features of the
aphasic deficit may provide diagnostic considerations not available by other

means; and (4) There is a heterogenous group of aphasic syndromes which
frequently pass unnoticed in the general physical and sometimes even in the
neurologic examination. The alert consultant can find a fair percentage of
such cases by constant readiness to pursue the required tests.
When the patient appears intact, he has to be presented with the most
difficult of aphasic tests. The purpose is not to analyze errors, but to
anticipate satisfactory performance. If the patient performs well, such tests
should put questions of aphasia to rest. If he does poorly, little or no

information regarding the nature of the aphasia has been provided. In such an
instance, the examiner has learned merely that tests which do permit analysis
of errors will be necessary. An example of a complex test is Marie’s three-

paper test. Others include a complex picture of incongruous situations used in
standard IQ tests, dictated or printed familiar metaphors (a rolling stone

gathers no moss, etc.) and word problems from many of the standard IQ tests;
the patient is required to describe or write his explanation or solution. In

special situations, when the patient’s deficits preclude lengthy written or
spoken responses, difficult tests involving several steps can be created to
permit a minimal motor response to reflect a great deal of complex
unobservable behavior. For example, when a patient is asked to hold up the
number of fingers that correspond to the position in the alphabet occupied by
that letter in the alphabet sequence that comes immediately after the first
letter in the name Boston. If he immediately puts up three fingers to
correspond to the letter “C,” a great deal of behavior has been assessed and
the question of aphasia is largely settled. Clearly, these complex tests are of
value only in saving examination time in the intact case.
Cases presenting a gross severe aphasia pose almost the opposite

problem. In this situation, one attempts to determine what behavior, if any, is
available to the patient. The patient should be roused to a state of full
alertness, if necessary, before concluding that the patient is untestable. Then,

initial attempts should be made to use the simplest and most direct
commands, with simultaneous demonstrations of the desired movements.
Should some response be forthcoming, it must be determined whether the

patient is mimicking the movements or is responding to the content of the
command. For spoken responses the examiner can dictate short sounds (ah)
and encourage repetition. For graphic responses, simple shapes (circle), etc.;
for motor responses, simple movements (wave) may serve to establish some
behavior. Any identity tests performed satisfactorily serve to indicate that the
input and response channels function per se.
Cases not coming under any form of identity test control can still be
profitably examined by using aversive stimuli. Inferences regarding right
hemisphere function can be gained in the patient for whom simple avoidance
behavior can be conditioned by preceding a noxious stimulus delivered to the
left side with a visual, auditory, or somesthetic stimulus. Some assessment of
memory can also be made by repeating these tests at regular intervals
without retraining.
If the simple identity tests can be performed, then simple nonidentity
forms of the same tasks can be done. Advantage should be taken of any
incidental movement by the patient, since such occurrence is proof of their
availability as behavior per se. Examples include coughing, smiling, turning
over in bed, etc. The words involved in commands for these movements
should be used for the tests of repeating from dictation and copying from
sight. Then these words can be used as dictated commands to try to elicit
written responses, and as visual commands for praxic motor or spoken
response. Should this much behavior be accessible, the patient can then be
further analyzed as outlined in the next section.
Whatever data are obtained provide a baseline for observation of later
changes. Declines in the behavioral state may prompt a change in the therapy,
or improvement may demonstrate the effectiveness of treatment.
Should the tests described above demonstrate some nonidentity
behavior, further analysis of the case is justified. The case may be one for
whom analysis of the aphasic syndrome will help clarify the diagnosis. Such
efforts can be expected to take time. It will be necessary to use a variety of
stimulus materials, to attempt to establish some form of behavioral control
with reinforcement techniques (using spoken words, such as good, money,
food, etc.), and the identity, then nonidentity, behavior with the various input,
and response modalities.
A gratifying by-product of such an analysis is a surprising number of
instances in which some differential performance profile emerges that
permits a diagnosis of one of the less severe aphasia syndromes. Most
frequently observed is a case whose deficit was initially interpreted as motor
aphasia or even total aphasia, and for whom analysis permits classification as
pure word mutism. Similarly, the rarer cases of pure word deafness usually
are considered initially to reflect central, or Wernicke’s, aphasia. In the more
severe syndromes, the main purpose of such analysis is to establish a baseline

for further changes. For example, a hypertensive hemorrhage frequently
evolves from a syndrome of minimal central aphasia to fully developed total
aphasia, as may temporal-lobe abscess and deep-seated primary or

metastatic brain tumor. By contrast, embolic involvement of the cerebrum
rather frequently begins as total aphasia only to change to motor aphasia or
central aphasia, and finally to a syndrome of amnestic aphasia. Evolution
toward or away from more serious deficits is frequently of great value in
establishing the etiologic diagnosis in an individual case.
The last group of patients are those for whom the diagnosis of a specific
syndrome may be overlooked in more routine clinical medical or neurologic

examination. These syndromes require the use of special techniques for their
delineation, but depend chiefly upon the awareness of the examiner that
these syndromes can exist in a patient whose conversational behavior
appears essentially normal. The syndromes include those of the pure alexias
with or without agraphia, amnestic aphasia, and the syndromes of
nondominant hemisphere ideomotor apraxia (not discussed in this chapter).
More exotic behavioral syndromes include “simultanagnosia” and Balint’s

syndrome. The failure of spontaneous speech with preserved repeating from
dictation which can transiently characterize involvement of the anterior
cerebral artery territory in the dominant hemisphere, and the syndromes of

grossly inappropriate factual content of conversation which may occur in
states of increased intracranial pressure and/or unilateral or bilateral frontal
disease, are all uncommon, and are beyond the scope of this chapter.
Bibliography
Adams, R. D. and J. P. Mohr. “Affections of Speech,” in M. M. Wintrobe et al., eds., Harrisons
Principles of Internal Medicine, 7th ed., pp. 137-148. New York: McGraw-Hill, 1974.
Alajouanine, T., A. Ombredame, and M. Durand. Le Syndrome de Disintégration Phonétique dans

I’Aphasie. Paris: Masson, 1939.
Balint, R. “Seelenlähmung des ‘Schauens,’ Optische Ataxie, Räumliche Störung der

Aufmerksamkeit,” Monatsschr. Psychiatr. Neurol., 25 (1909), 51.
Boller, F. and L. A. Vignolo. “Latent Sensory Aphasia in Hemisphere-Damaged Patients: An

Experimental Study with The Token Test,” Brain, 89 (1966), 815.
Brain, R. Speech Disorders. London: Butterworths, 1965.
Broca, P. “Remarques sur le siège de la faculté du langage articulé; suivies d’une observation
d’aphémie,” Bull. Soc. Anat., 6 (1861), 330.
Brown, J. W. Aphasia, Apraxia, and Agnosia. Springfield, Ill.: Charles C. Thomas, 1972.
Chester, E. D. “Aphasia,” Bull. Neurol. Inst., 6 (1937), 134-144.
Dejerine, J. and C. Mirallie. L’Aphasie Sensoriélle. Paris: Steinheil, 1896.
Dejerine, J. and N. Vialet. “La Localisation anatomique de la cécité verbale,” C. R. Soc. Biol. (Paris),
4 (1891), 61.
Denny-Brown, D. and R. A. Chambers. “The Parietal Lobe and Behavior,” Res. Publ. Ass. Res. Nerv.
Ment. Dis., 36 (1958), 36.
Eisenson, J. Examining for Aphasia. New York: The Psychological Corporation, 1954.
Gazzaniga, M. S., J. E. Bogen, and R. W. Sperry. “Observations on Visual Perception after

Disconnection of the Cerebral Hemispheres in Man,” Brain, 88 (1965), 221.
Geschwind, N. “Disconnection Syndromes in Animals and Man,” Brain, 88 (1965), 237, 585'
_____. “Focal Disturbances of Higher Nervous Activity,” in P. B. Beeson and W. McDermott, eds.,
Cecil-Loeb Textbook of Medicine, 13th ed., pp. 99-102. Philadelphia: Saunders, 1971.
Goldstein, K. Language and Language Disturbances. New York: Grune & Stratton, 1948.
Head, H. Aphasia and Kindred Disorders of Speech. New York; Macmillan, 1926.
Howes, D. “Application of the Word-frequency Concept to Aphasia,” in A. V. S. de Reuck and M.

O’Connor, eds., Disorders of Language, pp. 47-75. Boston: Little, Brown, 1964.
Jakobson, R. “Towards a Linguistic Topology of Aphasic Impairments,” in A. V. S. de Reuck and M.

O’Connor, eds., Disorders of Language, pp. 2-42. Boston: Little, Brown, 1964.
Kreindler, A. and A Fradis. Performances in Aphasia. Paris: Gauthier-Villars, 1968.
Kreindler, A. and V. Ionasescu. “A Case of ‘Pure’ Word Blindness,” J. Neurol. Neurosurg. Psychiatry,
24 (1961), 257.
Leicester, J., M. Sidman, L. T. Stoddard et al. “Some Determinants of Visual Neglect,” J. Neurol.
Neurosurg. Psychiatry, 32 (1969), 580.
_____. “The Nature of Aphasic Responses,” Neuropsychol., 9 (1971), 141.
Lhermitte, F. and J. C. Gautier. “Aphasia,” in R. J. Vinken and G. W. Bruyn, eds., Handbook of Clinical
Neurology, Vol. 4, pp. 84-104. Amsterdam: North-Holland, 1969.
Lichtheim, L. “On Aphasia,” Brain, 7 (1887), 433.
Liepmann, H. “Diseases of the Brain,” in W. Burr, ed., Curschmann’s Textbook on Nervous Diseases,
Vol. 1, pp. 467-80, 518-51. Philadelphia: Blakiston, 1915.
Liepmann, H. and M. Pappenheim. “Über einen Fall von Sogenannter Leitungsaphasie mit
Anatomischem Befund,” Z. Neurol. Psychiatr., 27 (1914), 1.
Luria, A. Higher Cortical Functions in Man. New York: Basic Books, 1966.
Marie, P. “Revision de le question de l’aphasie,” Sem Med., 26 (1906), 241, 493, 565.
Massachusetts General Hospital. Case Records, Autopsy No. 31772. Boston: 1968.
Mohr, J. P. “Rapid Amelioration of Motor Aphasia,” Arch. Neurol., 28 (1973), 77.
Mohr, J. P., J. Leicester, L. T. Stoddard et al. “Right Hemianopia with Memory and Color Deficits in
Circumscribed Left Posterior Cerebral Artery Territory Infarction,” Neurology, 21
(1971), 1104.
Mohr, J. P. and T. R. Price. “An Unusual Case of Dyslexia with Dysgraphia,” Neurology, 21 (1971),
430.
Mohr, J. P., M. Sidman, L. T. Stoddard et al. “Evolution of the Deficit in Total Aphasia,” Neurology,
23 (1973), 1302.
Pershing, H. “A Case of Wernicke’s Conduction Aphasia with Autopsy,” J. Nerv. Ment. Dis., 27
(1900), 369.
Pick, A. Die Agrammatischen Störungen. Berlin: Springer, 1913.
Porch, B. Porch Index of Communicative Abilities. Palo Alto: Consulting Psychologist Press, 1970.
Reitan, R. “The Significance of Dysphasia for Intelligence and Adaptive Abilities,” J. Psychol., 50
(1960), 355.
Russell, W. R. and M. L. E. Espir. Traumatic Aphasia. London: Oxford, 1961.
Schuell, H., J. J. Jenkins, and E. Jimenez-Pabon. Aphasia in Adults. New York: Hoeber, 1964.
Schwab, O. “Über Vorübergehende Aphasische Störungen nach Rindenexcision aus dem Linken
Stimhirn bei Epileptikem,” Dtsch. Z. Nervenkeilk., 94 (1926), 177.
Sidman, M. “The Behavioral Analysis of Aphasia,” J. Psychiatr. Res., 8 (1971), 413.
Sidman, M., L. T. Stoddard, J. P. Mohr et al. “Behavioral Studies of Aphasia: Methods of

Investigations and Analysis,” Neuropsychol., 9 (1971), 119.
Starr, M. A. “The Pathology of Sensory Aphasia with an Analysis of Fifty Cases in
Which Broca’s Centre was not Diseased,” Brain, 12 (1889), 82.
Teuber, H. L. “Lacunae and Research Approaches to Them,” in C. H. Millikan and L. Darley, eds.,
Brain Mechanisms Underlying Speech and Language, pp. 204-216. New York: Grune
& Stratton, 1967.
Weigl, E. “On the Construction of Standard Psychological Tests in Cases of Brain Damage,” J.
Neurol. Sci., 3 (1966), 123.
Weigl, E. and A. Fradis. “Semiologische Untersuchungen der Alexie,” Zh. Nevropatol. Psikhiatr., 59
(1959), 1425.
Weisenburg, T. and K. E. McBride. Aphasia. New York: Hafner, 1964.
Wernicke, C. Der Aphasische Symptomen-complex. Breslau: Cohn & Weigert, 1874.
_____. “The Symptomcomplex of Aphasia,” in A. Church ed., Modern Clinical Medicine, pp. 265-324.
New York: Appleton, 1908.
Whitaker, H. A. “Neurolinguistics,” in W. O. Dingwall, ed., A Survey of Linguistic Science, pp. 136-

252. College Park: University of Maryland Press, 1971.
Wolpert, I. “Die Simultanagnosie—Störung der Gesamtauffassung,” Z. Neurol. Psychiatr., 93

(1924), 397.
Notes
1 The preparation of this manuscript was supported in part by Grants number: H L 14888 from the
National Heart and Lung Institute and Public Health Service Grants HD 05124 and HD
04147 from the National Institute of Child Health and Human Development.
Chapter 12
Psychiatric Disturbances Associated with

Endocrine Disorders1
Edward J. Sachar
Introduction
The evaluation of psychopathology in patients with endocrine disorders
poses problems for the psychiatrist, especially in determining what specific

relation the endocrine disease has to the psychiatric abnormalities. In such
disorders, there are many nonspecific factors which can affect mental
functioning. Obviously, the mental status of the patient needs to be
interpreted in the light of his premorbid functioning. Beyond that, it should be

noted that endocrine disease is often a severe stress involving loss of
functions, feelings of illness, and changes in appearance, as well as sometimes
posing a threat to life itself; the vulnerable personality may well
decompensate under these conditions.
Furthermore, endocrine diseases have widespread biochemical and
physiological consequences, and it is often difficult to determine whether the
mental changes noted are due to direct hormonal influences on the brain, or
to associated disturbances in electrolyte metabolism, blood sugar, renal
function, and so forth. Unfortunately, much of the literature is obscure on
these important points. Furthermore, systematic psychiatric assessments
have not been reported as frequently as one would like. For example, a
description of a patient as being “agitated, confused, and delusional,” leaves it
unclear as to whether one is dealing with an organic mental syndrome or
another type of psychotic reaction. In addition, because of the great difficulty
of assembling nonbiased series and adequate control groups, precise data

about the incidence of mental dysfunction specifically due to endocrine
diseases are hard to gather. Elucidation of some of these issues is provided by
observation of patients receiving hormone therapy, although here too

consideration must be given to the mental effects of the medical illness being
treated. It is with these limitations in mind, then, that this summary of the
current status of knowledge about psychiatric disturbances in endocrine

disorders is presented.
For a full medical discussion of the endocrine disorders, as well as a

summary of related mental disturbances, the reader is referred to Williams’
Textbook of Endocrinology. For a recent comprehensive survey of the
psychiatric aspects of endocrine disease, with an extensive bibliography, see
Smith et al.
Adrenal Disorders
Cushings Syndrome
Cushing’s syndrome is produced by excessive secretion of

corticosteroids from the adrenal cortex. In about 70 percent of cases, the
adrenocortical hyperplasia is secondary to hypersecretion of ACTH
(adrenocorticotropic hormone) from the anterior pituitary, either because of
a tumor or a hypothalamic neuroendocrine disturbance. In these latter cases,

then, both ACTH and cortisol are secreted excessively. In the remainder of
cases, there is a secreting tumor of the adrenal cortex, with secondary
suppression of ACTH. Because of the effects of cortisol on intermediary

metabolism and electrolyte regulation, the illness is usually associated with
hyperglycemia, truncal and facial obesity, osteoporosis, muscle wasting and
weakness, and hypertension. Hypersecretion of adrenal androgens may lead
to hirsutism and intensification of libido in women (the latter probably

related, in part, to local effects on the clitoris).
The occurrence of significant mental disturbance in Cushing’s syndrome
has been noted since Cushing’s original paper—indeed, one of his cases was
found in a mental hospital. For reasons noted before, the precise incidence of
significant psychopathology in Cushing’s syndrome is hard to determine, but
it is quite high, perhaps up to half the cases, and the range of psychological
disturbances which occur is unusually wide. Rough estimates from the

literature (reviewed by Smith et al.) suggest that about 15 percent of
untreated cases become frankly psychotic, with another 35 percent
experiencing a significant mental disturbance of other types. The literature,
does not, however, distinguish between the aberrations seen in primary

pituitary from those seen in primary adrenocortical Cushing’s syndrome.
Depression (beyond the fatigue typical of the disease) is the most
commonly occurring symptom ranging from a moderately depressed mood
and overreactions to distressing life events, to severe depressive illness with

delusions. Suicidal attempts occur in about 10 percent of cases. Elation is also
occasionally observed, at times closely mimicking naturally appearing manic
psychoses, with grandiosity, mental and physical overactivity, sleeplessness

and inappropriate behavior. Irritability, anxiety, insomnia, difficulty with
concentration, and spells of agitation often occur. Paranoid states, sometimes

with hallucinations, are not uncommon. Patients may also experience periods
of amnesia, episodes of confusion, and outbursts of temper. The mental

changes may be quite fluctuant, with, for example, periods of elation,
depression, irritability, and lucidity rapidly succeeding each other. Organic
mental syndromes are sometimes seen, but they are more likely to be
associated with the medical complications of Cushing’s syndrome, e.g., severe
hypertension with encephalopathy or congestive heart failure, uncontrolled
diabetes, and electrolyte disturbances.
Prolonged corticosteroid therapy can induce somatic changes like those

seen in Cushing’s syndrome. Early psychiatric reports describe psychological
responses to ACTH and cortisone, which were very similar to the wide range
of mental disturbance seen in endogenous Cushing’s syndrome, although not
as common. (See references 12, 26, 38, 61, 66, 74, and 76.) At present, potent
steroid analogues, like prednisone, have generally replaced ACTH and
cortisone in medical practice, but the types of psychiatric complications
appear to be the same, although some clinicians have the impression that
depression was more common with ACTH therapy. Depression is much less
commonly associated with steroid treatment than with endogenous Cushing’s
syndrome and elation seems much more common. True organic mental
syndromes (in the absence of medical complications ) probably are not
common, and the confusional states appear to be primarily experiences of
depersonalization and unreality, with perceptual distortions.
Even with small doses of prednisone, mild changes of mood are
frequent, especially elation. Occasionally, patients accustomed to the mild

elation associated with steroid treatment become depressed after steroid
withdrawal. From our review of recent medical literature, major psychiatric
disturbances appear to be more likely in dose ranges above 20 mg. of
prednisone a day. But beyond that, a clear relation of psychiatric risk to dose
has not been established. The same dose may be well tolerated on one
occasion and not on another. Sometimes it is hard to separate the
psychological effects of the illness being treated from the drug effects
themselves, especially in steroid treatment of disseminated lupus
erythematosus with CNS (central nervous system) involvement.
As noted before, some of the psychological disturbances in Cushing’s
syndrome can be attributed to associated metabolic, cardiovascular, and
electrolyte complications; some of the depression, for example, may be
associated with hypokalemia. However, there appears little doubt that much
of the psychopathology is due to the effects of ACTH and corticosteroids on
the brain, although the mechanisms remain unclear. Corticosteroids have
important effects on intracellular sodium content, and on the excitability of

neural tissue, with alteration of the EEG (electroencephalogram) and
lowering of seizure thresholds. Both ACTH and corticosteroids exert

influences on the enzymes involved in the metabolism of catecholamines and
serotonin, biogenic amines which have been implicated in naturally occurring

affective disorders. Interesting effects of hyperadrenal-corticism on sensory
thresholds in taste, hearing and smell have been noted in patients with
Cushing’s disease. Cortisol also increases the reuptake of norepinephrine by
rat-brain tissue. Maas has recently reviewed the literature on the effects of
corticosteroids and ACTH on catecholamines and electrolytes, and suggests a
mechanism by which these effects may mediate depressive states when the
hormones are hypersecreted. In hypophysectomized animals, corticosteroids
prolong the extinction of learned avoidance behavior, while the opposite is
true of ACTH.
This experimental demonstration that ACTH alone has significant
psychological effects which differ from those of corticosteroids may have

important implications for understanding the differences in the psychological
concomitants of Cushing’s syndrome, Addison’s disease, ACTH therapy, and
corticosteroid therapy. It is possible, for example, that excess ACTH itself

exerts primarily a depressing effect on mood, while excess corticosteroids
may tend to produce mostly elation. This would account for the higher
frequency of depression in pituitary Cushing’s disease compared to steroid

therapy, and the preponderance of depressive symptomatology in primary
adrenal Addison’s disease (see below) in which ACTH is hypersecreted. It is
unfortunate that the older literature did not systematically and clearly
differentiate the psychiatric complications of ACTH therapy from that of

corticosteroid therapy; if ACTH is “depressogenic,” one would expect more
depressions with ACTH therapy. Similarly, the literature generally does not
distinguish between the psychological concomitants of primary hypothalamo-
pituitary from primary adrenal Cushing’s syndrome; one might expect a
higher incidence of depression in the former, if ACTH is “depressogenic.” It
also should be considered that in all three forms of Cushing’s syndrome—

hypothalamic, pituitary, and adrenal—a variety of corticosteroids are
hypersecreted, while in exogenous steroid therapy, a single synthetic steroid
is administered. It may be that certain corticosteroids differ in their euphoric

or depressive effects, and such differences may account for the differences in
psychological responses to exogenous and endogenous steroids. These could
be useful areas for future clinical investigation.
The treatment of choice for the psychiatric disturbances associated with
Cushing’s disease or corticosteroid therapy is to correct the disease or to

reduce or temporarily discontinue the hormone medication. When the
surgery must be delayed, or the medication continued for pressing medical
reasons, however, the problem of controlling the psychiatric state by other

means arises. We know of no definitive studies of the effectiveness of
phenothiazines or antidepressants in such situations. Our own experience
suggests that psychotropic drugs are often palliative, but rarely induce
complete remission of the mental symptoms, as long as the

hyperadrenalcorticism continues.
It should also be noted that certain naturally occurring psychotic states,
particularly acute schizophrenia with emotional turmoil and severe
depressive illnesses, are associated with excessive secretion of cortisol,
probably due to hyperactivity of the hypothalamic neuroendocrine cells
controlling the secretion of ACTH. Such patients never show the physical
stigmata of Cushing’s syndrome, but it remains a possibility that the increased
ACTH and cortisol secretion may have a secondary effect on CNS function,
perhaps aggravating the existing psychopathology.
Addison’s Disease (Hyposecretion of Cortisol)
While acute failure of the adrenal cortex is a medical emergency,
chronic adrenocortical insufficiency may lead to symptoms which are more
subtle. The main clinical features include weakness and fatigue increasing as
the day progresses; pigmentation of the skin; hypotension with associated
dizzy spells and fainting; hypoglycemia with associated periods of headache;
sweating; hunger; and gastrointestinal disturbances, including anorexia,

weight loss, and diarrhoea. In primary adrenocortical failure, there is a
secondary hypersecretion of ACTH in the absence of feedback inhibition by
cortisol.
The mental symptoms are now seen as an “integral part of the disease
syndrome.” Apathy and negativism are present in most cases, with depression
and irritability occurring in substantial numbers (although one German
report describes euphoria as a common complication). Delusions occur in a
small but significant percentage. Disorientation, confusion, delirium, and
convulsions are features of severely advanced Addison’s disease. As in
Cushing’s syndrome, the symptoms may fluctuate in intensity and gradually

alter in type.
There are several possible mechanisms for the psychiatric disturbances.

Profound debilitation and weakness certainly play a role in the depression of
many patients. The hypoglycemia (which, in the absence of cortisol, does not
have to be great) may also contribute to the confusion and irritability, as may
the decreased cerebral blood flow associated with marked hypotension.
Correction of the electrolyte disturbances only partially alleviates some of the
psychic disturbances. Because of the similarity of many psychic symptoms to

those of hypercalcemia, it is worth noting that Addison’s disease is on rare
occasions associated with elevated serum calcium levels. Pre-renal azotemia
may also play a role.
Not all of the psychiatric abnormalities can be directly related to the
severity of these metabolic complications, however, and there are significant
effects of both cortisol deficiency and of ACTH excess on the brain. These
include the previously mentioned effects on excitability of brain tissue, on
intracellular electrolytes, and on the metabolism of biogenic amines. The

paradox that depression is a common feature both of Cushing’s and Addison’s
disease could possibly be related to the fact that in both conditions ACTH can
be hypersecreted. With appropriate corticosteroid therapy (which also
suppresses the excessive ACTH secretion) the physical and mental
disturbances are nearly always reversed.
Adrenogenital Syndrome
In the adult, androgen-secreting tumors of the adrenal cortex produce
pronounced virilizing effects in the female, with intensification of libido and

associated psychological responses to the change in physical appearance.
It is in the virilized female infant, however, that the most enduring

effects on the psyche may be noted. An adrenogenital syndrome at birth may
be the result of inborn enzymatic defects in the synthesis of cortisol, or may
be secondary to the use of androgenic progestins in the treatment of the

pregnant mother to forestall impending abortion. Since there are frequently
marked effects on secondary sex characteristics, especially in the female, the

infant may be assigned to the wrong sex. The evidence, well reviewed by
Money, raises the possibility that gender identity is greatly influenced,
perhaps fixed, by the nature of the sex assignment and associated social and
psychological upbringing in early childhood, and that after gender identity is
formed, it is unwise to reassign the child to his “correct” chromosomal sex.
Of further interest is the evidence that even transient fetal
androgenization may have effects on the developing brain of the female,
leading to enduring psychological traits in childhood and adolescence. Such
effects were first noted in fetally androgenized female monkeys, who after
birth were significantly more aggressive in play and in other social situations
than their nonandrogenized female cohorts. There is some preliminary
evidence that there are analogous effects of fetal androgenization in human

females, who have been reported to be more tomboyish in interests and
behavior in childhood. More controversial are preliminary data, suggesting
that fetal exposure to androgens may be associated with a significant increase
in intelligence; artifacts in the sampling of the population may account for

these latter results.
Klinefelter’s Syndrome
This genetic disorder (XXY) of males is associated with hypogonadism

and decreased testosterone secretion. At puberty, testosterone secretion does
not increase, with resultant eunuchoid appearance and impotence.
For many years, an apparent increase in psychopathology in these
patients has been reported, well reviewed by Swanson and Stipes. The
available evidence (not conclusive) suggests that the average IQ of these

patients is less than would normally be expected, and that the incidence of a
variety of psychotic states is increased. The most common psychiatric
disturbances, however, are severe character disorders of several types,
especially schizoid withdrawal and antisocial psychopathy. It is not clear to
what extent the psychopathology is due to the patient’s psychological

response to his sexual disorder; however, the physical disability does not
become clinically manifest until puberty, and most psychological theories of
psychosis and severe character disorders predicate traumata in early
childhood. If indeed in such patients the IQ is lower and the incidence of

psychosis and severe character disturbance is higher, one must consider the
possibility of associated genetically determined mental aberrations, or of
effects of testosterone deficiency on the developing brain.
Testosterone replacement therapy in the adult appears to be of little

value in the treatment of either the impotence or the mental disturbance,
although it may possibly be of value in the child or adolescent.
Thyroid Disorders
Hyperthyroidism
Excessive secretion of thyroid hormone may be due to tumors of the
thyroid gland, or to excessive stimulation of the thyroid by extrathyroid
agents. Graves’s disease is an example of the latter and, in its clinically fully
manifest form, is characterized by thyrotoxicosis, goitre, and exophthalmus.
The disease is much more common in women. Recent evidence relates
Graves’s disease to the presence of an immunological blood factor of
extrapituitary origin, of which long-acting thyroid stimulator (LATS), 35 may

be an example.
The chief symptoms of thyrotoxicosis include an increase in metabolic

rate, with excessive heat production, and associated heat intolerance and
sweating; an increase in cardiac rate and output; weight loss despite
increased appetite and caloric intake; muscular weakness and easy
fatigability.
Mental symptoms are practically always present, with nervousness,
emotional lability, and hyperkinesia characteristic of most patients. To quote
Ingbar and Woeber, “The nervousness of the thyrotoxic patients is not that of
the patient who is chronically anxious, but rather is characterized by
restlessness, shortness of attention span, and a need to be moving around and

doing, despite a feeling of fatigue.” Other clinicians have noted that the warm
dry hands of the nervous hyperthyroid patient distinguish her from the
anxiety neurotic, whose hands tend to be cold and clammy. Crying spells,
irritability, and excessive startle reactions are also typical. (In older patients,
the muscular weakness may be so great as to preclude hyperkinesia, leading

to a predominantly apathetic picture.) Paranoid trends and suspiciousness
occasionally are present. Nevertheless, more severe psychiatric illness in
chronic hyperthyroidism is rare, except in the psychosis prone person.
The so-called thyroid “crisis” or “storm” is rarely seen since the advent
of modern antithyroid therapy. This fulminating attack of hyperthyroidism is
usually characterized by extreme hyperpyrexia, anxiety, and tachycardia;
delirium, coma, and even death may ensue. It may be precipitated by an

episode of anxiety, especially presurgically.
The mental symptoms of hyperthyroidism are evidently related to the

direct effect of thyroid hormones on the brain, and the symptoms can be
partially reproduced in normal subjects by the administration of thyroid
hormone, but the mechanism is not clear. Thyroid hormone increases the
sensitivity of neuroreceptors to catecholamines, decreases monoamine
oxidase activity, and decreases the turnover rate of norepeinephrine; these
actions may play a role in the mental states associated with thyrotoxicosis.
Recent investigations have raised questions about once prevalent

theories that Graves’s disease is likely to be precipitated by emotional stress,
especially object-loss, or that it is more likely to occur in patients with specific

personality types characterized by premature assumption of responsibility
and a martyrlike suppression of dependency wishes. Retrospective
evaluations, always difficult, have not reliably replicated these psychological
formulations. A prospective study has shown increased activity of subclinical,
but radiologically demonstrable, thyroid “hot spots” in association with
nonspecific life stress; the relation of these subclinical “hot spots” to the
etiology of Graves’s disease is unknown, however, and whether they even
have a role in the pathogenesis of toxic nodular goitre is not established. The
role of psychological factors in the etiology of hyperthyroidism remains, then,
an open question.
Hypothyroidism
Hypothyroidism in the adult is commonly caused by surgery or
radioactive-iodine therapy. The spontaneous form is usually secondary to
atrophy of thyroid tissue, probably due to an autoimmune thyroiditis. The

spontaneous disease usually has an insidious onset, and the changes may not
be noticed by the patient until the disease is far advanced. With the deficiency
of thyroid hormone the metabolic rate is markedly reduced, and nearly all
hypothyroid patients experience cold intolerance, decreased sweating, and
generalized weakness and lethargy. In addition, speech is slowed, eyes and
face become puffy, and the skin coarse and dry.
Mental symptoms are very common. Thinking is slowed in the great
majority, and memory is impaired in about two-thirds of the cases. Depressed
mood is typical although clinical depressive illness probably is not.
Psychological testing confirms the impression that the majority of
myxedematous patients suffer from at least a mild organic mental syndrome.
The psychoses which have been reported (“myxedema madness”) occur in a
small percentage of patients and appear to be mostly more dramatic and

severe organic mental syndromes, with the typical symptoms of confusion,
memory loss, and agitation, and occasionally paranoid ideas, delusions and
hallucinations.
Unfortunately, while appropriate thyroid- hormone-replacement
therapy reverses most of the clinical stigmata of myxedema, the organic
mental deficit does not always fully remit, especially in cases of long standing
hypothyroidism. In cretinism the prognosis is especially poor, with the degree
of permanent intelligence loss roughly correlated with the duration of the

untreated illness.
Parathyroid Disorders
Hyperparathyroidism
Parathyroid hormone promotes the absorption of calcium from the

gastrointestinal tract, the resorption of calcium from bone, and the excretion
of phosphate from the kidney, all of which actions increase the concentration
of circulating calcium ion. Chronic hypersecretion of the hormone, due to
tumor or neoplasia of the parathyroid gland, produces clinical symptoms
related to the disturbances in bone metabolism and the effect of
hypercalcemia on various organ systems: skeletal pains, anorexia, nausea,
constipation, muscular weakness, polyuria, renal calculi with renal colic, and
cardiac irregularities.
Mental symptoms are present in at least half the cases, the most
common being lassitude and depressive mood, with loss of interest and
anhedonia. A minority of patients develop organic mental syndromes, with
memory impairment, confusion, paranoid ideas, and hallucinations. In an
outstanding study of fifty-four cases, Petersen showed that the severity of
mental symptomatology increases with the blood calcium level, with organic
brain syndromes occurring primarily at concentrations of about 14-16 mg.

percent and above. Parathyroid hormone itself appears to have no mental
effects, since lowering blood calcium by dialysis (which does not affect
parathyroid hormone itself) immediately reverses the mental disturbances,

and patients with hypercalcemia due to other causes show similar mental
aberrations.
Calcium ion plays a significant role in altering permeability and

excitability of the nerve membrane, and also promotes the discharge and
depletion of norepinephrine and its biosynthetic enzyme, dopamine beta

hydroxylase, from nerve granules. It is not unlikely that these actions play
some role in the mental aberrations noted in hypercalcemia.
Hypoparathyroidism
Hypoparathyroidism is most commonly secondary to damage or

surgical removal of the thyroid gland. About 200 cases of idiopathic
hypoparathyroidism had been reported in the literature by 1962. In both
conditions symptoms develop which are closely related to the lowered blood
calcium concentration characteristic of the illness. Seventy per cent of cases

present manifestations of tetany, such as numbness, tingling, and cramps in
the extremities, leading to carpopedal spasm. In milder forms of the illness,
the patient complains of fatigue, weakness, and tingling sensations.
Mental symptoms are common. In an extensive review, collecting data
from 258 papers, Denko and Kaelbling attempted to classify the psychiatric
disturbances occurring in patients with both idiopathic and surgical
hypoparathyroidism. Because the disease is rare, and cases have generally

been reported by nonpsychiatrists, a clear picture of the psychiatric
symptomatology is difficult to form. In idiopathic hypoparathyroidism, about
one- third of the cases appeared to suffer intellectual deterioration, in many
instances reaching levels of mental retardation. At least a third also showed
symptoms of organic mental syndromes of various types, with some patients

experiencing both intellectual deficit and organic mental syndromes. There
also appear to be additional psychiatric disturbances which are hard to
classify, described as “nervousness,” “emotionality,” etc. In idiopathic
hypoparathyroidism, treatment of the endocrine disorder often leaves the
individual with intellectual deficit. In surgical hypoparathyroidism organic

mental syndromes also occur but intellectual deficit is seen less frequently. A
variety of other psychotic states are noted, but their vague descriptions leave
it unclear as to whether these are also organic mental syndromes or
psychoses of other types. Treatment of the endocrine disorder in surgical

hypoparathyroid cases (by Vitamin D) generally leads to complete remission
of symptoms.
Pancreatic Disorders
Diabetes
Diabetes in its usual form is believed to involve a genetic predisposition

and an evolution which goes through several stages before the manifest
clinical illness appears. Initially, the central disturbance may be a defect in the
metabolic action of insulin; during this latent period insulin may actually be
hypersecreted. In the later stages, when the disease is manifest, insulin
secretion is deficient, and the clinical symptoms are secondary to this
disturbance. As sugar fails to be metabolized, blood sugar rises and is
excreted in the urine, with secondary polyuria and polydipsia. Proteins and
fats are metabolized in excess, with associated weight loss, ketosis, ketonuria,
and potassium loss. Susceptibility to infection is increased, especially in the
skin and genital tract. The patient feels chronically weak and fatigued and
may complain of mental dullness and depression.
The mental symptoms become especially prominent in severe untreated

diabetic acidosis, which is associated with somnolence, difficulty in thinking,
confusion, obtundation, and eventually, coma and death.
The mechanism of the mental dysfunction in diabetic acidosis is

partially understood. The deficiency of insulin per se is not responsible, since
the brain does not require insulin to metabolize glucose, and although the
patient is severely dehydrated, cerebral blood flow is not decreased.

However, as shown in the classic study by Kety et al, cerebral oxygen
consumption is substantially reduced, the decrement correlated closely with
degree of stupor and also with the extent of ketosis. In all likelihood, certain
of the blood-borne ketones act like ether anesthetics on the CNS.
Physiological stress such as infection, fever, and obesity may precipitate
the onset of clinical diabetes, as well as exacerbate the established disease.

There is some evidence that emotional stresses may play a similar role. For
example, in a study of adult diabetics on a metabolic ward, emotional stresses
were shown to be associated with temporary increases in metabolic indices of
diabetes. The pathophysiological mediating mechanisms have not yet been
demonstrated. One possible pathway is the hypersecretion of cortisol and
adrenalin associated with severe emotional distress, since increases in both
cortisol and adrenalin secretion antagonize the action of insulin. In support of
the role of adrenalin, one study indicates that beta adrenergic blocking agents
can be helpful in stabilizing the medical management of brittle juvenile
diabetics, who show increased FFA (free fatty acids) and ketonuria during
stress interviews. It also may be relevant that nondiabetic patients who

develop depressive illnesses are noted to have a relative insulin resistance,
which reverts after recovery.
Although it is beyond the scope of this discussion, it should be noted
that severe diabetes poses a major burden on the psychological adaptative
mechanisms of many patients, particularly juvenile and adolescent diabetics

who must rigorously control diet and insulin dosage at a time when there is a
great need not to feel different from their peers. Other patients may
improperly manage their regimens in the context of periods of depression,
struggles with significant objects, needs for secondary gain, and so forth. The
fear of developing major medical complications from chronic diabetes also
may shadow the outlook of many patients. The need for psychological
sensitivity and understanding on the part of family members and primary

physicians is accordingly great.
Hyperinsulinism
Hyperinsulinism spontaneously occurs with insulin-secreting islet-cell
tumors of the pancreas, and more rarely, with insulin-secreting

extrapancreatic tumors. In patients with adrenocortical insufficiency, the
normal secretion of insulin is functionally excessive, giving rise to the
symptoms of hypoglycemia. There is also a group of patients who appear to

secrete excessive insulin postprandially with a drop to unusually low
concentrations of blood sugar two to four hours after meals. Most commonly,
however, hyperinsulinism occurs in diabetic patients who take more than
their metabolically required dose of insulin.
All of these states lead to hypoglycemia, and since brain metabolism is

completely dependent on glucose, the primary symptoms of hypoglycemia
are due to CNS glucose starvation, similar in its effects to cerebral anoxia.
Indeed, the degree of depression of CNS oxygen utilization in hypoglycemia
has been shown to be closely correlated with the CNS symptomatology. As

would be expected, preexisting brain damage or cerebrovascular insufficiency
significantly increases the sensitivity to the effects of hypoglycemia. The

initial effects are due to cortical depression and a concomitant release of
epinephrine from the adrenal medulla. The cortical symptoms include

headaches, faintness, confusion, restlessness, somnolence, hunger, irritability,
and visual disturbances. Adrenergic symptoms include anxiety, tremor,
perspiration, tingling of the fingers and around the mouth, tachycardia, and
pallor.
In patients with insulinomas or massive insulin overdose, progressive
CNS depression may occur: the patient loses consciousness, and often
manifests sucking, grasping, and grimacing movements, along with twitching

and clonic spasms. Further CNS depression leads to the neurological signs
associated with the involvement of deeper brain structures, such as Babinski
signs, inconjugate ocular deviation, tonic and extensor spasms, and so forth.
Death may ensue.
Administration of glucose promptly reverses the acute symptomatology.
However, those patients who suffer repeated or extended periods of severe

hypoglycemia frequently suffer some degree of irreversible brain damage.
The pathological and mental changes are similar to those seen after chronic
CNS anoxia.
Menstrual Disorders
Premenstrual Tension
Several systematic studies have confirmed what clinicians and women
have long believed, that the menstrual cycle is frequently associated with
definite changes in mental state, significant enough in some women to be
termed a premenstrual syndrome. Psychological assessments of large
samples of women reveal that, for the groups as a whole, negative affects
begin to increase about a week before menstruation, reaching a peak on the
day of menstruation, and then falling after the menstrual phase, reaching a
minimum during the middle portion of the cycle. One study also indicates that
positive pleasant feelings follow an inverse pattern, reaching a peak in
midcycle. The premenstrual feelings noted by the women included irritability,

hostility, depressed mood, emotional overreactions to trivial incidents, crying
spells, anxiety and tension, and mood swings. In addition, many women note
difficulties with concentration, forgetfulness, and judgment. Behavioral
changes, such as lowered school or work performance and withdrawal from

social activities, also occur. Other features of the premenstrual period are
fatigue, bodily aches, particularly headaches and backaches, as well as water
retention with uncomfortable feelings of distention. Moos has noted that the
psychological symptoms can be grouped in several categories (negative
affects, concentration disturbances, behavioral changes, and pain) of varying
prominence in different women, sometimes occurring together and

sometimes not.
What is of further significance to the psychiatrist is the evidence that

psychopathological disturbances of many types can be intensified during the
premenstrual and early menstrual phases. One study, for example, suggests
that preexisting neurotic traits become more prominent in the premenstrual
period. Others have noted that the incidence of suicide and hospitalization for
acute psychiatric illness is disproportionately great during this phase.
The pathophysiological mechanisms underlying the various

premenstrual syndromes are becoming clearer. While water retention
accounts for the bloating, swelling, and painful distention troublesome to
many women, it is not closely correlated with the onset and disappearance of
many of the psychological symptoms, and diuretic medication is not

particularly effective in relieving the purely psychological symptoms.
On the other hand, there is a growing body of circumstantial evidence

that progesterone, which is increasingly secreted in the premenstrual phase,
may play a primary role in the psychological symptomatology. Regimens of
combination-type oral contraceptives, which contain fixed doses of
progestogens and estrogens, are associated with a greater incidence of those

mental symptoms typically seen in the premenstrual syndromes, but also, as
might be expected, the fixed dose of progestogens throughout the cycle
appears to eliminate the psychological fluctuations seen during the normal

cycle. On the other hand, the oral contraceptive regimens which administer
only estrogens until the final five days of the cycle, at which point
progestogen is added (sequential type), are associated with fewer emotional
complications, although a premenstrual increase in symptomatology is once
again apparent.
A possible mechanism for the apparent mental effects of progesterone is
an influence on monoamine oxidase activity (MAO). Grant and Pryse-Davies
reported that increased uterine MAO activity normally occurs in the
premenstrual (progesterone) phase. Contraceptive agents which contain

strongly progestational compounds markedly increase uterine MAO activity
much earlier in the cycle, while agents that are primarily estrogenic in action
tend to inhibit uterine MAO activity. The incidence of depressive
symptomatology in their study roughly correlated with the effects of
contraceptives on MAO activity. If brain MAO is similarly affected, it is
possible that increased catabolism of biogenic amines may be involved in the

psychological symptoms, since such a neurochemical disturbance has been
proposed to occur in clinical depression.
These theories remain unsupported, however, and there are some

defects. The synthetic progestogens in oral contraceptives differ in several
ways from endogenous progesterone, and in some respects, resemble
androgens in their biological activity. Furthermore, a clear hormonal

difference between women with premenstrual tension and those without has
yet to be demonstrated. Finally, for some women with premenstrual tension,

progesterone administration appears to be helpful.
Functional Amenorrhea
It has long been recognized that under conditions of emotional stress
women frequently fail to menstruate for one or two months. As an extreme

example, a high incidence of amenhorrea was reported in women on
imprisonment in concentration camps during World War II, even before
starvation became a factor. Similar observations have been made in less grim
settings, however, for example among adolescent girls adjusting to boarding
school, summer camp, etc.
The mechanism appears to be a failure of ovulation, associated with an
absence of the usual midcycle burst of LH (luteinizing hormone) secretion by
the pituitary. Presumably, emotional stress in some way inhibits the

hypothalamic neuroendocrine cells producing LH releasing factor.
In anorexia nervosa, amenhorrea also typically occurs, not necessarily

associated with malnutrition.
There is also a group of women who fail to ovulate for long periods of
time in the absence of any demonstrable endocrine or gynecological
abnormality, other than the absence of the surge of secretion of LH
(luteinizing hormone) and related hormones at midcycle. In the past the
diagnosis of “functional” amenorrhea was made by exclusion of obvious
anatomical or endocrine pathology. Recently it has been possible to re-
establish ovulation by the use of such agents as clomiphene. There are very
few systematic psychological studies reported on such women, however, to
support the idea, once widespread, that the disturbance is primarily
psychogenic. The existing psychiatric case reports suggest in certain women

the prominence of conflicts over masculine and feminine strivings, and also
around separation-dependency issues with their mothers. It should be noted,
however, that these are common conflicts in women, while chronic functional
amenorrhea is relatively rare.
Failure-to-Grow Syndrome
Among children who fail to grow normally, a subgroup has been
identified in which psychosocial issues appear to play a significant role.
Frequently there is evidence of parental neglect, with associated behavioral
disturbances of many types in the children, including the syndrome of
anaclitic depression. Endocrine studies on the children have demonstrated a

failure to release growth hormone in response to the usual stimuli, such as
insulin-induced hypoglycemia. The disturbance appears likely to be in the
hypothalamus, involving the neural influences which normally control
secretion of growth hormone releasing factor or inhibiting factor from the
median eminence neuroendocrine cells. What is especially striking is that
after a period of emotionally supportive hospital care, behavior, growth, and
growth hormone secretion all frequently return to normal. Since growth
hormone secretion appears to be closely related to the metabolism of brain
catecholamines, and since these neurotransmitters also mediate mood, it is

possible that emotional deprivation alters growth hormone secretion via
these neurochemical mechanisms. In this respect, it is interesting to note that
depressive illness in adults is frequently associated with an inhibition of

growth hormone release.
Concluding Remarks
A review of the psychiatric disturbances associated with the major
endocrine disorders (excessive or deficient secretion of the adrenal cortex,

thyroid, parathyroids, and pancreatic islet cells) reveals a wide variety of
psychopathology. Certain mental symptoms appear to be especially common,
however, such as fatigue, depression, diffuse anxiety, and organic mental
syndromes. While the fully developed endocrine disease is usually quickly
recognizable by the psychiatrist, the early stages can frequently pass
unnoticed, leading to incorrect diagnoses and treatment. Since endocrine

disease is probably as frequent a cause of psychiatric disturbance as brain
tumor, it would seem appropriate for the psychiatrist to be as alert to the
possibility of the former as the latter, particularly in the presence of the
symptoms noted above. A definitive diagnosis requires a full endocrine
workup, of course, but screening information could easily be obtained by a
group of morning blood tests readily analyzed by any good commercial
laboratory: a fasting blood sugar, protein-bound iodine, calcium, cortisol,

sodium, and potassium. Such a battery of tests probably should be considered
as often as an electroencephalogram in the evaluation of the patient
presenting with psychiatric disturbance.
Finally, as has been indicated, the mechanisms by which hormonal
disturbances lead to mental aberration are in many instances still unclear.

Further research in this area not only offers the potential for clarifying the
pathophysiological effects of endocrine disease on the central nervous
system, but may also illuminate significant neurochemical and neuro-

physiological aspects of primary psychiatric disorders as well.
Bibliography
Agras, S. and D. C. Oliveau. “Primary Hyperparathyroidism and Psychosis,” Can. M. Assoc. J., 91
(1964), 1366-1367.
Alexander, F., ed. Psychosomatic Specificity, Vol. 1. Chicago: University of Chicago Press, 1968.
Axelrod, J. Neural and Endocrine Control of Catecholamine Biosynthesis. Proc. 4th. Int. Congr.
Endocrinology. Amsterdam: Excerpta Medica, 1973. In Press.
Azmitia, E. C. and B. McEwen. “Corticosterone Regulation of Tryptophan Hydroxylase in Midbrain
of Rat,” Science, 166 (1969), 1274-1276.
Baker, L., A. Barcai, R. Kaye et al. “Beta Adrenergic Blockade and Juvenile Diabetes: Acute Studies
and Long Term Therapeutic Trial,” J. Pediatr., 75 (1969), 19-29.
Bohus, B. “Central Nervous System Structures and the Effect of ACTH and Corticosteroids on
Avoidance Behavior,” in D. De Wied and J. A. W. M. Weijnen, eds., Progress in Brain
Research, Vol. 32, pp. 171-184. Amsterdam: Elsevier, 1970.
Boon, R. C., D. S. Schalch, L. A. Lee et al. “Plasma Gonadotropin Secretory Patterns in Patients with
Functional Menstrual Disorders and Stein-Leventhal Syndrome: Response to
Clomiphene Treatment,” Am. J. Obstet. Gynecol., 112 (1972), 736-748.
Brown, G. and S. Reichlin. “Psychological and Neural Regulations of Growth Hormone Secretion,”
Psychosom. Med., 34 (1972), 45-61.
Browning, T. B., R. W. Atkins, and Weiner. “Cerebral Metabolic Disturbances in Hypothyroidism,”

Arch. Intern. Med., 93 (1954), 938-950.
Carroll, B. J. “Hypothalamic Pituitary Function in Depressive Illness: Insensitivity to

Hypoglycemia,” Br. Med. J., 3 (1969), 27-28.
----. “Studies with Hypothalamic Pituitary-Adrenal Stimulation Tests in Depression,” in B. Davies,

B. J. Carroll, and R. M. Mowbray, eds., Depressive Illness: Some Research Studies, pp.
149-201. Springfield, Ill.: Charles C. Thomas, 1972.
Clark, L. D., W. Bauer, and S. Cobb. “Preliminary Observations on Mental Disturbances Occurring
in Patients under Therapy with Cortisone and ACTH,” N. Engl. J. Med., 246 (1952),
205-216.
Cleghorn, R. A. “Adrenal Cortical Insufficiency. Psychological and Neurological Observations,”

Can. Med. Assoc. J., 65 (1951), 449-454.
----. “Psychological Changes in Addison’s Disease,” J. Clin. Endocrinol., 13 (1953), 1291-1293.
Clower, C. G., A. J. Young, D. Kepes. “Psychotic States Resulting from Disorders of Thyroid
Function,” Johns Hopkins Med. J., 124 (1969), 305-310.
Coppen, A. and N. Kessel. “Menstruation and Personality,” Br. J. Psychiatry, 109 (1963), 711-721.
Cushing, H. “Basophil Adenomas of the Pituitary Body and their Clinical Manifestations,” Bull.
Johns Hopkins Hosp., 50 (1932), 137-195.
Dalton, K. The Premenstrual Syndrome. Springfield, Ill.: Charles C. Thomas, 1964.
----. “Antenatal Progesterone and Intelligence,” Br. J. Psychiatry, 114 (1968), 1377-1382.
Davis, J. “Theories of Biological Etiology of Affective Disorders,” Int. Rev. Neurobiol., 12 (1970),
145-175.
Denko, J. D. and R. Kaelbling. “The Psychiatric Aspects of Hypoparathyroidism,” Acta Psychiatr.

Scand., 38 (1962), 7-70.
De Wied, D., A. Witter, and S. Lande. “Anterior Pituitary Peptides and Avoidance Acquisition of
Hypophysectomized Rats,” in D. De Wied and J. A. W. M. Weijnen, eds., Progress in
Brain Research, Vol. 32, pp. 213-220. Amsterdam: Elsevier, 1969.
Engel, G. L. and S. G. Margolin. “Neuropsychiatric Disturbances in Internal Disease,” Arch. Intern.

Med., 70 (1942), 236- 259.
Feldman, S. and N. Dafny. “Effects of Adrenocortical Hormones on Electrical Activity of the Brain,”
in D. De Wied and J. A. W. M. Weijnen, eds., Progress in Brain Research, Vol. 32, pp.
90-101. Amsterdam: Elsevier, 1969.
Forsham, P. H. “The Adrenal Cortex,” in R. H. Williams, ed., Textbook of Endocrinology, pp. 287-
379. Philadelphia: Saunders, 1968.
Fox, H. M. and S. Gifford. “Psychological Responses to ACTH and Cortisone,” Psychosom. Med., 15
(1953), 631-641.
Ganz, V. H., B. J. Gurland, W. Deming et al. “Study of the Psychiatric Symptoms of Systemic Lupus
Erythematosus,” Psychosom. Med., 34 (1972), 207-220.
Goy, R. W. and J. A. Resko. “Gonadal Hormones and Behavior of Normal and Pseudo-
hermaphroditic Nonhuman Female Primates,” in E. B. Astwood, ed., Recent Progress
in Hormone Research, Vol. 28, pp. 707-733. New York: Academic, 1972.
Grant, C. and J. Pryse-Davies. “Effects of Oral Contraceptives on Depressive Mood Changes and on
Endometrial Monoamine Oxidase and Phosphates,” Br. Med. J., 28 (1968), 777-780.
Hare, L. and J. Ritchey. “Apathetical Response to Hyperthyroidism: Report of Two Cases,” Ann.
Intern. Med., 24 (1946), 634-637-
Henkin, R. “Effects of Corticosteroids and ACTH on Sensory Systems,” in D. De Wied and J. A. W.

M. Weijnen, eds., Progress in Brain Research, Vol. 32, pp. 270-294. Amsterdam:
Elsevier, 1969.
Hermann, H. T. and C. Quarton. “Psychological Changes and Psychogenesis in Thyroid Hormone

Disorders,” J. Clin. Endocrinol., 25 (1965), 327-338.
Himwich, H. E. Brain Metabolism and Cerebral Disorders. New York: Waverly, 1951.
Hinkle, L. E. and S. Wolf. “Importance of Life Stress in the Course and Management of Diabetes
Mellitus,” JAMA, 148 (1952), 513.
Ingbar, S. H. and K. A. Woeber. “The Thyroid Gland,” in R. H. Williams, ed., Textbook of

Endocrinology, pp. 105-286. Philadelphia: Saunders, 1968.
Kety, S. S., B. D. Polis, C. S. Nadler et al. “The Blood Flow and Oxygen Consumption of the Human
Brain in Diabetic Acidosis and Coma,” J. Clin. Invest., 27 (1948), 500-510.
Lidz, T. “Emotional Factors in the Etiology of Hyperthyroidism,” Psychosom. Med., 11 (1949), 2.
Lidz, T., J. D. Carter, B. I. Lewis et al. “Effects of ACTH and Cortisone on Mood and Mentation,”
Psychosom. Med., 14 (1952), 363-377.
Loeser, A. A. “Effect of Emotional Shock on Hormone Release and Endometrial Development,”
Lancet, 1 (1943), 518.
---- . “Behavioral and Psychoanalytic Aspects of Anovulatory Amenhorrea,” Fertil. Steril., 13

(1962), 20.
Maas, J. W. and M. L. Mednieks. “Hydrocortisone Effected Increase in the Uptake of

Norepinephrine by Brain Slices,” Science, 171 (1971), 178.
----. “Adrenocortical Steroid Hormones, Electrolytes, and the Disposition of the Catecholamines
with Particular Reference to Depressive States,” J. Psychiatr. Res., 9 (1972), 227-
241.
Mandell, A. and M. Mandell. “Suicide and the Menstrual Cycle,” JAMA, 200 (1967), 792.
Michael, R. P. and J. L. Gibbons. “Interrelationships Between the Endocrine System and

Neuropsychiatry,” in C. C. Pfeiffer and J. R. Smythies, eds., International Review of
Neurobiology, Vol. 5. New York: Academic, 1963.
Money, J. “Psychological Studies in Hypothyroidism,” Arch. Neurol. Psychiatry, 76 (1956), 296-

309.
----. Sex Errors of the Body: Dilemmas, Education, Counselling. Baltimore: Johns Hopkins, 1966.
----. “Pituitary-Adrenal and Related Syndromes of Childhood: Effects on I.Q. and Learning,” in D.
De Wied and J. A. W. M. Weijnen, eds., Progress in Brain Research, Vol. 32, pp. 295-
304. Amsterdam: Elsevier, 1970.
----. “Gender Dimorphic Behavior and Fetal Sex Hormones,” in E. B. Astwood, ed., Recent Progress
Money, J. and A. Ehrhardt. “Prenatal Hormonal Exposure: Possible Effects on Behavior in Man,” in
R. Michael, ed., Endocrinology and Human Behavior, pp. 32-48. London: Oxford
Moos, R. “Typology of Menstrual Cycle Syndrome,” Am. J. Obstetr. Gynecol., 103 (1969), 390-402.
Moos, R., B. Kopell, F. Melges et al. “Fluctuations in Symptoms and Moods During the Menstrual
Cycle,” J. Psychosom. Res., 13 (1969), 37-44.
Mueller, P. S., G. R. Heninger, and R. K. MacDonald. “Insulin Tolerance Test in Depression,” Arch.
Gen. Psychiatry, 21 (1969), 587-594.
Mueller, R. A., H. Thoenen, and J. Axelrod. “Effect of Pituitary and ACTH on the Maintenance of
Basal Tyrosine Hydroxylase Activity in Rat Adrenal Gland,” Endocrinology, 86
(1970), 751-755.
Nelson, D. H., J. W. Meakin, and G. W. Thorn. “ACTH-Producing Pituitary Tumors Following

Adrenalectomy for Cushing’s Syndrome,” Ann. Intern. Med., 52 (1960), 560-69.
Nelson, J. B., A. Drivsholm, F. Fischer et al. “Long Term Treatment with Corticosteroids in
Rheumatoid Arthritis,” Acta Med. Scand., 173 (1963), 177-183.
Paige, K. E. “Effects of Oral Contraceptives on Affective Fluctuations Associated with the

Menstrual Cycle,” Psychosom. Med., 33 (1972). 515-537.
Patton, R. G. and L. I. Gardner. “Short Stature Associated with Maternal Deprivation Syndrome:
Disordered Family Environment as Cause for So-Called Idiopathic
Hypopituitarism,” in L. Gardner, ed., Endocrine and Genetic Diseases of Childhood.
Philadelphia: Saunders, 1969.
Pederson, K. O. “Hypercalcemia in Addison’s Disease,” Acta Med. Scand., 181 (1967), 691.
Petersen, P. “Psychiatric Disorders in Primary Hyperparathyroidism,” J. Clin. Endocrinol., 28

(1968), 1491-1495.
Powell, G. F., J. A. Brasel, S. Raiti et al. “Emotional Deprivation and Growth Retardation Simulating
Idiopathic Hypopituitarism,” N. Engl. J. Med., 276 (1967), 1279-1283.
Quarton, G. C., L. D. Clark, S. Cobb et al. “Mental Disturbances Associated with ACTH and
Cortisone: A Review of Explanatory Hypotheses,” Medicine, 34 (1955), 13-50.
Rakoff, A. E. “Endocrine Mechanisms in Psychogenic Amenorrhea,” in R. Michael, ed.,
Endocrinology and Human Behavior, pp. 139-160. London: Oxford University Press,
1968.
Rasmussen, H. “The Parathyroids,” in R. Williams, ed., Textbook of Endocrinology, pp. 847-965.

Rees, L. “The Premenstrual Tension Syndrome and Its Treatment,” Br. Med. J., 1 (1953), 1014-
1016.
Robbins, L. R. and D. B. Vinson. “Objective Psychological Assessment of the Thyrotoxic Patient

and the Response to Treatment,” J. Clin. Endocrinol., 25 (1965), 327-338.
Rome, H. P. and F. J. Braceland. “The Psychological Response to ACTH, Cortisone, Hydrocortisone,

and Related Steroid Substances,” Am. J. Psychiatry, 108 (1952), 641-651.
Ross, G. T., C. M. Cargille, M. B. Lipsett et al. “Pituitary and Gonadal Hormones in Women During
Spontaneous and Induced Ovulatory Cycles,” in E. B. Astwood, ed., Recent Progress
Russell, G. and J. Beardwood. “The Feeding Disorders, with Particular Reference to Anorexia
Nervosa and Its Associated Gonadotrophin Changes,” in R. Michael, ed.,
Endocrinology and Human Behavior, pp. 310-329. London: Oxford University Press,
1968.
Sachar, E. J., J. Finkelstein, and L. Hellman. “Growth Hormone Responses in Depressive Illness. I.
Response to Insulin Tolerance Test,” Arch. Gen. Psychiatry, 25 (1971), 263-269.
Sachar, E. J., L. Hellman, D. K. Fukushima et al. “Cortisol Production in Depressive Illness,” Arch.
Gen. Psychiatry, 23 (1970), 289-298.
Sachar, E. J., L. Hellman, H. P. Roffwarg et al. “Disrupted 24-Hour Patterns of Cortisol Secretion in
Psychotic Depression,” Arch. Gen. Psychiatry, 28 (1973), 19-24.
Sachar, E. J., S. S. Kanter, D. Buie et al. “Psychoendocrinology of Ego Disintegration,” Am. J.

Psychiatry, 126 (1970), 1067-1078.
Sachar, E. J., G. Mushrush, M. Perlow et al. “Growth Hormone Responses to L-Dopa in Depressed
Patients,” Science, 178 (1972), 1304-1305.
Sayers, G. and R. H. Travis. “Adrenocorticotropic Hormone, Adrenocortical Steroids and Their

Synthetic Analogs,” in L. Goodman and A. Gilman, eds., Pharmacological Basis of
Therapeutics, pp. 1604-1642. New York: Macmillan, 1970.
Siegler, D. I. M. “Idiopathic Addison’s Disease Presenting with Hypercalcemia,” Br. Med. J., 2
(1970), 522.
Smith, C. K., J. Barish, J. Correa et al. “Psychiatric Disturbance in Endocrinologic Disease,”

Psychosom. Med., 34 (1972), 69-86.
Sorkin, S. A. “Addison’s Disease,” Medicine, 28 (1949), 371-425.
Spillane, J. D. “Nervous and Mental Disorders in Cushing’s Syndrome,” Brain, 74 (1951), 72-94.
Starr, A. M. “Personality Changes in Cushing’s Syndrome,” J Clin. Endocrinol., 12 (1952), 502-505.
Stein, S. P. and E. Charles. “Emotional Factors in Juvenile Diabetes Mellitus: A Study of Early Life
Experience of Adolescent Diabetics,” Am. J. Psychiatry, 128 (1952), 700-704.
Stoll, W. A. Die Psychiatrie des Morbus Addison. Stuttgart: Thieme, 1953.
Sturgis, S. H., ed. The Gynecologic Patient: A Psychoendocrine Study. New York: Grune & Stratton,
1962.
Swanson, D. and A. Stipes. “Psychiatric Aspects of Klinefelter’s Syndrome,” Am. J. Psychiatry, 126
(1969), 814-822.
Trethowan, W. H. and S. Cobb. “Neuropsychiatric Aspects of Cushing’s Syndrome,” Arch. Neurol.

Psychiatry, 67 (1952), 283-309.
Van de Wiele, R. L., J. Bogumil, I. Dyenfurth et al. “Mechanisms Regulating the Menstrual Cycle in
Women,” in E. B. Astwood, ed., Recent Progress in Hormone Research, Vol. 26, pp.
48-62. New York: Academic, 1970.
Voth, H., P. Holzman, J. Katz et al. “Thyroid ‘Hot Spots’: Their Relationship to Life Stress,”
Psychosom. Med., 32 (1970), 561-580.
lisWaldstein, S. S. “Thyroid Catecholamine Interrelationships,” Ann. Rev. Med., 17 (1966), 123-

132.
Weinshilbaum, R., and J. Axelrod. “Dopamine Beta Hydroxylase Activity in the Rat after
Hypophysectomy,” Endocrinology, 87 (1970), 894.
Whybrow, P. C., A. J. Prange, and C. R. Treadway. “Mental Changes Accompanying Thyroid Gland
Dysfunction,” Arch. Gen. Psychiatry, 20 (1969), 48-63.
Williams, R. H. “The Pancreas,” in R. H. Williams, ed., Textbook of Endocrinology, pp. 613-802.

----. “Hypoglycemia and Hypoglycemoses,” in R. H. Williams, ed., Textbook of Endocrinology, pp.

803-846. Philadelphia: Saunders, 1968.
Williams, R. H., ed. Textbook of Endocrinology. Philadelphia: Saunders, 1968.
Wilson, W. P., J. E. Johnson, and R. B. Smith. “Affective Change in Thyrotoxicosis and Experimental
Hypermetabolism,” in J. Wortis, ed.. Recent Advances in Biological Psychiatry, Vol. 4.
New York: Plenum, 1961.
Woodbury, D. M. “Relation Between the Adrenal Cortex and the Central Nervous System,”
Pharmacol., Rev., 10 (1958), 275-357.
Woodbury, D. M. and A. Vernadakas. “Effects of Steroids on the Central Nervous System,” Methods
Hormone Res., 5 (1966), 1-57.
Notes
1 Supported in part by NIMH Career Scientists Grant K2-MH-22613 and NIMH Project Grant MH-
13402. Peter Gruen assisted in the bibliographical review.
Chapter 13
Epilepsy: Neuropsychological Aspects1
Gilbert H. Glaser
Introduction
Epilepsy, as a state of disordered cerebral function, is derived from the
Greek “epilepsia,” meaning “a taking hold of or a seizing.” Because of the

existence of many kinds of seizures which appear in human disease under
numerous and varied abnormal circumstances, designation as “The
epilepsies” would be more appropriate.
The first definitive descriptions of both major and minor epileptic
seizures are found in the Hippocratic writings of the fifth century B.C., The
Sacred Disease. These actually localized the disturbances in the brain and
revealed such aspects as the premonitory experiences or auras, the
differentiation between so-called idiopathic and symptomatic epilepsy and
the important influences of age, temperament, and menstrual cycles. These
earliest considerations of human beings with epilepsy recognized the
profound emotional experiences which in many different ways are associated
with seizure phenomena. For example, in The Sacred Disease Hippocrates
says:
Patients who suffer from this disease have a premonitory indication of
an attack. In such circumstances they avoid company, going home if they are
near enough, or to the loneliest spot that they can find if they are not, so that
as few people as possible will see them fall . . . Small children, from
inexperience as being unaccustomed to the disease, at first fall down
wherever they happen to be. Later, after a number of attacks, they run to their
mothers or to someone who they know well when they feel one coming on.
This is through fear and fright at what they feel, for they have not yet learnt to
feel ashamed. [Sect. 15, p. 189]
Temkin quotes Herodotus as follows: “The great Persian king Cambyses
suffered from birth with a certain great disease which some people call
sacred and thus it would not be unlikely that if the body suffered from a great
disease the mind was not sound either”. Aretaeus of Cappadocia carried this
point further in commenting upon certain personality characteristics of the

epileptic: “They become languid, spiritless, stupid, inhuman, unsociable, not
disposed to hold intercourse, nor be sociable at any period of life, sleepless,

subject to many horrid dreams, without appetite and with bad digestion, pale,
of leaden colour, slow to learn from torpidity of the understanding and of the
senses.”
The fact that epilepsy could be manifest by phenomena other than
major convulsive movements was recognized relatively early. Bernard of
Gordon in 1542 described such a situation: “As I have often seen that the
attack was so short that the only thing necessary for the patients was to lean
against a wall or something similar and to rub his face, and it ceased.
Sometimes, however, he didn’t have to lean, he was seized by a confusion in
the head, and darkness in the eyes, and feeling it beforehand, he said an “Ave
Maria” and before it had finished, the paroxysm had passed. He spat once and
it was all over, but it came frequently during the day. There are some people
who after the paroxysm have absolutely no memory of their falling down or
of their affliction, whilst there are others who remember and feel ashamed.”
Throughout the Middle Ages there was fixation on the relationship between
epileptic phenomena and various magical, mystical, and religious

philosophies. These led to the inappropriate reactions to the epileptic as
being “possessed” and worsened the already existing fears, anxieties, and
feelings of shame and inadequacy in the afflicted individual. Many of the
present-day stigmas and the psychological and social problems of the

epileptic patient have their origins in this unfortunate history.
Beginning with the Renaissance, increasing insight and medical
understanding of epilepsy gradually developed, but it was not until the mid-
nineteenth century with its anatomical and physiological approaches to the
problem that the modern era began. Hughlings Jackson developed the first
comprehensive understanding of seizure origin from an abnormal focus of

excessive discharge of brain gray matter, with especially pertinent
descriptions of the “dreamy state” and uncinated-temporal lobe seizure,
differentiating these from major convulsive activity. Gowers, detailed the
extensive variety of clinical epileptic symptoms even further, and emphasized

states which he regarded as in a “borderland” between actual epileptic
seizure and certain psychological phenomena. Actually, it was gradually
recognized, during the 19th century, particularly by workers in France, e.g.,

Falret, that psychological disturbances may occur in the epileptic subject as
part of the seizure complex itself, i.e., ictal, or as an interictal disturbance
involving various behavioral and cognitive functions. Disruptions of mental
functions of severe degree such as psychoses were found, when brief and
paroxysmal, to be ictal, but being more often of long duration, as part of an
interictal state. The recognition of psychological precipitating factors both in

a direct emotional or affective way, as in relation to various sensory stimuli,
began in part with Richer of the Charcot school, leading to a differentiation

between “hystero-epilepsy” and what could be called “actual” epilepsy.
Problems still remain, however, in delineating the role of the epilepsy in
relation to mental disorder, and in separating out factors due to specific brain
lesion.
The twentieth century has seen extensive research in this field: in-depth
studies of the life history of the patients; finer neuropathological,
neurophysiological, and biochemical correlations; the use of
electroencephalography in diagnosis and in studying, in a concomitant way,

relationship between seizure discharges and psychological functions;
neuropsychological tests of increasing sophistication in delineating specific
brain dysfunctions; antiepileptic drugs with increasing knowledge of their
effects on seizures and mental functions correlated with blood levels; and,
finally, the combined approaches of both medical-pharmacological and
psychological-social management in the treatment of many epileptic patients,
leading to rehabilitation and placement in an effective role in society.
Incidence
It has been difficult to determine an accurate epidemiology of epilepsy,

particularly because of the increasing diagnostic awareness of the
paroxysmal, but nonconvulsive, types of seizure disorders, especially those
involving behavioral changes. The incidence may well be over l percent in the
general population. Epileptic seizures appear in all age groups from the
newborn to the elderly, but with different causes. There is a differential sex
ratio of 140 males per 100 females. There are variations with different
phenomena, for example the sex ratio with regard to the occurrence of
chronic epileptic psychoses is about equal.
Only when seizures recur is the designation epilepsy appropriate. Not
all epilepsy can be described in terms of convulsions, but the terms “fit,”
“attack,” or “spell” are considered vague and inappropriate. Any disorder
affecting brain function may result in seizures and the process must be
considered in terms of various factors which may or may not be present in
any individual instance, such as an anatomic substrate or actual physical
lesion of brain tissue, the development of physiological disturbance, and
biochemical and metabolic correlates. Genetic background and constitutional
predisposition may be significant, and psychological determinants or
“triggering” factors may be contributory.
Mechanisms and Etiology
Basic Mechanisms
Any neuron or aggregate of neurons may be made to discharge

abnormally, by electrical stimulation, by alterations in basic metabolic
environment, or by excitatory drugs. Thus, even a normal brain, may be made
to develop either generalized or focal seizures. The various pathological
disorders that produce recurrent seizures or epilepsy operate upon factors in
terms of basic predisposition, specific abnormal process and precipitating or
triggering circumstances. Certain regions of brain are considered seizure-
sensitive, with low threshold and high susceptibility. These are especially
related to motor and autonomic functions, such as motor cortex and the
complex of the “limbic” system. The temporal lobe and its deeper limbic
nuclear aggregates, the amygdala and hippocampus, are particularly involved
in the development of seizures. Their vascularity is vulnerable to
compression, and the neuronal structures in these regions are very sensitive
to metabolic disturbance such as hypoxia. It is difficult to separate cause and
effect in this regard, since structural lesions in these regions may be the result
of seizure activity with secondary vascular insufficiency and hypoxia;
however, such lesions, following severe convulsions or status epilepticus in

infancy, may themselves become epileptogenic and lead to further “limbic”
seizure activity.
Factors of age and development are important from the perinatal period
onwards. There often is a little-understood delay between the event of a
lesion (i.e., as due to trauma or encephalitis), and the appearance of seizure.

Certain seizure types are more common in infants, e.g., massive spasms; petit-
mal seizures appear in childhood after the age of four or five rather than later
in life. The occurrence of seizures with high fever is almost exclusively a

phenomenon of early childhood.
Seizure activity may develop from an abnormal focus or a number of
foci or may be generalized from the onset, seemingly without focal origin.
However, generalization of paroxysmal discharge throughout the brain may
occur from a focus so rapidly that the focal origin may be obscured. Many
patients with an epileptogenic cerebral lesion, especially in a temporal lobe,
are in this category. Certainly, however, major convulsions caused by such
metabolic distortions as hypoglycemia, hypocalcemia, water intoxication, or

the withdrawal of sedative drugs are examples of those generalized from the
onset. In these instances the initiation of the seizure may be in the subcortical
mesodiencephalic nonspecific reticular systems, with diffuse propagation
bilaterally into cerebral cortex, especially motor and autonomic pathways.

The rapid loss of consciousness which occurs first and the marked amnesia
for the seizure afterwards can be related to this type of patterned spread.
However, it is reasonable to consider, as did Jackson, that most other

seizures develop from a focus or aggregate of abnormally excitable neurons.
The neuronal disturbances involved are those of intrinsic membrane

instabilities related to both intra- and extracellular chemical derangements.
These produce excessive paroxysmal potential discharges, spreading then
through essentially normal neural pathways away from the focus. Thus, the
clinical manifestations of a particular seizure state depend upon both the
focus of origin and the region of brain involved in the propagated discharge.
However, epilepsy as a clinical phenomenon is a discontinuous process.
Seizures of any type have varying periodicity in any particular patient and
may relate to the sleep cycle, the menstrual cycle, or to unpredictable body
rhythms. Certain seizures may occur one or more times a day in some
subjects, but at much longer intervals in others. Yet, the clinical “interseizure”
state may be characterized by more or less continually abnormal electrical
activity as seen in the EEG. There are, therefore, two clinical states of the
epileptic, i.e., the actual overt seizure or ictal disturbance, and the interictal
state. Under certain circumstances the interictal state may be manifest by
subtle difficulties in cerebral function, such as in memory processing and
learning, or in behavioral distortions. Whether these, too, might be related to

actual subclinical ongoing seizure or ictal discharge remains a problem for
continued investigation (see below).
Much attention now is paid to “reflex” or sensory precipitating factors in

the production of seizures. These often are quite specific for individual
patients such as light flickering, i.e., photic sensitive and TV epilepsy, visual
patterns, reading, and sound (musicogenic).
Both physiological and biochemical processes must be considered not
only in our understanding of how epileptogenic neurons develop, but of how
such seizure activity ceases. A property of “neuronal exhaustion” may be

physiological, yet in some way due to depletion of metabolic substrates, along
with ionic shifts. Such a secondary clinical concomitant of generalized
convulsive activity as apnea contributes to cerebral hypoxia, if not controlled.
Actually cerebral blood flow does increase initially to meet cerebral oxygen
demands during such seizures, decreasing only later if the seizure is severe
and prolonged as in status epilepticus.
Etiology in Epilepsy
Idiopathic Epilepsy
Epilepsies, or recurrent seizures, appear in man in a great variety of
situations, and consideration of etiology must involve factors which may be

genetic and constitutional, or acquired and symptomatic. In individual
patients certain precipitating or contributing factors, while not specifically
causative, may be highly important. A major problem in the understanding of
epilepsy by the patient, his family, and even the physician, is the failure to find
a specific cause, such as a structural or biochemical lesion, in a large number
of patients (up to 75 percent). Even if such lesions are not found by the finest
diagnostic techniques, it is indeed possible that a minute epileptogenic lesion
could be present in a highly sensitive area of brain. One merely might

consider the relatively high incidence of unrecognized encephalopathies in
childhood associated with exanthema or head trauma to realize the
possibility of production of such a lesion. Therefore, we can divide epileptics
into two categories etiologically, the idiopathic and the secondary or
acquired. Idiopathic epilepsy is diagnosed when no specific cause can be
found. In acquired epilepsy such a cause is determined. Petit-mal epilepsy in
childhood is regarded as the classic example of an idiopathic disorder, yet
some cases are known to be associated with actual brain lesions.
The important question of genetics and heredity must be considered,

particularly since it often plays a significant role in reactive psychological
problems of the patient and his family. A genetically transmitted
predisposition for seizure tendency is present in certain families, especially
involving patients with onset of seizure in early life, as petit mal. There also
are families with a high incidence of febrile seizures in infants. Even some
familial focal patterning may occur. It has been determined that the relatives
of some epileptic patients have a 3-5 percent incidence of epilepsy and an

even higher incidence of electro-encephalographic abnormality. This is seen
particularly in studies of monozygotic twins in whom such abnormalities may
reach a correlation of over 40 percent. There may be a constitutional
susceptibility for seizure associated with a head injury or brain tumor. Yet,
since epilepsy is a symptom often associated with other neurologic
abnormalities such as motor disturbance and mental subnormality due to
various underlying cerebral diseases, an inheritance pattern for such specific

cerebral disease must be considered as well. In addition, there are a known
number of indirect factors, nongenetic, such as cerebral birth trauma
secondary to narrow maternal pelvis, which can be related to seizure
incidence in siblings.
Acquired or Symptomatic Epilepsy
Any disease or structural abnormality of the brain may be associated
with seizures, as well as other neurological dysfunctions including those
producing perceptual and intellectual disorders. These are listed below.
Congenital malformations of the brain cause varying incidence of
epilepsy, depending upon degree, location, and general genetic factors. These
include microgyria, porencephaly, hemangiomas, and Down’s syndrome.
Multiple anomalies may be associated with maternal rubella. Prematurity,

breech delivery, and neonatal asphyxia all may be important factors in
epileptogenesis.
Acute, subacute, and chronic infections are productive of epilepsy both
during the active process and later due to residual lesions. The incidence of
cerebral neurosyphilis has decreased. However, viral encephalitis, acute and
subacute, is increasingly prominent. Certain of these, such as acute herpetic

encephalitis, tend to localize in a temporal lobe.
Head injury is a major cause of acquired epilepsy, acutely and as a
chronic residual effect. Posttraumatic epilepsy may develop within three
years in up to 10 percent of cases after a closed head injury, and between 30
and 40 percent after open injuries. The seizure incidence depends upon the
severity of the wound, dural penetration, and location.
Brain tumors (gliomas, meningiomas, metastatic) are associated with
seizures, especially focal, in 30-40 percent of cases, the seizure being the first
sign in 15-20 percent. The incidence is highest in supratentorial convexity
tumors. Progression of symptoms from focal seizure to hemiparesis and
organic mental dysfunction should be highly suggestive of tumor.
Cerebral vascular disease is a cause of epilepsy more frequently than
usually realized, especially in older age groups. Seizures may occur in up to
25 percent of such patients due to localized vascular insufficiency and acute

ischemic hypoxia, as well as secondary to the lesions of embolism,
hemorrhage, and thrombosis. Prolonged syncope as in carotid sinus
sensitivity and Adams-Stokes syndrome may develop into seizure. Diffuse
cerebral arteriosclerosis, often associated with hypertensive disease, can

produce a syndrome of dementia and focal or generalized seizures.
Cerebral degenerative and demyelinating diseases have a significant
incidence of seizures. This reaches 5 percent in multiple sclerosis. The
incidence is relatively high in the presenile dementias (Alzheimer, Pick) with
both myoclonic and generalized seizures.
Toxic and metabolic cerebral disorders are associated with both
seizures and encephalopathy (dementia, stupor, precoma, coma). Various

drug intoxications as with alcohol, barbiturates, and other sedatives or
tranquillizers produce seizure induction usually in a withdrawal phase,
within forty-eight to seventy-two hours, often with delirium. Carbon

monoxide intoxication, hypoxia, water intoxication, lead poisoning,
hypoglycemia, hypocalcemia, and porphyria may cause seizures in individual
instances.
In many cases a combination of factors may be playing a role, such as
genetic predisposition, a toxic metabolic disturbance, a focal brain lesion,
vascular insufficiency and a nonspecific trigger such as an emotional crisis or
a flickering light. Each patient, therefore, must be evaluated diagnostically

from many different aspects in order to establish etiology on the different
levels leading to appropriate total therapy.
Clinical Epileptic Manifestations with Emphasis on Neuropsychological

Phenomena
Generalized Seizures
Major or Grand Mal Epilepsy
Within the major generalized seizure, a complex series of events occurs
which the patient usually does not remember. A description must be obtained
from witnesses, especially experienced, if possible, since details are extremely
important, particularly in relation to establishing focal origin or in
differentiation from a major hysterical state.
Such seizures usually start with a prodromal phase lasting minutes or
even hours, with a change in emotional reactivity or affective responses, such
as the appearance of increasing tension or anxiety, depression or elation. This
initial phase may be difficult to recognize, and more often the onset of the
seizure is regarded as the aura. This usually is a brief sensory experience
directly related to the locus of origin of the seizure. Frequently experienced
auras are a sense of fear and dread, a peculiar upper visceral epigastric
sensation welling up into the throat, an unpleasant odor, various formed and
unformed visual and auditory hallucinations and peculiar sensations in an

arm or leg. At times, localized movements of an extremity or portions of the
face precede the generalized seizure. The aura, as the initial phase, may allow
distinction between seizure generalized from the start or generalized with
focal onset. The convulsion itself often begins with sudden vocalization (the
“epileptic cry”), loss of consciousness, tonic extensor rigidity of trunk and

extremities, then clonic movements, impaired breathing with brief apnea,
cyanosis, and stertor. Incontinence of bladder and bowels, biting of the
tongue and inside of cheeks ensue in the clonic phase. Examination may
reveal marked pupillary inequality and extensor plantar responses. After
some minutes the excessive motor activity ceases, breathing becomes more
normal and consciousness gradually returns. However, a postictal state is

frequently present with confusion, general fatigue, headache, and at times
residual neurologic signs, such as hemiparesis, sensory disturbances, and
dysphasia. Postictal paralysis (Todd’s paralysis) may last from several

minutes to hours after the seizure. In general, there is complete amnesia for
the major events of the seizure, with the exception of possible recollection of
the prodromal phase and the aura. Knowledge and familiarity of this entire
sequence of events will help the physician to distinguish between actual
epileptic seizure and “functional” seizurelike states.
The EEG pattern associated with generalized seizure, during the seizure
itself, is difficult to distinguish from movement artifact, but otherwise may be
seen to consist usually of bilateral discharges from all areas with patterns of
high amplitude spikes and slow waves. These discharges may be present
intermittently in the interseizure state. However, between seizures many
patients (up to 25 percent) may have an EEG characterized by nonspecific
generalized slow wave changes or even essentially normal patterns. Localized

slow waves or discharges are suggestive of a focal cerebral lesion.
Generalized seizures appear in all etiologic circumstances and in all age
groups. The frequency may vary greatly, with about 20 percent of patients
only having nocturnal convulsions. In females, a cyclic occurrence may appear
with the menses. The designation “fragmentary seizure” may be utilized for
the occurrence of brief phases of the generalized complex, i.e., only auras
(frequent epigastric “butterflies”) or brief, abortive movements and
disturbance of consciousness. These may occur in some patients during
therapy with anticonvulsant drugs and relatively incomplete control.
Petit Mal Epilepsy
The seizure of “absence,” a minor form of “generalized” epilepsy, is
characterized primarily by a brief lapse of consciousness usually lasting 5-10
sec. but occasionally up to 30 sec. The petit-mal seizure ordinarily appears in
childhood, with onset between the ages of three and ten years. Usually no
specific cause is found, and this form of epilepsy is regarded as classically
idiopathic. It tends to diminish in incidence after puberty and persistence into
adult life is unusual, being quite infrequent after the age of thirty. In rare
instances a specific brain lesion, such as a frontal calcified tumor or diffuse
lipidosis, has been reported with petit mal.
Clinically, the patient is seen to have a sudden cessation of activity and
to stare, without any gross movements. However, blinking of the eyelids is
common and occasionally slight deviation of the eyes and head, along with
brief minor movements of the lips and hands may occur. When more complex
behavior alterations with motor acts are present, the pattern should be
regarded as a brief automatism or minor motor seizure. The term “akinetic
attack” refers to a generalized seizure with simple falling and loss of
consciousness. It may be accompanied by an absence seizure and minor

movements, but usually there is but a marked diminution of general postural
tone. Afterwards, the patient recovers normal posture and mental clarity,
though there may be a slight period of confusion.
The electroencephalographic correlate of petit-mal or absence seizure is
a rhythmic 3-Hz. spike-and-wave discharge appearing from all regions

synchronously both during and between seizures in about 85 percent of
patients. Usually a discharge of more than two seconds is associated with a
clinical seizure. Akinetic and myoclonic seizures may be associated with

atypical spike-wave discharges, often slower than 3 Hz.
Photic sensitivity is present in a number of patients and may be familial.
Flickering light at 12-14 Hz- most commonly triggers these seizures. In some
patients, mere exposure to bright sunlight may precipitate seizures; in others
the flickering of a television screen is effective. The phenomenon of self-
induction of seizure appears in this context, the patients inducing absence

seizure by looking at a light and passing a hand in front of the eyes. Self-
induced television epilepsy has been described. Apparently, in these
instances, a peculiar pleasurable sensation accompanies the experience of the
seizure. The incidence of absence attacks varies from very few, often in the
morning, to a great many, up to 100 or more per day (“pyknolepsy”). As the
frequency increases, the child may develop difficulties in continuing certain

tasks and in developing complex learning functions, since there may be a
defect in memory patterning induced by the absence. The designation “petit-
mal status” or “absence status” refers to many such attacks occurring close
together in time, lasting from minutes to several hours and producing

clouding of consciousness with marked confusion and disorientation. Close
observation may reveal minor twitching of the eyelids and upper limbs along
with a dull facial expression. The state is associated with prolonged EEG
discharge of the 3-Hz. spike-wave type as well as more irregular complex
slower and faster components with polyspikes. Instances of even more
prolonged mental dullness with profound psychic disturbances, a change in
personality, motor agitation, dreamy states, delusion and “dementing”

syndrome have been found associated with this type of EEG abnormality.
Myoclonic seizures as related seizure phenomenon in this group may be

localized or generalized and when severe are often associated with
impairment of consciousness. They involve sudden integrated contractions of

a single muscle or many muscle groups producing relatively simple
arrhythmic jerking movements of one or many joints or a body segment. They
can exist as an independent entity, as a phenomenon preceding a generalized
seizure, usually with a build-up in severity, or in association with petit mal
absence. They often are sensitive to sensory influences and may be
precipitated by light or sound stimuli, change in posture or movement of a

limb, by drowsiness or an emotional upset. In some instances cerebellar
dysfunction with ataxia may be present in an associated syndrome. The
myoclonus epilepsy of “Unverricht” refers to generalized myoclonus and

mental deterioration due to a diffuse degenerative metabolic disorder.
Myoclonic seizures associated with other signs of diffuse cerebral dysfunction
(confusion, stupor, dementia) occur in uremic encephalopathy, subacute
encephalitis, Creutzfeldt-Jakob chronic viral encephalitis, and cerebral
lipidoses.
A severe myoclonic seizure disorder appearing in the first eighteen
months of life and usually associated with general cerebral deterioration and
marked mental retardation is called infantile massive spasms or jackknife

seizure. The infant develops marked flexion spasms of head, neck, and trunk,
and extension of legs and arms. This probably is the most common major
seizure pattern in infancy. Some known causes of this disorder are
phenylketonuria, tuberous sclerosis, Down’s syndrome, bilateral subdural

hematoma, and marked porencephaly. However, the cause is often not
determined.
The EEG correlates of myoclonic seizures usually are synchronous 2-3
Hz. spike-wave complexes in bursts, with clear EEG patterns interspersed.
The massive spasm seizures are more associated with hypsarrhythmia, or
relatively asynchronous, asymmetric slow spike-wave and slow-wave
discharges.
Perceptual Functions during Seizures and EEG Discharges
A relatively controllable way of evaluating perceptual abilities during
epileptic activity has been to study the ability of patients to perceive and react
during overt electroencephalographic discharges. Because the petit-mal
absence type of epileptic seizure has a high degree of correlation (over 85

percent) with the typical 3 Hz. paroxysmal spike-and- wave activity in the
electroencephalogram, such studies were first carried out in subjects with
this disorder. Initially, Schwab was able to demonstrate that patients with
petit-mal seizures displayed a disturbance in response to auditory stimuli; the
responses were delayed during attacks lasting about five seconds, and in
those lasting more than eight seconds no response occurred. This was
regarded as due to the distorted awareness or “unconsciousness” caused by
the petit-mal seizure. Since that time, there have been a number of other
investigations of this phenomenon of delayed or disturbed reactivity
correlated with electroencephalographic discharges in subjects with petit mal
and other forms of epilepsy. This subject is of great importance in our
understanding of psychological disturbances in epilepsy and will be discussed
in some detail.
A high degree of variability has been reported, but the experimental
designs themselves have been very different, particularly in the types of tests
performed by the subject. Not all investigations utilized tests of actual
perceptual functions, although many cognitive elements were involved. Kooi
and Hovey studied the performance of standard psychological tests (i.e.,
Wechsler-Bellevue, particularly picture completion and digit symbol) during

continuous EEG recording of patients with mainly grand-mal or psychomotor
epilepsy, but with intermittent bilateral spike-wave discharges in the EEG.
The test performances always were impaired, often with nonanswer

responses during the EEG discharges. Similar results were reported by
Davidoff and Johnson. Visual motor continuous-performance tests showed
greater deficiencies during suppressed or flattened periods in the EEG, in an

unusual study by Prechtl et al. Courtois et al. reported an unequal affection
during petit-mal attacks of somatosensory modalities, i.e., light touch most
readily, then passive movement, and pain perception least. Goode et al. and
Mirsky and Van Buren have demonstrated that patients with petit-mal
epilepsy performed more poorly on a test of sustained attention, i.e., the
continuous-performance test, than did patients with focal motor epilepsy.
This test utilized a repeated specified visual signal, and it was found that the
ability to execute the simple repetitive discriminative response was lost if the
stimulus fell within a burst of spike-and-wave activity in the
electroencephalogram. Actually, the interpretation of the mechanism of this

disturbance still is not definite because it may be due (as Mirsky and Tecce
have emphasized) to reduced sensory input or reduced perception, to
weakened motor effective capacity, to temporary impairment of the central

integrative or decision-making process, to temporary forgetting of the task
instructions, or to a combination of these factors. Mirsky and Van Buren
suggested that both input and output might be affected by whatever produces
the spike-and-wave discharge, although reduced input or reduced perception
seemed to be more obviously disturbed than a weakened or reduced output.
Thus, in the sensory task the subject was presented with a visual auditory
stimulus with the instruction to hold it in mind until questioned by the
examiner. When stimuli were presented during the spike-and-wave burst and
the patient questioned a few seconds later, recall was severely impaired; the
degree of impairment was generally less than that seen with the ordinary
continuous-performance test. However, the interpretation of this as a
“purely” sensory perceptive impairment remains equivocal. The patient may

have registered the stimulus, but it may have been expunged from his
memory by the physiological phenomenon manifested by the spike-and-wave
burst. Alternatively, it may not be possible under these conditions to maintain
a stimulus trace without some initial subvocal verbalization or rehearsal;
there may be a subtle but important motor component even in this pure
sensory perceptive task. It should be mentioned that these workers found
that electroencephalographic bursts which were symmetrical, regular, and
bilaterally synchronous tended to produce more deficit in these tasks than
other less extensive EEG discharges. The interjected problem of memory
disturbance has been emphasized by the work of Hutt et al., who showed that
children with light-sensitive epilepsy demonstrated impaired recall of digits
during bioelectric paroxysms in the EEG evoked by stroboscopic light
stimulation.
Further analysis of this phenomenon has been carried out by Tizard and
Margerison. They showed that patients with petit-mal epilepsy worked more
slowly during the performance of various tests and made more errors during
electroencephalographic spike-wave discharges. Even very brief bursts of one

to one-and-one-half second’s duration, without overt behavioral
accompaniments, were shown to be associated with significantly slowed

response times. The psychological tests utilized by these workers were
simple, repetitive, and continuous, and involved responses to various
perceptual stimuli, such as auditory, visual, and tactile. The auditory stimuli
were of both numbers and tones, the visual stimuli were of different
combinations of numbers of lights and colors, and the tactile stimuli were
those of a tickling stimulus applied to the hand. In six patients studied, all but
one had an amnesia for the events occurring during clinical attacks or
correlated electroencephalographic discharges. Even this patient, however,
had some disturbance of recall. All of the patients exhibited defects in

performance in all tests during the discharges. The phenomenon was not
regarded as one merely of a loss of “consciousness” during spike-wave
discharges of sufficiently long duration. When the discharge lasted longer

than six to eight seconds, the disturbance of performance was much greater;
however, the important finding in this study is the demonstration of
disturbed performance during the very brief discharges of around one to two
seconds in duration, even though no clinical seizure or other behavioral
abnormality was observed. The implication from all of these studies is that
both perception and memory are disturbed during even brief seizure activity,
and that both of these processes probably interact in developing the actual
experience of the subject.
In many instances similar impairments of cognitive functions may be
present between bursts of paroxysmal EEG discharge, implying a more
persistent disturbance of integrating cerebral circuits. Another clinically
highly significant observation, often of practical significance in patient

management, is the frequently found suppression or limitation of paroxysmal
seizure activity (especially petit mal) during states of attention, stimulation,
concentration, and motor activity, particularly during periods of interest and
high motivation (See references 29, 40, 41, 83, 90, 94, and 134). However,
periods of inactivity, boredom, and irritability may trigger even more
seizures. The use of EEG telemetry on patients, especially school children in

various task settings is increasing our information and understanding of such
psychological factors in the triggering of epileptic discharges in the EEG and
actual seizures.
Sensony-Evoked Potentials during Epileptic Discharges
Disturbances of sensory perception already described as occurring in
epileptic patients and often correlated with electroencephalographic

discharges vary from simple to complex, and clearly involve different
portions of the sensory perceiving and analyzing cerebral structures. The

epileptic discharges may involve only certain systems or portions of systems
and produce the changes that vary in their complexity of expression. Not all
neuronal populations seem to participate fully in the different kinds of
seizure activity, even those characterized by the generalized high-amplitude
synchronous discharging seen during prolonged absence attacks.
Attempts have been made to study these phenomena by investigating
cerebral sensory-evoked potentials in epileptic subjects in the interseizure

state and during epileptic discharges. Cernacek and Ciganek found a
decreased amplitude of the earlier components of visual-evoked responses,
i.e., presumably that portion related to primary receiving activity, and an
increase in certain of the later secondary waves (especially their wave V), in
patients in the interseizure state. This effect was more pronounced at lower
frequencies of stimulation than at higher. Photogenic epileptic subjects did
not differ from those with psychomotor and grand-mal epilepsy. Potentials
from occipital cortex were not specifically enhanced. However, Gastaut et al.
studied hemianopic subjects with visual epileptic seizures in the blind field
and found, from the involved occipital regions, higher amplitude late
components of visual-evoked responses. Similarly, Bacia and Reid described
an increase in amplitude of somatosensory-evoked potentials on the side of

the epileptogenic focus in patients with focal epilepsy. They did not elicit
altered responses in patients with “centrencephalie” epilepsy, with a
prolonged high amplitude after discharge phenomenon. Gastaut and Regis
found the greatest changes in photosensitive generalized epileptics, with

markedly increased secondary components (especially wave V) being evoked,
correlated with the degree of photic sensitivity and seizure frequency. In

general, similar findings were reported by Morocutti and Sommer-Smith,
Hishikawa et al., and Green. The enhancement of the secondary component of

the evoked response is thought to be due to the related phenomena of
neuronal facilitation and recruitment at subcortical and cortical levels,
greater postinhibitory rebound, and hypersynchronization of neuronal
activity in cortical areas associated with epileptogenic activity.
Visual-evoked responses have been studied during physiological sleep
in “centrencephalie” epileptics. During the slow wave (first and second
phases), the responses are similar to those in the waking state with greater
amplitude of later components. In the paradoxical or REM sleep the responses

show less reactivity and late waves of longer duration and later peaking in
amplitude.
Rodin et al. investigated visual-evoked potentials during epileptic
discharges characterized as “petit-mal status,” classical petit mal seizure, and
tonic seizure with unresponsiveness. Evoked responses were “suggestively
present” in three subjects during grand-mal seizure discharges. The evoked

potentials were present in relatively unchanged fashion during petit-mal
seizure induced by bemigride activation. At times “some change in latencies”

during seizure activity was reported, but a quantitative analysis of these data
was not given. During grand-mal-seizure activity in man the elements of
evoked visual response were distinguishable during tonic and clonic phases,
but not clearly in the immediate postictal phase; this latter deficit was related
to hypoxia. These investigators also showed that photic responses could be
evoked unchanged from cat cerebral cortex during seizure discharges
produced by bemigride administration. The evoked responses could be

elicited immediately postictally in these experiments. The animals were
receiving artificial respiration and, therefore, the factor of hypoxia probably
did not play the apparent significant role that it did with humans. The authors
emphasized the importance of the elicitation of evoked responses during the
clonic portions of seizure activity, and suggested that a process of generalized

inhibition probably was not playing a significant role during such an epileptic
phase.
Mirsky and Tecce have conducted more elaborate investigations of
visual-evoked potentials during electroencephalographic spike- and-wave
activity in man. They demonstrated that the enhancement of the voltage of
the evoked potential was least evident from the parietal-occipital region and
more prominent from the anterior region, an effect which seemed to mirror
the distribution of voltages of the spike-wave discharge itself, which is

maximal in the frontal and less pronounced in the posterior region. Also, the
form of the average evoked potential appeared to be influenced by the
particular part of the spike-wave complex within which the stimulus was
administered. However, the nature of these changes is not clear. These
investigators also studied visual-evoked potentials during spike-wave

discharges produced by the administration of chlorambucil to monkeys. This
substance produced epileptiform activity thought to be similar to that

associated with petit-mal absence in man. In these experiments, visual-
evoked potentials were recorded during the spike-wave discharges; however
there was an apparent reduction in amplitude of the potentials from areas
associated with visual perception in the monkey including optic nerve and
chiasm, lateral geniculate, and occipital cortex. The reduction in evoked
potential amplitude was absent from regions usually not associated with
visual functions, such as the midline thalamus, frontal cortex, and pons. In
fact, there was probably an enhancement of the potential from these regions.
These results suggested to Mirsky and Tecce that “if the size of the evoked
potential reflects the amount of sensory information being transmitted, then
there is actually less visual input (as seen in visually related structures)
during spike and wave activity.” The interpretation of the enhancement, if it
be such, in nonvisual areas is problematical: “It may reflect differential
inhibitory and/or disinhibitory effects during spike and wave seizure activity
or some effect which serves to compensate for reduced information flow in

the primary receptor.” The other question suggested by this work is related to
the influence on the evoked visual potential of the specific period in the
development in the spike-and-wave burst into which the stimulus falls. These
authors indicate that there are behavioral data to suggest that the period just
prior to the appearance of the epileptiform burst is deleterious to
performance in any continuous-performance test and that absence-seizure

phenomenon may antedate the appearance of the paroxysmal burst in the
electroencephalogram.
Focal or Partial Seizures
Focal or partial seizures are characterized by manifestations indicating
involvement of a specific region of brain, and therefore usually represent an

acquired epilepsy. Rapid secondary generalization of seizure may develop
from a focus, but more usually the attack remains limited. Although any
region of cortex or subcortex may develop excitatory seizure activity, certain

regions are more frequently involved. Total loss of consciousness is
uncommon, but usually there is some altered conscious awareness with
varying degrees of amnesia for the events of the seizure. This is particularly
true when portions of the limbic system (i.e., hippocampus and amygdala)
and associated diencephalic structures are involved in seizure production.
The EEG concomitants of focal seizures including the psychomotor-
temporal-limbic variety are characterized by discharges of spikes, complexes,
and slow waves localized from the particular region involved in at least 75
percent of instances. Frequently, however, the discharges may be bilateral

and asynchronous, representing transmission and diffusion of the focal
abnormalities. This is especially true in the EEGs of children with focal

seizures. Also, at times, deeply situated lesions produce only minimal or no
significant scalp-recorded electroencephalographic abnormality. In adults,

recording during sleep may evoke focal discharges, especially from patients
with temporal-lobe limbic seizures.
Focal motor seizures are produced by lesions in any of the motor regions
of the brain, especially the motor (pre-RoIandic) cortex. The classic
Jacksonian motor seizure begins as a repetitive movement of a distal portion
of an extremity, such as fingers or toes, and then spreads by a march of clonic
contraction up the extremity toward the trunk. Consciousness seldom is
altered unless spread occurs contra-laterally. Focal motor seizures may affect
speech production with even an arrest of speech.
Focal sensory seizures may be Jacksonian with lesions in the sensory
(post-Rolandic) cortex producing a march of abnormal sensations, such as
numbness and tingling, spreading up an extremity. Seizures derived from
other sensory and receptive analyzing areas contain more complex visual,
auditory, olfactory, gustatory, and vertiginous components in varying degrees
of organization (see below).
Autonomic seizures are produced from cerebral foci associated with
autonomic functional representation, such as deep temporal-limbic or
diencephalic-hypothalamic. Many of the symptoms are associated with other
focal or generalized seizures, but, especially in children, they may exist more
or less by themselves as paroxysms of abdominal pain, sweating, piloerection,
incontinence, salivation, and fever.
Psychomotor-temporal-lobe (limbic) seizures represent the most
prominent and common form of focal or partial epilepsy. The temporal lobe
and its deeper nuclear masses, the amygdala and hippocampus and their
associated limbic structures, as indicated previously, are particularly
vulnerable to many pathological processes from the perinatal period onwards
throughout life. Such seizures may represent at least 25 percent of all seizures
in childhood and well over 50 percent in adult life, often coexisting with
grand-mal seizures. In over 60 percent of cases a definite structural lesion
may be found, secondary to trauma, encephalitis, ischemia, hypoxia, or tumor

(vascular malformation, hamartoma, glioma). The latter may be so small as to
escape detection by neurodiagnostic radiological methods and may only be
found within a temporal lobe resected for intractable incapacitating seizures.
Even when focal frontal lesions or diffuse cerebral disease are present, for
example, it is likely that clinical manifestations are evoked by propagation of
the discharge through temporal-limbic structures."
The most simple, but relatively rare, type of temporal-lobe seizure is
manifest by a paroxysmal dysphasic speech disturbance when the dominant
lobe is involved. This is usually an inability to form speech components, but

may be experienced as a blocking of the ideation necessary to produce
speech. It has been associated with visual hallucinations.
The clinical manifestations of psychomotor-temporal-limbic seizures
are characterized by an initial aura most frequently consisting of anxiety and
visceral symptoms, especially a peculiar epigastric sensation welling up into
the throat. (See references 8, 30, 31, 45, 51, 63, 93, 118, and 171). This is
followed by an alteration—not a loss—of consciousness, associated with
many varied, complex mental states and automatic somatic and autonomic
motor behavior. These phenomena are associated with at least a partial
amnesia, particularly for automatisms. Recollection of sensory experiences of
an aura, or of certain perceptual distortions early during the seizure, may be
obtained.
During the seizure itself, there is often arrest or suspension of ongoing
activity at first, then simple movements such as lip-smacking, chewing,
swallowing, sucking, and aimless motions of the arms and legs. These are
followed by repetitive stereotyped automatisms of varying complexity and

involving partially purposeful or inappropriate and bizarre behavior. The
latter can be associated with the environment and occasionally influenced by
psychological factors related to unresolved conflicts. For example, one of our

patients recited the “Apostles Creed” during his seizure. The activities in this
phase of the seizure may merge into normal behavior.
The occurrence of olfactory hallucinations— usually unpleasant—

associated with lesions of the mesial portions of the temporal lobe, the uncus,
was called “uncinate” seizure by Jackson, who also described the “dreamy”
state of the patient during the seizure, occasionally prolonged postictally. He
also reports the complex case of a physician with a temporal-lobe lesion who
was, however, capable of organized, appropriate activity, i.e., examination of a
patient, diagnosis, and prescription, with no recollection of these activities.
In children with this type of seizure there is emphasis on visceral
manifestations with expressions of hunger, nausea, retching, vomiting, and
abdominal pain. Spitting automatism is an unusual expression of temporal-

limbic seizure. Epileptic laughter or gelastic epilepsy may be part of this
complex.
Destructive, aggressive behavior occasionally occurs, but is not usually
purposeful (See references 31, 34, 43, 147, 157, and 164). The possibility of
paroxysmal, ictal violence leading to homicide is a problematic matter still
under intensive investigation. The implication of actual temporal-lobe seizure
in a specific directed violent attack remains difficult to prove.
Affective disturbances, particularly expressions of fear, anger, and
depression may be present ictally. Occasionally, prolonged fuguelike states

with running or wandering about may last many minutes. A fugue of longer
duration with the patient moving some distance and with amnesia for the
experience is more likely a postictal automatism.
During many seizures of this type, patients are involved in experiential
hallucinations, both visceral and auditory, as well as interpretive illusions
involving their own bodies or the immediate environment (i.e., micropsia,

macropsia). These symptoms are frequently associated with ideational
blocking and forced thinking. Common symptoms are the peculiar
experiences of false familiarity with places and people (deja vu), thoughts
(deja pen-see), and voices (deja entendu).
Ictal Perceptual Disturbances in Limbic Epilepsy
Ever since the fundamental descriptions of Jackson and Gowers the

occurrence of perceptual disturbances during epileptic seizures has been
studied particularly in patients with psychomotor-psychosensory seizure
complex originating from the temporal lobes or limbic system as listed in

Table 13-1. There have been many clinical investigations of these ictal
perceptual phenomena, with striking instances of both correlation and
noncorrelation with either focal or generalized electroencephalographic

discharges. However, it is well known that scalp electroencephalographic
recordings may give only incomplete or occasionally no reflection at all of

abnormal discharge activity present in deep cerebral nuclear structures.
Table 13-1. Perceptual Disorders in Limbic Epilepsy
SOMATIC VISCERAL
Olfactory Gastric, epigastric
Visual nausea
illusions hunger
deja vu thirst
hallucinations Abdominal
Auditory Pharyngeal
illusions Precordial
Respiratory
deja entendu
Genital, urinary
hallucinations
Vasomotor
Vestibular
vertigo
movement
loss of equilibrium
Gustatory
Somesthetic sensations of
face (nose, mouth)
half of body
extremities
To circumvent this problem, Penfield and his group in many thorough
and sustained investigations, have utilized electrical stimulation of temporal-
lobe structures in conscious patients to reproduce the psychological
disturbances experienced ictally. Similar methods and results have been

described by others. Penfield has classified the disordered perceptual
phenomena as follows:
1. Psychical hallucinations or experiential seizures: the recall of past
experiences in detail, with all the imagery that fell within the patient’s
attention at the time.
2. Psychical illusions: misrepresentations or altered interpretations of

present experience, better called illusions of comparative interpretation or
interpretive illusions. These are quite common, appearing in at least one third
of the patients studied, either spontaneously as part of the seizure or as a
result of temporal-lobe stimulation. During the illusory experience there is no

depersonalization or loss of identity; although a voice may sound remote or a
room may appear distorted and unfamiliar, the patient is usually able to
distinguish reality from unreality.
The perceptual illusions have been classified further as follows: (1)

auditory illusions, with sounds seeming louder or clearer, fainter or more
distant, nearer or farther; (2) visual illusions, with objects appearing clearer
or blurred, nearer or farther, larger or smaller, fatter or thinner, and so forth;

and (3) illusions of recognition, the present experience seeming familiar,
strange, altered and unreal. This includes the experience of the deja-vu
phenomenon. Less common illusions of perception are those of an increased
awareness of surroundings, illusions of alteration and speed of movement
and vestibular-visual disturbances in which objects appear tilted, along with
vertiginous sensations.
Penfield and his group found that auditory illusions could be produced
by cortical temporal-lobe stimulations bilaterally, but visual illusions mainly
from stimulations of the minor hemisphere. The latter finding may be
correlated with a number of psychological studies which were able to show

evidence of impaired eye-hand coordination, with difficulties in such tests as
trail making and picture completion, particularly in cases with epileptic
dysfunction of the nondominant temporal lobe.
Peculiar illusions of familiarity or of strangeness of the environment
also are frequent in these patients, and are predominantly associated with
epileptic discharge or electrical stimulation from the minor hemisphere.
Distortions of the body image involve experiences of feeling disconnected,

fragmented, malformed, or incomplete. A sensation of fear also is frequently
associated with perceptions of peculiar bodily sensations involving thoracic
and abdominal structures. Often feelings of lonesomeness, sorrow, absurdity,

and disgust have been recounted, but it is remarkable that pleasant
sensations are extremely rare.
In general, it is felt by these workers that the temporal-lobe functions
involved are largely devoted to comparative interpretations of perceptions of
the present environment and the analysis of the components of the different
sensory perceptions, comparing them with previous experiences; these
functions of analysis and comparison then transmit the experience into
consciousness of the present and immediate significance. These functions
become altered during states of seizure, producing the perceptual

disturbances as experienced by the patient. Penfield has used the term
“interpretive cortex” as applied to these regions of temporal lobe.
The disturbed perceptions in experiential hallucinations derived from
temporal-lobe epileptic activity occur also in at least 10 percent of patients.
These are similar to “flashback” phenomena which are past experiences and
happenings incorporated into the patient’s seizure pattern. They are more
usually produced by stimulation of the involved cortex and only relatively
infrequently are recalled otherwise by the subject. The phenomenon varies

from fragmentary to extensive elaboration of various sights, sounds, and
other perceptual experiences along with accompanying emotions, and the
patient usually recognizes these as coming from his past. Again, these states
appear almost twice as frequently in association with lesions of the

nondominant temporal lobe as compared with the dominant; auditory
experiences are about half as common as visual. Most such responses have
been produced by stimulations of the lateral and superior surfaces of the first
temporal convolution, and some can be produced by stimulations of the
medial border of the hippocampal gyrus. The hallucinations involving somatic
sensory perceptions are often associated with epigastric and other general
visceral sensations and it is not unusual for some patients to have an abortive
attack consisting of visceral experience alone. In many cases there is an

association with sensory or psychic precipitation as a form of reflex epilepsy.
For example, attacks beginning with hand tingling may in some instances be
precipitated by touching the hand, and certain attacks with visual

hallucinations by utilizing light stimuli. There may be a lower threshold and a
facilitation for these phenomenon in epileptogenic cortex involving these
functions.
The effects of seizure activity on perceptual functions and memory
processes reach profound complexities in relation to the temporal-lobe-

limbic epilepsies. It does seem likely that abnormal bioelectrical excitatory
states developing in and propagating through limbic-system structures can
interfere with perceptual functions of patients during overt clinical seizure,

but also in apparently interseizure states (see below) with no overt seizure
actually observable or experienced (i.e., subictal excitation).
Cortical sensory-evoked potentials during experimental limbic seizures

have been studied. Flynn et al, reporting a series of experiments on the
performance and acquisition of a conditioned avoidance response during

hippocampal after-discharge in cats, noted, in passing, that the potentials
evoked by the clicks which preceded the shock continued to arrive at the
cortex during the seizure. Experiments carried out by Prichard and Glaser
utilized auditory click and visual flash stimuli evoking cortical potentials in
cats, unanesthetized and with chronically implanted electrodes, during sleep,

wakefulness, and bilateral limbic seizures. The seizures were induced by
stimulation unilaterally across amygdala and hippocampus, which produced
propagated bilateral seizure activity. The evoked cortical potentials to both
auditory and visual stimuli during such seizures were of normal configuration
and amplitude and were undistinguishable from those recorded during the
waking state. There were no significant changes in the evoked responses even
during marked behavioral limbic seizures characterized by behavioral

changes in the animal which included alterations in posture, facial twitching,
pupillary dilatation, drooling, and some vocalization. There were no
differences either behaviorally or with regard to the evoked potentials
whether stimulation was begun with the animals awake or asleep. These
results indicated that during widespread limbic seizures the auditory and
visual systems were in a functional state, at least with regard to the pathways
generating the evoked potential to these sensory stimuli, similar to that
present during wakefulness. The findings are consistent with clinical

observations that some patients with psychomotor epilepsy can perform
certain complex integrated acts involving perception during their seizures
(even though the perceptions may be distorted), and with the studies of Flynn
et al. that cats could perform a conditioned leg withdrawal after a training
period in which the conditioned stimulus was paired with an unconditioned
stimulus only during hippocampal after-discharge. Further investigation, with
patients in a clinical setting, is necessary in this area.
Thus, it does seem clear that under certain conditions sensory

information presented to the brain only during limbic seizures can influence
both immediate and subsequent behavior, and that such seizures need not
disturb the occurrence in the cortex of the usual configuration of potentials
evoked by auditory and visual stimuli. On the other hand, the fact that
psychomotor epileptics are almost always at least partially amnesic for their
seizures implies a defect of storage, if not of actual reception of sensory
information, and the performance of certain previously conditioned
responses actually may be disrupted during limbic seizures. All these clinical
and experimental observations do present the consideration of a boundary

between what a brain can do and what it cannot do during seizure discharge
occurring in the involved cerebral structures, such as those regarded to be

within “limbic,” “centrencephalie,” or other epileptogenic aggregates. The
actual anatomical and physiological substrates finally responsible for the
perceptual distortions are less clear. The more precise definition of these
boundaries in both electrophysiological and behavioral terms, along with the
correlation with the nature and extent of seizure activity, are among the
avenues to a clearer understanding of epileptic processes in man.
The Interseizure State
The intellectual performance and behavior of a patient with epilepsy

between obvious clinical attacks, whatever the type, characterize the
interseizure or interictal state. (See references 12, 25, 27, 32, 37, 42, 52, 58,
65, 68, 7 1 , 84, 95, 96, 1 17 , 12 1 -12 3 , and 154). Generalizations are
difficult, but since the etiology is specific in up to 25 percent of cases, certain
points may be made. The interseizure disorder in a patient with a progressive
degenerative cerebral disease, encephalitis, or an expanding brain tumor who
develops changes in behavior, personality and intellectual-cognitive

functioning is probably not due to any seizure activity but to the underlying
brain disease. This applies as well to the child with extensive cerebral damage
or malformation.
However, the larger group consists of patients with seizures and an
otherwise presumably normal functioning brain at onset. A major question,

then, concerns the potential influence of the recurrent seizure state (clinical
and subclinical) upon total brain functioning. In the past, much attention was
paid to the possibility of a specific personality distortion in epileptic patients,
stated to be manifested by excessive irritability, arrogance, paranoid ideation,

religiosity, and often social withdrawal. This led to the persistence of
inappropriate restrictive actions by society and to general stigmatization.
However, the severe emotional problems and disturbances in the patients
have been found to develop most often as a reaction to such restrictions— to
the presence of an uncontrollable, overwhelming seizure disorder, and also,

at times even more common, intrafamilial denigration. Severely neurotic,
maladjusted behavior then developed into the so-called “epileptic
personality,” which is just a collection of secondary reactive psychological
phenomena. In Taylor’s sample of 100 patients with temporal lobe epilepsy,

only thirteen were considered psychiatrically normal; thirty were diagnosed
“neurotic;” forty-eight “psychopathic” (e.g., aggressive, immature and
inadequate, paranoid, antisocial, cyclothymic, schizoid, or sexual

deviationist); sixteen “psychotic” (with eight of “schizophreniform psychosis,”
five with paranoid-hallucinatory psychosis, and one each with abrupt onset
catatonic psychosis, “organic” psychosis, or simple schizophrenia). Two
children were called “psychotic.” Other patients were described as showing

psychomotor retardation in depressive psychosis. In twelve cases two
diagnoses were made. Five patients had an “epileptic personality,” in one

instance prior to onset of florid psychosis. Thus, practically all types of mental
disorders may accompany epilepsy. The specific relationships between the

two conditions require detailed psychiatric analysis by careful psychological
testing, especially of cognitive neuropsychological components. These
evaluations have practical therapeutic significance, since increasing
psychological difficulties often lead to increased seizure activity more difficult
to control. Yet, upon reviewing large populations of epileptic patients, one
finds that most do have, or are capable of, normal behavior and intellectual
functions, and can develop controlled personality characteristics which can
lead to appropriate, effective adjustments in society. History and the
literature is replete with descriptions of such individuals contributing to our
civilization in all walks of life.
A significant number of patients with frequent recurrent generalized
seizures, especially status epilepticus and excessive numbers of absences, and
particularly those with psychomotor-temporal-limbic seizures, may develop
disturbances of cognitive intellectual functions, including memory and
learning, and, at times interictal severe behavioral disorders and psychotic
states (See references 12, 14, 18, 20, 24, 27, 32, 37, 52, 54, 62, 68, 77, 87, 117,
122, 128, 137, 161, and 172). The actual definitive role of the seizure disorder
itself and its potential specificity in relation to these developments is difficult
to analyze. The effects on mental function of prolonged administration of

anticonvulsant drugs, and their resulting folate deficiency remain to be
clarified (See references 15, 16, 57, 96, 133, and 137). In many patients,
secondary social and psychological factors assume primary importance with

the production of withdrawal, depression, neurotic symptoms and apparent
impairment of intellectual performance of varying severity. Severe
hyperkinetic states may develop in epileptic children.
As described above, frequent absence attacks may interfere with tasks

requiring repetition and which may be involved in learning and memory
processing. This is unusual in most children with petit-mal seizures; in
general, they have no significant intellectual difficulties or personality

disturbance.
Certain patients with frequent grand-mal and/or psychomotor-
temporal-lobe seizures may develop a slowly progressive intellectual

disturbance. How often this occurs is not yet determined, nor is the general
distribution of these difficulties known. In some instances the chronic effects
of drugs such as phenobarbital and diphenylhydantoin may be important. In

clinical experience these changes in overall brain functioning may be quite
subtle in the early years of the epileptic disorder in a particular patient, and
would be most recognizable in individuals of high intellectual attainment.
There is increasing evidence that progressive damage in, or disturbed

function of, certain susceptible brain areas, particularly in the deep temporal
regions, occurs in association with poor seizure control (and perhaps
increasing dosages of medication) over a period of several years (i.e.,

“epileptogenic encephalopathy”). The mechanism of this process is not clear;
a concept of “consumptive hypoxia” of overactive cells leading to neuronal

cell loss has been invoked. In these patients, appropriate neuropsychological
tests reveal progressive impairment of concentration and attention, memory
defects, word finding distortions and subtle losses in ability to associate and
to track patterns (i.e., perceptual disorders). However, it must be emphasized
that the majority of patients with epileptic seizures under adequate control
escape these difficulties and retain normal intellectual function.
Neuropsychological Testing in Epilepsy
The effects of epileptic activity, both in the ictal and interictal states, on
intellectual performance, learning and memory, have not yet been clearly
elucidated (See references 18, 21, 24, 33, 65, 71, 87, 93, 100, 103, 128, 144,
145, 153, and 172). Perhaps more important to the patient is the fact that
anticonvulsant drugs still are administered over a long period of time without
clear knowledge of effects on such functions. Most studies thus far have used
a standard intelligence test such as the WAIS (Wechsler Adult Intelligence
Scale), to provide for some measure of mental status, together with the
Minnesota Multiphasic Inventory (MMPI), or, in earlier years, the Rorschach
test, as an estimate of personality traits. These tests of relatively random

populations of patients have demonstrated that there is a tendency for the
distribution of simple scores, especially in clinic groups, to be skewed
towards the lower end of the scale. Some authors have shown a discrepancy
between verbal and performance IQ figures, and have attributed the finding
to “organicity.” A few longitudinal studies indicate that this finding may be
true only for the patient at that particular time of testing. There is a lack of
good controlled testing, with age, sex, seizure history and frequency,
anticonvulsant drug levels and types, etc., taken into account.
More specific neuropsychological testing, using the more subtle

techniques devised for the assessment of localized brain damage, can aid
understanding of the epileptic patient at two levels. The first is a knowledge
of the general intellectual level, specific impairment associated with focal
dysfunction, learning and memory difficulties—often consequences of poor

attention and concentration —which may give invaluable help in vocational
guidance and specialized teaching. The epileptic is often an “underachiever,”
since much school time may be missed and social factors make job finding
difficult. It also can be important to find out how anticonvulsant drug therapy
is influencing mentation, especially since many such drugs have a sedative
effect. Thus, Cereghino and Penry note that brain damage may make the
patient susceptible to “mild depression and impairment of performance
secondary to drug administration (that) may go unnoticed.” One hopes that
neuropsychological tests not only are able to “notice” such impairments, but
also help balance the effects of maximum seizure control against possible
dulling of intellect due to drug effects, by reassessments at different doses of
the drugs. The now available sophisticated measures of anticonvulsant blood
levels may not be relevant unless an overall measure, at the same level of
sophistication, of the efficacy of the drug can be made. There has been but one
such controlled (but acute) study relating impairment in perceptual-motor
behavior distortion to blood phenobarbital level; a detailed study of chronic

effects needs to be performed with this and other drugs such as
diphenylhydantoin.
The other level at which neuropsychological testing can function has
been developed within the last thirty years. The neuropsychologist is
concerned with the relationship between psychological function and cerebral

structure. The effects on behaviour of localized lesions in the cerebrum have
been studied extensively, in the hope that this will lead to a better
understanding of the functions of these areas. The interpretation of these

studies is always subject to the limitations imposed by looking at a
malfunctioning system in order to understand the normal. However, any
theory of brain function must be able to account for changes observed during
pathological behaviour. Thus, the closer study of psychological function in the
epileptic—especially with focal seizures—may lead to a better idea of how
the brain functions.
A clearer idea of the effects of repeated focal and generalised seizures
on the specific areas involved, as well as on the ability of other areas of the
brain to compensate, may be found. How far does such interruption of normal
function give rise to permanent malfunction? How much compensation takes
place in such a situation? To what extent does a faulty input (perceptual
disorders in all modalities, often interrupted by ictal behaviour) give rise to
faulty output and inappropriate responses, seen as personality disturbances?

Does the clue to abnormal behaviour lie in the study, in particular, of
temporal-lobe or limbic epilepsy? Do changes in EEG activity, such as spike-
wave discharges, correlate with changes in mental activity? Does good seizure
control prevent intellectual deterioration, as has been suggested in some

studies (see above), or is some other variable more important?
The solution to these and many other problems may be found in part by
the application of neuropsychological measurement in which specific tests for
focal dysfunctions, using knowledge acquired through the study of localized

cerebral lesions, may lead to a better understanding of brain function, and the
means to achieve better treatment of the epileptic. A brief comment
concerning these tests follows. As has been noted previously,-in most studies
in which the psychological aspects of epilepsy have been commented upon,
the Wechsler Adult Intelligent Scale (WAIS) and Wechsler Memory Scale have
been used. Neither of these two tests really gives a good indication of more
subtle disturbances in brain function. The WAIS is a battery of tests in which

two IQ scores are obtained, one verbal and one performance. A simple
statement of these two scores, or one of the “full scale IQ” which is a
combination of the two, may obscure specific deficits. Thus, individually
lower scores on one of the subtests may show only in the overall figure,
without making it clear where the lower figure arose. Memory and
concentration difficulties may lower some scores, particularly on arithmetic

and digit span, not necessarily a purely verbal loss. Likewise, some of the tests
on the performance scale (which ostensibly measures nonverbal,
nondominant-hemisphere abilities) are not purely nonverbal or not purely

performance verbal, thus rendering the distinction between the two IQ scores
less significant. There is no valid reason why a lower score on the
performance scale should mean “organicity” as has been stated by some
authors. The WAIS has two “hold” tests, vocabulary and picture completion,
from which an estimate of deterioration can be computed. But the bluntness
of the total scores as instruments for measuring specific deficits may be the
reason for the discrepant findings obtained with the use of the WAIS to
distinguish groups of epileptics from each other and from control groups. It is
not a test battery which enables one to show objectively, that which has been
noted clinically.
Attempts to measure brain damage by the application of such tests have
not been very useful, since there is an underlying assumption that Lashley’s
law of mass action stands, and is mensurable. It is, however, possible to
measure some aspect of intelligence commensurate with Spearman’s g factor.
The discrepancy between scores on a standardized vocabulary test (such as
the WAIS or the Mill Hill), and the score on Raven’s matrices, may give a good
basic idea of dementia. Vocabulary tests reflect acquired information, and are
held to be good indicators, together with education and job history, of the
level which an individual can attain. Raven’s matrices2 are held to measure a
subject’s ability to “develop a systematic method of reasoning,” not subject to
previous training, cultural background, etc. Such a test can provide a useful
baseline from which specific difficulties can be assessed, and some idea of the
degree of dementia can also be found.
Memory and Temporal-Lobe Epilepsy
It has been shown repeatedly that the temporal lobe and related
structures are involved in memory (See references 13, 26, 28, 105, 146, and
169). Not only has it been shown that bitemporal lobectomy produces a dense
amnesia, both retrograde and anterograde (as in the well-known case of H.M.)
but much attention has been given to laterality effects. Thus, anterior
lobectomy in the dominant hemisphere for speech, causes a lasting
impairment in memory for verbal material. This is independent of whether
the presentation be auditory or visual, and also of the recall technique used.
Removal of the nondominant hemisphere, or damage to it, gives an
impairment in memory for visual material, such as places, faces, nonsense
designs, and music, i.e., material that is not easily coded verbally. A double
dissociation effect between visual perception and visual memory has also
been demonstrated in the nondominant hemisphere. Apart from simple free
recall experiments using verbal and nonverbal material, more complex

paradigms using learning also show laterality effects. Left-temporal
lobectomized patients show a deficit on Hebbs Digit Sequence task, right-
temporal lobectomized patients do not.
Experimental psychologists have also studied the various components
of memory, three of which are now generally distinguished: (l) immediate or

iconic memory having very limited capacity and a rapid decay of the stored
material of about one second; (2) short-term memory (STM) or primary
memory, having a trace of slightly longer but still limited duration (20-30
sec.) and with a slightly larger capacity; and (3) long-term memory (LTM) or
secondary memory, in which a stable trace or engram exists and may remain
permanently. Evidence exists that the anatomical localization of these

memory systems may be different. Thus the amnesic syndrome, characterized
by severe LTM loss in the presence of intact immediate and STM and intellect,
is thought to be a concomitant of bilateral lesions of the diencephalon,
thalamus, and hippocampus structures closely related to the temporal lobe. A

situation in which STM, particularly for auditorally presented material, is
grossly impaired in the presence of intact LTM has been described. The
critical lesion is thought to be in the dominant parietal lobe, in the region of
the supra-marginal and angular gyri.
It thus is clear that the temporal lobes are important to the proper
functioning of memory in man, as shown by a fairly extensive literature
concerning subjects with brain lesions. It is, therefore, surprising that the
problem of memory impairment in patients with epilepsy, especially
temporal-lobe epilepsy, has not yet been analyzed in the same depth, even
given the evidence that lack of any structural damage to the temporal area is
not always evident. Milner has pointed out that care must be taken to
distinguish between impairment of memory and impairment of attention or
vigilance. Thus “absence” in petit mal may be interpreted later as producing
memory loss, and generalised intellectual impairment may appear to the

patient as memory loss. Given that such situations exist, there remains a need
to study the memory problems that may be associated with epilepsy.
Examples of dense amnesia seen after bitemporal lobectomy for epilepsy

(H.M.), or in one case after right-temporal lobectomy have been studied. The
episodes of deja vu in temporal-lobe epilepsy have been interpreted as
abnormal activity in the temporal lobe, giving rise to a false sense of memory,
analogous, perhaps, to Penfield’s stimulation studies.
There have been studies of memory impairment in epilepsy, and many

workers have sought to find both the differentially affected temporal-lobe
epileptic, and the predicted laterality effects. Thus, Horowitz and Cohen in a
follow-up study of patients after surgery for temporal-lobe epilepsy, did not
find any consistent memory impairment (using the Wechsler memory scale
and Benton visual retention test, amongst other general tests of intellectual
performance such as the WAIS). They do not accept the view that
psychologists are able to demonstrate laterality effects, and argue that
temporal lobectomy merely leads to impairment of “organization.”
Serafetmides and Falconer studied thirty-four patients with right
anterior temporal-lobe ablations and showed that only two had some brief
postoperative memory impairment; six had persistent memory deficits, but
the authors state that “the type of memory deficit did not correlate with the
more formal psychometric test results.” They suggest that these six subjects
must have had bilateral temporal-lobe dysfunction. Meyer studied similar
patients and found that nondominant lobectomies produced no change, and
that dominant lobectomies produced auditory verbal learning difficulties.

Many studies have made comparisons between various types of seizure
patients. Guerrant et al. found no overall significant differences in any of their

groups of grand mal, petit mal and psychomotor (temporal-lobe) epileptics,
with respect to memory functioning, using the memory span for objects and
the Wechsler memory scale.
Mirsky, Primac et al. found no significant group differences on memory
tests between subjects with temporal-lobe epilepsy (TLE) of a focal and
nonfocal nature. Scott, Moffett et al. tested subjects with and without epilepsy,
matched for age and IQ and found no differences in their performance on
nonverbal tests in three modalities. Quadfasel and Pruyser predicted a

greater impairment in verbal skills and some memory difficulty in patients
with TLE, and Fedio and Mirsky and Dennerll demonstrated some laterality
effects in TLE patients.
Thus there is some confusion as to the precise nature of the memory
impairments in the epileptic patients. Memory tests have not differentiated
adequately between STM (short term memory) and LTM (long term memory)
components; indeed, there is little indication that very remote memory has
been tested at all. Although some studies have considered laterality effects,
more subtle tests have not been used. Thus, the use of tests of nonverbal
memory cannot be described as such, unless it is clear that no verbal labels
can be applied to the stimulus to be remembered, at least during the time of

presentation to the subject. Horowitz is of the opinion that no gross
differences between right and left foci in the temporal-lobe epileptic have yet
been demonstrated. It has yet to be proved definitively that the lack of
differentiation in these studies is a result of test inefficiency, or whether

temporal-lobe disturbances in epilepsy really do produce a different type of
dysfunction from other types of lesions, where perhaps the disturbance may
be more continuous. Lack of direct information about the true origins—i.e.,
perhaps subcortical—of discharges in many patients with temporal-lobe
epilepsy adds to the difficulties.
It has been noted that there is often a discrepancy between the
observed clinical findings, the patient’s subjective impression of memory

impairment, and psychological test findings. Since memory is so vital an
element in adequate functioning, good evaluation is important. More
discriminating tests, such as have been employed in other memory studies,
may improve the evaluation of this function in epilepsy. There is also a need
for more careful control of other influences, such as anticonvulsant levels,
seizure frequency, and the overall psychological state of the patient (i.e., level
of anxiety, depression, etc.).
Interictal psychotic states can develop, especially in certain patients
with psychomotor-temporal lobe epilepsy, and may be correlated with long-
standing disturbances in intellectual function, particularly in perceptual-

cognitive areas. The overall incidence of psychosis is relatively small and
difficult to determine, yet significant; if psychotic states in epileptic patients
are considered as the starting point of any study of this problem, then it is
likely that their coincidence is not just a matter of chance (See references 14,
27, 37, 54, 121, and 152).
A fluctuating episodic behavioral and personality disorder other than
actual seizure can exist in a patient. At times an alternation between seizure
and overt psychosis can be observed, especially in patients under medication.
However, it is often difficult to distinguish an ictal or postictal psychotic
episode from an interictal state. Ever since the midnineteenth century, so-
called acute epileptic psychotic reactions have been recognized as part of
what is now regarded as the psychomotor-temporal-lobe seizure complex,

and more prolonged psychotic disturbances with schizophreniclike
manifestations have been differentiated from actual seizure in some patients.
Epileptic “furor,” fugue, twilight and depersonalization phenomena have been
described in both settings.
The electroencephalogram has aided somewhat in these considerations.
Confusional states have been found to be more common in patients with
bilateral spike-wave discharges and prolonged petit-mal seizures. More

complex psychotic disturbances of schizophreniclike qualities in patients with
psychomotor seizures have been found with unmodified EEG rhythms,

desynchronization of the EEG, “forced normalization” with disappearance of
abnormal discharges or a reinforced temporal abnormality.
The interictal psychotic states may appear early in the history of the
patient, even at the onset of seizures, but more often some years later varying
from six to 14 years. The psychotic episodes may last from one to many days.
Reactions are paranoid, depressive, confusional, and hallucinatory along with
bizarre behavior. Episodes of self-mutilation have been reported. There
usually is little or no occurrence of otherwise goal-directed destructive,
violent behavior in these patients and no indications of major withdrawal or

atavistic mechanisms. Affect is often warm and appropriate with much reality
testing, a major difference from schizophrenic psychosis occurring in other
spontaneous circumstances. Affective flattening is unusual. Catatonic
disorders appear, but are usually transitory. Religious preoccupations are

frequent, as well as related obsessional activities. Impulsive, compulsive
eating and drinking may occur. Somnambulism has been reported. In some
patients, acute disorganization of verbal productions is present along with

bizarre distortions and many somatic delusions. Pregnancy fantasies have
existed in some females. Diminished libido and sexual functions are found in
some patients with temporal-lobe epilepsy Hypersexuality is unusual. Sexual
deviation, such as fetishism, has been reported in association with temporal-

lobe epilepsy, relieved, in one instance, by temporal lobectomy.
Over half the patients have fluctuating memory disturbances with mild
to moderate impairment, difficulty in attention and concentration and
disorientation to time. Extreme confusion occasionally appears, often lasting

several hours and not associated with the usual manifestations of seizure
with motor-sensory or visceral components. Partial to complete amnesia,
often for the psychosis, suggests subclinical “seizure” activity; in some of the
cases with confusion, bilateral EEG discharges suggesting subcortical origin
may be correlated.
Psychological testing of such patients requires not only scoring, but also
observation of performance and response. There is evidence of loss of trains

of association along with word finding and tracking difficulties, vacillation of
alertness, and fluctuation in the accuracy of perceptions. Looseness of
associations without bizarre content or mode of thought is common, along
with indications of concreteness. However, there is usually no clear sign of

autism or withdrawal; many patients make continued attempts to be in
contact with reality. There are usually no signs of archaic thinking or autistic
fantasy elaboration as would be found in more typical schizophrenic subjects.
Mild to moderate memory disturbances are frequent in these patients,
with both retention and recall difficulties in both short- and longterm
memory. Mere scoring of IQ levels is not very meaningful. Many patients

express concern over problems in the clarity of their thinking and make
concerted efforts to control, restrict, and contain emotions and actions in
order to become clear, accurate, and realistic. Misperceptions and arbitrary

thought processes usually involve relatively benign, neutral content, although
themes of religiosity are frequent. A degree of word-finding difficulty is often

apparent, and distinct dysphasia is occasionally present (in over 10 percent of
Slater’s cases). Flor-Henry and others have emphasized the correlation of
dominant temporal-lobe focal involvement and schizophreniclike psychosis
in these patients. Some patients experience weakness of spatial orientation
and fluctuating motor incoordination. Difficulty in arithmetic is sometimes

present.
The paranoid elements involve projection of thoughts and feelings, but

well-organized delusions of persecution, for example, are relatively
uncommon. Indications of contamination and feelings of depersonalization
and unreality are frequent. Disturbances of body image involve feelings of
being disconnected, fragmented, malformed, awkward, or incomplete.
Most epileptic patients with interictal psychosis are found to have
psychomotor temporal-lobe seizure disorders. The classification of the
seizure disorder must be on the basis of the clinical signs, not of the EEG,
since the latter might show fluctuating bilaterality of discharge. The onset of
the psychotic reaction does not appear to be clearly related to specific

psychological triggers in many instances, but often does follow increasing
buildup of tension and anxiety. Gradual intellectual disorganization, often
subtle at first, may initiate the process. Some patients remain in an impulsive,
aggressive, unstable, obsessional state without actual psychotic break. It
should be stated that the actuality of a “true” or non-directly related

schizophrenia could develop in patients with epilepsy, but the above
described schizophrenialike phenomena are qualitatively different.
Taylor has recently emphasized that, from the clinical point of view, the
epileptic schizophrenialike psychoses emerge as a group of disorders
following largely on psychomotor-temporal-lobe epilepsies involving mainly
the left temporal lobe either alone, or as part of a more generalized seizure
disorder, emerging mainly in the second and third decades, where mesial
temporal sclerosis is an improbable pathological substrate, to which females
are more prone, but in whom half the risk to psychosis is past by the twenty-
fifth year. Of interest is the increasing evidence that a number of cases of
childhood psychosis or “autism” follow episodes of infantile epilepsy,
especially of the myoclonic spasm type.
The therapeutic implications of these considerations are yet to be fully
realized. It might be expected that a psychotic reaction associated with a
seizure disorder would regress as seizures respond to treatment. Although
this does happen, the interictal behavioral disturbance occasionally persists

and may increase as seizures are controlled. Anticonvulsant drugs are to be
used, and the administration of certain psychotropic drugs such as “alerting”
phenothiazines (i.e., flu-phenazine) might be helpful. In selected cases with

intractable seizures and well-defined focus, temporal lobectomy has
produced some improvement in “schizophrenic” symptoms, but this is

unpredictable and does not correlate well with the response of the seizures.
Clinical Evaluation of the Patient
The patient with epilepsy should receive a thorough diagnostic
evaluation in order to determine the relative significance of the possible

etiologic factors as well as precipitating circumstances. This requires
thorough history taking, physical, medical, and neurologic examinations, and
selected laboratory investigations with particular reference to blood

chemistry studies, cerebrospinal fluid analyses, and electroencephalography;
special radiologic studies may be required. The collected data may lead to the
diagnosis of either a specific medical illness associated with seizures or a
focal cerebral lesion.
History
In order to establish whether recurrent seizures are being experienced,
a careful history should contain detailed descriptive material, usually from

sources other than the patient. Eye-witness accounts are helpful. As much
recollection as possible should be obtained from the patient, particularly of
experiences of the aura or the onset of the seizure. The patterning or course
of events during and after seizure episodes should be documented with

special attention to phenomena which might be of localizing significance.
Other information of great importance with regard to treatment concerns the
circumstances under which the seizure occurs, e.g., time of day or night,
frequency of attacks, and the influence of medication, menstrual cycle,
pregnancy, food intake, sound or light stimulation, intake of alcohol, and
psychological stress. Additional indications of neurologic disturbance should
be described, e.g., headache, hemiparesis, hemisensory symptoms, dysphasia,

and visual difficulties, especially loss of acuity and hemianopsia, and vertigo.
A family history may reveal data of importance, particularly with regard

to susceptibility to seizure. In a significant number of families a history of
febrile seizure in early childhood may be obtained, as well as seizures of both
generalized and focal types extending into later life. In addition, since a
number of genetically determined cerebral disorders may be associated with
seizure as well as other neurologic abnormalities, the family history may
include phenomena other than seizures as indications of brain disorder

related to structural or metabolic abnormalities.
The general medical history is significant, since seizure may be
associated with cardiovascular disease, various blood dyscrasias, and

metabolic and endocrine disorders; for example, the history of neoplasm
anywhere in the body is important, since a focal seizure may be the first
manifestation of a cerebral metastasis.
The past medical and developmental history of the patient is of great
significance in attempting to determine etiology; information concerning
pregnancy, delivery, the neonatal period, and the developmental neurological
milestones should be obtained. The position of the child on the
developmental scale should be determined, particularly with regard to motor
and intellectual skills. Past history should also include information regarding
head injuries, reactions to immunizations, childhood diseases such as

measles, mumps, and chickenpox, and any severe illness with delirium or
coma that might be considered related to an encephalitis. A history of
exposure to toxic substances is important, as well as the possibility of drug

intake, particularly in adults suspected of taking barbiturate or tranquilizing
drugs.
A detailed survey of the patient’s social development and behavior in
and out of the family setting is relevant, including an evaluation of intellectual
performance at school and vocational performance. Attention should be paid

to alteration in any of these phases of existence in relation to seizure
occurrence, as well as between seizures, and also to possible effects of
medication on seizure incidence or behavior.
Physical and Neurological Examination
Clinical examination of patients with seizures may not reveal significant
physical or neurologic abnormality in 75 percent or more of cases. However,
thorough physical examination is necessary to establish whether a general
medical disorder is present; even examination of the skin may produce the
requisite information for diagnosis of tuberous sclerosis, neurofibromatosis,
or cerebral hemangioma. Examination of the lungs may provide the
background for consideration of metastatic tumor or abscess; evaluation of

the peripheral circulation and blood pressure may give indication of the
possibility of the various types of cerebral vascular lesions, or aid in
differential diagnosis of syncope and seizure.
The neurological examination serves two functions: (1) to give
indication of general cerebral disorder, and (2) to demonstrate whether focal
signs are present, indicative of a localized cerebral lesion. Neurological
examination at the time of or shortly after a seizure may be important, since
hemiparesis and related signs may be revealed. Psychological testing may be

useful in the assessment of general intellectual status, possible deterioration
from a previously higher level of functioning, and the possibility of focal
cerebral damage. As discussed previously, the WAIS and Wechsler Memory

Scale give a very broad idea of the patient’s functioning, but more careful
evaluation of learning, memory, and perception is needed to distinguish

subtler disturbances, as discussed above. The Rorschach and other projective
tests have been used to demonstrate both “organicity” and the epileptic
personality, but doubt has been cast on the validity of such techniques for this
purpose. Attention should be paid to the patient’s performance during these
tests as well as to the actual scores.
Laboratory Investigations
Each patient with recurrent seizures, regardless of age, should be

subjected to selected laboratory investigations at least once during the course
of his history, particularly if changes in seizure patterns or neurologic signs
develop. There are no routines, but at different age levels certain tests are
more apt to produce results leading to specific etiologic diagnosis. In addition,
certain studies are necessary for the evaluation of the general health of the
patient and in following the effects of medication which may be toxic to
various body systems. Aside from electroencephalographic abnormalities,

there are no abnormal laboratory findings characteristically associated with
the seizure process. Urinalysis is important to determine the state of kidney

functioning, which, if abnormal, may preclude the use of certain drugs or may
suggest a specific diagnosis. Similarly, a complete blood count is necessary,

particularly if a blood dyscrasis is suspected. Severe seizure states, such as
status epilepticus, may be associated with proteinuria, leukocytosis, and fever
as secondary manifestations. In certain instances, special blood chemistry
studies are important, e.g., blood sugar and glucose-tolerance test in the
diagnosis of hypoglycemia and in the evaluation of a difficult-to-control
diabetic. Determinations of serum calcium are necessary in the evaluation of
infants and young children with seizure states, since hypocalcemia may cause
generalized seizures, distinct from tetany. Evaluation of serum electrolytes
and acid-base balance is extremely important in the study of both children
and adults with metabolic encephalopathies and seizures in various disorders

of the kidney, liver, heart, and lungs. As yet, no specific patterns of electrolyte
distortion are associated with seizures, but at times variations in these can be
so correlated. Determination of serum enzymes is mainly important in

establishing the presence of general medical disorders, and serologic tests are
helpful in the diagnosis of past infectious states.
The cerebrospinal fluid is apt to be normal except in a minority with
certain neurological disease. Following severe seizures there may be a slight
increase in cerebrospinal fluid protein and white cell counts, but this is
usually transitory. In structural neurological disorders with concomitant
seizures, the protein or pressure or both may be persistently elevated and the
diagnosis is then dependent on other tests, such as contrast radiologic

studies. Chronic infection of the nervous system can be associated with
increase in white cell count in the cerebrospinal fluid, and occasionally the
presence of cerebral neoplasm may be shown by neoplastic cells in the fluid,
diagnosed by cell block and appropriate histologic examination.
Radiologic Studies
All patients should have an X ray of the skull and chest. The plain X-ray
film may show abnormal calcifications and shift of the pineal or other signs of
increased intracranial pressure. The X ray of the chest is of two-fold
importance: (1) in the evaluation of any anomalous cardiopulmonary status
in an adult or a child; and (2) to reveal possible primary tumor in an adult.
The so-called contrast radiological studies of the intracranial contents
are extremely useful diagnostic procedures, but since they have a certain
morbidity they must be selected with great care and be performed when they
can be expected to be most informative. Certainly, such procedures must be
considered when there is suspicion of a focal intracranial lesion.
If there is increased intracranial pressure, particularly if there may be a

lesion involving the posterior fossa, ventriculography may be the procedure
of choice; however, this procedure generally gives incomplete information

with regard to the subarachnoid spaces. Ordinarily, if the pressure is normal,
a fractional pneumoencephalogram gives more information with regard to a
lesion occupying space in the brain substance or distorting the ventricular or
subarachnoid system. In addition, the presence of focal brain atrophy may be

shown by differential enlargements of specific spaces such as the temporal
horns of the ventricles.
Cerebral arteriography is useful in patients with and without evidence
of increased pressure, and may give important information, particularly if
there are focal or lateralizing signs. Abnormal vascular patterns are found in
particular types of tumors, intracranial hematomas, and vascular
malformations; the location of vascular occlusions may be found by
arteriography as well. There are instances when such studies are negative but
reveal a lesion when repeated later; occasionally such tests may be
worthwhile in initial base-line investigations of a case.
The use of brain scanning with radioactive isotopes requires more
evaluation, but there is increasing regard for these procedures as a means of
determining the presence of certain types of tumors, either single or multiple,

and of vascular lesions. In some instances a negative brain scan may eliminate
the necessity, for the moment, of a contrast radiological procedure. Also, a
significantly lateralized pickup in scanning may indicate the preferred side for
an arteriogram, an indication which otherwise might not be clear from the
neurological evaluation and the EEG.
Electroencephalography
The various electroencephalographic correlates of the different types of

seizures have been described above. The EEG, however, must be regarded
only as an indicator of a certain kind of cerebral activity determined by the
recording method using electrodes upon the scalp. This is important to
realize, since the EEG from a patient with known seizures of any type might
be normal, as it is the case in a single-sample recording in 25 percent of such
patients. Depth electrode recording techniques have shown that, in some of
these instances, there may be abnormal discharges in the deeper structures

such as the amygdala and hippocampus, while the electrical activity of the
cortex shows no change. The EEG; therefore, has limited diagnostic
applications, and it must be considered only as a reflection of certain cerebral
functions to be correlated with other information obtained from physical and

neurological examinations. The electroencephalographic findings are of
varying usefulness in the diagnosis of epilepsy, depending on their nature and
the circumstances under which they are obtained.
The EEG may be utilized as an aid in the confirmation of the presence of

a seizure state, particularly if paroxysmal discharges are recorded during and
correlated with a seizure; for example, in the petit-mal absence, up to 85
percent of children have the typical 3 Hz. spike-and-wave discharges both

between and during seizures. In addition, these may be precipitated by
overventilation and light stimulation. The EEG may merely contain

generalized nonspecific slow-wave discharges, which may be considered only
as an indicator of cerebral dysfunction, but not necessarily of a definite

seizure disorder. Focal slow-wave abnormality is suggestive of a localized
structural lesion and indicates the need for further investigations. In certain
forms of focal epilepsy the EEG may show focal discharges of spikes, sharp
waves, and complex components indicative of the epileptogenic nature of the
focus. However, in some of these instances such abnormality might be
transmitted from deeper, even centrally disposed, lesions.
In most laboratories of electroencephalography the procedure includes

recordings in the waking state and during hyperventilation. Frequently,
however, attempts are made to provoke generalized and focal paroxysmal
discharges by means of sleep, sensory stimulation with light or sound, or
certain metabolic and pharmacologic adjuvants. The EEG during sleep is

useful to demonstrate focal discharges in patients with psychomotor-
temporal-lobe epilepsy. Such discharges are increased during sleep in 50-75
percent of adults. The results in children are less definitive; in 25-35 percent
of young patients the temporal activity becomes more prominent during
sleep. However, in some patients sleep tends to produce increased bilaterality
of abnormal temporal discharges. The use of sphenoidal electrodes is

occasionally helpful in lateralizing temporal-lobe discharge, particularly when
patients are being evaluated for surgery. At times barbiturate-induced fast-
wave activity is found to be less marked in the involved temporal lobe. Photic
stimulation detects patients with light-sensitive epilepsy and occasionally

evokes lateralized discharges in patients with a sensitive focus.
There have been many attempts to alter the electrical activity of the
brain in susceptible patients by inducing metabolic changes, such as
hydration, following an injection of vasopressin or the induction of
hypoglycemia with small doses of insulin. Various stimulant drugs have been
used, e.g., pentylenetetrazol and bemegride. All of these methods, particularly

the use of drugs, may precipitate paroxysmal discharges as well as clinical
seizures; the latter are usually generalized, but occasionally activation of a
focus occurs. Attempts to measure seizure discharge threshold have been
largely unsuccessful because of great variability; in addition, many otherwise

normal subjects respond to these procedures with seizure activity. For these
reasons this approach is not recommended for general use in the diagnosis of
an epileptic state. Occasionally, however, it may be desirable to view in detail

the clinical phenomena of the seizure and to determine focal components
either in the EEG or clinically. At times this can be accomplished by the
administration of a controlled dose of a seizure-producing drug.
The degree of electroencephalographic abnormality, especially in its

paroxysmal characteristics, may be regarded as an objective indicator of the
severity of a particular seizure state in a patient; this may fluctuate with the
clinical behavior of the seizure disorder. However, the use of the EEG to
follow patients with epilepsy is limited since in many instances some degree
of electroencephalographic abnormality persists even when seizures are
controlled. This occurs most often in patients with psychomotor-temporal-
lobe epilepsy and least often in children with petit-mal and myoclonic
seizures.
The implications of a diagnosis of an epileptic disorder are so significant
both medically and psychologically that the diagnosis must be positive and
specific, excluding other disturbances characterized by similar transitory

abnormalities of neurological function that are not seizures. Consciousness
may be disturbed episodically by limitations of cerebral blood flow, either
generally or locally, e.g., in instances of cerebral vascular insufficiency and
syncope of various types, particularly the vasodepressor form. Disturbances

of cerebral circulation occur frequently in older age-groups; there is usually
evidence of hypertension and cerebral arteriosclerosis. Periodic blackouts

and general confusional states may result from basilar artery insufficiency;
however, there are usually other signs of brainstem and cerebellar

dysfunction. Patients with deficient carotid circulation may have transitory
hemiparesis and hemisensory disturbances along with dysphasia.
Electroencephalographic findings of paroxysmal discharge may suggest the
presence of a seizure state; however, rhythmic discharges may be related to

lesions of vascular origin in the upper brainstem. The differential diagnosis in
these patients involves careful evaluation of the history and general medical
state of the patient; arteriographic confirmation of a vascular lesion may be
necessary.
Syncopal episodes may resemble akinetic or minor motor seizure;
actually, prolonged syncope can develop into convulsions due to the
persistence of cerebral ischemia and hypoxia. The patient with syncope

usually has some indication of disturbed vasomotor reactivity with excessive
sweating, pallor, and tachycardia. Specific precipitating factors often are
present, such as fear or other psychological upset; the confusion, headache,
and drowsiness which occur after a generalized seizure do not usually

appear. During a simple syncopal episode the EEG consists of diffuse
asynchronous slow waves without paroxysmal or focal discharges.
Various disturbances of consciousness, from confusion to coma, may be
produced by metabolic disturbances not necessarily leading to seizures.
These conditions are important in the differential diagnosis, since in specific
instances of metabolic encephalopathy seizures may be only a minor clinical

concomitant, and the overall distortion of general cerebral function may be of
major concern. These clinical abnormalities appear in hypoglycemia,
hyponatremia, kidney failure with uremia, hepatic insufficiency, and

pulmonary insufficiency (with hypoxia and hypercarbia). The EEG in these
states contains generalized, often intermittent, intermediate (4-7 Hz.) and

very slow waves (1-3 Hz.). Rhythmic components (such as the triphasic
complexes in hepatic encephalopathy) may be present, but paroxysmal
discharges are unusual unless actual seizures are occurring. Hypocalcemia, as
in hypoparathyroidism, may produce tetanic spasms throughout the somatic
musculature; occasionally these may be unilateral and suggestive of localized

seizure, but consciousness is not lost and actual clonic contractions do not
occur. However, as mentioned previously, hypocalcemia may precipitate
actual convulsive seizures. Fluctuating distortions in behavior are also
characteristic of many endocrine disorders, e.g., hypoadrenalism and hyper-

adrenalism, hypopituitarism and hyperpituitarism, and myxedema. In none of
these states are seizure disorders particularly prominent.
Certain psychogenic disorders may resemble epileptic states and be
difficult to distinguish from them. Hysterical “seizures” may occur

independently, but are occasionally seen in patients with known seizures, i.e.,
so-called liystero-epilepsy. The clinical problem in these patients is often
difficult to solve because of the interrelationships between the seizure state

and the reactive development of the psychological disturbance. The hysterical
seizure is not associated with neurological signs of reflex abnormality; the

EEG contains no paroxysmal discharges. The hysterical seizure pattern is
bizarre and not a stereotyped tonic-clonic movement sequence, and self-

injury does not occur during, or as a result of, the hysterical seizure. The
postictal states of confusion, headache, and drowsiness are absent. The
diagnosis of hysterical seizure requires careful psychiatric evaluation because
of the deep-seated and severe neurotic process involved. Similarly, certain
hysterical or psychotic fugue disturbances and dissociative reactions may
need to be distinguished from psychomotor-temporal-lobe seizures.
Treatment
The treatment of a patient with an epileptic disorder must take into

account not only the patient and his disorder, but also his family and life
situation. Much depends on the diagnostic evaluation and the etiology or
precipitating factor. This can be clearly defined where a metabolic
disturbance is obvious, e.g., in a hypoglycemic or hypocalcemic patient cured

of seizures by administering glucose or calcium. Operable cerebral tumors
represent another such situation. However, in many cases of acquired

epilepsy the cause of the seizure cannot be treated directly, and symptomatic
therapy with anticonvulsant drugs together with the total management of the
patient are necessary. This may be true even in certain cases in which the
precipitating factor is known, e.g., an anticonvulsant drug may be temporarily
necessary in hypocalcemia, since a delayed response to calcium may be
present. Seizures may continue even after surgery for a brain tumor due to
postoperative scarring or incomplete excision. Immediate specific therapy is
not always indicated in patients with acquired epilepsy. Only a limited
number of patients with posttraumatic epilepsy are amenable to surgery for a
localized meningo-cerebral scar. For these reasons, only a relatively small
number of patients with seizures do not require anticonvulsant drugs and a
general psychosocial rehabilitative program.
Medical Therapy with Anticonvulsant Drugs
Drugs commonly used in the treatment of epilepsy are listed in Table
13-2 together with recommended dosage, indications, and toxic effects.
Table 13-2. Medical Therapy in Epilepsy: Anticonvulsant Drugs
Bromides
Daily Adults: 1.0-3.0 g. (not recommended for children)

dosage
Symptoms All types of seizures, especially grand mal and psychomotor; may be
combined with hydantoins
Toxic Drowsiness, dulling, rash, psychosis; rarely used now.

effects
Celontin (methsuximide)
Dose 0.3 g.
capsule
Daily Children: 0.6 g.; adults: up to 1.5 g.
dosage
Symptoms Petit mal, psychomotor seizures, myoclonic seizures, massive spasms
Toxic Ataxia, drowsiness, rarely blood dyscrasias, anorexia

effects
Dexedrine (dextroamphetamine)
Dose 5
mg. tablet;
10 and 15
mg.
spansules
Daily Children: 5-15 mg.; adults: 15-50 mg.

dosage
Symptoms Hyperkinetic behavioral disturbances in children, narcolepsy, to counteract

sedative effects
Toxic Anorexia, irritability, sleeplessness

effects
Diamox (acetazolamide)
Dose 250 mg. tablet
Daily Children: 0.75-1.0 g.; adults: 1.0-1.5 g. Use intermittently, as an adjuvant in

dosage all types of seizures, especially those in females related to menstrual cycles;
tolerance may develop
Toxic Anorexia, acidosis, drowsiness, numbness of extremities, rare blood

effects dyscrasia
Dilantin (diphenylhydantoin)
Dose 0.03 g. and 0.1 g. capsules; 0.05 g. tablet; 0.25 g./ml. suspension; 0.1 g. in oil
capsule; 0.25 g. ampul for parenteral use
Daily Children: 0. 1-0.3 g adults: 0.3-0.6 g. Effective blood level 10-20 μg/ml.
dosage
Symptoms Grand mal, psychomotor, and focal seizures; most useful in combination
with phenobarbital or primidone
Toxic Rash, fever, gum hypertrophy, gastric distress, diplopia, ataxia, hirsutism
effects (in young females); drowsiness uncommon; lymphadenopathy, rare
megaloblastic anemia, secondary folate deficiency, “encephalopathy,”
hepatitis rare, aplastic anemia, agranulocytosis rare
Gemonil (metharbital)
Dose 0.1 g.
Daily Children: 0. 1-0.3 g.; adults: 0.3-0.6 g.

dosage
Symptoms Mainly in children with petit mal, myoclonic seizures, massive spasms,
occasionally in grand mal
Toxic Drowsiness, rash
effects
Mebaral (mephobarbital)
Dose 0.03 g., 0.1 g. tablets. Demethylated to phenobarbital.
Daily Children: 0.06-0.3 g; adults: 0.3-0.6 g.

dosage
Symptoms Grand mal, petit mal, psychomotor, focal seizures; most useful in
combination with hydantoins
Toxic Drowsiness, irritability, rash

effects
Mesantoin (methylphenylethylhydantoin)
Dose 0.1 g.
Daily Children: 0.1-0.4 g.; adults: 0.4-0.8 g.

dosage
Symptoms Grand mal, psychomotor, focal seizures
Toxic Rash, fever, drowsiness, ataxia, gum hypertrophy, (less than dilantin),
effects neutropenia, agranulocytosis, aplastic and megaloblastic anemia.
Milontin (methylphenylsuccinimide)
Dose 0.5 g. capsules; 250 mg./4 ml. suspension.

dosage
Symptoms Petit mal, myoclonic, akinetic seizures, occasionally psychomotor seizures
Toxic Nausea, dizziness, rash, hematuria (may be nephrotoxic)

effects
Mysoline (primidone)
Dose 0.25 g. tablets; 250 mg./5 ml. suspension
Daily Children: 0.25-1.0 g.; adults: 0.75-2 g. The daily dosage should be built up
dosage very slowly. Blood levels: therapeutic range 5-15 /μg/ml.
Symptoms Grand mal, psychomotor, focal seizures, occasionally petit mal; useful in
combination with Dilantin
Toxic Drowsiness, ataxia, dizziness, rash, nausea, leukopenia rare

effects
Paradione (paramethadione)
Dose 0.15-0.3 g. capsules; 0.3 g/ml. solution.
dosage
Symptoms Petit mal, myoclonic and akinetic seizures, massive spasms, occasionally
psychomotor seizures (in children); often useful in combination with
Dilantin and phenobarbital; somewhat less effective and less toxic than
Tridione
Toxic Rash, gastric distress, visual symptoms (glare, photophobia), neutropenia,

effects agranulocytosis
Peganone (ethylphenylhydantoin)
Dose 0.25-0.5 g. tablets
Daily Children: 0.5-1.5 g.; adults: 2.0-3 g.

dosage
Symptoms Grand mal, psychomotor, focal seizures
Toxic Similar to Dilantin but less severe; may be substituted for Dilantin, but is
effects generally less effective
Phenobarbital
Dose 0.015, 0.030; 0.060, and 0.1 g. tablets; 4 mg./ml. elixir. Therapeutic blood
level 10-30 /μg/ml.

dosage
Symptoms All seizure states; grand mal, petit mal, psychomotor, and other focal; most
useful in limited dosage in combination with other drugs such as Dilantin
Toxic Drowsiness, dulling, rash, fever; irritability and hyperactivity in some

effects children
Phenurone (phenacemide)

dosage
Symptoms May be effective in all types of seizures, especially focal temporal-lobe or

other psychomotor seizures; should be used only in very resistant cases
Toxic A highly toxic drug, producing liver damage, agranulocytosis, psychotic

effects reactions, and rashes
Tridione (trimethadione)
Dose 0.15 g. tablet; 0.3 g. capsule; 0.15 g./4 ml. solution

dosage
Symptoms Petit mal, myoclonic and akinetic seizures, massive spasms, occasionally
psychomotor seizures (in children); often useful in combination with
Dilantin and phenobarbital
Toxic Rash, gastric distress, visual symptoms (glare, photophobia), neutropenia,
effects agranulocytosis
Zarontin (ethosuximide)
Dose 0.25 g. capsule
Daily Children: 0.75-1.0 g.; adults: 1.5 g.

dosage
Symptoms Petit mal seizures (the drug of choice, now); use with Dilantin in mixed
seizure states
Toxic Blood dyscrasias (pancytopenia, leukopenia), dermatitis, anorexia, nausea,

effects drowsiness, dizziness, euphoria; disturbance of mental functions reported
in some patients
The following drugs may be used in the emergency treatment of status
epilepticus:
Drug Dose
Sodium phenobarbital: 0.25-0.50 g., IV
Sodium amytal: 0.25-0.50 g., IV
Paraldehyde: 3.0 -5.0 g., IV diluted in saline, or 10-20 ml. IM
Dilantin sodium: (parenteral 0.25 g., IV or IM (to 0.5 g./24 hours)

prep.)
Valium (diazepam): 10 mg., IV
More general anesthetics, such as ether, avertin, and xylocaine, have a
limited usefulness in treatment of status epilepticus. Careful nursing and
attention to fluid and electrolyte balance, airway, cardiac, and renal functions,
and temperature control are essential. Adrenocorticotrophic hormone
(ACTH) and adrenocortical steroids are used as anticonvulsants in treating
massive spasm epilepsy in infancy associated with the “hypsarhythmic”
electroencephalogram. A “ketogenic” diet may be helpful in certain children
and young adults, with intractable seizures.
The basic mechanisms of anticonvulsant drugs are not clearly
understood. Most such drugs are neuronal depressants with certain
variations in action. The hydantoin drugs have been found to reduce the
synaptic activity of posttetanic potentiation; the oxazolidine (trimethadione)
drugs decrease transmission during repetitive stimulation. Increased
stabilization of excitable neuronal membranes probably takes place by action
upon electrochemical characteristics involved in ion permeability and

membrane polarization. These stabilizing effects presumably decrease the
activity of the abnormal hyperexcitable neuronal aggregates in an
epileptogenic focus and, more importantly, generally prevent the spread of

discharge through normal neuronal circuits.
While there are many anticonvulsant drugs, none is capable of total
seizure control in all patients. However, careful selection and utilization in
each individual case often leads to optimal results. Each physician should
learn to use a number of these drugs and to recognize disturbing side effects
as early as possible. Periodic blood counts, urinalyses, and liver-function tests
are necessary during administration of many of these drugs.
The majority of the anticonvulsant drugs are administered to achieve a
desired effect and the dosage must be increased to the point of tolerance
without untoward toxic reactions. Blood levels should be followed (see Table
13-2). It is best to start with a drug of choice; however, a single drug does not
usually achieve the desired degree of control and a second may be necessary;
two drugs may be indicated initially in patients with two different types of
seizure, e.g., grand mal and petit mal. The process may require weeks of
adjustment and during this time the patient’s and family’s cooperation in
reporting effects on seizure frequency or side reactions is most important.
Frequent changing of drugs is to be avoided.
Unfortunately, there is no specific anticonvulsant drug for each type of

seizure. However, there is one major therapeutic axiom; the petit-mal
absence does require a special anticonvulsant drug, either a succinimide
(Zarontin) or an oxazolidine (trimethadione). Ethosuximide (Zarontin) is

generally the drug of choice for this seizure state. This group of drugs is not
effective in the treatment of major generalized seizures; conversely, the
hydantoins are not generally effective in petit mal. Some authors state that
the drugs effective in petit mal may worsen a generalized seizure state and
vice versa; adequate evidence for this generalization has not been reported to
date.
Generalized seizures, grand mal, and minor motor seizures are best
treated with diphenylhydantoin sodium and phenobarbital. Initially, either
drug may be administered to patients with infrequent attacks, but generally
the combination of diphenylhydantoin and phenobarbital will achieve control
of seizure in up to 85 percent of patients. Dosages should vary as indicated in
Table 13-2. The average dose of diphenylhydantoin is 0.3-0.4 g. per day,
usually administered as 0.2 g. in the morning after breakfast and 0.2 g. after
dinner. The use of diphenylhydantoin has been enhanced by the
determination of blood levels of the drug. The effective therapeutic range is
between 10 and 20 μg/100 ml. Toxic effects usually appear at levels above
this. The dosage of phenobarbital is initially 60 mg. at bedtime, with 30-mg.
increments during the day if necessary; dosage is limited by its sedative

effect.
Patients with psychomotor-temporal-lobe epilepsy are often more
difficult to control. In these instances many trials may be necessary; the best
results are to be expected with diphenylhydantoin and either phenobarbital
or primidone. Although in some clinics the latter two drugs are used together,
their sedative effects combine to make such administration difficult. Actually
a significant amount of primidone is metabolized into phenobarbital. When
employing primidone it is very important to start with doses ranging from 50

to 125 mg. per day, increasing slowly at weekly intervals to a maximum of
0.75 or 1.0 g. per day. If untoward side effects occur with diphenylhydantoin,
substitution with the less reactive ethylphenylhydantoin is sometimes
successful, although this drug has a weaker anticonvulsant effect.

Mephenytoin and phenacemide are useful in difficult cases, but must be
utilized with extreme care because of their high toxicity.
Occasionally, a paradoxical reaction to diphenylhydantoin occurs, at a
time when a high or toxic blood level is reached, or, in some instances, even at
a level regarded as nontoxic but relatively high for the particular patient. This
clinical state is characterized by a lapse of seizure control with actual increase
in seizures, worsening of the EEG with increased paroxysmal discharges and

background slow waves, and a dulling of perceptual-cognitive functions (with
poor school or work performance, for example). Occasionally, focal

neurological signs, such as hemiparesis, appear. There may be no usual
“toxic” signs of diphenylhydantoin excess such as nystagmus or ataxia. Photic

stimulation or other “alerting” stimuli may actually reduce the EEG
phenomena. The term “diphenylhydantoin encephalopathy” has been applied
to this state, but the mechanism of its production remains unclear. It is
clinically significant, and can be treated by reduction of dosage.
Disturbances of intellectual function, along with psychotic states,
reported in children treated with ethosuximide have been difficult to evaluate
in relation to the seizure process and interictal state.
Certain stimulating drugs such as the amphetamines may be useful
adjuncts in the therapy of certain patients, particularly to counteract sedative
effects of phenobarbital or primidone without interfering with anticonvulsant

action.
It is of interest that certain drugs interfere with the metabolism of
diphenylhydantoin and increase its blood levels; these include dicoumarol,

phenylbutazone, disulfiram, p-aminosalicylate, and isoniazid.
Acetazolamide is (Diamox) an important adjuvant in some patients with

any type of seizure state, since it seems to have a general effect upon
hyperexcitable cerebral neurons because of its inhibition of carbonic
anhydrase or production of an acidosis. Since tolerance develops, the drug
should be administered intermittently; it is occasionally useful, for example,

in helping to control seizures occurring prior to or during the menstrual cycle.
Under these circumstances acetazoleamide is administered for a week before
and during the menstrual period. Some patients require its administration
continually; tolerance does not develop in all patients.
The results of drug therapy are difficult to predict. With careful

attention to individual details and general patient management, the patient
with occasional generalized and psychomotor seizure can achieve effective
control of seizure frequency. In children with petit-mal absences, the results
are generally quite satisfactory. There are in each group of patients, however,
a refractory number with increasing psychological and social problems as the
years go by. This is the group which requires frequent changes in drugs and in
which side effects become most troublesome.
Problems relating to drug withdrawal appear when patients achieve
complete seizure control for a number of years; after two years the question
of drug withdrawal is usually raised. However, in most adults with grand mal
and psychomotor epilepsy, continued therapy is necessary. In relatively few
patients can drug withdrawal be accomplished even after freedom from
seizures for three to five years; seizures usually recur. As has been pointed
out, the EEG may remain abnormal in clinically seizure free patients,
indicating seizure potentiality; and even in cases in which the EGG reverts to
normal, drug withdrawal may be unsuccessful.
However, a calculated risk of drug withdrawal should be considered in
some patients, since successful withdrawal could represent an important
psychological achievement. Drug withdrawal should be attempted extremely
carefully with small decrements over many weeks. Drug withdrawal can be
expected to be more successful in children with controlled petit-mal epilepsy,
particularly since there is a natural tendency for petit mal to diminish with
age and maturity. However, in some of these patients generalized convulsions
appear even after the absences have ceased.
Dietary Treatment
In general, there are no dietary restrictions for the patient with

epilepsy, nor is there a specific diet capable of aiding most patients. However,
a diet high in fat content producing significant ketosis, i.e., the “ketogenic
diet,” is occasionally helpful in young children, particularly those with
intractable absences and minor motor seizures. Anticonvulsant drugs usually

have to be continued and the diet is difficult to maintain because of its lack of
appeal.
Psychological Therapy and Sociological Management
Even though drugs may achieve a significant degree of seizure control in
individual patients, there are many problems related to the life and
adjustment of the patient that need additional management. These are
generally less marked when the seizures are under control, and require
greater attention when seizures create continued problems. There are certain
patients, particularly some children and adults with psychomotor-temporal-
lobe seizures, who develop increased personality and behavioral disorders
after seizure control; the reasons for this are not clear. In many patients, the
coexistence of seizure and personality problems requires a combination of
medical anticonvulsant therapy and psychologically oriented management.
Although many anticonvulsant drugs have sedative properties, these
usually are not used directly. The so-called tranquilizing drugs have limited
usefulness in the management of seizure patients. Chlordiazepoxide and

diazepam may reduce disturbed behavior, particularly in children. The
phenothiazine drugs have variable effects; the alerting phenothiazine,
fluphenazine, is of some use in controlling abnormal behavior in certain

patients with psychomotor seizures. However, other drugs in the
chlorpromazine group are known to provoke paroxysmal discharges in the
EEG and seizures.
In most patients there is a direct interplay of emotional disturbances

with clinical seizure activity; patients in a state of psychological turmoil have
increased seizure susceptibility and often require greater amounts of
anticonvulsant drugs. The achievement of psychological adjustment often

reduces seizure frequency and intensity, and lessens drug requirement. This
fact must be considered in relation to the individual patient, the age, family,
and social circumstances. Family understanding is of primary importance,
since the child with seizures must live, insofar as possible, as a normal
individual within home and school settings. A great problem, still to be

overcome, is the stigma attached to epilepsy and the lack of understanding
which exists not only among people in general but in relation to various
restrictive legal and social practices. Most children with seizures can attend
schools and vocational programs successfully; most adults with seizures can
develop productive careers and engage in activities, such as marriage,
childbearing, obtaining an education, driving an automobile, traveling, and
working successfully in business and industry; while so engaged they can and
should be protected by insurance and workmen’s compensation programs.
Only few patients require a protected environment in schools or “colonies”
specifically developed for the epileptic. Even these should not be institutions
in which many hundreds of epileptic patients are kept under essentially

custodial care. Special treatment units or “colonies” in Great Britain, Holland,
Denmark, and France are relatively small and homelike; they are designed to
provide care for usually small numbers of patients at a time, involved in
intensive programs of medical therapy, psychological management,

education, and vocational training. From these units increasing numbers of
adequately controlled patients are sent out into the general community
where they can live well-adjusted and productive lives.
There are only a few occupations contraindicated for patients with a
tendency toward seizures; these include activities of potential danger to
either the patient or others, e.g., work requiring climbing to great heights,
using heavy power equipment, or perhaps dangerous chemical substances;
there may be exceptions in individual cases.
There is no medical reason to restrict driving an automobile if the
patient has been seizure-free for at least two years. Furthermore, the work
records of many patients with a history of seizures show that they are seldom
involved in industrial accidents because they realize how important it is to
their welfare to be most careful.
In a family situation, therefore, the person with epilepsy must be

accepted on as normal a basis as possible; restrictive situations must be
minimal, if needed at all, and a regular program of education and vocational

planning should be developed. School officials frequently need appropriate
orientation; most children and young adults with seizures are accepted
without question by their associates.
In individual instances, both informal and formal psychotherapeutic
measures can be undertaken in order to reduce emotional disturbances. The
role of the family physician is all-important; often he alone can judge the
problems in a family, school, or social setting and can, by his guidance and
understanding, help the patient and his family overcome the feelings of
despair, anxiety, fear, and self-consciousness that interfere with everyone’s
normal adjustment. It is only when anxieties and depressive tendencies
develop into more severe reactions, associated with perhaps paranoid states,
increased withdrawal, and excessive obsessional tendencies, that more

intensive psychiatric treatment may become necessary. Occasionally, it is
found that brief periods of appropriately oriented hospitalization with
psychotherapy can help readjust or control such patients. This may also be
required to evaluate the intensity of the psychological disturbance and the
apparent intellectual difficulties that may be interfering with the patient’s
performance. Adjustment of drug schedules may be carried out at the same
time. With increased experience even the child with epilepsy and behavioral
disorder can be cared for best if he can attend a normal school with an
understanding environment and, in addition, be associated with a clinical
outpatient service in which the functions, of the physician and social service
department work together with the child and the family. It is becoming less
necessary to arrange for either home tutoring or placement of such children
into special schools or other facilities for the maladjusted.
“Conditioned Inhibition” or “Desensitization” Therapy
There has been much interest, in recent years, in attempting to reduce
or control seizures, particularly those triggered by sensory or reflex stimuli,
by “desensitization” techniques. Whether these represent “true conditioning”
in the Pavlovian sense remains problematic. However the results have
sometimes been interesting and therapeutically successful. Olfactory stimuli
have been known to arrest uncinate seizures since the time of Jackson, and
were studied in detail by Efron. Forster and his group have been involved in a
number of “conditioning” therapeutic trials in patients with various kinds of
sensory or reflex-induced epilepsies (reading, photic, audiogenic, especially
musicogenic). These phenomena have led to experimental studies as well. In

specifically selected patients, therefore, such techniques, utilizing the known
stimulus in a “desensitization” or “conditioning” paradigm, may lead to
effective therapy.
Surgical Therapy
There is no question that a patient with a lesion such as a brain tumor
should be considered for operation, regardless of the state of the seizures.
Surgical intervention with removal of a focus of abnormal discharge is

considered an appropriate treatment for certain patients who have
intractable focal epilepsy, after adequate trial of intensive medical care. The
evaluation of such a patient, therefore, must consist of careful medical and

neurological studies which should include a psychological consideration,
since rehabilitation may be affected by the procedure. A focally discharging

area should be determined by serial electroencephalographic studies as being
fixed, and the region of brain considered for excision must be such that the
patient will not be left with a severe speech, memory, or other neurological
deficit.
Patients so evaluated often do not have obvious brain tumors, but the
epileptogenic region involved as the discharging focus may contain a small
tumor, a vascular lesion, or a scar secondary to trauma or previous

encephalitis. This approach has been particularly used in patients with focal
motor seizures, especially psychomotor-temporal-lobe or limbic seizures. It
must be realized that even though many patients are considered for surgical
therapy, few are chosen; the number of surgically treated epileptic patients is
still only in the hundreds. Yet, the occasional patient carefully selected for
such surgical therapy may achieve significant control of seizures. In some

series good results have been reported in up to 50 percent; unfortunately,
this means that an equal number are not better controlled postoperatively. In
some cases, however, less anticonvulsant medication may be required.

Occasionally, generalized seizures appear instead of previous psychomotor-
temporal-lobe seizures. In most of these patients it would seem that the

regions of brain involved are too widespread for limited excisions to be
practicable. A small number of patients have experienced relief from severe

personality disturbances, particularly aggressive psychotic behavior, but the
surgical intervention usually has not been primarily directed toward this end.
Bilateral operations on the temporal lobe have only limited effectiveness and
may produce severe memory disturbances. The use of stereotaxic
neurosurgical techniques to destroy epileptogenic regions deeply seated in
brain, i.e., amygdala and hippocampus, has been recommended, particularly

for certain patients with psychomotor-temporal-lobe epilepsy where there is
such evidence from depth electroencephalographic studies. In a small number
of carefully selected children with severe infantile hemiplegia, intractable

convulsions, and behavior disturbance, cerebral hemispherectomy has been
performed with improvement in seizure state and behavior despite the
persistence of neurologic disability.
Concluding Remarks
Much more must be learned about the natural history of the epileptic in
order to evaluate thoroughly the different therapies. The question of treating
the young child who has had a single febrile convulsion is typical of the
problems involved. There is accumulating evidence that recurring seizures

(especially with status epilepticus) do produce cerebral damage which may
eventually cause clinical neurological dysfunction and further severe seizures.
On the other hand, many infants and young children have one or a few
seizures and then no more.
Proper medical therapy adequately controls most seizure states in over
60 percent of patients and partially controls an additional 25-30 percent. The
drugs involved are decreasingly toxic, although anticonvulsant medication
remains essentially nonspecific and broadly directed against mechanisms of
neuronal hyperexcitability that are little understood. The remaining
intractable patients may be considered for surgical therapy; such procedures

are applicable, however as stated, to only a very small selected group. Surgical
therapy is effective in only about 50 percent of those chosen. It is hoped that
combined physiological and biochemical studies of disturbed cerebral and

general bodily functions in epilepsy will lead eventually to more rational and
effective therapy.
Bibliography
Abraham, K. and C. Ajmone Marsan. “Patterns of Cortical Discharges and Their Relation to
Routine Scalp Electroencephalography,” Electroencephalogr. Clin. Neurophysiol., 10
(1958), 447-461.
Alstrom, C. H. “A Study of Epilepsy in its Clinical, Social and Genetic Aspects,” Acta Psychiatr.
Neurol. Scand. Suppl., 63 (1950), pp. 1-284.
Andermann, F. “Self-Induced Television Epilepsy,” Epilepsia, 12 (1971), 269-275.
Andermann, K., F. Berman, P. M. Cooke et al. “Self-Induced Epilepsy,” Arch. Neurol., 6 (1962), 49-
65.
Aretaeus. The Extant Works of Aretaeus, The Cappadocian. Libri Septema. Translated by Francis
Adams. London: Sydenham Society, 1856.
Bacia, T. and K. Reid. “Visual and Somato-sensory Evoked Potentials in Man, Particularly in
Patients with Focal Epilepsy,” Electroencephalogr. Clin. Neurophysiol., 18 (1965),
778.
Baddeley, A. and K. Patterson. “Relation Between Long-term and Short-term Memory,” Br. Med.
Bull., 27 (1971), 237-242.
Baldwin, M. and P. Bailey, eds. Temporal Lobe Epilepsy. Springfield, Ill.: Charles C. Thomas, 1958.
Barrow, R. L. and H. D. Fabing. Epilepsy and the Law, 2nd ed. New York: Harper & Row, 1966.
Bergamini, L. and B. Bergamesco. Cortical Evoked Potentials in Man, pp. 49-52. Springfield, Ill.:
Blumer, D. and A. E. Walker. “Sexual Behavior in Temporal Lobe Epilepsy,” Arch. Neurol., 16
(1967), 37-43.
Bingley, T., “Mental Symptoms in Temporal Lobe Epilepsy and Temporal Lobe Gliomas,” Acta
Psychiatr. Neurol. Scand. Suppl., 120 (1958), 151.
Brierley, J. B. “Neuropathology of Amnesic States,” in C. W. M. Whitty and O. L. Zangwill, eds.,

Amnesia, pp. 150-180. London: Butterworths, 1966.
Bruens, J. H. “Psychoses in Epilepsy,” Psychiatr. Neurol. Neurochir., 74 (1971), 175-192.
Buchanan, R. A. “Ethosuximide Toxicity,” in D. M. Woodbury, J. K. Penry, and R. P. Schmidt, eds.,

Antiepileptic Drugs, pp. 449-454. New York: Raven, 1972.
Cereghino, J. J. and J. K. Penry. “Testing of Anticonvulsants in Man,” in D. M. Woodbury, J. K. Penry,

and R. P. Schmidt, eds., Antiepileptic Drugs, pp. 63-73. New York: Raven, 1972.
Cèrnacĕk, J. and L. Cigànek. “The Cortical Electroencephalographic Response to Light Stimulation

in Epilepsy,” Epilepsia, 3 (1962), 303-314.
Collins, A. L. and W. G. Lennox. “The Intelligence of 300 Private Epileptic Patients,” Res. Publ.
Assoc. Res. New. Ment. Dis., 26 (1947), 586-603.
Courtois, G. A., D. H. Ingvar, and H. H. Jasper. “Nervous and Mental Defects During Petit Mal
Attacks,” Electroencephalogr. Clin. Neurophysiol, Suppl., 3 (1953), 87.
Currie, S., K. W. G. Heathfield, R. A. Henson et al. “Clinical Course and Prognosis of Temporal Lobe
Epilepsy—A Survey of 666 Patients,” Brain, 94 (1971), 173-190.
DallaBarba, G. “Mental Capacities of Epileptics at Intelligence Test 1,” Arch. Psycol. Neurol.
Psychiatr., 18 (1957), 459-488.
Davidoff, R. A. and L. C. Johnson. “Paroxysmal EEG Activity and Cognitive-Motor Performance,”

Delay, J., P. Pichot, T. Lamperiere et al. The Rorschach and the Epileptic Personality. New York:
Logos, 1958.
Dennerll, R. D. “Cognitive Deficits and Lateral Brain Dysfunction in Temporal Lobe Epilepsy,”
Epilepsia, 5 (1964), 177-191.
Detre, T. and R. G. Feldman. “Behavior Disorder Associated with Seizure States,” in G. H. Glaser,
ed., EEG and Behavior, pp. 366-376. New York: Basic Books, 1963.
Dimsdale, H., V. Logue, and M. Piercy. “A Case of Persisting Impairment of Recent Memory
Following Right Temporal Lobectomy,” Neuropsychologia, 1 (1964), 287-298.
Dongier, S. “Statistical Study of Clinical and Electroencephalographic Manifestations of 536

Psychotic Episodes Occurring in 516 Epileptics Between Clinical Seizures,”
Epilepsia, 1 (1960), 117-142.
Drachman, D. A. and J. Arbit. “Memory and Hippocampal Complex,” Arch. Neurol. list15 (1966),
52-61.
Efron, R. “The Effect of Olfactory Stimuli in Arresting Uncinate Fits,” Brain, 79 (1956), 267-281.
----. “The Conditioned Inhibition of Uncinate Fits,” Brain, 80 (1957), 257— 262.
Falconer, M. A. “Some Functions of the Temporal Lobes with Special Regard to Affective Behavior
in Epileptic Patients,” J. Psychosom. Res., 9 (1967), 25.
Falret, J. “De l’Etat Mental des Epileptiques,” Arch. Gén. Méd. 16 (1860), 666— 679; 17 (1861),
461-491; 18 (1861), 26-37.
Fedio, P. and A. F. Mirsky. “Selective Intellectual Deficits in Children with Temporal Lobe or
Centrencephalic Epilepsy,” Neuropsychologia, 7 (1969), 287-300.
Fenton, G. W. and E. L. Udwin. “Homicide, Temporal Lobe Epilepsy and Depression: A Case
Report,” Br. J. Psychiatry, 111 (1965). 304-306.
Ferguson, S. M. and M. Rayport. “The Adjustment to Living Without Epilepsy,” J. New. Ment. Dis.,
140 (1965), 26-37.
Fischer-Williams, M., R. G. Bickford, and J. P. Whisnant. “Occipito-parieto-temporal Seizure

Discharge with Visual Hallucinations and Aphasia,” Epilepsia, 5 (1964), 279-292.
Flor-Henry, P. “Ictal and Interictal Psychiatric Manifestations in Epilepsy: Specific or Non-specific.

A Critical Review of Some of the Evidence,” Epilepsia, 13 (1972). 772-783.
Flynn, J. P., P. D. MacLean, and C. Kim. “Effects of Hippocampal After-discharges on Conditioned

Responses,” in E. D. Sheer, ed., Electrical Stimulation of the Brain, pp. 380-386.
Austin: University of Texas Press, 1961.
Flynn, J. P., M. Wasman, and D. Egger. “Behavior During Propagated Hippocampal After-
discharges,” in G. H. Glaser, ed., EEG and Behavior, pp. 134-148. New York: Basic
Books, 1963.
Forster, F. M. “Clinical Therapeutic Conditioning in Reading Epilepsy,” Neurology, 19 (1969). 717-

723.
Forster, F. M. and G. B. Campos. “Conditioning Factors in Stroboscopic-induced Seizures,”

Epilepsia, 5 (1964), 156-165.
Freud, S. (1923) “A Seventeenth-Century Demonological Neurosis,” in J. Strachey, ed., Standard
Edition, Vol. 19, pp. 72-105. London: Hogarth, 1955.
----. (1928) “Dostoevsky and Parricide,” in J. Strachey, ed., Standard Edition, Vol. 21, pp. 177-194.
Gascon, G. G. and C. T. Lombroso. “Epileptic (Gelastic) Laughter,” Epilepsia, 12 (1971), 63-76.
Gastaut, H. “So-called ‘Psychomotor’ and ‘Temporal’ Epilepsy,” Epilepsia, 2 (1953), 59-96.
Gastaut, H. and H. Colomb. “Etude du comportement sexual chez les epileptiques

psychomoteurs,” Ann. Méd. Psychol., 112 (1954), 657-696.
Gastaut, H., G. Franck, W. Krolikowska et al. “Phénomènes de Déafferentation sensoriélle

spécifique decélés par l’enregis-trement transcranien des potentials évoqués
visuels chez des sujets présentant des crises épileptiques visuelles dons leur champ
hemianapsique uni-ou bilateral,” Rev. Neurol. (Paris), 109 (1963), 249.
Gastaut, H. and H. Regis. “Visually Evoked Potentials Recorded Transcranially in Man,” in L. D.

Proctor and W. R. Adey, eds., Symposium on the Analysis of Central Nervous System
and Cardiovascular Data Using Computer Methods, pp. 8-34. Washington: NASA,
SP72, 1964.
Gastaut, H., J. Roger, R. Soulayrol et al. “Childhood Epileptic Encephalopathy with Diffuse Slow
Spike-waves (Otherwise known as “Petit Mal Variant”) or Lennox Syndrome,”
Epilepsia, 7 (1966), 139-179.
Gastaut, H. and C. A. Tassinari. “Triggering Mechanisms in Epilepsy: The Electroclinical Point of

View,” Epilepsia, 7 (1966), 85-138.
Gastaut, H. and M. Vigoroux. “Electroclinical Correlations in 500 Cases of Psychomotor Seizures,”

in M. Baldwin and P. Bailey, eds., Temporal Lobe Epilepsy, pp. 118—128.
Springfield, Ill.: Charles Thomas, 1958.
Gibbs, F. “Ictal and Non-ictal Psychiatric Disorders in Temporal Lobe Epilepsy,” J. Nerv. Ment. Dis.,
113 (1951), 522-528.
Glaser, G. H. “Visceral Manifestations of Epilepsy,” Yale J. Biol. Med., 30 (1957), 176-186.
----. “The Problem of Psychosis in Psychomotor Temporal Lobe Epileptics,” Epilepsia, 5 (1964),
271-278.
----. “Limbic Epilepsy in Childhood,” J. Nerv. Ment. Dis., 144 (1967), 391-397.
----. “Epilepsy and Disorders of Perception,” Assoc. Res. Nerv. Ment. Dis., 48 (1970), 318-333.
----. “Diphenylhydantoin Toxicity,” in D. M. Woodbury, J. K. Penry, and R. P. Schmidt, eds.,

Antiepileptic Drugs, pp. 219-226. New York: Raven, 1972.
Glaser, G. H., R. J. Newman, and R. Schafer. “Interictal Psychosis in Psychomotor-Temporal Lobe

Epilepsy. An EEG-psychological Study,” in: G. H. Glaser, ed., EEG and Behavior, pp.
345-365. New York: Basic Books, 1963.
Glaser, G. H. and E. C. Zuckermann. “Potassium Accumulation in Extracellular Spaces of Brain as a

Possible Cause of Epileptogenic Activity,” in G. Alemà, G. Bollea, V. Floris et al., eds.,
Brain and Mind Problems, pp. 309-329. Rome: II Pensiero Scientifico, 1968.
Goldensohn, E. S. “EEG and Ictal and Post-ictal Behavior,” in G. H. Glaser, ed., EEG and Behavior,
pp. 293-314. New York: Basic Books, 1963.
Goode, D. J., J. K. Penry, and F. E. Dreifuss. “Effects of Paroxysmal Spike-wave on Continuous

Visual-Motor Performance,” Epilepsia, 11 (1970), 241-254.
Goodglass, H., M. Morgan, A. T. Folsom et al. “Epileptic Seizures, Psychological Factors and
Occupational Adjustments,” Epilepsia, 4 (1963), 322-341.
Gowers, W. R. (1881) Epilepsy and other Chronic Convulsive Disorders. London: Churchill, 1881;
reprinted New York: Dover, 1964.
Green, J. B. “Reflex Epilepsy. Electroencephalographic and Evoked Potential Studies of Sensory

Precipitated Seizures,” Epilepsia, 12 (1971), 225-234.
Guerrant, J., W. W. Anderson, A. Fischer et al. Personality in Epilepsy. Springfield, Ill.: Charles C.
Thomas, 1962.
Guey, J., M. Bureau, C. Dravet et al. “A Study of the Rhythm of Petit Mal Absences in Children in
Relation to Prevailing Situations,” Epilepsia, 10 (1969), 441-451.
Hecker, A., F. Andermann, and E. A. Rodin. “Spitting Automatism in Temporal Lobe Seizures,”
Epilepsia, 13 (1972), 767-772.
Hill, D. “Psychiatric Disorders of Epilepsy,” Med. Press, 229 (1953), 473-475.
Hippocrates. Translated by J. Chadwick and W. N. Mann. Medical Works of Hippocrates, Sect. 15, p.
189. Oxford: Blackwell, 1950.
Hishikawa, Y., J. Yamamoto, E. Furija et al. “Photosensitive Epilepsy: Relationships Between the
Visual Evoked Responses and Epileptiform Discharges Induced by Intermittent
Photic Stimulation,” Electroencephalogr. Clin. Neurophysiol., 23 (1967), 320-334.
Horowitz, M. J. Psychosocial Function in Epilepsy. Rehabilitation after Surgical Treatment for

Temporal Lobe Epilepsy. pp. 180. Springfield, Ill.: Charles C. Thomas, 1970.
Horowitz, M. J. and F. M. Cohen. “Temporal Lobe Epilepsy. Effect of Lobectomy on Psychosocial

Functioning,” Epilepsia, 9 (1968), 23-41.
Hunter, R., V. Logue, and W. H. McMenemy. “Temporal Lobe Epilepsy Supervening on

Longstanding Transvestism and Fetishism,” Epilepsia, 4 (1963), 60.
Hutt, S. J. “Experimental Analysis of Brain Activity and Behavior in Children with ‘Minor’
Seizures,” Epilepsia, 13 (1972), 520-534.
Hutt, S. J., P. M. Jackson, A. Belsham et al. “Perceptual-motor Behavior in Relation to Blood

Phenobarbitone Level. A Preliminary Report,” Develop. Med. Child Neurol., 10
(1968), 626-632.
Hutt, S. J., D. Lee, and C. Ounsted. “Digit Memory and Evoked Discharges in Four Light-Sensitive
Epileptic Children,” Develop. Med. Child Neurol., 5 (1963), 559-571.
Ives, L. A. “Learning Difficulties in Children with Epilepsy,” Br. J. Disord. Commun., 5 (1970), 77-
84.
Jackson, J. H. On Epilepsy and Epileptiform Convulsions. Vol. 1, Selected Writings, J. Taylor, ed.,
London: Hodder and Stoughton, 1931.
Jackson, J. H. and W. S. Colman. “Case of Epilepsy with Tasting Movements and ‘Dreamy State’ A
Very Small Patch of Softening in the Left Uncinate Gyrus,” Brain, 21 (1898), 580-
590.
Jasper, H. H. “Some Physiological Mechanisms Involved in Epileptic Automations,” Epilepsia, 5

(1964), 1-20.
Jasper, H. H., A. Wards, and A. Pope. eds. Basic Mechanisms of the Epilepsies. Boston: Little, Brown,
1970.
Jordan, E. J. “MMPI Profile of Epileptics: A Further Evaluation,” J. Consult. Psychol., 27 (1963), 267-
269.
Jung, R. “Blocking of Petit-mal Attacks by Sensory Arousal and Inhibition of Attacks by an Active
Change in Attention During the Epileptic Aura,” Epilepsia, 3 (1962), 435-437.
Karagullia, S. and E. E. Robertson. “Psychical Phenomena in Temporal Lobe Epilepsy and the
Psychoses,” Br. Med. J., 1 (1955). 748-752.
Kenna, J. C. and G. Sedman. “Depersonalization in Temporal Lobe Epilepsy and the Organic
Psychoses,” Br. J. Psychiatry, 111 (1965), 293-299.
Kimura, D. “Right Temporal Lobe Damage,” Arch. Neurol., 8 (1963), 264-271.
----. “Cognitive Deficit Related to Seizure Pattern in Centrencephalie Epilepsy,” J. Neurol.

Neurosurg. Psychiatry, 27 (1964), 291-295.
Kolvin, I., C. Ounsted, and M. Roth. “Cerebral Dysfunction and Childhood Psychoses,” Br. J.
Psychiatry, 118 (1971), 407-414.
Kooi, K. A. and H. B. Hovey. “Alterations in Mental Function and Paroxysmal Cerebral Activity,”
Arch. Neurol. Psychiatry, 78 (1957), 264-271.
Kreindler, A. “Active Arrest Mechanisms of Epileptic Seizures,” Epilepsia, 3 (1962), 329-337.
Landolt, H. “Serial Electroencephalographic Investigations During Psychotic Episodes in Epileptic

Patients and During Schizophrenic Attacks,” in A. M. Lorentz De Haas, ed., Lectures
on Epilepsy, Suppl. 4, pp. 91—133. Amsterdam: Elsevier, 1958.
Lennox, W. G. “Bernard of Gordon on Epilepsy,” Ann. Med. Hist., 3 (1941), 372-383.
Lennox, W. G. and M. A. Lennox. Epilepsy and Related Disorders. Boston: Little Brown, 1960.
Lockard, J. S., W. L. Wilson, and V. Uhlic. “Spontaneous Seizure Frequency and Avoidance
Conditioning in Monkeys,” Epilepsia, 13 (1972), 437-444.
Lorentz De Haas, A. M. and O. Magnus. “Clinical and Electroencephalographic Findings in

Epileptic Patients with Episodic Mental Disorders,” in A. M. Lorentz De Haas, ed.,
Lectures on Epilepsy, pp. 134-167. Amsterdam: Elsevier, 1958.
Loveland, W., B. Smith, and F. Forster. “Mental and Emotional Changes in Epileptics on
Continuous Anticonvulsant Medication,” Neurology, 7 (1957), 856-865.
Lugaresi, E., P. Pazzaglia, and C. A. Tassinari. “Differentiation of ‘Absence Status’ and ‘Temporal
Lobe Status,”’ Epilepsia, 12 (1971), 77-87.
MacLean, P. D. “The Limbic System and Its Hippocampal Formation. Studies in Animals and Their
Possible Application to Man,” J. Neurosurg., 11 (1954), 29-44.
Margerison, J. H. and J. A. Corsellis. “Epilepsy and the Temporal Lobes,” Brain, 89 (1966), 499-
530.
Matthews, C. G. and H. Kløve. “Differential Psychological Performance in Major Motor,

Psychomotor, and Mixed Seizure Classifications of Known and Unknown Etiology,”
Epilepsia, 8 (1967), 116-128.
Meyer, V. “Cognitive Changes Following Temporal Lobectomy for Relief of Temporal Lobe
Epilepsy,” Arch. Neurol. Psychiatry, 81 (1959). 299-309.
Meyer, V. and A. Yates. “Intellectual Changes Following Temporal Lobectomy for Psychomotor
Epilepsy,” J . Neurol. Neurosurg. Psychiatry, 18 (1955), 44-52.
Mignone, R. J., E. F. Donnelly, and Sadowsky. “Psychological and Neurological Comparisons of

Psychomotor and Non-psychomotor Epileptic Patients,” Epilepsia, 11 (1970), 345-
359.
Milner, B. “Psychological Defect Produced by Temporal Lobe Excision,” Res. Publ. Assoc. Res. Nerv.
Ment. Dis., 36 (1956), 244-257.
----. “Alteration of Perception and Memory in Man: Reflections on Methods,” in L. Weiskrantz, ed.,
Analysis of Behavioral Change, pp. 268-375. New York: Harper & Row, 1968.
----. “Interhemispheric Differences and Psychological Processes,” Br. Med. Bull. 27 (1971), 272-
277.
Milner, B., S. Corkin, and H. L. Teuber. “Further Analysis of Hippocampal Amnesic Syndrome: 13
year Follow-up of M.,” Neuropsychologia, 6 (1968), 215-234.
Mirsky, A. F., D. W. Primac, C. A. Marsan et al. “A Comparison of the Psychological Test

Performance of Patients with Focal and Non-focal Epilepsy,” Exper. Neurol., 2
(1960), 75-89.
Mirsky, A. F. and J. L. Tecce. “The Analysis of Visual Evoked Potentials. During Spike and Wave
EEG Activity,” Epilepsia, 9 (1968), 211-220.
Mirksy, A. F. and J. M. Van Buren. “On the Nature of the ‘Absence’ in Centrencephalic Epilepsy: A
Study of Some Behavioral, Electroencephalographic and Autonomic Factors,”
Mitchell, W., M. A. Falconer, and D. Hill. “Epilepsy with Fetishism Relieved by Temporal
Lobectomy,” Lancet, 2 (1954), 626-630.
Morocutti, C. and J. A. Sommer-Smith. “Etude des Potentials evoqués visuels dans l’epilepsie,” Rev.
Neurol., 115 (1966), 93-98.
Naquet, R. “Conditonnement de décharge hypersynchrones epileptiques,” in J. F. Delafresnaye,

ed., Brain Mechanisms and Learning, pp. 625-640. Oxford: Blackwell, 1961.
Newcombe, F. “Memory for Designs Test,” Br. J. Soc. Clin. Psychol., 4 (1965), 230.
Ounsted, C. “The Hyperkinetic Syndrome in Epileptic Children,” Lancet, 2 (1955), 303-311.
Ounsted, C., D. Lee, and S. J. Hutt. “Electroencephalographic and Clinical Changes in an Epileptic
Child During Repeated Photic Stimulation,” Electroencephalogr. Clin. Neurophysiol.,
21 (1966), 388-391.
Ounsted, C, J. Lindsay, and R. Norman. Biological Factors in Temporal Lobe Epilepsy, p. 135.
London: Heinemann, 1966.
Penfield, W. and H. Jasper. Epilepsy and the Functional Anatomy of the Human Brain, p. 896.
Boston: Little, Brown, 1954.
Penfield, W. and P. Perot. “The Brain’s Record of Auditory and Visual Experience,” Brain, 86
(1963), 595-696.
Piercy, M. “The Effects of Cerebral Lesions on Intellectual Function: A Review of Current Research
Trends,” Br. J. Psychiatry, 110 (1964), 310-352.
Pond, D. A. “Psychiatric Aspects of Epilepsy,” J. Indian Med. Profess., 3 (1957), 1441-1451.
----. Psychiatric Aspects of Epileptic and Brain-damaged Children,” Br. Med. J., 2 (1961), 1377-
1382, 1454-1459.
----. “Psychological Disorders of Epileptic Patients,” Psychiatry Neurol. Neurochir., 74 (1971), 159.
Prechtl, H. F. R., P. E. Bocke, and T. Schut. “The Electroencephalogram and Performance in

Epileptic Patients,” Neurology, 11 (1961), 296-304.
Price, J. C. and T. J. Putnam. “The Effect of Intrafamily Discord on the Prognosis of Epilepsy,” Am. J.
Psychiatry, 100 (1944), 593-598.
Prichard, J. W. and G. H. Glaser. “Cortical Sensory Evoked Potentials During Limbic Seizures,”
Putnam, T. J. and H. H. Merritt. “Dullness as an Epileptic Equivalent,” Arch. Neurol. Psychiatry, 45

(1941), 797-813.
Quadfasel, A. F. and P. W. Pruyser. “Cognitive Deficit in Patients with Psychomotor Epilepsy,”

Epilepsia (Ser. 1), 4 (1955), 80-90.
Rapoport, D., M. Gill, and R. Schafer. Diagnostic Psychological Testing. London: University of
London Press, 1970.
Raven, J. C. Guide to Using the Mill Hill Vocabulary Scale with Progressive Matrices. London: Lewis,
1948.
----.Guide to Using Progressive Matrices. London: Lewis, 1949.
Rennick, P. M., C. Perez-Borja, and E. A. Rodin. “Transient Mental Deficits Associated with
Recurrent Prolonged Epileptic Clouded State,” Epilepsia, 10 (1969), 397-405.
Reynolds, E. H. “Mental Effects of Anticonvulsant Drugs and Folate Metabolism,” Brain, 91 (1968),
197-214.
Ricci, G., G. Berti, and E. Cherubini. “Changes in Intrictal Focal Activity and Spike-wave Paroxysms
During Motor and Mental Activity,” Epilepsia, 13 (1972), 785-794.
Richer, P. Etudes Cliniques sur L’Hystéro-épilepsie ou Grande Hystérie. Paris: Adrien Delahaye et
Emile Lecrosnier, 1881.
Robertson, E. G. “Photogenic Epilepsy: Self-Precipitated Attacks,” Brain, 77 (1954), 232-261.
Rodin, E. A. The Prognosis of Patients with Epilepsy. Springfield, Ill.: Charles C. Thomas, 1968.
Rodin, E. A., R. N. DeJong, R. W. Waggoner et al. “Relationship between Certain Forms of
Psychomotor Epilepsy and ‘Schizophrenia,’ ” Arch. Neurol. Psychiatry, 77 (1957),
449-463.
Rodin, E. A., S. Gonzalez, D. Caldwell et al. “Photic Evoked Responses During Induced Epileptic
Seizures,” Epilepsia, 7 (1966), 202-214.
Rodin, E. A., D. W. Mulder, D. L. Faucet et al “Psychologic Factors in Convulsive Disorders of Focal

Origin,” Arch. Neurol. Psychiatry, 74 (1955), 365-374.
Roger, J., H. Grangeon, J. Grey et al. “Psychiatric and Psychological Effects of Ethosuximide
Treatment in Epileptics,” Encephale, 57 (1968), 407-438.
Roth, M. and M. Harper. “Temporal Lobe Epilepsy and the Phobic-Anxiety Syndrome, Part 2,”
Compr. Psychiatry, 3 (1962), 215-226.
Schwab, R. S. “Method of Measuring Consciousness in Attacks of Petit Mal Epilepsy,” Arch. Neurol.
Psychiatry, 41 (1939), 215-227.
Schwartz, M. L. and R. D. Dennerll. “Neuropsychological Assessment of Children with, without and

with Questionable Epileptogenic Dysfunction,” Percept. Mot. Skills., 30 (1970), 111-
121.
Scott, D. F., A. Moffett, A. Mathews et al. “Effect of Epileptic Discharges on Learning and Memory
in Patients,” Epilepsia, 8 (1967), 188-194.
Scoville, W. B. “Amnesia after Bilateral Mesial Temporal-lobe Excision: Introduction to Case H.M.”
Serafetinides, E. A. “Aggressiveness in Temporal Lobe Epileptics and Its Relation to Cerebral

Dysfunction and Environmental Factors,” Epilepsia, 6 (1965), 33-42.
Serafetinides, E. A. and M. A. Falconer. “Some Observations on Memory Impairment after

Temporal Lobectomy for Epilepsy,” J. Neurol. Neurosurg. Psychiatry, 25 (1962),
251-255.
Servit, Z., J. Machek, A. Stercova et al. “Reflex Influences in the Pathogenesis of Epilepsy in the
Light of Clinical Statistics,” Epilepsia, 3 (1962), 315-322.
Shallice, T. and E. K. Warrington. “Independent Functioning of Verbal Memory Stores: A

Neuropsychological Study,” Q. J. Exp. Psychol., 22 (1970), 261-273.
Shimazono, Y., T. Hirai, T. Okuma et al. “Disturbance of Consciousness in Petit Mal Epilepsy,”
Epilepsia, 2 (1953), 49-55.
Slater, E., A. W. Beard, and E. Glithero. “The Schizophrenia-like Psychoses of Epilepsy,” Br. J.
Psychiatry, 189 (1963), 95-150.
Small, J. G., V. Milstein, and J. R. Stevens. “Are Psychomotor Epileptics Different?” Arch. Neurol., 7
(1962), 187-194.
Stevens, J. R. “Psychiatric Implications of Psychomotor Epilepsy,” Arch. Gen. Psychiatry, 14 (1966),

461-471.
Stevens, J. R., G. H. Glaser, and P. D. MacLean. “The Influence of Sodium Amytal on the Recollection
of Seizure States,” Trans. Am. Neurol. Assoc., 79 (1954), 40-45.
Symonds, C. “Excitation and Inhibition in Epilepsy,” Brain, 82 (1959), 133-146.
Taylor, D. C. “Aggression and Epilepsy,” J. Psychom. Res., 13 (1969), 229-235.
----. “Sexual Behavior and Temporal Lobe Epilepsy,” Arch. Neurol., 21, (1969), 510-516.
----. “Ontogenesis of Chronic Epileptic Psychoses: A Reanalysis,” Psychol. Med., 1 (1971), 247-253.
----. “Psychiatry and Sociology in the Understanding of Epilepsy,” in E. M. Mandelbrote and M. G.

Gelder, eds., Psychiatric Aspects of Medical Practice, pp. 161-187. London: Staples
Press, 1972.
----. “Mental State and Temporal Lobe Epilepsy. A Correlative Account of 100 patients Treated
Surgically,” Epilepsia, 13 (1972), 727-765.
Temkin, O. The Falling Sickness, p. 380. Baltimore: The Johns Hopkins Press, 1945.
Tizard, B. and J. H. Margerison. “Psychological Functions during Wave-Spike Discharge,” Br. J. Soc.
Clin. Psychol., 3 (1963), 6-15.
Walker, A. E. “Murder or Epilepsy?” J. Nerv. Ment. Dis., 133 (1961), 430-437.
Warrington, E. K. “Neurological Deficits,” in P. Mittler, ed., The Psychological Assessment of Mental

and Physical Handicaps, pp. 261-287. London: Methuen, 1971.
Warrington, E. K. and M. James. “Disorders of Visual Perception in Patients with Localized

Cerebral Lesions,” Neuropsychologia, 5 (1967), 253-266.
Warrington, E. K. and P. Rabin. “A Preliminary Investigation of the Relation between Visual

Perception and Memory,” Cortex, 6 (1970), 87-96.
Wechsler, D. The Measurement of Adult Intelligence, 3rd ed., Baltimore: Williams & Wilkins, 1944.
Whitty, C. W. M. and O. L. Zangwill, eds. Amnesia. London: Butterworths, 1966.
Williams, D. “The Structure of Emotions Reflected in Epileptic Experience,” Brain, 79 (1956), 29-
67.
----. “Man’s Temporal Lobe,” Brain, 91 (1968), 639-654.
Yeager, C. L. and J. S. Guehrant. “Subclinical Epileptic Seizures: Impairment of Motor Performance

and Derivative Difficulties,” Calf. Med., 86 (1957), 242-247.
Notes
1 The assistance of Helen Sanders Brittain in the preparation of portions of this chapter is gratefully
acknowledged.
2 Raven’s matrices consists of a graded series of patterns in which one part is missing and the correct
missing part is chosen by the subject from a collection of six (or later in the test eight)
alternatives. At its simplest, the task requires only matching a pattern, but at its most
complex, the grasp of a subtle relationship between the parts of the system is required.
Chapter 14
Psychoses Associated with Drug Use
Malcolm B. Bowers, Jr. and Daniel X. Freedman
Introduction
This chapter deals with the genesis of psychotic behavior in which
intake of a pharmacologic compound plays a significant role. As used here,
psychosis refers to an experience of self and external world, which, for a

significantly prolonged period, is at marked variance with generally accepted
notions of reality and which is not under individual control. Psychotic

behavior may become manifest at a variety of stages in the course of drug use:
during acute or chronic drug ingestion, during drug withdrawal, or at varying

intervals following drug use. In the latter instance the contribution of the
drug to the genesis of the psychotic behavior is often hard to assess.
The phenomena of drug-induced altered states of consciousness which
involve marked but usually temporary distortion in self-image, feeling states,
and perception of external reality, remind psychopathologists that one
component of many major psychiatric syndromes are just such alterations in
consciousness. In the naturally occurring psychotic reaction such states of
mind may be long lasting, recurrent, evoked in response to individually

perceived experience, and with time variously assimilated or rejected by the
individual. The fact that the same or similar statements can currently be made
about many drug-related states encountered clinically indicates just how
instructive the drug model has become.
Psychotic behavior is more likely to occur in a higher dose range and
following prolonged use of a given compound with psychotogenic potential.
When such behavior occurs at a lower dose, is not associated with delirium,
and extends beyond the known period of drug action, one suspects the
presence of other factors which may have predisposed the individual to such
a response. Such factors may include a broad range of conscious and
unconscious situational or maturational stresses—psychosocial stresses,

which might threaten the coping capacities of the individual. Such stresses
may have been involved in the original motivation to use the drug in question.
A classification of syndromes produced by drugs with psychotogenic

potential with regard to the presence or absence of delirium, the contribution
of psychosocial stress, and relative similarity to naturally occurring states is

somewhat arbitrary. However, the classification proposed by Brawley and
Duffield in their review of hallucinogenic drugs, has some utility for the
purposes of this survey.
Many active drugs, administered long enough and in sufficient quantity,
produce psychotic behavior as part of a more extensive spectrum of general
metabolic, neurologic, or toxic effects. The psychic syndrome thus produced is
usually associated with some evidence of intellectual impairment, such as

restricted consciousness, memory loss, or disorientation. Thus many of the
symptoms of acute toxic psychosis are those of acute brain syndrome. We
recognize in reality that a continuum exists between compounds which
produce psychotic phenomena in a clouded as opposed to a clear sensorium.
With some exceptions, compounds which produce primarily acute brain
syndrome or neurotoxic effects usually do not produce psychotic syndromes

akin to the naturally occurring psychoses nor do their effects usually persist
after the drug has been withdrawn, unless damage to the central nervous
system has occurred. Brawley and Duffield refer to these compounds as

“poisons,” though actually they represent a heterogeneous group.
A group of drugs with anticholinergic properties tends to produce
delirium without extensive toxic effects on other systems. This clinical

syndrome is characterized by restricted consciousness; disorientation to
time, place, and person; impairment in recent memory; visual hallucinations;

and some degree of retrograde amnesia. Yet a third group of drugs—the
Psychotomimetic hallucinogens—can produce acute psychotic states
without markedly clouding consciousness or producing other signs of
intellectual impairment. These states resemble more closely some
manifestations of the naturally occurring psychoses but are usually
approximately limited in time by the duration of drug action. However, in
some instances, use of these compounds is coincidental with or effective in
precipitating extended psychotic states in some vulnerable individuals.

Neither the nature of such vulnerability nor the role of drug effects
interacting with such factors has been defined.
Psychotogenic Drugs with Generalized Metabolic or Toxic Effects
Almost any potent pharmaceutical agent can potentially be placed in
this category. Drugs which mimic or alter hormonal systems seem
particularly likely to produce psychotic reactions in some individuals. High
doses of adrenal steroids and ACTH are noted for their potential
psychotomimetic effects. Although the literature is not in complete accord,
many psychotic reactions produced by these agents have not been associated
with delirium and have resembled so-called schizoaffective reactions. There
is no mandatory mood change contingent upon hormonal excesses or

deficiencies but euphoria as a component of mood change with steroid
medication is not uncommon; perceptual changes with reference to the body
and the environment can accompany any of these mood changes. We are
aware of a few instances of self-medication with drugs such as prednisone in
order to enhance affect. Psychosocial factors contributory to
psychotomimetic reactions may be important when the steroid treatment is

administered for life-threatening illness (for instance, systemic lupus
erythematosus) or produces gross weight gain and change in facial
appearance. In the case of systemic lupus erythematosus vascular changes in

the central nervous system may be contributory to behavioral change. In the
treatment of thyroid dysfunction a variety of behavioral reactions may ensue
contingent upon thyroid status, treatment agent, or change in psychological
organization. Psychotic reactions have been reported in association with the
administration or withdrawal of oral contraceptive preparations.
Although little used today, bromide preparations used to be a major
cause of psychotic reactions. Usually such psychoses were associated with
significant disorientation, but Levin has described a “bromide schizophrenia”

which he feels differs from bromide delirium in that clouding of
consciousness was not a symptom in the former condition, and differential
diagnosis on admission for such disorders presented a challenge to the astute
clinician. The variety of psychological states which bromides can produce are
not familiar to many clinicians today, but Levin’s studies document an array
of syndromes more prominent when bromides were more readily available in
proprietary sedative preparations. Replacement of retained bromide with
saline was a useful therapy. Bromides are still present in a few over-the-
counter preparations, but they have largely been replaced by belladonna
alkaloids.
Acute inhalation of a variety of volatile organic solvents can result in

unusual states of consciousness. These agents vary in their toxicity. Gasoline,
toluene, ethyl acetate, and trichlorethylene are among the compounds which
can produce “inhalation psychoses.” Some individuals may develop
habituation to such practices and polyneuropathy has been reported. Most of

these compounds are anesthetics and acute inhalation in poorly ventilated
surroundings can result in unconsciousness and death from suffocation (glue
sniffing) or a primary cardiac toxicity from fluorinated hydrocarbons in

aerosols (Freon). The acute brain syndrome produced by inhalation of
organic solvents is usually attended by clouding of consciousness and
terminated soon after the offending compound has been removed.
Unique psychopharmacological properties have been described for the
anesthetic phencyclidine (Semyl) now primarily used in veterinary medicine.
Extensively studied by Domino, Luby, and their colleagues, this compound in

subanesthetic doses produces a unique picture of dissociation of
consciousness akin to sensory isolation in which the individual may

experience a variety of distortions in body image. Although clouding of
consciousness may be present, cognitive and body image changes produced
by phencyclidine have reminded some investigators of the primary clinical
symptoms of schizophrenia. This compound has recently been found
extensively on the illicit drug market (known as PCP) and often is an

unexpected adulterant of material sold as LSD or mescaline.
Use of the antimalarial drug atabrine was associated with psychotic

reactions during World War II. Most of these cases were apparently
characterized by disorientation but several were quite prolonged. Some
correlation with accumulated drug or metabolite was apparent and paranoid
features were prominent, presenting problems for differential diagnosis.
Psychosis may occur as part of a syndrome of withdrawal from drugs
which produce tissue dependence such as the major narcotics and sedative
antianxiety drugs, including ethyl alcohol, barbiturates, meprobamate, and
the benzodiazepines. Withdrawal from sedative compounds generally
produces neurological symptoms such as tremor and convulsions but, as

classic studies have shown, hallucinations and delirium can be a prominent
aspect of the syndrome of sedative withdrawal. As is generally known, the
onset of all or part of this syndrome may be delayed following withdrawal of

sedative compounds. In part, this phenomenon is related to a long half-life of
certain drugs such as meprobamate or chlordiazepoxide. The classic state of

sedative withdrawal (delirium tremens) which occurs following ethyl alcohol
is not considered a specific indication for antipsychotic phenothiazine drugs.
In fact under certain conditions such drugs may be contraindicated as they
are in belladonna delirium (central anticholinergic syndrome).
Deliriants-Atropinelike Drugs
Many drugs used in medical practice have atropinelike properties. In

general these compounds are quite potent and may produce psychotic effects
at doses of a few milligrams. The psychosis thus produced is the typical
“belladonna delirium” or central anticholinergic syndrome characterized by

disorientation, dry skin, mydriasis, tachycardia, visual hallucinations,
amnesia, and slowing of the electroencephalogram. This clinical picture
usually subsides within twenty-four hours after the offending drug or drug
combination has been discontinued. Older individuals with chronic brain

syndrome or other factors predisposing to delirium are usually susceptible to
psychotic reactions produced by these compounds. This syndrome can be
specifically reversed by the administration of physostigmine, but
conservative management is usually sufficient once the atropinelike drug has

been withdrawn. Phenothiazines (which possess anticholinergic properties)
have been reported to exacerbate atropinelike psychosis so that differential
diagnosis of this state from psychosis related to amphetamine or LSD-like

drugs is essential, for in the latter cases phenothiazines and sedative
antianxiety compounds, respectively, are usually helpful. The atropinelike
psychosis frequently emerges in clinical psychiatric practice when a patient is
receiving a combination of drugs which have anticholinergic properties such
as phenothiazines, tricyclic antidepressants, and anti-Parkinsonian

compounds. It is generally believed that these psychotic reactions are related
to the interruption of function in the central cholinergic neuronal systems.
However, it is unclear why higher psychic, function is affected early in the

dose-response spectrum of the centrally acting anticholinergics, whereas
anticholinesterase compounds tend to produce more widespread and life-
endangering neurotoxic effects and a different pattern of altered psychic
function with some similarities to depressive states.
Psychotomimetic Drugs
Amphetaminelike Drugs
Compounds with actions similar to amphetamine (methamphetamine,
cocaine, methylphenidate, phenmetrazine, and diethylproprion) may produce
psychotic reactions without marked clouding of consciousness. Three years

after the first use of amphetamine in the treatment of narcolepsy, psychotic
reactions were reported. These authors also speculated on the possible
vulnerability of persons with psychopathic traits to such drug use and

reactions. In more recent years, the use of amphetaminelike drugs for
appetite suppression and psychomotor stimulation has led to periodic
occurrence of such reactions.
At higher doses and with continuing use amphetaminelike drugs
reliably produce psychotic symptoms which often cannot be distinguished
from those of naturally-occurring paranoid psychoses. It has been recently

shown under certain experimental conditions that these compounds
regularly produce a syndrome of psychotic suspiciousness and ideas of
reference. These clinical studies, in which amphetamine has been repeatedly
administered to volunteer subjects so a relatively large cumulative intake is

achieved over a few days, suggest that virtually all subjects will eventually
become psychotic on such a regimen. Since the subjects have been
amphetamine users, the factor of prior state (including personality) must be

considered as a component in the response. Many investigators consider this
high-dose amphetamine reaction the closest experimental analogue of the
naturally-occurring psychoses. Bell, however, has recounted administration

of higher doses of intravenous methamphetamine in amphetamine addicts.
He frequently observed very prompt onset of symptoms. These, however, are
initially changes in perception, illusions, tension, and difficulty in locating the
source and meaning of such changes. Paranoid interpretations followed later,

as did the more typical ideas of reference and delusions. He observes this
pattern in one group of cases encountered clinically whose symptoms
eventually subsided while another group with auditory hallucinations had
persisting symptoms. These changes are not unlike the sequence of events
observed with the psychotomimetic indoles (LSD, psilocybin, DMT [N,N1-
dimethyltryptamine]) and phenylethylamines (mescaline). Indeed sharp

observation and reconstruction of the early onset of amphetamine psychoses
indicate sensitivity to lights and reflections; perceptual changes precede and
are later “explained,” resulting in the more characteristic clinical signs

(paranoid delusions) by which the amphetamine reaction is generally
compared to acute schizophrenia.
The fact that clinically effective antipsychotic compounds can
antagonize the effects of amphetamine, and the differential effects of
stereoisomers of this drug upon catecholamine systems strengthens the

argument that the effects of amphetamine may be a clue to neuronal
mechanisms involved in some manifestations of the naturally-occurring
psychoses. This subject has recently been reviewed by Snyder. Many

similarities exist between experimental amphetamine intoxication in animals
and the clinical behaviors which are encountered, notably stereotypy.
Ellinwood and his coworkers have analyzed amphetamine intoxication in
several species from behavioral, histochemical, neurophysiological, and

neuropathological points of view.
Even at low doses amphetaminelike compounds may occasionally
produce psychotic states and such psychoses may be prolonged, resembling
naturally-occurring paranoid psychosis. Under these circumstances one may
speak of a drug-precipitated or drug-induced psychosis, the assumption being
that amphetamine ingestion facilitated some process already moving the

individual in the direction of a psychotic state. The following case illustrates
the way in which amphetaminelike drugs may act synergistically to
exacerbate a nascent psychotic state.
A twenty year-old woman, socially undeveloped and insecure, began her
first job in a clothing store following graduation from high school. She became
self-conscious when male employees made sexually provocative remarks.
Soon she began to believe that other employees were saying and doing things
designed to tell her that she should “grow up and masturbate.” In this context
she took one 5-milligram amphetamine tablet furnished by her brother. Her
thought processes accelerated greatly, and her self-experience rapidly
became severely disorganized. In a few days she was admitted to a hospital

with a diagnosis of acute schizophrenia. Four months of hospitalization and
phenothiazine drugs were required to bring her psychotic state under

control.
It has become common practice for psychiatrists to assert that
individuals who suffer prolonged psychotic reactions following low doses of

amphetamine, cannabis, or LSD-like drugs were “already schizophrenic” or
“latent schizophrenics.” This judgment is always made retrospectively and
involves some assumptions about schizophrenia which are unproven,
including the idea that the preschizophrenic state can be characterized and
recognized. The implication in these instances that the drugs play a relatively
unimportant role in the emergence and perpetuation of psychotic symptoms
may be unwarranted.
Several interesting clinical interactions of amphetamine with
schizophrenia add to the puzzles as to underlying mediating systems that
might be common to drugs and naturally occurring syndromes. There are
some instances of amphetamine psychoses which persist and can be
explained very much as persisting hallucinosis as explained in alcoholism, i.e.,
the evocation of or unmasking of some prior psychotic disorder or symptom.

When amphetamine was given to catatonic schizophrenics, they showed a
“paradoxical” reaction of drowsiness and unresponsiveness (also seen in
delirium tremens), whereas amytal “awoke” the catatonic patients and

seemed to relax them sufficiently to relate with some degree of normalcy for a
brief period. When methylphenidate was given to persons recovering from

acute schizophrenic episodes, the schizophrenic behavior was observed to
recur, but when sufficient time for remission had taken place, the
methylphenidate no longer evoked schizophrenic symptomatology. The
utility of these various cross comparisons probably lies in the spur they give
to empirical research both at the clinical pharmacological and observational
levels and in animal brain-behavior research: it is as if one is constantly
narrowing down a focus upon the differentiating mechanisms.
Amphetaminelike drugs have recently been extensively used by the
illicit drug community. High doses are frequently administered orally or

intravenously. In such a setting, brief psychotic reactions are common and
often accompanied by dangerously aggressive behavior. Such amphetamine
abuse can also be associated with consequences which are life-threatening to
the user, including subarachnoid hemorrhage and the usual serious medical
complications of intravenous drug abuse.
Amphetaminelike compounds combined with other drugs are

frequently employed as bronchodilators for the treatment of asthma and
other upper respiratory syndromes. Psychotic reactions have been reported
following the use of such preparations, but so too has the phenomenon of
alternating psychosis and asthma in a few individuals.
LSD-like Drugs
The discovery of d-lysergic acid diethylamide (LSD) by Hoffman gave

the world its most potent known mind-altering substance. Quantities less
than 1 mg. of this compound produce a syndrome which may resemble
certain stages in the naturally-occurring psychoses. Other related compounds
such as psilocybin and dimethyltryptamine produce similar acute behavioral
responses. This reaction is characterized by dramatic visual illusions and by a
unique destructuring of the usual psychic defenses. Giarman and Freedman’s
description aptly characterizes this altered state of consciousness:
Psychotomimetic drugs such as d-lysergic acid diethylamide . . . reliably

and consistently produce periods of altered perception and experience
without clouded consciousness or marked physiological changes; mental
processes that are usually dormant and transient during wakefulness
become “locked” into a persistent state. The usual boundaries which
structure thought and perception become fluid; awareness becomes vivid
while control over input is markedly diminished; customary inputs and
modes of thought and perception become novel, illusory, and portentous;
and with the loss of customary controlling anchors, dependence on the
surroundings, on prior expectations, or on a mystique for structure and
support is enhanced. Psychiatrists recognize these primary changes as a
background state out of which a number of secondary psychological states
can ensue, depending on motive, capacity and circumstance. This is
reflected in the terminology that has grown around these drugs; if
symptoms ensue, the term psychotomimetic or psychodysleptic is used;
and if mystical experience, religious conversion, or a therapeutic change in
behavior is stressed, the term psychedelic or mind “manifesting” has been
applied.
The drugs and clinical states set up a “search for synthesis,” and the
motives and capacities of subjects and patients to achieve this are
obviously of importance if one is to assess outcomes and compare and
contrast these states, [p. 2]
The following example of LSD-induced altered state of consciousness

exemplifies the kind of experiential destructuring which may attend the use
of this and similar compounds. This letter was written by a young college
student during the ten hours of an LSD experience. He recovered completely
at the end of this period and did not, in retrospect, regard this drug
experience as a “bad trip.”
Hi again Marilyn. I think that you hurt me and I haven’t had the honesty
to admit it so there I have admitted it and you can be happy. ... It is late and
I’m getting very high with a gross and stupidly terrible idea. I must admit
Marilyn, yes, that you are so much like my mother. It’s like Mom when she
used to punish me, she used to hit me and I think you will hit your children a
lot like my mother. Yes, in your admonishing role you are like my mother,
with the same kind of disapproval of my behavior it’s the same feeling that I
used to get when my mother disapproved of my doing something that I get
now when Marilyn says I’m irresponsible. It’s the same feeling I mean that
when I was young I had a kind of feeling of guilt, remorse, anger, and shame—
all of the normal little child’s feelings. I have the same kind of feeling now
when Marilyn my mother admonishes and reprimands me for my
irresponsibility and I fear that when she gives me the same feeling I used to
get from my mother, then she couldn’t be good for my children and my
children are very important. ... I think I have finally figured it out! I’m afraid
that I am going to die. If I die and I am not a Christian I will go to hell. God, am
I afraid to die! I might commit suicide. My papers are due—my papers are
due. . . . Why am I so afraid to lose Marilyn. There is a sense in which my fear
of going insane is linked with losing her. ... I am only now very tired, a bit
depressed about my papers and sorry about Marilyn so I am really alright. ...
At least I have enough sense to go to bed now. I fear being crazy and
admitting it to myself because then I might commit suicide like my brother.
I’m going to bed. If Bill goes to the University Health he might be right and if
they found out that I’m crazy I might really be crazy and if I were crazy I
might commit suicide. I’m afraid everything is closing in on me, troopers and
everything. I’m so tired! I’m going to bed—good night Marilyn.
This excerpt is not presented as a typical LSD experience, but rather as
an experiential account suggesting the manner in which this kind of altered
consciousness may reactivate certain painful intrapsychic issues and heighten

the experience of conflict at certain critical developmental periods. Such an
interaction between drug-induced state and intrapsychic conflict and defense
may be involved in many “bad trips” or extended psychotic states related to

drug use. Bridger’s ideas concerning the interaction of stress and
psychotomimetic drug effect seem relevant in this context. He notes that
animal experiments suggest that psychotomimetic drugs facilitate the
association of a conditioned and an unconditioned stimulus so long as the

animal is still under the stress of a learning paradigm where an aversive
unconditioned stimulus is being used. Bridger concludes that such drugs
facilitate the intrapsychic merging of symbol and the object symbolized.
We have noted that conflicts which are depicted in the phenomenology

of psychotomimetic drug-induced states can be understood as genuine
conflictual issues for the individual which were under control prior to the
drug-induced state. The drug experience appeared to have breached an

intrapsychic buffer zone between certain kinds of current experience and
internal “symbols” of vulnerability, similar to the way an antigen-antibody
response might be facilitated. A similar mechanism has been called
“catathymic” and proposed by Faergeman as operative in “psychogenic

psychoses”. The ability of the individual to control, tolerate, or modulate this
“anamnestic response” would be expected to vary, as it does in drug-induced
states.
That stress or conflict occurring during a psychotomimetic episode can
lead to further dyscontrol over the content, intensity, and quality of subjective
experience has been noted by the adherents of the Peyote ceremonies, “lay
pharmacologists” using these drugs, and medical scientists. Blacker
speculated that avoidance of aversive stimuli, learned in the drug state (in
which the least stressful adaptation is to cease vigilant reaction and “go with”
the experience) may characterize some of the passivity and amotivational
behavior of chronic drug users. The loss of perceptual constancies, of

“barrier” functions from the banal to those regulating reality adaptations, has
been noticed, and the inability to ward off or put bounds around intrapsychic
or external stimuli has been noted in the so-called “flashback” phenomenon.
The model of the traumatic neuroses in which repetitive noxious experience
recurs after the mastery of ongoing stimuli was unexpectedly disrupted (or
the “stimulus barrier” breached), and the need to synthesize the intensities of
experience, has been noted as a possible mechanism in this inconstantly
occurring after effect of LSD or mescaline. The phenomena occurs generally
briefly, and not as the lay imagination conceives it, as a miniature “rerun” of
hours of a particular LSD episode; thresholds for observations of minor
alterations of states of consciousness are often enhanced—both by publicity
and perhaps by the drug experience—and the interpretation of these effects

can lead to panic and excessive focus upon subjective states. In any event, the
experience and its mastery during the drug state possibly accounts for the
variability of outcomes, and certainly defines the chief characteristics of these
states in which the operations of variables such as expectation, group

structuring and reinforcement, and individual experience and coping, are
strikingly revealed as both crucial and variable. It is nevertheless noteworthy

that animals can detect very low and behaviorally in apparent doses of these
drugs and distinguish LSD from mescaline, for example. Accordingly, the
neural and chemical mechanisms evoking these perceptions are of some
interest in understanding brain function and psychotic like behaviors.
Initial comparisons of the LSD state with naturally occurring psychoses
tended to conclude that the two were not related. Later comparisons have
shown that some psychotic reactions can be characterized by the
“psychedelic” form of experience which may accompany the use of LSD-like
drugs. Cumulative-dose experiments performed with LSD-like compounds
tend to produce tolerance unlike the effects in amphetamine experiments (in
which psychosis supervenes). Response to and resistance to noxious stimuli

after several days of LSD has not been systematically examined in man. In
animals on tolerance dosage schedules, such stimuli can enhance or disrupt
certain performances and apparently do not show tolerance. The LSD-
precipitated psychotic reaction—an extended psychosis following LSD use—

tends to be somewhat different from the amphetamine-induced psychoses.
The former may be associated with more ecstatic elements and less routinely
with psychotic suspiciousness. Drugs in these two classes also tend to

produce different EEG effects in animals and these differences have led
investigators to propose these drugs as prototypes of two distinct classes of
psychotomimetic drugs. Whether the effects of cumulative doses of

amphetamine (or the immediate as well as prolonged effects of acute doses of
methamphetamine) are linked to persisting effects of intermediate
metabolites of the drug is not precisely known. The presence of LSD in the
body can be roughly correlated with different phases in the drug response.
For example, it is apparent that four to eight hours after the acute LSD effects
(which correspond to the half-life of the drug in plasma), suspiciousness and
ideas of reference are characteristic when the acute “TV show in the head” is
over. It would be misleading to suggest, therefore, that the syndromes are
distinctively different with the two drugs at the clinical level, as evident from
the following example.
The patient was Nancy, a twenty-year-old female in her second year at
college. She was basically rather easygoing but was particularly influenced by
her father whom she described as a “man of principle,” and who was
frequently very critical of her. She took a summer trip alone and was given
LSD by some travelers she met along the way. The psychosis which resulted
was later described by Nancy during her recovery in the following manner:
I had spent the whole summer testing out life styles. So I decided to take
a trip out west to see what I could learn from others. That’s when I met this
fellow Ray. I was fascinated by the life they lived—lots of drags and sex. I felt
this was the opening up of sex for me. You have to understand that this was a
complete change in life style for me, a new world completely. Some parts
were beautiful. I took several capsules of acid over the two-week period and
began to see significance in things. They mentioned a dog and I thought I had
become a dog sexually. Maybe, I thought, they were trying to teach me not to
be up tight about sex. I began to have the notion that I would have a sex-
change operation. Maybe I was a guy trapped in a woman’s body. My mind
was running like crazy. I thought I was adopted, maybe sterile or suffering
from mental retardation. I saw a double rainbow and that made me believe
there was hope. Noises were especially loud. Anything I ever had as a
problem my mind dug up. Particularly problems with my father and with
church. All the books I had ever read in my life seemed to come back to me. I
thought I might have a terminal disease, be sterile or pregnant. So much was
hitting my head at once. I often had a very strong urge to laugh. My body was
supersensitive. I thought my bed would separate and that I would be torn in

half, that the top half of me belonged to the devil and I would pay for what I
had done. On my way to a hospital I noticed that everything behind me was
being burned or destroyed. Again the idea of the atom bomb having been
dropped came to me. I thought I would die and be reborn. In the hospital I
thought one of the nurses was the devil. That meant I was split in quarters—
half of me was a devil and half a woman. Also I was afraid to move for fear
that something terrible would happen. I thought there was something

registering my movements. I had an idea that I had to save the neighborhood.
Sometimes I felt only capable of destruction, other times I thought I could

save others.
Of particular significance in this kind of syndrome are the dynamic

issues related to guilt and self-debasement. Such concerns have emerged
repeatedly in cases we have seen and in reports of psychotic reactions related
to LSD ingestion. In some ways the prolonged LSD-psychosis is similar, at
least at the level of clinical analysis, to psychotic depression. Conflictual
issues of guilt and shame seem uniquely heightened and thrust into
awareness by these drugs. Long-term ingestion of LSD-like compounds may

result in amotivational states which can be ego-syntonic and associated with
atypical belief systems or delusional ideas.
Although the actual mechanism of action of LSD-like drugs is unknown,
a remarkably reliable property of psychoactive drugs in this class is their
biochemical and physiological effect upon 5-hydroxytryptamine-containing

neurons. There is tentative evidence that psychotic reactions following LSD
may be associated with decreased formation of 5-hydroxyindoleacetic acid, a
metabolite of 5-hydroxytryptamine, in cerebrospinal fluid, a finding

consistent with the neurochemical effect of acute administration of LSD-like
drugs to animals. (See references 47, 50, and 86).
Cannabis
Although there has been some controversy concerning the
psychotogenic potential of cannabis-containing compounds, the question,
apparently, is primarily one of dose. In countries where strong cannabis
preparations are available, psychotic reactions are not uncommon (See

references 58, 71, 73, 81, 94, 97, and 106). Although the basic pharmacology
is somewhat different, the spectrum of psychotic reactions to cannabis
compounds is quite similar to that seen in LSD-related psychoses. Under
experimental conditions with human subjects, Jones has shown that higher
doses of cannabis produce effects indistinguishable from LSD on many

behavioral scales. An unusual study documents the strikingly increased
incidence of quasi-schizophrenic psychoses in a group of American
servicemen during a period when hashish usage was extensive. With high
doses of the active ingredient, Ag-THC (delta-g-tetrahydrocannabinol) a

number of LSD-like psychotomimetic effects occur, but the dysphoric episode
is generally terminated by drowsiness—unlike LSD effects.
Experienced users are aware of paranoid like responses after
unexpectedly high doses, i.e., a hypervigilance and ideas of reference. There

are many features and factors in psychotic reactions to cannabis which
require differentiation in future research. These include the role of prior
state. Most studies, such as the report of Mayor LaGuardia’s Committee on

Marihuana in 1944, indicate a small incidence of paranoid reactions although
a general harmlessness of the experience for most individuals. Paranoid

reactions have been ascribed to the use of prepsychotic or vulnerable
subjects. The role of active metabolites in any persisting effects and the role
of factors in both cumulative effects of moderately small, frequent dosages
and of high dosage of the more potent hashish require further attention and
clarification.
L-Dopa
Psychotic reactions following L-Dopa therapy for Parkinsonism occur in

a substantial portion of treated patients. Perhaps because this population is
an older one and often uses anticholinergic drugs in addition to
L-Dopa, a significant number of these reactions are associated with
some of the symptoms of delirium. Although actual reports are rare according
to Snyder, apparently L-Dopa can induce psychotic symptoms in a clear
sensorium in some cases. L-Dopa can induce a manic reaction or exacerbate

psychotic symptoms in individuals who have a prior history of manic and
schizophrenic behavior. Celesia and Barr emphasize that patients with
postencephalitic Parkinsonism appear most susceptible to the spectrum of

psychoses induced by L-Dopa. The role of “prior state” (perhaps prior
imbalances in neurohumoral storage and release involving receptors and
systems reacting to acetylcholine, catecholamines, and indoleamines) recurs

as an explanatory factor in individual response. Celesia and Barr describe the
unique characteristics of central L-Dopa intoxication; namely, psychosis and
various dyskinetic symptoms, particularly facial and lingual dyskinesias.
When LSD was given forty-eight hours following reserpine pretreatment,

oculogyric crises and dystonia were observed. Interestingly, such dyskinetic
and extrapyramidal syndromes have not been a prominent aspect to the
amphetamine psychoses, although stimulation of dopamine receptors is
thought to play a major role in the mediation of several components of the
amphetamine psychoses. Preexisting receptor sensitivity may be a

differentiating factor in the clinical manifestations of dopaminergic
stimulation.
Drugs Used in the Treatment of Psychological Depression
The monoamine oxidase inhibitors and tricyclic antidepressants,
compounds effective in the treatment of certain depressive syndromes, may
be associated with acute psychotic reactions even when employed at the
usual therapeutic doses, as illustrated by the following case.
Example. A 28-year-old man, depressed and seclusive for months, was

treated with a monoamine oxidase inhibitor. After two weeks he became
more verbal and less depressed. However, he soon began to be hyperactive,

agitated, and grandiose as exemplified in the following excerpt from a letter
he wrote at that time to a woman whom he had known only a few days and
who had been frightened by his intensity:
Dear Jane: I know the reason you have run away from everyone and
from me, the man you said you would share everything openly with, who
believed in you and who trusted you to keep your word, not to be childish or
afraid, is because you had a difficult menstrual period for a week and a very
upsetting one which both of us can’t take. I pray desperately every night that
you will phone me or come back to me for help. Do you think everything we
ever said and did together meant nothing [his emphasis] or was false or
sinful? Dear God in Heaven, give me strength to face this crisis. If Jane has
sinned please let me take her sins as mine so that she may come to me or
heaven, serene and unmolested. If Jane or any other girl I’ve known should
need blood or eyes or even a heart, let them be compatible with mine that I
may give my organs freely to them, though my worthless, homely self dies.
Amen. ... I started excellent dancing lessons and want you to come. I brought
you a six hundred dollar wedding night ceremony present, about a thousand
dollars of clothes and apartment furnishings, and I’ve dusted my hope chest
off to share with you alone.
This mania like state with elements of elation and depression subsided
over several days following the withdrawal of the drug. Elation or psychotic
suspiciousness may be observed in the course of tricyclic antidepressant drug

treatment and tends to subside rapidly following drug withdrawal and
antipsychotic drug therapy. In such cases one assumes that there is some
innate proclivity to psychotic or manic states. These drugs have been shown
to exacerbate psychotic symptoms in individuals who have been diagnosed as
schizophrenic. Tricyclic compounds, as noted above, also possess significant
anticholinergic activity and may be associated with delirium. The clinical
distinction between a primary manic or psychotic state versus delirium with
psychosis during tricyclic therapy may be difficult, but can usually be made by
noting the presence or absence of significant disorientation. It is sometimes
possible to achieve useful antidepressant results without the recurrence of
delirium by a reduction in dosage.
Treatment
The most important step in the treatment of drug-related psychotic
episodes is proper diagnosis and removal of the offending drug when
possible. With potent pharmacological substances so readily available, a drug-

induced reaction should be part of the differential diagnosis of any acute
psychotic syndrome. The role of careful history, of “mismatches” between
factors such as current stress and prior adjustment and the current mental
status, the presence of amnesia or delirioid features may occasionally help in
this, although there are few clear-cut pathognomonic features. Conservative
management is always indicated where diagnosis is in doubt. The classical

principles involved in the treatment of drug-induced delirium apply here:
protection of the individual, general nursing care, and a supportive, simplified
environment. Unless a pharmacological addition to therapy is clearly
indicated, it is wise to avoid compounding the trouble with yet another drug.
Where hyperactive behavior is a problem, acute sedation with barbiturates
may be as useful as phenothiazine administration. The important role of
setting and psychological support for the treatment of psychotic drug

reactions has recently been reemphasized. (It is a curious observation that
psychotic reactions clearly related to drug use rarely evoke the same
sympathy or therapeutic zeal in treatment personnel as do other psychotic

states.) If the psychotic reaction is brief and essentially terminated within
twenty-four hours one may be justified in providing acute treatment only.
However, if the reaction is prolonged or uniquely disturbing to the individual,
responsible treatment should include several follow-up visits to determine
whether characteristic defensive forces have been redeployed and to evaluate
current life stresses the individual is facing which may have contributed to
the dysphoric reaction. Where drug use initiates a psychotic process which
seems to gain momentum and continue beyond the known duration of drug
action, psychiatric hospitalization may be necessary. Flashbacks or related
recurrent phenomena present interesting treatment problems in their own

right. In general the therapeutic approach involves an avoidance of undue
attention to the phenomena themselves and a focus upon attendant life tasks
which are being avoided. Sedative antianxiety drugs or low doses of
phenothiazines may be of some benefit as in other nonpsychotic conditions
where symptom relief facilitates psychological work.
Bibliography
Abramson, H. A. in H. A. Abramson, ed., Conference on Neuropharmacology, Trans. 3rd Conf., p.

268. New York: Josiah Macy, Jr., Foundation, 1957.
Aghajanian, G. “Influence of Drugs on the Firing of Serotonin-Containing Neurons in Brain,” Fed.

Proc., 31 (1972), 91-96.
Aghajanian, G. and O. Bing. “Persistence of Lysergic Acid Diethylamide in the Plasma of Human
Subjects,” Clin. Pharmacol. Ther., 5 (1964), 611-614.
Anderson, E. “Propylhexedrine (Benzedrex) Psychosis,” N.Z. Med. J., 71 (1970), 302.
Angrist, A. and S. Gershon. “The Phenomenology of Experimentally Induced Amphetamine

Psychosis-Preliminary Observations,” Biol. Psychiatry, 2 (1970), 95-107.
Angrist, B., J. Schweitzer, A. Friedhoff et al. “The Clinical Symptomatology of Amphetamine

Psychosis and Its Relationship to Amphetamine Levels in Urine,” Int.
Pharmacopsychiatry, 2 (1969), 125-139.
Angrist, B., J. Schweitzer, S. Gershon et al. “Mephentermine Psychosis: Misuse of the Wyamine
Inhaler,” Am. J. Psychiatry, 126 (1970), 1315-1317.
Angrist, B., B. Shopsin, and S. Gershon. “Comparative Psychotomimetic Effects of Stereoisomers of

Amphetamine,” Nature, 234 (1971), 152-153.
Baldessarini, R. and R. Willmuth. “Psychotic Reactions During Amitriptyline Therapy,” Can.

Psychiatr. Assoc. J., 13 (1968), 571-573.
Bass, M. “Sudden Sniffing Death,” JAMA, 212 (1970), 2075-2079.
Bell, D. “A Comparison of Amphetamine Psychosis and Schizophrenia,” Br. J. Psychiatry, 3 (1965),

701-706.
----. “The Experimental Reproduction of Amphetamine Psychosis,” Arch. Gen. Psychiatry, 29
(1973). 35-45.
Bethell, M. “Toxic Psychosis Caused by Radioactive Iodine,” Br. J. Psychiatry, 117 (1970), 473-479
Blacker, K., R. Jones, G. Stone et al. “Chronic Users of LSD: The ‘Acidheads’,” Am. J. Psychiatry, 125
(1968), 341-351.
Blatherwick, C. “Understanding Glue Sniffing,” Can. J. Public Health, 63 (1972), 272-276.
Bowers, M. “Acute Psychosis Induced by Psychotomimetic Drug Abuse,” Arch. Gen. Psychiatry, 27
(1972), 437-442.
Bowers, M., A. Chipman, A. Schwartz et al. “Dynamics of Psychedelic Drug Abuse,” Arch. Gen.
Psychiatry, 16 (1967), 560-565.
Bowers, M. and D. Freedman. “‘Psychedelic’ Experiences in Acute Psychoses,” Arch. Gen.

Psychiatry, 15 (1966), 240-248.
Bowers, M., E. Goodman, and V. Sim. “Some Behavioral Changes in Man Following
Anticholinesterase Administration,” J. Nerv. Ment. Dis., 138 (1964), 383-389.
Bowers, M. and D. Singer. “Thyrotoxicosis and Psychological State,” Psychosomatics, 5 (1964),

322-324.
Braceland, F. “Mental Symptoms following Carbon Disulphide Absorption and Intoxication,” Ann.
Intern. Med., 16 (1942), 246-261.
Brawley, P. and J. Duffield. “The Pharmacology of Hallucinogens,” Pharmacol. Rev., 24 (1972), 31-
66.
Bridger, W. “Psychotomimetic Drags, Animal Behavior, and Human Psychopathology,” in J. O.

Cole, A. M. Freedman, and Friedhoff, eds., Psychopathology and
Psychopharmacology, pp. 133—142. Baltimore: The Johns Hopkins University
Press, 1973.
Bridger, W. and I. Mandel. “Excitatory and Inhibitory Effects of Mescaline on Shuttle Avoidance in
the Rat,” Biol. Psychiatry, 3 (1971), 379-385.
Cameron, O. “Stimulus Properties of Drugs: LSD as SD and UCS,” Dissertation, University of

Chicago, August 1972.
Celesia, G. and A. Barr. “Psychosis and Other Psychiatric Manifestations of Levodopa Therapy,”
Arch. Neurol., 23 (1970), 193-200.
Celesia, G. and W. Wanamaker. “Psychiatric Disturbances in Parkinson’s Disease,” Dis. Nerv. Sys.,
33 (1972), 577-583.
Clark, L., W. Bauer, and S. Cobb. “Preliminary Observations on Mental Disturbances Occurring in
Patients Under Therapy with Cortisone and ACTH,” N. Engl. J. Med., 246 (1952),
205-216.
Connell, P. Amphetamine Psychosis. Maudsley Monogr. no. 5, p. 5. London: Oxford University

Press, 1958.
Crowell, E. and J. Ketchum. “The Treatment of Scopolamine-Induced Delirium with

Physostigmine,” Clin. Pharmacol. Ther., 8 (1967), 409-414.
Daly, R., F. Kane, and J. Ewing. “Psychosis Associated with the Use of a Sequential Oral
Contraceptive,” Lancet, 2 (1967), 444-445.
Damasio, A., J. Lobo-Antunes, and Macedo. “Psychiatric Aspects in Parkinsonism Treated with L-
Dopa,” J. Neurol. Neurosurg., Psychiatry, 34 (1971), 502-507.
Domino, E. F. “Neurobiology of Phencyclidine (Sernyl), a Drug with an Unusual Spectrum of

Pharmacological Activity,” Int. Rev. Neurobiol., 6 (1964), 303-347.
Domino, E. F. and E. Luby. “Abnormal Mental States Induced by Phencyclidine as a Model of

Schizophrenia,” in J. O. Cole, A. M. Freedman, and A. Friedhoff, eds., Psychopathology
and Psychopharmacology, pp. 37-50. Baltimore: The Johns Hopkins University
Press, 1973.
Duvoisin, R. and R. Katz. “Reversal of Central Anticholinergic Syndrome in Man by
Physostigmine,” JAMA, 206 (1968), 1963-1965.
Edison, G. “Hallucinations Associated with Pentazocine,” N. Engl. J. Med., 281 (1969), 447-448.
Elkes, J. “Effects of Psychotomimetic Drags in Animals and Man,” in H. A. Abramson, ed.,

Conference on Neuropharmacology, Trans. 3rd. Conf., pp. 205-295. New York: Josiah
Macy, Jr., Foundation, 1957.
Ellinwood, E. “Amphetamine Psychosis 1: Description of the Individuals and Process,” ]. Nerv.

Ment. Dis., 44 (1967), 273-280.
----. “Effect of Chronic Methamphetamine Intoxication in Rhesus Monkeys,” Biol. Psychiatry, 3

(1971), 25-32.
----. “Assault and Homicide Associated with Amphetamine Abuse,” Am. J. Psychiatry, 127 (1971),
1170-1175.
Ellinwood, E. and O. Escalante. “Behavior and Histopathological Findings During Chronic

Methedrine Intoxication,” Biol. Psychiatry, 2 (1970), 27-39.
Ellinwood, E., A. Sudilovsky, and L. Nelson. “Behavioral Analysis of Chronic Amphetamine

Intoxication,” Biol. Psychiatry, 4 (1972). 215-230.
Erikssen, J. “Atropine Psychosis,” Lancet, 1 (1969), 53-54.
Escalante, O. and E. Ellinwood. “Central Nervous System Cytopathological Changes in Cats with
Chronic Methedrine Intoxication,” Brain Res., 21 (1970), 151-155.
Flowers, N. and L. Horan. “The Electrical Sequelae of Aerosol Inhalation,” Am. Heart J., 83 (1972),
644-651.
----. “Nonanoxic Aerosol Arrhythmias,” JAMA, 219 (1972), 33-37-
Freedman, D. “Studies of LSD-25 and Serotonin in the Brain,” Proc. 3rd World Congr. Psychiatry, 1
(1961), 653-658.
----. “On the Use and Abuse of LSD,” Arch. Gen. Psychiatry, 18 (1968), 330-347.
Freedman, D. and N. Giarman. “Brain Amines, Electrical Activity, and Behavior,” in G. H. Glaser,
ed., EEG and Behavior, pp. 198-243. New York: Basic Books, 1963.
Freedman, D., R. Gottlieb, and R. Lovell. “Psychotomimetic Drugs and Brain 5-Hydroxytryptamine
Metabolism,” Biochem. Pharmacol., 19 (1970), 1181-1188.
Gershon, S. and B. Angrist. “Drug-Induced Psychoses,” Hosp. Practice, 2 (1967), 36-39, 50-53.
Giarman, N. and D. Freedman. “Biochemical Aspects of the Actions of Psychotomimetic Drugs,”

Pharmacol. Rev., 17 (1965), 1-25.
Glass, G. and M. Bowers. “Chronic Psychosis Associated with Long-Term Psychotomimetic Drug
Abuse,” Arch. Gen. Psychiatry, 23 (1970), 97-103.
Gonzales, E. and J. Downey. “Polyneuropathy in a Glue Sniffer,” Arch. Phys. Med. Rehahil., 53
(1972), 333-337-
Goodwin, F. “Psychiatric Side Effects of Levodopa in Man,” JAMA, 218 (1971), 1915-1920.
Gordy, S. and M. Thumper. “Carbon Disulfide Poisoning with a Report of Six Cases,” JAMA, 110
(1938), 1543-1549.
Griffith, J., J. Cavanaugh, J. Held et al. “Dexroamphetamine-Evaluation of Psychotomimetic

Properties in Man,” Arch. Gen. Psychiatry, 26 (1972), 97-100.
Grossman, W. “Adverse Reactions Associated with Cannabis Products in India,” Ann. Intern. Med.,
70 (1969), 529-533.
Hedley, A. and P. Bewsher. “Psychosis and Antithyroid Drug Therapy,” Br. Med. J., 3 (1969), 596-
597.
Hoch, P., J. Cattell, and H. Pennes. “Effects of Mescaline and LSD,” Am. J. Psychiatry, 108 (1952),
579-584.
Hoff, E. “Brain Syndromes Associated with Drug or Poison Intoxication,” in A. Freedman and H.
Kaplan, eds., Comprehensive Textbook of Psychiatry, pp. 759-775. Baltimore:
Williams & Wilkins, 1967.
Hollister, L. Chemical Psychosis. Springfield, Ill.: Charles C. Thomas, 1968.
Hollister, L., R. Richards, and H. Gillespie. “Comparison of Tetrahydrocannabinol and Synbexyl in

Man,” Clin. Pharmacol. Ther., 9 (1969), 783-791.
Horn, A. and S. Snyder. “Chlorpromazine and Dopamine: Conformational Similarities that

Correlate with the Antischizophrenic Activity of Phenothiazine Drugs,” Proc. Natl.
Acad. Sci. USA, 68 (1971), 2325-2328.
Hussain, M. and J. Murphy. “Psychosis Induced by Oral Contraception,” Can. Med. Assoc. J., 104
(1971), 984-986.
Isbell, H., R. E. Belleville, and H. F. Fraser. ’’Studies on Lysergic Acid Diethylamide (LSD-25),” Arch.
Neurol. Psychiatry, 76 (1956), 468-478.
Isbell, H., A. B. Wolbach, A. Winkler et al. “Cross Tolerance Between LSD and Psilocybin,”
Psychopharmacologia, 2 (1961), 147-159.
Janowsky, D., M. El-Yousef, J. Davis et al. “Provocation of Schizophrenic Symptoms by Intravenous

Methylphenidate,” Arch. Gen. Psychiatry, 28 (1973), 185-193.
Jones, R. “Drug Models of Schizophrenia—Cannabis,” in J. O. Cole, A. M. Freedman, and A.

Friedhoff, eds., Psychopathology and Psychopharmacology, pp. 71-86. Baltimore:
The Johns Hopkins University Press, 1973.
Kane, F. and R. Florenzano. “Psychosis Accompanying Use of Bronchodilator Compound,” JAMA,

215 (1971), 2116.
Keup, W. “Psychotic Symptoms Due to Cannabis Abuse,” Dis. Nerv. Syst., 31 (1970), 119-126.
Kimura, E., D. Ebert, and P. Dodge. “Acute Toxicity and Limits of Solvent Residue for Sixteen
Organic Solvents,” Toxicol. Appl. Pharmacol., 19 (1971), 699-704.
Klee, G. “Marihuana Psychosis—a Case Study,” Psychiatr. Q., 43 (1969), 719-733.
Levin, M. “Transitory Schizophrenias Produced by Bromide Intoxication,” Am. J. Psychiatry, 103

(1946), 229-237.
----. “Bromide Psychosis: Four Varieties,” Am. J. Psychiatry, 104 (1948), 798-800.
Lidden, S. and R. Satran. “Disulfiram (Antabuse) Psychosis,” Am. J. Psychiatry, 123 (1967), 1284-
1289.
Louria, D., T. Hensle, and J. Rose. “The Major Medical Complications of Heroin Addiction,” Ann.
Intern. Med., 76 (1967), 1-22.
Luby, E., B. Cohen, G. Rosenbaum et al. “Study of a New Schizophrenomimetic Drag-Sernyl,” Arch.
Meyer, J., F. Greifenstein, and M. Devault. “A New Drug Causing Symptoms of Sensory
Deprivation,” J. Nerv. Ment. Dis., 129 (1959), 54-61.
Newell, H. and T. Lidz. “The Toxicity of Atabrine to the Central Nervous System,” Am. J. Psychiatry,
102 (1946), 805-818.
Perna, D. “Psychotogenic Effect of Marihuana,” JAMA, 209 (1969), 1085-1086.
Quarton, G., L. Clark, S. Cobb et al. “Mental Disturbances Associated with ACTH and Cortisone,”
Medicine (Baltimore), 34 (1955), 13-50.
Redlich, F. and D. Freedman. The Theory and Practice of Psychiatry, p. 741. New York: Basic Books,
1966.
Reich, P. and R. Hepps. “Homicide During a Psychosis Induced by LSD,” JAMA, 219 (1972), 869-
871.
Rome, H. and F. Braceland. “Psychological Responses to Corticotropin, Cortisone, and Related
Steroid Substances,” JAMA, 148 (1952), 27-30.
Rosecrans, J., R. Lovell, and D. Freed man. “Effects of Lysergic Acid Diethylamide on the
Metabolism of Brain 5-Hydroxytryptamine,” Biochem. Pharmacol., 16 (1967), 2011-
2021.
Salvatore, S. and R. Hyde. “Progression of Effects of LSD,” Arch. Neurol. Psychiatry, 76 (1956), 50-
59.
Shick, J. and D. Smith. “Analysis of the LSD Flashback,” J. Psychedel. Drugs, 3 (1970), 13-19.
Shilliro, F., C. Drinker, and T. Shaughnessy. “The Problem of Nervous and Mental Sequelae in
Carbon Monoxide Poisoning,” JAMA, 106 (1936), 669-674.
Smith, D. “An Analysis of 310 Cases of Acute High-Dose Methamphetamine Toxicity in Haight-
Ashbury,” Clin. Toxicity, 3 (1970), 117-124.
Snyder, S. “Catecholamines in the Brain as Mediators of Amphetamine Psychosis,” Arch. Gen.

Psychiatry, 27 (1972), 169-179.
Snyder, S., K. Taylor, J. Coyle et al. “The Role of Brain Dopamine in Behavioral Regulation and the
Actions of Psychotropic Drugs,” Am. J. Psychiatry, 127 (1970), 199-207.
Soskis, D. and M. Bowers. “The Schizophrenic Experience—A Follow Up Study of Attitude and
Posthospital Adjustment,” J. Nerv. Ment. Dis., 149 (1969), 443-449.
Spencer, D. “Cannabis Induced Psychosis,” Br. J. Addict., 65 (1970), 369-372.
Spensley, J. and D. Rickwell. “Psychosis during Methylphenidate Abuse,” N. Engl. J. Med., 286
(1972), 880-881.
Stockings, G. “A Clinical Study of the Mescaline Psychosis, with Special Reference to the
Mechanism of the Genesis of Schizophrenic and Other Psychotic States,” J. Ment.
Sci., 86 (1940), 29-47.
Talbott, J. and J. Teague. “Marihuana Psychosis,” JAMA, 210 (1969), 299-302.
Taylor, R., J. Maurer, and J. Tinklenberg. “Management of ‘Bad Trips’ in an Evolving Drug Scene,”
JAMA, 213 (1970), 421-425.
Tennant, F. and C. Groesbeck. “Psychiatric Effects of Hashish,” Arch. Gen. Psychiatry, 27 (1972),
133-136.
Thomas, D. and D. Freedman. “Treatment of the Alcohol Withdrawal Syndrome,” JAMA, 188
(1964), 316-318.
Ullman, K. and R. Groh. “Identification and Treatment of Acute Psychotic States Secondary to the
Usage of Over-the-Counter Sleeping Preparations,” Am. J. Psychiatry, 128 (1972),
1244-1248.
Victor, M. and R. Adams. “The Effect of Alcohol on the Nervous System,” Assoc. Res. Nerv. Ment. Dis.
Proc., 32 (1953), 526-573.
Wallach, M., R. Angrist, and S. Gershon. “The Comparison of the Stereotyped Behavior-Inducing
Effects of d- and 1-Amphetamine in Dogs,” Comm. Behav. Biol., 6 (1971). 93-96.
Wallach, M., E. Friedman, and S. Gershon. “2,5-Dimethoxy-4-Methylamphetamine (DOM), a

Neuropharmacological
Examination,” J. Pharmacol. Exp. Ther., 182 (1972), 145-154.
Wallach, M. and S. Gershon. “A Neuro-psychopharmacological Comparison of D-Amphetamine, L-

Dopa, and Cocaine,” Neuropharmacology, 10 (1971), 743-752.
Weil, A. “Adverse Reactions to Marihuana,” N. Engl. J. Med., 282 (1970), 997-1000.
Weil-Malherbe, H. and S. Szara. The Biochemistry of Functional and Experimental Psychoses.

Springfield, Ill.: Charles Thomas, 1971.
Weinstein, M. and A. Fischer. “Benztropine Toxicity and Atropine Psychosis,” JAMA, 220 (1972),
1616-1617.
Yost, M. and F. McKegney. “Organic Psychosis Due to Talwin (Pentazocine),” Conn. Med., 34
(1970), 259-260.
Young, D. and W. Scoville. “Paranoid Psychosis in Narcolepsy and the Possible Dangers of
Benzedrine Treatment,” Med. Clin. North Am., 22 (1938), 637-646.
Chapter 15
Alcoholism: A Biobehavioral Disorder1
Nancy K. Mello and Jack H. Mendelson
Introduction
This chapter presents an overview of our current state of knowledge
concerning the actions of alcohol, the disease of alcoholism, and patterns of

use and abuse in contemporary American society. The basic pharmacology of
alcohol effects is reviewed, and the medical, psychological, and social
consequences of prolonged alcohol abuse and alcoholism are described.
Comparisons are made between alcohol addiction and drug addiction
wherever possible. The limitations in our current understanding of the
factors which influence the development and maintenance of alcohol abuse

and alcoholism are discussed, and the potential efficacy of existing treatment
approaches is evaluated. We conclude that significant progress in combating

alcohol abuse requires clarification of the basic mechanisms of the addictive
process to permit development of effective therapies as well as productive
strategies for prevention.
Alcohol: Beverage and Drug
All beverage alcohols, wine, beer and distilled spirits, contain the same
primary ingredient, ethyl alcohol or ethanol. Ethanol is a relatively simple

organic molecule which is produced in abundance by the fermentation
processes of microorganisms. Virtually all unicellular organisms have the
capacity to produce ethanol given the availability of sugar, water, yeast,
oxygen, warmth, and an appropriate acid-base balance. These basic

ingredients have been present on earth since paleozoic times.
Beverage alcohols differ primarily in ethanol concentration which

usually ranges from less than 4 percent for beer, to over 12 percent for wine,
to 40-50 percent for distilled spirits. Under ordinary biological conditions,
microorganisms do not produce alcohol concentrations in excess of 12-14

percent. However, man’s discovery of distillation processes has permitted
production of beverage alcohols with a higher concentration of ethanol.
Alcohol boils at a lower temperature than water and therefore can be
separated from its vehicle and concentrated. The term brandy derives from a
German term for burnt distilled wine. Beverage alcohols also differ in terms
of congener content or nonethanol impurities which include vitamins, organic
and amino acids, minerals, salts, sugars, etc., as well as low concentrations of
the higher alcohols (known as fusel oils) which are relatively toxic. The
nonnutritional congener content of distilled spirits is higher than that of wine
or beer and has been shown to increase as a function of aging.
It is well known that the rate of alcohol absorption into the blood varies
markedly between beer, wine, and distilled spirits. Some congeners also affect
the rate of alcohol absorption. Generally, the higher the alcohol concentration,
the more rapid its absorption, whereas the higher the congener
concentration, the slower its absorption.
The nutrient value of alcohol is negligible following distillation. The
caloric content of beverage alcohols varies between 100 and 200 calories per
ounce. However, the extent to which calories in alcohol are equivalent to
calories derived from food remains a subject of controversy. Alcoholics tend
to eat poorly while they are drinking and it has often been suggested that this
is due to the high caloric yield from alcohol. However, it has recently been
observed that alcohol addicts receiving a daily total combined caloric intake
from food (about 2000 calories) and alcohol averaging 4000 to 5000 calories
did not gain weight over a two-month period. The small effective contribution
of calories from alcohol to the total caloric pool may reflect the fact that
utilization of calories from vitamin-deficient sources such as alcohol is
impaired when food intake is adequate.
Alcohol Use in Historical Perspective
Alcohol was first discovered perhaps 200 million years ago and relics of
the earliest civilizations show that alcohol was used in religious ceremonies,
medical treatment, and in many aspects of daily life. It has been speculated
that Paleolithic man learned to ferment honey and that the development of
agriculture was paralleled by the improvement of techniques for

fermentation of fruits and grains, culminating in the process of distillation
during the first century a.d. The legendary origins of alcohol are intermixed
with the religious beliefs of many cultures, and it was commonly considered
to be a gift of the Gods. In ancient Egypt and Greece, Osiris and Dionysus were
worshipped as the givers of wine. It was believed that the Gods could use this
gift to cause madness or enhance pleasure and awareness in the drinker.
Later, alcohol itself was imbued with an autonomous power and a trace of
animistic thinking about alcohol still persists.
Although festival drunkenness was condoned, the secular use of alcohol
was accompanied by many warnings against excessive drinking throughout

history. One of the oldest temperance tracts, entitled The Wisdom of Ani, was
written in Egypt about 3000 years ago. Denunciation of excessive drinking
can be found throughout ancient writings of Greece, Rome, India, Japan, and
China as well as in the Old and New Testaments.
The early temperance movement of the 1830s recommended
abstinence only from distilled spirits. Subsequently, there developed an
increasing opposition to all alcoholic beverages, which were finally banned by
the eighteenth amendment in 1920. National prohibition was repealed in
1933 by the twenty-first amendment in response to a complex series of
attitude changes about self-regulation of drinking and the dangers of
bootlegging. Legal sanctions2 proved ineffective in controlling alcohol abuse

and in modifying the fact that many people like to drink. In contemporary
American society, most adults consume some alcoholic beverages, and,
apparently, most do so in a responsible and healthy way.
Medical Use of Alcohol
There is no current medical use of alcohol. Before the introduction of
anesthesia, alcohol was used during surgical procedures in an effort to
alleviate pain. However, since the dosage of alcohol required to produce loss
of consciousness is close to a lethal dose for normal drinkers, alcohol is

impractical as an anesthetic agent.
During the early part of the century, alcohol was occasionally used to
counteract the alcohol-withdrawal syndrome. Although alcohol did reduce
tremor briefly, its duration of action was too short to be practical. Moreover,
prolonged use of alcohol merely reinstated the condition of chronic
intoxication which leads to withdrawal symptoms following alcohol
termination.
Until recently, alcohol was the drug of choice for the treatment of
familial action tremor. This condition is now treated with propranolol (a beta-
adrenergic blocking agent used in the clinical management of cardiac
arrhythmias). The efficacy of both alcohol and propranolol in reducing

symptoms of familial action tremor suggests that both may have a common
receptor site in the central nervous system (CNS).
Current Patterns of Alcohol Use and Abuse
According to a recent survey of American drinking practices, an

estimated two thirds of all adults use alcohol occasionally. Total abstinence
accounted for 32 percent of the 2746 representative persons surveyed. There
were considerable regional variations in beverage preference and in the usual

amount of alcohol consumed.
Of the alcohol users studied, 12 percent were categorized as “heavy”

drinkers; i.e., persons who drank almost daily or once a week and often
consumed five or more drinks per occasion. There are several problems
associated with a compilation of a meaningful volume-frequency index of
alcohol consumption. Although people may drink comparable total quantities
of alcohol over a particular time interval, the extent to which they space
drinking or concentrate drinking within a brief period may reflect distinctly
different drinking patterns. In contrast to the “heavy” drinker, an alcohol
addict may drink between 24 to 32 oz. per day in increments of 2 or 3 oz. per
occasion. The length of a drinking spree may vary from a few days to two
weeks or more.
A follow-up survey of American drinking practices revealed that there
was considerable dynamic change in composition of the “heavy” drinking
group and of moderate and infrequent drinking groups. During the three-year
interval between two successive surveys, 15 percent of the sample had

moved out of or into the heavy drinking group. Even in the abstinent group,
one third reported that they once used to drink. This high turnover rate is
somewhat encouraging insofar as it indicates that heavy drinking does not

invariably progress towards alcohol abuse or alcoholism.
Many interrelated sociological, demographic, economic, and
psychological variables affect drinking patterns. The largest proportion of

problem drinkers appear to be persons of lower socioeconomic status living
in urban areas. The highest rates of alcohol-related problems were found in
urban men, under 25, single and divorced, who often reported disrupted
childhoods and a transition from rural to city living. The proportion of heavy
drinkers among white and black males was comparable (22 vs. 19 percent),
whereas black women showed a considerably higher rate of heavy drinking
(11 percent) than white women (4 percent). However, estimates of alcohol
abuse prevalence rates based on arrested or hospitalized alcoholics show a
higher rate of severe drinking problems among ghetto-reared black males.

American Indians and Eskimos have also been shown to be at high risk for the
development of alcoholism.
The commonalities that have emerged from cross-sectional survey
studies do not permit reliable prediction of the development of problem
drinking. Both heavy drinkers and abstainers have been described as more
discontented and alienated from society than persons who use alcohol in
moderation. Data from longitudinal studies suggest that the same childhood
patterns predict drinking problems for ghetto-reared blacks and whites.

Among both whites and blacks, adult drinking problems appear to be
associated with early school problems, delinquency, drug use, and broken
homes. These data have been interpreted to suggest that attention to early
school problems might avert the subsequent progression of school failure and
dropout, early drug exploration, and adolescent delinquency.
It is important to recognize that alcohol problems are not restricted to

the disadvantaged, but can develop in anyone who drinks alcohol to excess.
Alcoholism is considered to be the major drug-abuse problem in

contemporary American society. It has been estimated that perhaps 5 million
persons suffer from alcoholism. However, it should be emphasized that
accurate case finding in alcoholism has been severely limited by the social
stigma associated with this disorder. Consequently, accurate estimates of
incidence and prevalence have been difficult to obtain. An additional 4 million

persons are thought to abuse alcohol and therefore to be at high risk for the
development of alcoholism. If these estimates are valid, perhaps 7 percent of
the adult population have drinking problems.
The social costs to the afflicted individual and to his family are
incalculable. In its severest form, chronic alcoholism is associated with
disruption of normal social and family ties; job loss and diminution of earning
capacity; compromised physical and psychological health and decreased life
expectancy. A profound and progressive isolation and alienation from self and
society may sometimes terminate in violent death or suicide.
There is no simple formula to calculate the cost to society of the loss of a
productive individual. The social costs of alcoholism have been estimated at

levels of $750 million, $2 billion, and $15 billion dollars annually. Recent
estimates suggest that $10 billion may be spent each year as a function of lost
work time in every sector of the economy. Health and welfare services for
alcoholics and their families cost an estimated $2 billion per year. An
estimated 45 percent of all arrests in 1965 were for public intoxication,

disorderly conduct, and vagrancy. Estimated medical expenses and property
damage associated with alcohol problems bring the yearly cost of alcoholism
to a total of $15 billion. These estimates, considered in connection with the
human costs of alcohol-related traffic fatalities and disrupted lives, testify to
the destructive toll of this poorly understood, complex bio-behavioral

disorder.
Definitions of Alcoholism and Alcohol Abuse
The terms “alcohol abuse” and “alcoholism” are not synonymous, but
rather reflect stages in a continuum of severity from problem drinking to

chronic alcohol addiction. Traditionally, there has been relatively poor
agreement concerning definitions of alcoholism and alcohol abuse. Although
the definition: “repetitive, excessive drinking that results in injury to an
individual’s health, adequate social function, or both,” would be generally

accepted, considerable variation continues to exist in the formulation of more
precise definitions with concomitant criteria for differential diagnosis and
implications for treatment (See references 7, 9, 66, 74, 119, 125, and 189).
Definitions are important since they affect the management of the problem.
The lack of an adequate definition has often impeded progress in our
understanding of alcohol problems.
Sociocultural Definitions
Although at first glance it may not appear difficult to arrive at a
consensus for definition of an alcohol-related problem, there are many
conflicting social, cultural, and religious perceptions which contribute to
continuing disagreement. Some attempts have been made to define alcohol
abuse on the basis of a volume-frequency index of alcohol consumption. This
approach is limited, since a particular drinking pattern will not be uniformly
accepted in different regions or across various cultures. The Expert

Committee of the World Health Organization defines abnormal drinking as
that form of drinking which transgresses the normal social and dietary habits
of the community. Therefore, heavy drinking in a society which condones
drinking would not constitute alcohol abuse, whereas consumption of any

alcohol in a society which has rigorous standards of abstinence would be
considered alcohol abuse. Depending on the standards employed, any
definition of alcohol abuse results either in over-inclusion or under-inclusion

of a large number of cases. Consequently, definitions which involve primarily
social criteria are limited by the enormous variation in acceptable drinking
habits within and between countries.
Pharmacological Definitions
One resolution of the difficulties associated with sociocultural
definitions is to establish diagnostic criteria for alcoholism based on the
pharmacological criteria of addiction: tolerance and physical dependence.
Tolerance for and physical dependence upon alcohol is similar to phenomena
which may develop following the abuse of other drugs which affect the
central nervous system, such as opiates and barbiturates. Tolerance for

alcohol refers to the fact that progressively larger quantities are required to
produce changes in feelings or behavior which had previously been attained
with smaller doses of alcohol. Physical dependence is demonstrated by the

fact that the alcoholic experiences discomfort and physical illness when he
stops drinking or decreases his alcohol intake. It is not necessary for an
alcoholic to stop drinking completely before he experiences withdrawal
symptoms, since a relatively small decrease from high blood-alcohol levels
may precipitate the onset of this disorder.
The pharmacological definition of alcoholism has the advantage of
referring to a series of observable events, i.e., the alcohol withdrawal
syndrome. This objective definition permits selection of comparable patients

for research and treatment evaluation and thereby increases the
generalizability of the results. However, the pharmacological definition is
limited in that it applies only to the alcohol addict and does not include the
early problem drinker. The skid-row alcoholic is the most visible victim of
alcoholism and accounts for an estimated 3-5 percent of Americans with
alcohol problems. The extent of physical dependence among the middle and
upper socioeconomic classes is unknown.
The Disease Concept of Alcoholism
Demonstration that alcoholism is a form of addiction has led to a

gradual acceptance of the idea that alcoholism is an illness and a medical
problem. For many decades, alcoholism was considered primarily within the
context of moral transgression and social deviancy, and public drunkenness

was dealt with in a punitive, criminal-justice system. It has become
increasingly evident that legal sanctions and moral pressures have not
provided an adequate remedy for this problem. An unfortunate result of the
moralistic view of alcoholism was to limit interest in biomedical research on

this condition. Our heritage from these years of scientific neglect is relative
ignorance concerning even the basic phenomenology of alcoholism. Now that

alcoholism, the disease, is considered an appropriate subject for laboratory
and clinical investigation and federal resources are available for research,
biomedical research interest has increased fourfold in six years (1966-1972).
The disease concept of alcoholism is sometimes criticized because it is
thought to be overly restrictive and to imply a linear physical causality
without sufficient attention to social and psychological factors. This criticism
is based upon a misunderstanding of the disease model of alcoholism. In fact,

the model assumes that expression of the disorder depends on an interaction
between the individual, the agent of the disease (alcohol) and the
environment in which the disease process develops (see Figure 15-1). It is
well known that disease processes can rarely be explained on the basis of any
specific factor within these three categories, but rather on their

interrelationships. Even infectious disease is often more closely related to
host-resistance factors and environmental variables than to the presence or
even the virulence of any given infectious agent.
Figure 15-1.
Schematic diagram of a disease model of alcoholism depicting the
interaction between host, agent (alcohol) and the environment.
One important advantage of a disease model of alcoholism is to

stimulate biomedical research and to redirect the attention of physicians to
the medical aspects of this disorder. Traditionally, physicians have shown
considerable reluctance to treat alcoholics for a variety of reasons and it has
been difficult for alcoholics to gain admission to general hospitals. Insofar as
alcoholism is now considered to be within the province of medicine, there
should be an improvement in the quality of care for the medical complications
of alcohol abuse. Moreover, as the physician begins to accept responsibility
for the alcoholic patients, he may become more interested in and skillful at
detecting early warning signals of the illness within the context of general
medical practice.
A Practical Solution Comprehensive Diagnostic Criteria
A constructive and direct outgrowth of the general acceptance of the

disease model of alcoholism is the development of comprehensive diagnostic
guidelines by the National Council on Alcoholism. These criteria specify
behavioral and attitudinal changes, as well as medical problems, to aid the
physician in the early detection of alcohol problems and to permit differential
diagnosis of late-stage alcoholism. There has been an attempt to compare the
significance of certain subjective reports and objective signs in diagnosing
alcohol problems. Common medical complications of alcoholism are

specifically indicated and evaluation of possible concurrent psychiatric
problems is urged.
Early detection is probably a critical aspect of prevention. Individuals at
high risk for alcoholism characteristically deny the contribution of alcohol to
any physical or psychological problems that led them to seek medical advice.
By careful description of the types of behavioral and medical problems
associated with excessive alcohol use, these diagnostic criteria provide a basis
for increased awareness of the danger signs of alcoholism and the possibility
of early intervention by the alert physician. The extent to which the
availability of these diagnostic criteria may increase physicians’ acceptance of

the patient with alcohol problems remains to be determined.
Pharmacology of Alcohol and Alcohol Abuse
Mechanism of Action of Alcohol
The exact pharmacological mechanisms of the actions of alcohol are
unknown. The targets of central and peripheral effects can be specified with
some confidence, but the way in which alcohol produces physiological and
behavioral changes is not understood. In addition to the effects of alcohol on
the central nervous system, which are associated with the subjective and
behavioral correlates of intoxication, alcohol ingestion may also result in a

sensation of warmth and flushing of the skin (due to dilation of the peripheral
blood vessels), muscular relaxation, and stimulation of gastric secretion and

peristalsis.
Some of the physiological changes produced by alcohol may be
determined by selective and perhaps even genetically controlled factors
within an individual. Flushing and peripheral vasodilatation following alcohol
consumption has been found to occur with greater frequency and intensity in
Orientals than in occidentals. Studies of infant responses to alcohol indicate
that this phenomenon is not due to cultural, cognitive, or experiential factors.

These findings have recently been confirmed and extended to adults. This
increased sensitivity of Orientals to alcohol may have some influence on their
perception of drinking as relatively aversive or pleasurable.
Ethanol is absorbed primarily from the small intestine and its rate of
absorption into the blood is influenced by several factors. Rapid drinking
produces a higher concentration of alcohol in blood than slowly sipping a
comparable amount of alcohol. The rate of absorption increases with
increasing concentrations of ethanol (up to a maximum of about 40 percent).

However, increasing concentrations of congeners are associated with a
slower rate of ethanol absorption. The presence of food in the stomach
substantially reduces the rapidity of alcohol absorption, as does a variety of

other factors which may slow the emptying time of the stomach. Given the
same alcohol intake under the same conditions, a 180-pound man has a lower
blood-alcohol level than a 130-pound man. Body weight influences blood
alcohol concentrations because alcohol is uniformly distributed throughout

the body tissue fluids following absorption. Once alcohol attains equilibrium,
its concentration in body tissues is directly proportional to their water
content. Regional concentrations of alcohol are partly dependent on regional
differences in water concentration.
Because of these interacting variables, it is impossible to accurately
predict the blood-alcohol concentration following alcohol ingestion. However,
it has been estimated that the usual legal limit of intoxication for operating a
motor vehicle (100 mg. alcohol per 100 ml. of blood) is attained after
consumption of 6 oz. of distilled spirits on an empty stomach. Three ounces of
alcohol may yield a blood-alcohol level of 50 mg./100 ml. whereas 12 oz. yield
a level of 200 mg./100 ml. In general, the behavioral effects of alcohol are
directly dose related.
Most alcohol is removed by metabolic processes in the liver and only an

estimated 2-10 percent is excreted via the kidneys and lungs. The rate of
alcohol metabolism is the same in normals and in abstinent alcohol addicts.
However, it has been shown that rates of alcohol metabolism may increase as
a function of the amount and duration of ethanol ingestion. At the present

time, there are no pharmacological agents available which significantly
enhance rates of ethanol metabolism with a concomitant reduction of acute
intoxicating effects of alcohol.
Intoxication: Short-Term Effects of Alcohol
The behavioral level of intoxication is a function of the concentration of
alcohol in the blood. It has been shown that low doses of alcohol act as a
stimulant whereas higher doses result in central nervous system depression.
Increases in intoxication as a function of increased alcohol dosage comprise a
continuum from relaxation and mild euphoria to hyperactivity, garrulousness,
and aggression to incoordination, confusion, disorientation, stupor, and
possibly coma or death. A pleasant tranquility and mild sedation may

accompany a blood alcohol level of about 50 mg./100 ml. Motor
discoordination may occur at levels of about 100 mg./100 ml.
Above that level, intoxication is obvious and may produce
unconsciousness in normal (non-tolerant) drinkers. Concentrations above
500 mg./100 ml. may be fatal. The exact mechanisms by which alcohol effects
the brain to produce the behavioral expression of intoxication is unknown.
It was once thought that these sequelae of intoxication reflected a
hierarchical disruption of brain centers progressing from structures which
control complex cognitive and motor behaviors and critical faculties to
structures which control essential life functions such as breathing. It was

suggested that the hyperactivity and emotionality associated with
intoxication could reflect stimulation of relevant neural structures or
depression of other neural complexes which normally inhibit the expression

of these behaviors. It now appears that alcohol acts on a regulatory system,
the reticular activating system, which, in turn, concurrently effects the
activity of both the cerebral cortex and subcortical structures.
There is no simple relationship between moderate levels of alcohol
intoxication and an individual’s capacity to perform a variety of cognitive3

and motor tasks. In part because of the tranquilizing effects of alcohol, some
individuals show improved performance at low doses. The behavioral
tolerance for alcohol which accompanies alcohol addiction is defined by the
lack of impairment of skilled-task performance even at very high blood-
alcohol concentrations (150-200 mg./100 ml.).
Yet, it has been shown that moderate alcohol doses may impair visual
sensory capacities, i.e., specifically brightness discrimination and
readjustment after exposure to bright lights. Auditory and tactile sensitivities
are not dramatically affected and sensitivity to taste and odor is somewhat
impaired. It is attention, judgment, and the integration and evaluation of
sensory information rather than the quality of sensory information per se
that seems to be most affected by alcohol. For example, during intoxication,

people tend to underestimate object speed and distance as well as the
passage of time.
The contribution of alcohol intoxication to accidents is probably a
complex combination of sensory-motor impairments, poor judgment, and
emotional liability and aggressivity. The effects of alcohol on emotionality and
aggressivity are poorly understood. Although alcohol is generally believed to
increase emotional liability, considerable evidence suggests that the social
context strongly influences both the type and direction of emotional
expression during intoxication. Consumption of large amounts of alcohol may

facilitate, and perhaps induce, violent and aggressive behavior including
homicide, armed robbery with aggravated assault, and other crimes of
violence. The possible relationship between alcohol-induced aggressivity and

the preponderance of fatal accidents during intoxication remains to be
determined.
The role of alcohol intoxication in fatal accidents has been clearly
demonstrated. Over half the nonhighway accident fatalities have been shown
to involve known alcoholics or alcohol abusers. In the sample studied, work-

related fatal injuries occurred far less frequently than accidents in the home.
A comparison of the number of positive blood-alcohol levels among accident
victims admitted to a hospital emergency ward showed a decrease from
highway accidents (30 percent), to home accidents (22 percent) to

occupational accidents (16 percent).
The high concordance between automobile accidents and alcohol abuse

is well known. The Injury Control Program of the Public Health Service has
estimated that alcohol contributes to or is associated with 50 percent of fatal
motor vehicle accidents. An estimated 28,000 highway fatalities were
associated with alcohol intoxication during a recent 12 month period.
Statistics on drunken-driving fatalities show that a preponderance of the
victims had blood-alcohol levels above 150 mg./100 ml. These high blood-
alcohol levels suggest that the single vehicle casualties studied were not
social drinkers, but alcohol addicts with substantial behavioral tolerance for
alcohol. The nontoloerant individual would show severe motor and cognitive
dysfunction at these blood alcohol levels which could interfere with driving
altogether.
The effect of alcohol intoxication on sexual function has been the subject
of many anecdotes in the nonscientific literature which usually concur with
Shakespeare’s observation that intoxication provokes desire but impairs

sexual performance. Male alcohol addicts are usually described as
experiencing diminished heterosexual desire and activity and sexual
impotence. Female alcoholics tend to report initiation or increased drinking

during the premenstrual period. There are biological data which indicate that
chronic alcohol abuse may impair sexual function through a disruption of

gonadal function. It is well known that chronic alcoholism in males may be
associated with the development of gynecomastia and testicular atrophy,

which in turn may be related to a derangement in androgen metabolism.
Alcohol intoxication has recently been shown to suppress plasma
testosterone levels to well below the normal range in alcohol addicts. Other
centrally acting depressant drugs (i.e., heroin, barbiturates, and high dosages
of methadone) also suppress plasma-testosterone levels in addicts. Following
alcohol, methadone, and heroin withdrawal, plasma-testosterone levels

return to predrug baseline or to normal levels. The possible endocrine
mechanisms which influence the behavioral expression of sexuality (and
aggression) are as yet unclear.
Following acute intoxication, a generalized somatic discomfort,
commonly called “the hangover,” may occur. The physiological determinants

of the hangover are not understood. It has not been shown that mixing drinks
or the congener content of drinks specifically leads to the development of a
hangover. There are no specific treatments for a hangover and little scientific
support for the efficacy of the popular remedies.
Alcohol Addiction: Long-Term Effects of Alcohol Abuse
Drug addiction is defined by the pharmacological criteria of tolerance
and physical dependence. Some chronic alcohol abusers eventually develop
physical dependence upon alcohol. This end stage of alcohol abuse has been
clearly shown to be an addictive disorder on the basis of both clinical and
experimental observations. It was once thought that physical dependence, the
alcohol withdrawal syndrome, reflected intercurrent illness or vitamin and
nutritional deficiencies. It has now been shown that withdrawal signs and
symptoms occur in healthy well-nourished alcoholics solely as a function of
cessation of drinking. It has also been possible to induce physical dependence
upon alcohol in a variety of experimental animals (See references 22, 27, 30,
32, 104, 137, 187, and 188).
The crucial determinants of the development of alcohol addiction are

unknown, and the nature of the addictive process remains a matter of
conjecture. Thus far, no single theory has proved adequate to explain the
complex multilevel symptoms which we collectively term alcoholism. Most
probably, alcoholism, like any other behavior disorder, derives from many
diverse factors in the individual and his environment. The factors which effect
a particular individual’s susceptibility to alcohol addiction, given a prolonged

pattern of heavy drinking, remain to be determined.
Tolerance
The process described as “tolerance” occurs as a function of prolonged

exposure to a drug. This term refers to the observation that progressively
higher doses of a drug are required to produce comparable subjective and
behavioral effects. The development of tolerance is far more rapid than that of
physical dependence, both for alcohol and for narcotics. Tolerance and
physical dependence were once believed to be sequential and inseparable
aspects of the same underlying addictive process. However, our current
understanding of the relationship between tolerance and physical
dependence suggests that, although physical dependence is invariably
accompanied by the development of tolerance, drug tolerance may occur

independently of physical dependence.
The alcohol addict shows three types of tolerance which are common to
other addictive disorders; i.e., behavioral tolerance, pharmacological
tolerance and cross tolerance to other potentially addictive drugs. Behavioral
tolerance for alcohol is illustrated by the fact that an alcohol addict can drink
as much as a quart of bourbon per day without signs of gross intoxication. A
number of investigators have found that task performance during sobriety
and inebriation may not differ significantly even when blood-alcohol levels
are twice 100 mg/ml, the legal limit of intoxication in many states (See
references 11 , 25, 103, 105, and 159-161).
Associated with behavioral tolerance is pharmacological tolerance for

alcohol. Consistent consumption of as much as a quart of bourbon per day
may result in unexpectedly low levels of alcohol in the blood. It has been
shown that alcohol ingestion does increase the rate of alcohol metabolism in
alcoholics and in controls as a function of both amount and duration of
alcohol ingestion. However, the ethanol-induced enhancement of the rate of

ethanol metabolism appears to be transient and does not persist long after
cessation of drinking. A number of studies have shown that the rate of ethanol
metabolism in abstinent alcoholics and nonalcoholics is not significantly
different (See references 13, 53, 63, 110, 120, and 128). The dramatic
behavioral tolerance for alcohol shown by the alcohol addict cannot be

accounted for by a more rapid or effective capacity to metabolize alcohol. This
is evidenced by the fact that alcoholics can perform well on difficult tasks
even with very high blood-alcohol levels (above 200 mg./100 ml.). These data
suggest that the adaptive processes subserving tolerance occur in the central
nervous system rather than at a metabolic level.
Cross tolerance refers to the general phenomena of reduced responsivity
to drugs other than the primary addicting agent. It has been shown that sober
alcoholics metabolize a number of drugs more rapidly than nonalcoholics,

and there are reports that alcohol addicts undergoing surgery require far
larger doses of anesthetics than nonaddict patients to induce a surgical level
of anesthesia. Similarly, the alcohol addict may show cross tolerance to other
potentially addictive agents such as barbiturates, hypnotics, and sedatives. No
cross dependence has been shown between alcohol and opiate narcotics.
Finally, the alcoholic shows tolerance for many toxic alcohols and is able to
ingest these in quantities that would be fatal for nonalcoholics. It should be

emphasized that the phenomena of cross tolerance occurs in the sober alcohol
addict. Under conditions of intoxication, many drugs contribute to the effects
of alcohol, and the alcoholic individual may metabolize these drugs more
slowly than normal subjects.
Although alcohol tolerance is striking in the alcoholic, the degree of
tolerance, on a comparable dosage basis, is much less for alcohol than for
opiates or barbiturates. For example, barbiturate addicts may ingest twenty

to thirty times the average hypnotic dose in a twenty-four-hour period.
Heroin addicts show similar increases in self-administration over their initial
dosage levels. It is well known that some heroin addicts go through
withdrawal in order to reduce their tolerance and thereby lower their daily
maintenance dosage requirements. The physical limit of tolerance for the
alcoholic is more firmly fixed, and even though the alcoholic does develop
behavioral tolerance, blood-alcohol levels rarely exceed 450 mg./100 ml. The
lethal level of alcohol dosage also remains close to that for normal drinkers,
and blood-alcohol concentrations in excess of 500-600 mg./100 ml. result in
severe respiratory depression.
Physical Dependence
The usual alcohol withdrawal syndrome occurs between twelve and
seventy-two hours following cessation of drinking, although the course and
severity are quite variable. For clinical description see pp. 383-385.
Abstinence signs and symptoms may include tremor, profuse sweating,
gastrointestinal disorders, nystagmus, hyperreflexia, sleep disturbances,
hallucinations, and occasionally, seizures. Remission of major symptoms is
usually complete within three to five days. The usual alcohol withdrawal
syndrome is generally similar to mild barbiturate, opiate, and nonbarbiturate

sedative withdrawal.
The biological mechanisms underlying alcohol withdrawal and

abstinence syndromes generally are unknown. The development of physical
dependence is thought to be multiply determined by a complex interaction of
neural, endocrine, and metabolic variables. Most attempts to account for the
characteristic psychomotor and autonomic hyperactivity associated with
drug-withdrawal syndromes have postulated a heightened CNS excitability.
The basis for CNS hyperexcitability during withdrawal has often been
attributed to a rebound effect following drug-induced depression of neural
activity. There is considerable neurophysiological evidence consistent with
the notion that the CNS becomes more excitable during drug withdrawal.
The role of alcohol in facilitating seizure disorders in persons with an
underlying epileptic disorder has long been a subject of considerable
controversy. It is now thought that alcohol intoxication rather than alcohol

withdrawal may increase the probability of seizures in persons with
idiopathic or traumatic epilepsy.
Recent data suggest that, following removal of the depressant effect of
alcohol, there is an increased sensitivity of the respiratory center to carbon
dioxide and hyperventilation. It was once thought that alcoholics became
acidotic during alcohol withdrawal. However, it has recently been shown that
alcoholics develop a significant respiratory alkalosis which correlates both
with susceptibility to stroboscopically induced seizures and the occurrence of
delirium tremens. These data are of particular interest since several other
hyperventilation syndromes, also associated with a respiratory alkalosis,
yield clinical syndromes similar to those of alcohol withdrawal. Attempts to
treat the alcohol-withdrawal syndrome by administering carbon dioxide to
reduce the respiratory alkalosis were rather promising, despite technical

difficulties in administering carbon dioxide. The efficacy of pharmacological
agents to correct the respiratory alkalosis is currently being evaluated.
Psychological Dependence
Definitions of drug dependence are often subdivided into physical
dependence and psychological dependence. Psychological dependence is

usually inferred when drug use takes priority over other coping mechanisms
and assumes a central focus in the organization of daily behavior. The term
“psychological dependence” is imprecisely defined and usually used to refer
to the motivational factors which underlie drug-seeking behavior and to the
psychological effects of drug use. This semantic confusion between
motivational and drug effect aspects of dependence reflects our current
limited understanding of the factors which initiate and maintain drinking
episodes. The conditions which initiate and perpetuate heavy drinking

behavior are unknown. The resumption of addictive drinking after a period of
abstinence probably reflects many psychogenic and stress factors. The
possible contribution of the condition of physical dependence upon alcohol to

reinitiation of drinking after sobriety is undetermined. It is unlikely that the
condition of physical dependence in the sober alcoholic influences drinking
behavior in the same way that the presence or absence of food-deprivation
affects food seeking behavior. There are no satisfactory explanations for the
repetition of excessive drinking and withdrawal sequences, despite the totally
predictable adverse medical, social, economic, and often legal consequences.

It is the immediate rather than the long-range consequences of alcohol abuse
which appear to control drinking behavior.
In trying to account for the persistence of addictive drinking, it is
tempting to extrapolate from one’s own enjoyment of alcohol and to imagine
that the immediate pleasures of drinking negate either the awesome prospect
or the concurrent awareness of its many aversive consequences. However, it

has been shown repeatedly that alcoholics become progressively more
dysphoric, anxious, agitated, and depressed during a chronic drinking
sequence. A comparable dysphoria during chronic drug use has been
observed in morphine addicts and it has been suggested that increased
narcotics intake may be motivated by an effort to regain an initial euphoria. It
has also been shown that drinking tends to confirm and aggravate feelings of
inadequacy and low self-esteem in alcoholics. Although the voluminous
psychiatric literature on alcoholism has tended to present “the alcoholic” as
an impulsive hedonist who drinks to dissolve his anxieties and achieve a

diffuse sense of omnipotence, direct observations of intoxicated alcoholics
reveal a pathetic failure to attain such goals.
The somewhat paradoxical increase in disturbing affect observed in
alcoholics during studies of experimentally induced intoxication is difficult to
reconcile with information that most alcoholics provide about their drinking
experiences during sobriety. It appears that the sober alcoholic does not
recall the seemingly aversive aspects of his drinking experience during a
subsequent period of sobriety and therefore these aversive consequences

cannot effectively modify his future behavior. There are considerable data
which converge to suggest that there is a substantial dissociation of
experience during drinking, and subsequent recall and expectancy during
sobriety. It is possible that psychotherapeutic techniques which involve

efforts to integrate experiences during inebriation with awareness during
sobriety through the use of videotaped interviews may provide an effective
tool for bridging this alcohol-induced dissociation.
A second factor often advanced to account for the perpetuation of

drinking is the notion of “craving” which implies that once an alcoholic starts
to drink, “he is compelled to continue until he reaches a state of severe
intoxication.” The circularity inherent in this reasoning is evident, i.e., the

concept of “craving” is defined by the behavior that it is evoked to explain.
The concept of “craving” with its implication of “loss of control” over drinking
has been the source of considerable confusion in the literature on alcoholism
and has stimulated continuing debate. There has been no empirical support
for the notion of “craving” on the basis of direct experimental observations of
alcoholics given alcohol and clinical material. Although this construct appears
to be of limited utility, it has long formed the basis for the usual therapeutic
goal of total abstinence in the treatment of the alcoholic patient. (See also
discussion on Treatment of Alcoholism, pp. 394-395).
A third factor assumed to be related to the maintenance of addictive

drinking is the avoidance of withdrawal signs and symptoms which follow an
abrupt reduction in blood-alcohol concentration. If the avoidance of
withdrawal signs is the factor which motivates an alcoholic to continue

drinking, it would be expected that during a drinking spree, he should drink
quite consistently and maintain stable blood-alcohol levels. However, recent

data have shown a considerable cyclicity of alcohol self-administration both
in primate and human alcohol addicts. Despite the attendant discomfort, the
alcoholic does not invariably respond to these partial withdrawal signs by
increased drinking. This situation may resemble that of the narcotics addict in
which it has been suggested that incipient withdrawal signs may add both to
the gratification and perpetuation of drug use. The relationship between
physical dependence and subsequent drug self-administration is, at best,
ambiguous. The assumption that physical dependence is one aspect of an
addict’s motivation for drug use is a complex and elusive issue to approach
experimentally. Logically, it is difficult to account for the reinitiation of an
addictive drinking sequence, after a prolonged period of sobriety, in terms of
physical dependence alone. Presumably, whatever factors first prompted

excessive drinking before the development of physical dependence, continue
to affect resumption of alcohol abuse.
At the core of the many dynamic formulations concerning the basis of
alcohol abuse are two related notions: (1) the alcoholic drinks to achieve a
pleasurable subjective state; and
the alcoholic drinks to avoid or reduce the impact of current problems.
Until progress in behavioral science permits more precise specification of the

factors which initiate and perpetuate addictive drinking, the efficacy of
attempts to intervene and avert repetition of destructive drinking sequences

will be greatly limited. At present, we can only speculate about the possible
psychological and social determinants of alcohol dependence.
Clinical Disorders Associated with Alcohol Abuse

and Alcoholism
Factors in the Development of Alcoholism
Alcoholism can develop in any man or woman, irrespective of individual
personality characteristics, educational, cultural, religious, ethnic, or
socioeconomic background. No single psychological, social, or biological

variable has yet been shown to predict the development of problem drinking
or to uniquely differentiate alcoholics from nonalcoholics. The differences
between alcoholic individuals far outweigh the commonalities of repetitive

excessive drinking and tolerance for and physical dependence upon alcohol.
Many individuals develop alcohol problems independently of any family
history of alcoholism. However, recent evidence suggests the possibility of a

genetic component associated with the genesis of alcohol problems.
Dissociation of familial learning factors from genetic variables is a difficult
methodological problem. However, a study of fifty-five adult males, separated

during infancy from their biological parents (one of whom had been
hospitalized for alcoholism) had a significantly higher incidence of alcoholism
than matched adoptee controls. Another study of 164 adoptees showed a
significantly greater tendency to develop alcohol problems if the biological
parent was an alcoholic than if the adopted parent was alcoholic.
The psychiatric literature on alcoholism contains countless theories
which attempt to conceptualize alcoholism in terms of a psychodynamic
formulation, a psychosocial developmental model, or as the outgrowth of

specific personality characteristics such as depression, dependency,
immaturity, hostility, and social isolation. An excellent comprehensive review
of psychodynamic and personality factors in alcoholism appears in the first
edition of this Handbook. This chapter does not attempt to recapitulate this
material, in part because there has been little in the way of novel or
substantive revision of the various psychological theories of alcoholism since

the Handbook was first published in 1959. Some more recent
conceptualizations seem little more than relabeling exercises with terms
currently in fashion, e.g., “systems theory” etc. More important, the most
plausible and ingenious theories concerning the psychological determinants
of alcoholism have contributed little to the development of effective

treatment and, for the most part, have been difficult to subject to rigorous
experimental scrutiny.
Motivation for drinking varies greatly between individuals as well as

within an individual from occasion to occasion. Drinking patterns are
idiosyncratic; no consistent behavioral or biological correlates have yet been
identified. Anxiety and depression may be far less at the beginning of a
drinking episode than during or following prolonged intoxication. Stressful
incidents may correlate with either the initiation or the cessation of drinking
in alcohol addicts. Alcohol intoxication does not appear to produce any
reproducible pattern of social interactions. Often it appears that alcohol may
accentuate a person’s characteristic mode of coping with his environment and
social world. Efforts at objective behavioral analysis of drinking patterns are

very new, and the findings are gradually dispelling some basic
misconceptions about alcoholism derived from retrospective, self-report data
from the sober alcoholic.
The Alcohol-Withdrawal Syndromes
Hippocrates was the first to report an association between alcohol
abuse and tremulousness, delirium, and seizure disorders. However, it was
not until the late eighteenth and early nineteenth century that the alcohol-
abstinence syndrome was accurately described in the medical literature.

Despite a long history of clinical observation of the association between
cessation of drinking and signs and symptoms characterizing the withdrawal
state, the basis of the alcohol-abstinence syndrome was not determined until
the mid twentieth century. Studies carried out by Victor and Adams in 1953
provided the first careful clinical documentation of the alcohol-withdrawal
states and an accurate classification of the withdrawal syndromes. Based
upon these observations three unique, but not mutually exclusive withdrawal
states were differentiated: the tremulous syndrome, alcohol-related seizure

disorders, and delirium tremens.
The critical determinants of the onset of withdrawal symptoms are
unclear, since either a relative decrease in blood-alcohol levels or the abrupt
cessation of drinking may precipitate the syndrome. The severity and
duration of withdrawal symptoms also do not appear to be directly related

either to the volume of alcohol consumed or to the duration of a drinking
spree. It appears that the pattern of drinking may be more important than the
duration of drinking in accounting for the expression of the alcohol-

abstinence syndrome. (See also p. 375 and pp. 380-381.)
Tremulousness is the most common withdrawal sign observed following
cessation of drinking. Tremulousness may be relatively mild with

involvement of only the distal upper extremities, or it may be severe,
involving upper and lower extremities as well as tongue and trunk. The onset
of tremulousness may occur as early as six hours following cessation of

alcohol intake but the peak of intensity of the syndrome usually occurs after
24 to 48 hours of abstinence. Tremor is usually relatively coarse and may be

exaggerated or exacerbated when the patient is asked to extend his arms with
palms either separated or pronated. Duration of the tremulous state rarely
extends beyond seventy-two hours following cessation of drinking but in
some cases it may last as long as four or five days.
Tremulousness is often associated with a subjective sensation of
moderate to severe anxiety. Hallucinations may also accompany the acute
alcohol withdrawal state. Acute alcoholic hallucinosis is usually auditory and

there is little support for the notion that these hallucinatory events are
related to an underlying schizophrenia. It is also important to emphasize that
hallucinosis is not necessarily an index of the severity of the abstinence
syndrome. Recent data, obtained under experimental research ward
conditions, have shown that hallucinations may occur when alcohol addicts
are severely intoxicated as well as following cessation of drinking.
Seizure disorders due to alcohol withdrawal are often associated with
antecedent and consequent states of tremulousness, although isolated seizure
disorders without tremulousness do occur. Seizure disorders associated with

alcohol withdrawal may occur as early as several hours following the last
intake of alcohol, but the peak incidence of this syndrome is usually twelve to
twenty-four hours following cessation of drinking. Seizures are usually grand

mal in nature and are rarely preceded by auras but usually followed by a
post-ictal state. Seizures may occur during alcohol withdrawal in patients

who have no other evidence of neurological disease and have normal EEG’s
during sobriety. The occurrence of seizure disorders may herald subsequent
development of overt delirium tremens. According to Victor and Adams,
approximately one third of all patients who have seizure disorders during
alcohol withdrawal eventually develop delirium tremens.
Seizure disorders are not unique to alcohol-withdrawal states and have
been observed following withdrawal of many centrally acting drugs. Seizure

disorders are commonly seen during barbiturate withdrawal and following
cessation of prolonged use of high dosages of meprobamate, chloral hydrate,
and paraldehyde. In contrast, the heroin abstinence syndrome is rarely
associated with seizure disorders. Although it has been suggested that seizure
disorders observed during the alcohol abstinence state represent a latent
form of epilepsy which is precipitated either by heavy alcohol use or

withdrawal, there is no evidence to support this hypothesis. At present the
underlying mechanisms which produce seizure states during alcohol
withdrawal are not known.
The term “delirium tremens” is often erroneously used as a generic
description of most alcohol-withdrawal states. However, delirium tremens is
a distinct and specific disorder which occurs with relative infrequency. In

contrast to the common alcohol-withdrawal syndrome, delirium tremens
usually occurs late, i.e., seventy-two to ninety-six hours following cessation of

drinking. It may be preceded by tremulousness and is often preceded by
seizure disorders.
Delirium tremens is characterized by profound confusion,

disorientation, delusional states, and hallucinatory episodes as well as motor
and autonomic dysfunction. Confusional states and delirium are rarely
observed in the common tremulousness syndrome of alcohol abstinence.
Hallucinations associated with delirium tremens tend to be visual rather than

auditory. However, there is little empirical support for the popular notion of a
“typical” hallucinatory pattern. Although frightening and dysphoric
hallucinations may occur, comforting, pleasurable and euphoric
hallucinations are also observed, and it is the sensory and perceptual richness
of the hallucinatory event that is distinctive. Hallucinations associated with
delirium tremens are distinguished from hallucinations of schizophrenia by

the intense visual nonideational quality, increased frequency of occurrence at
night, and reports of subjective intensification when the patients’ eyes are
closed.
In addition to disorders of the sensorium, patients with delirium
tremens frequently show profuse sweating, tachycardia, hyper-reflexia, mild
to severe tremulousness, hypertension, and fever. Intercurrent illness,

particularly pulmonary and gastrointestinal disorders, are also common in
these patients. Delirium tremens is a potentially lethal condition in contrast

to the relatively benign common tremulous syndrome.
In the process of establishing a differential diagnosis between acute
alcoholic tremulousness, seizure disorders, and delirium tremens, it is
essential to consider the time course as well as the presence or absence of
confusion, disorientation, and autonomic dysfunction. It is also important to
remember that alcohol withdrawal is not an all-or-none phenomenon. During
the course of chronic drinking, alcohol addicts may experience wide
fluctuations in blood alcohol levels as a function of periodicity of alcohol

intake plus alterations in the rate of absorption and metabolism of alcohol. A
number of clinical and laboratory studies have demonstrated that onset of the
withdrawal syndrome, particularly tremulousness, may occur when
alcoholics are consuming ethanol, but have a relative decrease in their blood-
alcohol levels. It is impossible to arbitrarily define a critical blood alcohol
level for any given individual which either initiates or suppresses the
withdrawal state. For example, alcohol addicts who have blood alcohol levels
of 300 mg./100 ml. may experience severe abstinence syndromes when their
blood alcohol levels fall 100 or only 50 mg./100 ml.
In addition to symptoms which appear to be directly related to alcohol
(or partial alcohol) withdrawal, a number of associated disorders may
contribute to the severity and duration of the withdrawal syndromes. Alcohol

addicts may have disturbances in acid-base, water, and electrolyte balance
during alcohol withdrawal. Hyperventilation is frequently observed in the
early hours following cessation of drinking and this phenomenon may be
associated with induction of respiratory alkalosis and elevated blood pH.
Hypomagnecemia may also be found in patients in alcohol withdrawal.
Low serum magnesium levels are probably the result of two factors:
poor dietary intake and malabsorption of magnesium associated with heavy

drinking, and a shift of magnesium from the intravascular to intracellular
fluid compartments. Although a state of dehydration may be present in some
patients during withdrawal, overhydration may also be a problem.
Somatic Disorders
Prolonged alcohol abuse has been shown to have toxic effects on a

number of organ systems as well as secondary effects on metabolic processes.
Since the liver is the major drug-metabolizing organ in the body, perhaps it is
not surprising that liver damage is both the earliest and most profound
consequence of excessive alcohol use. Alcohol has been shown to induce a
transient development of fatty liver in normal drinkers in as little as two days.
In chronic alcoholism, there may be a temporal progression from alcohol-
induced fatty liver to alcoholic hepatitis or cirrhosis, a potentially fatal

condition. The extent to which alcoholic hepatitis, characterized by extensive
necrosis and inflammation, may in turn initiate scarring, fibrosis, and finally
cirrhosis is unclear. Moreover, although excessive alcohol use almost
invariably induces fatty liver, not all alcoholics develop cirrhosis. Recent data
suggest that the development of alcohol-induced hyperlipidemia may be
related to genetic factors, since alcoholics with primary hypertriglyceridemia
develop striking lipid abnormalities during experimentally induced chronic

intoxication. Normal drinkers with primary hypertriglyceridemia also
develop marked increases in triglyceride levels after acute administration of
low doses of alcohol.
Gastrointestinal disorders associated with alcohol abuse are very
common. Gastritis and pancreatitis are probably the most frequently
encountered gastrointestinal disorders in alcohol abusers. Gastritis may
progress to gastric or duodenal ulcers which, in turn, may lead to potentially
fatal gastrointestinal bleeding. Pancreatitis is also a potentially lethal

consequence of alcohol ingestion. The mechanism of pancreatitis production
in relation to alcoholism is unknown. Excessive alcohol use may also interfere
with the absorption of essential nutrients and vitamins from the small
intestine into the blood stream. The nutritional malabsorption syndrome, so
frequently observed secondary to alcoholism, may also contribute to the

compromised nutritional status often seen in the alcohol addict.
The neurological disorders frequently associated with alcohol addiction
are also related to malabsorption of critical nutrients. The most frequently

observed disorder of the peripheral nervous system in alcoholics usually
involves motor and sensory nerves in the arms and legs. These peripheral
neuropathies are characterized by pain, impaired movement and
coordination, and eventually by muscle wasting. This condition is usually
reversible with an adequate diet and cessation of drinking.
Disorders of the central nervous system may also be associated with
chronic alcohol abuse. Until recently, it has not been clear whether these
disorders were caused by the direct action of alcohol or a combination of
alcohol abuse and poor nutrition. It is now generally believed that nutritional
deficiencies are the most important etiological factor in most neurological
diseases associated with chronic alcoholism. The incidence of CNS diseases
associated with nutritional deficiency and alcohol abuse is very low. Even in
1953, neurological disease in hospitalized alcoholics ranged only between 1

and 3 percent. There has been a persistent mistaken impression that certain
CNS diseases are uniquely associated with alcoholism. Table 15-1
summarizes some other conditions in which CNS diseases traditionally

associated with alcoholism are also seen. The clinical neurology and
neuropathology associated with amblyopia, cerebellar cortical degeneration,

central pontine myelinolysis, myelopathy, Marchiafava-Bignami disease, and
Wernicke-Korsakoff syndrome has recently been reviewed by Dreyfus.
The latter two syndromes require some special emphasis because of

their historical association with the condition of alcoholism. Marchiafava-
Bignami disease is a rare condition of unknown origin, which presents a
clinical picture rather similar to delirium tremens, and is characterized by
demyelination of the central portion of the corpus collasum. Only about sixty-
four cases have been reported in the world literature. The disorder was once
thought to occur only in Italian males who drank large amounts of crude red
wine. This syndrome has subsequently been observed in non-Italian alcoholic
patients after abuse of various types of alcohol. The pathological changes
associated with Marchiafava-Bignami disease have also been found in

patients with Wernicke-Korsakoff syndrome.
Table 15-1. Disorders of the Central Nervous System Associated with Alcoholism
and Other Specific Conditions4
DISEASES OF THE NERVOUS SYSTEM
ASSOCIATED WERNICKE- AMBLYOPIA CEREBELLAR CENTRAL

CONDITIONS KORSAKOFF CORTICAL PONTINE
SYNDROME DEGENERATION MYELINOLYS
Liver Disease
Thyro Toxicosis ü28
Pernicious ü18
Vomiting of
Pregnancy
Strachan’s
Disease
Nutritional Factors
Chronic ü35,76,153
Malnutrition
Chronic ü6, 17,80, 98,15

Malnutrition
Associated
with Disease
Nutritional ü94
Depletion
Thiamine ü171
Deficiencies
Vitamin B ü171 ü54

Deficiencies
Pellagra
Treatment Variables
Chronic ü89
Hemodialysis
Isonicotinic Acid ü73

Hydrazide
Wernicke’s syndrome is an encephalopathy frequently associated with
alcohol abuse. Prolonged alcohol intake, even in the presence of an adequate
diet, may result in impairment of eye muscle control due to nerve
dysfunction. Although this condition is usually benign and readily reversible
following cessation of alcohol intake, it may herald a potentially serious
disorder which could lead to a permanent incapacity. This more serious
disorder has been termed Wernicke’s disease and Korsakoff’s psychosis and
is characterized by opthalmoplegia, ataxia, weakness, profound disorders of
memory and deranged process of thinking.
This syndrome results primarily from vitamin deficiency and, in
particular, a deficiency of thiamin. Alcohol abusers are at a high risk for the
development of vitamin deficiencies because they eat poorly and alcohol may
inhibit absorption and transport of vitamins from the GI (gastrointestinal)
tract. Remission of opthalmoplegia usually occurs promptly after parenteral
administration of vitamin B complex. Ataxia and confusional states clear more

slowly. The prolonged derangements of memory (Korsakoff’s psychosis) are
discussed under Disorders of Memory Function (p. 389).
The possible contribution of alcoholism to heart disease is, as yet,

unknown. Alcohol is a myocardial depressant and may play some role in the
development of cardiomyopathies. A comparison of clinically normal
alcoholic patients with cardiomyopathy and normal groups showed

abnormalities of cardiac function similar to but quantitatively less than in the
cardiomyopathy group.
Less frequent but not uncommon conditions associated with chronic
alcohol abuse include disturbances in blood-cell formation and anemia, muscle
disease, and enhanced susceptibility to infection. An interaction between
poor nutrition and excessive drinking is probably most important in the
genesis of these disorders. It is known that alcoholics have a very high
incidence of tuberculosis and this infectious disease is most common in
individuals who are debilitated and have poor dietary intake.
Affective Disorders and Psychosis
Depression as an antecedent or consequent phenomenon in patients
with alcohol-abuse problems has been well documented in the clinical
literature (see references). However, the causation of alcohol problems as
unique sequela of affective disorders has never been substantiated. Some
individuals with neurotic and psychotic affective disorders may abuse
alcohol, but many individuals with these symptoms do not drink heavily and
may even abstain from using alcoholic beverages. Although it is tempting to
postulate that alcoholics drink to alleviate depression, there is some evidence
that chronic drinking enhances depression. A number of studies have shown
that depression and dysphoric states are precipitated by or perhaps

increased during chronic intoxication. It is therefore important for the
physician to recognize that depression is not a necessary “underlying” basis
for alcohol abuse and to avoid simplistic formulations for “treatment of the
depression” rather than employing a more comprehensive therapeutic
approach.
Alcoholism is a common finding in individuals who attempt or commit
suicide. It has been estimated that one third of all reported suicides are
associated with chronic alcohol abuse. However, the available statistics
indicate that this figure may be valid only for white middle-aged males.
Suicide rates appear to be relatively low for black males over thirty-five,
although problem drinking in this group is more likely to occur at an earlier

age than for white males. Until more comprehensive data are available, the
precise interaction between alcoholism and suicide will remain obscure. On
the other hand, there is very good evidence that alcohol consumption
frequently occurs prior to suicidal behavior, since about 25 percent of suicide
victims have detectable amounts of alcohol in tissue on necropsy
examination. It is tempting to postulate that this finding supports the

observation that alcohol may enhance dysphoric mood states. Since there are
no data available concerning the number of individuals who contemplate
suicide, drink, but do not attempt the act, or who are even dissuaded from
suicide as a consequence of drinking, the relationship between suicidal

behavior and drinking is unclear.
The causal relationship often assumed to exist between alcoholism and
a number of psychiatric states is also tenuous at best. The “alcoholic paranoid
state” has been listed in the Diagnostic and Statistical Manual (DSM-II),
published in 1968 by the American Psychiatric Association. There is no
evidence that this behavior disorder is a unique psychosis caused or even

aggravated by drinking. An examination of the clinical literature reveals no
convincing data which demonstrate either acquisition or remission of a
psychiatric disorder as a function of alcohol intake. However, it is not unlikely
that patients may initiate drinking or abuse alcohol as one of a series of

behaviors associated with recrudescence of a psychotic episode. Assignment
of a causal rather than an associational relationship between alcohol abuse
and psychotic disorders is naive and impedes development of the basis for a
comprehensive differential diagnosis.
“Pathological intoxication” is a term often found in the literature and it
is most commonly characterized as uncontrolled and usually violent
aggressive behavior and rage following alcohol intake. Rage states have been
associated with even very small volume alcohol intake, and a causal basis has
been assigned to alcohol in producing the disordered behavior. No such

causal basis has been verified in controlled studies, nor has an association
between blood alcohol levels, abnormal brain-wave activity, and violence

been experimentally validated. As noted previously, some patients may
exhibit increased aggressive behavior when intoxicated. However other
individuals may become more friendly, while others show no change in
behavior. So-called “pathological intoxication” is probably more closely
related to host and environmental determinants than to a specific
pharmacological effect of alcohol in the CNS.
During recent years, it has been reported that a large number of new
admissions to state mental hospitals have alcoholism as a primary diagnosis.
Among those patients a significant number have “organic brain dysfunction”
which has been linked to alcohol abuse. It should be kept in mind that these
patients have a number of similar features in addition to a history of alcohol

abuse, e.g., most are poor; most have a past history of marginal nutritional
status; most have family backgrounds of low socioeconomic status and poor
educational achievement. The apparent increase in the number of admissions

of these patients does not necessarily reflect a true increase in prevalence of
alcoholism. Rather it may reflect the increased willingness of state
institutions to admit these patients as a consequence of decreased duration of

hospitalization for other psychiatric patients who are more amenable to
psychopharmacological interventions.
The entire category of the organic brain disorders is poorly understood.

More rigorous and obsessive relabeling will not provide better insight into
the causal determinants of the disorders of cognition, perception, and

memory function. Much more knowledge is necessary before the role of
alcohol abuse, alone or in combination with other disorders of behavior, can
be determined in the genesis and progression of deranged intellectual
function and aberrant thought processes.
Disorders-of-Memory Function
Excessive alcohol use has been associated with several types of

impaired memory function. These range from a severe persistent amnestic
disorder, Wernicke’s Korsakoff syndrome, to the transient total memory loss
which may accompany heavy intoxication, i.e., the alcoholic “blackout” to the
fragmentary absence of recall of events during drinking which has been
described as a dissociative state. The mechanisms which account for these
alcohol-induced memory impairments are unknown.
Wernicke’s Korsakoff syndrome is usually associated with pathological
changes of the mammillary bodies and the medial thalamus and

hypothalamus. The patient presents with anterograde and retrograde
amnesia. Although memory of early life experiences is intact, there is usually
an inability to recall more recent life circumstances. Patients are unable to
acquire new information and often cannot recall, for example, the route to the
hospital dining room, the food served at lunch, the name of their doctor, etc.
The most comprehensive analysis of the memory deficits associated with the
Wernicke’s Korsakoff syndrome has been completed by Talland. The extent to
which this complex memory disorder is a function of impairment in
information storage, or in retrieval of that information is the subject of
continuing study.
The alcoholic “blackout” is a general term used to describe a total loss of
memory for events during an episode of heavy intoxication. In some
instances, intoxicated individuals may drive long distances, fight, be arrested,

and subsequently awaken without any recollection of their activities for the
past several hours or days. The incidence of “blackouts” is unknown. In a
sample of one hundred alcoholics about two-thirds reported experiencing
“blackouts”. The degree of intoxication does not reliably predict the
occurrence of this profound memory loss. Moreover, alcohol-induced periods
of amnesia may occur in moderate or heavy drinkers as well as in alcoholics.

The frequency of blackout occurrence does appear to correlate with severity
of alcoholism, a history of head trauma, malnutrition, and fatigue. It is
unlikely that deliberate malingering often accounts for these clinical

phenomena. Total loss of memory for significant events is a frightening
experience for most patients and “blackouts” do not appear to have any
motivational consequences for the maintenance of drinking behavior. The
occurrence of blackouts is not necessarily correlated with a history of head

trauma. No information is available to rule out the possibility that alcohol-
induced blackouts reflect an underlying neuropathological process such as
impaired temporal-lobe function which is accentuated by intoxication.
Comparable reports of hours or days of amnesia are not a prominent feature
of heroin or barbiturate intoxication.
It has been suggested that the “blackout” may be explained in terms of a
disruption of “short-term” memory5 consolidation by alcohol. It is argued that

information lost to “short-term” memory would not be available subsequently
from “long-term” storage and so could account for a period of global memory
loss. The validity of this hypothesis has been the subject of controversy. An
alcohol-induced decrement in “short-term” memory function was observed in
alcoholics with a clinical history of “blackouts” but not in alcoholics without
such a history. However, these findings are inconclusive since no measures of
memory function were taken during sobriety and, therefore, it is impossible

to establish that memory function did not differ between these two groups
before alcohol administration. Another report indicated that alcoholics with a
clinical history of blackouts showed “short term” memory impairment during
intoxication but not during sobriety. Since no comparison of the effect of

alcohol on memory function in alcoholics without a clinical history of
blackouts was made, the extent to which blackout history and alcohol may
interact uniquely to affect memory function was not determined. A third
study compared the performance of alcoholics with and without a clinical
history of blackouts, during sobriety, and acute and chronic alcohol
intoxication and found no impairment of short-term memory in either group
under any condition. It appears that when alcoholic subjects are adequately
motivated to perform a task, their behavioral tolerance for alcohol permits
accurate performance, even at very high blood alcohol levels. Visual short-
term memory can be disrupted by relatively low doses of alcohol in normal
drinkers who lack behavioral tolerance. Data collection on alcoholics with no
history of blackouts and rhesus monkeys also failed to reveal any direct effect
of alcohol on “short-term” memory.
A third form of memory dysfunction associated with alcohol

intoxication is the fragmentary absence of recall of some events during a
subsequent period of sobriety. In some instances, events during intoxication
(e.g., hiding money or alcohol) are only recalled during a subsequent period
of intoxication, and therefore fall into the framework of state-dependent
effects. The observation that behavior learned during a drug state may not
occur during a nondrug state, then reoccur during reinstitution of a drug

state, has been demonstrated in experimental animals. Simply stated,
responses established under specific conditions are most easily elicited once
these conditions are re-established. State-dependent dissociation of recall for
verbal materials learned during alcohol intoxication has also been shown in
normal college students.
Clinically, the dissociative effect of alcohol is most often expressed by a
failure to recall aversive consequences of drinking (e.g., depression, anxiety,
illness) during a subsequent period of sobriety. Alcohol addicts form positive
expectancies about a forthcoming drinking experience, and, following a
period of chronic intoxication, they tend to recall their experience in terms of

the predrinking expectancy, rather than the events that actually transpired.
The implications of this dissociative phenomena for treatment of the alcoholic
were first noted in 1962 by Diethelm and Barr. Patients interviewed under
conditions of acute intoxication talked more freely and described emotions,

especially guilt and hostility, which they had not discussed during sobriety.
Usually these patients forgot the content of these interviews once they
became sober again. Traditionally, physicians have tended to refuse

treatment to intoxicated alcoholics. A reevaluation of this principle and an
effort to assist patients in integrating feelings expressed during intoxication
with self-perception during sobriety could result in more effective
psychotherapy for alcoholic individuals.
Sleep Disturbances
There is a prevailing impression that alcohol facilitates sleep. Although
this notion is consistent with the usual classification of alcohol as a CNS
depressant, it is not supported by electroencephalographic analysis of the

effects of alcohol on sleep. It has been generally agreed that “poor sleep” is
characterized by a decrease in REM activity and a decrease in stage 4 sleep. It
is now well established that acute administration of alcohol does produce a
relative suppression of REM activity in normal individuals, alcohol addicts,
and experimental animals. The effect of alcohol on stage 4 sleep is a

controversial issue, but it is agreed that stage 4 is decreased during alcohol
withdrawal. Sleep of alcoholics is generally light and somewhat fragmented.
Such sleep disturbances and insomnia seem to be characteristic symptoms of

chronic alcoholism.
There has been considerable interest in the possibility that

hallucinations often seen in alcohol addicts during alcohol withdrawal may
reflect a REM “overshoot” following a period of alcohol-induced REM
suppression. Hughlings Jackson and William James were among the first to
suggest the possibility of a neuro-physiological continuity between dreaming
sleep and waking hallucinatory activity. Hallucinosis is sometimes associated
with difficulty in discriminating between sleeping and waking states. The idea
that REM sleep and dreams are isomorphic is no longer accepted since
dreamlike activity has also been reported during non-REM awakenings.
However, the hypothesis that REM suppression as a function of chronic
alcohol intoxication may facilitate the eruption of hallucinations during

withdrawal has received confirmation in several studies of alcohol addicts
during a period of acute alcohol withdrawal. Interpretation of reports of EEG
correlates of sleep activity during alcohol withdrawal must be made with
caution since it has usually been impossible to obtain adequate baseline sleep
measures. Consequently, the high levels of REM activity observed may reflect
a combined effect of acute hospitalization and alcohol withdrawal. It is

seldom possible to determine the number of hours since the last drink with
any degree of accuracy in acute hospital admissions, and this can confuse
differential diagnosis of alcoholic hallucinosis versus delirium tremens (see

discussion on p. 385).
A recent study of alcohol addicts before, during, and after a period of

chronic alcohol consumption did not reveal a consistent REM hyperactivity
during alcohol withdrawal. Although hallucinations were frequently
associated with an antecedent REM suppression or insomnia, there were no

invariant relationships between hallucinosis and REM activity. Also,
hallucinations were reported during intoxication as well as during alcohol
withdrawal. There were no consistent dose-response relationships between

alcohol intake and the subjective intensity of reported dreams or
hallucinations. It may be somewhat premature to assume an invariant
association between dream-hallucinatory episodes and REM activity, and the
drug-suppression-withdrawal overshoot REM hypothesis is currently being

reevaluated in several laboratories. Attempts to discern relationships
between the presumed physiological accompaniments of the behavioral
expressions of intoxication and withdrawal are necessarily restricted by
limitations inherent in existing techniques, and the notion of a physiology of
dreaming remains a provocative but hypothetical construct.
Treatment of Acute and Long-Term Alcohol

Problems
Treatment for the alcohol-related disorders will be described separately
for the acute effects of alcohol intoxication and withdrawal and the chronic
phase of the illness. The implications of problems in establishing outcome

criteria for current treatment approaches will also be considered in the
discussion of treatment evaluation and prevention.
The Treatment Setting
Most physicians treat patients with alcohol-related problems in two
clinical situations, each of which involves substantially different problems. In

hospital practice, patients are rarely seeking assistance for alcohol problems
per se, but are usually under treatment for intercurrent illness associated
with alcohol abuse. Therapy is often directed towards solving medical

problems of acute illness, with minimal attention to the underlying alcohol
problem. Many such patients return to problem drinking once they are
discharged from the hospital and then are frequently readmitted with
identical or similar disorders. This unfortunate recidivism often promotes an
attitude of despair in the patient and disdain in the physician and other
hospital personnel.
In office practice, despair and disdain are fostered by other factors.
Patients seeking aid in this situation generally initiate therapy because of

some degree of external coercion. Such coercion may range from threats of an
employer to terminate employment to threats of a spouse to end a marriage
unless the patient seeks and obtains assistance. In this situation, the patient is
usually both frightened and angry and the sum of both conditions is often
interpreted by the physician as evidence of lack of motivation to do
something about his or her drinking problem. Motivational factors have

become so emphasized in diagnosis and therapy that they have frequently
been assigned predictive value in determining efficacy of treatment. It is
therefore possible for a physician to prematurely assume a poor prognosis for

a patient who appears “poorly motivated” and then to employ a “poor-
motivation” vs. “good-motivation” dichotomy to account for either success or

failure of the treatment provided. Since motivational states are rarely static in
patients treated for any disorder, it is obvious that this criterion is not of
great value.
Although there have been significant advances in public perception of
alcoholism as a disease rather than evidence of “moral weakness”, a severe

stigma continues to be associated with this disorder. In most instances,
patients with alcohol-related illness recognize this stigma and are reluctant to
fully discuss the duration or severity of their drinking problems. Successful

case finding and elucidation of past and current problem history taking
involve techniques which are common to all psychiatric interviewing
procedures. Since these are discussed in other portions of this Handbook (see
Volume 1, Chapters 53 and 54), they will not be repeated here.
Much attention has been paid to the role of attitudes and values held by
physicians in determining their diagnostic approach to patients with alcohol
problems. Similar contingencies probably apply to all categories of mental

disorders and perpetuation of emphasis on the importance of this issue
provides a rationale for accepting or rejecting patients. At the present time,
there are no data which specify the optimal qualities, attitudes and
approaches in the treating physician as a determinant of treatment outcome.
The process of differential diagnosis for alcohol related problems

requires a conceptual approach which has been employed by physicians for
many decades in general medicine. In psychiatric practice, this approach
often suffers because of lack of basic information about causation and natural
history of mental illness. An attempt has recently been made to systematize
the diagnostic criteria for alcohol abuse and alcoholism. These criteria include
behavioral, physiological, and attitudinal factors, with particular attention to
the major illnesses associated with alcoholism and the related patterns of
clinical laboratory test abnormalities. Although this system is imperfect, it
represents a considerable advance which deserves attention and critical
appraisal by physicians.
Treatment of Alcohol Intoxication
There are no effective, readily available means of rapidly reducing the
blood-alcohol concentration of a severely intoxicated individual. Although the
rate of ethanol metabolism can be increased by fructose administration, this
technique has found little successful clinical application since its discovery
thirty-five years ago. Recent explorations of hemodialysis procedures to
rapidly reduce blood-alcohol concentrations have limited general

applicability because of their expense and potential risk of infection.
Fatal alcohol poisoning is very rare. There are occasional reports of
children or adolescents who die of respiratory depression following an

overdose of alcohol. However, in view of the many people who drink and the
large volumes of alcohol consumed, it must be concluded that alcohol is a
relatively safe drug in comparison to the opiate narcotics. It is virtually
impossible to drink an acutely toxic amount of alcohol before vomiting or
unconsciousness occurs.
The comparative safety of alcohol may also be related to its dual
properties as a drug and a food. Alcohol does contain calories and is
metabolized like other carbohydrates. The principal enzyme responsible for

alcohol metabolism, alcohol dehydrogenase, is ubiquitous in body organs and
most highly concentrated in liver. Consequently, the lethal toxic potential of
alcohol is counteracted by nature’s provision for its rapid degradation.
The recent increase in polydrug abuse requires added caution in
treatment of acute intoxication. The concurrent use of several drugs which
may act synergistically can result in overdose. Improved techniques for
determining the blood concentrations of, e.g., heroin and barbiturates as well
as ethanol, can aid the physician in accurate diagnosis. Fast acting
pharmacological antagonists are currently available for heroin but not for
barbiturates or alcohol.
Since acute intoxication in the chronic inebriate is usually complicated

by other medical problems (see pp. 385-388) it is essential that the care of
afflicted individuals occur in the context of good medical management. Until
recently, it has been difficult, especially for impoverished alcoholics, to obtain
adequate medical treatment for the acute effects of alcohol. However, it is
likely that most of these patients are admitted to hospitals for treatment of
acute intoxication under the guise of some other diagnostic criteria.
Following the recent change in the legal status of intoxication and
alcoholism in 1966, a number of detoxification centers were established to
treat the acute inebriate. While these facilities do provide some resource for
patient care, they were seldom established within the mainstream of medical
care. Consequently, there is great danger that these centers may become
nothing more than a respectable version of the traditional “drying-out”
facilities, i.e., the jail or the drunk tank.
Treatment of Alcohol Withdrawal
Rather good progress has been made by biomedical scientists in
devising new methods for the treatment of the alcohol withdrawal syndrome.
Improvements in treatment have occurred primarily because of general
advances in medicine which provide more accurate diagnosis and better

patient management, i.e., treatment of metabolic disturbances and infections
which frequently accompany the abstinence syndrome. Less than twenty
years ago, the mortality associated with delirium tremens was reported as
about 15 percent in various hospitals and institutions. Today, the incidence of
death associated with delirium tremens has fallen to less than 1 percent.
The development of new psychopharmacological agents, particularly
the minor tranquilizers, has provided a means of mildly sedating patients and
reducing severity of agitation and tremor without compromising the patient’s
ability to eat well and receive other medical care. Chlordiazepoxide (Librium)
has been reported to be an effective anticonvulsant in the treatment of
withdrawal seizures (see also pp. 383-385).
Treatment of Alcoholism
At present, there is no specific and uniformly efficacious treatment
either for the disease of alcoholism or for problem drinking. The treatment
techniques that have been used include individual and group psychotherapy,
Alcoholics Anonymous, aversive conditioning therapies, Antabuse, vitamin
therapies, and LSD treatment, singly or in various combinations. In the few
relatively controlled therapy evaluation studies, the rate of improvement or
alcohol abstinence following therapy was very low. Since the spontaneous
recovery rate for alcoholics has been estimated at about 20 percent, the
efficacy of the existing therapies is discouragingly low. These figures compare
rather poorly with the improvement rate of heroin addicts treated with
methadone, an estimated 70 percent.
The complexities and difficulties involved in treating the chronic alcohol

abuser have been thoroughly reviewed by many concerned investigators.
Since all variants of alcoholism are multiply determined, the treatment of
alcohol problems presents the challenge of any complex behavioral disorder.
The dynamic conceptualizations of an “alcoholic personality” have received
no empirical support, and there is considerable heterogeneity on many

dimensions, even among the end stage, “skid-row” alcoholics. Although there
is no evidence to indicate that alcoholism is invariably associated with a
predisposing psychiatric illness, the development of problem drinking rarely
occurs in isolation from emotional, interpersonal, and job-related problems.

Whatever its origins, alcoholism is characterized by a vast diversity of related
difficulties.
The treatment of alcoholism is further complicated by the fact that most
people with alcohol problems tend to deny the reality of their illness and to
reject treatment. It has been shown that patient acceptance of treatment can
be greatly improved if initial hospital contacts are sympathetic and positive.
However, physicians have tended to reject alcoholic patients and to avoid

diagnosing the problem unless it was glaringly apparent in the terminal
phase. Frustration with relapsing patients who deny the significance of their
alcohol problems, and limitations of available treatments have contributed to
physicians’ negative attitudes. The point has often been made that treatment
goals for the alcoholic should have limited objectives and a multimodality
therapy suited to the needs of the individual and his resources should be
offered. The logic of this position is obvious and can be extended to argue for
treatment of the alcoholic within the mainstream of medical practice, where
the greatest range of medical, psychiatric, and social services is potentially
available. However, the question of which treatment will most benefit the
patient with alcohol problems remains unanswered. Until there is a better
understanding of the disease process of alcoholism, and better treatments
available, it is unlikely that the incidence of alcoholism will be greatly

reduced, despite the recent improvements in the delivery of health-care
services to alcoholics.
The low success rate of current treatment approaches seems to point to
the need for an effective pharmacotherapy for alcohol addiction. The recent
advances in the treatment of heroin addiction have occurred largely because

of the availability of blocking agents or antagonists. However, the use of
blocking agents for heroin addiction has been criticized because these agents
have high addictive potential. An ideal blocking agent for any centrally acting
drug of abuse, including alcohol, would have the following characteristics: (1)
low addictive potency; (2) little or no synergistic action with other drugs; (3)
no central nervous depression or excitatory effects. In essence, the drug of
choice for treating alcoholics would be more closely analogous to a narcotic

antagonist than a blocking agent. It should be emphasized that the rationale
for the use of blocking agents which reduce the subjective effect of a drug is
very different from that for the use of Antabuse which produces severe
discomfort, and potentially lethal consequences if taken in combination with
alcohol.
In view of the wide spectrum of alcohol-related problems, drug therapy
alone would not suffice. A variety of other psychological and social

interventions would probably be necessary to produce the greatest change in
alcoholics with diverse behavioral, biological, and social problems. However,
an effective drug therapy would permit other types of therapeutic
intervention to occur under conditions where confounding effects of

perpetuation of alcohol intake were significantly reduced.
Treatment Evaluation
One of the most important and frequently ignored issues related to the
treatment of alcoholism is the problem of evaluation. Unless there are

adequate evaluation and follow-up data, it is not possible to demonstrate the
efficacy of any treatment approach. One fundamental issue in evaluation is
the establishment of valid outcome criteria. The establishment of
comprehensive criteria of efficacy which can be uniformly applied to all

treatment programs is critical for adequate evaluation. There has been no
consensus that the traditional goal of absolute abstinence is the optimal
therapeutic goal for the alcoholic. Indeed, it appears that for many alcohol
abusers, giving up drinking completely can also result in severe social and
psychological dysfunction. There is accumulating evidence that some alcohol
addicts may be able to return to social drinking. The persistent rationale for
the treatment criterion of absolute abstinence is based on the erroneous

concept of “craving”, which is discussed under Psychological Dependence, p.
382.
Once outcome criteria have been formulated, construction of an
adequate clinical research design assumes paramount importance.
Traditionally, it has been argued that clinical research cannot yield “hard
data” because of the complexity of the dependent variables, the difficulties in
controlling relevant factors as well as ethical constraints. It is curious that the
expectancy for objectivity, sophistication, and accuracy in basic research has

not been extended to treatment research. A lack of these qualities in the
laboratory would have severe consequences for research development, and it
could be argued that casual evaluation of treatment programs could have

even more profound consequences for longevity and quality of human life. It
does not seem unreasonable to require an even more precise specification of

methods and outcome criteria for treatment programs which involve human
beings than for isolated physical and chemical studies involving in vitro
biochemical constituents. Enthusiastic testimonials by proponents of a
particular treatment approach are too often substituted for adequate data.
Awareness of the difficulties attendant on clinical treatment research should
not constitute an excuse for neglecting or evading basic tenets of
experimental design. A lucid summary and discussion of basic requirements
for the design of clinical research has recently been prepared by Ludwig.
Prevention
There is little question that the best treatment for any disorder is
prevention, and significant emphasis has been placed on public education
concerning use hazards in virtually all drug-abuse areas. Evaluation of the

impact of such public education and prevention efforts is extremely difficult.
The problem is complicated by the lack of good data on the incidence and
prevalence of alcohol abuse and alcoholism, and the many difficulties

associated with adequate case finding (see discussion on pp. 374-376). In the
absence of firm incidence data, it is difficult to demonstrate conclusively that
public-education programs or attempts to shape attitudes have had a
significant impact on alcohol-abuse problems. Some preliminary evidence
suggests that naive programs of public education and attitude shaping may
sometimes prompt exploration and thereby increase the incidence of drug-

abuse-related problems. Unfortunately, problem drinking usually occurs in
situations where behavior is not determined by logical thinking, but rather by
internal and external stress-contingent factors which are not highly amenable
to rational persuasion. People with well-established alcohol related problems
may be unresponsive to reminders that a certain pattern of drinking can be
dangerous to their health. There is probably no substitute for the early
development of responsible attitudes about alcohol use and awareness of the

nature of alcohol problems.
Prevention techniques designed to change attitudes are quite distinct
from coercive efforts to control distribution of alcohol or to prevent some
individuals from drinking through imposition of age limits, etc. Attempts to
control alcoholism through prohibition were a dramatic and unequivocal

failure. There has been little systematic study of the effects of increased
taxation or restricted hours for bars and liquor stores in areas where these
techniques have been applied. It is often argued that consumption of low-

alcohol-content beverages such as beer may prevent alcoholism. This
argument is somewhat misleading in that consumption of large enough
quantities of a 6-percent alcohol beverage can yield an alcohol intake

equivalent to that of the distilled spirits drinker. Physical dependence upon
alcohol has been seen in individuals who consume large quantities of beer
and wine.
Until there is a better understanding of the many factors which
contribute to the development and maintenance of alcohol abuse, it will be

difficult to formulate more effective approaches to the prevention and
treatment of alcoholism.
Bibliography
Bacon, S. D., ed. “Studies of Drinking and Driving,” Q. J. Stud. Alcohol, Suppl. no. 4 , 1-10.
Belfer, M. L., R. I. Shader, M. Carrol et al. “Alcoholism in Women,” Arch. Gen. Psychiatry, 25 (1971),
540-544.
Bloomquist, E. R. “Addiction, Addicting Drugs and the Anesthesiologist,” JAMA, 171 (1959), 518-
523.
Blum, E. M. and R. H. Blum. Alcoholism: Modern Psychological Approaches to Treatment. San

Francisco: Jossey-Bass, 1967.
Boston University Law-Medicine Institute. Legal Issues in Alcoholism and Alcohol Usage. Boston
University Law-Medicine Inst. Proc., 1965.
Cadman, T. E. and L. B. Rorke. “Central Pontine Myelinolysis in Childhood and Adolescence,” Arch.
Dis. Child., 44 (1969), 342-350.
Cahalan, D. Problem Drinkers. San Francisco: Jossey-Bass, 1970.
Cahalan, D., I. H. Cisin, and H. M. Crossley. American Drinking Practices: A National Study of
Drinking Behavior and Attitudes, Monogr. no. 6. New Brunswick, N.J.: Rutgers Center
of Alcohol Studies, 1969.
Cahn, S. The Treatment of Alcoholics: An Evaluative Study. New York: Oxford University Press,
1970.
Cameron, D. C. “Abuse of Alcohol and Drugs: Concepts and Planning,” WHO Chron., 25 (1971), 8-
16.
Carpenter, J. A. “Effects of Alcohol on Some Psychological Processes,” Q. J. Stud. Alcohol, 23 (1962),
274-314.
Carpenter, J. A. and B. M. Ross. “Effect of Alcohol on Short-Term Memory,” Q. J. Stud. Alcohol, 26

(1965), 561-579.
Carpenter, T. M. “The Metabolism of Alcohol: A Review,” Q. J. Stud. Alcohol, 1 , 201-226.
Carpenter, T. M. and R. C. Lee. “The Effects of Glucose on the Metabolism of Ethyl Alcohol in Man,”
J. Pharmacol. Exp. Ther., 60 (1937), 264-285.
Chafetz, M. E. “The Prevention of Alcoholism,” Int. J. Psychiatry, g (1970-71), 329-348.
Chafetz, M. E., H. T. Blane, H. S. Abram et al. “Establishing Treatment Relations With Alcoholics,” J.
Nerv. Ment. Dis., 134 , 395-409.
Chason, J. L., R. W. Landers, and J. E. Gonzalez. “Central Pontine Myelinolysis,” J. Neurol.

Neurosurg. Psychiatry, 27 (1964). 317-325.
Chaturachinda, K. and E. M. McGregor. “Wernicke’s Encephalopathy and Pregnancy,” J. Obstet.

Gynaecol. Br. Commonw., 75 (1968), 969-971.
Cochin, J. “The Pharmacology of Addiction to Narcotics,” in G. J. Martin and B. Kisch, eds., Enzymes
in Mental Health, pp. 27, Philadelphia: Lippincott, 1966.
Collins, J. R. “Major Medical Problems in Alcoholic Patients,” in J. H. Mendelson, ed., Alcoholism,

Vol. 3, pp. 189-214. International Psychiatry Clinics. Boston: Little, Brown, 1966.
Davis, D. L. “Normal Drinking in Recovered Alcohol Addicts,” Q. J. Stud. Alcohol, 23 (1962), 94-104.
Deneau, G., T. Yanagita, and M. H. Seevers. “Self Administration of Psychoactive Substances by the
Monkey,” Psychopharmacologia, 16 (1969), 30-48.
Department of Health, Education, and Welfare. Alcohol and Health, First Special Report to
Congress, Publ. no. DHEW 72-9009. Washington: U.S. Govt. Print. Off., 1971.
Diethelm, O. and R. M. Barr. “Psychotherapeutic Interviews and Alcohol Intoxication,” Q.J. Stud.
Alcohol, 23 (1962), 243-251.
Doctor, R. G., P. Naitoh, and J. C. Smith. “Electroencephalographic Changes and Vigilance Behavior
during Experimentally Induced Intoxication with Alcoholic Subjects,” Psychosom.
Med., 28 (1966), 605-615.
Dreyfus, P. M. “Diseases of the Nervous System in Chronic Alcoholics,” in B. Kissin and H.

Begleiter, eds., The Biology of Alcoholism, Vol. 3, pp. 265-290. Clinical Pathology.
Ellis, F. W. and J. R. Pick. “Ethanol Intoxication and Dependence in Rhesus Monkeys,” in N. K.

Mello and J. H. Mendelson, eds., Recent Advances in Studies of Alcoholism, Publ. no.
(HSM) 71-9045, pp. 401-412. Washington: U.S. Govt. Print. Off.. 1971.
Enoch, B. A. and D. M. Williams. “An Association Between Wernicke’s Encephalopathy and

Thyrotoxicosis,” Postgrad. Med. J., 44 (1968), 923-930.
Essig, C. F. ‘“Alcohol and Related Addicting Drugs,” in R. J. Catanzaro, ed., Alcoholism, the Total
Treatment Approach, pp. 69. Springfield, Ill.: Charles C. Thomas, 1968.
Essig, C. F. and R. C. Lam. “Convulsions and Hallucinatory Behavior Following Alcohol Withdrawal
in the Dog,” Arch. Neurol., 18 (1968), 626-632.
Ewing, J. A., B. A. Rouse, and E. D. Pellizzari. “Alcohol Sensitivity and Ethnic Background,” Am. J.
Psychiatry, 131 (1974), 206-210.
Falk, J. L. “Behavioral Maintenance of High Blood Ethanol and Physical Dependence in the Rat,”
Science, 177 (1972), 811-813.
Feinberg, I. “Hallucinations, Dreaming and REM Sleep,” in W. Keup, ed., Origins and Mechanisms of
Hallucinations, pp. 125, New York: Plenum, (1970).
Feinberg, I. and E. V. Evarts. “Some Implications of Sleep Research for Psychiatry,” in J. Zubin and
C. Shagass, eds., Neurobiological Aspects of Psychopathology, PP-334-393. New
York: Grune & Stratton, (1969).
Fisher, C. M. “Residual Neuropathological Changes in Canadians Held Prisoners of War by the
Japanese,” Can. Serv. Med. J., 11 (1955), 157-199.
Forbes, R. J. Short History of the Art of Distillation. Leiden, Netherlands: E. J. Brill, 1948.
Gearing, F. R. Successes and Failures in Methadone Maintenance Treatment of Heroin Addiction in

New York City, Proc. of the 3rd Natl. Conf. on Methadone Treatment, NAPAN-NIMH,
PHS Publ. no. 2172. Washington: U.S. Govt. Print. Off., 1970.
Gerard, D. L. and G. Saenger. Out-Patient Treatment of Alcoholism, Brookside Monogr. no. 4.

Toronto: University of Toronto Press, 1966.
Ginsberg, H., J. Olefsky, J. W. Farquhar et al. “Moderate Ethanol Ingestion and Plasma Triglyceride
Levels,” Ann. Intern. Med., 80 (1974), 143-149.
Goldstein, A., L. Aranow, and S. M. Kalman. Principles of Drug Action. New York: Harper & Row,
1968.
Goodwin, D. W. “Is Alcoholism Hereditary? A Review and Critique,” Arch. Gen. Psychiatry, 25
(1971), 545-549.
----. “Alcohol in Suicide and Homicide,” Q. J. Stud. Alcohol, 34 (1973), 144-156.
Goodwin, D. W., J. B. Crane, and S. B. Guze. “Phenomenological Aspects of the Alcoholic Blackout,”
Br. J. Psychiatry, 115, 1033-1038.
----. “Alcoholic Blackouts: A Review and Clinical Study of 100 Alcoholics,” Am. J. Psychiatry, 126
(1969), 191-198.
Goodwin, D. W., E. Othmer, J. A. Halikas et al. “Loss of Short Term Memory as a Predictor of the
Alcoholic ‘Blackout’,” Nature, 227 (1970), 201-202.
Goodwin, D. W., B. Powell, D. Bremer et al. “Alcohol and Recall: State-Dependent Effects in Man,”
Science, 163 (1969), 1358-1360.
Goodwin, D. W., F. Schulsinger, L. Hermansen et al. “Alcohol Problems in Adoptees Raised Apart
From Alcoholic Biological Parents,” Arch. Gen. Psychiatry, 28 (1973), 238-243.
Grenell, R. G. “Alcohols and Activity of Cerebral Neurons,” Q. J. Stud. Alcohol, 29 (1959), 421-427.
Gross, M. M., E. Lewis, and J. Hastey. “Acute Alcohol Withdrawal Syndrome,” in Kissin and H.
Begleiter, eds., The Biology of Alcoholism, Vol. 3, pp. 191-263. Clinical Pathology,
Gross, M. M., D. R. Goodenough, J. Hastey et al. “Sleep Disturbances in Alcohol Intoxication and
Withdrawal,” in N. K. Mello and J. H. Mendelson, eds., Recent Advances in Studies of
Alcoholism, Publ. no. (HSM) 71-9045, pp. 317-397. Washington: U.S. Govt. Print.
Off., 1971.
Gusfield, J. R. “Status Conflicts and the Changing Ideologies of the American Temperance
Movement,” in D. J. Pittman and C. R. Snyder, eds., Society, Culture and Drinking
Patterns, pp. 101-120. New York: Wiley, 1962.
Haggard, H. W., L. A. Greenberg, and Lolli. “The Absorption of Alcohol with Special Reference to
Its Influence on the Concentration of Alcohol Appearing in the Blood,” Q. J. Stud.
Alcohol, 1 (1941), 684.
Harger, R. N. and H. R. Hulpieu. “The Pharmacology of Alcohol,” in G. N. Thompson, ed.,

Alcoholism, pp. 103-232. Springfield, Ill.: Charles C. Thomas, 1956.
Heaton, J. M., A. J. McCormick, and A. G. Freeman. “Tobacco Amblyopia: A Clinical Manifestation of

Vitamin B12 Deficiency,” Lancet, 2 (1958), 286-290.
Howe, L. P. and V. D. Patch. “Rehabilitating the Tuberculosis Alcoholic,” Final Report: Research
Study no. RD-2138-P. Washington: Social and Rehabilitative Service, DHEW, 1971.
Iber, F., R. M. Kater, and N. Caruli. “Differences in the Rate of Ethanol Metabolism in Recently
Drinking Alcoholic and Non-Drinking Subjects,” Am. J. Clin. Nutr., 22 (1969), 1608-
1617.
Ironside, R., F. D. Bosanquet, and W. H. McMenemey. “Central Demyelination of the Corpus
Collosum (Marchiafava-Bignami Disease); With a Report of a Second Case in Great
Britain,” Brain, 84 (1961), 212-230.
Isbell, H., H. Fraser, A. Wikler et al. “An Experimental Study of the Etiology of Rum Fits and
Delirium Tremens,” Q. J. Stud. Alcohol, 16 (1955), 1-33.
Ishizaki, T., H. Chitanondh, and U. Laksanavicharn. “Marchiafava-Bignami’s Disease: Report of the

First Case in an Asian,” Acta Neuropathol., 16 (1970), 187-193.
Israel, Y. and J. Mardones, eds., Biological Basis of Alcoholism. New York: Wiley-Interscience, 1971.
Isselbacher, K. J. and E. A. Carter. “Effect of Alcohol on Liver and Intestinal Function,” in N. K.

(HSM) 71-9045, pp. 42-58. Washington: U.S. Govt. Print. Off., 1971.
Isselbacher, K. J. and N. J .Greenberger. “Metabolic Effects of Alcohol on the Liver,” N. Engl. J. Med.,
270 (1964), 35 402-410.
Jacobsen, E. “The Metabolism of Ethyl Alcohol,” Pharmacol. Rev., 4 (1952), 107-135.
Jaffe, J. H. “Psychopharmacology and Opiate Dependence,” in D. H. Efron, ed.,

Psychopharmacology: A Review of Progress 1957-1967, PHS Publ. no. 1836, pp. 853-
864. Washington: U.S. Govt. Print. Off., 1968.
----. “Drug Addiction and Drug Abuse,” in L. S. Goodman and A. Gilman, eds., The Pharmacological
Basis of Therapeutics, pp. 276-313. New York: Macmillan, 1970.
Jellinek, E. M. The Disease Concept of Alcoholism. Highland Park, N.J.: Hillhouse Press, 1960.
Johnson, L. C. “Sleep Patterns in Chronic Alcoholics,” in N. K. Mello and J. H. Mendelson, eds.,

Recent Advances in Studies of Alcoholism, Publ. no. (HSM) 71-9045, pp. 288-316.
Washington: U.S. Govt. Print. Off., 1971.
Kaim, S. “Drug Treatment of the Alcohol Withdrawal Syndrome,” in N. K. Mello and J. H.

Mendelson, eds., Recent Advances in Studies of Alcoholism, Publ. no. (HSM) 71-9045,
pp. 767-780. Washington: U.S. Govt. Print. Off., 1971.
Kalant, H. “Effects of Ethanol on the Nervous System,” in J. Tremolieres, ed., International
Encyclopedia of Pharmacology and Therapy, Sect. 20, Vol. 1. Alcohols and
Derivatives. New York: Pergamon, 1970.
----. “Absorption Diffusion, Distribution and Elimination of Ethanol: Effects on Biological

Membranes,” in B. Kissin and Begleiter, eds., The Biology of Alcoholism, Vol. 1, pp.
1-62, Biochemistry. New York: Plenum, 1971.
Kalant, H., A. E. LeBlanc, and R. J. Gibbins. “Tolerance To, and Dependence On Some Non-Opiate
Psychotropic Drugs,” Pharmacol. Rev., 23 (1971), 135-191.
Kater, R. M. H., D. Zeive, F. Tobin et al. “Heavy Drinking Accelerates Drugs’ Breakdown in Liver,”
JAMA, 206 (1968), 1709.
Keeping, J. A. and C. W. A. Searle. “Optic Neuritis Following Isonaizid Therapy,” Lancet, 2 (1955),
278.
Keller, M. “The Definition of Alcoholism and the Estimation of Its Prevalence,” in J. Pittman and G.
R. Snyder, eds., Society, Culture and Drinking Patterns, pp. 310-329. New York:
Wiley, 1962.
----. “On the Loss-of-Control Phenomenon in Alcoholism,” Br. J. Addict., 67 (1972), 153-166.
King, J. H. Jr., and J. W. Passmore. “Nutritional Amblyopia: A Study of American Prisoners of War
in Korea,” Am. J. Opthalmol., 39 (1955), 173-186.
Kissin, B. and H. Begleiter, eds. The Biology of Alcoholism, Vol. 1. Biochemistry, 1971; Vol. 2.
Physiology and Behavior, 1972. New York: Plenum.
Kissin, B., A. Platz, and W. H. Su. “Selective Factors in Treatment Choice and Outcome in
Alcoholics,” in N. K. Mello and J. H. Mendelson, eds., Recent Advances in Studies of
Off., 1971.
Knupfer, G. “Some Methodological Problems in the Epidemiology of Alcoholic Beverage Usage:

Definition of Amount of Intake,” Am. J. Public Health, 2 (1966), 237-242.
Landers, J. W., J. L. Chason, and V. N. Samuel. “Central Pontine Myelinolysis: A Pathogenic
Hypothesis,” Neurology, 15 (1965), 968-971.
Leake, C. D. and M. Silverman. Alcoholic Beverages in Clinical Medicine. Chicago: Yearbook Medical
Publishers, 1966.
----. “The Chemistry of Alcoholic Beverages,” in B. Kissin and H. Begleiter, eds., The Biology of
Alcoholism, Vol. 1. Biochemistry, pp. 575-612. New York: Plenum, 1971.
Lee, T. K., M. H. Cho, and A. B. Dobkin. “Effects of Alcoholism, Morphinism, and Barbiturate
Resistance on Induction and Maintenance of General Anesthesia,” Can. Anaesth. Soc.
J., 1 (1964), 354-381.
Lieber, C. S. “Alcohol and the Liver,” in E. Bittar, ed., The Biological Basis of Medicine, Vol. 5, pp.
317-344. London: Academic, 1969.
Lieber, C. S., E. Rubin, and L. M. DeCarli. “Chronic and Acute Effects of Ethanol on Hepatic
Metabolism of Ethanol, Lipids and Drugs: Correlation with Ultrastructural
Changes,” in N. K. Mello and J. H. Mendelson, eds., Recent Advances in Studies of
Alcoholism, Publ. no. (HSM) 71-9045, pp. 3-41. Washington: U.S. Govt. Print. Off.,
1971.
Liebmann, A. J. and B. Scherl. “Changes in Whiskey While Maturing,” Ind. Eng. Chem., 41 (1949),
534.
Lindenbaum, J. and C. S. Lieber, “Effects of Ethanol on the Blood, Bone Marrow, and Small
Intestine of Man,” in M. K. Roach, W. M. Mclsaac, and P. J. Creaven, eds., Biological
Aspects of Alcohol, pp. 27-53. Austin, Texas: University of Texas Press, 1971.
Lolli, G. and L. Meschieri. “Mental and Physical Efficiency After Wine and Ethanol Solutions
Ingested on an Empty and on a Full Stomach,” Q. J. Stud. Alcohol., 25 (1964), 535-
540-
Lopez, R. I. and G. H. Collins. “Wernicke’s Encephalopathy. A Complication of Chronic

Hemodialysis,” Arch. Neurol., 18 (1968), 248-259.
Lowenstein, L. M., R. Simone, P. Boulter et al. “The Effect of Fructose on Blood Ethanol
Concentrations in Man,” JAMA, 213 (1970), 1899-1901.
Ludwig, A. M. “The Design of Clinical Studies in Treatment Efficacy,” in M. E. Chafetz, ed., Proc. 1st
Annual Alcoholism Conf. N.I.A.A.A., DHEW no. (HSM) 73-9074. Washington: U.S.
Govt. Print. Off., 1973.
Ludwig, A. M., J. Levine, and L. H. Stark. LSD and Alcoholism. Springfield, Ill.: Charles C. Thomas,
1970.
Lundwall, L. and F. Baekeland. “Disulfiram Treatment of Alcoholism,” J. Nerv. Ment. Dis., 153
(1971), 381-394.
Mancall, E. L. and W. J. McEntee. “Alterations of the Cerebellar Cortex in Nutritional

Encephalopathy,” Neurology, 15 (1965), 303-313.
Marchiafava, E. and A. Bignami. “Sopra UnAlterazione del Corpo Calloso Osservata in Soggetti
Alcoolisti,” Riv. Patol. Nerv. Ment., 8 (1903), 544-549.
Mardones, J. “The Alcohols,” in W. S. Root and F. G. Hofmann, eds., Physiological Pharmacology.

New York: Academic, 1963.
Mayer, R. F. “Peripheral Nerve Conduction in Alcoholics,” Psychosom. Med., 28, 475-483.
McCormick, W. F. and C. M. Danneel. “Central Pontine Myelinolysis,” Arch. Intern. Med., 119
(1967), 444-478.
McGuire, M. T., J. H. Mendelson, and S. Stein. “Comparative Psychosocial Studies of Alcoholic and
Non-Alcoholic Subjects Undergoing Experimentally-Induced Ethanol Intoxication,”
Psychosom. Med., 28 (1966), 13-26.
McNamee, H. B., N. K. Mello, and J. H. Mendelson. “Experimental Analysis of Drinking Patterns of

Alcoholics: Concurrent Psychiatric Observations,” Am. J. Psychiatry, 124 (1968),
1063-1069.
Mello, N. K. “Some Aspects of the Behavioral Pharmacology of Alcohol,” in H. Efron, ed.,
Psychopharmacology: A Review of Progress 1957-67, PHS Publ. no. 1863, pp. 787-
809. Washington: U.S. Govt. Print. Off., 1968.
----. “Alcohol Effects on Delayed Matching to Sample Performance by Rhesus Monkey,” Physiol.
Behav., 7 (1971), 77-101.
----. “Behavioral Studies of Alcoholism,” in B. Kissin and H. Begleiter, eds., The Biology of
Alcoholism, Vol. 2. Physiology and Behavior, pp. 219-291. New York: Plenum, 1972.
----. “A Review of Methods to Induce Alcohol Addiction in Animals,” Pharmacol. Biochem. Behav., 1
(1973), 89-101.
----. “Short-Term Memory Function in Alcohol Addicts During Intoxication,” in M. M. Gross, ed.,
Alcohol Intoxication and Withdrawal: Experimental Studies, Proc. 30th Int. Congr. on
Alcoholism and Drug Dependence pp. 333-344. New York: Plenum, 1973.
----. “A Semantic Aspect of Alcoholism,” in H. D. Cappell and A. E. Leblanc, eds., International

Symposium on Alcohol and Drug Research. Toronto: Addiction Research Foundation,
forthcoming.
Mello, N. K. and J. H. Mendelson. “Experimentally-Induced Intoxication in Alcoholics: A

Comparison Between Programmed and Spontaneous Drinking,” J. Pharmacol. Exp.
Therap., 173 (1970), 101-116.
----. “Drinking Patterns During Work-Contingent and Non-Contingent Alcohol Acquisition,”

Psychosom. Med., 34 (1972), 139-164.
Mendelson, J. H., ed. “Experimentally-Induced Chronic Intoxication and Withdrawal in

Alcoholics,” Q. J. Stud. Alcohol, Suppl. 2 (1964).
----. “Ethanol-1-C14 Metabolism in Alcoholics and Non-Alcoholics,” Science, 159, 319-320.
----. “Biochemical Pharmacology of Alcohol,” in D. H. Efron, ed., Psychopharmacology: A Review of

Progress 1957-67, PHS Publ. no. 1836, pp. 769-785. Washington: U.S. Govt. Print.
Off., 1968.
----. “Biological Concomitants of Alcoholism,” N. Engl. J. Med., 283 (1970), 24-32, 71-81.
----. “Biochemical Mechanisms of Alcohol Addiction,” in B. Kissin and H. Begleiter, eds., The
Biology of Alcoholism, Vol. 1, Biochemistry, pp. 513-544. New York: Plenum, 1971.
Mendelson, J. H. and N. K. Mello. “Alcohol-Induced Hyperlipidemia and Beta Lipoproteins,”

Science, 180 (1973), 1372-1374.
----. “Alcohol, Aggression and Androgens,” Proc. Assoc. Res. Nerv. Ment. Dis., 52 (1974), 225-247.
----. “Plasma Testosterone Levels During Chronic Heroin Use and Protracted Abstinence,”
Pharmacologist, 16 (1974), 193 (Abstract 020).
Mendelson, J. H., J. E. Mendelson, and V. D. Patch. “Plasma Testosterone Levels in Heroin

Addiction and During Methadone Maintenance,” J. Pharmacol. Exp. Therapeutics,
192 (1975), 211-217.
Mendelson, J. H., M. Ogata, and N. K. Mello. “Effects of Alcohol Ingestion and Withdrawal on
Magnesium States of Alcoholics: Clinical and Experimental Findings,” Ann. N.Y.
Acad. Sci., 162, 918-933.
Mendelson, J. H. and S. Stein. “The Definition of Alcoholism,” in J. H. Mendelson, ed., Alcoholism,

Vol. 3, pp. 3-16. International Psychiatry Clinics. Boston: Little, Brown, 1966.
Mendelson, J. H., S. Stein, and N. K. Mello. “Effects of Experimentally-Induced Intoxication on

Metabolism of Ethanol-1-C14 in Alcoholic Subjects,” Metabolism, 14 (1965), 1255-
1266.
Mendelson, J., D. Wexler, P. Leiderman et al. “A Study of Addiction to Nonethyl Alcohols and Other
Poisonous Compounds,” Q. J. Stud. Alcohol, 18 (1957), 561-580.
Mulford, H. A. “Drinking and Deviant Drinking,” Q. J. Stud. Alcohol, 25 (1964), 634-650.
Myerson, R. M. “Effects of Alcohol on Cardiac and Muscular Function,” in Y. Israel and J. Mardones,
eds., Biological Basis of Alcoholism, pp. 183-208. New York: Wiley-Interscience,
1971.
Nathan, P. E.. N. A. Titler, L. M. Lowenstein et al. “Behavioral Analysis of Chronic Alcoholism,”

Arch. Gen. Psychiatry, 22, 419-430-
National Council on Alcoholism. “Criteria for the Diagnosis of Alcoholism,” Am. J. Psychiatry, 129
(1972), 127-135.
National Institute of Mental Health. Alcohol and Alcoholism, PHS Publ. no. 1640. Washington: U.S.
Govt. Print. Off., 1968.
Neville, J. N., J. A. Eagles, G. Samson et al. “Nutritional Status of Alcoholics,” Am. J. Clin. Nutr., 21
(1968), 1329-1340.
Newman, H. W. “Acquired Tolerance to Ethyl Alcohol,” Q. J. Stud. Alcohol, 2, 453-463.
Newman, H. W. and M. Abramson. “Absorption of Various Alcoholic Beverages,” Science, 96

(1942), 43.
----. “Some Factors Influencing the Intoxicating Effect of Alcoholic Beverages,” Q. J. Stud. Alcohol, 3
(1942), 351-370.
Ogata, M., J. H. Mendelson, and N. K. Mello. “Electrolytes and Osmolality in Alcoholics During
Experimentally-Induced Intoxication,” Psychosom. Med., 30 (1968), 463-488.
Overton, D. A. “State-Dependent Learning Produced by Alcohol and Its Relevance to Alcoholism,”

in B. Kissin and H. Begleiter, eds., The Biology of Alcoholism, Vol. 2. Physiology and
Behavior, pp. 193-217. New York: Plenum, 1972.
Pant, S. S., A. N. Bhargava, M. M. Singh et al. “Myelopathy in Hepatic Cirrhosis,” Br. Med. J., 5337
(1963), 1064-1065.
Pattison, E. M. “A Critique of Alcoholism Treatment Concepts; With Special Reference to

Abstinence,” Q. J. Stud. Alcohol, 27 (1966), 49-71.
Pattison, E. M., E. B. Headley, G. C. Gleser et al. “Abstinence and Normal Drinking,” Q. J. Stud.
Alcohol, 29 (1968), 610-633.
Pearson, W. S. “The ‘Hidden’ Alcoholic in the General Hospital. A Study of ‘Hidden’ Alcoholism in
White Male Patients Admitted for Unrelated Complaints,” N.C. Med. J., 23 (1960), 6-
10.
Pieper, W. A., J. J. Skeen, H. M. McClure et al. “The Chimpanzee as an Animal Model for
Investigating Alcoholism,” Science, 176 (1972), 71-73.
Pittman, D. J. and C. W. Gordon. Revolving Door: A Study of the Chronic Police Case Inebriate,
Monogr. no. 2. New Brunswick, N.J.: Rutgers Center for Alcohol Studies, 1958.
Pittman, D. J. and C. R. Snyder. Society, Culture and Drinking Patterns. New York: Wiley, 1962.
Plaut, T. F. A. Alcohol Problems: A Report to the National Cooperative Commission on the Study of
Alcoholism. New York: Oxford University Press, 1967.
Roach, M. K., W. M. McIsaac, and P. J. Creaven. eds., Biological Aspects of Alcoholism. Austin, Texas:
University of Texas Press, 1971.
Robbins, E., G. Murphy, R. Wilkenson et al. “Some Clinical Considerations in the Prevention of
Suicide Based on a Study of 134 Successful Suicides,” Am. J. Public Health, 49
(1959), 888-899.
Robins, L. N. and S. B. Guze. “Drinking Practices and Problems in Urban Ghetto Populations,” in N.
K. Mello and J. H. Mendelson, eds., Recent Advances in Studies of Alcoholism, Publ.
no. (HSM) 71-9045, pp. 825-842. Washington: U.S. Govt. Print. Off., 1971.
Roueche, B. The Neutral Spirit: A Portrait of Alcohol. Boston: Little, Brown, 1960.
Rubin, E., H. Gang, P. Misra et al. “Inhibition of Drug Metabolism by Acute Ethanol Intoxication: A
Hepatic Microsomal Mechanism,” Am. J. Med., 49, 800-806.
Rubin, E. and C. S. Lieber. “Alcohol-Induced Hepatic Injury in Nonalcoholic Volunteers,” N. Engl. J.

Med., 278 (1968), 869-876.
Schapiro, H., L. D. Wruble, and L. G. Britt. “The Possible Mechanism of Alcohol in the Production of
Acute Pancreatitis,” Surgery, 60 (1966), 1108-1111.
Schuckit, M. A., D. A. Goodwin, and G. Winokur. “A Study of Alcoholism in Half Siblings,” Am. J.
Psychiatry, 128 (1972), 1132-1136.
Seevers, M. H. and G. A. Deneau. “Physiological Aspects of Tolerance and Physical Dependence,” in

W. S. Root and F. G. Hofman, eds., Physiological Pharmacology, pp. 565-640. New
York: Academic, 1963.
Seixas, F. A. and S. Eggleston, eds. “Alcoholism and the Central Nervous System,” Ann. NY. Acad.
Sci., 215 (1973).
Shurtliff, L. F., E. T. Ajax, E. Englert et al. “Central Pontine Myelinolysis and Cirrhosis of the Liver,”
Am. J. Clin. Pathol., 46 (1966), 239-244.
Smith, A. A. “Inhibitors of Tolerance Development,” in D. H. Clouet, ed., Narcotic Drugs:

Biochemical Pharmacology, pp. 424-431. New York: Plenum, 1971.
Smith, D. A. and M. F. A. Woodruff. Deficiency Diseases in Japanese Prison Camps, Medical Research
Council, Special Report Series, no. 274. London: Her Majesty’s Stationery Office,
1951.
Spodick, D. H., V. M. Pigott, and R. Chirife. “Preclinical Cardiac Malfunction in Chronic Alcoholism,”
N. Eng. J. Med., 287 (1972), 677-680.
Sundby, P. Alcoholism and Mortality, Publ. no. 6. Oslo, Norway: The National Institute for Alcohol
Research, 1967.
Sutton, T. Tracts on Delirium Tremens, on Peritonitis and Other Inflammatory Afflictions. London:
Thomas Underwood, 1813.
Sydenstricker, V. P. and E. S. Armstrong. “Review of 440 Cases of Pellagra,” Arch. Intern. Med., 59
(1937), 883-891.
Talland, G. A. Deranged Memory. New York: Academic, 1965.
----. “Effects of Alcohol on Performance on Continuous Attention Tasks,” Psychosom. Med., 28
(1966), 596-604.
Talland, G. A., J. H. Mendelson, and P. Ryack. “Experimentally-Induced Chronic Intoxication and

Withdrawal in Alcoholics. Pt. 4, Tests of Motor Skills,” Q. J. Stud. Alcohol, Suppl. 2
(1964), 53-73.
----. “Experimentally-Induced Chronic Intoxication and Withdrawal in Alcoholics. Pt. 5, Tests of

Attention,” Q. J. Stud. Alcohol, Suppl. 2 (1964), 74-86.
Tamerin, J. S., S. Weiner, and J. H. Mendelson. “Alcoholics’ Expectancies and Recall of Experiences
during Intoxication,” Am. J. Psychiatry, 126 (1970), 1697-1704.
Tamerin, J. S., S. Weiner, R. Poppen et al. “Alcohol and Memory: Amnesia and Short-Term
Function during Experimentally Induced Intoxication,” Am. J. Psychiatry, 127
(1971), 1659-1664.
Tavel, M. E., W. Davidson, and T. D. Batterton. “A Clinical Analysis of Mortality Associated with
Delirium Tremens; Review of 39 Fatalities in a g-Year Period,” Am. J. Med. Sci., 242
(1961), 18-29.
Tinklenberg, J. R. “Alcohol and Violence,” in P. Bourne and R. Fox, eds., Alcoholism: Progress in
Treatment, pp. 195-210. New York: Academic, 1973.
Tygstrup, N., K. Winkler, and F. Lundquist. “The Mechanism of the Fructose Effect on the Ethanol
Metabolism of the Human Liver,” J. Clin. Invest., 44 (1965), 817-830.
Vanderpool, J. A. “Alcoholism and the Self-Concept,” Q. J. Stud. Alcohol, 30 (1969), 59-77-
Victor, M. “Treatment of Alcoholic Intoxication and the Withdrawal Syndrome. A Critical Analysis
of the Use of Drugs and Other Forms of Therapy,” Psychosom. Med., 28 (1966), 636-
650.
----. “The Pathophysiology of Alcoholic Epilepsy,” Res. Publ. Assoc. Nerv. Ment. Dis., 46 (1968), 434-
454.
Victor, M. and R. D. Adams. “The Effect of Alcohol on the Nervous System,” in Res. Publ. Assoc.
Nerv. Ment. Dis., 32 (1953). 526-573.
----. “On the Etiology of the Alcoholic Neurologic Diseases with Special Reference to the Role of
Nutrition,” Am. J. Clin. Nutr., 9 (1961), 379-397.
Victor, M., R. D. Adams, and H. G. Collins. The Wernicke-Korsakoff Syndrome. Philadelphia: Davis,
1971.
Walder, A. I., J. S. Redding, L. Faillace et al. “Rapid Detoxification of the Acute Alcoholic with
Hemodialysis,” Surgery, 66, 201-207.
Waller, J. A. “Factors Associated with Alcohol and Responsibility for Fatal Highway Crashes,” Q. J.
Stud. Alcohol, 33 (1972), 160-170.
Waller, J. A. and R. G. Smart. “Impaired Driving and Alcoholism: Personality or Pharmacologic

Effect?” J. Safety Res., 1 (1969), 174-177.
Wallgren, H. and H. Barry. Actions of Alcohol, Vol. 1. Biochemical and Physiological Aspects.
Amsterdam: Elsevier, 1970.
----. Actions of Alcohol, Vol. 2. Chronic and Clinical Aspects. Amsterdam: Elsevier, 1970.
Weschler, H., E. H. Kasey, D. Thom et al. “Alcohol Level and Home Accidents,” Public Health Rep.,
84 (1969), 1043-1050.
Wikler, A. “On the Nature of Addiction and Habituation,” Br. J. Addict., 57 (1961), 73-79.
----. “Personality Disorders. Ill: Sociopathic Type, The Addictions,” in A. M. Freedman and H. I.
Kaplan, eds., Comprehensive Textbook of Psychiatry, pp. 939-1003. Baltimore:
Williams & Wilkins, 1967.
Winkler, G. F. and R. R. Young. “The Control of Essential Tremor by Propranolol,” Trans. Am.
Neurol. Assoc., 96, 66-68.
Wintrobe, M. M., R. D. Adams, I. L. Bennett et al. Harrisons Principles of Internal Medicine, 6th ed.
New York: McGraw Hill, 1970.
Wolfe, P. H. “Ethnic Differences in Alcohol Sensitivity,” Science, 175 (1972), 449-450.
Wolfe, S. M., J. Mendelson, M. Ogata et al. “Respiratory Alkalosis and Alcohol Withdrawal,” Trans.
Assoc. Am. Physicians, 83 (1969). 344-352.
Wolfe, S. M. and M. Victor. “The Physiological Basis of the Alcohol Withdrawal Syndrome,” in N. K.
(HSM) 71-9045, pp. 188-199. Washington: U.S. Govt. Print. Off., 1971.
Wolin, S. J. and N. K. Mello. “The Effects of Alcohol on Dreams and Hallucinations in Alcohol
Addicts,” Ann. N.Y. Acad Sci., 215 (1973), 266-302.
Woods, J. H., F. I. Ikoni, and G. Winger. “The Reinforcing Properties of Ethanol,” in M. K. Roach, W.
M. Mclsaac, and P. J. Creaven, eds., Biological Aspects of Alcoholism, pp. 371-388.
Austin, Texas: University of Texas Press, 1971.
Woods, J. H. and G. D. Winger. “A Critique of Methods for Inducing Ethanol Self-Intoxication in

Animals,” in N. K. Mello and J. H. Mendelson, eds., Recent Advances in Studies of
Off., 1971.
World Health Organization. Expert Committee on Alcohol, First Report, Technical Report Series,
no. 84. Geneva: WHO, 1955.
World Health Organization. Expert Committee on Drug Dependence, Technical Report Series no.
407:6. Geneva: WHO, 1969.
Younger, W. Gods, Men and Wine, The Wine and Food Society. Cleveland, Ohio: World Publishing
Co., 1966.
Zieve, L., D. F. Mendelson, and M. Goepfert. “Shunt Encephalomyelopathy. II. Occurrence of

Permanent Myelopathy,” Ann. Intern. Med., 53 (1960), 53-63.
Zilborg, G. and G. W. Henry. A History of Medical Psychology. New York: Norton, 1941.
Zwerling, I. and M. Rosenbaum. “Alcoholic Addiction and Personality,” in S. Arieti, ed., American
Handbook of Psychiatry, 1st ed., Vol. 1, pp. 623-644. New York: Basic Books, 1959.
Notes
1 Portions of this chapter are taken from an administrative report on Alcohol Use and Alcoholism pre-
pared for the Special Action Office for Drug Abuse Prevention of the Executive Office of
the President by the senior author.
2 Recent reviews of the legal status of intoxication and alcoholism may be found in Chapter 7 of Legal
Issues in Alcoholism and Alcohol Usage
3 The effects of alcohol intoxication on memory function and sleep will be discussed under Clinical
Disorders.
4 This material is abstracted from Dreyfus. Numbers refer to bibliographic entries.
5 Most concepts of memory function differentiate between a “short-term” registration phase and a
“longterm” consolidation phase, with the implication that these are sequential processes
required for subsequent information retrieval. A recurrent source of confusion in the
short-term memory literature has been the inconsistency in definition of this term.
Short-term memory has been variously defined as l sec., 5 sec., 1 min., 5 min., and 30
min.
Chapter 16
Psychosis Associated With Hereditary Disorders
I. Herbert Scheinberg
Introduction1
The effects of hereditary abnormalities on the central nervous system

may be manifested as mental retardation, disturbances of neurological
function, or psychiatric disorders. Where the abnormal heredity is confined to
a single gene, or gene pair, it is, paradoxically, rather more common for two
or three of these phenotypic disturbances to be seen than is true where more
numerous and less well-defined genetic abnormalities are present. Thus
Huntington’s chorea and Wilson’s disease generally produce neurological and
psychiatric dysfunction, though a single dominant gene or a single pair of

recessive ones, respectively, is the cause of each disease. Yet the poorly
understood combinations of several genes which predispose to senile

psychoses are not generally also associated with impairment of intellectual
and neurologic function.
Mental retardation is by far the commonest hereditary disorder of the
central nervous system associated with genetic abnormalities that are more
or less well-defined biochemically. In phenylketonuria, maple syrup urine
disease, homocystinuria, histidinemia, and galactosemia—to cite the best
known of perhaps fifty nonchromosomal disorders—a specific block in
normal amino acid metabolism leads to the accumulation of sufficient
amounts of intermediate compounds to be toxic to the brain. In other

instances of mental retardation, such as the autosomal recessively
transmitted Tay-Sachs disease, or the chromosomal abnormality associated
with the cri-du-chat syndrome, there is little knowledge of the biochemical
mechanisms involved.
Neurological dysfunction—alone or with other manifestations of CNS
disorder—is characteristic of Huntington’s chorea, Wilson’s disease, familial
or hereditary tremor, and the genetically heterogeneous group of congenital

disorders, of which a number are hereditary, collectively diagnosed as
cerebral palsy.
Both psychotic and nonpsychotic psychiatric disturbances may be seen

in a number of hereditary disorders which are either well-defined syndromes,
such as Huntington’s chorea, or are the result of a complex interplay of
hereditary endowment and environment, such as the senile psychoses. Both

classes can be due, in large measure, to the indirect effects on the ego’s
functioning of a crippling or life-threatening disease, as discussed below
under Wilson’s disease. There is little doubt, however, that the specific and
direct biochemical effects of a disorder, e.g., the accumulation of large and
toxic excesses of copper in the brains of patients with Wilson’s disease, can
sufficiently derange brain function to produce psychiatric disorders.
Huntington’s Chorea
Huntington’s chorea is a widespread hereditary disorder of the CNS
which is transmitted as an autosomal dominant and has an incidence of about

four per 100,000 in Europe and the United States and about four per
1,000,000 in Japan. Clinical manifestation of the illness is rarely noted in
childhood; the onset, generally, occurs between the fourth and sixth decades.
Classically, chorea and the existence of the disease in members of previous

generations of the patient’s family are sufficient criteria for the diagnosis.
Frequently, “. . . ataxia, dysarthria, dysphagia, dysphasia . . .” may be present;
onset may occur in childhood; there may be, not uncommonly antedating
peripheral neurological disturbances, . . amnesia, judgment, and/or

orientation defects . . . ;” and there are almost always concomitant emotional
disturbances including depression, with suicidal impulses, or a clinical picture
indistinguishable from schizophrenia.
There is no biochemical knowledge of the disease; there is no chemical,
clinical, or pathological test or finding which is diagnostic; and there is no
specific treatment known. Except, possibly, for a test based on the
administration of L-Dopa, diagnosis is made solely on clinical grounds and the
physician is totally unable to tell if a child of a patient carries the dominant

abnormal gene which causes the disease or is free of this abnormal allele, and
will neither contract nor be able to transmit the disorder. Until diagnostic
clinical manifestations are noted, every such child has to be considered to
have an even chance of possessing, or not possessing, the abnormal gene.

Since signs and symptoms may not occur until the sixth decade, the problem
of genetic counselling becomes difficult indeed.
Management of patients, once it is clear that Huntington’s chorea is
present, is limited to nonspecific chemotherapy, for both the neurological and

psychiatric disturbances, and to supportive psychotherapy. Because of the
physician’s inability to diagnose the illness before clinical manifestations have
appeared, the uncertainties that surround the individual and his relatives are
almost as tragic as the effects of the disorder itself on the afflicted individual.
Wilson’s Disease
Wilson’s disease, with an incidence of about one in 200,000, is similar to
Huntington’s chorea in being hereditary (though transmitted in autosomal
recessive fashion), in severely affecting the CNS, both neurologically and
psychiatrically, and in not manifesting itself clinically early in life. In contrast,
however, there is a great deal of biochemical information about the disease,
diagnostic chemical tests can be applied, and specific therapy is available.
The etiologic agent causing the pathological changes which underlie the
disease is copper, toxic excesses of which are accumulated in the CNS.
Diagnosis is possible in the asymptomatic as well as the ill patient by the

demonstration of a deficiency (less than 20 mg./100 ml. of serum) of the
plasma copper-protein, ceruloplasmin, and an excess (greater than 250 μg./g.
dry liver) of hepatic copper. Specific treatment consists of the administration
of D-penicillamine, which removes copper from the symptomatic patient, in
whom marked clinical improvement generally results, and from the
asymptomatic one, in whom manifestations of the disease may be indefinitely

prevented.
Almost all diets contain 2-5 mg. of copper and this amount is more than
sufficient to supply the body’s need for this essential element, which is
present in a number of proteins such as cytochrome oxidase and tyrosinase.
The total body content of copper is about 150 mg., and virtually none is lost in
the urine so that the normal individual excretes in his stools, principally from
bile, almost precisely the amount absorbed from the diet. In Wilson’s disease,
a defect in the excretion of the absorbed copper has been inherited so that the
metal accumulates slowly, but steadily, in the liver. Eventually destruction of
hepatic parenchyma results in the release of relatively large amounts of
copper to the blood whence it diffuses into the brain, the corneas (where it
produces the diagnostic Kayser-Fleischer rings), the kidneys, and into almost
every other tissue and organ. The toxic effects of copper in all these sites
constitute Wilson’s disease.
From this sequence it is apparent that copper first reaches toxic levels
in the liver and, indeed, this organ almost invariably shows pathological
changes by the time the diagnosis of Wilson’s disease is first made even
though the patient may be asymptomatic. Yet in only about 40 percent of
patients who become symptomatic is the liver the source of the initial clinical
manifestations of the disease. In another 30-40 percent neurological signs are
first noted while neurotic, psychotic, or bizarre behavioral disorders herald

the onset in perhaps 25 percent. Many patients suffer from significant
psychiatric disturbance after an initial hepatic or neurological onset. Thus, in
one group of twenty-two patients with Wilson’s disease, nine, or 41 percent,

had a psychiatric diagnosis of which three appeared to be psychotic.® Of
forty-nine of our patients with Wilson’s disease, thirty, or 61 percent, had

significant psychiatric disturbances, of which nine were classified as
psychotic.
The emotional disturbances seen in these patients do not appear to be

associated with significant mental retardation or impairment. (Emphasis on
the intellectual impairment due to hereditary defects has probably tended to
obscure the fact that more subtle forms of psychological disease can also be
so caused.) Of the group of forty-nine patients just referred to, nineteen were
evaluated on the Wechsler Adult Intelligence Scale (or the Wechsler

Intelligence Scale for Children): individual IQ scores ranged from 57 to 135,
with an average full-scale IQ for the group of 94.
Very few sophisticated psychiatric studies of patients with Wilson’s
disease have yet been made. Before the introduction of penicillamine, the
hepatic and neurological disease, progressive and fatal, overshadowed the
psychiatric illness. With the availability of effective chemotherapy, on the
other hand, treatment—and prophylaxis—of hepatitis, tremors, and
dysarthria have been so dramatically successful that recently attention has

been given to investigating the frequent accompanying psychiatric disorder
which is usually not life-threatening.
Beard, writing in 1959 before penicillamine was generally available,

described a patient with indubitable Wilson’s disease who also suffered from
schizophrenia. He defined the latter as consisting of delusions of reference,
and hallucinations and affective flatness in a setting of clear consciousness

without insight. Although he found a number of patients in the literature who
were said to suffer from both Wilson’s disease and schizophrenia, he

considered the latter diagnosis generally to be incorrect, with the patients
suffering instead from less well-defined “. . . confusional state(s) or dementia.”
This conclusion follows from Beard’s assumption that schizophrenia is a
specific illness developing in a patient with “... a schizoid personality or
hereditary disposition . . . ,” and he clearly differentiates the latter from the

abnormal pair of genes which causes Wilson’s disease.
In the relatively superficial psychiatric studies reported since, it is

impossible either to describe a particular psychiatric syndrome specific for
Wilson’s disease or to differentiate the patients’ manifestations from the
psychiatric disorders seen in general practice. Six representative examples,
selected from our patients, follow:
1. A middle-aged man spent the last ten years of his life in a (New York
State) mental hospital, which he entered, before the diagnosis of Wilson’s
disease was made, with a diagnosis of paranoid schizophrenia.
2. A young man, of high intelligence and normal stability, suddenly
began to suffer from, and act out, voyeuristic compulsions which soon led to
his arrest, and a suicidal attempt while in jail.
3. An adolescent girl manifested neurotic disturbances to such a degree

that psychoanalytic treatment was initiated. Within six years mild
neurological abnormalities appeared and she became psychotically depressed
and withdrawn.
4. An adolescent boy pushed a woman visitor into a swimming pool and

chased his father with a shotgun before either neurological or hepatic
abnormalities of Wilson’s disease had become observable.
5. A married man in his early thirties attacked without warning an

elevator operator in the belief that this man was threatening to kill his
children.
6. A woman in her thirties had, over a period of about ten years, several
alternating episodes of mania and depression which have required

hospitalization in a state mental hospital.
Since 1960, the majority of patients with Wilson’s disease have received
regular therapy with penicillamine with marked clinical improvement which
has, obviously, been particularly well documented with respect to hepatic and
neurological disease. There is little doubt, however, in the minds of physicians
who have treated more than one or two patients with this disease, that the
psychiatric disorders also improve to a greater extent than would be expected
in a similar group of patients without Wilson’s disease. Although this is as
difficult to document as is the efficacy of any psychiatric therapy, the courses

of the six patients described above are of some interest:
1. This man remained hospitalized and, despite intensive treatment to
remove the excess copper, worsened progressively and died.
2. Life-long treatment with penicillamine, begun in 1960, was initially
accompanied by weekly sessions of therapy with a psychiatrist which later
were occasionally reinstituted for several months at a time. Neurological

recovery from a state of near-incapacity has been complete. The patient has a
wife and three children, effectively manages a moderately large and complex
family business, and is active in civic and charitable activities.
3. Psychiatric and penicillamine treatment resulted in disappearance of
the patient’s mild neurological manifestations. A psychotic episode with
depressive and schizophrenic overtones ended her marriage and required

almost six months of hospitalization. Following discharge, treatment with
penicillamine was accompanied by psychiatric treatment, chiefly involving a

variety of tranquilizing and mood-elevating drugs. She married a second time,
adopted a child and, despite continued immaturity, has managed to live a
reasonably fulfilling life as a housewife in a city 1000 miles from her mother,
on whom she remains quite dependent.
4. This boy, whose older untreated brother had died of Wilson’s disease,
was treated with penicillamine and manifested no further psychiatric

abnormalities. Mild neurological disabilities supervened before treatment
was begun and these have persisted but produce no significant incapacity.
5. Treatment with penicillamine, and brief psychiatric hospitalization
and treatment, have returned this man to a normal neurological and

psychiatric state.
6. One further episode of mania and depression required hospitalization

after regular treatment with penicillamine was instituted.
In the ensuing twelve years, however, only two episodes, requiring brief
hospitalization, have interrupted her normal life.
These results, and the impression that “. . . the incidence of psychiatric
disturbances is higher in patients with Wilson’s disease than it is in the
average neurological patient population . . .” make it difficult to escape the

conclusion that the psychiatric abnormalities of Wilson’s disease represent
more than the reactions of a patient to a crippling and life-threatening
disease. Such reactive emotional abnormalities are clearly part of the picture,
but the toxic neurological effects which copper deposits can produce, the fact
that there is “. . . widespread cortical damage . . . ,” and the improvement in
psychiatric dysfunction which follows removal of some of the excess copper,
strongly suggest that too much of this metal can directly derange the
integrative functions of the brain.
Acute Intermittent Porphyria
The term “porphyria” is used to describe a number of disorders of
porphyrin metabolism, some of which are inherited. Acute intermittent

porphyria is the best known, the most intensively studied, and the form
usually associated with psychiatric findings. The incidence of the disease,
which probably occurs in all races, is around one in 5000. It is generally

thought to be transmitted as an autosomal dominant. However, incidental and
incomplete data which are given in two reports not primarily concerned with
genetic aspects do not support this. They present no evidence of occurrence
in successive generations, and they indicate an incidence in affected families

of 22 and 20 percent when the propositus of each sibship is subtracted from
its number of patients. These characteristics are more consonant with an
autosomal recessive mode of inheritance than with a dominant mode, where

one expects to find patients in successive generations and an incidence of 50
percent among sibs of affected families.
Acute intermittent porphyria is characterized by episodes of severe

abdominal pain with nausea and vomiting. There may be accompanying fever
and leukocytosis, and paresis or even paralysis of various muscle groups.
Attacks may last for hours or days and are followed by long periods of good
health. The ingestion of barbiturates—or perhaps other drugs—and acute

infections are generally considered to be capable of precipitating attacks.
Biochemically the illness is associated with the excretion of
porphobilinogen and its metabolic precursor, S-aminolevulinic acid, in the
urine in amounts which may exceed 100 mg. daily. Because of the
nonspecificity of the clinical picture a firm diagnosis should not be made
unless these intermediates of heme biosynthesis can be demonstrated.
Acute intermittent porphyria has been considered by many authors to
be characterized by psychiatric complications. Most commonly, these are
thought to accompany the acute episodes with a “. . . complete return to
clarity and reason . . .” when the attack subsides. The description of these
manifestations varies from mild irritability or depression to delirium or frank
psychosis. In a rather widely publicized paper in the British Medical Journal
the episodic madness of King George III has been unequivocally attributed to
acute intermittent porphyria. Presumably by referring his aberrant behavior
to a genetically caused excess of porphobilinogen and 8-aminolevulinic acid

rather than to unknown mechanisms these authors conclude that “. . . this
diagnosis clears the House of Hanover of an hereditary taint of madness. . . .”
Unfortunately, the psychiatric investigation of this disease has been

relatively naive and confined to conscious manifestations. Investigators have
differed widely in their conclusions, as is implicit in a review of previous
studies by Ackner, Cooper et al. The psychiatric disorders noted have been
considered to be (1) a consequence of the inherited metabolic error, though
by unknown pathogenic mechanisms; (2) reactions to a recurrent but solely
somatic disorder which the patients generally know to be life-threatening; (3)
causative of the acute attack; or (4) coincidental findings. In the study by
Ackner et al. the “. . . importance of emotional disturbances in precipitating

acute attacks . . and the suggestion that the “. . . porphyric patient has a
background of neurotic instability . . .” are not considered to be supported by
the evidence in the literature. In their study of thirteen patients they could
find no evidence for a psychogenic factor in the etiology of the disorder, nor
for a neurotic predisposition. Although “. . . psychiatric symptoms commonly
occur during an acute attack of porphyria .. . (they may) be largely
psychogenic and unrelated to the underlying metabolic defect.”
Clearly, treatment of the psychiatric manifestations which may

accompany the acute attacks of porphyria is necessarily nonspecific. As noted,
these disturbances subside when the attacks are over.
There are several other disturbances in porphyrin metabolism2 which

are inherited, but they have little or no association with psychiatric
abnormalities.
Discussion
Wilson’s disease, Huntington’s chorea, and acute intermittent porphyria
are similar in that each is caused by the inheritance of only one, or a pair of,
abnormal genes. Their dissimilarities are greater than this shared
characteristic. Thus, we know nothing of the biochemical defect caused by the
abnormal gene of Huntington’s chorea and have no chemical or pathological
means of confirming the diagnosis, before or after the disease is clinically

manifest; there is no effective treatment. There is no doubt that psychiatric
disturbance is a major characteristic of the disease, but we do not know if the
emotional disorder is a reaction to the somatic, neurological disease or is a

direct result of the unknown biochemical defect, or is due to both.
We know at least the probable chemical locus of the biochemical defect

which underlies acute intermittent porphyria—somewhere in the pathway of
the biosynthesis of heme— but we know neither what the primary gene
product—enzyme or protein—of the abnormal, or normal, gene is, nor how

or if the abnormal amounts of porphobilinogen and 8-aminolevulinic acid
produce the somatic symptoms of the acute attack. Unlike what appears to be
true of Wilson’s disease and perhaps Huntington’s chorea, the available data
leave quite uncertain whether the psychiatric manifestations which have

been observed are in any way specifically related to the biochemical defect, or
whether they solely constitute the reactions to a recurrent and life-
threatening illness.
Although we also do not know what the primary gene product of the
“Wilson’s disease gene,” or its normal allele is, we have considerably more
information about the etiology and pathogenesis of this disorder. The inborn
metabolic error results in gradually increasing deposits of copper throughout
the body, and the clinical manifestations of the disorder, very probably
including to a significant degree the psychiatric disturbances, are the direct
result of copper toxicity. In part, of course, the emotional abnormalities also
represent reactions to a chronic disease which, untreated, is progressively
disabling and ultimately fatal. Freud predicted, in 1920, that deeper

molecular knowledge about psychiatric disease would make psychoanalytic
techniques of treatment obsolete. His prediction is, to a modest degree,
fulfilled by the unquestionable improvement, in the psychiatric disease of a

significant number of patients with Wilson’s disease, which accompanies the
pharmacological removal of a portion of excess copper. Such improvement
appears to be accelerated if psychotherapy, or nonspecific chemo-
psychotherapy, or both, accompanies the life-long administration of d-

penicillamine to remove copper.
These diseases are the only instances of hereditary psychosis about

which we have any biochemical genetic knowledge. Unfortunately, they
constitute an insignificant proportion of all psychiatric disease. There is little

doubt that heredity plays a significant, if not the dominant, role in the etiology
of the psychoses, and of other psychiatric disturbance, but those causative
effects are probably a summation of at least several synergistic genes. We
have little knowledge about the linkages of these genes, the disorders
associated with them, and no knowledge of the biochemical consequences of
having inherited the normal or abnormal allele. Pick’s disease is apparently

associated with a dominant gene and, perhaps, Alzheimer’s and Jakob-
Creutzfeldt’s presenile dementias have genetic determinants, but these vague
bits of data are of little aid to diagnosis and of none to therapy.
Jervis summarizes our ignorance of these hereditary, emotional
disorders: “. . . the precise nature of these genetic factors remains

undetermined . . .” This ignorance includes for each such psychiatric disease,
the number of genes involved as well as the structure, function, and
concentration of their primary gene product and the manner in which the
genetic endowment interacts with the individual’s physical and emotional
environment. At present, we have a significant part of such knowledge for
only a few hereditary diseases of the CNS. In these, furthermore, psychosis is

not the dominant clinical manifestation, and the primary interaction of the
abnormal genes is with physical, not emotional, aspects of the environment.
In phenylketonuria, galactosemia, the sphingolipidoses, and Wilson’s disease
the single-gene defect results in the accumulation of a normal chemical

metabolite to concentrations which are toxic to the CNS. Just to speculate on
the number of genes possibly involved etiologically in schizophrenia, and how
they may interact with the patient’s emotional milieu, internal and external, is
to make depressingly obvious how far we are from the time predicted by
Freud fifty years ago: “the deficiencies in our description (of emotional
disorders) would probably vanish if we were already in a position to replace

the psychological terms by physiological or chemical ones . . . On the other
hand it should be made quite clear that the uncertainty of our speculation has
been greatly increased by the necessity for borrowing from the science of
biology. Biology is truly a land of unlimited possibilities. We may expect it to
give us the most surprising information and we cannot guess what answers it
will return in a few dozen years to the questions we have put to it. They may
be of a kind which will blow away the whole of our artificial structure of
hypotheses.” [pp. 82-83]
Genetic Terminology
Every inherited characteristic of a living organism is a consequence of a
particular gene or of gene interaction. For some organisms, which are called
“haploid”, each characteristic is governed by unpaired genes; other
organisms, including human beings, are termed “diploid” and possess a pair
of genes for each characteristic, with one member of the pair derived from the
father and the other from the mother. The number of genes in each human
individual is unknown, but may approach 1,000,000.
A gene may be “autosomal,” in which case it is present on one of the
forty-four nonsex determining chromosomes; or it may be sex-linked, in
which case it is located on the X chromosome. A gene is linked to other genes
when all are present on the same chromosome, and are generally inherited as
a unit.
A gene is termed “dominant” if the possession of one gene of a pair is
sufficient to produce a specific disease, irrespective of the nature of its paired
mate. A gene is “recessive” if both members of the pair must be abnormal for
the disease to be produced. There are often two or more forms of a given
gene, each of which is called an allele, and only one, or a pair, of which can be
present in an individual. Where a disease-associated gene is recessive, the
heterozygote, i.e., the individual with one abnormal and one normal allele, is
called a “carrier” of the disease and, generally, does not manifest any clinical
abnormalities.
All genes function either by determining the structure of a protein,
termed the “primary gene product,” or by regulating the rate and conditions
under which the primary gene product is synthesized.
Inherited diseases may also be the consequence of the possession of
more, or less, than the normal complement of forty-six chromosomes, or of

abnormal forms of chromosomes. Such diseases are generally much more
gross in their clinical effects than single-gene disorders for the obvious
reason that a chromosome contains many genes.
Bibliography
Ackner, B., J. E. Cooper, C. H. Gray et al. “Acute Porphyria: A Neuropsychiatric and Biochemical
Study.” J. Psychosom. Res., 6 (1961), 1-24.
Beard, A. W., “The Association of Hepatolenticular Degeneration with Schizophrenia,” Acta

Psychiatr. Neurol. Scand., 34 (1959), 411-427.
Carney, M. W. P. “Hepatic Porphyria with Mental Symptoms,” Lancet, 2 (1972), 100-101.
Freud, S. (1920) “Beyond the Pleasure Principle,” in J. Strachey, ed., Standard Edition, Vol. 18, pp.
7-64. London: Hogarth, 1950.
Goldstein, N. P., J. C. Ewert, R. V. Randall et al. “Psychiatric Aspects of Wilson’s Disease

(Hepatolenticular Degeneration): Results of Psychometric Tests During Long-Term
Therapy,” Am. J. Psychiatry, 124 (1968), 1555-1561.
Jervis, G. A. “The Presenile Dementias,” in Mental Disorders in Later Life, 2nd ed., pp. 262-288.
Stanford: Stanford University Press, 1956.
Kallman, F. J. “The Genetics of Psychoses; An Analysis of 1232 Index Families,” Congres

International de Psychiatrie, VI. Genetique et Eugenique, pp. 1-40. Paris: Hermann,
1950.
Kallmann, F. J., L. Feingold, and E. Bondy. “Comparative Adaptational, Social, and Psychometric
Data on the Life Histories of Senescent Twin Pairs,” Am. J. Human Genet., 3 (1951),
65-73.
Klawans, H. C., G. W. Paulson, and A. Barbeau. “Predictive Test for Huntington’s Chorea,” Lancet, 2
(1970), 1185-1186.
Lynch, H. T., W. L. Harlan, and J. S. Dyhrberg. “Subjective Perspective of a Family with
Huntington’s Chorea,” Arch. Gen. Psychiatry, 27 (1972), 67-72.
Macalpine, I. and R. Hunter. “The ‘Insanity’ of King George III: A Classic Case of Porphyria,” Br.
Med. J., 1 (1966), 65-71.
Scheinberg, I. H. and I. Sternlieb. “Wilson’s Disease,” Ann. Rev. Med., 16 (1965), 119-134.
----. “Copper Metabolism and the Central Nervous System,” in O. Walaas, ed., Molecular Basis of
Some Aspects of Mental Activity, Vol. 2, pp. 115-116. New York: Academic, 1967.
Scheinberg, I. H., I. Sternlieb, and J. Richman. “Characterization of the Psychiatric Manifestations

of Wilson’s Disease,” in D. Bergsma, I. H. Scheinberg, and I. Sternlieb, eds., Wilsons
Disease, Birth Defects Original Article Series, Vol. 4, no. 2, pp. 85-87. New York: The
National Foundation—March of Dimes, 1968.
Slater, E. and V. Cowie. The Genetics of Mental Disorders. London: Oxford University Press, 1971.
Sternlieb, I. and I. H. Scheinberg. “Prevention of Wilson’s Disease in Asymptomatic Patients,” N.

Engl. J. Med., 278. 352-359.
Whittier, J. R. “Genetics in Psychiatric Practice,” Eugenics Q., 5 (1958), 9-15.
----. “Clinical Aspects of Huntington’s Disease,” in A. Barbeau and J.-R. Brunette, eds., Progress in
Neurogenetics. Proc. 2nd Int. Congr. of Neuro-Genetics and Neuro-Ophthalmology,
World Fed. Neurol., Montreal, Sept., 1967. Vol. 1. Huntington’s Disease, pp. 632-644.
Amsterdam: Excerpta Medica Foundation, 1969.
Whittier, J. R., G. Haydu, and J. Crawford. “Effect of Imipramine (Tofranil) on Depression and
Hyperkinesia in Huntington’s Disease,” Am. J. Psychiatry, 118 (1961), 79.
Whittier, J. R., A. Heimler, and C. Korenyi. “The Psychiatrist and Huntington’s Disease (Chorea),”
Am. J. Psychiatry, 128, 1546-1550.
World Health Organization Scientific Group. “Screening for Inborn Errors of Metabolism,” WHO
Tech. Rep. Ser. no. 401. Geneva: WHO, 1968.
Notes
1 A section on the genetic terminology used in this chapter appears at the end.
2 Porphyria variegata, hereditary coproporphyria, erythropoietic porphyria, and erythropoietic

protoporphyria.
Chapter 17
A. Clinical Aspects1
John R. Whittier
Introductory Remarks
A brief historical review of events since the first edition of the American
Handbook of Psychiatry is of interest. The first printing of the Handbook was

in 1959, and it had run through nine printings by 1967. In that year, by
coincidence, a remarkable wave of attention was paid to Huntington’s disease
(chronic progressive hereditary chorea). This was evidenced by the fact that
during the decade ending 1959 there had been approximately 120
publications in the scientific literature on the disease. The number had
increased to over 350 during the decade ending 1969. Furthermore, the first
international symposium on the disease was held in September of 1967 in
Montreal. This symposium brought together a group of investigators which

reviewed what was known of the disease to that time, and proceedings were
subsequently published by the hosting Congress of Neurogenetics and Neuro-
ophthalmology of the World Federation of Neurology. In 1967 there was also
created the Committee to Combat Huntington’s Disease, spurred by the
interest of a single individual, Marjorie Guthrie, whose husband died of
Huntington’s disease. The Committee grew from a single small group in that
year to a national organization with headquarters in New York and more than
fifty chapters in the United States and other countries by 1974. This
Committee was also responsible for assisting the World Federation of

Neurology Research Commission on Huntington’s Chorea not only in holding
its 1967 symposium but also in holding a centennial symposium in 1972
celebrating the description by George Huntington of the disease and resulting
in publication of the first book devoted entirely to its present status. The
publication is a comprehensive review to which anyone interested in special
aspects of the disease, including those of interest to psychiatrists, may refer.
In the relatively short time since 1967, there has been a great increase
in the number of investigators devoting a major part of their efforts to clinical

and pathological aspects of Huntington’s disease (H.D.). New concepts
regarding aspects of the underlying pathological physiology have appeared.
The effect of L-Dopa, other chemicals, and of neurotransmitters on the
disease has been studied. Development of new techniques and the refinement
of previous techniques have progressed, including fluorescence microscopy,
electron microscopy, and methods of chemical analysis of human brain
obtained at autopsy or by biopsy.
The role of the psychiatrist with regard to the disease varies, depending
on the orientation of the patient or family member and the nature and setting
of the psychiatrist’s practice. Useful previous reports dealing with the role of
the psychiatrist in summary manner are available.
Nature of the Disease
The disease is unusual by reason of its genetic mechanism. It passes
from one generation to another by a Mendelian pattern of autosomal
dominant gene with almost complete penetrance. This means that a parent
who carries the gene and lives long enough will ultimately develop the
disease. If there are offspring, of either sex, the probability for each of
acquiring the disease and passing it to their offspring in the same manner is
50 percent. Although the disease has been thought to “skip” generations there
is general agreement that this never occurs. “Skipping” is usually the result of
inadequate family history, or of death of a gene-carrying parent prior to the
appearance of symptoms. The underlying pathology is that of a slowly
progressive atrophy limited to selected sites in the brain only. It is

characterized by distinctive neuropathological changes (see section on
Neuropathology) in a process usually extending over a period of ten to fifteen
years. Onset of more or less blatant symptoms only after the first three
decades insures that a pool of individuals “at risk” for the disease is almost
always available. In most populations studied to date, a prevalence of six per
100,000 general population is found. Some pockets of exceptionally high
prevalence are known, as in Maracaibo, Venezuela, and in the Moray Firth

area of Scotland. Knowledge of and attitudes toward the disease by the
populations in areas of high prevalence should be of special interest to
psychiatrists.
Clinical Picture
The symptoms of the disease may be considered as “usual early
patterns” and “usual advanced patterns.” The usual early patterns may have
an “early onset” form with severe mental retardation, rigidity, and epileptic
seizures appearing in the first year of life and rapidly progressing to profound
neurological disability and death in three to five years. This early onset form
has recently been shown to occur more often when the affected parent of
such an offspring was the father. The attention of psychiatrists is usually not
drawn to such patients. Other patterns of early onset occur in the juvenile and
adolescent period. Here behavior disorders occur, including asocial,
antisocial, and withdrawal disorders, emotional lability, depression, a strong

tendency to sexual promiscuity, and abuse of drugs and alcohol. These
patients are likely to come to the attention of psychiatrists. Recognizing the
symptoms either as reactive to the presence of known disease in the family
(even in instances where the offspring eventually can be shown to be gene-
free by their subsequent course) or as those generated from early influence
by the gene in initial stages of the actual disease presents as a challenging

situation.
The symptoms in the usual advanced state are the result of years of the
slow progressive selective atrophy of the brain which characterizes the
disease. Symptoms and signs appear gradually, and are slowly progressive
with onset in the second and third decades. In the fourth and fifth decades
they are fully developed. They include psychiatric symptoms such as
irritability, hostility, assaultiveness, and depression, and behavioral
symptoms including alcoholism, drug abuse, and promiscuity. Neurological

symptoms appear, including chorea, incoordination, dysarthria, aphasia,
ataxia, pseudo bulbar palsy and bulimia, and defects in memory, orientation
and judgment. For psychiatrists it is important to recognize that psychiatric

symptoms may long precede the appearance of the neurological symptoms. A
tendency for depression and suicide appears to occur more frequently in
females, and for assaultiveness and homicide more frequently in males.
Despite the relatively low reported prevalence, there are many investigators
who believe it is considerably higher. Psychiatrists should always elicit as
complete a family history as possible from any patient coming to their
attention because of the serious personal, social, economic and other
complications arising from a failure to make early diagnosis. Psychiatric
symptoms may be the only ones present for many years before the typical
choreic symptoms appear. Conversely, chorea alone, late in onset, may exist
with very little dementia.
The chorea is typical in pattern, characterized by the occurrence of
abnormal involuntary movements (AIMS), caused by contractions of muscle
groups occurring at different sites in irregular sequence. Collaboration of
contracting and relaxing muscle groups is preserved, so that movements of

body surfaces or segments take place. Contractions may not be of sufficient
magnitude or arrangement to cause displacement of a limb or body segment,
but they can be detected by careful continuous observation. They do not

occur during sleep. Standardized motion picture recording over a period of
years has been extremely helpful in distinguishing at risk individuals with
abnormal involuntary movements patterned as chorea from at risk

individuals with normal involuntary movements (NIMS) resulting from
anxiety. When sufficiently forceful and occurring at appropriate sites, the
movements produce a sequence of grotesque posturing and distorted or
uncoordinated voluntary movements.
Chorea may occur in any part of the visible, voluntary, muscular

apparatus such as face musculature, especially perioral and periorbital, and
the chest, including diaphragmatic musculature and resulting in markedly
irregular breathing patterns which in themselves contribute to speech
abnormalities. Speech abnormalities and very slight movements of axial
musculature and of fingers tend to occur during the early stages of the
disease. The inability to keep the tongue protruded is almost pathognomonic
in advanced cases, and reduction in time of maintained tongue protrusion
often occurs early in the adult. A tendency to familial stereotype appears not
only in the time of onset of the disease (juvenile or adolescent as compared to

adult) but also in the sites of choreic activity. A rigid form without chorea is
recognized. A tendency also appears for offspring of patients with
Huntington’s Disease to display increased frequency of medical disorders

unassociated with Huntington’s Disease.
A remarkable tendency to promiscuity in both young and old (lack of
sexual inhibition, remarked upon in 1872 by Huntington for elderly patients)
favors on the one hand illegitimacy with its attendant difficulties in tracing
family lines, and, on the other hand, what appears to be a real tendency to
high fecundity; families of a parent with the disease tend to be unusually

large. This latter observation may very well be related to abnormally high
sexual activity by reason of the underlying degeneration of especially caudate

and putamen nuclei, whose purpose includes many aspects of inhibition of
behavior. The apparently high parental fecundity may also be interpreted,
however, as deriving from the denial mechanism which is so common in the
disease.
The rate of progression of the disease may vary greatly between
individuals. It is much more rapid with early than late onset cases. The
influence of stress in some form of other appears unequivocal in causing

symptoms to appear for the first time, or in worsening symptoms already
present. Pregnancy and head injury have been reported as unusually common
stressor events.
Diagnosis
Probably because of the sites of degeneration in the brain and the stress
generated even in gene-free at risk individuals with a family history of the
disease, an unusually long list of psychiatric and neurological disorders

require consideration and exclusion. It must be repeatedly emphasized that
only the affirming of a positive family history after energetic tracking of the
family line, pursued with such persistence and in such depth as is perhaps
done properly only by a geneticist, permits the differentiation of H.D. from
other disorders. Psychiatric disorders include anxiety, which is capable of
ubiquitous manifestations, and schizophrenic reactions, especially paranoid
and catatonic, torticollis, tic (including the syndrome of Gilles de la Tourette),

and especially depressions of one or another variety. Perioral, periorbital, and
facial choreic movements are occasionally mistaken for schizophrenic
grimaces. Among neurological disorders, Huntington’s disease is most
frequently misdiagnosed as Parkinson’s disease or multiple sclerosis.
Sydenham’s chorea, and chorea occasionally presenting with general medical

disorders should provide no diagnostic problem, but the disorders of
Creuzfeldt-Jakob and Hallervorden-Spatz, familial paroxysmal
choreoathethosis, cerebellar disorders including olivopontocerebellar
atrophy, and the diseases of Alzheimer and Pick may present diagnostic
problems resolved only by a neurologist.
“Senile chorea” probably is an entity, but can usually be distinguished
from Huntington’s disease by the pattern of severe AIMS in the presence of
relatively mild or absent dementia, and a well-established negative family

history. Posthemiplegic chorea is almost invariably unilateral. A recent
review listed eighty-five diseases to be considered in differential diagnosis.
Urgent search is underway for a specific test capable of detecting the

disease before the onset of symptoms. The effort has been notably
unsuccessful, except perhaps for evidence that an L-Dopa challenge may
evoke choreic AIMS in at risk subjects (and worsen chorea if present already).
The lack of an early sensitive test prior to onset of recognizable early
symptoms has been probably the single most troublesome aspect of the
management of Huntington’s disease, since the stress of knowledge of its
presence in the family and the drive to child bearing precede the signs and
symptoms required for diagnosis in at risk individuals. Specifically, lumbar
puncture and specialized examination of spinal fluid have had no value. The
electroencephalogram has been shown to be without value in early stages of

the disease. When disease is advanced, abnormal EEG patterns usually appear
as flattening of wave forms. Pneumoencephalography shows dilated lateral
ventricles and widened sulci, which characterize the ultimate generalized
atrophy of affected brains. Psychological testing offers no diagnostic help.

Electromyography has nothing specific to offer. Special applications of
tremometry may ultimately be helpful in early diagnosis. Electro-oculography
is still in the experimental stage but shows considerable promise.

Cineseismography is one of the newer methods for quantifying abnormal
involuntary movements of all types, and may be helpful in a battery of tests
for secondary phenomena. By this method, motion-picture records are made
of movements and their detection by the sensitive surface of a metabolic

scale. Brain biopsy is now being performed, and the tissue studied by a
variety of sophisticated methods, but this is not practical for routine

purposes, although some abnormalities in cortical tissue may ultimately be
accepted as specific.
Management
The way in which psychiatrists become drawn into what is best referred
to as a management relation to patients (referred to as probands in the case
of the first in the family coming to his attention) and their family depends
upon many factors, including the psychiatrist’s type of practice, his
geographic location, the administrative setting in which he may operate, and
the special diagnostic resources available to him. Most patients hospitalized
for Huntington’s disease are in its advanced stages, and are usually found in
state hospitals, Veterans Administration hospitals, or nursing homes.
Patients usually appear as troubled family members either from a direct
line who are at risk and have not yet developed the disease or who are
showing early signs of the disease. In either case, anxiety and depression and
combinations of these may be present.
Collateral members of affected families may come to the psychiatrist’s

attention with symptoms of anxiety and depression arising from their
awareness of the disease if it has only recently come to their attention and
they have little knowledge of its nature. In any case, psychotherapy is
indicated in whatever form the psychiatrist can offer, and this does not
exclude patients with the disease suffering from its nonneurological
consequences. The first priority of therapy should be to insure that the
patient’s knowledge of the disease is as complete as he is capable of

comprehending, the information being communicated by a therapist who is
free of anxiety. This may take preliminary exploration of the area, and
instruction over a period of time. Indeed this educational process alone may,
if properly handled, alleviate much of the symptomatology. If a definite
diagnosis has not been made, there should be no hesitation by the

psychiatrist to refer to a neurologist or a medical center. Most experience,
contrary to what might be expected, is that a positive diagnosis is less likely
to generate symptoms than it is to relieve them. This is apparently because
uncertainty by itself creates fear or anxiety. It is always desirable to proceed

carefully giving knowledge concerning the disease, and especially in
conveying the fact that diagnosis has been made. Many patients stoutly assert
that they wish to know whether they have the disease when, in fact, at least
for the moment, they do not. However, if a patient is asked, why he wishes to
know, one can be guided by the answer: “I would find the nearest tall building
and jump off it.” This carries quite different implication than “At least I would
know and be able to plan in advance depending on how bad my condition

might become.” Psychotherapy should resort to the aid of professional genetic
counseling if available, Sometimes it is not; references to detailed reports of

management are provided in this chapter. In addition, referral may be made
to special resources, such as geographical listing of genetics counseling

centers regularly updated by the National Foundation-March of Dimes. The
Committee to Combat Huntington’s Disease now has chapters in almost every
state, and the national organization in New York can provide information
about a nearby chapter. Contact by patients with these chapters usually
provides strong additional support for psychotherapy. In some situations,
physical, social and economic assistance may be available, as in the Veterans
Administration. Legal referral may occasionally be necessary because
individuals may have problems relating to vocational, professional, and
economic planning, marital and parental situations, or insurance and driving
coverage. With regard to application forms, individuals should usually be

informed that if they are truthful concerning the presence of Huntington’s
disease in the family, they may risk rejection or increased insurance
premiums, or be subjected to special tests for a driver’s license. If they are not
truthful, and difficulties arise they may lose insurance coverage and be
subject to heavier penalties for damages incurred in accidents. Problems of
this nature often require a psychiatrist, but unfortunately they do not always
have the information to offer. Very often the expectation is that somebody
else will take care of this responsibility, such as a neurologist or a geneticist.
The result is that the patient is never provided with the information he
requires in order to advance the psychotherapeutic relation which should

always include correct information, appropriately presented. The situation is
analogous to many of those arising from overspecialization in medicine,
unless provision is made for specifying functions in an organization. Of
course, in some rural situations a psychiatrist may be the only individual

available to a family either to alert a family to the presence of Huntington’s
disease or to see that their needs are properly met.
A variety of medications are effective in the psychiatrist’s handling of
patients, whether they are symptomatic with chorea and non-neurological
problems, or at risk. A series of effective antichoreic medications include
reserpine in doses increasing from 2 to 12 mg. per day; chlorpromazine in

appropriate dosage, usually 50 mg. three times a day or single dose at
bedtime, and fluphenazine or halo-peridol, either given in dosage from 2 to
15 mg. per day. All these medications usually are increased by steps over a
period of several weeks. Benefit to the chorea, anxiety, and delusions or other
mental aberrations should be expected before adverse side effects, usually
drowsiness or dystonic reactions. The latter can be appropriately managed
with benztropine in dosage of 2 mg. or biperiden (2 mg.) 2 mg. twice a day or
more. Diazepam is useful during the day and for sleep, as is the newer
compound fluorazepam.
Depression, which is so frequent and common, responds to
antidepressant medications, which the psychiatrist should choose as he
desires. Imipramine in dosage of 50 mg. three times a day or single dose at

bedtime is quite reliable. In some instances antidepressants alone may
worsen the chorea.
It is more generally recognized that neurosurgical procedures on brain
or peripheral nerves is of no benefit, and may damage a tissue already
undergoing progressive handicap.
Complications in early stages include depression of suicidal degree

which should be handled appropriately; Huntington’s disease is no
contraindication of electroconvulsive therapy. As the disease advances, the
neurological symptoms singly or in combination usually lead to bedfast state,

and watch must be kept for the usual complications of pneumonia, skin
ulcers, fractures of long bones or skull, urinary tract infections, and the like.
In conclusion, Huntington’s disease can be seen as a condition that may

be rightfully judged a paradigm for hereditary medical disorders in general
and for psychiatric disorders in particular, complicated by neurological
symptoms.
B. Neuropathology
Leon Roizin and Mavis A. Kaufman
Dunlap supplemented the literature review (See references 1, 2, 8, 9, 33,
38, 39, 40, 43, 45, 47, 48, 51, 82, and 90) with a personal detailed
neuropathologic study based on seventeen positive2 cases of Huntington’s
chorea, twelve questionable cases, and thirty or more control cases. Many
selective destructive lesions in the human striatum had failed to give clear
evidence of any definite function of this region. Wilson’s experimental work
on anthropoid animals “in which the striatum was first electrically stimulated
and then in large part destroyed on one side,” showed little, if any, difference
from normal controls. Therefore Dunlap attempted (in the above mentioned
study) to determine whether gross or microscopic changes could be found in
the central nervous system “in all cases of Huntington’s chorea which would
distinguish this disease process from all others.”
Grossly, the brains in the “positive” cases of Huntington’s chorea were

small and of diminished weight. The reduction was chiefly, if not entirely, in
the forebrain, with marked general atrophy affecting the convolutions, the
deep white matter, and particularly the corpus striatum, which was less than
half the normal size. The cerebellum was regarded as essentially normal in all
cases except one, and its average weight equaled that of the controls, but
further study would have been desirable. No conclusions were reached
regarding the other nuclear constituents of the extrapyramidal system.
Microscopically, the corpus striatum showed a remarkable loss of nerve
cells in the putamen, especially in the posterior three fourths; less loss in the
anterior fourth and in the head of the caudate nucleus; and probably no loss
of nerve cells in the globus pallidus. In the majority of cases, an extensive
neuroglial proliferation, most marked where the neurons were fewest, was
noted. In the red nucleus no constant or definite neuronal or neuroglial
changes were identified. The corpus subthalamicum and the substantia nigra
were too little studied to justify a definite opinion.
The nerve cells of the cerebral cortex were nearly always “dark staining,
small, and shrunken in appearance.” The cytoarchitecture was not obviously

disorganized, and as a whole, the neurons were “probably” not reduced in
number as compared with the control cases. The neuroglial nuclei of the
cortex looked smaller, darker, and more abundant than in the control cases.
The neuroglial fibers were usually most abundant in the zone of junction of
gray and white matter or in the deepest layers of the gray matter, where
many of the glial nuclei were large, pale, and vesicular.
The white matter of the cerebral hemispheres, in general, was thought
to be considerably more reduced in amount than the gray matter. No
abnormality in the gray or white matter of the cerebellum or in the dentate

nucleus was observed, with the exception of one case (see further comments
on pp. 421-422; electron-microscopic observations on pp. 425-432, and H.C.
in children on p. 422).
In conclusion, Dunlap felt that there were constant lesions of a definite
type in the corpus striatum and in the gray and white matter of the cerebrum.
Several authors (See references 34, 49, 57, 59, and 60) have found changes
similar to those described by Dunlap. Some authors, in addition, have
described areas of tissue necrosis which doubtless had a vascular origin but
such lesions sometimes appeared distant from the involved blood vessels,
being then possibly a sequence to angiospasm. Such findings, however, were

not specific or of constant character and were found not to be related to the
duration of the disease.
Subsequent studies by Davidson et al. essentially confirmed Dunlap’s
findings, with the exception that these investigators observed more marked
changes in the third cortical layer of the cerebral cortex and changes in the
cerebellum in two of the three cases studied. In contrast to Dunlap’s cases,
but in conformity with Jakob’s, they found that the rostral portions of the
striatum were more involved than the caudal.
In view of the fact that these minor discrepancies could also be
attributed to some individual variability of the disease process and possibly
some difference in investigative techniques, we (Roizin and Kaufman)

reviewed some of Dunlap’s original material and added ten selected
unquestionable cases of chronic, progressive Huntington’s chorea. We shall
mention only some of the most outstanding neuropathological findings in our

series.
Microscopic examination of the CNS revealed, in general, various
degrees of atrophic changes of the cerebrum (Figure 17-1) and loss of weight.
The leptomeninges, particularly over the atrophic gyri, often appeared
thickened. Coronal or horizontal sections of the brain revealed various
degrees of narrowing of the cerebral convolutions, deepening and widening
of the sulci, thinning of the gray and white matter of the cerebrum and corpus
callosum, variable atrophic changes of the caudate nucleus and putamen, and
variable degrees of internal hydrocephalus frequently, but not exclusively, of
the anterior horns of the lateral ventricles (Figure 17-2). In some cases the
brain stem also appeared somewhat smaller than in comparable controls.
Figure 17-1
Huntington’s chorea. Gross appearance of the brain, revealing pronounced

atrophic changes.
Figure 17-2.
(a) Coronal section through a control brain; (b) Huntington’s chorea as

described in the text.
Figure 17-3.
Figure 17-3.
(a) Section from the frontal lobe of a control case; (b) section from the same
region (approx.) of a case of Huntington’s chorea, revealing prominent
reduction in number of the nerve cells in various cyto-architectural areas.
Nissl stain. Low-power magnification.
Microscopic examination disclosed a degenerative, generally chronic,
process of variable intensity and distribution. In some instances the middle
layers appeared more prominently involved (Figure 17-3 (b)), in others the
deeper layers; in still others, the involvement appeared more diffuse in
character (Figure 17-4 (a)). Here and there, circumscribed neuronal

rarefraction or small acellular areas were also encountered (Figure 17-4 (b)).
Though frequently the smaller neurons appeared severely involved, in some

instances the large pyramidal cells showed chromatolysis as well as lipid
degeneration. Increased neuroglial density (marginal or subcortical) was
observed particularly in association with the more pronounced degrees of
atrophy. Neuronal degeneration and various degrees of numerical reduction
were observed in the putamen and the head of the caudate nucleus. Generally,
the most marked involvement was of the smaller nerve cells (Figure 17-5 (a)),
but the larger neurons Figure 17-5 (b)) in the putamen and caudate nucleus
as well as in the globus pallidus were not always spared. As a matter of fact,
Sudan III and Sudan black stains, particularly in long-standing chronic cases,
revealed the presence of increased intraneuronal lipid material. Similar
changes were also encountered, in various degree, in the hypothalamus, in
the different nuclear formations of the brain stem and medulla (particularly
the inferior olives), and in the Purkinje cells and dentate nucleus of the
cerebellum. In some cases the Ammon’s horn also appeared to be involved.
Increased satellitosis, pseudoneuronophagia, and neuronophagia were, at
times, prominent in the caudate nucleus and putamen. In the same structures,
increased gliosis (Figure 17-6), fibrillary as well as protoplasmic, was
frequent. In some instances hypertrophic astrocytes were quite prominent

and frequently independent of the blood-vessel walls. There was
periaqueductal gliosis in some cases, and in one case marked atrophy and
severe gliosis of the inferior olivary nuclei of the medulla were noted. Myelin-
sheath stains disclosed in four cases some sub-cortical pallor and myelin
rarefaction as well as poor differentiation of the tangential systems. Almost
complete status dysmyelinatus was present in two cases. Moderate
arteriosclerotic changes with some lipid deposits and perivascular fibrosis
were noticed in five cases. In one instance calcium deposits within the walls
and in a perivascular location were observed. Abundant deposits of calcium
and amorphous material giving an intense iron reaction, involving
particularly the basal ganglia, were found in one case. Now and then, amyloid
bodies in a periventricular location, in perivascular areas, or in the white

matter were also identified. Senile plaques were detected with silver
impregnation in one case.
Figure 17-4.
Figure 17-4.
Huntington’s chorea. Cortical regions showing (a) diffuse and (b) small, focal
areas with reduction in number of neurons. Nissl stain. Medium-power
magnification.
Clinicopathological studies on Huntington’s chorea occurring in the first

decade are considered to represent about 1 percent of the total number of
patients. The incidence of this disease in the general population is one in
24,000. In addition, typical choreatic movements are often absent in children.

Instead they may have hypokinesia, muscular rigidity, epilepsy, cerebellar
symptoms, and mental retardation. The cause of death is frequently

bronchopneumonia.
Figure 17-5.
Figure 17-5.
Huntington’s chorea. Putamen: (a) Various degrees of very pronounced

diminution of the neurons (particularly of the small nerve cells) and (b)
neuronophagia and increased density of glial nuclei. Nissl stain. Low-power
magnification.
Figure 17-6.
Huntington’s chorea. Putamen: Astrocytic gliosis as described in the text.

Cajal’s gold sublimate impregnation. High-power magnification.
Grossly the cerebrum and the cerebellum show various degrees of

generally diffuse3 atrophy (brain weight 940-980 g.). There is a striking
decrease in size of the caudate nucleus, less marked reduction of the putamen
and slight of the globus pallidus.
The most common microscopic findings consist of various degrees of
decrease in neurons throughout the cerebral cortex. Pronounced to complete
loss of neurons in the caudate nucleus is the most frequent feature. In the
putamen often only a few large neurons are present with frequent absence of
all small ones. The globus pallidus may show some loss of neurons or be well-
preserved. Decrease of neurons is also encountered in the subthalamic and
red nuclei. The substantia nigra contains less pigment than expected, usually
without loss of neurons.
In the cerebellum, the folia are atrophic and the molecular layer
reduced in width. The Purkinje cells are particularly depleted. Granular and
dentate nuclei neurons are also reduced in number.
In some instances considerable loss of neurons was observed in the

inferior olives of the medulla.
Sparse fat-laden cells in the perivascular regions, moderate decrease of
myelin in the globus pallidus, very pale or diminished strionigral fibers were
prominent in certain cases. Also dense gliosis of globus pallidus, putamen,

and Bergmann’s layer, as well as increased glial reaction in the molecular
layer and dentate nuclei of the cerebellum have been observed in several
cases.
It appears from earlier clinicopathological studies that, in the classical
type of Huntington’s chorea, the neuropathological process is of a

degenerative, chronic, and progressive character, involving principally the
neurons of the caudate nucleus and putamen, and to a somewhat lesser
degree the cerebral cortex. However, in some cases correlated systems also
are affected, though to a lesser degree and inconsistently.
From an etiopathogenetic point of view, some authors have interpreted
the lesions as a primary degeneration of the small cells of the putamen
caudate system and of the third and fifth cortical layers. The Vogts Jakob, and
others assumed that these two sets of structures comprised a “biologically

combined organ” subjected to an abiotrophic4 process As was demonstrated
above, however, the lesions in Huntington’s chorea are generally diffuse and
not specific in character. Other authors regarded the lesions as being due to a
“primary progressive gliosis” and the neuronal degeneration as being
secondary in character. On the other hand, some investigators believed that
vasular involution comes first, and that both parenchymatous and glial
changes are secondary. The diversity of opinion seems to indicate that, thus
far, specific and consistent data are not available for conclusive determination
of the pathogenetic mechanisms in Huntington’s chorea (See references 27,
28, 58, 65, 67, 75, and 92). It would appear that the choreic individual is
congenitally predisposed to develop, at a certain period of life, the

characteristic clinicopathologic syndrome which we have briefly reviewed.
Hence, heredity has assumed the role of the principal “etiopathogenetic”
factor.
Inborn errors of metabolism in degenerative processes (See references
25, 31, 76, 77, and 84) and mental disorders have been suggested as possible
factors, based upon the assumption that the morbid changes may be caused
by the lack of specific enzymes. Mental abnormalities as by-products of
inborn biochemical errors of different degree have been ascribed to
phenylketonuria, porphyria, methemoglobinemia, amaurotic idiocies,
gargoylism, and other cerebral lipoidoses, as well as to some involutional

degenerative processes such as Alzheimer’s and Pick’s presenile psychoses,
although the pathognomonic enzyme abnormality has not been specifically
identified as yet. A similar parallel inborn biochemical abnormality also could
be assumed for Huntington’s chorea. In support of this suggestion, one should

consider that, according to some investigators, hereditary dispositions due to
metabolic errors are mainly of two kinds. The first type is almost always
genetically homozygous and the affected subject lacks an enzyme because the
abnormal genes present in duplicate fail to produce it. These people show
signs of a constant abnormality throughout life, or at least from an early age.
A carrier with one normal and one abnormal gene is still able to make the
necessary enzyme. The second type is less regular in appearance and can
have a dominant inheritance. At times, the inborn error gives rise to
symptoms only under special circumstances or stress (see below).
During the last two years our combined electron-microscope and
histochemical-enzyme studies revealed the following salient findings: (1) The
fine structure of the nuclei of cerebral cortical neurons appeared, at times,
denser than usual and contained clumps of circumscribed masses of compact
osmiophilic granules and/or irregularly dispersed particulate material. The

nuclear membranes and their “pores” also show fine structural alterations.
Enzyme reaction products of acid phosphatases (AcP) and glucose-6-
phosphatase (G-6-P) were usually observed in higher concentrations in the

denser regions of the nucleus and at the periphery. (2) Some nucleoli also
showed changes and only the pars granulosa and chromosa were
differentiated. At times the nucleolus contained dense and light zones
composed of granular material.
The rough endoplasmic reticulum was scanty and irregularly

distributed. Frequently there were abnormal enlargements of the cisternae.
In some instances the cisternae showed varying degrees of degranulation.
Free ribosomal granules were irregularly dispersed and often reduced in

number (Figure 17-7). (4) The Golgi canaliculi formed irregular patterns and
frequently the canalicular outlines were blurred and their lumens not
discernible (Figure 17-8). The distribution of AcP, G-6-P, and TPP (thiamine
pyrophosphatase) reaction products differed and, at times, they had an

extracanalicular location. (5) The lysosomes displayed marked variations in
number and many were pleomorphic. They showed various stages of
metamorphosis particularly in the vicinity of or within areas containing lipid
products and lipofuscin bodies (Figure 17-9). AcP, G-6-P, and, to a lesser
degree, TPP reaction products were distributed in various concentrations and
configurations in lysosomes which were in various stages of auto- and

heterophagism. (6) Degenerative products showing variations in osmiophilia
were frequently observed in contact with or intertwined with multiforme
varieties of lipofuscin bodies (Figure 17-10). The latter were most often
observed in the cytoplasm of neurons, particularly in the perinuclear regions.
They were also encountered in the glial cells (Figure 17-11), in perivascular
regions, and in lesser numbers within the blood-vessel walls. AcP, TPP and G-
6-P reaction products were irregularly distributed in differing concentrations,
except within vacuolated structures where they were lacking (Figure 17-12).
(7) Glycogen granules were found particularly in glial cell processes in the
neurophil often in perivascular areas. They were occasionally seen in the
axoplasm of neurons or in the presynaptic terminals. (8) Mitochondria

(polymorphometabolosomes) showed variation in number, shape and size.
There were also concomitant variations in the configuration of the cristae and
osmiophilia of the matrix. Some mitochondria contained AcP reaction
products. (9) Multi vesicular bodies and heterogeneous bodies which varied
in number, configuration, and osmiophilia also contained AcP, TPP, and G-6-P
reaction products. Centrioles were sometimes seen in the vicinity of the Golgi
system. (10) Of the synaptic complex, the presynaptic terminals often showed
reduced numbers of vesicles, which, at times, were associated with variable
numbers of organelles some of which were undergoing degenerative changes.
Variations in the fine structure and osmiophilic character of the synaptic cleft
and subsynaptic web were observed. (11) In several instances the axoplasm
contained variable numbers of mitochondria and organelles which gave an
appearance resembling axonal dystrophy (Figure 17-13). In addition, AcP and
G-6-P reaction products were found in differing concentrations independent

of the presence of organelles (Figure 17-12). (12) Intra- and interlamellar
myelin degeneration was observed in some cases. Our control material is still
inadequate to make appropriate comparisons. However, these findings in

cerebral biopsies of Huntington’s chorea5 augment those reported previously
by Tellez-Nagel et al. in that additional histochemical studies were carried out
which have enabled us to demonstrate previously undescribed pathological

features.
Figure 17-7
Figure 17-7
Various degrees of fine structural changes of the rough endoplasmic

reticulum and RNA distribution in the cytoplasm of some neurons as
described in the text. Magnification: (a) X29,500; (b) X35,400; (c) X39,530.
Scale: 1 mm = 1000μ
Explanation of symbols: Gc = Golgi complex or the smooth component of the
endoplasmic reticulum; M = mitochondrian; MVB = multivesicular body; Nm
= nuclear membrane; N = nucleus; RER = rough component of the
endoplasmic reticulum; RNA = ribosomal granules.
Figure 17-8.
Various stages of fine structural changes and disorganization, especially of

the Golgi system as described in the text. Magnification: (a) and (b) X64,900;
(c) X45,815
Scale: 1mm. = 1000μ
Explanation of symbols: Gc = Golgi caniculi; L = lysosomes; M =
mitochondrian; MVB = multivesicular body; N = nucleus; Nm = nuclear
membrane.
Figure 17-9.
Figure 17-9.
Pronounced degeneration of the neuronal cytoplasm associated with lipid

products of degeneration and lipofuscin. Lipid products of degeneration
intertwined with lipofuscin pigment associated with increase in number of
lysosomes. Magnification: X28,560
Explanation of symbols: L = lysosomes; Lp = lipofuscin compounds; M =
mitochondrian; N = nucleus; Nm = nuclear membrane.
Figure 17-10.
Figure 17-10.
Multivacuolated lipofuscin structures intertwined with degenerative lipid

material. Magnification: X 25,960
Scale: 1mm. = 1000μ.
Explanation of symbols: L = lysosomes; Lp = lipid with lipofuscin vacuolated
structures; M = mitochondrion.
Figure 17—11.
Figure 17—11.
Composite lipid products undergoing digestive processes in cytolysomes as

described in the text. Magnification: X26,550.
Explanation of symbols: CLP = composite lipid products; CM = cellular
membrane; HB= heterogeneous body; L = lysosome; M = mitochondria; N =
nucleus; Nm = nuclear membrane.
Although our understanding of possible pathogenic mechanisms based
on electron-microscope studies is limited, since only the cerebral cortex was

examined, similar investigations will be carried out on basal ganglia tissue
when it becomes available. With these factors in mind we would like to
hypothesize as follows: (1) The ultrastructural alterations in the nucleus and
nucleolus, the changes in the endoplasmic reticulum including degranulation,
and the irregular distribution and decrease in the number of cytoplasmic

ribosomes may be related to disordered protein metabolism. Further studies
are needed to determine whether these findings can be correlated with the
protein abnormalities recently reported in Huntington’s chorea by Igbal et al.
(2) Some investigators (Novikoff et al. and Roizin et al.) have suggested that
the endoplasmic reticulum is in communication with the nuclear membranes,
lysosomes (and correlated structures), and multivesicular bodies and that it

serves as a unitary system concerned with intracellular transport
mechanisms. In light of these considerations, it appears possible that the fine
structural alterations and irregular distribution of the AcP., G-6P, and TPP
reaction products in the Golgi complex and related organelles might be due to
a disorder of intracellular transport mechanisms. With respect to the latter it
would be of interest to consider its possible significance in lipofuscin body
formation in the sense that the degenerative changes of the Golgi canaliculi
and its subunits may interfere with or deprive the lysosomes of a continuous
supply of the enzyme systems necessary for digestive mechanisms (DeDuve
and Wittaux). The subsequent accumulation of the lipofuscin bodies may not
only be the result of a failure of cell exocytosis (Brunk and Ericsson10), but it
may also be due to the fact that the accumulated “residues” were
incompletely digested or metabolized as a result of a lack of some lysosomal

enzymes. This might result in a molecule which is too large to pass readily
through the membranes. (3) The axonal involvement and some of the fine
structural alterations of the synapses and their respective subunits may
represent some functional and histochemical disorders of the neuronal
communication mechanisms.
Figure 17-12.
Combined electron-microscope and histochemical reaction for glucose-6-

phosphatase showing presence of various amounts of glucose-6-phosphatase
reaction products as described in the text. Magnification: X45,720.
Explanation of symbols: L = lysosme; Cp = composite lipofuscin, glucose-6-
phosphatase enzyme reaction products distributed over portions of dense
lipofuscin structures.
Figure 17-13.
Figure 17-13.
(a) Myelinated axon showing pleomorphism of neural tubules and increased

number of organelles. Magnification: X30,480. (b) Myelinated axon with
axoplasm containing a large number and variety of organelles undergoing
some degenerative changes. Magnification: X28,650. (c) Myelinated axon
revealing dense osmiophilic material as described in text. X40,650. (d)
Axoplasm field with acid phosphatase reaction products. X77,290.
Scale: 1mm. = 1000μ.
Explanation of symbols: AcP = acid phosphatase reaction product; Ax = axon;
DOM = dense osmiophilic material; L = lysosomes; M = mitochondrian; MVB =
multivesicular body; My = myelin; Tu = neural tubules.
Bibliography
Aitken, W. “Morbid Appearance in a Case of Chorea. The Connection of This Disease with
Imbecility and an Alteration in the Substance of the Brain,” Glasgow Med. J.,
1(1853), 92.
Alzheimer, A. “Uber die Anatomische Grundlage der Huntingtonschen Chorea und der
Choreatischen Bewegungen Uberhaupt,” Z. Ges. Neurol. Psychiatr., 3 (1911), 566.
Anton, G. “Uber die Beteiligung der Grossen Basalen Gehirnganglien bei Bewegungsstorungen
und Insbesondere bei Chorea,” Jahrb. Psychiatr., 14 (1896), 141.
Barbeau, A. “Parental Ascent in the Juvenile Form of Huntington’s Chorea,” Lancet, 2 (1970), 937.
Barbeau, A. and J.-R. Brunette, eds., Progress in N euro genetics, Proc. 2nd Int. Congr. Neuro-
Genetics and Neuro-Ophthalmology, World Fed. Neurol. Montreal, Sept., 1967, Vol.
1, Huntington’s Disease, pp. 509-694. Amsterdam: Excerpta Medica Foundation,
1969.
Barbeau, A., T. N. Chase, and G. W. Paul son, eds. Advances in Neurology, Vol. 1. Huntington’s
Chorea, 1872-1972. New York: Raven, 1973.
Bercsma, D., H. T. Lynch, and R. J. Thomas, eds. International Directory of Genetic Services, 4th ed.
New York: The National Foundation-March of Dimes, 1974.
Bonhoeffer, K. “Ein Beitrag zur Localisation der Choreatischen Bewegungen,” Monatsschr.

Broadbent, W. H. “Remarks on the Pathology of Chorea,” Br. Med. J. (1869), 345; also reported
before the London Med. Soc., 1865-66.
Brunk, U. and J. L. E. Ericsson. “Electron Microscopical Studies on Rat Brain Neurons. Localization
of Acid Phosphatase and Mode of Formation of Lipofuscin Bodies,” J. Ultrastruct.
Res., 38 (1972), 1.
Bruyn, G. W. “Clinical Variants and Differential Diagnosis,” in A. Barbeau, T. N. Chase, and G. W.

Paulson, eds., Advances in Neurology, Vol. 1, Huntington’s Chorea, 1872-1972, pp.
51-56. New York: Raven, 1973.
Buzzard, E. F. and J. G. Greenfield. Pathology of the Nervous System. London: Constable, 1921.
Byers, R. K. and J. A. Dodge. “Huntington’s Chorea in Children. Report of Four Cases,” Neurology,
17 (1967), 587.
Canfield, R. M. and J. J. Putnam. “A Case of Hemiplegic Chorea with Autopsy and Remarks,” Boston
Med. Surg. J., 11 (1884), 220.
Courville, C. B. Pathology of the Central Nervous System. Mountview, Calif.: Pacific Press Publ.
Assoc., 1945.
D’Antona, S. “Contributo alTAnatomia Patalogica della Corea di Huntington,” Riv. Patol. Nerv.
Ment., 19 (1914), 321.
Davidson, C., S. P. Goodhart, and H. Shlionsky. “Chronic Progressive Chorea, The Pathogenesis and
Mechanism; A Histopathologic Study,” Arch. Neurol. Psychiatry, 27 (1932), 906.
De Duve, C. “General Properties of Lysosomes, The Lysosome Concept,” in A.V.S. de Rouck and M.
P. Cameron, eds., Ciba Foundation Symposium on Lysosomes, pp. 1-31. Boston: Little,
Brown, 1963.
De Duve, C. and R. Wattiaux. “Functions of Lysosomes,” Ann. Rev. Physiol., 28 (1966), 435'
Dewhurst, K. “Personality Disorder in Huntington’s Disease,” Psychiatr. Clin., 3 (1970), 221-229.
Dewhurst, K. and J. Oliver. “Huntington’s Disease of Young People,” Eur. Neurol., 3 (1970), 278-
289.
Dewhurst, K., J. E. Oliver, and A. L. McKnight. “Sociopsychiatric Consequences of Huntington’s

Disease,” Br. J. Psychiatry, 116 (1970), 255.
Dewhurst, K., J. Oliver, K. L. K. Trick et al. “Neuro-psychiatric Aspects of Huntington’s Disease,”

Confin. Neurol., 31 (1969), 255-258.
Dunlap, C. B. “Pathologic Changes in Huntington’s Chorea,” Arch. Neurol. Psychiatry, 18 (1927),
867.
Elliot, K. A. C., I. H. Page, and J. H. Quastel. “Neurochemistry: The Chemical Dynamics of Brain and
Nerves,” Springfield, Ill.: Charles C. Thomas, 1955.
Falek, A. “An Ongoing Study in Early Detection as Part of a Comprehensive Program in

Huntington’s Chorea,” in A. Barbeau, T. N. Chase, and G. W. Paulson, eds., Advances
in Neurology, Vol. 1. Huntington’s Chorea, 1872-1972, pp. 325-327. New York:
Raven, 1973.
Feremutsch, K. “Vascular Disease of Striatum Producing Clinical Picture of Chronic Progressive

Chorea in Two Siblings,” Monatsschr. Psychiatr. Neurol., 127 (1954), 227.
Fromenty, M. L. “Progressive Chorea with Dementia Due to Murine Typhus,” Presse Med., 59
(1951), 91.
Frotscher, R. “Ein Beitrag zum Krankheitsbild der Chorea Chronica Progressiva,” Arch. Psychiatr.,
47 (1910), 790.
Garrod, A. E. Inborn Errors of Metabolism, 2nd ed. London: Hodder, 1923.
Gates, R. R. Human Genetics, Vol. 2. New York: Macmillan, 1946.
Gowers, W. R. Lectures in the Diagnosis of the Disease of the Brain. London: Churchill, 1885.
Hammond, W. A. A Treatise on the Diseases of the Nervous System, 6th ed., p. 722. New York:
Appleton, 1876.
Hassin, G. B. Histopathology of the Peripheral and Central Nervous System, p. 433. Chicago:
Hamilton, 1948.
Hemphill, M. “Tests for Presymptomatic Huntington’s Chorea,” N. Engl. J. Med., 287 (1972), 823-
824.
----. “Pretesting for Huntington’s Disease,” Hastings Center Rept., 3 (1973), 12-13.
Hoffmann, J. “Uber Chorea Chronica Progressiva (Huntingtonsche Chorea, Chorea hereditaria),”
Arch. Pathol. Anat., 111 (1888), 513.
Hughes, M. “Social Significance of Hunting ton’s Chorea,” Am. J. Psychiatry, 3 (1925), 537-
Hunt, J. R. “Progressive Atrophy of the Globus Pallidus,” Brain, 40 (1917), 58.
Huntington, G. “On Chorea,” Med. Surg. Reptr., 26 (1872), 317.
Husquinet, H., G. Franck, and C. Vranckx. “Detection of Future Cases of Huntington’s Chorea by the
L-Dopa Load Test: Experiment with Two Monozygotic Twins,” Adv. Neurol., 1
(1973), 301-310.
Igbal, K., I. Grundke-Igbal, M. L. Shelanski et al. “Abnormal Proteins in Huntington’s Disease,” J.

Neuropathol. Exp. Neurol., 33 (1974), 172.
Jackson, J. H. “Observations on the Psychology and Pathology of Hemichorea,” Edinburgh Med. J.,
14 (1868), 294.
Jakob, A. “Die Extrapyramidalen Erkrankungen im Lichte der Pathologischen Anatomie und

Histologie und die Pathophysiologie der Extrapyramidalen Bewegungsstorungen,”
Klin. Wochnschr., 3 (1924), 865.
Jelgersma, G. “Neue Anatomische Befundebei Paralysis Agitans und bei Chronische Chorea,”
Neurol. Zentralbl., 27 (1908), 995.
Jervis, G. A. “Huntington’s Chorea in Childhood,” Arch. Neurol., 9 (1963), 244.
Josephy, H. “Huntingtonsche Krankheit,” in O. Bumke, and O. Foerster, eds., Handbuch der

Neurologie, Vol. 16, p. 729. Berlin: Springer, 1936.
Kalkhof, J. and O. Ranke. “Eine Neue Chorea Huntington-Familie,” Z. Ges. Neurol. Psychiatr., 17
(1913), 256.
Kiesselbach, G. “Anatomischer Befund eines Falles von Huntingtonscher Chorea,” Monatsschr.
Klawans, H. L., G. W. Paulson, S. P. Ringel et al. “The Use of L-Dopa in the Presymptomatic
Detection of Huntington’s Chorea,” in A. Barbeau, T. N. Chase, and G. W. Paulson,
eds., Advances in Neurology, Vol. 1. Huntington’s Chorea, 1872-1972, pp. 295-310.
New York: Raven, 1973.
Kleist, K. “Anatomischer Befund bei Huntingtonschen Chorea,” Z. Ges. Neurol. Psychiatr., 6 (1913),
423.
Korenyi, C. and J. R. Whittier. “The Juvenile Form of Huntington’s Chorea: Its Prevalence and
Other Observations,” in A. Barbeau, T. N. Chase, and G. W. Paulson, eds., Advances
in Neurology, Vol. 1. Huntingtons Chorea, 1872-1972, pp. 75-77. New York: Raven,
1973.
----. “Dyskinesia Analysis,” Dis. Nerv. Syst., 35 (1974), 169-171
Korenyi, C., J. R. Whittier, and D. Conchado. “Stress in Huntington’s Disease (Chorea): Review of
the Literature and Personal Observations,” Dis. Nerv. Syst., 33 (1972). 339-344.
Korenyi, C., J. R. Whittier, and G. Fischbach. “Cineseismography: A Method for Measuring

Abnormal Involuntary Movements of the Human Body,” Dis. Nerv. Syst., 35 (1974).
63-65.
Korenyi, C. and R. Wittman. “Prevalence of Medical Disorders Other than Huntington’s Disease in
Offspring of Symptomatic and at Risk Parents,” Dis. Nerv. Syst., 35 (1974), 17-19.
Lewandowsky, M. and E. Stadelmann. “Chorea Apoplectica,” Z. Ges. Neurol. Psychiatr., 12 (1912),

530.
Lewy, F. H. “Historical Introduction: The Basal Ganglia and Their Diseases,” Assoc. Nerv. Ment. Dis.
Proc., 21 (1940), 1.
Lhermitte, J. and P. Pagniez. “Anatomie et physiologie pathologiques de la choree de Sydenham,”

Encephale, 25 (1930), 24.
Lichtenstein, B. W. A Textbook of Neuropathology, p. 80. Philadelphia: Saunders, 1949.
Marie, P. and J. Lhermitte. “Les Lesions de la choree chronique progressive (choree

d’Huntington). La degeneration atrophique cortico-striee,” Ann. Med., 1 (1914), 18.
Markham, C. H. and J. W. Knox. “Observations on Huntington’s Chorea in Childhood,” J. Pediatr., 67

(1965), 45.
Myrianthopoulos, N. C. “Review Article: Huntington’s Chorea,” J. Med. Genet., 3 (1966), 298-314.
----. “Huntington’s Chorea: The Genetic Problem Five Years Later,” in A. Barbeau, T. N. Chase, and
G. W. Paulson, eds., Advances in Neurology, Vol. 1. Huntingtons Chorea, 1872-1972,
pp. 149-159. New York: Raven, 1973.
Notkin, J. “Convulsive Manifestations in Huntington’s Chorea,” J. Nerv. Ment. Dis., 74 (1931), 149.
Novikoff, A. B. “Lysosomes in Nerve Cells,” in H. Hyden, ed., The Neuron, p. 319. Amsterdam:
Elsevier, 1967.
Noyes, A. P. Modern Clinical Psychiatry, Philadelphia: Saunders, 1939.
Oppenheim, H., and H. Hoppe. “Zur Pathologischen Anatomie der Chorea Chronica Progressiva
Hereditaria,” Arch. Psychiatr., 25 (1893), 617.
Palm, J. D. “Longitudinal Study of a Preclinical Test Program for Huntington’s Chorea,” Adv.
Neurol., 1 (1973),311-324.
Pearson, J. S. “Behavioral Aspects of Huntington’s Chorea,” Adv. Neurol., 1 (1973), 701-715.
Penrose, L. S. “Inborn Errors of Metabolism in Relation to Mental Pathology,” in K. A.
Elliott, I. H. Page, and J. H. Quastel, eds., Neurochemistry, p. 807. Springfield, : Charles C. Thomas,
1955.
Petit, H. and G. Milbled. “Anomalies of Conjugate Ocular Movements in Huntington’s Chorea:
Application to Early Detection,” in A. Barbeau, T. N. Chase, and G. W. Paulson, eds.,
Advances in Neurology, Vol. 1. Huntingtons Chorea, 1872-1972, pp. 287-294. New
York: Raven, 1973.
Roizin, L., K. Nishikawa, J. Koizumi et al. “The Fine Structure of the MVB and Their Relationship to
the Ultracellular Constituents of the CNS,” J. Neuropathol. Exp. Neurol., 26 (1967),
223.
Roizin, L., S. Stellar, N. Willson et al. “Electron Microscope and Enzyme Studies in Cerebral
Biopsies of Huntington’s Chorea,” Trans. Am. Neurol. Assoc., 99 (1974), in press.
Rosenbaum, D. “Psychosis with Huntington’s Chorea,” Psychiatr. Q., 15 (1941), 93.
Sjogren, T. “Vererbungsmedizinische Untersuchungen fiber Huntington’s Chorea in einer

Schwedischen Bauem Population,” Z. Menschl. Vererb. Konstitutionslehre, 19 (1935),
131.
Stern, C. Human Genetics. San Francisco: Freeman, 1949.
Stevens, D. L. “The Classification of Variants of Huntington’s Chorea,” in A. Barbeau, T. N. Chase,

and G. W. Paulson, eds., Advances in Neurology, Vol. 1. Huntington’s Chorea, 1872-
1972, pp. 57-64. New York: Raven, 1973.
Tamer, A., J. Whittier, and C. Korenyi. “Huntington’s Chorea: A Sex Difference in

Psychopathological Symptoms,” Dis. Nerv. Syst., 30 (1969), 103.
Tellez-Nagel, J., A. B. Johnson, and R. D. Terry. “Studies of Brain Biopsies of Patients with
Huntington’s Chorea,” J. Neuropathol. Exp. Neurol., 33 (1974), 172.
Toth, S. E. “The Origin of Lipofuscin Age Pigments,” Exp. Gerontol., 3 (1968), 19.
Vogt, C. “Quelques Considerations generals a propos du syndrome du corps strie,” J. Psychol.

Neurol., Ergh., 4 (1911-12), 479.
Vogt, C., and O. Vogt. “Zur Lehre der Erkrankungen des Striaren Systems,” J. Psychol. Neurol., 25,
Ergh., 3 (1920), 631.
----. “Precipitating and Modifying Agents in Chorea,” J. Nerv. Ment. Dis., 116 (1952), 601.
Wagner, R. and H. K. Mitchell. Genetics and Metabolism. New York: Wiley, 1955.
Werner, A. and J. J. Folk. “Manifestations of Neurotic Conflict in Huntington’s Chorea,” J. Nerv.

Ment. Dis., 147 (1968), 141.
Whittier, J. R. “Management of Hunting ton’s Chorea: The Disease, Those Affected, and Those
Otherwise Involved,” in A. Barbeau, T. N. Chase, and G. W. Paulson, eds., Advances
in Neurology, Vol. 1. Huntingtons Chorea, 1872-1972, pp. 743-753. New York:
Raven, 1973.
Whittier, J. R., G. Haydu, and J. Crawford. “Effect of Imipramine (Tofranil) on Depression and
Hyperkinesia in Huntington’s Disease,” Am. J. Psychiatry, 118 (1961), 79.
Whittier, J. R., A. Heimler, and C. Korenyi. “The Psychiatrist and Huntington’s Disease (Chorea),”
Am. J. Psychiatry, 128 (1972), 1546-1550.
Wilson, S. A. K. “Progressive Lenticular Degeneration: A Familial Nervous Disease Associated with

Cirrhosis of the Liver,” Brain, 34 (1912), 295.
----. Modern Problems in Neurology, Chaps. 7-11. New York: Wood, 1929.
----. Neurology, Vol. 2. Baltimore: Williams & Wilkins, 1940.
Notes
1 The author wishes to acknowledge the assistance of Pearl Band and Roslyn Laiterman in preparation
of the clinical aspects of this chapter.
2 Every member of this group had, in addition to the characteristic motor disorders and mental
symptoms of Huntington’s chorea, a family history of uninterrupted heredity from
parent to child, and was considered free from all objections.
3 In some instances particularly fronto-parietal.
4 This is a term coined by Gowers to indicate an inherent constitutional weakness or a “defective vital
endurance” and “premature decay” of the affected parts of the nervous system.
5 This biopsy material is part of a multidisciplinary research investigation on Huntington’s chorea

carried out in cooperation with S. Stellar, N. Willson, and J. Whittier, supported in part by
the St. Barnabas Medical Center Research Foundation for the Neural Sciences.
Chapter 18
MENTAL RETARDATION
I. Nature and Manifestations
Sterling D. Garrard and Julius B. Richmond
Mental retardation is an arbitrary concept. It is often discussed in a
medical and psychiatric context as if it were a homogeneous clinical entity, a
disorder, or even a disease. This clinical viewpoint is reinforced somewhat
circularly for physicians by the inclusion of the rubric in the classification of
diseases in medicine and psychiatry. From a rigorous clinical standpoint,

however, mental retardation is an imprecise, lumping term rather than a
single, homogeneous entity. Unfortunately, a discussion of the “nature and
manifestations” of mental retardation may further reinforce the notion that it

is a naturalistic phenomenon.
The individuals who are assigned to the category of “mentally retarded”
through clinical processes vary widely with respect to their genotypic,
etiologic, anatomic, neurophysiologic, psychometric, cognitive, prognostic,
and most other characteristics. For many, if not most, traits the scale of the
phenotypic variation within the retarded population approximates that in the
population at large. Since most traits vary continuously rather than
discontinuously between the two populations, the retarded and nonretarded

groups tend to merge without a sharp line of demarcation. Their separation
ultimately depends upon the application of arbitrary criteria. While the
differences between the populations are primarily those of degree rather
than of kind, there is a group of persons with mentally retarded behavior

which represents a separate population. This group is set apart chiefly by its
association with genetic mutations, cytogenetic abnormalities, and
biomedical disorders of the central nervous system.
The heterogeneity within the category of mental retardation sharply

limits the utility of the term for medical-psychiatric, educational,
psychological, administrative, and scientific purposes. Because of the large
numbers of variables which influence behavior within the total population of

retarded individuals, different samples of the population tend to in-elude
differing mixtures of subgroups. Even when carefully matched on a selected

set of variables, homogeneous comparison groups are difficult to obtain. Over
the years, this problem undoubtedly has confounded the interpretation and
replication of innumerable studies in the field of mental retardation. The
heterogeneity of the population highlights the fact that mental retardation is
not a medical, psychological, educational, or sociological entity. For this
reason, in part, mental retardation cannot be fully understood from the
perspective of any one discipline.
Mental retardation does not stand alone as a field for scientific
investigation. Its scientific roots lie within the subdivisions of developmental

psychology, e.g., intelligence and cognition, attention and habituation,
learning theory and behavior principles, language, and psycholinguistics. The
understanding of mental retardation is advanced only as far as investigations
in the component fields of developmental psychology. Although particular

developmental issues may be studied to advantage within the retarded
population, developmental psychology is the mirror within which mental
retardation must be viewed for scientific purposes.
Definition and Classification
An awareness of two constructs is necessary for an understanding of
mental retardation. The first construct pertains to intelligence. It is assumed
heuristically here that quantities of “intelligence” are normally distributed in
the population. Within this framework, psychometric tests have been

constructed to yield a normal distribution of test abilities with respect to a
reference population. These tests provide an objective basis for measuring
and defining low intelligence. Mental retardation is a second construct which
is dependent upon the preceding one but is not identical with it. This
construct is derived, in part, from the nontest behaviors of individuals at the
low end of the distribution of measured intelligence. Within this framework,
mental retardation may be attributed to persons with low measured

intelligence whose adaptive behavior is also judged to be impaired or
unintelligent. Accordingly, low measured intelligence is not always synonymous
with mental retardation. From the perspective of learning theory, mental
retardation reflects both insufficient and inappropriate learning. In the final

analysis, however, “mental retardation” is a clinical term which refers to a
reduced velocity and deviant direction of behavioral development.
The formal definitions of mental retardation, which are pertinent to
clinical practice in the United States, are discussed in two reference books.
These definitions reflect a consensus of prevailing professional views and are
subject to periodic revisions as concepts change. The Manual on Terminology
and Classification in Mental Retardation, 1973 Revision, of the American

Association on Mental Deficiency (AAMD) defines mental retardation as
follows: “Mental retardation refers to significantly subaverage general

intellectual functioning existing concurrently with deficits in adaptive
behavior, and manifested during the developmental period.” The interrelated

Diagnostic and Statistical Manual of Mental Disorders (DSM-II, 1968) of the
American Psychiatric Association (APA), which adapts the International
Classification of Diseases (ICD-8, 1968) of the World Health Organization to
American usage, defines mental retardation in somewhat similar terms as
follows: “Mental retardation refers to subnormal general intellectual
functioning which originates during the developmental period and is

associated with impairment of either learning and social adjustment, or
maturation, or both.”
These definitions assign two essential properties to mental retardation,
namely, low intellectual functioning and deficient adaptive behavior. In
keeping with these definitions, dual criteria are required for an inference of
mental retardation at an operational level, namely, measured intelligence at
or below a selected level and demonstrated deficiencies in adaptive behavior.
Strictly speaking, only the combination of a low IQ score plus deficient

adaptive behavior equals mental retardation. Any other combination of
impairment and nonimpairment in these two areas does not equal mental
retardation. “Learning disabilities,” many poverty-associated learning

“failures,” and other forms of intellectual growth deflections are automatically
excluded from the clinical category of mental retardation by these criteria,
even though causal and functional continuities may exist between them.
Table 18-1. Levels of Severity of Mental Retardation by Measured Intelligence

(AAMD)
REPRESENTATIVE IQ SCORES
DESCRIPTIVE STANDARD STANFORD-BINET AND WECHSLER
LEVELS DEVIATION RANGES CATTELL (S.D. 16) SCALES (S.D. 15)
Mild —2.01 to —3.00 68-52 69-55
Moderate —3.01 to —4.00 51-36 54-40
Severe —4.01 to —5.00 35-20 39-25*
Profound Below 19 and below 24 and below*
* Extrapolated.
The necessity for dual criteria for a “diagnosis” of mental retardation
reflects a distrust of either criterion alone as a basis for identification. An

exclusive reliance on intelligence test scores would result in the labeling of
many individuals whose behavioral adequacy could be demonstrated in a
variety of circumstances. In addition, minority-group members would be
inappropriately included within the clinical category of mental retardation in

appreciable numbers. In a sense, the adaptive behavioral criterion is intended
to provide a double check on the psychometric criterion in the clinical labeling
process. Unfortunately, the relative lack of precision of adaptive behavioral

scales in separating retarded from nonretarded behaviors at borderline levels
leaves considerable room for subjective judgments in this area. These
judgments may ultimately be crucial in the labeling of large numbers of

children, especially in minority groups. Because of the subjective latitude
which enters into the application of the adaptive behavioral criterion, the
category of mental retardation cannot be clearly delineated throughout its
entire range. Except for measured intelligence, the available diagnostic tools
lack sufficient discriminatory power to be useful for identification in many

instances.
The APA manual distinguishes five levels of mental retardation, based
entirely upon measured intelligence in this system; adaptive behavior is not
considered. Levels are delineated by ranges of IQ scores (test unspecified) as
follows: (1) borderline, IQ 68-85; (2) mild, IQ 52-67; (3) moderate, IQ 36-51;
(4) severe, IQ 20-35; and (5) profound, IQ less than 20. The borderline level in
this classification has been widely criticized because it would result in the
potential inclusion of at least 16 percent of the total population within the

category of retardation.
The AAMD manual, on the other hand, classifies the severity of mental
retardation independently in the areas of measured intelligence (i.e., test

behaviors) and adaptive behavior (i.e., nontest behaviors). In each behavioral
domain four levels of severity are distinguished. The criterion for mental
retardation is fulfilled with respect to measured intelligence by scores which
are more than two standard deviations below the mean of a standardized test.
In the AAMD system, the controversial borderline category of the APA manual
is eliminated. The remaining four levels of severity with respect to
intelligence test scores are delineated by standard deviation intervals as

shown in Table 18-1.
The adaptive behavioral criterion is fulfilled in the AAMD system when
rating scales and observer judgments lead to the conclusion that adaptive
behavior is significantly below the population norms for the age group.
Adaptive behavior here refers to the behavioral phenomena which contribute
most strongly to the social perception of retardation. Areas of interest in this
context include self-help and personal independence, sensorimotor
development, communication, socialization, reasoning, and judgment in

meeting societal expectations, academic skills pertinent to community living,
self-direction and responsibility, occupational attributes, maladaptive
behaviors, and the like. Levels of adaptive behavioral deficiency are labeled
mild, moderate, severe, and profound. At its upper limit the mild level of
deficiency corresponds to a significant, negative deviation from population
norms (analogous to -2 standard deviations for intelligence test scores, but
lacking in this degree of precision). At its lower limit the profound level of
deficiency corresponds to an almost complete lack of adaptation. The AAMD
manual provides descriptive patterns of adaptive behavioral functioning by
age and level which may be helpful in estimating severity. It is intended,

however, that standardized scales, e.g., the Vineland Social Maturity Scale and
the AAMD Adaptive Behavior Scales, will be used in combination with clinical
judgment to classify levels of adaptive behavioral deficiency.
Biomedical “Causation”
In a strictly logical framework, medical diagnoses, diseases, and
pathological processes do not define mental retardation; only behavioral
criteria do this. Conversely, behaviors which are labeled mentally retarded do
not define or signify pathological processes or medical disorders; only
biomedical criteria do this.
There are no direct relationships between specific medical diagnoses
and specific learning or adaptive behavioral characteristics. Many interacting
variables, including innumerable environmental contingencies, are
interposed between biomedical phenomena and particular behaviors. From
this perspective, a medical diagnosis or disorder can never be viewed as the
sole or proximate “cause” of mental retardation. Lately, the behaviorists have
been particularly vocal in indicating that the explanatory power of medical
diagnoses for mentally retarded behavior is limited and that the techniques of
behavioral intervention are independent of the dictates of medical etiologies.
General associations are noted, however, between mental retardation
and various medical diseases, syndromes, disorders, findings, and events.
Presumably, these associations are mediated through pathological processes

which affect the response capacities for learning and predispose individuals
to behaviors which may be labeled abnormal. The correlation between a
medical diagnosis and mental retardation approaches unity in the case of

Down’s syndrome or mongolism. Here, the association is so strong that the
recognition of the medical syndrome at birth is considered tantamount to the
identification of mental retardation, even though the behavioral criteria may
not be fulfilled until some time in the future. A number of additional medical
disorders are correlated with retardation in this way at different levels of

probability. The AAMD manual includes a separate medical classification for
the coding of conditions which are presumed to be etiologically associated
with retardation. Similar coding requirements are contained in the APA
manual.
When viewed from a medical perspective, the mentally retarded
population is roughly separable into the following two groups: Group 1, a
small group with abnormal medical findings, and Group 2, a large group
without abnormal medical findings. The divisibility of the retarded

population into two groups on the basis of medical findings has been noted in
the literature for many years. In the past, various terms have been applied to
these groups as follows: extrinsic and intrinsic, secondary and primary,

exogenous and endogenous, organic and subcultural, pathological and
physiological, and the like. Although these terms imply a binary view of
causation which is no longer tenable, the separation into two groups is useful
for medical diagnostic purposes. The relationships between these two groups
and the major etiological categories which are postulated within the retarded
population are shown in Table 18-2.
Table 18-2. Relationships between two medically distinguishable groups within
the retarded population and postulated etiological categories
MEDICAL DIAGNOSES MULTIFACTORIAL-POLYGENIC
(20-25 percent of total retarded (75-80 percent of total retarded
population) population)
Single mutant genes

(metabolic diseases)
Malformation syndromes Complex causation Tail of “normal”

(including cytogenetic) distribution of
low socioeconomic intelligence.
status
learning
experiences
Sequelae of prior disease disadvantaged or

(prenatal, perinatal, postnatal) predisposing to
retardation
subclinical or
undiagnosed prior
disease
Miscellaneous
progressive neurological diseases
Group 1. Abnormal medical findings: Group 2. No abnormal medical findings.

includes more than 20-25% of the total
retarded population.
From a practical standpoint, the yield of medical diagnoses will be
limited to Group 1. Some individuals in this group will have specific medical
diagnoses which can be currently and directly verified; included in this
category will be the metabolic diseases, malformation syndromes, and certain

progressive neurological diseases, e.g., subacute sclerosing panencephalitis.
Other individuals in this group will have medical disorders which cannot be
currently or directly verified, because the findings represent sequelae of
conditions which were active for a limited time only during the prenatal,
perinatal, or postnatal periods. In these instances, the applicable diagnoses

must be inferred retrospectively; the validity of these inferences will depend
upon the degree of specificity of the residual findings and/or of the available
historical data. If neither the findings nor the history justify a specific
diagnostic inference, the abnormal findings must be considered to be
idiopathic or undiagnosable. Individuals with idiopathic findings contribute
to the size of Group 1 in indeterminate numbers. It is commonly estimated,
however, that persons with assignable medical etiologies account for 20-25
percent of the total retarded population. Table 18-2 shows the proportionate
representation (estimated) of medical findings and diagnoses within the

retarded population. Table 18-3 presents a simplified medical classification
which can serve as a framework for the medical diagnostic approach.

Representative medical disorders which are included in Table 18-3 for
illustrative purposes will not be discussed here.
Group 1 is delineated by five sets of medical findings which provide
access to the etiologic categories in Table 18-3. Since these findings are
always presumptive of a medical etiology or “cause” for mentally retarded
behavior, the medical examination should be directed toward their
identification. These findings are not mutually exclusive and may occur in any
combination in a single individual. The five sets of findings with a high
diagnostic payoff in relation to the etiologic categories in Table 3 are the
following: (1) a cluster of abnormal neurological signs; (2) neurological

deterioration or developmental regression; (3) a malformation cluster; (4)
positive laboratory tests for abnormal concentrations of metabolites in body
fluids; and (5) a documented neurological disease in the past. These findings
and their diagnostic implications will be discussed briefly below.
Positive neurological signs are, perhaps, the most frequent indications of

medical abnormality which are associated with Group 1. Significant here are
one or more localizing or major signs; two or more nonlocalizing, minor, or
“soft” dysfunctional signs; or a developmental or IQ which is three standard

deviations or more below the mean of a standardized test (roughly equivalent
to a score of 50 or below). Since the latter finding is regularly associated with
major pathology of the central nervous system (CNS), a low IQ per se at these
levels is usually interpreted as an abnormal neurological sign. Identifiable
medical diseases and syndromes are heavily concentrated among individuals
at these low IQ levels. If identified, positive neurological signs dictate
additional investigations for disorders in the categories of metabolic

abnormalities, malformation syndromes, and progressive neurological
diseases, as shown in Table 18-3.
Neurological deterioration or developmental regression points to
currently active diseases. Evidence for deterioration should be obtained from
documented, longitudinal observations whenever possible, but lacking this,
from the history as provided by family members or other significant
nonprofessionals. Rates of regression may be rapid or exceedingly slow and
difficult to recognize, either intermittent or continuous. If abnormal
neurological signs are identified in a person with mental retardation, active

disease of the CNS must be considered. Evidence for progressive neurological
deterioration points to the metabolic disorders and active neurological
diseases as shown in Table 18-3. Evidence for nonprogressive neurological
abnormalities (especially when accomplished by a continuous advance in

developmental level) points to the residual effects of prior disease. In these
instances, the etiology may or may not be assignable.
Table 18-3. Simplified Classification of Medical Disorders Which May Be

Etiologically Associated with Mentally Retarded Behavior
METABOLIC DISEASES SINGLE MALFORMATION NEUROLOGICAL MISCELLANEOUS
MUTANT GENES SYNDROMES AND SEQUELAE OF PROGRESSIVE
CLUSTERS, TIME-LIMITED NEUROLOGICAL
CYTOGENETIC AND DISORDERS: DISEASES
NONCYTOGENETIC PRE-, PERI-, OR
POSTNATAL
Phenylketonuria Malformation Prenatal Subacute sclerosing

Histidinemia cluster with a panencephalitis
Teratogenic
cytogenetic agents Lead intoxication
Homocystinuria
anomaly;
Maple syrup urine disease Maternal Hydrocephaly
pattern of
phenylketonuria
Argininosuccinic acidemia anomalies may Rubella virus
Glycosaminoglycans: or may not be Cytomegalovirus
mucopolysaccharidoses specific
Herpesvirus
Galactosemia Down’s syndrome hominis
Gangliosidoses: E₁-trisomy (47,18+) Perinatal
Tay Sachs, etc.
D₁-trisomy (47,13+) Low birth
weight
Cat-cry syndrome (46, prematurity;
5P-) small for
gestational age
Malformation
cluster without Malnutrition
demonstrable
Asphyxia;
cytogenetic acidosis
abnormality;
Hypoglucosemia
recognizable
pattern of Rh
anomalies isoimmunization
and kemicterus
Acrocephalosyndactyly
(Apert’s syndrome) Postnatal
Oral-facial-digital Child abuse

syndrome
Intracranial
Rubenstein-Taybi trauma
syndrome
Meningitis
Cornelia de Lange
syndrome Encephalitis
Malformation
cluster; no
demonstrable
cytogenetic
abnormality; no
recognizable
pattern
Malformation clusters are important contributors to the abnormal
medical findings which characterize Group 1. Significant here is the
combination of two and, especially, three or more malformations, either of
major organs or of minor structures, including dermatoglyphics. In some
instances, the cluster of anomalies may be associated with a cytogenetic
abnormality. In other instances, the cluster of anomalies may conform to a
recognizable syndromic pattern in the absence of a demonstrable cytogenetic

abnormality. In still other instances, the cluster of anomalies may be
unclassifiable and unassociated with a cytogenetic abnormality. Malformation
clusters suggest disordered embryogenesis. If accompanied by mental
retardation and abnormal neurological signs, they generate an inference that

structural abnormalities of the CNS are also present. Regardless of the
specificity of the clinical pattern, malformation clusters provide an indication
for cytogenetic studies. Several useful catalogues are now available to aid the
physician in the clinical identification of malformation syndromes.
Positive laboratory tests for abnormal concentrations of metabolites in

body fluids, or for deficient enzyme activity, point directly to the genetic
disorders of metabolism. Pre-determined protocols of qualitative or semi
quantitative screening tests for metabolic diseases, especially for the amino
acid disorders, are often applied in the medical evaluation of individuals with
mental retardation. Positive results from these tests must always be
confirmed by specific procedures. Assays for enzyme activity are undertaken
selectively in situations in which a specific disease, e.g., a ganglioside storage
disease, is suspect on the basis of the family history or clinical findings.
A documented disease or insult to the central nervous system in the past
may be crucial for the subsequent assignment of etiology in instances of

nonprogressive neurological abnormalities. Presumably, abnormalities of this
type represent the sequelae of prior time-limited diseases. Precise diagnoses
of these diseases must be established during their active phase. Retrospective
diagnoses, which are based entirely upon the recall of events, or nonspecific,
residual findings, are at best speculative. Prenatal or fetal diseases are
presumed to be major contributors to the residual category in Table 18-3.
Since intrauterine disorders are exceptionally difficult to identify, either

concurrently or retrospectively, the etiology of many nonprogressive
neurological abnormalities cannot be assigned. The findings are labeled
idiopathic under these circumstances.
These five sets of findings are not the only presumptive indications for a
medical etiology or “cause” in individuals with mental retardation. Many
other pathological findings (e.g., cutaneous lesions of neuroectodermal

disorders, chorioretinitis, microcephaly, intracranial calcifications, and the
like) may be identified during the course of medical examinations and

contribute to diagnostic or etiologic inferences. In addition to the neurological
abnormalities which may be elicited by the medical examinations of
physicians, psycholgists regularly find evidence for impaired cortical and
neurointegrative functions during psychological and psychoeducational
testing. In the future, neurophysiological techniques may also be applied

clinically and permit the recognition of subtle biological abnormalities which
now cannot be identified, e.g., in the areas of evoked potentials, attention and
habituation, expectancy patterns, sleep patterns, and the like. Developments
of this type may expand the numbers of individuals with retardation in whom
biological abnormalities can be demonstrated.
Group 2 of the retarded population is distinguished by an apparent
absence of the abnormal medical findings which characterize Group 1. Group
2 includes the majority, perhaps 75-80 percent, of the total retarded

population. The severity of the retardation here is limited to the mild level,
whereas all levels are included in Group 1. Several etiologic subgroups
undoubtedly exist within Group 2 which are not separable through medical
technology. The causes of mentally retarded behavior here are believed to be
multifactorial and to involve complex interactions between polygenic

inheritance factors, experiential factors, and subclinical medical factors.
Polygenic “Causation”
Geneticists estimate that 70 percent of all mental retardation can be
encompassed etiologically within the framework of polygenic inheritance of a
graded characteristic. In this context, each of the segregating polygenes is
assumed to have a small effect on trait variation by comparison with the total
variation observed for the trait. Gene effects of this type presumably account
for “physiological” trait variations which conform to a normal or continuous
distribution. By contrast, major or single mutant gene effects may account for
discontinuous or “pathological” traits.
Tests for the measurement of intelligence have been constructed and
standardized to yield a normal distribution of test abilities or scores with
respect to a reference population. These tests, in turn, generate the
assumption that a trait “intelligence” exists which is normally distributed and
polygenically determined. If normally distributed, 99.73 percent of

intelligence test scores will predictably lie within three standard deviations
above or below the mean of a standardized test. On the Stanford-Binet with a
standard deviation of 16, scores from 52-148 would be included within this
range; on the Wechsler Scales with a standard deviation of 15, scores from
55-145 would be included. These ranges presumably reflect the

“physiological” spread of intelligence due to polygenic inheritance.
A normal frequency distribution also predicts that 2.14 percent of
intelligence test scores will lie between two and three standard deviations
below the mean. Many individuals with scores in this range are labeled mildly
retarded. Those who are distinguished by an absence of abnormal medical
findings may reflect the low end of the continuum of intelligence due to the
segregation of polygenes. The observed frequency of IQ scores in this range,
however, exceeds the predicted frequency due, presumably, to medical

pathology and other influences which will be examined subsequently.
The concept of polygenic inheritance in relation to measured

intelligence has been supported by numerous studies which involve
correlational pairings. These studies have indicated that intragroup
resemblance in intellectual abilities increases in proportion to the degree of
genetic relationship, i.e., the greater the gene overlap the greater the
similarity in intelligence, whether or not the paired individuals have shared
the same environment. Empiric risk figures for mild mental retardation, as
derived from family studies, have also been consistent with a polygenic
hypothesis. Finally, the distribution of IQ scores along a social class gradient
has been regarded as consistent with the distributional expectations due to

polygenic inheritance given conditions of social mobility and assortative
mating.
Multiple studies in white populations in more or less uniform

environments have estimated that heritability accounts for 60-80 percent of
the total variance in intelligence test scores. On the assumption that the
variance attributable to heritability is equally high in all groups, it has been
reasoned that differences in mean IQ scores between black and white
populations or social classes are genetically determined, i.e., are due to
differences in the distribution of genotypes for high and low.
Environmentalists, on the other hand, have argued that statistical estimates of

heritability apply only to a particular population in a relatively constant
environment. Measures in another population with a different distribution of
environmental characteristics do not necessarily show the same proportion
of genetic and environmental variances. From this standpoint, it is

hypothesized that heritability will account for more of the variance in optimal
environments and less of the variance in suboptimal environments.
Accordingly, differences in mean IQ scores between racial and social groups

are attributed to environmental disadvantage. It is concluded in this
framework that a phenotypic distribution of IQ scores neither reflects the
distribution of genotypes for intelligence nor is immutable.
Obviously, psychometric instruments influence the phenomena which

are measured and the conclusions which are reached concerning polygenic
and sociocultural “etiologies.” If cognitive capacity is not fully matched by

cognitive competence or performance in response to the demands and
conditions of a test, an artifact of measurement will occur. In recent years,

interest in the concept of general intelligence has yielded somewhat to the
study of differentiated intelligence, i.e., of the various subabilities which are
hypothesized to affect mental functioning. If not necessarily clarifying the
genotypic issues, such studies provide a refined view of the differences in
performance between subgroups of the population (or individuals) under
specific demand situations. While some abilities may be more resistant to

training and experience than others, psychometric items are always culture-
bound.
Sociocultural “Causation”
As has been noted, the majority of individuals in the retarded category

are classified as mildly retarded. Usually, no single etiological or causal
influence can be identified in this group. Presumably, mental retardation at
this level represents a final symptomatic pattern of IQ and adaptive

behavioral effects due to multiple interacting variables. Because correlations
with social class and ethnic minority status are high in this group, the terms
“cultural-familial” and “sociocultural” are frequently applied to it.
Epidemiological and prevalence studies provide a useful perspective
from which to view the social implications of mild mental retardation. It
should be noted first that all studies of prevalence have shown that severe
mental retardation (i.e., moderate, severe, and profound levels) is distributed
across social classes without a significant gradient. Prevalence has been
remarkably constant in all studies at approximately three to four per 1000
children between five and eighteen years of age. Virtually all individuals with
severe retardation have significant signs of medical pathology. For this
reason, biomedical causalities are thought to account for the excess frequency
of low IQ scores (below 52-55) beyond the predictions of a normal frequency

distribution.
The prevalence of mild mental retardation, on the other hand, has

varied between studies according to the criteria, instruments, population
characteristics, and sampling techniques employed, and the locale or country
studied. Roughly, prevalence ratios by severity are as follows: mild twenty,
moderate four, severe one. Aside from actual prevalence rates, however,
three important epidemiological characteristics of mild mental retardation
emerge from these studies.
The most striking epidemiological feature of mild mental retardation is
its disproportionate social distribution, i.e., its social gradient. The
discrepancy between the top and the bottom of the social scale is marked
enough to suggest that this form of mental retardation is virtually specific to
the lowest social classes. A dramatic increase in prevalence occurs
particularly at IQ levels equal to or greater than sixty between social classes 3

to 5 (as determined by the occupation of the head of the household). As a
generalization, it may be concluded that the prevalence of mild mental

retardation increases by a factor of two for each step downward in social
class.
The second outstanding epidemiologic characteristic of mild mental

retardation is its disproportionate age distribution. This distribution has been
designated as the “schologenic hump.” Mild mental retardation has a low
prevalence in the preschool years, increases rapidly in frequency during the
early school years, peaks dramatically during puberty and adolescence, and
declines sharply again thereafter, in part, as a reflection of the role of the
schools in identification. In some studies, the prevalence of mild mental
retardation reaches twenty to forty per 1000 population in the age group 10-
14 years. It is assumed that movement of many individuals into and out of the
category of mild mental retardation accounts for these age specific prevalence
rates. The importance of the behavioral demands of particular social settings

and of the labeling process on the prevalence of mild mental retardation is
highlighted by these studies. Since the label of mental retardation is difficult
to remove, professionals should be exceedingly wary of stigmatizing anyone

at the mild level who might move out of the category.
The third outstanding epidemiological characteristic of mild mental
retardation is the frequent absence of abnormal medical findings. This feature

was documented most clearly by Birch et al. in a superb epidemiological
study of mental retardation in eight- to ten-year old children in Aberdeen,

Scotland. In this homogeneous white population, one third of the children
with IQ scores above 50 (up to 75) had abnormal neurological findings as
defined by one localizing or two nonlocalizing signs. However, only one
fourth of children with IQ scores equal to or greater than 60 (up to 75) had
abnormal neurological findings as defined. The numbers of children with

neurological abnormalities in the latter group were ten times greater than in
a sample of normal children. In other studies, it has been estimated that 20-
50 percent of mildly retarded children will present abnormal medical
findings.
Medical findings and social class often interact to influence the
prevalence of mild mental retardation. This relationship is demonstrated
dramatically with respect to low birth weight and severe perinatal stress.
Low-birth-weight infants (above 3% lb.) in upper social-class families reveal

minimal IQ effects, while decreasing birth weight is associated with a marked
increase in the frequency of low IQ scores in other social classes. Severe
perinatal stress also appears to be compensable in good postnatal

environments. The interaction between reproductive and environmental
hazards produces a cumulative risk which has a profound effect on the IQ

levels of lower class children who are exposed to the severest forms of
perinatal stress.
Epidemiological evidence suggests that mild mental retardation is not

randomly distributed within low social classes. In a study of prevalence in an
American slum, for example, Heber demonstrated that mild retardation was
concentrated in families of mothers with low IQ scores. Although mothers
with an IQ less than 80 made up 40 percent of the total surveyed, they
accounted for four fifths of the children with IQ scores less than 80. The
offspring of these mothers experienced a marked decline in measured
intelligence between three to five years which was followed by a further
modest decline until the average measured IQ at twelve to fourteen years
approximated the maternal average of 68. The probability of children testing

between IQ 55-67 on the Wechsler Scales at twelve to fourteen years was
fourteen times greater if the IQ scores of their mothers were in this range
than if the mothers’ scores were at or above IQ 100. The mothers in this study
were comparable in economic level, living conditions, educational
background, and the like, and varied only on measured intelligence. This
study suggested that a threshold level of maternal IQ might be correlated with
most instances of mild mental retardation in low social classes.
Other studies have seemingly corroborated the existence of a
progressive form of intellectual retardation (and mild mental retardation)

which is associated with low social class for some children (See references 15,
27, 31, 32, and 55). Cross-sectional data have indicated that groups of
disadvantaged children compare unfavorably with children of high
socioeconomic status on intelligence test measures at least by four years of
age, and differences tend to increase with increasing age. Groups of
disadvantaged children also perform below the national average on all
measures of school achievement at all grade levels, and the absolute
discrepancies in age levels increase with time. Not all children in low
socioeconomic circumstances, however, reveal indications of progressive
intellectual or mental retardation.
It is commonly hypothesized that progressive retardation in low social
classes results from a deprivation of experiences which are necessary for the
development of cognitive competencies for academic learning. Untangling the

web of class and specific environmental differences which may contribute to
differences in intellectual functioning, however, is a complicated process.
Child-rearing practices which favor one cognitive style rather than another,
specific types of class-related interpersonal communications which result in
specific deficits in intellectual functioning, differences in linguistic styles and
form which make mainstream English syntax and vocabulary a second

language, differences in patterns of reinforcement contingencies, differences
in motivation, differences in pregnancy, nutrition, and health factors, and the
importance of social “models,” all and more have been postulated and
explored.
Race and social class contributions to the mildly retarded category also
interact. White group mean IQ scores and black group mean IQ scores may
differ by as much as one standard deviation or roughly 15 points. Among the
blacks, 18 percent may score below IQ 70, while only two percent of whites
score in this range. Mercer has shown, however, that low scores for black and
Mexican-American children in Riverside, California, were correlated more

with sociocultural status than ethnic or racial background. In each group,
mean IQ scores converged progressively toward standard norms as
sociocultural background characteristics were successively controlled for
similarity to the dominant society.
Mercer’s study demonstrated the importance of the labeling process in
the determination of the category of mild mental retardation. As a result of
her findings, she is currently developing differential ethnic norms for
adaptive behavior by subculture in order to obviate the labeling of school

children who meet social expectations and demands in their own cultural
group. In Mercer’s view, low IQ scores predict the need for appropriate
educational supports, while adequate adaptive behavior in relation to an

appropriate (nonschool) reference group should predict the capacity to fill an
adult role acceptably. From this perspective, the category of mild mental
retardation should be reserved for those children who are “comprehensively”
retarded in terms of IQ scores and adaptive behavioral criteria as applied

within a cultural context. Much of the confusion regarding the category of
mild retardation and the prognosis for those assigned to it results from the
unavailability of discriminating criteria for adaptive behavioral adequacy.
From a dynamic viewpoint, the test and nontest behaviors which define
mental retardation always reflect the interaction of multiple variables, not
only at mild levels but at all levels of severity. In this sense, the assignment of
the cause of mental retardation to a single variable or etiology represents an

oversimplification. At any given time, mentally retarded behavior may be
conceptualized as resulting from an interplay between the person’s response
potentialities (i.e., the polygenetic, physiological, and pathological limitations
imposed upon his reacting and coordinating systems), his learned responses
or competencies (i.e., his cumulative or antecedent learning history as
acquired through interactions with his personal, cultural, social, and physical
environments), and his current stimulus-response environment (i.e., the

specific circumstances in which his present specific behaviors are arising).
Mutability of IQ
Logically, an increase in IQ scores above the criterion level for mental
retardation should result in a “cure.” IQ changes with time occur at all levels
of retardation, either upwardly or downwardly and with or without

intentional intervention. As noted previously, the progressive downward
movement of group mean IQ scores of low socioeconomic status children
corresponds with an increasing frequency of mild mental retardation at
puberty and adolescence. In an institutional population, Fisher and Zeaman
found the growth of mental age (MA) to be roughly linear between the ages of
five and sixteen years at all levels of retardation. The IQ scores declined
precipitously during this period, however, due to the slow rate of MA

increase. Since the mildly retarded group continued to exhibit MA growth
through the late thirties, IQ scores in this group subsequently rose after age
sixteen years. Non-institutionalized children with culturally associated
retardation have also been reported to make IQ gains in early adulthood.
In general, the greatest potential for IQ change is associated with the
most unfavorable social and educational origins of a group. The frequency
and extent of IQ changes in retarded children from advantaged environments
remain moot questions, especially as consequences of training and education.

Intelligence test scores, however, place a primary emphasis upon the
products of cognition. During the past two decades, numerous investigations
have explored the process of learning among the retarded ( See references 5,
7, 24, 51, 54, and 57). These studies have contributed to a growing technology
of education which has permitted retarded individuals to learn complex tasks

previously thought to be impossible. Even without IQ change, remarkable
changes in performance can be achieved through strategies derived from

discrimination learning, information theory, learning theory, and the like.
Some aspects of an effective educational program for the retarded child
may involve the following: (1) the definition of specific objectives for learning
in accord with the present stage and learning characteristics of the child; (2)
the ordering of the sequential tasks necessary to achieve a learning objective;
(3) the ordering of the physical and spatial environment to direct attention to
the relevant stimulus dimensions of tasks; (4) the ordering of tasks in
magnitudes of difficulty which insure a high probability of successful
achievement; (5) the use of a range of reinforcing techniques which is
appropriate to the task and child; (6) the provision of an appropriate

response model which the child can also emulate and imitate; and (7) the
creation of a social relationship which enhances motivation and encourages
movement toward autonomy.
Mutability of Adaptive Behavior
Logically, an increase in adaptive behavior above the criterion level for
mental retardation should also result in a “cure” even without an IQ increase.
There are no generalized behaviors, however, which are specific to
retardation. At mild levels, adaptive behavioral retardation is often defined in

relation to the specific demands of a particular social setting, especially the
schools. Rightly or wrongly, the child’s responses in coping with the
particular environment serve as the basis for the definition of retardation

within that environment. Adaptive behavioral change under these
circumstances requires a clear delineation of the behaviors which are
contributing to the social definition and a specific strategy for intervention, an
endeavor which is often questionable from an ethnic and subcultural
perspective.
There are behavioral phenomena, however, which distinguish a child as

atypical in virtually all social settings. Basic social skills which are
appropriate to the chronological age of the child, for example, may be missing
from the behavioral repertoire. These missing skills may relate to toileting,
feeding, dressing, bathing, ambulation, play, and communication. The

complexity of the skills which are lacking may increase at successive ages.
These absent behaviors have the effect of depriving the retarded person of
independence and movement through the expected range of social settings

for age. There are also maladaptive behaviors which distinguish a person as
atypical. These behaviors may involve stereotyped or repetitive acts which
consist of body rocking, head rolling, hand flapping, bruxism, twirling, pill-
rolling, unusual limb posturing, object spinning, vocal sounds, and the like. A
closely related group of self-injurious behaviors may also be observed which
includes head-banging, face slapping, self-biting, trichotillomania, and eye
poking. Tantrums, aggressive and destructive acts, explosive outbursts,

hyperkinesis, lack of impulse control, unconcealed masturbation,
inappropriate channeling of erotic feelings, compulsions, unusual fears,
negativism, and withdrawal, all represent behaviors which are considered to
be undesirable in most settings, and hence, maladaptive. Manifestations of
these types are generally independent of social class and are closely
correlated with IQ levels and abnormal medical findings. A number of scales

are available for the assessment of adaptive behavior in these areas which
may serve as useful guides for the specification of training objectives (AAMD
Fairview, Cain-Levine, Balthazar, and Watson).
A vast experimental and clinical literature now supports the potency of
the techniques of behavior modification for changing behaviors of the

preceding types. Through these techniques, maladaptive behaviors can
become less frequent; likewise, adaptive behaviors which are available to the
child, but infrequent, can become more frequent. Developmentally

appropriate behaviors which are not in the behavioral repertoire may also be
generated through the chaining of separate steps in a complex behavior or
through shaping, i.e., the successive approximation of a terminal behavior.

Through these techniques, even severely and profoundly retarded children
can learn toileting, self-feeding, self-dressing, communication, and other
skills. At the present time, therefore, it is probably appropriate to conclude
that all retarded children can be helped to become less retarded in the area of
adaptive behavior.
The professional framework in which a child is viewed may determine
the interpretation or label which is applied to his adaptive behavior. Many of
the behaviors which have been described here may be interpreted in a
psychiatric context. In this light, several epidemiological studies have shown
that mental retardation is associated with a wide range of psychiatric

disorders. In general, the frequency of psychiatric diagnoses is inversely
correlated with IQ levels. Although psychoses, especially in mentally retarded
adults, are frequently noted, the psychiatric disorders of children with
retardation are heterogeneous and nonspecific. The traditional psychiatric

syndrome of infantile autism is highly correlated with mentally retarded
behavior.
Conclusion
Mental retardation can be viewed from at least three perspectives,

namely, medical, behavioral, and sociological. The medical orientation
(including the genetic) tends to assign the causes for the behaviors which are
labeled abnormal to deficiencies and pathological processes within the
individual. In this context, the focus is often directed toward the assignment
of etiology to biomedical diseases and events. Mental retardation may be
considered to be a unitary condition here and the individual with retardation
to be a patient who requires treatment to achieve health or normalcy. The

behavioral orientation tends to ignore medical and other etiologies and
relates the behaviors which are labeled maladaptive to learning experiences
and current-stimulus response events within particular environments; in this
context, many of the retarded behaviors are considered to be trainable,
manipulable, or extinguishable under specified environmental conditions.

The person with retardation is considered here to be one who needs
environmental modification to permit appropriate learning and behavior. The
sociological orientation focuses on differences in the distribution of

socioeconomic-cultural variables and upon the labeling process per se. In this
context, mental retardation is seen as an artifact of society, of social
influences and of social organization. Mental retardation here is regarded as
essentially non-clinical, and the burden of causation is placed outside the
individual.
The heterogeneity of the retarded group defies a single, all-inclusive
conceptualization. The medical or clinical perspective, however, limits the
view of retardation to instances which are categorized through professional

activities and clinical procedures. The sociological perspective broadens the
scope of interest to include equivalent sets of behavioral phenomena whether
or not they are clinically labeled. Although not mutually exclusive, these two
orientations generate different views of the nature and manifestations of

mental retardation and somewhat different strategies for intervention. Social
change rather than individual change represents the primary difference in
emphasis.
Bibliography
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 2nd ed.,
Washington: American Psychiatric Association, 1968.
Ampola, M. G. “Phenylketonuria and Other Disorders of Amino Acid Metabolism,” Pediatric Clin.
North Am., 20 (1973), 507-536.
Balthazar, E. E. Balthazar Scales of Adaptive Behavior. Champaign, Ill.: Research Press, 1971.
Baumeister, A. A. and R. Forehand. “Stereo-typed Acts,” in N. R. Ellis, ed., International Review of

Research in Mental Retardation, Vol. 6, pp. 55-96. New York: Academic, 1973.
Baumeister, A. A. and G. Kellas. “Process Variables in Paired-Associate Learning of Retardates,” in

N. R. Ellis, ed., International Review of Research in Mental Retardation, Vol. 5, pp.
221-270. New York: Academic, 1971.
Bergsma, D., ed. Birth Defects: Atlas and Compendium. Baltimore: Williams & Wilkins, 1973.
Berkson, G. “Behavior,” in J. Wortis, ed., Mental Retardation and Developmental Disabilities: An

Annual Review, Vol. 5, pp. 55-71. New York: Brunner/Mazel, 1973.
Birch, H. G. and J. D. Gussow. Disadvantaged Children: Health, Nutrition and School Failure. New
York: Grune & Stratton, 1970.
Birch, H. G., S. A. Richardson, D. Baird et al. Mental Subnormality in the Community: A Clinical and
Epidemiological Study. Baltimore: Williams & Wilkins, 1970.
Bortner, M. and H. G. Birch. “Cognitive Capacity and Cognitive Competence,” Am. J. Ment. Defic., 74
(1970), 735-744.
Burt, C. “Intelligence and Social Mobility,” Br. J. Statist. Psychol., 14 (1961), 3-24.
Cain, L. F., S. Levine, F. F. Elzey. Cain-Levine Social Competency Scale. Palo Alto: Consulting
Psychologist’s Press, 1963.
Cavanagh, J. B. The Brain in Unclassified Mental Retardation. Baltimore: Williams & Wilkins, 1972.
Crome, L. and J. Stern. The Pathology of Mental Retardation. London: Churchill, 1967.
Das, J. P. “Cultural Deprivation and Cognitive Competence,” in N. R. Ellis, ed., International Review
of Research in Mental Retardation, Vol. 6, pp. 1-53. New York: Academic, 1973.
Dingman, H. F. and G. Tarjan. “Mental Retardation and the Normal Distribution Curve,” Am. J.
Ment. Defic., 64 (1960), 991-994.
Doll, E. A. Vineland Social Maturity Scale. Circle Pines, Minn.: American Guidance Service, n.d.
Drillien, C. M. Growth and Development of the Prematurely Born Infant. Baltimore: Williams &
Wilkins, 1964.
Eastham, R. D. and J. Jancar. Clinical Pathology in Mental Retardation. Baltimore: Williams &
Wilkins, 1968.
Ellingson, R. J. “Neurophysiology,” in J. Wortis, ed., Mental Retardation: An Annual Review, Vol. 4,

pp. 123-139. New York: Grune & Stratton, 1972.
Erlenmeyer-Kimbling, L. and L. F. Jarvik. “Genetics and Intelligence: A Review,” Science, 142

(1963), 1477-1479.
Farber, B. Mental Retardation: Its Social Context and Social Consequences. Boston: Houghton
Mifflin, 1968.
Fisher, M. and D. Zeaman. “Growth and Decline of Retardate Intelligence,” in N. R. Ellis, ed.,
International Review of Research in Mental Retardation, Vol. 4, pp. 151-191. New
----. “An Attention-Retention Theory of Retardate Discrimination Learning,” in N. R. Ellis, ed.,
Fox, R. M. and N. H. Azrin. Toilet Training the Retarded. Champaign, Ill.: Research Press, 1973.
Gardner, W. I. Behavior Modification in Mental Retardation. Chicago: Aldine-Atherton, 1971.
Girardeau, F. L. “Cultural-Familial Retardation,” in N. R. Ellis, ed., International Review of Research

in Mental Retardation, Vol. 5, pp. 304-348. New York: Academic, 1971.
Gottesman, I. I. “Genetic Aspects of Intelligent Behavior,” in N. R. Ellis, ed., Handbook of Mental

Deficiency: Psychological Theory and Research, pp. 253-296. New York: McGraw-
Hill, 1963.
Grossman, H. J., ed. Manual on Terminology and Classification in Mental Retardation, 1973
Revision. Washington: American Association on Mental Deficiency, 1973.
Gruenberg, E. M. “Epidemiology,” in H. A. Stevens, and R. Heber, eds., Mental Retardation: Review

of Research, pp. 259-306. Chicago: University of Chicago Press, 1964.
Haywood, H. C., ed. Socio-Cultural Aspects of Mental Retardation. New York: Meredith, 1970.
Haywood, H. C. and J. T. Tapp. “Experience and the Development of Adaptive Behavior,” in N. R.

Ellis, ed., International Review of Research in Mental Deficiency, Vol. 1, pp. 109-151.
New York: Academic, 1966.
Heber, R. F. “Culture and Familial Retardation,” in M. Cohen, ed., International Research Seminar
on Vocational Rehabilitation of the Mentally Retarded, Special Publications Series,
no. 1. pp. 313-324. Washington: American Association on Mental Deficiency, 1972.
Heber, R. F. and R. B. Dever. “Research on Education and Habilitation of the Mentally Retarded,”
in H. C. Haywood, ed., Socio-Cultural Aspects of Mental Retardation, pp. 395-427.
New York: Meredith, 1970.
Holmes, L. B., H. W. Moser, S. Halldorsson et al. Mental Retardation: An Atlas of Diseases with
Associated Physical Abnormalities. New York: Macmillan, 1972.
Jensen, A. R. “How Much Can We Boost I.Q. and Scholastic Achievement?” Harvard Educ. Rev., 39
(1969), 1-123.
----. “A Theory of Primary and Secondary Familial Mental Retardation,” in N. R. Ellis, ed.,
Kennedy, W. A., V. Van De Riet, and J. C. White, Jr. A Normative Sample of Intelligence and
Achievement of Negro Elementary School Children in Southeastern United States,
Monographs of the Society for Research in Child Development, 28 (1963), no. 6.
Leland, H. “Mental Retardation and Adaptive Behavior,” J. Spec. Educ., 6 (1972), 71-80.
Lewontin, R. C. “Race and Intelligence,” Bull. Atomic Scientists, 26 (1970), 2-8.
McKusick, V. A. Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal

Recessive, and X-Linked Phenotypes. 3rd ed. Baltimore: The Johns Hopkins
Menolascino, F. J., ed. Psychiatric Approaches to Mental Retardation. New York: Basic Books, 1970.
Mercer, J. R. Labeling the Mentally Retarded: Clinical and Social Systems Perspective on Mental
Retardation. Berkeley: University of California Press, 1973.
Nihira, K., R. Foster, M. Shellhaas et al. Adaptive Behavior Scales. Washington, C.: American
Association on Mental Deficiency, 1969.
Reed, E. W. and S. C. Reed. Mental Retardation: A Family Study. Philadelphia: Saunders, 1964.
Ross, R. T. Fairview Self-Help Scale (1970); Fairview Social Skills Scale (1972). Costa Mesa,
California: Research Department, Fairview State Hospital.
Rutter, M. L. “Psychiatry,” in J. Wortis, ed., Mental Retardation: An Annual Review, Vol. 3, pp. 186-
221. New York: Grune & Stratton, 1971.
Rutter, M. L., ed. Infantile Autism: Concepts, Characteristics, and Treatment. Baltimore: Williams &
Wilkins, 1971.
Scarr-salapatek, S. “Race, Social Class, and Q.,” Science, 174 (1971), 1285-1295.
Scriver, C. R. and L. E. Rosenberg. Amino-Acid Metabolism and Its Disorders. Philadelphia:

Saunders, 1973.
Sersen, E. A. “Conditioning and Learning,” in J. Wortis, ed., Mental Retardation: An Annual Review,
Vol. 1, pp. 28-41. New York: Grune & Stratton, 1970.
Skinner, B. F. Technology of Teaching. New York: Appleton-Century-Crofts, 1968.
Smith, D. W. Recognizable Patterns of Human Malformation. Philadelphia: Saunders, 1970.
Spitz, H. H. “Consolidating Facts into Schematized Learning and Memory System of Educable
Retardates,” in N. R. Ellis, ed., International Review of Research in Mental
Retardation, Vol. 6, pp. 149-168. New York: Academic, 1973.
Stein, Z. and M. Susser. “Mutability of Intelligence and Epidemiology of Mild Mental Retardation,”
Rev. Educ. Res., 40 (1970), 29-67.
Stevenson, G. S. in New Directions for Mentally Retarded Children. New York: Josiah Macy, Jr.,
Foundation, 1956.
Stevenson, H. W. Children’s Learning. New York: Meredith, 1972.
Tharp, R. G. and R. J. Wetzel. Behavior Modification in the Natural Environment. New York:
Academic, 1969.
Watson, L. S., Jr. “Application of Operant Conditioning Techniques to Institutionalized Severely

and Profoundly Retarded Children,” Mental Retardation Abstracts, 4 (1967), 1-18.
----. How to Use Behavior Modification with Mentally Retarded and Autistic Children: Programs for
Administrators, Teachers, Parents, and Nurses. Columbus, Ohio: Behavior
Modification Technology, 1972.
Werner, E., J. M. Bierman, F. E. French et al. “Reproductive and Environmental Casualties: A

Report on the 10-year Follow-up of the Children of Kauai Pregnancy Study,”
Pediatrics, 42 (1968), 112-127.
World Health Organization. International Classification of Diseases, 8th Revision. Geneva: WHO,
1968.
Chapter 19
MENTAL RETARDATION
II. Care and Management
Sterling D. Garrard and Julius B. Richmond
Today, patterns of service in the area of mental retardation are
undergoing a progressive change and differentiation which eventually may
enable most persons considered handicapped to live in communities
throughout most or all of their lives. Under the impact of the normalization
principle and strong advocacy for the retarded at many levels, a range of
family support services, training and educational options, domiciliary options,
and work options is being developed. In many places, traditional residential
institutions have redefined their programs, dispersed some of their functions

among small specialized facilities in communities, and/or have become the
hub of regional programs. All services are being ordered along a continuum
which will allow progressive movement of the individual toward as much
independence in adult life as the degree of normative skill development will
permit.
Services
Two major groups of services may be considered within the emerging
service system as follows: (1) those which are directed toward the maximum
cognitive competency and adaptive behavioral outcomes of the
developmental period; and (2) those which are directed toward the
maintenance of functional and productive capacities in adult life.
Developmental Services
Training and education are the one constant feature of programming
throughout the developmental period. During this time, all other professional
services are titrated for their specificity against the assessed needs of the
child and family.
If identification of developmental retardation occurs in early infancy,

home-training programs may be instituted in order to provide parents with
the knowledge of appropriate developmental and behavioral objectives and
to assist them in acquiring effective techniques of support. These programs

may be especially important if the infant or young child with mental
retardation, cerebral palsy, or multiple disabilities presents unusual cues or
stimuli to parents. In these instances, the automatic or untutored parental
responses may be inappropriate, may impede effective learning progress, and
may even reinforce maladaptive behaviors. During the preschool period, the
focus of training and education shifts to extrafamilial, developmental day-care
programs, often with the continuation of a parent educational component. It
is noteworthy that preschool programs, such as Head Start, are increasingly
accepting children with mental retardation and other handicapping

conditions into their services.
By school age, preparation begins for the range of social environments
which may be open to the person in adult life. At this time, a few profoundly
retarded or multiply handicapped children may be placed in medically
oriented institutions or nursing-home programs, where they ideally will

receive systematic stimulation, behavior shaping, care, and consistent social
contacts. Other children, who are severely or moderately retarded, may enter
self-contained special educational programs either in regular schools or in a

segregated community facility. Children with mild retardation may receive a
variety of educational programs in regular schools as follows: self-contained
special education, split regular and special education, regular classroom with
special resource teachers, regular classroom with tutors and programmed

instructional aids, or regular classroom with no special supports. By the teen
years, training and education are vocationally and work oriented and may
terminally involve work-study experiences.
The family is viewed as the major resource for the care of the child with
mental retardation during the developmental period. All necessary medical,
allied health, social, counseling, mental health, recreational, transportational,
protective, legal, and other services must be available in order to support the
continuation of community living in the nuclear family, if feasible and

appropriate. Alternate living arrangements should also be available in foster
homes or group homes on a short-or long-term basis, as indicated by the
capacities of the nuclear family. Generic service agencies should include staff
skills in the range of problems which may be associated with mental

retardation.
Massive traditional institutions are now viewed as an option of last
resort for developmental services for children with mental retardation. Many
institutions at present, however, are integrating their activities with the

continuum of community services. A range of services may be offered to the
population of a region, for example, in support of continued family care.
Specialized residential programs may be provided for multiply disabled

children, especially for those from non-urban areas. For many profoundly
retarded children with continuing medical needs, developmentally oriented

nursing-care programs may be provided in residence. Habilitative residential
programs may also be offered with the aim of returning the child to the family
or community after specific developmental or behavioral objectives have
been achieved. In some instances, a reverse flow is affected in which
institutional residents receive all or most of their educational programming in
the community. New residential facilities are being constructed in many parts
of the country which imaginatively exploit architectural possibilities for
normalizing institutional environments. Recently, minimum institutional

standards have been adopted for the accreditation of residential facilities
which ensure a basic quality of professional care and service.
Ideally, the available range of domiciliary options, work options, and
guardianship arrangements should permit parental responsibilities for the
person with retardation to end when he reaches adult life. Except in a few
instances, this ideal is not yet realized.
Adult Services for the Enhancement and Maintenance of Functional and Productive
Capacities
The need for special adult services is determined by the amount of

social structuring which the individual requires, i.e., whether independent or
dependent living is possible. In either case, the usual generic human-service
agencies and programs must be available on a need basis. Special
consideration must be given to domiciliary arrangements, work provisions,

heterosexual (or homosexual) activities, and legal rights. It is axiomatic that
living and work arrangements should enable the person to approximate
normative experiences as nearly as the behavioral potential permits.
Domiciliary arrangements may involve institutions, half-way houses,
hostels, or small group homes for individuals at moderately and mildly
retarded levels. Progression toward decreasing supervision within facilities
should be possible as competence for work and independence increases. The
psychological meaning of useful and remunerative work for the retarded is
underscored here. Vocational rehabilitation services and a spectrum of
settings for productive employment are necessary if community living is to

succeed. Possibilities for heterosexual relationships and marriage are just
beginning to be explored systematically in the face of long-standing social
biases.
Edgerton has provided a poignant documentation of the quality of life
associated with unsupervised community living for a number of individuals
with mental retardation.
Identification
The responsibility for the identification of children with mental
retardation is shared by all persons who are concerned with the development
of the child, including the parents. Physicians are in a particularly strategic
position to identify the children who come through medical channels.
Presumptive identification may be achieved in medical office settings if

sensorimotor, language, or social development deviates markedly from the
norms of screening instruments such as the Denver Developmental Screening
Test. Other infants and young children who do not receive care in physicians’
offices may be identified in well-child clinics or in their own homes by public
health nurses who are trained in developmental surveillance. Many other

children are identified first in relation to the demands of day-care, nursery, or
preschool programs. The importance of the schools as a source of
identification of mild forms of retardation has been previously emphasized.
Finally, developmental delay or mental retardation may be suspected first by

parents, especially in high socioeconomic families, although even
sophisticated parents occasionally overlook signs of difficulty for long periods
of time.
Except for school identification, these activities serve chiefly to identify

children with the most obvious manifestations of mental retardation. Other
agencies, including physicians, may be somewhat less effective in identifying
mildly retarded children, especially in the absence of neurological or somatic

abnormalities. Unless the objectives of identification are related to specific
forms of intervention which can be immediately activated, however, early

labeling is a sterile exercise which may have harmful consequences for some
children. The state of the art in the area of screening and assessment of young
children at developmental risk has been recently reviewed by Meier.
Evaluation
The “diagnosis” of mental retardation may have different connotations
in different settings. It may refer to the formal labeling of a child through

professional studies which identify the psychometric and adaptive behavioral
criteria. It may refer to a medical evaluation for the identification of etiologies
or remediable disorders which may be compounding the developmental and

behavioral issues. In still other settings, it may refer to a comprehensive,
interdisciplinary study of the child’s functional characteristics for the purpose
of identifying appropriate objectives for intervention, assigning professional
responsibilities, or designating appropriate service resources. None of these

“diagnostic” activities is necessarily confined to one location or a single
discipline.
Medical Evaluation
The physician follows a definite agenda in the medical evaluation of
children with mental retardation. He must identify associated medical
disorders which are heritable, thereby permitting genetic counseling for the
parents, amniocentesis for intrauterine diagnosis in subsequent pregnancies

(where possible), or early recognition in subsequent offspring. In rare
instances, a specific treatment may be available which will permit the
amelioration or interruption of an underlying genetic disease. As noted in the
preceding chapter, the clues which are presumptive of a specific medical
disease, including those which are heritable, are the following: (1) positive
neurological signs; (2) neurological deterioration; (3) malformation clusters;
(4) positive biochemical screening tests; (5) other physical signs, including
macular degeneration, ectodermal lesions, and the like; and (6) prior family
history of a heritable disorder. The physician must also identify remediable
medical disorders which are actively inhibiting development through the
restriction of response capabilities. Areas of concern here may include visual

acuity, auditory function, convulsive activity, neuromuscular impairment,
otologic, orthopedic, cardiac, or similar disorders. The physician may be
assisted in this endeavor by a variety of medical specialists and allied health

professionals. Many children with mental retardation will have additional
disabilities which require treatment. The physician may also be assisted by
social workers and psychologists in recognizing potentially remediable
psychosocial factors which are actively interfering with cognitive growth and
adaptive behavioral development.
Functional Evaluation
Present-day management of mental retardation during childhood is

directed toward the production of specified changes in a child’s competencies
and adaptive behavior. Intervention of this type requires a definition of
specific learning and behavioral objectives. A functional analysis of the child’s
current, observable behaviors is the necessary first step in defining these
objectives. Measures of intelligence which compare a child with a
standardization group for the primary purpose of categorization have limited

usefulness for this purpose; likewise, etiologic diagnoses are meaningless in
this context.
A functional analysis of the child’s behavior may involve any or all of the
following: (1) a determination of his current developmental locus (i.e., his
learned behaviors); (2) observation of his learning behaviors or processes;

(3) observation and specification of his maladaptive behaviors; (4)
observation of the environmental consequences (and possibly antecedents)
of his maladaptive behaviors; and (5) delineation of the limitations which are
imposed by medical findings on his response capabilities under specific
demand situations.
The identification of the child’s present locus in a known developmental

sequence automatically defines his next developmental steps and delineates
appropriate objectives for intervention. In recent years, studies in cognitive
psychology, psycholinguistics, and social adaptive behavior (among children

with mental retardation) have refined our knowledge of the hierarchical
sequences of development, and, in some instances, have contributed to the

construction of ordinal or other scales for the purpose of assessment (See
references 21, 22, 25, 26, 28, and 29). It is now possible to specify a child’s
locus in any of several developmental streams with considerable precision.
Likewise, a child’s educational locus and learning behaviors can be analyzed
through psychoeducational instruments and educational observations. Again,

the child’s locus and functional characteristics delineate the appropriate
educational objectives and approaches.
Maladaptive behaviors and those which are inappropriate and
unacceptable in particular settings may also be observed and specified. When
defined with sufficient precision, maladaptive behaviors can be rank-ordered
in terms of importance, counted, and specified as potential targets for
modification. The target behaviors which are selected for modification are
usually determined in consultation with parents or other involved persons.

The attempt to change adaptive behavior requires an analysis of the
environmental consequences of the child’s behavior as well. Consequent
parental behavior and that of other significant persons with whom the child
interacts must be specified in this context as simultaneous targets for
modification.
Prescriptive Programming
From the preceding discussion, it is apparent that a new model has
evolved in community and residential facilities for professional intervention
with children with mental retardation. Prescriptive programming is the
keystone of intervention within this model. A prescription is based upon the
results of the analysis of a child’s current, observable, functional
characteristics. When all objectives have been identified and clearly specified,
appropriate techniques for intervention can be prescribed, either in the area
of training and adaptive behavior, or education. Behavior principles and
modern educational concepts supply the technology for intervention of this
type. Some features of behavior modification and effective educational

programming were noted briefly in the preceding chapter.
A pragmatic test is an essential ingredient of prescriptive intervention.
The program which is prescribed must finally be shown to be feasible for
implementation within the home, the community facility, or the school, and to
have demonstrable efficacy in the production of movement toward the
specified objectives. If neither feasible nor effective, the objectives or the
techniques of intervention, or both, must be modified.
Interdisciplinary Model
The interdisciplinary model is an organizational structure through

which professional services are delivered to persons with mental retardation.
The model is based upon the assumption that the complexities of the
problems of the individual with mental retardation exceed the resolving
power of any single discipline. The professional composition of the
interdisciplinary group varies according to the forms and severity of the
problems and the age of the person. The professional group at one time or
another and in different circumstances may include some combination of the

following: psychologists, educators, audiologists and speech pathologists,
social workers, vocational counselors and rehabilitationists, allied health
professionals, physicians from any of several specialties, including psychiatry,
and care staff members. The contributions of each discipline are determined
by the match between its specific skills, the functional characteristics of the
person, and the priorities for intervention which are established through the
interdisciplinary group process. Except for the continuing importance of

education during childhood, the contributions of other disciplines may vary
from person to person and at different points in the life of the same person.
The interdisciplinary model ensures the availability of appropriate
professional skills for the person. In addition, it minimizes professional

redundancy by requiring each discipline to define clearly its special expertise
vis-a-vis other disciplines. Through the interdisciplinary group process, the

disciplines frequently generate a multifaceted view of the person, his
problems, and the objectives for intervention which can rarely be duplicated
by professionals who work independently.
Parental Involvement
Many early-infant educational projects have included a subsidiary
parent-educational component, and several have worked primarily with

parents in the home. These programs have demonstrated that specific
direction of the maternal transactions with an infant or young child can
influence developmental outcome under the conditions of the studies. In

addition, the growing literature in the field of behavior modification has
indicated that parents can be effective agents for intervention in relation to a
wide spectrum of behavioral phenomena if provided with knowledge of
appropriate objectives and techniques. It has now been recognized that

parents can be taught to be effective teachers, that they can profit from formal
specific child-rearing education, and that they can modify their behavior to
some degree if they are reinforcing maladaptive behavior.
Present approaches to the education of parents of children with mental
retardation often emphasize instruction in the techniques of behavior
modification. Although few studies have been designed to date with sufficient
rigor to permit an objective evaluation of this approach, the education of
parents in specific techniques to support the development of their own
children has a strong intrinsic appeal. When the education of parents involves
the use of the techniques of behavior modification, the parent becomes a

contributing and participating member of the professional team concerned
with intervention. The parent may then be regarded as a manpower resource
for the conduct of the child’s program in the natural setting of the home. In
the process of generating a prescription for intervention in conjunction with
professionals, parents can learn appropriate developmental objectives,

participate in the delineation of maladaptive behaviors, and acquire
techniques and behaviors through which to fulfill a supportive and effective
role with the child. Under these circumstances, the parental role acquires
direction and specificity, and the parent assumes an active rather than a
passive stance in relation to the child’s problems.
Obviously, the educational approach to parents need not be limited to
indoctrination in the techniques of behavior modification. The latter may lead
at times to the delineation of objectives which are too narrowly defined from
a comprehensive perspective. Any additional combination of the following
techniques may be employed in working with parents: individual educational
discussions, informational classes, group work, modeling experiences,

feedback experiences—possibly with immediate cueing or delayed videotape
viewing—and insight counseling.
Family Support
It is easy to overgeneralize concerning the psychological adaptations of
parents, siblings, and the retarded child or adult. Often discussions
concerning these adaptations are based upon stereotypes derived from
experiences limited to high socioeconomic-status parents who have a
severely retarded child. Obviously, the psychological adaptations of parents
may vary according to multiple idiosyncratic factors as follows: the severity of

mental retardation and the extent of the child’s deviancy in behavior and
appearance; age of the child; sex of the child and of the parent; age of the
parent; sociocultural background; investment in the child for achieving
unfulfilled parental ambitions; duration of the marriage and its mutuality and
stability; presence or absence of other normal children in the family; religious
orientation; orientation toward achievement; past experiences in dealing
with adversity; previous attitudes toward handicaps and minority groups;

need for social approval; need for utilization of the child in neurotic patterns
which may defeat professional efforts for change or improvement.
In general, the adaptational problems of parents reflect anticipated
psychological responses to the degree of realistic stress which the child poses.
If the child is severely impaired, parents may exhibit a predictable sequence
of reactions leading eventually to adjustment in accord with crisis theory. A

phase of initial stress, shock, grief, and disorganization may be followed by a
prolonged phase of reintegration in which feelings of denial and guilt may be

associated with the observed behavioral patterns. Eventually, an adaptation is
reached which will permit internal comfort and constructive action by most
parents. The passage of time and a prolonged expenditure of effort in behalf
of the child may be necessary before the latter stage of resolution is reached.
During the interim period, specific instruction and concrete assistance for
increasing parental effectiveness with the child may be at least as important

for psychological movement as the gaining of psychological insight.
Within the broad phases of adaptation, points may occur at which
psychological stresses are intensified for parents in association with the
maturation of the child. After initial recognition, these points may include: (1)
the period at which the child’s chronological age ordinarily would permit
school attendance; (2) the period of pubescence with increased physical
growth, sexual maturity, and sexual or erotic interests; and (3) the period of
entry into adult life with the necessity for decisions concerning provisions for
living and supervision.
Although the psychological reactions of parents may be homeostatic for
them, the overt behavioral correlates of these reactions may be maladaptive

for the support of the cognitive and adaptive growth of the child. Management
goals are required for parents and the child, therefore, which are both
separate and interrelated. In general, the dual objectives can be met most
effectively in the context of the child’s program setting. Under these
circumstances, it is least likely that the professional focus upon the child will
be subordinated to an interest in the psychodynamic reactions of the parents.
The experienced professional will observe the course of parental adaptations
with time, however, as indications of denial, guilt, dependency, and projection
are revealed. Individual psychotherapeutic efforts for parents, when
indicated, should occur in facilities appropriate for them.
It is inevitable that some of the difficulties associated with the presence
of a retarded child in the family, especially at severe levels, will impinge upon
the normal siblings and create adjustment problems for them. Again, their
problems may be seen as anticipated responses to stress which can usually be
assimilated without major disruptive effects. Professional counseling for the
parents or the normal siblings may be helpful at times in support of the
adaptational processes. The fact that an affected child was born into the
family may raise doubts for teenagers regarding their own capacity for
parenthood. The provision of accurate information in clear, objective terms
will be helpful in dispelling these apprehensions.
The management of erotic feelings and sexual behavior generates more

uncertainty and concerns in relation to the child or adult with mental
retardation than any other aspect of behavior. Many individuals with
retardation reach puberty and adult life without adequate information,

understanding, or opportunities to learn appropriate mechanisms for coping
with sexual feelings. Parents and professionals alike may systematically avoid
specific preparatory efforts in these areas. Parental concerns at adolescence
often focus upon unconcealed masturbation, sexual exploitation (either
heterosexually or homosexually), pregnancy, and lack of control of sexual
impulses. The recent emphasis upon normalization and the increased
movement of individuals with retardation in society has highlighted the

potential sexual risks. At least at an academic level, attention is now being
directed toward the necessity for instituting curricula and training programs
for the preparation of children to fill adult social (including sexual) roles.
Parental instruction is almost universally needed as a means of enabling them

to provide appropriate support for developmental growth in this area.
Professional Decorum
The overt behavior which the professional person manifests in fulfilling
his specific responsibilities for the child may have powerful, nonspecific side
effects for families. In utilizing himself as an instrument for parental support,
the professional person should demonstrate technical competence, provide
an appropriate behavioral model with the child, and demonstrate a constancy
of interest in the child and family. He should also maintain an expectation of

developmental movement in the child in line with the prevailing optimism
surrounding present-day approaches to intervention and in recognition of the
shaping effect of expectations. Finally, he should respond positively to

appropriate parental behaviors and neutrally to inappropriate behaviors as a
means of reinforcing parental strengths and attenuating weaknesses. The
professional person should be aware, however, of the emotional turmoil
which parents may feel and the range of behavioral responses which they
may exhibit in relation to a child with severe mental retardation. He may then
provide an important, nonspecific source of comfort, if needed, through his
listening skills.
Drug Treatment
The physician may be an instrument for increasing the effectiveness of

learning and behavioral intervention for some children by prescribing
neuropharmacological agents which may modify distracted behavior or
control seizures. In these instances, the choice of an appropriate agent and

dosage requires the joint participation of educators and other disciplines as
objective observers of behavioral effects through the use of rating scales and
other quantitative measures. Drug therapy, however, cannot substitute for
appropriate educational or intervention programs. At times, the behaviors,
which a physician is asked to modify through drug treatment, represent
behavioral responses to inappropriate or nonindividualized programs or to

maladaptive parental behavior. Appropriate program prescriptions should
always precede medicinal prescriptions. Neuropharmacological agents do not
have the potentiality for modifying basic behavioral patterns or learning
characteristics. Only appropriate behavioral programming can accomplish the
objective of basic behavioral change.
When prescribing neuropharmacological agents, the physician may be
advised to follow the format of a behavior-modification prescription. Thus,
the behavior(s) to be modified should be clearly defined and specified in

concrete terms. The frequency of the target behavior should be counted with
and without medication in the child’s home and/or school setting. Measurable
changes in school-learning behavior should likewise be demonstrated if
academic objectives are the defined targets. Since neuropharmacological

agents are potent drugs with significant potential side effects, treatment should
be discontinued if it fails to produce quantitative evidence for the intended
behavioral effects.
Ethical, Moral, and Legal Issues
Mental retardation pinpoints sharply many ethical, moral, and legal
dilemmas for the professions and society at large. Judgments concerning the
withholding of life-saving medical treatments in individuals who are
demonstrably retarded; human experimentation in retarded populations with

attendant issues concerning risks and consent; sterilization procedures on
the indication of retardation alone; marital prohibitions; institutional
commitment procedures; denial of rights and unequal treatment before the
law; all and many more discriminatory practices are currently being
questioned and sharply attacked. The values and fabric of our society are
threatened as long as these inequities are permitted to exist. Strong advocacy
for individuals with mental retardation has become a major responsibility for
all who are concerned with human life, dignity, and pluralism.
Conclusion
Within the recent past, major changes have occurred, and are
continuing to occur, in concepts and practices related to intervention with

children and adults with mental retardation. These changes have generated
an expectation that the developmental velocity and adaptive behaviors of all
children can be modified through specified forms of environmental
intervention. During the developmental period, community services in

support of family care have supplanted the large institution as a major
resource for service and care. In adult life, the thrust toward normalization
has led to a variety of living and work options which have contributed to a
clarification of the ultimate objectives for developmental interventions. To an

important extent, social changes have occurred which have increased the
options for a retarded person even when the possibilities for individual
change are sharply limited. But communities must be conscious of the extent
of the commitment which is required to build a spectrum of community-
based services (integrated with institutional services) in order to make these
options realistic. Without the commitment of adequate resources, community
programs risk the same disenchantment which historically overtook
residential institutions.
Bibliography
Adams, M. E. “Siblings of the Retarded: Their Problems and Treatment,” Child Welfare, 46 (1967),
310-316.
----. “Science, Technology, and Some Dilemmas of Advocacy,” Science, 180 (1973), 840-842.
Baumeister, A. A., E. C. Butterfield, eds. Residential Facilities for the Mentally Retarded. Chicago:
Aldine-Atherton, 1970.
Berkowitz, B. P., and A. M. Graziano. “Training Parents as Behavior Therapists: A Review,” Behav.
Res. Ther., 10 (1972), 297-317.
Cohen, M., ed. International Research Seminar on Vocational Rehabilitation of the Mentally
Retarded, Special Publication Series, no. 1, pp. iii-vii. Washington: American
Association on Mental Deficiency, 1972.
De La Cruz, F. F. and G. D. La Veck. Human Sexuality and the Mentally Retarded. New York:
Brunner/Mazel, 1973.
Doernberg, N. L. “Parents as Teachers of Their Own Children,” in J. Wortis, ed., Mental

Retardation: An Annual Review, Vol. 4, pp. 33-43. New York: Grune & Stratton,
1972.
Edgerton, R. B. The Cloak of Competence. Berkeley: University of California Press, 1967.
Frankenberg, W. K., J. B. Dodds, and W. Fandal. Denver Developmental Screening Test. 1970 Rev.
ed. Denver: University of Colorado Medical Center, 1970.
Freeman, R. D. “Psychopharmacology and the Retarded Child,” in F. J. Menolascino, ed., Psychiatric

Approaches to Mental Retardation, pp. 294-368. New York: Basic Books, 1970.
Garrard, S. D. “Role of the Pediatrician in the Management of Learning Disorders,” Pediatric Clin.
North Am., 20 (1973), 737-754.
Garrard, S. D. and J. B. Richmond. “Psychological Aspects of the Management of Chronic Diseases

and Handicapping Conditions in Childhood,” in H. I. Lief, V. F. Lief, and N. R. Lief,
eds., The Psychological Basis of Medical Practice, pp. 370-403. New York: Harper &
Row, 1963.
Hallenbeck, P. “A Note on a ‘New’ Method of Studying Change,” Rehabil. Lit., 34 (1973), 138-139.
Heber, R. Unpublished study. Johnson, C. A. and R. C. Katz. “Using Parents as Change Agents for
Their Children: A Review,” J. Child Psychol. Psychiatry, 14 (1973), 181-200.
Joint Commission on Accreditation of Hospitals. Standards for Residential Facilities for the
Mentally Retarded. Chicago: Joint Commission on Accreditation of Hospitals, 1971.
Karnes, M. B., I. A. Teska, A. S. Hodgins et al. “Educational Intervention at Home by Mothers of

Disadvantaged Infants,” Child Dev., 41 (1970), 925-935.
Klaus, R. A. and S. W. Gray. The Early Training Project for Disadvantaged Children: A Report After
Five Years," Monographs of the Society for Research in Child Development, 33
(1968), no. 4.
Koch, R. and J. C. Dobson. The Mentally Retarded Child and His Family: A Multidisciplinary
Handbook. New York: Brunner/Mazel, 1971.
Kugel, R. B. and W. Wolfensberger. Changing Patterns in Residential Services for the Mentally
Retarded. Washington: The President’s Committee on Mental Retardation, 1969.
Laurendeau, M. and A. Pinard. Causal Thinking in the Child. New York: International Universities
Press, 1962.
----. The Development of the Concept of Space in the Child. New York: International Universities
Press, 1970.
Meier, J. Screening and Assessment of Young Children at Developmental Risk. DHEW Publication no.
(OS) 73-90. Washington: The President’s Committee on Mental Retardation, 1973.
Richmond, J. B., G. E. Tarjan, and R. S. Mendelsohn, eds. Mental Retardation: An AM A Handbook for
the Primary Physician, 2nd ed. Chicago: American Medical Association, 1974.
Sailor, W., D. Guess, and D. M. Baer. “Functional Language for Verbally Deficient Children,” Ment.
Retard., 11 (1973), 27-35.
Schiefelbusch, R. L., ed. Language of the Mentally Retarded. Baltimore: University Park Press,
1972.
Sroufe, L. A. and M. A. Stewart. “Treating Problem Children with Stimulant Drugs,” N. Engl. J. Med.,
289 (1973), 407-413.
Uzgiris, I. C. and J. McV. Hunt. An Instrument for Assessing Infant Psychological Development.
(Unpublished study.) Champaign, Ill.: Psychological Development Laboratory,
University of Illinois, 1966.
Watson, L. S., Jr. How to Use Behavior Modification with Mentally Retarded and Autistic Children:
Programs for Administrators, Teachers, Parents, and Nurses. Columbus, Ohio:
Behavior Modification Technology, 1972.
Wolfensberger, W. The Principle of Normalization in Human Services. Toronto: National Institute

on Mental Retardation, 1972.
Wolfensberger, W. and R. A. Kurtz, eds. Management of the Family of the Mentally Retarded.
Chicago: Follett Educational Corporation, 1969.
Chapter 20
Biomedical Types Of Mental Deficiency
George A. Jervis
The first attempts to isolate specific types of mental retardation in the

large population of defectives dates from the last century when cretinism,
mongolism, and tuberosclerosis were identified. These attempts have
continued with increased success and at present a few hundred biomedical
types are on record.
The purpose of this chapter is to describe briefly some of these types.
They can be classified into two large categories according to the etiology, i.e.,
the genetically determined and the environmentally determined. A third
category may be added to include types of mental defect of unknown etiology.
The genetically determined types are usually classified into three
groups: due to (1) mental defect associated with chromosomal abnormalities;
(2) recessive genes, and (3) dominant genes.
Chromosomal Abnormalities
Downs Syndrome, Mongolism
Frequency is estimated at about 1 in 600 births and increases some ten-
fold in children born of women over forty years of age. The symptomatology
consists of a conglomeration of abnormal physical traits: stunted growth,
brachycephalic small skull, round flat face, almond-shaped palpebral fissures
which slant inward and downward, epicanthus folds, large tongue, and small
chin. The extremities are small, the fifth finger is usually curved and the palm
of the hands shows a marked transverse line. There is general muscular
hypotonicity. Congenital defects of heart or other organs are common. Mental
retardation varies from severe to mild but the majority show a moderate
degree of it. See Figure 20-1.
Figure 20-1.
Down’s syndrome.
In about 90 percent of the cases, the abnormality of chromosomes
consists in an extra chromosome in the twenty-one chromosomes of group G.

There are, therefore, forty-seven chromosomes instead of the normal
complement of forty-six. In a small percentage of patients there is a different
chromosomal arrangement, the extra chromosome is not free but is attached
(translocated) to a large chromosome, usually of D group. The total

complement is therefore apparently the normal forty-six chromosomes. In a
situation of this type the mother may have also a similar translocation, the
total amount of her chromosomes being forty-five. The mother, then, has a
theoretical chance of one out of three of having other affected children.
Edwards Syndrome, Trisomy E
Frequency is about 1 in 3500 births. Clinical manifestations consist of

hypertelorism, palpebral ptosis, small chin, low-set malformed ears,
macrognathia, shield chest, flexion deformity of finger, short neck, and

congenital heart disease. Mental retardation is severe. Early death is common.
The diagnosis rests on the demonstration of extra chromosome eighteen in
the E group.
Patau Syndrome, Trisomy D
This is rarer than Trisomy E, the incidence being about 1 in 6000.
Clinically, there is microcephaly, microthalmia, cleft lip, cleft palate,
malformed ears, polydactily or syndactily, and other malformations. Mental
retardation is profound and life expectancy short, from a few months to a few
years. The extra chromosome in the D group is number thirteen.
Cat-Cry Syndrome
This syndrome—deletion of short arm of chromosome 5—is
characterized by microcephaly, round face, hypertelorism, micrognathia and
severe mental retardation. The voice in infancy has a characteristic catlike
quality. Numerous other abnormalities in number or structure of autosomal

chromosomes resulting in mental deficiency are documented. They are,
however, rarer than the ones mentioned.
Several aberration of sex chromosomes in mentally defective

individuals are known. The major categories are the following:
Klinefelter disease is clinically manifested by tall stature,
underdeveloped secondary sexual characteristics, small and firm testes,

clinodactily, cubitus valgus, and often obesity. Mental retardation when
present is mild. The karyotype is XXY. The number of chromosome thirty-
seven.
In the same group of excessive number of sex chromosomes are cases
with karyotype of XXXY and XXYY, clinically similar to XXY male. Patients with
the karyotype XXXXY (thirty-nine chromosome) show, in addition, more
severe mental retardation. The hypogenitalism is more evident and several
skeletal abnormalities are present.
In the female, the major categories of aberrations of sex chromosomes
associated with mental retardation are the multiple X types. In patients with
three X (instead of two) there is no distinct phenotype and mental retardation
is not always observed and, when present, is mild. Cases with four or five X
have been occasionally reported. These women are usually mentally
defective. The syndrome of multiple X may be promptly diagnosed by
examining a buccal smear. The epithelial cells of the mouth mucosa have one
less Barr bodies than the number of X’s.
Mental Deficiency Due to Recessive Genes
Numerous uncommon types of mental defect may be grouped under
this heading. In each condition the family data of the patients are consistent
with the hypothesis of a recessive gene being associated with the disease.
Therefore, in a group of affected families, when the sibships are examined
with proper statistical methods, the ratio of affected to normal sibs is 1 to 3
and the rate of consanguinity among parents of affected children is
significantly higher than in the general population. A number of recessive
types, in addition, are characterized by the defect of a specific enzyme.
However, the causal relationship between the biochemical abnormality and

mental defect is not always clear.
Among this group, the following may be briefly described.
Phenylketonuria
The incidence is of the order of x in 15,000 children, the highest in these
metabolic types. The degree of mental retardation varies but it is usually
severe. Physical development is little impaired and life expectancy is not

much shorter than normal. Seizures are often present and minor neurological
abnormalities can be demonstrated in most patients. The diagnosis is based
on the finding of phenylpyruvic acid in the urine. In addition, phenylalanine
(an essential amino acid) is present in abnormal quantity in the blood. The
demonstration of excess phenylalanine in the blood is diagnostic in the
newborn infant when phenylpyruvic acid is not yet present. Early diagnosis is
crucial for a successful treatment of the disease. The metabolic abnormality
consists in the absence of a specific liver enzyme which metabolizes

phenylalanine. The unmetabolized phenylalanine or some of its derivatives
are apparently toxic, interfering with normal postnatal development of the
brain. Treatment consists of special diets poor in phenylalanine.
Homocystinuria
The main clinical manifestations are arachnodactyly, stiff joints, high
stature, long limbs, and dislocation of the lenses. The presence of peculiar
malar flush may be of help in the diagnosis. Glaucoma and cataracts may be
present. Arterial and venous thromboses are frequent. Mental retardation,
when present, varies from very mild to moderate. The metabolic abnormality
consists of the absence of cystothionine synthetase, the enzyme of sulfur
amino acid metabolism catalyzing the conversion of homocystine to

cystothionine. The unmetabolized excess of homocystine is excreted in the
urine and is easily recognized by a simple test. Low methionine diet may help
in the treatment and in a certain number of cases the administration of
Vitamin B6 is useful.
Maple Sugar Urine Disease
The first clinical manifestations occur in early infancy. There are feeding
difficulties, vomiting, spasticity, generalized seizures and unresponsiveness.
Hair is coarse, sparse, and kinky (hence the term of kinky hair disease). The
urine has a strong odor similar to maple sugar. The metabolic abnormality is
in the branched amino acid metabolism. Leucine, valine, isoleucine, and their
corresponding keto acids accumulate in blood and urine because of a lack of
their proper enzymes. Keto-aciduria results which is diagnostic of the disease.
Unless controlled with very difficult dietary measures, the disease is fatal.
Histidinemia
There are no distinct clinical manifestations aside from mild mental
deficiency which is present only in about 50 percent of the cases. Speech
defect is noted in some 60 percent.
The metabolic abnormality consists of a missing enzyme (histidase) in

the catabolism of histidine. The absence of histidase results in the presence of
an abnormal amount of histidine and of its ketoacid (imidazole pyruvic acid)
in the blood and urine of patients. A few other rare amino aciduriae with
mental defect have been reported.
Neurolipidoses
The term is used to denote a group of diseases of the central nervous
system characterized by the storage of lipid in the brain and other organs.
Mental retardation is always present and the conditions are fatal.
Tay-Sachs Disease, the onset of this disease (infantile amaurotic idiocy)
is during the first years of life and leads to death in a few years. Neurological
deterioration, blindness, and convulsions are major symptoms.
Pathologically, the nerve cells are ubiquitously distended and repleted with
gangliosides, a complex lipid, small amounts of which are normally present in
the brain (see Figure 20-2). The disease is prevalent among Ashkenazi Jews.
Prenatal diagnosis may be made by demonstrating the defect of a specific

enzyme, hexoseaminidase A, in the cells of the amniotic fluid.
Figure 20-2.
Swollen “balloon like” nerve cells characteristic of amaurotic idiocy .
Batten Disease, this disease, neuronal ceroidlipofuscinosis, is a widely
investigated lipidosis causing progressive mental retardation and blindness.
There are several varieties which are classified according to age of onset and
duration. Their common trait is the storage of a complex lipid (lipofuscin) in
the brain cells. The nature of the defective enzyme (if any) is not known.
Nieman-Piek disease, in its infantile form, is characterized by a severe
progressive mental retardation, blindness, and hepatospenomegaly. The
substance accumulating in brain, liver, and spleen is sphingomylin, a lipid
normally present in the brain but in smaller quantity. The missing enzyme is
sphingomyelinase which normally breaks down sphingomyelin.
Gaucher disease, in the acute infantile cerebral types, with severe mental
deterioration is usually fatal. Spleen and liver are enlarged because of the
accumulation of a glycolipid (glucocerebroside) which cannot be metabolized
because of the congenital lack of its specific enzyme.
Mucopolysaccharidoses
This is a group of diseases characterized by accumulation of
mucopolysaccharides in the cells of various organs, including the brain. With

few exceptions the children are mentally defective. Several varieties have
been recognized showing minor clinical differences but distinct enzymatic
characteristics. The most common are:
Type I, Hurler Syndrome, characterized by stunted growth, large head,
distorted coarse facial features, clouding of the corneas, large nose, thick
tongue, abnormalities of osseous system, short neck, gibbus, and hirsutism
(see Figure 20-3). Mental retardation is usually severe and slowly
progressive. Mucopolysaccharides in the form of dermatan sulfate and
heparan sulfate are present in the urine and the tissues of the body. The
enzyme which is missing is alpha-L-Iduzonidase.
Figure 20-3.
Figure 20-3.
Hurler syndrome.
Type II, Hunter Syndrome, has clinical features similar to Type I but
cornea clouding is lacking, mental retardation is less severe, and life
expectancy longer. The disease is recessive but sex-linked, so that the patients
are only boys. The biochemical characteristics are also similar to Type I, but
the missing enzyme is different (sulfoiduromate sulfatase).
Type III, Sanfilippo syndrome, has physical features similar to Type II
and I in the other varieties of the disease but mental retardation is usually
much more marked. In the urine, blood, and tissues mostly heparan sulfate is
present. The specific missing enzyme is heparan sulfate sulfatase.
Galactosemia
The main symptoms of this disease are mental deficiency,
hepatosplenomegaly, and cataracts. In newborn, jaundice is usually present.

Biochemically, large amounts of galactose and its phosphate are found in the
urine and body fluids. The enzymatic defect is in the metabolic pathway from
galactose to glucose where a block exists after the galactose phosphate step,
due to the missing enzyme which converts galactose phosphate to uridine-
galactose. This disease is rare, about 1 in 60,000-70,000 births and can be
treated by eliminating milk and milk products from the diet of the infant.
Wilson Disease
This disease, hepato lenticular degeneration, is a recessive condition,
characterized clinically by progressive extrapyramidal syndrome with
intellectual deterioration, and pathologically by cirrhosis of the liver and
degeneration of the basal ganglia of the brain. Biochemical alterations consist
of very low blood copper, increased excretion of copper in the urine and
deposit of copper in the brain, liver, and other organs. Normally, blood copper
is closely bound to ceruloplasmin, a blood protein. In Wilson disease,

ceruloplasmin cannot bind copper because of a genetically determined
structural alteration (for further review see Chapter 16). Free copper, then, is
deposited in the brain, liver, and other organs causing degenerative change.
Treatment by chelating agents such as penicillamine is of benefit.
Hyperucemia
In this disease, Lesch-Nyhan, mental and motor retardation are

accompanied by athetoid movements and spasms. Peculiar self mutilating
behavior, such as lip-biting and finger-chewing are characteristic.
Biochemically, there is an increased production of uric acid, due to a defect of
inhibitory enzyme in the uric acid metabolism.
In a second group of recessive conditions associated with mental
deficiency, no biochemical abnormalities have been detected thus far.
Primary Microcephaly
Patients are of small stature and the head is particularly small (see
Figure 20-4). There are no neurological manifestations but mental deficiency

is usually serious. The condition should be differentiated from secondary
microcephaly which is more common and is caused by various environmental
factors.
Figure 20-4.
Microcephaly. Chronological age fifteen, mental age three.
Ataxia Telangiectasia
In this disease, Louis-Barr syndrome, mental defect is accompanied by
progressive cerebellar dysfunction and by characteristic telangiectasiae of the

bulbar conjunctiva. There is in addition immune incompetence due to the
deficiency of immune globluline A.
Laurence-Moon Syndrome
This disease is easily recognized by a cluster of abnormalities, such as
pigmentary degeneration of the retina, mental retardation, polydactyly,
obesity, and hypogenitalism.
Sjögren-Larson Syndrome
This disease consists of congenital generalized ichtyosis, pigmentary

degeneration of the retina, slowly progressive spastic extensor plantar
response, and mental defect. Epileptic seizures are not uncommon.
Cockayne Syndrome
Mental defect is usually severe and associated with dwarfism,
microcephaly, pigmentary degeneration of the retina, hypogenitalism, and
malnutrition. The condition is often progressive.
Lowe Syndrome
Cataract is present early, often at birth, and is frequently accompanied

by glaucoma. Metabolic acidosis, rickets, and organic aciduria of renal origin
are usually present. Life expectancy is reduced. Mental deficiency is usually
severe. The condition is X-linked recessive affecting only boys.
Smith-Lemli-Opitz Syndrome
The features consist of microcephaly, epicanthus with ptosis,
strabismus, small upturned nose with broad bridge, micrognathia, lowset

upturned ears, syndactyly or polydactyly, and various deformities of the
lower extremities. Mental defect is usually severe and patients fail to thrive.
Mental Deficiency Associated with Dominant Genes
In this group are a few types of genetically determined instances of

mental deficiency which are transmitted directly from affected parent to half
of the offspring. The occurrence of sporadic forms is explained by assuming
that the isolated instance is caused by a mutation in the parental gene. The
mutated gene is then transmitted to the offspring. If there are no offspring the
instance remains unique. Incomplete symptomatology is often noted in
dominant conditions thus adding difficulties to the recognition of the disease.
Tuberosclerosis
This disease is characterized by the triad mental deficiency, adenoma
sebaceous, and epilepsy. Other skin lesions are common, such as areas of
discoloration, cutaneous fibroma, and shagreen patches. Retinal nodules and
intracranial calcifications are often present (see Figure 20-5). Mental
retardation varies from profound to mild. Occasionally, patients with normal
intelligence have been on record. Incomplete forms (“formes’ frustes”) are

not rare.
Figure 20-5.
Figure 20-5.
Tuberosclerosis.
Achondroplasia
Shortening of the limbs, particularly of the proximal segments, large

head with prominent forehead, and short broad hands are the main physical
features of this disease. Mental retardation, usually mild, is present in no
more than a third of the patients.
Craniofacial Dysostosis
In this disease (Crouzon), distorted shape of head, exopthalmos
strabismus, and hypertelorism are characteristic. The orbits are poorly
developed. Mental deficiency is mild or moderate, increased intracranial
pressure may develop.
Acrocephalosyndactylia
In this disease (Apert), the head is misshaped, resembling that of

Crouzon disease. There is, in addition, fusion of fingers and toes (see Figure
20-6). Several varieties have been described. Mental defect is usually less
mild than in Crouzon disease.
Arachnodactyly
In this disease (Marfan), long limbs, spidery fingers and toes, dislocation
of lenses, and cardiac defects are the main physical features. Mental
deficiency, when present, is mild.
Figure 20-6.
Figure 20-6.
Acrocephalosyndactilia.
Mental Deficiency Caused by Environmental Factors
Known types of mental deficiency caused by exogenous factors are not
as many as those genetically determined, but include a higher incidence in
each category.
Mental Defect Due to Infection
Infection may damage the nervous system during intrauterine life, or
during infancy and childhood. Damage varies according to the type of

infectious agent, the age of subject, and the severity of the acute infection.
Among prenatal infections causing mental retardation are rubella,
cytomegalovirus, toxoplasmosis, and syphilis.
Rubella
Infection of the mother during the first trimester of pregnancy may be

transmitted transplacentally to the developing fetus, and damage various
organs and systems, including the developing central nervous system. Clinical
manifestations in the child are microcephaly, cataract, retinopathy, hepatitis
thrombocytopenia, heart defect, and other malformation. Anamnestic data
and the clinical picture make possible a prompt diagnosis. Rubella virus can
be isolated at birth or shortly after. The widespread vaccination of girls
against rubella has considerably reduced the incidence of this condition.
Cytomegalovirus Infection
This is increasingly recognized as a significant cause of mental
retardation. Usually the disease develops during intrauterine life. Apparently

nonimmune women who acquire the infection during pregnancy are the most
likely to transmit the disease to the fetus. Mild microcephaly is the major
clinical manifestation. Chorioretinitis, intracranial calcification, and

hepatosplenomegaly may be present. Mental deficiency varies from mild to
severe. Excretion of the virus may persist for months after birth. Treatment is
of little avail but preventive vaccination has been attempted.
Toxoplasmosis
Transplacental intrauterine transmission of toxoplasmosis is well
known although its frequency has not been established. Clinical
manifestations in the child consist of microcephaly or, at times, hydrocephaly,
with intracranial calcifications. Chorioretinitis is common, cataract, glaucoma,
or micropthalmia may be present. Mental retardation is often severe. There is
no satisfactory treatment of the disease although the toxoplasm responds to

certain sulfa drugs.
Syphilis
Congenital syphilis is the classical example of prenatal infection causing
mental deficiency—but its symptoms and signs—saddle nose, notched teeth,
interstitial keratosis, deafness, bone lesions and others—are rarely seen
among mentally retarded. On the other hand, positive serology in a mentally
defective is no evidence that the intellectual impairment is due to syphilis. A
peculiar, but today rare, type of congenital syphilis is “juvenile paralysis.” This
serious deteriorating disease, due to multiplication of the syphilic agent in the
brain, shows progressive mental defect, motor paralyses, and often epilepsy.
Encephalitis in Infancy or Childhood
Encephalitis is not rare in children and the accompanying brain damage

may result in various degrees of mental retardation. The clinical history of the
acute phase is usually characteristic and dramatic. Upon recovery from the
acute episode, mental retardation becomes apparent. It is rarely progressive

and, in fact, is often regressive. A first group of encephalitides is caused by
neurotropic viruses of which many are known.
A particularly severe form is the herpes encephalitis in newborn,
probably acquired during delivery from the infected genitalia of the mother.
A second group of encephalitis is due to bacteria and is usually
associated with meningitis. The increasing use of antibiotic treatment during
the acute phase of bacterial meningo-encephalitis has resulted in a dramatic
decrease of the death rate but in a noticeable increase of the number of
partially recovered, and often defective, children.
A third group of encephalitides follows common diseases of childhood

such as measles, scarlet fever, or chickenpox. Brain involvement usually
develops after the original disease has subsided. An allergic mechanism is
apparently responsible for this encephalitic reaction.
The clinical picture of the postencephalitic retardate shows a few
distinct features indicative of the type of the original disease. Evidence of
brain damage often present includes paresis, spasticity, speech defect,

disturbance in eye movements, and behavior alterations. The degree of
mental retardation varies considerably from case to case and usually cannot
be correlated with the type of encephalitis.
Mental Retardation Clinical Syndromes
In numerous clinically characteristic types of mental deficiency, the data

are not sufficient to establish the genetic or environmental nature of the
condition.
De Lange Syndrome
Moderate microcephaly and small stature are usually present. Facies is
characterized by bushy eyebrows with synophrys, small upturned nose, wide
philtrum, low set ears, small mouth, and small chin. There is inability to
extend the elbow completely. Syndactily, micromelia oligodactily, actodactily,
and clinodactily are often present. Characteristic is a shortening and proximal
placement of the thumb. Hirsuitism is common. Mental deficiency is usually
severe.
Rubinstein-Taybi Syndrome
Mild microcephaly, hypertelorism, strabismus, antimongoloid slant of

the eyes, beak nose, and high palate are common features. The most
characteristic trait consists of broad terminal phalanx of the thumb or first
toe. At times duplication of the first toe is noted. Laxity of joint ligament,
hyperactive reflexes, stiff gait, and unfrequent seizures are other signs.
Mental retardation is always present.
Sturge-Weber Syndrome
This is easily recognized because of the presence of angioma covering
unilaterally a usually large area of the face. This is accompanied by a calcified

angioma of the meninges in the occipital region on the same side as the facial
angioma. Associated angioma of the choroid with glaucoma is not rare.

Epilepsy is common and hemiplegia often develops. The disease is slowly
progressive. Mental retardation is generally present but its severity varies
considerably.
Praders Syndrome
This consists of small stature, striking obesity, particularly in the lower
parts of the body where characteristic cuffs around the ankles usually
develop. Feet and hands are very small. Secondary sex characteristics are
underdeveloped. There is characteristic muscular hypotonia, particularly in

infancy. Mental retardation is usually moderate. Diabetes has often been
observed in adult patients.
Sotos Syndrome
This is characterized in infancy by the very large proportions of height

and weight which are above the 90 percentile. Therefore the term “cerebral
gigantism.” The head is also large and often dolicocephalic in shape. There
are, in addition, hypertelorism, antimongoloid slant of the eyes, drooping
eyelids, large ears, and prognathism. Various degrees of mental retardation

are noted. The adult patient may have normal height and weight.
Beckwith-Wiederman Syndrome
Large tongue, omphalocele, large kidneys, and a large liver in a large
body are distinct features. Hypoglycemia at birth and polycythamia are often
seen. A common finding is hyperplasia of endocrine glands. Mental
retardation is not always observed and when present is not severe.
Angelmcin Syndrome
This curious condition (happy puppet syndrome) is recognized by

peculiar paroxysms of unjustified laughter and severe mental retardation.
Other signs are microcephaly with flat occiput, hypertelorism, prognathism,
muscular hypotonia with hyperreflexia, and incoordinated, jerky movements.
Epileptic seizures are usually present. A curious trait is the tendency of the
child to protrude the tongue for long periods of time.
Williams-Beuren Syndrome
A so-called “elfin face” is characteristic of the syndrome with

hypertelorism, epicanthus, upturned small nose, wide mouth, full cheeks, low-
set ears, and small chin. Hypercalcemia and supravalvular aortic stenosis are
features of the syndrome. Mental retardation, which is not always present, is

usually moderate.
Bibliography
Crome, L. Pathology of Mental Retardation. Baltimore: Williams & Wilkins, 1971.
Gellis, S. S. and M. Feingold. Atlas of Mental Retardation Syndromes. Washington: U.S. Department
of Health, Education, and Welfare, 1968.
Holmes, L. B., H. W. Moser, S. Haldorsson et al. Mental Retardation: An Atlas of Disease with
Associated Physical Abnormalities. New York: Macmillan, 1972.
McKusick, V. A. Mendelian Inheritance in Man, 3rd ed. Baltimore: The Johns Hopkins University
Press, 1964.
Moser, H. W. and P. A. Wolf. The Nosology of Mental Retardation. Baltimore: Williams & Wilkins,
1971.
Penrose, L. S. The Riology of Mental Defect, 3rd ed. New York: Grune & Stratton, 1963.
Stanbury, J. B., J. B. Wyngaarden, and D. S. Fredrickson. The Metabolic Basis of Inherited Disease,
3rd ed. New York: McGraw-Hill, 1973.
Stevens, H. A. and R. Heber. Mental Retardation. Chicago: University of Chicago Press, 1964.
Vinken, P. J. and G. W. Bruyn, eds. Handbook of Clinical Neurology, Vols. 10, 13, and 14. New York:
American Elsevier, 1973.
PART TWO
Psychosomatic Medicine
Chapter 21
Changing Theoretical Concepts In Psychosomatic

Medicine1
Morton F. Reiser
Introduction
Ever since man first experienced a sense of self-awareness, he has been
intrigued with the challenge of understanding the relationship of mind to

body, and has worked diligently toward developing empirically based
conceptual solutions to the mystifying problems it presents. To this day, the

problem eludes solution. The early history of these efforts has been reviewed
and this account will pick up the thread of the story toward the end of World
War II when experiences in military psychiatry were generating considerable
serious interest in dynamic psychiatry and in exploring the interrelationships
between mind and body in the etiology and pathogenesis of physical as well
as mental disorders. This chapter takes an historical perspective and is

presented in three parts. It begins with a review of earlier theories and the
empirical context from which they emerged. It emphasizes the important
clinical psychiatric observations and attempts to define some of their
limitations for theory, while underlining those aspects of earlier data and
theory that seem still to be relevant and cogent. Part 2 reviews findings that
for the most part followed the main portion of earlier theory construction,
though in fact the time periods overlap, Part 1 roughly covering 1940-1960
and Part 2, 1955-1972. The work of this second period immensely widened
our data bases and added important new dimensions to available information
about the interrelationship between physiological and psychological aspects
of bodily function both in health and in disease. Accordingly, it forces
reconsideration of earlier theoretical ideas and calls for drastically modified,
if not entirely new, formulations. Part 3 begins with the conclusion that it is
not possible at this time to construct a satisfactory and empirically sound

general theory of etiology and pathogenesis. Rather, attempts are made in the
last part of the chapter to extract a general conceptual scheme for

approaching the problem of understanding man in health and disease.
Throughout the chapter an effort is made to offer some suggestions as to

possible shapes and directions for future work and theory construction, and,
wherever possible, to bring older ideas into perspective in regard to present

thinking.
Part 1: Earlier Theories
In the first part of the epoch bounded roughly by the years 1940-1960,
work proceeded mainly along two lines. First there was combined medical
and psychological investigation of selected medical patients. This work aimed
at identification and elucidation of the role of psychological conflict (and
emotional arousal) in etiology and pathogenesis of medical illness, and in
influencing the course of disease, for example, as in inducing remissions or

exacerbations or in affecting the rate of progression. Meticulous and detailed
combined clinical studies by internists and psychiatrists (Weiss, Engel, Ferris,
Wolff, Wolf, Grace, Mirsky, Romano, Levine, Rosenbaum, Saslow, Lidz, and
Binger, to name just a few) demonstrated beyond a doubt that many medical
diseases first became clinically manifest during periods of psychosocial crisis
and that the course of disease can indeed be profoundly influenced by

psychological factors. Complications were observed to occur in conjunction
with serious psychological stress, disease processes were observed to

accelerate during periods of sustained psychosocial turmoil, and remissions
were observed in conjunction with periods of relative psychological
tranquility. Further it become clear that the doctor-patient relationship by
modulating and ameliorating psychological distress of patients could exert
beneficial effects on the symptoms and progression of illness, and could at
times augment desired pharmacologic effects of drugs (converse effects were
observable as well, albeit with some reluctance on the part of clinicians.)
Relationships of this nature are regularly observed in hospitals and clinics
when healthcare personnel are interested and when they have been trained
to observe and to listen. The limited implications of such observed
relationships for theories of etiology and pathogenesis will be discussed
below.
The second major line of investigation was more experimental and
involved the study of patients at first, and “healthy” subjects later, in the
clinical psychophysiological laboratory. Although many variations were
developed, the basic experimental design consisted of continuous, or
repeated, measurements of (relevant) physiological functions during periods

of “base line” or “rest” and during periods when attempts were made to
manipulate the patient’s or subject’s emotional state by discussing conflictual
topics and/or by exposing him to stimuli designed to elicit specific affects, e.g.,
anger, anxiety, etc. In this way virtually every tissue and organ of the body
innervated by the autonomic nervous system and available for observation or
intubation, or accessible to electronic recording from surface or depth
electrodes in unanesthetized humans, was shown to be capable of

considerable functional variability in reaction to a wide variety of provocative
experimental manipulations. The ultimate goal of such experiments was to
produce measurable functional changes experimentally in target organs that
would mimic or reproduce pathological-physiological patterns of function
associated with specific disease states, e.g., gastric hyperacidity and
hypermotility, tachycardia, elevated blood pressure, changes in measures of

external respiratory dynamics, etc. In fact, it has been possible to
demonstrate repeatedly that a wide variety of impressive physiological
changes may be so induced but not with the degree of regularity,

predictability, and experimental control required for rigorous support of
specific etiologic and/or pathogenic hypotheses. As our experience and
sophistication have increased, innumerable technical, methodological, and
experimental variations on the basic theme have evolved, but a myriad of
highly complex problems (control, instrumentation, data reduction, statistical
evaluation, and interpretation) connected with such experiments remain, and

their limitations for contributing to the solution of problems of etiology and
pathogenesis are indeed still considerable.
The central theoretical issue of the epoch (1940-1960) was specificity.
What determines whether a patient falls ill of one disease rather than another
(why peptic ulcer instead of rheumatoid arthritis, for example)? More to the
point in the context of psychosomatic medicine, do specific psychological

factors constitute necessary and/or sufficient factors in determining choice of
organ system and disease? Specificity in this sense refers to a different
phenomenon from that observed in individual patients whereby a repetitive
theme may be repeatedly activated at critical points in the history of the
disease, making it a repetitive “core issue” for the particular patient, but not
generalizable to others. In retrospect it is clear that the clinical and laboratory

findings of the period under discussion implicated both specific and
nonspecific mechanisms, but more attention and interest was directed to the
search for specificity.
Before undertaking a review of the major theories that represented this
point of view, it might be well to mention first some of the more general
conceptual issues and problems that complicate the field and frustrate
attempts to build and evaluate theory. Regardless of our ultimate conviction
that mind and body constitute a true functional unity, the fact remains that as
observers, investigators, and theorists, we are obliged (whether we like it or
not) to deal with data from two separate realms, one pertaining to mind and
the other to body. The science of the mind and the science of the body utilize
different languages, different concepts (with differing levels of abstraction
and complexity), and different sets of tools and techniques. Simultaneous and
parallel psychological and physiological study of a patient in an intense
anxiety state produces of necessity two separate and distinct sets of

descriptive data, measurements, and formulations. There is no way to unify
the two by translation into a common language, or by reference to a shared
conceptual framework, nor are there as yet bridging concepts that could
serve, as Bertalanffy suggests, as intermediate templates, isomorphic with
both realms. For all practical purposes, then, we deal with mind and body as
separate realms; virtually all of our psychophysiological and psychosomatic

data consist in essence of covariance data, demonstrating coincidence of
events occurring in the two realms within specified time intervals at a
frequency beyond chance. Such findings—our very best ones— tell us nothing
in and of themselves about time sequences or causality as ordinarily
understood in a linear sequential model. Confronted, then, by covariance
findings of this nature, for example an association between a specified
dysphoric affect or mood state and the development of a bodily lesion, such as
a duodenal ulcer, there are essentially four conceptual schemes that can be
evoked to relate the physical to the mental findings (see Figure 21-1). First
we might say that there is no more than a coincidental relationship between
the psychological and somatic spheres (Figure 21-1 (a)); in essence the
duodenum represents a constitutional “weak link in the chain,” hence that
part of the body is expected to break down in response to stress of any type. A
second model would postulate a somatopsychic sequence stating that the
dysphoric state represents a psychological response to the organic lesion

(Figure 21-1 (b)). A third model would postulate a psychosomatic sequence
stating that the physiological changes accompanying the dysphoric mood are
pathogenic and, if sustained, lead to peptic ulceration of the duodenal mucosa
(Figure 21-1 (c)). (Both of the preceding models would also allow for
secondary reactive sequences in opposite directions, allowing for feedback
from psyche to soma in the first instance, or soma to psyche in the second,
thus explaining cyclic (escalating) feedback reactions such as pain, anxiety,
spasm, increased pain, etc.) Finally there is a fourth conceptual model which
states that the coincident psychic and somatic phenomena in fact represent
separate and parallel reflections of a common underlying constitutional

factor(s) usually postulated to be related to genetic and early experiential
factors (Figure 21-1 (d)). Such a model also allows for secondary reciprocal
interplay between the psychic and somatic spheres, as in the preceding two
schemes. In essence this is a somatopsychosomatic model.
Figure 21-1.
Figure 21-1.
Conceptual schemes for relating covariant physical and psychological

findings in psychosomatic research. (For explanation see text.)
Another source of theoretical confusion can arise from overlooking the
fact that there are at least three phases or epochs in the natural history of any
disease. These are probably best considered separately when attempts are
made to reconstruct pathogenesis. First is the period preceding manifest
clinical appearance of the disease. During this period interest centers on
predisposing causes, i.e., the various possible combinations of constitutional
(genetic and experiential developmental) factors that may be thought of as

programming a capacity for a specific disease into the organism. The second
phase is that of the actual onset or precipitation. Here interest centers on the
forces and mechanisms that precipitate the illness. These ordinarily need be
in force only for relatively short periods of time, and need not be (and usually
probably are not) the same as those involved in generating predispositions; of
course the physiological mechanisms involved in different diseases must be
quite different from one another. Third is the last epoch, i.e., the period
following the establishment of the disease process. Here interest is on those
factors and mechanisms influencing the course of the disease, such as
remissions, exacerbations, accelerations, and so on, and these again may be
expected to be different from those involved in the two preceding phases. For
example, once a disease has become established and the individual has
become aware of it, knowledge of the lesion and sensations related to it

become incorporated into the self-image and are then subject to symbolic
elaboration and incorporation into preexistent conflictual psychological

structures. In the somatic realm, as a disease progresses, the role and
importance of a variety of influencing factors may change profoundly. For
example, the potential of salt to aggravate or accelerate the course of long-
standing established essential hypertension in a patient with considerable
loss of renal reserve, is very much greater than it is in a patient much earlier
in the course of essential hypertension whose renal reserve is still within
normal limits. Likewise, in essential hypertension the relative and
proportional contributions of neurogenic and humoral factors in maintaining
increased peripheral resistance change with time. In duodenal ulcer scarring,
pyloric sphincter hypertrophy, sclerosis of blood vessels, etc., all change

markedly with time, and play increasingly important roles late in the course
of the disease, whereas they may well have been negligible factors earlier in
the course. The main point is that both the psychological and the
physiological medical data differ in fundamental and important ways,

depending upon the phase of the natural history of the disease that is under
study, and it clearly may be misleading, and probably quite incorrect, to
assume that analysis of the circumstances and mechanisms involved in

precipitation of an illness, or in influencing its course (no matter how
thoroughly studied and formulated), would necessarily bear any direct
relevance for understanding the mechanisms that had been involved in

establishing predisposition. A priori, one might very well expect that in
considering predisposing factors, disease-specific influences might very well
overshadow nonspecific mechanisms in importance, whereas it is entirely
plausible that mechanisms involved in precipitating the onset of disease, and

in influencing the course of disease once established, might involve
nonspecific mechanisms more importantly. These matters will be discussed
further at the end of the chapter.
Turning now to a review of the major theories of the 1940s and 1950s,
as noted above, the issue of specificity captured the imagination and attention
of the major workers of that period. Generally speaking, the observations of

experienced clinicians working at that time strongly suggested that it would
indeed be both rational and worthwhile to search for specific elements in the
personality structure and psychological life of patients that might participate
in etiologic and pathogenic processes and contribute to the choice of
symptoms and illness. Not only general clinical experience, but systematic
profiles of personality (obtained either by structured interview, or projective
and inventory-type psychological tests), led to the inescapable conclusion
that patients with certain medical disorders, for example, duodenal ulcer, do
in fact resemble one another psychologically more than they do members of

the general patient population, or homogeneous groups of patients with other
specified diseases. George Engel described the situation very aptly by stating
that, if one tells an experienced clinician that he has a patient with ulcerative
colitis, the clinician might very well give a surprisingly accurate thumbnail
personality sketch of that patient without ever having seen him. The
converse, however, Engel is quick to point out, does not hold, that is, given
even a detailed account of the patient’s personality, it is by no means possible
to predict with any degree of confidence what disease, if any, the patient
might have. A major question, of course, is whether the psychological
personality features, shared by patients with the same disease, may not be
shared because they, in fact, arise in reaction to the disease and hence would
be expected to be shared. A more subtle but nonetheless cogent question is
whether such shared somatic-psychic features may arise in response to an
implicit perception or awareness of vulnerability or predisposition even

before the disease becomes clinically manifest. This question is posed in
beginning the review of the early specificity theories, since it is of central
importance in a discussion of linear sequential cause-effect models, as in fact
all of these early theories are. It is now generally appreciated that this critical
question is unanswerable in retrospective studies, and probably only partially
answerable in most longitudinal prospective studies that are feasible of

execution in clinical investigations with human subjects. As will be clear later,
with respect to more recent field theories, such as currently obtain generally
in human biology, this question is much less important, at least in this
particular form.
One of the first and most detailed attempts to relate personality to
specific illness was the “personality profile” proposed by Flanders Dunbar.

While its extensive clinical observations were quite accurate, its clinical and
theoretical utility turned out to be very limited, and it is now generally
regarded as having mainly historical interest and importance.
A second important theoretical framework emerged from the extensive

research program headed by Harold Wolff and his collaborators. The full
scope of his investigations can only be appreciated by consulting some of the
major original publications such as Human Gastric Function, the classic study
of a patient with a gastric fistula by Harold Wolff and Stewart Wolf. In essence
Wolff postulated that stress diseases arise as part of the human physiological
reaction to stress, i.e., “forces or individuals that jeopardize the life or love of
a human being . . . which interfere with the realization of his aspirations and
needs or block the exercise of his potential. These threats are reacted to by
mobilization of an individual’s defenses.” [p. 1059] Thus, the bodily reactions
were regarded as having been set in motion as adaptive, protective, or

defensive or offensive responses, depending upon the subject’s nature, his
past experience, and the situation. “They are more or less effective and more
or less costly to the individual, depending on these and other factors, such as
the nature and integrity of the structures participating in the protective
reaction.” [p. 1060] Wolff and his co-workers postulated patterns of defensive
reactions which, they felt, were specifically associated with defensive
responses, in particular organ systems, and affecting specified functions such

as eating, ejection-riddance, etc. The psychological formulations were based
upon personality features and behaviors that were directly observable with
minimal or no inference, and that pertained primarily to conscious layers of
the patient’s personality function and life experiences. Further focus was on
psychological observations that could be carried out simultaneously with
detailed study and observation of the patient’s clinical status, and with
measurement of the function of affected organ systems in the physiological
laboratory. Naturally, the formulations looked and sounded quite different
from those of contemporary psychoanalytic investigators (as will be noted

below) but in retrospect, it can be seen that the specificity formulations of
Wolff and of Franz Alexander, in particular, are in fact quite compatible in
regard to the central themes, though they differ considerably in respect to the
level of mental functions emphasized, in the amount of inference involved in
constructing theory from observation, and in the dynamic richness and scope
of the formulations, as well as the .ease with which such formulations could
be apposed to (or fitted with) concurrent measures of clinical status and
organ function. For example, the following statement by Harold Wolff

regarding “protective patterns of defense involving eating: the stomach and
the duodenum,” can be compared to Alexander’s formulations (quoted later)

concerning the specific psychological contributions to disorders of the same
organs. Wolff states:
One of the earliest aggressive patterns to manifest itself in the infant is that
associated with hunger and eating. In later life, this pattern may reassert
itself in certain individuals when they feel threatened; at such times of
danger, feelings of anger and deprivation, of longing for emotional
support, or of need for being “cared for,” may be repressed by the equally
insistent assertion that the individual is strong, independent, capable of
doing alone, or standing ‘on his own feet,’ either through actual
deprivation of emotional support or an unwillingness to accept it. This
feeling state shows itself in the stomach as one of readiness for eating;
hypersalivation may also occur. The gastric hyperfunction associated with
these feelings is manifested by increased blood flow, motility, and acid
secretion. Under such circumstances the mucous membrane was found to
be unusually fragile. The hyperdynamic state of the stomach was found to
be associated with symptoms, namely heartburn and localized epigastric
pain, relieved by food and soda whether or not ulceration was present, [p.
1064]
Later, two of Wolff’s students, Grace and Graham, formulated a
derivative hypothesis which they named “specificity of attitude” hypothesis.

This hypothesis states that there is associated with each psychosomatic
disease a specific attitude toward the life events that precipitate the first
appearance or later exacerbations of the disease. Attitude was defined as: “(1)
How a person perceives his own position in a situation—what he feels is

happening to him, and (2) What action, if any, he wishes to take.” [p. 159] It
was postulated that attitudes are different for different diseases but that all
persons with a given disease would have the same attitude. For comparison
with the Wolff and Alexander formulations, the attitude leading to duodenal
ulcer was described by Graham as “felt deprived of what was due him and
wanted to get even (didn’t get what he should, what was owed or promised,
and wanted to get back at, get revenge, do to him what he did to me).” Thus,
Graham and his co-workers extracted from a broader formulation a distilled
statement about attitude which then could be tested quite explicitly by a
variety of techniques, including induction of attitudes under hypnosis, while
measuring appropriate bodily system responses, as well as by postdiction
from interview material by blind raters— postdiction which would match

patients with diseases by detecting evidences of “specific attitudes” in the
interview material.
Franz Alexander and his associates in 1932 began a series of
psychoanalytic studies of patients suffering from chronic organic ailments in
which emotional conflicts were thought possibly to play an etiologic role

either as primary or contributing factors. Alexander’s studies utilized mainly
the investigative method of psychoanalysis and proceeded on the basis of a
fundamental distinction between “visceral neurosis” and conversion hysteria

which he first articulated in 1939. Freud, in his studies on hysteria with
Breuer in 1895, had demonstrated that specific unconscious contents could
be symbolically expressed in the body language of somatic symptoms through

the mechanism of conversion. In 1910, Freud also noted that there could be
mechanisms other than conversion whereby unconscious attitudes might
alter physiological functions without symbolizing any definite psychic
meaning, but did not further specify their possible nature. Alexander
formalized the distinction between hysteria and the “visceral neuroses,” a
term he used in referring to those disorders which were identified with the
field of psychosomatic medicine. He pointed out that whereas in conversion
hysteria symptom formation acts to resolve unconscious conflict, in the
visceral neuroses, the basic conflict remains unresolved; he postulated that
the chronic affect associated with unresolved conflict, even though repressed
or suppressed, would nonetheless be accompanied by its (appropriate)
physiologic concomitants. Alexander theorized that the physiological changes
accompanying the chronic emotions associated with unresolved conflict were

the physiological changes then that would give rise, first to altered function in
the appropriate organ systems and, if long enough sustained, to alterations in
structure and disease. Thus, for each of the seven diseases that he and his
colleagues studied, a formulation of specific conflict was derived from the
clinical data produced in the course of psychoanalytic treatment and/or
investigation. For comparison with the preceding formulations, Alexander’s

formulation regarding duodenal ulcer is quoted below:
The central dynamic feature in duodenal peptic ulcers is the frustration of

dependent desires originally oral in character. The craving to be fed
appears later as a wish to be loved, to be given support, money, and advice.
This fixation on early dependent situations of infancy comes in conflict
with the adult ego and results in hurt pride, since the infantile craving for
help is contrary to the standards of the adult, to his wish for independence
and self-assertion. Because of this conflict, the oral craving must be
repressed. Oral receptiveness when frustrated often changes into oral
aggressiveness, and this also becomes repressed because of guilt feelings it
provokes. Both oral dependent and oral aggressive impulses may then be
frustrated by internal factors—shame and guilt.
The most common defense against both oral dependent and oral
acquisitive impulses is overcompensation. The latently dependent or
acquisitive person overtly appears as an independent, hard-working
individual who likes responsibility and taking care of others. He responds
to challenges with increased activity and ambition, works hard and
assumes greater and greater responsibilities. This in turn increases his
secret longing to lean on others. To be loved, to be helped is associated
from the beginning of life with the wish to be fed. When this help-seeking
attitude is denied its normal expression in a give-and-take relationship
with others, a psychological regression takes place to the original form of a
wish to ingest food. This regressive desire seems to he specifically correlated
with increased gastric secretion. (Italics mine.)
Not all patients suffering from duodenal ulcer overcompensate for their
dependent desires with an outward show of ‘go-getting’ activity. Many of
them are overtly dependent, demanding, or disgruntled persons. In such
individuals, the dependent tendencies are frustrated not by internal
repudiation, but by external circumstances. But even in these overtly
demanding patients, a definite conflict about dependent cravings can be
discovered. The crucial psychological finding in all ulcer patients is the
frustration (external or internal) of passive, dependent, and love-
demanding desires that cannot be gratified in normal relationships.
Onset of illness occurs when the intensity of the patient’s unsatisfied

dependent cravings increases either because of external deprivation or
because the patient defends against his cravings by assuming increased
responsibilities. The external deprivation often consists in the loss of a
person upon whom the patient has been dependent, in leaving home, or in
losing money or a position that had given the patient a sense of security.
The increased responsibility may take the form of marriage or the birth of
a child or the assumption of a more responsible job. [pp. 15-16]
The other six diseases studied by the Chicago psychoanalytic group of
Alexander, were bronchial asthma, rheumatoid arthritis, ulcerative colitis,
essential hypertension, neurodermatitis, and thyrotoxicosis. For each specific
psychodynamic constellation, there was postulated also a specific related
“onset situation” i.e., the life conditions preceding illness that affected
patients emotionally at the time of onset (by reactivating old conflicts); and a
third factor which Alexander designated an X factor by which he meant a

constitutional vulnerability of a specific tissue, organ, or system. This then
was a multiple factor model in which each of the three factors was considered
a necessary but not sufficient cause, with the development of manifest disease
depending upon presence and activation of all three in appropriate
combination. In Alexander’s words, the operational hypothesis of this work
could be reduced as follows: “A patient with vulnerability of a specific organ
or somatic system and a characteristic psychodynamic constellation develops

the corresponding disease when the turn of events in his life is suited to
mobilize his earlier established central conflict and break down his primary
defenses against it. In other words, if the precipitating external situation

never occurs, a patient may, in spite of the presence of the predisposing
emotional patterns and of organ vulnerability, never develop the disease.” [p.
77]
This then was a linear psychosomatic theory (Figure 21-1 (c)). A central
feature to note is the postulation that the pathogenic physiological changes

involved were conceived of as physiological concomitants of emotion, such as
are encountered in mature adult organisms and patterned on the fight-flight
physiology of Cannon, namely sympatho-adrenal and/or parasympathetic
activation. For example, essential hypertension was seen as resulting from
chronically suppressed and repressed rage with concomitant sympatho-

adrenal activation and elevation of blood pressure, such as might be seen in
acute rage attacks; gastric hypermotility and hypersecretion of acid were
seen as the physiological concomitants of vagal stimulation accompanying

repressed and suppressed longing for love (equated with longing to be fed).
These psychophysiological characteristics of the theory appear as well in the
formulations of Harold Wolff and his co-workers.
In retrospect, these early specificity formulations appear rather narrow
and oversimplified; to a large degree this may be the result of preoccupation

with what we now realize to be a relatively narrow and limited sector of the
field. While giving little more than lip service to multiple-factor concepts,
these early writers limited their attention to predominantly intrapsychic

issues and proximate interpersonal transactions in the psychological realm,
and to peripheral autonomic effector mechanisms and end-organ systems in
the physiological realm, while relatively little attention was paid to external
social systems, to central nervous system mechanisms, or to cellular and

molecular biological phenomena. In other words, the formulations may have
been premature in the sense that they will have turned out to be incomplete
and overinclusive rather than intrinsically incorrect.
Other psychoanalytic investigators of the same time period, particularly

Grinker, Schur, and Deutsch, were impressed not only with the ubiquity in
“psychosomatic” patients of core conflicts around pregenital issues (as
Alexander had been) but also with the extensive and impressive evidence of
regression and primitivization of ego functions in these patients, particularly
at the time of the life crises associated with precipitation and/or aggravation
of the disease and during periods of prolonged active illness. Impressed by
the resemblance of pathological physiological function in “visceral neurosis”

to the labile relatively unmodulated patterning of physiological responses in
infancy and very early childhood, they speculated about its possible
significance. Their (essentially epigenetic developmental) theories regard the

pathological physiology of psychosomatic diseases as being patterned
according to the physiology of infancy and early childhood and postulate the
physiological anlagen (X factors) to be constitutional (genetic and early

experiential), possibly or probably fixed or programmed into the organism by
coincidence (conditioning), and later reinforced in the mother-infant and
child-family interactive relationships during development. Two of the
investigators of that era, Margolin and Szasz, also were impressed with the
primitive “regressive” nature of the physiology, and Szasz spoke of
“regressive innervation.” These theories stand in sharp contrast to
Alexander’s theory in two ways: (1) they utilize transactional field rather than
linear models, and (2) they postulate the physiological components to be
more primitive and less well regulated than the adult patterns evoked in
Alexander’s theory. Grinker postulated an infinite series of progressive stages

of differentiation of body systems from psychosomatic unity at birth to the
highly complex differentiated and integrated adult organism. He saw a
breakdown in adaptation involving progressive dedifferentiation of varying

degrees regressively back through stages of psychosis and various
psychosomatic disorders all the way to primitive disorganized and
overwhelming panic states (roughly equivalent to the neonatal conditions of
total response). Schur conceptualized the progressive maturation from
infantile “psychosomatic unity” as occurring in two spheres: (1) progressive
desomatization of reactions to danger in the physiological sphere (a gradual

refinement from general chaotic uncontrolled total-body responses to the
finely modulated, discrete and homeostatically balanced responses of the

adult, such as “signal anxiety”), and (2) progressive refinement from primary
process thinking to secondary process-controlled thinking (mediated and

modulated by small discrete quantities of “delibidinized and deaggressivized”
energy) in the psychologic sphere. He emphasized that the ego reacts

simultaneously to danger in two ways: evaluating danger and responding to
danger. If failure of defensive ego functions under stress and reactivation of
unconscious conflict occur, he postulates that danger signals are increasingly
evaluated along progressively more (primitive symbolic) primary-process
modes and also that there is a concomitant (but not necessarily entirely
synchronous) “resomatization” of the response. As the resomatization
proceeds to primitive levels, old infantile patterns of bodily response can be
reactivated and result finally in disease (the specific organs and processes
involved having been predetermined by constitutional factors). He
considered that alterations in “ego state” in reaction to stress were of utmost

importance in permitting and/or promoting emergence of primitive
pathophysiological patterns of function that could then lead to disease.
Deutsch also emphasized return to infantile, or primitive developmental
points of physiological “fixation” and was, at the same time, quite impressed
with the primitive body language (symbolism) encountered in psychosomatic
patients and included important elements of pregenital conversion as well as
conditioning and genetic endowment in his thinking about specificity of organ

and symptom choice. Needless to say, none of these theoretical systems is
amenable to empirical testing (given the present “state of the art”) but they
do bear an interesting conceptual compatibility with many of the newer

biological findings to be reviewed later.
A few psychoanalytic clinical investigators, such as Garma and Sperling

have continued the conceptual tradition begun with Groddeck that considers
psychosomatic visceral disorders to arise mainly on the basis of symbolic
conversion mechanisms. The observations and rich clinical data about
symbolic significance of bodily symptoms and changes are not in question;
they are prominent in the data whenever clinicians work at psychological
depth with medical patients. But these theories regarding pathogenesis are
neither empirically testable at present, nor are they readily reconciled
conceptually with recent developments in the biology of disease, nor as noted
earlier is it possible in a retrospective historical study to distinguish whether

such psychological meanings occur as reactions to the presence and
knowledge of illness or whether they antedated illness and may have
contributed to its genesis.
The work and the theories of several investigators of this epoch have
been reviewed in considerable detail not only because they are considered to
be important and representative (and responsible for stimulating a highly
productive era of psychophysiological research); but also because many of
the main ideas contained in them should ultimately be brought into proper
perspective and reconciled with more recent findings and theoretical models.
This period produced an enormously rich yield of carefully detailed and
documented observations, and of derivative formulations. Many of the clinical
observations themselves have been confirmed and replicated many times over
and by this time have been incorporated into the general body of information
about clinical medicine. Many of the psychodynamic formulations,
particularly Alexander’s work, have been supported as valid psychological
findings and formulations by other investigators (Mirsky, Weiner, Dongier,
Wittkower et al., Wallerstein et al., see below). On the other hand, original
psychosomatic formulations regarding the direct role of specific

psychodynamic factors in etiology and pathogenesis of disease have not fared
as well in attempts to validate them in careful and often highly sophisticated
and elaborate clinical research. Yet at the same time there has been enough
partial empirical support to preclude their being summarily dismissed. It
seems certain that future theories will have to account for the observations,
and it is also likely that the general shape of the major hypotheses may still be
discernible in future formulations albeit with different emphases and
perspectives, when information from broader data bases and newer systems
and transactional theoretical models are taken into account.
Part 2: Modern Developments,
1955-1972
As noted earlier, the work of the first part of the epoch 1940-1960
concentrated mainly on intrapsychic mechanisms, peripheral autonomic and
humoral mechanisms in control of target organs and organ systems, and
phenomena that seem to bear directly on the issue of specificity, with less
attention being paid to broader interpersonal and social ecological factors, to
the role of the central nervous system (CNS) in mediating between cognitive
emotional and peripheral neurovegetative effector mechanisms, to cellular

and molecular biologic processes, and to mechanisms of genetic transmission.
And there were relatively few studies concerned with dissecting mechanisms
and relative contributions of genetic transmission, neonatal, early infant, and
child development in determining “constitutional” predisposition, and with

the role of nonspecific bodily responses in medical pathogenesis. All of this
has changed radically with the tremendous expansion of information that has
occurred in the human life sciences and neurobiology since the mid 1950s.
Technical breakthroughs in electronics and instrumentation, along with the
rapid development of computer science, have now made it possible to
investigate biological processes that previously had been inaccessible to

experimental analysis, and to obtain answers to questions that were
previously out of reach. Currently there is a much fuller appreciation of the
fact that understanding states of health and disease requires understanding
of biological, psychological, and social parameters to be complete. More
investigators and theoreticians are appreciative of the obligation to address
the complexity of interacting factors and mechanisms in these three spheres

as they contribute to the development of an actual phenotype from a
genotypic blueprint. This broadened understanding has made it clearer than
ever that mind and body cannot be regarded, or dealt with, as separate much
longer despite our bondage to Cartesian dualism. Corollary to this is the
recognition that subclassification or distinction of psychosomatic from other
disorders is rapidly losing (perhaps has already lost) its meaning and utility.
The next section will review selected sectors of clinical and related
neurobiological research that have contributed to newer perspectives in the
field. It is not intended to be a fully comprehensive review, but rather to

concentrate on selected fields of study and data that have had major impact
on our perspectives regarding relations between mind, brain, and body.

Important new work and perspectives in the social, epidemiologic, and
transcultural aspects is not included here. For this the reader is referred to
Chapter 25.
Longitudinal “Predictive” Studies of Persons at Risk
This section deals with studies of predisposing (physical and
psychological) factors and of precipitating (psychosocial) factors in
longitudinal studies of populations identified as being at risk for a particular
disease by virtue of possessing known biological markers. The best known of
such studies are those of Mirsky and co-workers on duodenal ulcer which
further refined the Alexander concept. Mirsky identified the physiological
(genetically-determined) condition necessary, but not sufficient, for the
development of duodenal ulcer; that is, the hypersecretion of pepsinogen into

the blood. He postulated that this inborn trait, through its influence on the
mother-infant relationship, would also play a central role in personality
development and in determining the type of social-conflict situation that
would later be pathogenic for the individual in adult life. This, then, is a
circular rather than linear theory, i.e., it suggests somatopsychosomatic
sequences rather than linear psychosomatic ones. It is supported by empirical

data gathered in a study on duodenal ulcer by Weiner, Thaler, Reiser, and
Mirsky in which independently studied psychological data were used to

predict (using Alexander’s formulations of core conflict specific for peptic-
ulcer) which, of a large number of potential ulcer patients (as determined by

pepsinogen level), would actually develop the disease under the psychosocial
stress of basic military training. These data, as noted earlier, lend validity to
the psychodynamic formulations that Alexander and his colleagues derived
from psychoanalytic studies of patients with duodenal ulcer. At the same time
it should be emphasized that these studies by Mirsky et al. do not address the
question of what the physiological mechanisms may be that lead to actual
ulcer formation in the duodenum, and thus do not bear directly at all on the
psychophysiological psychosomatic hypotheses advanced by Alexander et al.
Similarly, partial support of Alexander’s psychodynamic formulations about
thyrotoxicosis is provided by the work of Dongier and Wittkower, and of
Wallerstein et al., which demonstrates an association in euthyroid subjects
between a high propensity of the thyroid to incorporate I and the

psychological personality characteristics described by Alexander et al. in
patients with thyrotoxicosis. The relationship, if any, of this physiological trait
and thyroid disease is not clear, and as Weiner has pointed out, the
psychological traits may be linked with a tendency toward involvement of the

thyroid gland in diseases affecting its secretory function (in either an upward
or a downward direction).
In an unfinished statement written shortly before his death, Alexander

took into account the findings of Mirsky and others on these newer
demonstrated interrelationships of biological, psychological, and social

factors in etiology and pathogenesis and indicated some readiness to modify
his theoretical model:
These three variables—inherited or early acquired organ or system

vulnerability, psychological patterns of conflict and defense formed in
early life, and the precipitating life situations—are not necessarily
independent factors. It is possible that constitution at least partially
determines both the organ vulnerability and the characteristic
psychological patterns. At present little is known about the
interdependence of these two variables. There is strong indication,
however, that the correlation between constitution and characteristic
psychiatric patterns is not a simple one. Constitution alone without certain
emotional experiences of early life, particularly the early mother-child
relation, may not produce a consistent pattern. [P. 17]
The power of such risk studies (which are possible only when biological
“anlagen” such as pepsinogen are known) can be further amplified when

applied to studies of discordant disease incidence in monozygotic and dizygotic
twins. Katz and Weiner point out that risk strategy could be applied in gout
(utilizing hyperuricemia to identify subjects at risk); it might also be
applicable for the study of rheumatoid arthritis, utilizing certain immune
proteins as indicators of risk. Another appropriate application might be in
coronary artery disease where there are multiple factors (such as obesity,
cigarette smoking, exercise habits, heredity, hypertension, blood lipids, etc.)

that are known to affect the risk of myocardial infarction in additive and
combined ways (see Chapter 26). In longitudinal risk studies of coronary
disease, it would seem worthwhile to study in detail both the nature of the
precipitating circumstances, and the psychological personality characteristics

of subjects. Such data might then be useful in helping to clarify: (1) the
relative roles of specific vs. nonspecific ubiquitous psychosocial stress
situations (like bereavement, see below) in precipitation of myocardial

infarction; and (2) the relation of “predisposing” psychological
characteristics, such as the Type A personality of Friedman and Rosenman, to
incidence of myocardial infarction. Does “Type A personality” lead to disease
by making the person’s life stressful, or is it rather a parallel psychological
manifestation of an underlying predisposing constitutional factor that also
leads to coronary artery disease? (Figure 21-1 (d).)
Mortality and Morbidity of Bereavement
Studies on the mortality and morbidity of bereavement exemplify the

emergence of data emphasizing the importance of nonspecific effects of
psychosocial stress on physical health. Rees and Lutkins reported in 1967 on
the study of a small community in Wales in which a cohort of 903 close
relatives of patients who had recently died were identified as experimental

subjects. A group of 878 control subjects from the same community matched
for age, sex, and marital status were also identified. The health of the
experimental and control subjects was followed for one year following death
of the relative or selection as a control subject. During the year of

bereavement the death rate in the bereaved subjects was seven times that of
the controls! A related, and perhaps even more impressive finding was that
the risk of death was twice as high if the relatives had died outside the home
(including in the hospital) than when they had died in the home. A study of
widowers in Britain by Parkes, Benjamin and Fitzgerald yielded similar
results and showed that the majority of deaths in the first six months of
widowerhood could be accounted for by coronary artery disease in subjects
of the appropriate age group. A controlled study by Bennet following the
Bristol flood (July 1968) in Britain demonstrated in the twelve months
following the flood an increase in morbidity and a 50 percent increase in

mortality in subjects whose homes had been flooded compared to those
whose homes had not been so affected! The earlier findings of Engel and
Schmale, demonstrating the high frequency with which real, threatened, or

symbolic object loss and separation precede development of illness of any
type, are quite consistent with the findings of these British investigators.
Taken altogether, the data convincingly demonstrate that bereavement,
object loss, and the associated reactive affective states may have profound
reverberations in the physical sphere, affecting even the capacity to sustain
life itself. The affective and psychological characteristics of these states span a
wide spectrum: natural bereavement, aggravated or serious bereavement,
depression of various types, and include states that Engel and Schmale feel
deserve special designation as “helplessness and hopelessness” associated
with attitudes of “giving up” and “given up.” Engel postulates that there may
be a fundamental biological stress or danger response state in addition to
“fight-flight” which he has named “conservation withdrawal.” He points out

that the metabolic changes associated with such a response would be
anabolic, as opposed to the catabolic activation responses of the “fight or
flight” reaction described by Cannon, which was used as the exclusive
physiological referent for earlier psychosomatic theories. Engel considers
that the physiological changes he postulates to occur in “conservation
withdrawal” would act in an entirely nonspecific manner by rendering the
organism less resistive to a variety of pathogenic factors. While the
physiology of conservation withdrawal as such has not been documented,
there is much evidence that psychoendocrine phenomena may well play an
important role in clinical events of this kind (see below).
Psychoneuroendocrinology
Psychoneuroendocrinology constitutes the third major section for
discussion here. This field of study serves as a major link between clinical and
basic research endeavors. While its main relevance pertains to nonspecific
mechanisms in pathogenesis and precipitation of a wide variety of illnesses, it
may also have some interesting and provocative indirect implications for the
issue of specificity as well. Studies in the psychoneuroendocrine sector
probably more than any other single sector have (1) contributed to our
growing recognition of the overwhelming importance of nonspecific

mechanisms in development of disease; and (2) provided a beginning of
vitally important insights into the fascinating and intricate (still incompletely
understood) mechanisms by which the CNS is able to mediate between higher
mental functions (and psychological responses to psychosocial events) on one
hand, and maintenance of metabolic processes and integrity in body tissues
and systems on the other hand. It has, in fact, provided us with an
overwhelming sense (incomplete in fine detail) of the highly complex
integrated linkages between the limbic forebrain system and (1) the
autonomic nervous system (which extends outward to innervate peripheral
tissue); and (2) the pituitary (via the hypothalamus) and through it, the entire
endocrine system, thus making it possible for the hormones to act as

circulating extensions of the nervous system. These relationships and
linkages are summarized and discussed fully in Chapters 22, 23, and 24 by
Weiner, Hofer, and Mason, respectively. The discussion here will highlight
only some issues that are of interest in the context of this particular chapter.
First is the fact that alterations in endocrine function occurring in

experimental animals in response to psychosocial stresses have been shown
to influence host resistance to a variety of pathogenic organisms and to affect
the viability and rate of growth of implanted neoplastic tissue. In this

connection it should be noted that there is also considerable evidence that
central neurophysiological mechanisms may participate more directly in
these psychosocial stress effects on host resistance by influencing
immunological reactions, including tissue sensitivity to histamine and levels

of circulating antibodies (see Chapter 29 by Schiavi and Stein). It appears
then that the hormones, separately and in combination as described by
Mason (see Chapter 21), may play a role not only in stress and hormone-
dependent diseases, but also in infectious and neoplastic processes as well.
A second important feature is the phenomenon of reciprocity between
the effectiveness of ego defenses and the level of activation of stress hormone
systems (mainly the sympathoadrenal system and the pituitary-adrenal axis).

This was first demonstrated in man in a classic study by Sachar et al. in
patients with acute schizophrenic excitement. Subsequently it has been
shown to operate in a wide variety of both acute and chronic conditions (as
noted in several of the chapters that follow). The demonstration of this

phenomenon has proved to be of fundamental theoretical significance and
brings us a giant step closer to understanding the way in which intrapsychic
phenomena may be interposed between psychosocial vectors on the one hand

and alterations in body physiology on the other. Ego defenses may protect
against excessively brisk endocrine activation by functioning effectively;
conversely vigorous endocrine activation may take place when ego-defense

functions in the psychological sphere are inefficient or totally inadequate. The
clinical significance of these findings is further enhanced when it is realized
that the pathogenic effects of the adrenal steroids may be mediated not only
by their influence on peripheral tissue metabolism, but also in less obvious

but nonetheless highly important ways by their effects on CNS function (to be
discussed below).
Third, the endocrine system, like the autonomic nervous system, shows
evidence of a waxing and waning of its level of activity in association with
regular biologic rhythms— principally the circadian diurnal rhythms, but also
longer seasonal rhythms, the menstrual ovulation cycle in females, and
certain ultradian rhythms such as the 90-min. REM cycle in sleep. Ordinarily
these multiple rhythms, each with different periods, are considered to be in
some way synchronized or accommodated to each other. Curtis has reminded

us that the potential for psychopathological and pathophysiological effects,
when desynchronization between these multiple biologic rhythms takes
place, is just beginning to be appreciated and studied. A number of
investigators, including Sachar, Roffwarg, Heilman, and their associates, have

demonstrated important differences in patterns of endocrine function during
different stages of sleep. They have also shown that there are alterations in
these patterned relationships in patients in active episodes of psychotic

depression. Of related interest are the observations described in this volume
by Hofer (Chapter 23), and by Williams and Karacan (Chapter 35), to the
effect that autonomic-nervous-system function varies dramatically in

different stages of sleep, e.g., the marked increase in variability of some
autonomic functions during REM periods has led to considerable interest in
possible pathogenic effects, e.g., in certain cardiovascular conditions such as
coronary insufficiency with nocturnal angina. Friedman and Fisher and

Kripke have adduced evidence that an ultradian ninety-minute rhythm
persists throughout a twenty-four-hour period and is not just confined to
sleep although its (behavioral) manifestations are different during waking
hours. The fact that these sleep and related waking ninety-minute rhythms
are, or may be, linked with fluctuations in levels of consciousness (and
possibly with changes in patterns of homostatic physiologic regulation) is
especially provocative when recalling Schur’s formulations regarding the
significance for medical pathogenesis of “altered ego states”—a psychological
term that refers at least partially to altered states of consciousness. It should
be recalled also that Breuer and Freud, in their original “Studies on Hysteria,”
postulated an altered “hypnoidal state” of consciousness as providing the
biologic substrate for actual symptom formation.
This sector of work has been (and bears promise of continuing to be) an
especially fruitful area for collaboration between psychiatric clinicians and
clinical physiologists. Stressful periods of life provide opportunities for

intensive parallel and simultaneous application of depth psychological
techniques with neuroendocrine techniques, and for attempts to arrive at

integrated formulations concerning the biological significance of the changes
observed. The psychoanalytic technique is particularly well suited for
elucidating critical and important details of the psychological aspects, since it

provides opportunity for repetitive finely detailed studies at those very times
when major changes in balance of intrapsychic forces and in levels of
consciousness and ego state are occurring. Since earlier theories, for the most
part, took physiological “mechanisms” for granted, it would be desirable to
conduct new studies now (such as those carried out by Knapp et al.) in which
psychological observations are made in conjunction with observations of

these complex biological mechanisms. This will be required before
empirically sound improvements can be made in the realm of theory.
Finally it should be noted that Henry, Axelrod, and collaborators have
demonstrated increases in adrenal weight and marked increases in adrenal
tissue content of the biosynthetic enzymes of norepinephrine in response to

an intense psychosocial stress in mice (the same stress that simultaneously
leads to development of sustained hypertension and renal pathology in the
experimental animals). The enzymes involved in synthesis and metabolism of

catecholemines in the CNS have also been shown to be influenced by the
hormones of the adrenal cortex (see Weiner, Chapter 22), and it even seems
possible that psychoneuroendocrine stress responses may in some way be

involved in CNS regulation of biogenic amine metabolism, and thus
participate in development of those major affective disorders that are
considered possibly to reflect disturbances in biogenic amine systems.
Autonomic Conditioning
The fourth section, instrumental conditioning of autonomic responses,
is reviewed in Hofer’s chapter on the autonomic nervous system. These
studies, pioneered by DiCara and Miller and associates, hold major and
fundamental significance in regard to etiology and pathogenesis of medical
illness. Older specificity theories evoking early life “conditioning” as a factor

in constitutional predisposition were limited in the scope of possible visceral
changes that could be conditioned to those that could be evoked by an
unconditioned stimulus as long as the Pavlovian paradigm of classical
conditioning was considered the only form applicable to the autonomic

nervous system. The demonstration that instrumental conditioning of the
autonomic nervous system can occur means that virtually any change in the
functional repertoire of the viscera bears the potential for “shaping” and
augmentation by instrumental learning. Hofer discusses how this might
operate during development, to influence later predisposition to disease.
These findings also make it evident that there are, in fact, important
functioning afferent pathways to the brain from autonomically innervated

structures, and that feedback effects on the brain from the viscera via the
autonomic nervous system pathways are far more important than was
previously thought. Study of these pathways and mechanisms should clarify
and elucidate many of the previously somewhat mysterious somatopsychic

effects encountered in clinical medicine, and, as Hofer points out, may have
far-reaching fundamental implications for understanding the
interrelationships of the CNS and the autonomic-nervous-system function in
integrating behavior and bodily function.
Developmental Psychophysiology
A fifth section deals with research in developmental psychophysiology,
which is of course highly cogent to the questions regarding the role that early-
life experiences may play, along with conditioning and genetic endowment, in
determining “constitution.” The most important findings in this field derive

from experimental studies on laboratory animals that reach maturity in a
short period of time, thus permitting later adult effects of early-life
experimental behavioral manipulations to be observed within convenient
time periods. For example, Levine and collaborators have developed

extensive data on the effects of subtle early manipulations such as “handling”
on important parameters of adult behavioral (e.g., excitability) and
physiological responses to novel stimulation and stress (responsiveness of

the pituitary adrenal system). Levine has also studied long term behavioral
influences of sex hormones administered during critical periods of infantile
development, elucidating some important developmental aspects of

hormonal effects on complex adult patterns of sexual and aggressive
behavior. Ader and Friedman, in extensive programmatic studies, have
developed several animal models of disease susceptibility in which
experimental manipulation of infantile experience (such as solitary vs.
crowded conditions of raising) has been shown to influence subsequent adult
susceptibility or resistance to a number of pathogenic challenges, including
various pathogenic microorganisms and viruses, as well as a number of
behavioral manipulations known to be stressful. Their data clearly

demonstrate marked effects on “host resistance” in both directions—
augmentation or decrease of resistance depending upon the nature of the
early life experimental manipulations, and upon the pathogens and/or

stresses employed. Hofer and collaborators have studied maturation of
physiological mechanisms regulating heart rate and rhythm in rats, and have
demonstrated asynchrony of maturation of sympathetic and vagal systems,
and have identified developmental epochs of possible significance as “critical
periods” (perhaps even as anlagen of adult pathological response patterns,
such as the fatal bradycardia known to occur in certain adult rodents under
threat of severe attack). By combining longitudinal developmental studies
with techniques of selective breeding, the distinct possibility exists for

elucidating the interaction of genetic and experiential factors in determining
predispositions or specific susceptibilities of organ systems to specified types

of disorders, and even to differential responsiveness to specific
pharmacologic agents as Corson has shown in hyperkinetic dogs. A highly

important aspect of the work of Henry et al., mentioned above, consists of the
fact that it clearly demonstrates the influence of differential conditions of
early rearing and experience upon later susceptibility to developing
hypertension and associated adrenal changes in mice exposed to the
psychosocial stress he employs. This work is truly noteworthy in that it
addresses the entire span of the biological, psychological and social aspects of
the experimental disease model; it provides important details of the social
stress employed, of behavior, of pathological physiology, of organ pathology,
of changes in endocrine and metabolic enzyme systems, and of early
developmental parameters as well!
In summary, psychosomatic research has gradually evolved from early
case and clinical psychophysiological experiments, to include extensive basic
and clinical research that addresses issues ranging from discrete cellular
functions at one extreme to transcultural comparisons at the other. Whereas
the earliest contributions came mainly from medical psychiatric and
psychoanalytic clinicians and from experimental psychophysiologists, an
extremely wide range of neurobiological and behavioral scientists are now

actively engaged in work related to the field of medicine. A great deal of
research is increasingly directed to a study of the mechanisms whereby the

brain subserves, regulates and coordinates higher mental and social functions
on the one hand, and widespread physiological functions throughout the body
on the other. These have become possible because of the technical and
methodological breakthroughs that have occurred in the life sciences, in
neurophysiology, in endocrinology, in computer science, and in the social and
behavioral sciences as well.
Part 3: Toward a Theory
Considering the findings reviewed in the preceding section, it seems
reasonable to think of man as existing in a “bio-psycho-social” field as

illustrated in Figure 21-2. This depicts an open transactional system that
allows uninterrupted bidirectional flow of information and energy
transactions extending from the deepest and most minute recesses of the
body (intracellular metabolic processes) to the social field, encompassing

cultural forces, even historical forces that contributed to shaping the culture.
In the center is the brain which both subserves mental functions and
influences (and is influenced by) body function. On the one hand, the higher
mental functions, which include mechanisms for regulating interpersonal
relations, mediate the individual’s transactions with his social environment
including family, social groups, and society at large. On the other hand, the
brain also in some fashion (mysteriously) “transduces” nonphysical
immaterial aspects of the social field (that is, symbolic meanings) into
physical-physiological events within the CNS, and these in turn initiate
physiological changes throughout the body. At the same time brain function
itself is, in turn, influenced by physiological changes occurring in the
periphery of the body. These two-way interchanges of information and
energy between the central nervous system (brain) and the periphery (body)
are negotiated by the central and autonomic nervous systems and the
neuroendocrine systems. This transactional continuity extending from
subcellular metabolic processes throughout the body via the brain to the
social environment makes it understandable that major life experiences, such

as bereavement, can influence even the capacity to sustain the life process
itself. A unique feature, not explicitly depicted in the diagram, is that the brain,
which occupies this interface position between mind and body, is at the same
time itself an organ of the body, subject to influence by the very same
alterations in the body’s internal environment that it, in fact, helps to
generate. Viewed in this way, the brain can be thought of as a possible “target
organ” in sustained and profound stressful reactions. It may not be entirely
fanciful to speculate that some forms of functional psychosis may in fact
represent “stress diseases” in which the brain is the “target organ.”
Figure 21-2.
Figure 21-2.
The Bio-psycho-social field. (For explanation see text.)
Considering the apparent complexity of relationships and the
incompleteness of our knowledge concerning the mechanisms involved, we
do not yet seem to be in a position to construct a satisfactory general theory
of etiology and pathogenesis that would account in a parsimonious fashion
(as a good theory should) for the variety of ways in which psychosocial forces
may be involved in the development of bodily illness. All the same, some
implications for the general shape and character, and for some components,
of a future theory can be drawn. If etiology and pathogenesis are conceived of
as stepwise processes, and the natural history of disease is considered in
respect to the separate phases (the phase preceding manifest disease, the
phase of precipitation, and the phase of established disease), it appears that
varying admixtures of specific and nonspecific mechanisms are involved, the
relative proportions depending upon the stage of pathogenesis and phase of

the disease process.
In phase 1, the period preceding the development of manifest disease,

the important issue to be understood is if—and if so, how—a predisposition
to a specific disease may be programmed into an individual who is later to be
affected. Here we face a complex of elements ordinarily referred to as
“constitution.” It appears likely that specific programming could involve (1)
peripheral tissues in patterns or characteristics of organ function or tissue
response, e.g., rate of pepsinogen secretion; (2) the CNS in modular central-
nervous-system circuits (see Chapter 19 for a review of central-nervous-
system circuits influencing various organ systems); and (3) both peripheral
and central: parallel tissue-response pattern and central-nervous-system

circuits, with appropriate autonomic and endocrine effector linkages.
For many diseases it is clear' that necessary but not sufficient
programming information is transmitted in the genes; but since the

transmission pattern seems to be one of incomplete penetrance, other factors,
such as early experience very probably interact and contribute in

fundamental ways to determination of “constitutional” predispositions, and it
appears that this could occur in several ways.
Developmental physiology suggests that there may be “critical periods”

representing crucial stages in maturation when neurovegetative systems
responsible for regulation of important visceral functions (such as heart rate
and rhythm, peripheral resistance, etc.) may be particularly amenable to
sensitizing or conditioning, and sensitive or open to influences by experiential

events. Particularly intriguing is the possibility of autonomic conditioning
(visceral learning) occurring during such “critical periods,” and eventually
shaping a predisposition stored in central-nervous-system circuits for highly
specific (pathogenic) visceral innervative patterns that could become
activated (and pathogenic) under appropriate conditions later in life. The
credibility or face validity of such an idea is enhanced by considering the

possibilities for continuing reinforcement and further shaping provided by
the continuing transactions between infant and mother, and later between
child and family, that take place throughout development. Mirsky in his
formulations about duodenal ulcer, has described how a basically genic
constitutional predisposition in an organ, if expressed in behavior (e.g., as an

excessive need to be nurtured and nourished in the case of gastric
hypersecretion), may influence the mother’s behavior in response to the

infant. This in turn would modify subsequent behavior in the infant (perhaps
by frustration and intensification of need) which would then feed back to the
mother’s behavior etc., etc., gradually creating a nidus of “core conflict” in the
developing personality which would be specifically and inextricably related to
the genic constitutional predisposition. At the same time in the course of
development, reactive or protective ego defenses would develop around this

vulnerable part of the personality system, and the nature and potential
imperfections in this defensive matrix might very well determine the kind of
psychosocial stress situation that could be expected to overwhelm the

defenses and activate the conflict. Regardless of whether a constitutional
predisposition originated in genic transmission and/or autonomic
conditioning and/or classical conditioning (by repetitive fortuitous
coincidence of stressful events with periods of illness), an epigenetic
developmental sequence similar to this might well be expected to take place
and eventuate in an individual with specifically patterned interrelated

biological, psychological, and social vulnerabilities. Thus the emphasis in
regard to this preillness phase of disease seems to weigh heavily in favor of

specific preprogramming, with the evidence suggesting that both genetic and
early developmental factors are involved and in complex interrelated ways.

But the data do not permit us to do more than speculate about the possible
nature of the interrelationships and the specific mechanisms whereby such

effects might actually be induced.
A rather different set of questions arise in considering the phase of
precipitation of active disease. Here the problem is one of understanding how
psychosocial stress is to be related to activation of illness. In approaching
these questions, primary emphasis shifts to the nonspecific factors reviewed
in Part 2, i.e., the nonspecific effects of the psychoneuroendocrine stress

responses on “host resistance” through effects on immune mechanisms, and
through interfering with synchronization of circadian, ultradian and seasonal
rhythms, etc. As noted earlier, the nature of the psychosocial stress situations
that might be expected to overwhelm psychological defenses and allow for
reactivation of conflict in any given individual would be related to his history,
and to his personality organization, more precisely to the nature of whatever
unresolved core conflicts remain active in him, and require continuing
defensive activity. If under stress his defenses fail and his adrenal cortical and
other endocrine activity is affected, he might, for example, be less resistant to

infection, and develop a clinical infection more readily on exposure to an
infective challenge that he would resist under more favorable circumstances.

Such nonspecific reactions affect all people and their effects seem to be
ubiquitous in medical practice.
But what about that relatively small group of persons supposed to be
preprogrammed or predisposed as described above? In such individuals the

proximal pathogenic vector is not thought to be external (as in the case of
pathogenic organisms) but rather internal, i.e., a predisposition, albeit
previously latent and inactive. In what way, if any, could the intrinsically
nonspecific changes attendant to psychoneuroendocrine stress response be
related to activation of such a process? Or to put the question differently: in
what way, if any, could the changes ultimately induced in the body by the
endocrine response be favorable or permissive to actual expression of the
previously inactive but potential pathogenic mode of function? The findings
suggest that this could happen in a number of ways. Neurovegetative and

endocrine changes in response to psychosocial stress have been shown to
affect higher mental processes such as cognition, and could in this way
influence perception and evaluation of danger signals and anxiety proneness.
It could be hypothesized then that sustained pressure from active
psychological conflict, with weakening of defenses, might set into motion a
cyclic reaction whereby psychological processes involved in evaluation of

danger would become increasingly more primitive and symbolic (regressive)
as a consequence of the physiological responses they evoke, and that the

physiological responses would become increasingly more vigorous as danger
signals were evaluated with increasing alarm (Figure 21-3, step 1). One could
speculate further that exposure of the brain to vigorous and continuous
changes in circulating hormones (changes in the amounts and rates of rise

and fall of individual hormones, in profiles among various hormones, in
rhythms, etc.) could so affect patterns of central-neurophysiologic regulation
that preprogrammed but inactive pathogenic circuits would become active
and make connection with appropriate efferent fibers to the viscera, and
thereby induce altered visceral function (Figure 21-3, step 2). I have
speculated previously that such hypothesized altered CNS conditions might
be manifested behaviorally in the form of subtly altered states of
consciousness (altered “ego states” in psychoanalytic terms as described by
Schur; or “hypnoidal” states as hypothesized by Breuer and Freud). Such a
notion is fully compatible with clinical observations of patients with high

levels of free anxiety, and with a number of experimental observations: (1) at
least one known state of consciousness (REM sleep) is well known to be
associated with markedly altered (less well regulated, more “primitive”)
patterns of autonomic function; (2) some serious illness episodes (e.g.,

myocardial infarction, status asthmaticus, hemorrhage from duodenal ulcer,
etc.) are known to be precipitated or exacerbated in sleep; and (3) it has been
shown that the ultradian ninety-minute rhythm seen in sleep (REM cycle)
may continue throughout the twenty-four-hour period and be manifest in
behavior (e.g., increased eating behavior) during waking hours.
Figure 21-3.
Figure 21-3.
Hypothesized steps in precipitation of disease in conjunction with psycho-
social stress.
Finally, in order to activate the specific pathological physiology involved
in pathogenesis of a particular disease state (Figure 21-3, step 3) the altered
visceral function produced in step 2 (as outlined above) would need to be
combined with other factors essential to the particular disease (such as

exposure to allergens, pathogens, compensatory and secondary changes in
the same and other systems, e.g., circulatory adjustments, etc.) Of course
these would be entirely different for each disease, depending upon the nature
of its pathological physiology and pathology.
This conceptual schematization of phase 2 (precipitation) of disease
emphasizes a series of nonspecific psychoneuroendocrine changes that may
operate to aid in inducing illnesses of all sorts in all people, but which also
might facilitate or induce in a smaller group of people so predisposed an
altered state of CNS function permissive for activation of specific
preprogrammed pathogenic patterns of visceral innervation. In other words,
a nonspecific response would prepare the way for emergence of a more

specific pathogenic process, with the specific predisposition having been laid
down by interaction of psychologically meaningful early experiences with
genic endowment in a series of epigenetic somatopsychosomatic transactions
throughout development.
In phase 3 of disease, i.e., that in which the disease has already been
established, it is likely that both nonspecific and specific mechanisms as
described above would operate separately or in combination to influence the

course and induce exacerbations or complications. But two modifications
should be added. First, with increasing progression of disease and diminution

in organ reserve, it is entirely possible and plausible that nonspecific changes
might very well play an increasingly significant role with time, since less and
less functional reserve in organs and resilience in homostatic mechanisms

would be available to moderate the disruptive effects of nonspecific stress
responses. Second, with time, perception of the disease and its meaning
become increasingly elaborated within the individual’s self-image and
increasingly incorporated into ongoing mental life, particularly in the conflict
sphere (Hartmann). Accordingly, symbolically meaningful ideas would with
increasing frequency and importance be associated with periods of activated

or aggravated pathogenic physiologic responses. It would be expected then
that idiosyncratic symbolic meanings connected with the disease would, with
increasing frequency, become enmeshed in important issues in the patient’s

psychosocial field, and in ongoing intrapsychic conflicts as well. This would
result in heavy emphasis on symbolic meanings associated with the disease,
its signs and symptoms, in the patient’s associations in psychoanalysis or
psychotherapy, thereby creating the (probably false) impression that the
disease had originated as a symbolic conversion mechanism.
In presenting these admittedly fanciful speculations in the final part of
this Chapter, I have attempted mainly to have them reflect back to earlier
theories while remaining consistent with the ever increasing wave of new
empirical data, and to offer them as guides to possibly fruitful areas for
research and as rough forecasts or previews of the nature and shape of
(components of) future theory which is yet to be developed on a sound
empirical basis. In any event, it seems reasonably clear to me that

understanding the brain and its relation to the body on one hand, and to the
mind and social environment on the other, will probably ultimately provide
the key to the riddle; i.e., full understanding will come from discovering how
the brain orchestrates, integrates, and at points transduces across the
biological, the psychological, and the social realms. In keeping with this view,
Part Two of this volume begins with central regulation of autonomic-nervous-

system function, followed by discussion of the autonomic nervous system
itself, and then by reviews of psychoendocrinology and the data pertaining to
the psychosocial parameters of illness in man. Finally come the separate

chapters dealing with specific organ systems and diseases.
Bibliography
Ader, R. “The Influences of Psychological Factors on Disease Susceptibility in Animals,” in M. L.

Conalty, ed., Husbandry of Laboratory Animals, pp. 219-238. London: Academic,
1967.
Ader, R. and S. M. Plaut. “Effects of Prenatal Maternal Handling and Differential Housing in
Offspring Emotionality, Plasma Corticosterone Levels and Susceptibility to Gastric
Erosions,” Psychosom. Med., 30 (1968), 277-286.
Alexander, F. “Fundamental Concepts of Psychosomatic Research: Psychogenesis, Conversion,

Specificity,” Psychosom. Med., 5 (1943), 205-210.
----. Psychosomatic Medicine, pp. 104-106. New York: Norton, 1950.
Alexander, F., T. M. French, and G. H. Pollock. Psychosomatic Specificity. Chicago: University of

Chicago Press, 1968.
Alexander, F. and S. Selesnick. The History of Psychiatry. New York: Harper & Row, 1966.
Bennet, G. “Bristol Floods 1968; Controlled Survey of Effects on Health of Local Community
Disaster,” Br. Med. J., 3 (1970), 454-458.
Binger, C. A. L., N. W. Ackerman, A. E. Cohn et al. “Personality in Arterial Hypertension,” in F.

Dunbar, ed., Psychosomatic Medicine Monographs, pp. 1-228. New York: Hoeber,
1945.
Breuer, J. and S. Freud. (1895) “Studies on Hysteria,” in J. Strachey, ed., Standard Edition, Vol. 2,
pp. 183-252. London: Hogarth, 1955.
Callaway, E. and S. V. Thompson. “Sympathetic Activity and Perception,” Psychosom. Med., 15

(1953), 433-455.
Corson, S. A., E. Corson, V. Kirilcuk et al. “Differential Effects of Amphetamines on Clinically

Relevant Dog Models of Hyperkinesis and Stereotypy: Relevance to Huntington’s
Disease,” in A. Barbeau et al., eds., Advances in Neurology, Vol. 1. Huntingtons
Chorea, 1872-1973. New York: Raven, 1973.
Curtis, G. C. “Psychosomatics and Chronobiology: Possible Implications of Neuroendocrine

Rhythms,” Psychosom. Med., 34 (1972), 235-250.
Deutsch, F. The Psychosomatic Concept in Psychoanalysis, pp. 158-161. New York: International
Dicara, L. “Learning of Cardiovascular Responses: A Review and a Description of Physiological

and Biochemical Consequences,” Trans. N.Y. Acad. Sci., 33 (1971), 411-422.
Dongier, M., E. D. Wittkower, L. Stephens-Newsham et al. “Psychophysiological Studies in Thyroid

Function,” Psychosom. Med., 18 (1956), 310—323.
Dunbar, H. F. Psychosomatic Diagnosis. New York: Hoeber, 1943.
Engel, G. L. “Studies of Ulcerative Colitis,” Am. J. Med., 16 (1954), 416-433.
----. “Studies of Ulcerative Colitis III; The Nature of the Psychologic Processes,” Am. J. Med., 19
(1955), 231-256.
----. “A Psychological Setting of Somatic Disease: The ‘Giving Up—Given Up’ Complex,” Proc. Roy.
Soc. Med., 60 (1967), 553-555.
Engel, G. L. and J. Romano. “Studies of Syncope; Biologic Interpretation of Vasodepressor

Syncope,” Psychosom. Med., 9 (1947), 288.
Ferris, E. B., M. F. Reiser, W. W. Stead et al. “Clinical and Physiological Observations of

Interrelated Mechanisms in Arterial Hypertension,” Trans. Assoc. Am. Physicians, 61
(1948), 97-107.
Freud, S. (1910) “The Psychoanalytic View of Psychogenic Visual Disturbance,” in J. Strachey, ed.,
Standard Edition, Vol. 11, pp. 209-218. London: Hogarth, 1957.
Friedman, M., R. H. Rosenman, R. Straus et al. “The Relationship of Behavior Pattern ‘A’ to the
State of the Coronary Vasculature,” Am. J. Med., 44 (1968), 525-537.
Friedman, S. and C. Fisher. “On the Presence of a Rhythmic, Diurnal, Oral Instinctual Drive Cycle
in Man: A Preliminary Report,” J. Am. Psychoanal. Assoc., 15, 317-343.
Friedman, S., L. B. Glasgow, and R. Ader. “Psychosocial Factors Modifying Host Resistance to
Experimental Infections,” Ann. N.Y. Acad. Sci., 164 (1969), 381-393.
Garma, A. Peptic Ulcer and Psychoanalysis. Baltimore: Williams & Wilkins, 1958.
Grace, W. J. “Life Situations, Emotions and Chronic Ulcerative Colitis,” in H. Wolff, S. Wolf, Jr. and
C. Hare, eds., Life Stress and Bodily Disease, pp. 679-692. Baltimore: Williams &
Wilkins, 1950.
Graham, D. T., J. D. Kabler, and F. K. Graham. “Physiological Response to the Suggestion of

Attitudes Specific for Hives and Hypertension,” Psychosom. Med., 24, 159-169.
Graham, D. T., R. M. Lundy, L. S. Benjamin et al. “Specific Attitudes in Initial Interviews with
Patients Having Different ‘Psychosomatic’ Diseases,” Psychosom. Med., 24 (1962),
257-266.
Grinker, R., Sr. Psychosomatic Research. New York: Norton, 1953.
----. “Psychoanalytic Theory and Psychosomatic Research,” in J. Marmoston and E. Stainbrook,
eds., Psychoanalysis and the Human Situation, pp. 194-226. New York: Vantage,
1964.
Groddeck, G. W. (1926) The Book of the It; Psychoanalytic Letters to a Friend. New York: Random
House, 1961.
Harris, G. W. and S. Levine. “Sexual Differentiation of the Brain and Its Experimental Control,” J.
Physiol. (London), 181 (1965), 379-400.
Hartmann, H. Ego Psychology and the Problem of Adaptation. New York: International Universities
Press, 1958.
Henry, J. P., P. M. Stevens, J. Axelrod et al. “Effect of Psychosocial Stimulation on the Enzymes
Involved in the Biosynthesis and Metabolism of Noradrenaline and Adrenaline,”
Psychosom. Med., 33 (1971), 227-237.
Hofer, M. A. and M. F. Reiser. “The Development of Cardiac Rate Regulation in Preweanling Rats,”
Psychosom. Med., (1969). 372-388.
Katz, J. L. and H. Weiner. “Psychosomatic Considerations in Hyperuricemia and Gout,” Psychosom.

Med., 34 (1972), 165-179.
Knapp, P. H., C. Mushatt, J. S. Nemetz et al. “The Context of Reported Asthma during
Psychoanalysis,” Psychosom. Med., (1970), 167-188.
Kripke, D. F. “An Ultradian Biologic Rhythm Associated with Perceptual Deprivation and REM
Sleep,” Psychosom. Med., 34 (1972), 221-233.
LaBarba, R. C. “Experiential and Environmental Factors in Cancer; A Review of Research with

Animals,” Psychosom. Med., 32 (1970), 259-274.
Levine, M. Psychotherapy in Medical Practice. New York: Macmillan, 1942.
Levine, S. and V. H. Denenberg. “Early Stimulation; Effects and Mechanisms; Stimulation in Early
Infancy,” in A. Ambrose, ed., Stimulation in Early Infancy, pp. 3-72. Proceedings of
the Study Group on the Functions of Stimulation in Early Post-Natal Development,
London, 1967. New York: Academic, 1969.
Levitt, E. E., H. Persky, J. P. Brody et al. “The Effect of Hydrocortisone Infusion in Hypnotically
Induced Anxiety,” Psychosom. Med., 25 (1963), 158-161.
Lidz, T. and J. Whitehorn. “Life Situations, Emotions and Graves Disease,” in H. Wolff, S. Wolf, Jr.,
and C. Hare, eds., Life Stress and Bodily Disease. Baltimore: Williams & Wilkins,
1950.
Maas, J. W. “Adrenocortical Steroid Hormones, Electrolytes, and the Disposition of the

Catecholamines with Particular Reference to Depressive States,” J. Psychiatr. Res., 9
(1972). 227-241.
Margetts, E. L. “Historical Notes on Psychosomatic Medicine,” in E. D. Wittkower and R. A.

Cleghorn, eds., Recent Developments in Psychosomatic Medicine, pp. 41-
Philadelphia: Lippincott, 1954.
Margolin, S. G. “Genetic and Dynamic Psychophysiological Determinants of Pathophysiological

Processes,” in F. Deutsch, ed., The Psychosomatic Concept in Psychoanalysis, pp. 3-
36. New York: International University Press, 1953.
Mason, J. W. “ ‘Over-All’ Hormonal Balance as a Key to Endocrine Organization,” Psychosom. Med.,

30 (1968), 791-808.
Miller, N. “Learning of Visceral and Glandular Responses,” Science, 163 (1967), 439-445.
Mirsky, I. A. “Physiologic, Psychologic, and Social Determinants in the Etiology of Duodenal

Ulcer,” Am. J. Dig. Dis., 3 (1958), 285-314.
Mirsky, I. A., P. Futterman, and S. Kaplan. “Blood Plasma Pepsinogen II; the Activity of the Plasma
from ‘Normal’ Subjects, Patients with Duodenal Ulcer, and Patients with Pernicious
Anemia,” J. Lab. Clin. Med., 40 (1952), 188-199.
Mirsky, I. A., D. Futterman, S. Kaplan et al. “Blood Plasma Pepsinogen 1, The Source, Properties,
and Assay of the Proteolytic Activity of Plasma at Acid Reactions,” J. Lab. Clin. Med.,
40 (1952), 17-26.
Mirsky, I. A., S. Kaplan, and R. H. Broh-Kahn. “Pepsinogen Excretion (Uropepsin) as an Index of

the Influence of Various Life Situations on Gastric Secretion” in H. Wolff, S. Wolf, Jr.,
and C. Hare, eds., Life Stress and Bodily Disease, pp. 628-646. Baltimore: Williams &
Wilkins, 1950.
Mullins, R. F. and S. Levine. “Hormonal Determinants during Infancy of Adult Sexual Behavior in
the Rat,” Physiol. Behav., 3 (1968), 333-338.
Parkes, C. M., B. Benjamin, and R. G. Fitzgerald. “Broken Heart: A Statistical Study of Increased
Mortality among Widowers,” Br. Med. J., 1 (1969), 740-743.
Pilot, M. L., E. Prelinger, R. Schafer et al. “Use of a Twin Pool in Developing Interdisciplinary
Research,” (Abstract), Psychosom. Med., 23 (1961), 443-451.
Pilot, M. L., J. Rubin, R. Schafer et al. “Duodenal Ulcer in One of Identical Twins,” Psychosom. Med.,
5 (1963), 285-290.
Pollin, W. and S. Goldin. “The Physiological and Psychological Effects of Intravenously

Administered Epinephrine and Its Metabolism in Normal and Schizophrenic Men,
II,” J. Psychiatr. Res., 1 (1961), 50-67.
Przbylski, A. “Effect of Stimulation and Coagulation of the Midbrain Reticular Formation on the
Bronchial Musculature; A Modification of Histamine Susceptibility,” J. Neuro-Visc.
Rel., 31 (1969), 171-188.
Rees, W. D. and S. G. Lutkins. “Mortality of Bereavement,” Br. Med. J., 4 (1967), 13-16.
Reiser, M. F. “Research Findings on the Influence of Countertransference Attitudes on the Course

of Patients with Hypertension in Medical Treatment,” Round Table on
Hypertension, Mid-Winter Meeting; American Psychoanalytic Association, New
York; December, 1952. Abstracted in Report of Round Table. J. Am. Psychoanal.
Assoc., 1 (1953), 562-574.
----. “Reflections on Interpretation of Psychophysiological Experiments,” Psychosom. Med., 23
(1961), 430-439.
----. “Toward an Integrated Psychoanalytic-Physiological Theory of Psychosomatic Disorders,” in

R. M. Lowenstein, M. Newman, M. Schur et ah, eds., Psychoanalysis—A General
Psychology, pp. 570-582. New York: International Universities Press, 1966.
----. “Models and Techniques in Psychosomatic Research,” Compr. Psychiatry, 9, 403-413.
Rosenbaum, M. “Psychosomatic Aspects of Patients with Peptic Ulcer,” in E. D. Wittkower and R.

A. Cleghorn, eds., Recent Developments in Psychosomatic Medicine, pp. 326-344.
Rosenman, R. H., M. Friedman, R. Straus et al. “A Predictive Study of Coronary Heart Disease,”
JAMA, 189 (1964), 15-22.
Sachar, E. J., L. Hellman, H. P. Roffwarg et al. “Disrupted 24-Hour Patterns of Cortisol Secretion in
Psychotic Depression,” Arch. Gen. Psychiatry, 28 (1973), 19-24.
Sachar, E. J., J. Mason, H. S. Kolmer et al. “Psychoendocrine Aspects of Acute Schizophrenic

Reactions” Psychosom. Med., 25. 510-537.
Saslow, G., G. Gressel, F. Shobe et al. “The Possible Etiological Relevance of Personality Factors in
Arterial Hypertension,” in Wolff, S. Wolf, Jr., and C. Hare, eds., Life Stress and Bodily
Disease, pp. 881-899. Baltimore: Williams & Wilkins, 1950.
Schmale, A. H., Jr. “A Relationship of Separation and Depression to Disease,” Psychosom. Med., 20
(1958), 259-277.
Schmale, A. H., Jr. and G. L. Engel. “The ‘Giving Up—Given Up’ Complex Illustrated on Film,” Arch.
Gen. Psychiatry, 17 (1967), 135-145.
Schur, M. “The Ego in Anxiety,” in R. M. Loewenstein, ed., Drives, Affects, Behavior, Vol. 1, pp. 67-
103. New York: International Universities Press, 1953.
----. “Comments on the Metapsychology of Somatization,” in The Psychoanalytic Study of the Child,
Vol. 10, pp. 110-164. New York: International Universities Press, 1955.
Shapiro, A. “Influence of Emotional Variables in the Evaluation of Hypotensive Agents,”
Psychosom. Med., 17 (1955), 291-305.
Sperling, M. “Psychoanalytic Study of Ulcerative Colitis in Children,” Psychoanal. Q., 15 (1946),

302-329.
----. “The Psycho-analytic Treatment of Ulcerative Colitis,” Int. J. Psycho-Anal., 38 (1957). 341-349.
----. “A Psychoanalytic Study of Bronchial Asthma in Children,” in H. I. Schneer, ed., The Asthmatic
Child, pp. 138-165. New York: Hoeber, 1963.
— . “A Further Contribution to the Psycho-Analytic Study of Migraine and Psychogenic

Headaches,” Int. J. Psycho-Anal., 45 (1964), 549-557.
Stein, M. “The What, How, and Why of Psychosomatic Medicine,” in D. Offer and D. X. Freedman,
eds., Modern Psychiatry and Clinical Research, pp. 44-58. New York: Basic Books,
1971.
Stein, M., R. C. Schiavi, and T. J. Luparello. “The Hypothalamus and Immune Process,” Ann. N.Y.
Acad. Sci., 164 (1969), 464-472.
Szasz, T. S. “Psychoanalysis and the Autonomic Nervous System,” Psychoanal. Rev., 39 (1952),
115-151.
Von Bertalanffy, L. “The Mind-Body Problem,” Psychosom. Med., 26 (1964), 29-45.
Wallerstein, R. S., P. S. Holzman, H. M. Voth et al. “Thyroid ‘Hot Spots’: A Psychophysiological

Study,” Psychosom. Med., 27 (1965), 508-523.
Weiner, H. “The Specificity Hypothesis Revisited,” Psychosom. Med., 32 (1970), 543.
----. “Presidential Address: Some Comments on the Transduction of Experience by the Brain;
Implications for Our Understanding of the Relationship of Mind to Body,”
Psychosom. Med., 34 (1972), 355-375.
Weiner, S., D. Dorman, H. Persky et al. “Effects on Anxiety of Increasing the Plasma by
Hydrocortisive Level,” Psychosom. Med., 25 (1963), 69-77.
Weiner, H. and M. F. Reiser. “Methodological Issues in Psychosomatic Research on Cardiovascular

Problems; Retrospect and Prospect,” in Proc. 4th World Congr. Psychiatry, pp. 2746-
2748. Excerpta Medica International Congress Ser. no. 150. Amsterdam: Excerpta
Medica Foundation, 1966.
Weiner, H., M. Thaler, M. F. Reiser et al. “Etiology of Duodenal Ulcer I,” Psychosom. Med., 19
(1957), 1-10,
Weiss, E. and O. English. Psychosomatic Medicine. Philadelphia: Saunders, 1957.
Wolf, S. and E. M. Shepard. “An Appraisal of Factors that Evoke and Modify the Hypertensive
Reaction Pattern,” in H. Wolff, S. Wolf, Jr., and C. Hare, eds., Life Stress and Bodily
Disease, pp. 976-984. Baltimore: Williams & Wilkins, 1950.
Wolf, S. and H. G. Wolff. Human Gastric Function, 2nd ed. London: Oxford University Press, 1947.
Wolff, H. G. “Life Stress and Bodily Disease—A Formulation,” in H. Wolff, S. Wolf, Jr., and C. Hare,
eds., Life Stress and Bodily Disease, pp. 1059-1094. Baltimore: Williams & Wilkins,
1950.
Notes
1 This Chapter introduces the second part of the Volume and refers extensively to material covered in
chapters that follow, particularly Chapters 22, 23, 24, 25, and 26. To avoid unnecessary
duplication, many of the bibliographic references listed in those Chapters have not been
repeated. Readers interested in a thorough follow-up of literature sources, therefore, are
advised to consult those Chapters and their bibliographies as well as the bibliography of
this one.
Chapter 22
Autonomic Psychophysiology: Peripheral

Autonomic Mechanisms And Their Central
Control
Herbert Weiner
Introduction
Social and psychological stimuli, tasks and constraints and the

physiological responses they engender in human and animal subjects, are
mediated by hormonal, autonomic, and neuromuscular mechanisms. For this

reason, some data and concepts about the organization and function of the
autonomic nervous system (ANS) in particular will be presented here in order

to add meaning to the psychophysiological relationship which will be outlined
in Chapter 23. Little discussion of the control of the neuromuscular system
will take place in this Chapter because there is only limited information
available about the control of electromyographically recorded activity from
muscle. In addition, a full discussion of the neuromuscular transmission
would lead the reader too far afield from the main interests of the clinical
psychophysiologist.
By definition, the psychophysiologists attempt to record physiological
changes after social and psychological stimulation in the intact subject with
an absolute minimum of interferences such as the taking of blood samples

and intubating blood vessels. At the same time, it behooves the investigator to
make absolutely certain that his measurements, which are indirect, validly
reflect changes in the functioning of the system or organ under study. Once
having made certain of the change he is measuring, he must ascertain that the
change occurred from a steady-state baseline. This steady-state probably
reflects the product of a number of different physiological parameters: the
intrinsic activity of the organ (the denervated heart beats regularly and
slowly); the tonic innervation of the organ through the autonomic nervous
system which solely modifies the intrinsic rhythm; the effect of
neurotransmitter release into the circulation from autonomic nerve endings

and the adrenal medulla; the rate of reuptake and metabolism of the free
transmitter; the regulation of neurotransmitter biosynthesis, release, and
metabolism by the adrenal gland which is under combined hormonal and
neural control; and the nature and state of the receptor mechanism for the
neurotransmitter at the end organ.
Once the steady-state is disturbed by environmental and psychological
variables, dynamic physiological changes begin to occur. The change in
physiological function—for instance, an increase in the heart rate from a
steady-state level—may be the combination of a large variety of physiological
factors, such as a change in cardiac filling, and phasic adrenergic discharge

affecting, for example, the sino-auricular node, and increasing
atrioventricular conduction velocity, etc. This phasic discharge may, in turn,
be regulated by complex central-nervous circuits which lie in all parts of the
brain, but particularly in the midbrain, hypothalamus, brain stem, and spinal
cord.
Among the important psychological parameters affecting acute
physiological changes are: the novelty of the stimulus; the expectations of the
investigator and the subject; anticipation by the subject of the task ahead;
individual response tendencies which, in part, are determined by earlier
experiences of the subject; the length of time the subject is given before
engaging in a specific task; and the nature and duration of the task or stress.
The kinds of physiological responses which prolonged stresses elicit are
different, and are mediated by different mechanisms, than those which are
elicited by acute psychological stresses.
With the exception of the EEG,1 evoked and other potentials, and
electromyographic responses studied by psychophysiologists, all the
physiological functions which psychophysiologists record depend primarily
on autonomic regulation and control. For example, changes in pupillary size,
salivary flow, heart rate, blood pressure, respiratory rate and volume, blood
flow through the skin, sweating, gastric motility and secretion, urinary flow,
or uterine contraction are to a large extent under autonomic control, although

the hormonal regulation of a function also plays a role. Uterine contractility,
for example, depends on the stage of the menstrual cycle and the amounts of
circulating estrogen and progesterone, etc., while the contractile responses of

the pregnant uterus to neural stimuli differs from the nonpregnant one.
This Chapter also attempts to review new information about the

autonomic nervous system which has changed our concepts about its
functioning.
It used to be said that the sympathetic-adrenergic system mainly

discharged as a unit, especially in situations in which the organism responded
with the emotions of fright or rage. It used to be believed that the
parasympathetic-cholinergic nervous system was mainly organized for

discrete and localized discharge and not for mass responses; from a
teleonomic point of view, it was considered that it subserves conservative
and restorative processes.
These generalizations, however, do not hold in the light of new
evidence. Discrete sympathetically mediated responses can be elicited by
operant conditioning. Therefore, only under some circumstances does mass
discharge of the sympathetic nervous system occur.
Secondly, it is now quite clear that the autonomic nervous system is not
only “involuntary.” In fact, it can be manipulated by operant techniques which
a subject may learn. Furthermore, some “involuntary” functions (such as the

alpha rhythm of the EEG) cannot only be recognized but also controlled by
their owner. Subjects can also be “taught” to lower their blood pressure. In
other words, voluntary control can be achieved over “involuntary” function.
Another new discovery indicates that, in some instances, the
transmitter substance of the postganglionic sympathetic nervous system is
not norepinephrine but acetylcholine. Therefore, it cannot be correctly
assumed that the sympathetic nervous system is exclusively “adrenergic.” For

example, vasodilatation in skeletal muscle is, in part, brought about by a
sympathetic cholinergic system.
In addition, the effects of the norepinephrine release at postganglionic

synapses and of epinephrine are, in part, determined by the nature of the
receptor. Norepinephrine and epinephrine can cause either excitation or
inhibition of smooth muscle, depending on the site and to some extent on its
amount. For example, sympathetic discharge produces contraction of the
radial muscle of the iris, constriction of the blood vessels of the skin mucosa
and lungs, contraction of pilomotor muscles in the skin and the intestinal
sphincters, but it also brings about relaxation of the ciliary muscle of the eye,
of the bronchial muscles of the lung, and detrusor muscles of the bladder.
Where contraction is produced, physiologists classify the receptor as

belonging to the a-type, where relaxation occurs they call it the β-type. Some
catecholamines mainly affect one type of receptor to produce excitation and
others to produce inhibition. Thus, norepinephrine is the most powerful,

excitatory catecholamine and mainly affects a-receptors, whereas
isoproterenol exhibits the opposite effect. Epinephrine has both excitatory
and inhibitory properties. The majority of adrenergic blocking agents act
selectively on the excitatory or inhibitory effects of the catecholamines, and

can thus be classified as a-(e.g., phenoxybenzamine) or β-(e.g., 3.4-
dichloroisoproterenol) blocking agents.
Cardiac nodes and muscles respond to an increase in sympathetic
discharge or the catecholamines, by an increase in rate of discharge and
contractile vigor respectively, but have the properties (as defined by their
responses to pharmacological agents, i.e., isoproterenol) of the β -receptors.
The Autonomic Nervous System: Anatomy and Physiology
The more we know about the functioning of the ANS, the better are we
able to grasp the meaning of psychophysiological correlations. This leading
statement has often been contradicted by psychophysiologists, many of
whom tend to be concerned only with demonstrating empirical relationships,
or to use psychophysiological techniques to study “covert” behaviors. They

argue, with some conviction, that it is not absolutely necessary to understand
mechanisms, if it can be demonstrated that training techniques affect
physiological function which has been disturbed in disease states, e.g., to
lower blood pressure in a patient with essential hypertension by operant

techniques.
It is our conviction that such a pragmatic approach evades the basic
question of why the blood pressure became elevated in essential
hypertension. Although we cannot give an answer to this question, it is fairly

widely accepted that an elevated diastolic pressure is but a symptom of
essential hypertension, not the disease itself, and represents the end product
and an adjustment to altered functions in several different systems—e.g., the

brain, adrenal gland, kidney, arteriolar tree, etc.
Therefore, it would seem to be an omission not to be aware of the role
of the ANS in a wide variety of bodily functions, including important

metabolic and behavioral ones.
Anatomy of the Autonomic Nervous System
All structures within and on the surface of the body are innervated by
the autonomic nervous system. Obviously, the main motor nerves to skeletal
muscle belong to the “voluntary” nervous system, but blood flow within such
muscle is autonomically regulated.
One major difference between the motor nerves of the autonomic and
the neuromuscular systems is that synaptic connections between the
preganglionic and postganglionic fibers of the autonomic system are made
outside the neuraxis in a system of ganglia. Emerging from these ganglia, the
postganglionic “motor” nerves are further organized into a system of
peripheral plexuses, the constitutent fibers of which are largely unmyelinated
and, therefore, have much slower conduction velocities. They reveal other
characteristics than the motor neurons of the neuromuscular system.
Denervation of autonomically innervated structures does not preclude their
function in the same manner that the function of striated (noncardiac) muscle
does.
The two divisions of autonomic efferent fibers—the sympathetic and
parasympathetic —innervate the heart, and the same glandular and other
structures which are composed of smooth muscle. Traditionally, this
arrangement has led to the concept, very popular in psychophysiology, that
their functions are antagonistic. Actually, the level of activity in an effector

organ at any one moment is the algebraic sum of many influences, i.e., a
decrease in adrenergic excitation, while keeping cholinergic excitation steady,
may appear as if cholinergic excitation had increased. In fact, recent advances
have forced a modification of the old view. For instance, vasodilatation in
muscle is mediated by a sympathetic, postganglionic cholinergic mechanism.

The algebraic sum is also influenced by circulating neurohumors.
The efferent cells of preganglionic sympathetic fibers lie in the

intermediolateral columns of the spinal cord from the level of the eight
cervical to the second or third lumbar vertebra. Their axons pass with the
anterior nerve roots to a series of twenty-two interconnected, paravertebral
ganglia where they form synaptic connections with postganglionic
sympathetic fibers. Among the most important of these fibers are the ones
passing from the superior cervical ganglion to the eye, the lacrimal,
submaxillary, and parotid glands, and the heart. The heart also receives
postganglionic sympathetic innervation from the middle and inferior cervical
ganglia. The superior cervical ganglion also sends postganglionic fibers up the
carotid canal to innervate the pineal gland. The biosynthesis of melatonin in
that gland is regulated by the light-stimulated release of norepinephrine from

the terminals of these sympathetic fibers.
The receptors of the radial muscle of the iris are of the a-type; an
increase in sympathetic activity produces contraction, /8-receptors obtain in

the ciliary muscle of the eye, sinoatrial and atrioventricular nodes, cardiac
atria, ventricles, and conduction system of the heart. Excitation therefore
produces relaxation of the ciliary muscle, an increase in heart rate and
conduction velocity, in the force of contraction of the heart and in the rate of
its intrinsic pacemaker.
The stellate ganglion receives its input mainly from T1 (first thoracic
vertebral level) and sends postganglionic fibers to the heart, lungs, and
bronchi whose muscles contain mainly β -receptors which are relaxed by an
increase in sympathetic activity. However, the musculature of the lungs also
contains α-receptors and is, therefore, subject to constriction by sympathetic
excitation.
The celiac ganglion receives sympathetic input from T5-9 through the
greater splanchnic nerve which also directly innervates the adrenal medulla.
Other ganglionic input comes from the lesser splanchnic (T10-11) and the least
splanchnic nerves (T11-12). Postganglionic fibers from the celiac ganglion
innervate the liver, bile ducts, gall bladder, splenic capsule, stomach, small
bowel, proximal colon, kidney, and ureter. Sympathetic excitation is mediated
by /8-receptors in the stomach and intestine to decrease motility and tone,
and by α-receptors to contract its sphincters. The capsule of the spleen is

contracted by the mediation of a-receptors. Sympathetic discharge induces
the biosynthetic enzymes of norepinephrine and epinephrine, so that adrenal-

gland levels of these enzymes are raised. On the other hand, dopamine blood
levels are raised by an increase in biosynthesis in sympathetic fibers, and not
by its liberation from the adrenal medulla.
From the levels of T12-13 preganglionic fibers pass to the superior and
inferior mesenteric ganglia. The former innervate the distal colon and rectum
to decrease motility and increase the contraction of the anal sphincters; the
latter supplies the urinary bladder whose β -receptors relax the detrusor
muscle while a-receptors of the trigone and sphincter are made to contract.
Ejaculation of semen is produced by sympathetic activity. The type of
receptor in the appropriate muscle is not known.
Fibers from the lower thoracic and the first three lumbar segments also
supply the sacral ganglia which send postganglionic fibers to blood vessels,
hair follicles, and sweat glands of the legs.
Their postganglionic fibers (“gray rami”) are carried in spinal nerves for
distribution to blood vessels of the skin, sweat glands, hair follicles and the
vessels in skeletal muscle. Except for a double system of receptors in the

skeletal muscles of the legs, all of these structures contain a-receptors. Thus,
constriction of blood vessels and slight local secretion of sweat glands are
produced when these receptors are stimulated.
Anatomy of the Parasympathetic Nervous System
The cells of origin of the parasympathetic nervous system reside in
nuclei of the third, seventh, ninth, and tenth cranial nerves, and in the gray
matter of the second, third, and fourth segments of the sacral spinal cord. The
axons of these cells pass to ganglia which lie close to the organs which they
innervate. From the E dinger-Westphal nucleus of the oculomotor nerve, cells
pass to the ciliary ganglion whose postganglionic fibers innervate the
sphincter muscle of the iris and ciliary muscle, both of which contract on
nerve or ganglionic stimulation.
Excitation of fibers from the nucleus of the facial nerve pass to the
sphenopalatine ganglion and thence to the lacrimal gland to cause tears to
flow. Parasympathetic excitation produces salivation and vasodilation in the
nasal and oral cavity by virtue of outflow from the same nerve via the chorda
tympani and ganglia which innervate the sublingual and sub-maxillary gland.
The glossopharyngeal nerve sends preganglionic fibers to the otic ganglion

from which postganglionic fibers pass to the parotid gland. The motor
nucleus of the vagus nerve sends very long preganglionic fibers to all the
viscera except the distal colon, bladder, ureter, and genitalia which receive
innervation from cell bodies in S2-4, spinal cord segments via the pelvic
nerves. The parasympathetic ganglia lie on or in the organs they innervate.

Short postganglionic fibers pass to the receptor sites in them. In the wall of
the gastrointestinal tract, vagal preganglionic fibers synapse around the
ganglion cells of the plexuses of Auerbach and Meissner. Parasympathetic
excitation produces dilatation of blood vessels in most organs; other muscles
such as those in the bronchial tree, stomach, intestine, gall bladder, and the
detrusor muscle of the bladder are made to contract, or their tone and
motility is increased by parasympathetic discharge. A decrease in heart rate
to the point of atrioventricular (AV) block is produced by vagal discharge
which also reduces conduction velocity in, and the contractile force of the
heart. Secretion of all exocrine glands is increased by parasympathetic
discharge. Penile erection is produced by it.
In other words, most organs are doubly innervated, except for the
adrenal medulla, pilomotor muscles, many vascular beds in skin, and muscle
and the sweat glands of the skin.
Neurotransmission in the Autonomic Nervous System
Central to our understanding of the function of the autonomic nervous
system is the concept of neurotransmission. Autonomic nerve impulses elicit

responses in smooth and cardiac muscle, exocrine and some endocrine
glands, and postsynaptic neurons by the liberation of specific, identified
chemical substances. Great strides have been made in our understanding of
the storage, release, biosynthesis, and removal of these substances. But our
understanding of the receptor mechanisms by which these substances exert
their effect postsynaptically is just barely beginning.
Acetylcholine is the neurotransmitter of all postganglionic

parasympathetic fibers and a few postganglionic sympathetic fibers, such as
those leading to the sweat glands and the sympathetic vasodilator fibers.
Preganglionic sympathetic and parasympathetic fibers release acetylcholine. A
branch of the greater splanchnic nerve which innervates the adrenal medulla
also releases acetylcholine, and may influence the biosynthesis of
norepinephrine and epinephrine in this gland by the induction of the enzyme,
tyrosine hydroxylase (TH). 2
Norepinephrine is the principal sympathomimetic substance in

postganglionic sympathetic nerves (It may also play a role as an inhibitory
neurotransmitter in clearly defined tracts in the brain such as the median
forebrain bundle and a tract from the locus coeruleus to Purkinje cells in the
cerebellum. Other amines such as histamine, serotonin, and certain amino
acids, y-aminobutryic acid and glycine—may also play unidentified roles in
central neurotransmission.)
The effect of the neurotransmitter substances on end organs and
postsynaptic fibers is in part a function of whether they produce excitation or

inhibition; the intrinsic activity of the innervated structure; the state of the
receptor of that structure; and the rates of synthesis, release, reuptake and
enzymatic destruction or diffusion of the neurotransmitter. All these factors
determine the ultimate response of the end organ whose activity the
psychophysiologist wishes to measure.
There are, of course, fundamental differences between the responses of
autonomically innervated structures and those innervated by striated muscle.
Seeing that psychophysiologists are interested in responses from both types

of structures, these differences might be worth dwelling upon. Preganglionic
autonomic fibers are typically myelinated and have the properties of B-fibers,
whereas motoneurons (A-fibers) have a larger diameter and thus a much
greater conduction rate and shorter spike duration and absolute refractory
period. Postganglionic sympathetic axons are unmyelinated (sC-fibers), have
smaller fiber diameters, the slowest conduction velocity (in comparison to A
and B fibers) and a relatively long spike-potential and absolute refractory

period.
The responses of the effector organ is, in part, also the product of
relatively slower destruction and thus more prolonged action of the

transmitter.
Skeletal muscle responds to a single stimulus to its motor nerve by a
brief solitary event—the action potential of the muscle, measured by EMG
(electromyogram), followed by the muscle twitch which can be recorded as a
smooth increase and then decrease in muscle tension. When a sympathetic
axon is stimulated, a muscle action potential shows an initial deflection
followed by a series of asynchronous deflections which continue for several
seconds after repolarization of the nerve fiber has occurred. The tension
record of the smooth muscle shows a gradual and prolonged buildup

associated with each muscle action potential change. The transmitter agent
remains and continues active long after nerve action has ceased.
Synaptic Transmission
The same mechanism of axonal transmission applies in postganglionic
adrenergic and cholinergic fibers. The nerve-action potential consists of a
self-propagated reversal of negativity of the axonal membrane (seen from the

point of view of the internal potential of the axon) as a result of the admission
of sodium and egress of potassium ions. When the action potential arrives at
the presynaptic terminal either excitatory or inhibitory transmitter is
released by a mechanism that is not wholly understood.
In all probability, and based on the model of neuromuscular
transmission, there is a continuous quantal release of transmitter during the

resting state which does not, however, produce enough depolarization of the
post-synaptic membrane to reach the “firing level.” When the “firing level” is
reached, a postsynaptic action potential is generated.
When the excitatory transmitter combines with postsynaptic receptors,
a localized depolarization occurs which can be recorded by means of an
intracellular electrode, as an excitatory postsynaptic potential (EPSP)—that
is, a decrease in negativity of the direct current (DC) potential by virtue of an
increase in permeability of all ions, particularly those of sodium and
potassium. Inhibitory transmitters produce the opposite effect—that is,
hyperpolarization with an increase in negativity of the DC (the inhibitory

postsynaptic or IPS) potential due to an increase in permeability to potassium
and chloride ions.
When the “firing level” has been reached, a propagated action potential
is produced in the nerve, and a muscle action potential in most skeletal and
cardiac muscle. In certain types of tonic skeletal muscle and in smooth muscle
in which propagated impulses do not occur, an EPSP initiates a local
contraction, while in gland cells it initiates secretion, probably by means of

the induction of enzymes.
Acetylcholine
The excitatory transmitter in autonomic ganglia is acetylcholine. It is
probably synthesized by choline acetylase in the region of axon terminals and
stored in highly concentrated, ionic form in synaptic vesicles. Acetylcholine is
rapidly removed presumably by a specific and specialized enzyme,
acetylcholinesterase, which splits the molecule into choline and acetic acid,
once acetylcholine is liberated into the synaptic cleft. Acetylcholinesterase, on
the other hand, is located at the surface in the infoldings of the postjunctional
membrane, and in the subneural apparatus of the motor end plate of most
skeletal muscle. In the superior cervical ganglion of the cat, the enzyme is
located external to the presynaptic membrane.
Modification of synaptic transmission at ganglia is produced by
epinephrine and norepinephrine. They can depress transmission in low
doses, and in even lower concentrations enhance it. Thus, it has been
proposed that the regulation of transmission may occur by an interaction of
acetylcholine and these two catecholamines.
In sympathetic postganglionic fibers, Burn has suggested that
acetylcholine is released on stimulation which, in turn, causes the release of
norepinephrine to act on effector organs. However, this hypothesis which
would explain many diverse observations is not generally accepted. If

confirmed, it would give acetylcholine a role additional to that of a
neurotransmitter.
In fact, such a role is suggested by the fact that acetylcholine, choline
acetylase and acetylcholinesterase are present at a variety of nonsynaptic
sites. It has also been suggested that it plays a role in axonal conduction, in
the regulation of membrane transport and permeability, and as a local
hormone.
Physiological Effects of Acetylcholine
All of the physiological effects of acetylcholine are very brief because of
the speed with which it is hydrolysed by acetylcholinesterase. The effects

noted are mainly those that might be expected after stimulation of
postganglionic parasympathetic nerve fibers.
In the cardiovascular system, it may produce vasodilatation, a decrease
in blood pressure, bradycardia, arrhythmias, including partial or complete
atrioventricular block, and ventricular standstill, etc. But most of these effects
are counteracted because of the simultaneous release of catecholamines by
the adrenal medulla. In fact, in man, the drug has to be given in large doses
and rapidly, to produce these and other effects such as lacrimation, salivation,
sweating, cough, and vomiting which are due to increase in tone, amplitude,
and peristaltic activity of the stomach.
Catecholamines and Adrenergic Transmission
We owe to Elliot the concept of adrenergic transmission, to von Euler

the identification of norepinephrine as the adrenergic transmitter, and to
Axelrod the explanation of the metabolic disposition and some of the steps in
the biosynthesis of norepinephrine and epinephrine. From the point of view
of integrative behavioral biology and psychophysiology in particular, recent
advances in understanding the role of the catecholamines in the brain and
periphery have wide-ranging significance.
Epinephrine is synthesized in five steps from the amino acid
phenylalanine:
The enzymes involved in this biosynthetic pathway are not specific and
it may be that other biosynthetic steps to epinephrine are possible.
Furthermore, the enzyme L-aromatic amino acid decarboxylase also

participates in the synthesis of important biogenic amines such as histamine,
tyramine and serotonin.
Also of interest is that epinephrine, the end product of biosynthesis,
inhibits tyrosine hydroxylase (TH) while TH is induced trans-synaptically and
by cortisol. In the same manner PNMT is induced, while dopamine is liberated
into the blood stream by adrenergic nerve endings.
Once synthesis has occurred norepinephrine is stored in the terminals

of postganglionic sympathetic fibers and brain, while epinephrine is thought
largely to be localized in chromaffin cells, particularly of the adrenal medulla.
Both are stored as catecholamine-adenosine triphosphonucleotide salts in

storage granules. During their synthesis, the biosynthetic step from dopa to
dopamine takes place in the cytoplasm of nerve terminals. Dopamine enters
the granules of postganglionic nerves and the adrenal medulla, and is then
converted into norepinephrine. In the adrenal medulla, norepinephrine

leaves the granules, is converted to epinephrine in the cytoplasm and
reenters another set of granules where it is stored. After nerve stimulation
and when norepinephrine appears in the blood stream, about half is taken up
again and stored intracellularly in neurons, and the other half is rapidly
degraded by two enzymes, monoamine oxidase (MAO) and cate-cholamine-O-
methyl transferase (COMT), to produce 3,4-dihydroxymandelic acid (by
MAO), 3-methoxy-4-hydroxymandelic acid (by COMT), and normetanephrine

(by COMT). Normetanephrine is further degraded into 3-methoxy-4-
hydroxyphenylglycol by MAO, and conjugated with sulfate or glucoronide.
The mechanism of release of norepinephrine by the nerve action
potential is as yet unknown (see above). In the adrenal medulla,
preganglionic fibers release acetylcholine which may combine with receptor
sites at the surface of the chromaffin cells, following which calcium ions may
enter these cells to mobilize stored catecholamines.
The fate of released epinephrine is similar to that of norepinephrine
according to the following scheme:
Physiological Effects of Adrenergic Transmitter Substances
Catecholamines can produce powerful excitation and inhibition of
smooth muscle, depending on which muscle it acts and in which dosage. As

mentioned in the introduction, norepinephrine’s action is chiefly excitatory
and isoproterenol’s chiefly inhibitory; epinephrine has equivalent excitatory

and inhibitory effects. In the CNS norepinephrine is postulated to be an
inhibitory transmitter.
Physiological Effects of Epinephrine
Epinephrine and norepinephrine have different effects on heart rate,
epinephrine being more likely to increase it. Both increase the reflex vagal
tone through stimulation of mechanoreceptors in the carotid sinus and aortic
arch; but the vagal afferent activity after epinephrine is less than after
norepinephrine. Furthermore, epinephrine has a more potent effect in
stimulating the β-receptors of the heart to keep the blood pressure
comparatively low. Epinephrine also reduces peripheral resistance when

compared to norepinephrine. The net effect is that norepinephrine tends to
increase heart rate less, but to increase diastolic and systolic blood pressure
and peripheral resistance more. In fact, the main effect of epinephrine is to

raise the systolic blood pressure, the mean pulmonary-artery pressure, stroke
volume, cardiac output, and coronary blood flow. It is well known that it may
cause cardiac arrythmias (especially premature ventricular contractions).
Muscle blood flow is greatly increased to the detriment of the blood flow in
the skin which is much reduced. Splanchnic blood flow (especially hepatic
flow) is increased by it, as are oxygen consumption, blood sugar, lactic acid
levels, free fatty acids, plasma cholesterol, phospholipids, and some

lipoproteins.
The chief effect of epinephrine is to constrict arterioles, thereby raising

the blood pressure. But the action of epinephrine on other smooth muscle
depends on the type of epinephrine receptor involved. Bronchial smooth
muscle is dilated by it and gastrointestinal muscle relaxed or inhibited. On the

other hand, the splenic capsule is contracted by epinephrine, partly
accounting for the increase in circulating red blood cells following stress, or
hemorrhage.
The behavioral effects of epinephrine injected into human subjects are
headache, apprehension, restlessness, and tremor. Such effects are, however,
not always produced in all subjects. Much depends on the prevailing mood of
the subject, the circumstances under which the drug is given, and what kinds
of previous experiences are aroused in the subject.
Physiological Action of Norepinephrine
In contrast to epinephrine, norepinephrine acts mainly on α-receptors

except for its action on the β-receptors of the heart. It has much fewer
metabolic effects than epinephrine, although in some cells it stimulates the
induction of adenylcyclase and thus cyclic AMP in the same manner as

epinephrine does. Hyperglycemia is produced by norepinephrine. As
mentioned earlier, its cardiac effects are mainly to increase diastolic blood
pressure, although systolic blood pressure is also increased; cardiac output

remains unchanged or is decreased. Blood flow is reduced through the brain,
kidney, liver, and skeletal muscle by virtue of its vasoconstrictor action, while
coronary blood flow is increased. Bradycardia is produced reflexly, by
norepinephrine; it may cause cardiac arrhythmias.
Integrative Autonomic Mechanisms
Afferent Fibers of the Autonomic Nervous System
A very rich system of visceral afferent fibers, about which still relatively
little is known, passes from most organs by means of nonmyelinated fibers

into the nervous system via the pelvic, splanchnic, vagus, and other nerves.
Visceral afferent fibers make up a major proportion of the total fiber content
of these nerves. About one-half of the splanchnic nerve and even more of the
vagus are afferent. Other autonomic afferent fibers from skin structures and
blood vessels in striated muscle run centripetally in somatic nerves. The cell
bodies of most visceral afferent fibers are located in the dorsal root ganglia of
spinal nerves, and in the equivalent sensory ganglia of cranial nerves, e.g., the
nodose ganglion of the vagus and the petrosal ganglion of the ninth nerve.
Visceral afferent impulses then pass into the dorsal horns of the spinal cord
and make synaptic connections with cells in the intermediolateral columns of
the spinal cord and in respective cranial nerve nuclei. These cells give rise to
afferent fibers which pass to the autonomic ganglia outside the spinal cord.
Autonomic afferent fibers mediate visceral sensation (including pain

originating in organs, and are, in part, responsible for “referred” pain). They
regulate visceral and hormonal interrelationships and a number of very
important respiratory, visceromotor, vasomotor, bladder, and cardiac
reflexes. The mechanoreceptors of the carotid sinus and aorta, and the
chemoreceptors of the carotid and aortic bodies play a crucial role in the
regulation of respiration, heart rate, and blood pressure. These receptors are
also involved in the regulation of aldosterone production. Stimulation of the

mechanoreceptors at the junction of the thyroid and carotid arteries in the
dog inhibits aldosterone3 production, while a fall in blood pressure increases

the output of this steroid. Cutting the thyrocarotid branch of the vagus nerve
or occluding the inferior vena cava also increases the production of

aldosterone. In addition, an increase in carotid sinus activity reflexly reduces
adrenal catecholamines and antidiuretic hormone output.
The principal arterial baroreceptors are in the aortic arch and carotid
sinus. Sudden increases in pressure at the carotid sinus produce a marked
increase in frequency of discharge in baroreceptor afferent units, which adapt
slowly during continued elevation of pressure. When the pressure is pulsatile
rather than constant, the firing rate is greater and in concert with the
ascending limb of the pressure change. Afferent activity in the mesenteric

nerves may also be increased by perfusion of the duodenum with various
food stuffs.
Pulmonary artery baroreceptors are active at normal pulmonary artery
pressures and seem to respond mainly to the rate of pressure change with
each pulse. Pressure receptors within the atrium and ventricle of the heart
also produce two types of afferent neuronal activity. A burst of activity occurs
with each atrial contraction and is proportional to its amplitude. Another
burst of activity occurs at the time of ventricular systole; in other words,
these neuronal units fire proportional to the amount of filling of the

pulmonary and systemic venous system. Ventricular receptors provide inputs
proportional to changes in systolic ventricular tension.
The arterial chemoreceptors adapt slowly and are mainly influenced by
variations in arterial pO2, pCO2, and pH. In the steady-state, there is a
continuous discharge which is markedly enhanced by changes in the partial
pressure of oxygen in arterial blood, an increase in arterial CO2 tension, or a
fall in blood pressure.
The largest group of vagal afferents comes from the lungs. Stretching of
lung inflation receptors in bronchioles and bronchi increases the firing rate of
these afferent units; some adapt rapidly, others slowly. Those receptors
which are slowly adapting are probably involved in cardiovascular reflexes.
Sensory inputs which travel in somatic, not sympathetic afferent nerves,
arise from muscle, the skin of the face, and from viscera and are involved in
reflex cardiovascular adjustments which occur with exercise, with facial
stimulation, or stimulation of the vibrissae in mammals, during the diving
reflex, or visceral irritation and inflammation. Other sources of input,
probably mediated by autonomic afferents, arise from the gut, kidney, and
bladder.
From the viscera, sympathetic afferents travel either by an extra spinal

pathway by way of the sympathetic chain which finally enters the spinal cord,
or by way of the ipsilateral spinal fasciculus gracilis, or by a bilateral pathway
in the anterolateral region of the white matter of the cord. Some of the
pathways of splanchnic origin reach the cerebral cortex via the thalamus,
others pass to the posterior hypothalamus.
In other words, a wide variety of physiological stimuli may influence

afferent activity in autonomic nerves, and therefore act as input to the CNS.
This input, in turn, interacts with ongoing central activity, so that regulation
of a wide variety of peripheral physiological processes occurs. Probably the
regulation of blood pressure is the best understood process. A review of the

integration and regulation of blood pressure by the nervous system allows
one to conclude that only some afferent impulses from mechanoreceptors and
chemoreceptors in the heart and major blood vessels, and from the peripheral
vascular tree, ascend higher in the nervous system than the medulla and
pons. Yet, the vasomotor system of the brain stem is also in turn under the
control of two major circuits, one of which—the sympathetic vasodilator

system—has in all probability important implications for psychophysiology,
as the following account will show.
Organization of Autonomic Reflexes
There is some evidence that autonomic reflex activity may be mediated
by autonomic ganglia without the participation of the spinal cord.

Preganglionic fibers may give off collaterals to ganglia other than the ones
they innervate, so that stimulation of the distal part of a preganglionic fiber
isolated from the spinal cord may activate ganglia lying proximally. Although
such evoked activity is known as an “axon” reflex, it is not a reflex in the true
sense. Axon reflexes play a part in man in the vasodilatation produced in
muscle after contraction. Postganglionic “axon” reflexes have also been
invoked to explain local sweat responses to electrical stimulation of the skin,

but this response may be due to branching postganglionic fibers; branching
occurs near the innervated area so that fibers are sent in all directions. To
explain the local sweat response one would have to postulate that stimuli
pass antidromically up one fiber and orthodromically down another to cause

sweating. Other vasomotor responses of the skin are truly reflex. The afferent
arc of the reflex may either be sensory or autonomic.
Visceral autonomic afferents may also produce reflex striped muscle

contraction. The abdominal muscles contract when the gut or peritoneum are
irritated.
Two main kinds of regulatory mechanisms determine activity in
preganglionic autonomic neurons which are maintained in a continuous but
variable state of neuronal activity. There are segmental sensory and
autonomic inputs through dorsal roots, inputs from pontomedullary neurons,
and finally from neural circuits which descend from structures which lie
rostral to the brain stem.
In animals whose spinal cords have been cut above the thoracic level, a
state of spinal shock is present and all autonomic reflexes are depressed:
Blood pressure and peripheral resistance are low, the urinary bladder is
paralyzed, there is no regulation of body temperature and no sweating. But
after several weeks, blood pressure levels rise; further rises occur when the
skin of the body is touched or pinched below the level of transection. After the
“spinal shock” passes off, some body-temperature control and sweating is

then reestablished. For example, profuse sweating can be provoked by
stimulation of the skin of the body. Urination, defecation, and sexual reflexes
reappear and can also be stimulated by stroking the appropriate segments of

the body. Chronic decerebrate preparations demonstrate many of the
characteristics of the spinal animal with regard to autonomic reflexes, except

that arterial pressure is well-maintained, and none of the profound blood-
pressure changes, which are precipitated by changes in posture and seen in

spinal animals, occur.
Decorticate animals do not show any of the changes in autonomic
reflexes seen when more extensive amounts of the nervous system are
removed. But these animals do respond to pinching of the skin by “sham” rage
behavioral responses and a coordinated massive autonomic (sympathetic)
discharge.
Spinal reflexes may be monosynaptic or multisynaptic. Their segmental
arrangement is as follows:
Head and neck T1-5
Pupillodilatation C8-T1
Arms T2-9
Lacrimal gland T1-3 (sympathetic)
Cardiac acceleration T2-6
Vasomotor responses, sweating:
Upper trunk T4-9
Lower trunk T9-L2
Lower extremities T12-L2
Abdominal viscera T4-L2
Genitourinary and anorectal (sympathetic) reflexes L1-2
Central (Supramedullary) Control of Autonomic Functions
We have seen that autonomic reflexes can either be local or spinal. And
it is characteristic of the reflexes in spinal man that they are massive and can
be set off by trivial cutaneous stimulation or by temperature alterations.
Generally speaking, these very marked responses are attenuated by a
complex series of neuronal circuits that course throughout the nervous
system. As mentioned earlier, amongst the most important regulatory devices
are those to be found in the hypothalamus. At least, and in the case of the
body-temperature control system, these mechanisms are arranged in such a
reciprocal manner that negative feedback characterizes their interactions.
The posterior and lateral nuclei of the hypothalamus are concerned with the
regulation of food intake and temperature; their stimulation leads to massive

sympathetic discharge including norepinephrine release.
In the hypothalamus, parasympathetic functions are regulated by
midline nuclei in the region of the tuber cinereum and nuclei lying closer to
the anterior section. Inputs from the limbic system, cortex, thalamus, and
striatum probably modulate the activity of these hypothalamic centers.

Stimulation of the perifornical hypothalamus can alone elicit complex
emotional behaviors in cats as well as marked sympathetically mediated
changes in blood pressure and heart rate, and produce piloerection, etc.
Regulation of Blood Pressure
Central (Brain-Stem) Mechanisms
Before going on to speak about the neurogenic control of blood pressure
and peripheral resistance, some general remarks seem in order.
Concepts about the neurogenic control of blood pressure are, in part,
limited by the fact that so much of our knowledge of cardiovascular

regulation, and the control of blood pressure in particular, derives from
observations made on excised organs and anesthetized animals while varying
a single input. Only with the development of new recording methods has it
been feasible to make observations on intact unanesthetized animals.
These new techniques eliminate various kinds of artifacts caused, for

example, by exposing the heart and lungs in acute experiments, and by
anesthesia. In addition, behavioral observations can be made in
unanesthetized animals while studying cardiovascular function during
exercise or while the animal is interacting with its environment, or during
brain stimulation, etc.
Chronic brain stimulation may be used to induce elevations of blood
pressure while the animal’s behavior is observed. Finally, the hope would be
to develop in the future, knowledge of the complete neural and neuronal

pathways and the activity in them during such manipulations.
The rapid cardiovascular adjustments which precede and accompany
exercise demonstrate a case in point. Whereas these adjustments were once
considered to be instigated purely by peripheral mechanisms, it is now
believed that the onset of vasodilation and increased flow in muscle, heart
rate, and output, etc., at the start of exercise, emanate from the nervous
system as an autonomic concomitant to the muscular activity which is under
volitional control. These cardiovascular changes at the start of exercise can be

abolished by lesions in the fields of Forel, and can be replicated by stimulation
in this area.
In other words, there exist integrated patterns of cardiovascular and
motor activities, exemplified by the changes with exercise. Furthermore,
these cardiovascular adjustments seem quite specific to a given behavioral
activity; other adjustments probably occur with other activities.
In this way one might expect that our ignorance about the neuronal
activity which must underlie volitional activity, its correlated affect, and
circulatory changes would gradually be dispelled. At present, we know little
about the pathways which subserve the emotions of anger, fear, resentment,
or the adjustments with exercise.
We also know little about how these emotional states influence

homeostatic cardiovascular mechanisms. It is not unlikely that they do so by
biasing tonic neuronal activity in complex circuits which run between the
mechanoreceptors, the medulla, the midbrain, the hypothalamus, and limbic
and cerebral cortices. If different cardiovascular adjustments accompany
different behavioral activities, then it is likely that central excitatory
influences on the brain stem and hence vasoconstrictor outflow may be quite
selective. For example, the sympathetic vasodilator discharge pattern
emanating from the hypothalamus is characterized by adrenergic discharge
to almost the entire vascular bed, with the exception of skeletal muscle. The
same differential effects occur in vasoconstrictor fibers when activated by
cortical stimulation.
The foregoing statements must have some validity in the light of Miller’s
work and from studies on the organismic response known as the “defense”
reaction which was first described by Hess. Sympathetic vasodilation in

muscle, increased heart rate, vasoconstriction in vascular beds other than
muscle, and increased secretion of catecholamines occur during the defense
reaction. Analogous vascular changes are found in man during states of fear,
and mental arithmetic, and may occur during anticipatory states.
The behavior of cats when the defense reaction is elicited consists of
growling, hissing, running, pupillary dilation, and piloerection. The defense

reaction occurs not only when the hypothalamus near the entrance of the
fornix is stimulated, but also with stimulation of the dorsomedial amygdala
and striae terminalis. The axonal connections between these nuclear regions
and others are still not certain. That other connections must exist is suggested
by the fact that it is known that the cerebral cortex attenuates the violence of
the defense reaction.
The defense reaction is mentioned as an example of a selective
vasomotor and behavioral response, and because Folkow and Rubinstein

have been able to produce sustained hypertension by mild and intermittent,
daily stimulation for several months in the area of the hypothalamus known
to elicit the defense reaction.
Different affective states in man can be accompanied by other and
different cardiovascular changes. For example, when a man is hostile or
resentful the blood vessels of the gastrointestinal mucosa dilate.
Peripheral Resistance by the CNS
Central to current notions about CNS regulation of blood pressure is
that vasomotor regulation is brought about through variations in

vasoconstrictor tone. Decreased vasoconstrictor discharge leads to
vasodilation, increased discharge to constriction.
Afferent impulses pass from the carotid sinus and aortic arch
mechanoreceptors responsive to stretch, and from chemoreceptors which are
sensitive to increases in arterial pC02. Stimulation of the mechanoreceptors
leads to vasodilation by inhibition of tonic vasoconstrictor outflow, while
stimulation of the chemoreceptors causes vasoconstriction. From the carotid
mechanoreceptors, afferent impulses pass via the sinus nerve to the
medullary vasomotor centers. At high blood pressures neural discharge is
sustained, not phasic, and adaptation may occur to such pressures. However,
different firing patterns in the sinus nerve occur and depend on fiber size,
because the sinus nerve contains fibers of varying diameters. In view of the
fact that cutting the sinus nerve increases blood pressure, tonic discharge
from the mechanoreceptors must also be present.
Afferent impulses also arise from the atrial walls of the heart and
ventricles, and from the walls of the great veins. Sensory, especially pain
receptors, influence vasomotor tone, possibly via the agency of the medullary
center. In addition to input to the vasomotor center from mechano- and
chemoreceptors, etc., input may travel in sympathetic afferent fibers to enter
the cord.
We owe to Ranson and Alexander most of our knowledge about the
vasomotor center. The pressor area lies in the lateral reticular formation of
the rostral two-thirds of the medulla, while the depressor center lies medially
in the reticular formation and more caudally in the medulla. Tonic inhibition
of spinal cardiovascular mechanisms largely emanates from the depressor
zone. The neurons of both of these medullary areas are continually active.
Tonic excitatory influences from the pressor area impinge on the same spinal
neurons. But the synaptic events at spinal vasomotor neurons and the
patterns of interactions of the two descending influences on them largely

remain unknown. The intensity of the discharge in preganglionic
vasoconstrictor neurons must be the resultant of the two descending tonic
influences. The frequency of tonic discharge in the thoracic sympathetic
outflow is relatively low, and discharge occurs in rhythmic bursts, in concert

with the pulse beat and respiration. Thus, the afferent discharge is probably
driven by input to the medullary center from mechanoreceptors in the great
vessels and its branches.
The fall in arterial pressure on activation of mechanoreceptors is

probably largely accomplished by peripheral vasodilation in muscle, the
splanchnic bed, and the skin through inhibition of vasoconstrictor tone.
The mechanisms subserving vasomotor tone have been reviewed above

because of the role that mechanoreceptor activity has played in the
hypotheses about the maintenance of elevated blood pressure.
Acute and chronic elevations in arterial pressure result from
denervation of the sino-aortic region. But, in animals, at least, the resulting
hypertension is labile and accompanied by tachycardia. The elevated blood
pressure could be lowered in dogs by exercise and hypotensive drugs with
considerably more ease than essential hypertension can be in man.
The effects of denervating mechanoreceptors, though instructive in

their own right, do not necessarily prove or disprove their role in naturally
occurring essential hypertension. There is considerable evidence to suggest
that the carotid sinus reflex remains active and functioning in essential
hypertension but that the mechanoreceptors adapt to high levels of blood
pressure and, therefore, no longer act maximally to reduce pressure levels.
This adaptation occurs in dogs within one to two days after a renal artery is
clamped, and is characterized by an increase both in threshold and the range

of response of the mechanoreceptors. Recordings from the sinus nerve show
a decrease in discharge frequency with changes in pressure in these
hypertensive animals. It is not as yet clear what the nature of this adaptation
to higher blood pressure is. It is likely to be due to the direct effect of a high
systemic pressure rather than to a chemical substance. Such an adaptation to
an elevated mean blood pressure would act to sustain it; the decrease in
afferent discharge would lead to decreased inhibition of vasomotor tone and

therefore further vasoconstriction. These data have led to therapeutic
measures designed to counteract the adaptation of the mechanoreceptors.
Electrical stimulation of the sinus nerve lowers blood pressure in

hypertensive patients.
Stretching of the mechanoreceptors has effects on the CNS in addition to
lowering the blood pressure. Bonvallet et al. have distended the carotid sinus
while maintaining blood pressure at a constant level, to produce cortical
synchronization. They believe that an increase in afferent activity occluded
the tonic, corticopetal, desynchronizing influences of the midbrain reticular
activating formation. Therefore, one might postulate that if mechanoreceptor
adaptation occurs in hypertension, there would be a tendency in the opposite

direction, i.e., for cortical desynchronization and behavioral arousal.
An elevated blood pressure may affect the CNS directly and in addition
to the effects mediated by mechanoreceptors. Thus Baust et al. reported that
raising the blood pressure may directly cause desynchronization of the EEG in
the encephaleisole cat, by virtue of its effect on the mesencephalic reticular
formation. The mechanical effect of a rise in blood pressure may cause the
firing rate of single posterior hypothalamic and mesencephalic reticular

neurons to increase. One might well ask, therefore, if this mechanical stimulus
also causes the release of humoral substances (for example, vasopressin).
Central Control of the Vasomotor Center
In the cerebral cortex, for example, there are widely distributed points
which, on stimulation, modify the blood pressure and which may be way
stations in complex circuits of which the medullary and spinal centers are a
part.
Stimulation of the gyrus poreus and the sigmoid gyrus in cats and the
motor strip in monkeys increases the blood pressure. In addition, when the
sensorimotor cortex of the cat is stimulated changes in renal volume occurred
without blood-pressure changes, while chronic stimulation of the anterior
sigmoid gyrus in cats produced renal vasoconstriction and renal cortical

ischemia.
Presumably, these cortical stimuli facilitate vasomotor discharge by

pathways and synaptic connections which largely remain unknown. One of
the known outflow tracts from the sigmoid gyrus and the pericruciate cortex
is the pyramidal tract. In fact, there is evidence that this tract is involved in
the regulation of vasomotor activity, possibly by means of collaterals to the
pons and medulla or by influencing spinal autonomic mechanisms directly.
Other cortical areas may produce their effects by other pathways,
presumably to the hypothalamus. Lesions of the hypothalamus yielded

vasomotor responses to stimulation of the surfaces of the posterior orbital
gyrus.
On stimulation of frontal, and temporal cortical structures, pressor and
depressor effects occur in many mammals including man. The corticofugal
pathways mediating such effects are largely unknown; they are believed not
to synapse in the hypothalamus.
On the other hand, the effects of rhinen-cephalic stimulation are most

probably transmitted via the hypothalamus. Several rhinen-cephalic areas
(the anterior limbic cortex, anterior insula, and the hippocampal gyrus) on
stimulation produce changes in blood pressure. The cingulate gyrus, both in
man and apes, is involved in blood-pressure regulation. Amygdala stimulation

reduces blood pressure. When a number of midline structures—the
nonspecific thalamic nuclei and the midbrain reticular system—are subjected
to high-frequency stimulation, marked elevations of blood pressure occur.

The effects of such stimulation persist after stimulation stops. Pressor and
depressor reflexes may be inhibited by stimulation of the vermis of the
cerebellum, presumably by modifying ongoing activity in bulbopontine

vasomotor and hypothalamic centers.
The synaptic interactions of these various regions of the brain have not
been worked out by intracellular methods. Interactions of the foregoing areas
with hypothalamic neurons and with inputs from the mechanoreceptors to

the medullary centers may be particularly important in the regulation of
blood pressure.
Not only does high-frequency stimulation of the hypothalamus produce
acute phasic increases in blood pressure, but the rate of hypothalamic
stimulation is linearly related to the impulse frequency in single fibers of the
inferior cardiac and the cervical sympathetic nerves. An occlusive interaction
between activity produced by baroreceptor activation and hypothalamic
stimulation has also been found, while blood-pressure increments produced

by stimulation of a peripheral sensory nerve are facilitated by hypothalamic
stimulation.
Following the end of simple hypothalamic stimulation, the blood
pressure continues to stay elevated for some minutes, possibly due to the
release of vasopressin, and perhaps norepinephrine. Furthermore, varying

the frequency of stimulation of a particular hypothalamic site may change a
pressor to a depressor response by causing tonic vasoconstrictor discharge to
cease. Effects on local changes in blood vessels have also been noted upon
stimulating the hypothalamus. In unanesthetized animals blood-pressure
increases may be accompanied by expressions of rage when the
hypothalamus is stimulated.
From the hypothalamus pathways involved in vasomotor regulation
may pass to, or through the mesencephalon. Axons may then travel directly to
the spinal cord, or synapse in the tegmentum of the midbrain and the
periaqueductal gray matter, or they may travel via the median longitudinal
fasciculus to end on medullary neurons. Other descending brainstem
pathways, such as the ventrolateral reticulospinal pathway, have also been
implicated in vasomotor regulation. Therefore, it seems likely that midbrain
reticular formation contributes to cardiac control.
In summary, there is still considerable controversy about the detailed
anatomy of supramedullary and suprasegmental outflow from the brain
responsible for vasomotor control. From the medulla, excitatory impulses

pass to spinal vasomotor neurons in the ventrolateral portion of the spinal
cord, while inhibitory influences travel in crossed pathways in the
dorsolateral columns.
Spinal and Peripheral Vasomotor Regulation
Stimulation in the medullary pressor area causes bilateral increase in
the tonic discharge frequency in the inferior cardiac nerve, and an ipsilateral
increment of discharge in cervical sympathetic neurons. Presumably, the
inputs from higher centers modify spinal vasomotor reflexes which are
released when the spinal cord is cut. Tonic vasoconstrictor discharge still
occurs in spinal animals, or in animals in whom the buffer nerves have been
cut. Spinal vasomotor neurons continue to be responsive to afferent inputs
even after cord transection. Sympathetic pathways extend from the lateral
horn of the spinal gray matter to sympathetic paravertebral ganglia.

Vasoconstrictor fibers to blood vessels and skin emanate from the
thoracolumbar outflow. Their effects are transmitted by postganglionic nerve
terminals.
Single unit recordings of pre- and postganglionic sympathetic fibers
yield data as to a low rate of transmission and frequency of discharge. The
degree of regional vasoconstriction is proportional to the rate of stimulation
of the cervical sympathetic trunk. Most significantly, a small change in the

rate of stimulation may bring about a marked change in resistance to flow, so
that there is a hyperbolic relationship between frequency of stimulation and
peripheral resistance.
In most vascular compartments, the narrow range of sympathetic
vasomotor discharge exerts virtually full control over the smooth muscle
effector cells. Folkow and Uvnas have suggested that there are regional
differences in vasoconstrictor discharge. It is plausible that central autonomic
neuronal pools regulating tonic discharge to different vascular regions, may
exhibit different excitability levels. Some, while remaining active, may not
increase sympathetic discharge in one vascular region but may do so in
another. If excitatory drive increases or release from inhibition occurs in
neuronal circuits, sudden phasic enhancement of vasoconstrictor discharge

may occur in one region and not another.
Neural mechanisms probably exist for massive, phasic increase of
vasomotor discharge in appropriate circumstances but also for finely graded
differential activity of automatic control over vasoconstrictor tone, due to
quantitative differences in excitability levels of neuronal discharge to
different parts of the vascular tree.
In addition to the regulation of vasomotor tone by mechanisms outlined
above, there are other sympathetic vasodilator mechanisms. Such vasodilator

nerves to skeletal muscles of mammals may be regulated by pathways from
the motor cortex via the hypothalamus, tectum of the midbrain, and the
ventrolateral medulla oblongata, from where they travel to the spinal cord.
When stimulated, vasodilation in skeletal muscle is accompanied by

constriction in the splanchnic bed and skin. As far as is known this second
system is tonically active. Its outflow runs peripherally to muscle in cats and
dogs and possibly to the skin. Little is, as yet, known about the nature of the
transmitter substance, or the more intimate neurophysiological properties of
this system.
The blood-pressure changes that occur with stimulation of various

areas of the brain are, therefore, in part, mediated by the medullary
vasomotor center and, in part, by spinal mechanisms to bring about changes
in peripheral resistance. Unfortunately, neurophysiologists interested in

using blood pressure as their dependent variable do not usually measure
changes in cardiac output or resistance to account for the changes in blood
pressure. They then fall into the same mistake as many psychophysiologists,
which is to measure only a single dependent variable.
Regulation of Respiration: Central Mechanisms
The regulation of rhythmic respiration depends on the alternation of
activity of neurons lying in two parts of the pontomedullary respiratory
center. The inspiratory center lies in the ventral reticular formation of the
upper medulla. Its neurons are driven by the C02 tension of arterial blood and
by input from chemoreceptors to produce an increase in depth of inspiration
finally leading to active expiration. The expiratory center lies lateral, dorsal,
and rostral to the inspiratory center in the medulla, and has a tonic inhibitory
function on the inspiratory center.
These two centers are the minimal mechanism for the regulation and
maintenance of respiratory rhythm. They are profoundly influenced in the
intact organism by neural influences coming from more rostral levels.
In the rostral part of the pons lies an inhibitory center, while in the
middle and caudal part of the pons a center is found which tonically controls
the inspiratory center to prevent respiratory arrest in inspiration with

maximal inflation of the lungs.
Several midbrain centers control the lower ones; e.g., stimulation of the
posterior hypothalamus produces a paroxysmal increase in respiratory rate.
The lateral thalamus reduces the rate of respiration on stimulation. As one
would expect, the main cortical sites in mammals from which changes of
respiratory rate, depth, and rhythm can be obtained are the temporal,
inferior, and superior precentral and orbito-frontal (inhibitory) cortices. This
expectation is based on the fact that respiratory patterns can be altered “at
will,” or in coordination with speaking, singing, laughter, and breath-holding.
From a physiological point of view, normal respiration is regulated by
rhythmic periods of inhibition of the tonically active, medullary inspiratory
center. This inspiratory tonus is modulated not only by the medullary
expiratory center which is progressively excited during inspiration; it begins
to discharge during inspiration to inhibit activity in the inspiratory center.
Further control on inspiration is exerted by inhibition of the medullary

inspiratory center by the pontine centers so that inspiratory tonus, mediated
by the phrenic nerve, is transformed into rhythmic respiration by a series of

reciprocally inhibiting interactions amongst brain-stem neurons which
regulate respiration.
Of particular interest to psychophysiologists is that the respiration can
be markedly influenced by intellectual work which increases its frequency

and reduces its amplitude. The type and frequency of respiration may also be
changed by exercise and emotional states, such as anticipation, excitement
(sexual or otherwise), anxiety, and depressive mood. These states are
accompanied by changes in respiratory rhythm. In the hyperventilation
syndrome, both the depth and frequency of respiration are enhanced.
Because of the close interaction of psychological factors and respiration,
and of respiration and circulation, it becomes incumbent on the

psychophysiologist to monitor respiration when measuring cardiovascular
variables.
Interaction of Cardiac and Respiratory Function
Rhythmic fluctuations of blood pressure and heart rate are seen in the
steady-state in concert with inspiration and expiration. Integration of cardiac
and respiratory function is achieved centrally. The receptor sites are: (1) The
pulmonary artery baroreceptors which are particularly sensitive to changes
in the rate of pressure with each pulse mainly to adjust respiratory

ventilation to changes in venous return; (2) The arterial chemoreceptors
which respond to a fall in arterial oxygen tension and/or a rise in the partial
pressure of arterial C02. When stimulated, there is a marked increase in
respiration, a reflex fall in heart rate, and a rise in blood pressure, due to an
increase in peripheral resistance. There is also vasoconstriction in muscle,

skin, viscera, and the kidney, and increased catecholamine production. These
responses are mediated, in part, by the hypothalamus; and (3) The lung
inflation receptors which respond to stretching of smooth muscle in the lung
with inflation to produce a cessation of inspiration. These receptors are also
responsible for most of the cardiovascular changes seen during the normal
respiratory cycle. Vagal afferent pathways mediate the responses to stretch.
Increased pulmonary stretching suppresses the reflex inhibitory effects on
the heart when arterial chemoreceptors are stimulated. The central pathways
mediating stretching pass both to the bulbar respiratory center and to the
hypothalamus and cerebral cortex.
Central Regulation of the Galvanic Skin Resistance
One of the most frequent tools used by psychophysiologists is galvanic
skin resistance, or conductance (the reciprocal of resistance). The local
factors which are responsible for conductance or resistance changes most
likely have to do with sweating and blood flow through the skin. The more
general factors influencing it are psychological stimuli and states.
Removal of the telencephalon, forebrain, and thalamus in cats causes a
marked increase in the galvanic skin response, while diencephalic destruction
causes it to decline and finally to disappear, suggesting that the telencephalon
exerts inhibitory control on the diencephalon in the regulation of the reflex.

Yet there is additional evidence that another set of inhibitory influences on
the reflex stem from the ventromedial portion of the medullary reticular
formation which, when released from facilitatory diencephalic inputs, causes
the reflex to disappear. When this caudal set of neurons is cooled or blocked
by anesthesia, the reflex is very active. Spinal transection at the level of the
first cervical vertebra abolishes the GSR (galvanic skin response).
There is further evidence that there are neuronal mechanisms

modulating the bulbar mechanism for GSR regulation in the caudate nucelus
and anterior cerebellar lobe.
Central Regulation of Rody Temperature
Two important psychophysiological variables—the moisture of the skin,
and respiration—are also involved in heat loss and conservation. Perspiration
and panting are processes which cause the body to lose heat.
The hypothalamus is involved in the control of these functions when
environmental temperature changes.
Animals, including man, with lesions of the anterolateral hypothalamus
cannot regulate their temperature in a warm environment. Body temperature

will then rise. When placed in a cold environment, body temperature is
maintained because the physiological changes for heat loss fail. In man, heat
loss is usually achieved by vasodilatation of the skin, perspiration, and
increased respiration.
If lesions are placed in the dorsolateral portion of the posterior

hypothalamus, the animal cannot make the necessary physiological
adaptations, either to a cold or a hot environment. Why should both forms of
adaptation be lost? In all probability, fibers from the anterior (heat loss)
hypothalamic nuclei are interrupted by the lesion which also destroys the
posterior (heat conservation) mechanisms. The heat conservation
mechanisms of the body include epinephrine secretion and shivering to
increase heat production, and cutaneous vasoconstriction and piloerection to

conserve heat within the body.
Stimulation or local heating of the anterior hypothalamic centers
produces sweating, panting, and cutaneous vasodilation and causes core

temperature to drop, especially if the environmental temperature is low.
Cold-induced shivering is prevented by anterior hypothalamic stimulation.
Yet, when the animal is exposed to cold, the threshold to stimulation is
increased.
The two hypothalamic centers seem, therefore, to regulate each other
reciprocally. The input to these centers is probably a dual one— one for cold
and the other for heat-—from cutaneous thermoreceptors, and from
thermoreceptors within the body (especially within the cranial cavity)
sensitive to internal changes in temperature.
It follows from this review that it is essential to maintain a constant

environmental temperature if one is measuring skin resistance or
conductance in psychophysiological experiments.
Central Control of Gastric Secretion
There is evidence to suggest that intracerebral stimulation and lesions
of various parts of the nervous system may stimulate or inhibit the secretion
of acid and pepsin, or change the production and quality of gastric mucus. For
example, low intensity (but long-term) stimulation of the anterior

hypothalamus in cats has produced hyperplasia of the gastric mucosa. In
dogs, a lesion of the anterior hypothalamus increased the basal acidity of the
gastric contents, but did not change the secretory response to maximal
histamine stimulation. It may be that the cerebral cortex tonically inhibits
gastric secretion. Both in dogs and in man, decortication raised the basal
secretion of acid in the stomach.
These findings are difficult to interpret. Obviously, species differ in their
responses to brain stimulation. In addition, the effects of stimulation on the

nervous system are always difficult to interpret; partly because different
stimulus strengths and frequencies produce different results.
Presumably, the excitatory effects of brain stimulation are mediated by
the vagus nerve. But we do not know how these excitatory effects interact
with known central inhibitory influences on vagal discharge. An increase in
neural activity in the vagus nerve causes an increase in gastric motility and
secretion. But the vagus is not purely excitatory; it also mediates inhibitory
influences on the physiological activities of the stomach. We still do not now
very much about just how these two opposing influences affect the stomach,
for example, we do not know how increased vagal discharge can cause a
dissociation of acid from pepsin secretion. The kind of information that is

needed to resolve this problem is exemplified by the work of Iggo and Leek,
who have recorded the action potential from single axons of the vagus nerve
of sheep, and related the pattern of discharge from some of these to

contractile movements of the stomach.
A dual mechanism for the regulation of gastric acid secretion also seems
to be present in the hypothalamus. Acute increases in gastric acid secretion,

as evidenced by a decrease in the pH of gastric juices, can be induced by
anterior hypothalamic stimulation. Vagotomy abolishes this response.
Stimulation of the posterior hypothalamus produces a delayed increase in

gastric acid secretion which reaches its peak after three hours; this response
is not mediated by the vagus nerve, but may be mediated by adrenal cortical
hormones because bilateral adrenalectomy abolishes it.
Chronic posterior hypothalamic stimulation can produce gastric and

duodenal hemorrhage due to ulceration. The increase in gastric acid secretion
produced by insulin also seems to act by the medium of the hypothalamus
and vagal afferent outflow.
All the mechanisms which produce acid secretion in the stomach are
still not known. Vagal afferents to the stomach may control gastrin and
pepsinogen secretion. Gastrin is a polypeptide which regulates acid secretion

in the stomach, and is, in turn, regulated both by the vagus and by a negative
feedback mechanism by increases in the acid content of gastric juice.
The Hypothalamus and Other Psychophysiological Relationships
Sexual Behavior
The autonomic nervous system is clearly involved in the sexual act, both
erection and ejaculation are under its control. In addition, during sexual
intercourse changes in heart rate, blood pressure, respiratory rate and depth,
vasomotor changes, and sweating have been recorded. Psychological factors

are presumed to play a considerable role in determining the range and extent
of such changes, and the responsiveness of the subject during sexual

intercourse.
Very much less is known about the role of the autonomic nervous
system in sexual behavior other than sexual reproduction. However, it is
known that in mammals the posterior hypothalamus plays a part in sexual
behavior and oestrus.
In fact, most of the work on sexual behavior has focused on its hormonal
control. The hypothalamus is also involved in patterned emotional behaviors
—such as the “defense reaction”—which always has very marked
concomitants of autonomic arousal. Involved in these patterns is the complex
relationship between the limbic input to hypothalamic activity.
The hypothalamus also plays a role in behavioral states such as sleep
and wakefulness, in immune responses, in stress reactions, in the prevention

of pulmonary edema, in eating behavior, in aggressive behavior, and in the
control of the secretion of pituitary trophic hormones. The implication of the

autonomic nervous system in these responses remains to be elucidated.
Other Psychophysiological Phenomena
Psychophysiologists also measure electrical phenomena, such as the
electroencephalogram (EEG), “evoked” potentials (EP), the “contingent
negative variation” potential (CNV), and the electromyogram (EMG).
Despite the fact that it is over forty years since the EEG was first
described, we still do not know what aspects of neuronal or other neural
functioning it reflects. It is used to measure differences of activity in
behavioral steady-states such as sleep and quiet wakefulness, delirium and
coma. It is affected in its activity by drugs, mental activity, sensory input, and
by changes in the blood pressure, etc.
Evoked potentials (EP) can be recorded from the scalp following
stimulation of receptors—such as in the eye, ear, or skin—by means of special
computer techniques which accumulate time-locked signals. Much
controversy has surrounded the EP, because in the intact subject time-locked
scalp muscle potentials must be differentiated from a signal of cerebral origin.
EP’s reflect the activity of sensory receiving areas to incoming impulses in
specific sensory tracts produced by the stimulus. The early waves of the EP
are believed to consist of activity in thalamocortical projections, the arrival of

impulses in cortical neurons and their responses to them. No one knows what
central processes the later waves represent. In fact, the mechanism of EP

wave forms has resisted analysis to date.
A special form of EP is the CNV, a slow negative D.C. wave recorded from
the forehead which is produced when a subject attends to a task. It again
must be differentiated from muscle EMG activity such as produced by

blinking of the eyes.
General speaking, EP and CNV are influenced mainly by central states—
such as variations in attention, sleep, drugs, etc. However, it should be noted
that in animals, at least, the early components of the EP are largest in deep
barbiturate narcosis.
The EMG’s are usually recorded from the skin surface by means of
special electrodes, and reflect tonic and phasic changes in tension in large
numbers of muscle fibers. They are particularly useful in demonstrating
changes in eye, neck, or submental muscle tone during sleep stages. Eye
movements are present and tonic submental activity is minimal during REM
period sleep. Muscle tension is increased during apprehensive or alerted
states.
The regulation of muscle tone is not fully understood. It is reflexly
maintained by segmental mechanisms, and regulated by two sets of afferent

input. Inhibitory and excitatory influences play upon the alpha-motoneuron
through the mediation of the inhibitory Renshaw cell of the cord, and by
descending pyramidal, vestibulospinal, rubrospinal, reticulospinal, and other
pathways.
Further Integrative Mechanisms
The Relationship Between the Autonomic and Endocrine System
Many of the problems in inference and interpretation about the results
of psychophysiological experiments would be simplified if multiple rather
than single physiological variables were measured. This would allow the
psychophysiologist to obtain a broader view of the biology of responses to the
independent variables which he has chosen for his experiment.
For it is increasingly apparent that there are very important
interactions between central and peripheral autonomically mediated
responses and the endocrine system, and, therefore, metabolic processes.
What is more, the interactions between these systems occur in both
directions. We have seen that ACTH (adrenocorticotrophic hormone) by
increasing cortisol production in the adrenal cortex, induces PNMT which, in
turn, catalyzes the biosynthesis of epinephrine from norepinephrine.
Epinephrine, in turn, mobilizes liver glycogen, through the medium of cyclic
AMP (adenosine monophosphate) to increase blood sugar. Insulin increases

gastric secretion reflexly through the vagus nerve. Mechanoreceptors in the
great blood vessels reflexly and, in part, regulate the release of the mineralo-
corticoid, aldosterone, which plays a central role in the control of electrolyte
metabolism and hence body water, and at the same time regulate
catecholamine and ADH release. Sympathetic discharge can bring about renin
release from the kidney, hence angiotensin production, and thereby influence
the blood pressure. Angiotensin II may increase the firing rate of supraoptic
neurons, and hence increase the release of antidiuretic hormone, thereby
diminishing urine production. Angiotensin II may also influence CNS
mechanisms directly to increase the blood pressure. The sympathetic nervous
system mediates the light-induced regulation of melatonin which, in turn, at

least, and in some mammals, influences oestrus behavior.
The central integration of autonomic outflow, as well as many metabolic
processes, occurs in the hypothalamus. The control and regulation of the
pituitary trophic hormones is carried out by hypothalamic cells. These are
believed to “transduce” electrical impulses into chemical substances, by the

release of biogenic amine neurotransmitters which, in turn, control the
release of corticotrophin, follicle-stimulating and thyrotrophin releasing and
other factors. Posterior pituitary hormones such as ADH are particularly

sensitive to environmental and other (such as painful) stimuli through the
medium of the anterior hypothalamus and the hypothalamico-
neurohypophysial tract.
Generally speaking, responses to rapid and short-term environmental
changes are mediated neurally by the autonomic nervous system by means of
ganglionic relays and postganglionic terminals to release neurotransmitter

substances at local sites. Physiological adaptations to slowly changing or long-
term environmental stimuli or situations are carried out both by neuronal

and hormonal agents. These hormones act “at a distance” and often at
widespread sites. The release of each hormone has its own time course as
discussed in Chapter 24. Intermittent and repeated environmental changes
may bring about eventual physiological adaptation. When repeated or
continuous environmental factors are imposed on young animals, their

physiological responses later in life are determined by the earlier experience,
thus providing a basis for our understanding of a critical problem in all
psychophysiological research, i.e., that of individual differences in response
tendencies.
A special and very interesting interaction between the autonomic
nervous system, behavior, and hormones has been worked out in the pineal
gland.
Fiske et al. had shown that the weight of the pineal gland decreases
when rats are kept in continuous light. Under such lighting conditions female
rats remain in continuous vaginal oestrus. These, and the observation that
extracts of the pineal gland of cattle inhibits oestrus, led to the observation
that melatonin reduces the incidence of oestrus in the rat.
We owe to Axelrod and his group the elucidation of the biosynthetic

pathway of melatonin from tryptophane:
Wurtman, Axelrod, and Phillips showed that levels of hydroxyindole-O-
methyltrans-ferase (HIOMT) in the pineal gland are elevated when rats are
kept in continuous light. Therefore, light reduces the synthesis and release of
melatonin, and this would explain why continuous light produces persistent
oestrus.
Axelrod and his associates have worked out the rather complex and
indirect pathway from retina to pineal and the manner in which the
biosynthetic machinery of the gland is influenced:
Environmental light in the mammal passes via the retina → inferior
accessory optic tract → medial forebrain bundle to the medial terminal
nucleus of the accessory optic system → preganglionic sympathetic fibers of
the spinal cord → the superior cervical ganglion from which postganglionic
fibers pass upward to the parenchymal cells of the pineal gland whose
terminal release norepinephrine.
At the same time light clearly also stimulates the retina to entrain
impulses which pass via the classical visual pathways to the visual cortex, and
in an as yet mysterious way to produce the experience of discriminated light.
The release of noradrenaline in the pineal gland influences the

formation of melatonin from tryptophane by inducing the enzyme, N-
acetyltransferase (which converts serotonin into N-acetylserotonin).
Two further points about the regulation in the pineal gland need,
however, to be made. One highlights the importance of taking into account
the time during a biological rhythm, and, the second, the importance of the
age of the animal, at which an experiment is done.
The first case is illustrated by the fact that there is a biological rhythm
for the content of serotonin in the pineal—one of the important precursors of
melatonin—and for norepinephrine in the pineal gland. The content is high
during the day under normal lighting conditions, and low at 11:00 p.m. This
rhythm is endogenous, although its driving oscillator is unknown. Despite its

endogenous nature, the oscillator can be entrained by light, e.g., when day and
night are reversed experimentally.
Norepinephrine content, on the other hand, which reaches its highest
levels at night is not controlled by an endogenous oscillator but is under the
direct environmental control of light. Thus, its high nocturnal content

corresponds to the high nocturnal content of HIOMT, and, therefore, of
melatonin synthesis.
It is, however, of great interest that the oscillator for serotonin is not
operative until the rat is six days old. Furthermore, in young rats before they
are twenty-seven days old. light affects the serotonin level in the pineal gland
by an extraretinal pathway; after this age this earlier pathway is no longer
operative.
Integrative Function of the Autonomic Nervous System
Certain generalizations about the overall function of the ANS in
maintaining homeostasis have beclouded the fact that sympathectomized
animals do survive and lead quite a normal existence. They eat, grow, sleep,
and reproduce in the laboratory. They may not be able to suckle their young,
and may be unduly cold-sensitive. Only under conditions of stress do
responses fail but even then stresses must be quite severe (such as asphyxia
stress) to reveal the absence of sympathetic regulatory devices. In other
words, there seem to be adaptations to the absence of the sympathetic

nervous system, in which otherwise redundant mechanisms take over its
function.
Modern Concepts
Modern concepts about the autonomic nervous system no longer tend
to focus as much on its role in maintaining the “constancy of the internal
environment.” Rather, its role is seen as one of the three main mediators of
the organism’s responses to his natural or social environment.
This view is implicit in Walter Cannon’s work but in retrospect it is a

point of view that has been underplayed. Rather, the field of
psychophysiology has moved in the direction of the study of controllable
psychological and sociological variables in the laboratory while measuring
single physiological ones. Furthermore, such studies deal only with responses
in the acute experimental situation. We know very much less about the
autonomically mediated responses to chronic “stresses.”
The study of organismic responses, that is, the integrated psychological
and a broad range of physiological responses, to everyday, naturally

occurring situations requires different methodologies. The responses
obtained by new techniques may require further analysis in the laboratory.
However, a giant step has been taken in this direction by the research
performed in the laboratories of Axelrod, Henry, and Kopin. They have
combined a number of techniques, taken from such diverse fields as ethology,
experimental psychology, biochemical pharmacology, and enzymology, to

demonstrate the effects on animals of short-term and long-term exposure to
stress and how such exposure affects mediating autonomic mechanisms.
Very acute stresses, preparation for activity and novel experiences, are
now known to be divided into anticipatory and reactive phases, and are
associated with increases in systolic blood pressure, heart rate, and
catecholamine and steroid excretion, etc. In all likelihood these changes are
largely mediated neuronally. The mechanism underlying the increase in

catecholamines, especially norepinephrine secretion, appears to be due to a
sharp increase in norepinephrine synthesis from tyrosine but not dopa, when
an increase in sympathetic nerve activity occurs. However, no increase in
tyrosine hydroxylase activity occurs, so that either no new enzyme is formed

or formation is inhibited by norepinephrine.
The absence of change in tyrosine hydroxylase content of tissue during
acute stresses or stimulation stands in contrast to the change that is produced

by sustained stress or sympathetic nerve activity.
Thoenen, Mueller, and Axelrod have shown that a reflex increase in
sympathetic nerve activity over several days produced a marked increase in

TH activity in the adrenal gland and in the superior cervical ganglion of the
rat, and in the brain stem of the rabbit. The activity of PNMT is also increased.
By a number of experimental procedures Axelrod and his co-workers have
shown that the changes in content of these enzymes in the adrenal gland and
in the superior cervical ganglion are not only neuronally mediated but
depend on the formation of new protein. In other words, they have shown
that the increase in TH activity is transsynaptically induced.
The increase of PNMT produced by neuronal activity is, however, also
under the control of ACTH. It depends on new protein (enzyme) synthesis and
occurs even in hypophysectomy and the administration of ACTH. To a much

lesser degree, the two other biosynthetic enzymes, TH and dopamine
hydroxylase, are similarly controlled.
That these changes in enzyme activity with sustained neuronal activity

are not only the product of the laboratory is attested to by the exquisite work
of Henry and his co-workers. It confirms the fact that chronic stress produces
marked changes in the biosynthetic enzymes of norepinephrine, but, in
addition, it produces correlated changes in blood pressure and renal

pathology.
The results of this research have been confirmed by the use of the
restraint technique. Further evidence for the dually mediated changes in

adrenal enzyme content has been obtained. Other work, using this method,
provides insight into some of the possible brain mechanisms mediating these
changes.
Restraint-immobilization has potent effects on the peripheral and
central content of biogenic amines. Kvetnansky and Mikulaj have shown that
in rats immobilization for ninety minutes produces an increased excretion
level of norepinephrine and epinephrine, associated with a decrease in
adrenal epinephrine (but not norepinephrine) content which persisted for
twenty-four hours after its conclusion. With persistent immobilization,
adrenal epinephrine content was unaffected, but norepinephrine content

increased, while the urinary excretion of epinephrine remained increased.
These results suggest that the adrenal medulla enhances its ability to replace
released epinephrine with repeated immobilization stress. This “adaptation”
to stress appears to be due to a neuronally dependent elevation of TH and

PNMT in the adrenal medulla. When immobilization is stopped, TH levels
diminish with a half-life of about three days.
Following the end of immobilization there is a latency period of about

six hours for levels of TH and PNMT to become elevated. Further elevations of
levels occur in the next seven days of immobilization, but after six weeks of
daily immobilization, no further increases occur.
The long-term increase in catecholamine levels in the adrenal medulla
produced by immobilization are not only neuronally dependent but are also
under the control of ACTH. After hypophysectomy, depletion levels with

restraint are greater than in control animals, and levels of TH and PNMT fall.
On repeated immobilization, TH levels but not PNMT in hypophysectomized
rats do, however, rise but never to control levels. The use of TH levels in
operated rats is neuronally dependent in the main, whilst the rise in PNMT,
and some of the rise in TH levels, depends almost entirely on ACTH

administered prior to the stress.
On the other hand, serum dopamine-β-hydroxylase (which transforms

dopamine into norepinephrine) was increased after one thirty-minute
immobilization of rats, and continues to increase with daily immobilization
for a week. The source of this increase is not, however, the adrenal gland but
sympathetic nerves.
Immobilization stress of three hours also significantly accelerates the
disappearance of radioactive norepinephrine from heart and kidney. The
question of how immobilization stress is centrally translated into these
neuronally and hormonally dependent peripheral changes is unanswered
except for some very interesting work by the Welches. They showed that
restraint stress can cause a greater elevation of brain norepinephrine and
serotonin in mice who previously had spent eight to twelve weeks in
isolation, when compared to littermates housed in groups.
This elevation of brain amines occurs despite the fact that the isolated
mice have slower baseline turnover of brain biogenic amines than those
housed with others.
This work has several important implications. The isolated mice were
behaviorally more hyperexcitable than the housed controls. In other words,

previous experience affected behavioral response tendencies, while the
finding of different turnover rates and greater elevations with immobilization
clearly indicates that previous experience may lead to individual differences

in brain biogenic amines as well as behavior.
This work further points up the contention brought forth in this chapter
that autonomic and endocrine mechanisms are closely interrelated and

interacting. The full range of these interractions and mutually regulating
mechanisms is still to be worked out.
Finally, psychophysiology brings us face to face with a major scientific
and philosophic issue. Which are the means by which psychological responses
—thoughts, feelings, their awareness, etc.—are translated, if indeed they
directly are, into autonomically mediated responses? In other words—the
mind-body problem. There is no answer to this question, and therefore, much

of the meaning of psychophysiological correlations and concomitances
remains obscure, meaningless, or without significance.
Technical Aspects
In addition to having mastered a number of skills, psychophysiologists
must have considerable expertise in instrumentation. Special attention must
be given to make their instruments reliable and valid: For example, special
instruments have been devised for measuring blood pressure in intact
subjects.
All the techniques which have been devised require some knowledge of
electronic recording devices. For the technical aspects of psychophysiology,
the reader is referred to the Manual of Psychophysiological Methods.
Concluding Remarks
The data and concepts reviewed in this chapter are mainly derived from
acute experiments performed on anesthetized animals. In addition, these
experiments tend to have as their purpose the study of a single dependent

autonomic variable, while varying an independent other variable. Such
analytic experiments tend to obscure the complex, integrated adjustments

that occur in autonomic function in intact, free-ranging animals, and to
obscure patterns of autonomic change brought about by changes in the
animal’s environment. There is some evidence that patterned autonomic
changes (and behavioral changes) may be quite specific to particular
situations. They may be different in an animal anticipating avoidance

conditioning than they are in anticipation of muscular exercise. Or, they may
be different in an animal anticipating a fight with another, than during the
actual engagement.
Yet, any understanding of autonomic functioning must be based on
knowledge of the intrinsic mechanisms which underlie them. For this reason
these mechanisms have been reviewed. In Chapter 23, Hofer will review the
principles which govern autonomic psycho-physiological relationships in the

natural life of man and animals. These relationships have been studied in the
laboratory or field in intact animals. The data derived from these studies
reveal a different level of organization of autonomic functioning than an
analytic experiment can do.
Bibliography
Ahlquist, R. P. “A Study of the Adrenotropic Receptors,” Am. J. Physiol., 153 (1948), 586-600.
Alexander, R. S. “Tonic and Reflex Functions of Medullary Sympathetic Cardiovascular Centers,” J.

Neurophysiol., 9 (1946), 205-217.
Axelrod, J. “The Pineal Gland,” Endeavor, 29 (1970), 144-148.
----. “Noradrenaline: Fate and Control of Its Biosynthesis,” Science, 173 (1971), 598-606.
Baust, W., H. Niemczyk, and J. Vieth. “The Action of Blood Pressure on the Ascending Reticular
Activating System with Special Reference to Adrenaline-Induced EEG Arousal,”
Bonvallet, M., A. Hugelin, and P. Dell. “The Interior Environment and Automatic Activities of the
Reticular Cells of the Mesencephalon,” J. Physiol. (Paris), 48 (1956), 403-406.
Burn, J. N. and M. J. Rand. “Sympathetic Postganglionic Mechanism,” Nature, 184 (1959). 163-165.
Eccles, J. C. The Physiology of Synapses. Berlin: Springer, 1964.
Elliot, T. R. “The Action of Adrenaline,” J. Physiol., 32 (1905), 401-467.
Fiske, V. M., G. K. Bryant, and J. Putnam. “Effect of Light on the Weight of the Pineal in the Rat,”
Endocrinology, 66 (1960), 489-491.
Folkow, B. and E. H. Rubinstein. “Cardiovascular Effects of Acute and Chronic Stimulation of the
Hypothalamic Defense Area in the Rat,” Acta Physiol. Scand., 68 , 48-57.
Folkow, B. and B. Uvnas. “Do Adrenergic Vasodilator Nerves Exist?” Acta Physiol. Scand., 30
(1950), 329-337.
Goodman, L. S. and A. Gilman. The Pharmacological Basis of Therapeutics, 3rd ed. New York:
Macmillan, 1965.
Henry, J. P., D. L. Ely, and P. M. Stephens. “Role of the Autonomic System in Social Adaptation and
Stress,” Proc. Int. Union Physiol. Sci., 8 (1971), 50-51.
Henry, J. P., P. M. Stephens, J. Axelrod et al. “Effect of Psychosocial Stimulation on the Enzymes
Psychosom. Med., 33 (1971), 227-237.
Hess, W. R. Das Zwischenhim. Basel: Schwabe, 1949.
Hodgkin, A. L. The Conduction of the Nervous Impulse. Springfield: Charles C. Thomas, 1964.
Iggo, A. and B. F. Leek. “An Electrophysiological Study of Single Vagal Efferent Units Associated
with Gastric Movements in Sheep,” J. Physiol., 191 (1967), 177-204.
Katz, B. “Quantal Mechanism of Neural Transmitter Release,” Science, 173 (1971), 123-126.
Klein, D. C. and J. Weller. “Serotonin N-Acetyl Transferase Activity is Stimulated by
Norepinephrine and Dibutyryl Cyclic Adenosine Monophosphate,” Fed. Proc., 29
(1970), 615.
Korner, P. I. “Integrative Neural Cardiovascular Control,” Physiol. Rev., 51 (1971), 312-367.
Kuntz, A. The Autonomic Nervous System. Philadelphia: Lea & Febiger, 1953.
Kvetnansky, R. and L. Mikulaj. “Adrenal and Urinary Catecholamines in Rats during Adaptation to
Repeated Immobilization Stress,” Endocrinology, 87 (1970), 738-743.
Kvetnansky, R., V. K. Weise, and I. J. Kopin. “Elevation of Adrenal Tyrosine Hydroxylase and
Phenylethanolamine-N-Methyl Transferase by Repeated Immobilization of Rats,”
Endocrinology, 87 (1970), 744-749.
McCubbin, J. W., J. H. Green, and I. H. Page. “Baroreceptor Functions in Chronic Renal

Hypertension,” Circ. Res., 4 (1956), 205-210.
Masters, W. H. and V. E. Johnson. Human Sexual Response. Boston: Little, Brown, 1966.
Miller, N. E. “Learning of Visceral and Glandular Responses,” Science, 163 (1969), 434-445.
Moore, R. Y., A. Heller, R. J. Wurtman et al. “Visual Pathway Mediating Pineal Response to
Environmental Light,” Science, 155 (1967), 220-223.
Mueller, R. A., H. Thoenen, and J. Axelrod. “Increase in Tyrosine Hydroxylase Activity after
Reserpine Administration,” J. Pharmacol. Exp. Ther., 169 (1969), 74-79.
----. “Inhibition of Transsynaptically Increased Tyrosine Hydroxylase Activity by Cycloheximide

and Actinomycin D,” Mol. Pharmacol., 5 (1969), 463-469.
Nachmahnson, D. Chemical and Molecular Basis of Nerve Activity. New York: Academic, 1959.
Ranson, S. W. “New Evidence in Favor of a Chief Vasoconstrictor Center in the Brain,” Am. J.
Physiol., 42 (1916), 1-8.
Rushmer, R. F. Cardiovascular Dynamics. Philadelphia: Saunders, 1970.
Seeds, N. W. and A. G. Gilman. “Norepinephrine Stimulated Increase of Cyclic AMP Levels in

Developing Mouse Brain Cultures,” Science, 174 (1971), 292.
Snyder, S. H., J. Axelrod, and M. Zweig. “Circadian Rhythm in the Serotonin Content of the Rat
Pineal Gland: Regulating Factors,” J. Pharmacol. Exp. Ther., 158, 206-213.
Thoenen, H., R. A. Mueller, and J. Axelrod. “Increased Tyrosine Hydroxylase Activity after Drug-
Induced Alteration of Sympathetic Transmission,” Nature, 221 (1969), 1264.
Venables, P. H. and I. Martin, eds. A Manual of Psychophysiological Methods. New York: Wiley,
1967.
Von Euler, U. S. “Adrenergic Neurotransmitter Functions,” Science, 173 (1971), 202-206.
Weiner, H. “Psychosomatic Research in Essential Hypertension,” Bibl. Psychiatr., 144 (1970), 58-
116.
----. “Some Comments on the Transduction of Experience by the Brain,” Psychosom. Med., 34
(1972), in press.
Welch, B. L. and A. S. Welch. “Differential Activation by Restraint Stress of a Mechanism to

Conserve Brain Catecholamines and Serotonin in Mice Differing in Excitability,”
Nature, 218 (1968), 575-577.
Wurtman, R. J. and J. Axelrod. “Control of Enzymatic Synthesis of Adrenaline in the Adrenal

Medulla by Adrenal Cortical Steroids,” J. Biol. Chem., 241 (1966), 2301-2305.
Wurtman, R. J., J. Axelrod, and E. W. Chu. “Melatonin, A Pineal Substance: Effect on Rat Ovary,”
Science, 141 (1963), 277-278.
Wurtman, R. J., J. Axelrod, and D. E. Kelly. The Pineal. New York: Academic, 1968.
Wurtman, R. J., J. Axelrod, and L. S. Phillips. “Melatonin Synthesis in the Pineal Gland: Control by
Light,” Science, 142 (1963),1071-1072.
Notes
1 Even the EEG may be influenced by changes in cardiovascular dynamics.
2 Acetylcholine is, of course, the transmitter substance at all neuromuscular junctions involving
skeletal muscle and may play a role in neurotransmission in the CNS.
3 Aldosterone is the principal steroid, produced by the adrenal cortex, regulating body salt.
Chapter 23
The Principles Of Autonomic Function In The Life

Of Man And Animals
Myron A. Hofer
Introduction
When Galen described the anatomy of the visceral neural network 1800
years ago, he was led to conclude that this structure functioned to promote
“sympathy” or communication and harmony between internal organs.
Although the use of the word “autonomic” nervous system dates from a mere
seventy-five years ago, parts of Galen’s hypothesis regarding its function have
survived, and the word “sympathetic” is used to denote the thoracolumbar

portion of the system.
The modern literature on autonomic psychophysiology is immense and
I will not attempt to survey the field; the reader is referred to recent books
and review articles for this purpose (See references). Rather this chapter will
deal with a few studies selected to illustrate the principles which appear to
govern autonomic-nervous-system (ANS) functions in the organism during its
natural life. The concepts which arise from new data will be emphasized, and
will be related to disease processes. Emphasis will be placed on

interpretation, on clinical implications, and on future directions, in this way
hoping to represent the current state of our understanding of the field.
The previous chapter has dealt with the organization of the ANS at the
level of its peripheral and central mechanisms, and reviewed the contribution
of laboratory studies to our understanding. This chapter will consider the
properties of the ANS as it functions while the organism interacts with its
environment. What are the characteristics of its functioning while the subject
is at rest, in response to changes in the environment and as a part of

emotional and behavioral responses to signals processed by the central
nervous system (CNS)? Is the system organized differently at different
developmental stages? Is it primarily an effector system or are there major

roles for its afferent pathways? Does activity of the autonomic system show
effects of learning as does the musculoskeletal system, and to what extent do

the systems differ? Finally, what processes may account for the appearance of
the unusually intense or poorly coordinated responses which can produce

lasting damage or even death?
Our understanding of the role of the ANS in the economy of the
organism was greatly advanced by Claude Bernard and W. B. Cannon, whose
elegant experiments led them to an understanding of the negative feedback
properties of autonomic function which served to maintain relative constancy
of the “milieu interieur,” or “homeostasis,” in the face of constantly varying

environmental conditions. It has since been recognized that such control
systems are a general property of biological organization and are present in
endocrine, metabolic, and cellular systems in the human." They are also
thought to be a characteristic of central neural functioning, mediating

conscious experience. Since the time of Cannon, accumulating data has forced
modification in our concept of homeostasis to account for the fact that
hierarchies are established in the organization of central integration, so that

certain functional levels may be maintained at the expense of homeostasis in
another area or system. An example of this is the maintenance of temperature
regulation at the expense of water and electrolyte balance during extreme
heat. Observations such as these have led to the concept of variable set points
and a servomechanism model. That is, the central nervous system, under
certain conditions, can raise or lower the level of function in a given system
toward which adjustments are made. It is in this way that central neural
states may act to modify autonomic regulation.
The complex interplay of neural, endocrine, and cellular metabolic
processes outlined in the previous chapter illuminates the multiple
determinants of level of autonomic function and has important consequences
for further understanding. The first is that any given function controlled by
the ANS, for example, heart rate, can only approximate a steady state and in
reality is subject to a constantly fluctuating interplay of feedback from

numerous other systems such as carotid baroreceptors, pulmonary tension
receptors, gastric mechanoreceptors, etc., as well as being affected by many
systems outside the ANS. The second consequence is that a given change in
level of any one autonomic effector system can be produced by one of several
different mechanisms. A rise in heart rate, for example, may be produced by a
decrease in vagal tone secondary to subsidence of a gastric contraction, or by
an increase in sympathetic tone following baroreceptor stimulation,
occasioned by a fall in blood pressure due to pooling of extracellular fluid in
the legs while sitting down after walking; the list can go on and on. The third
consequence of this multiple servocontrol organization is that the response
(to a standard environmental stimulus) in any given ANS effector function is

greatly affected in degree and even in direction by the current status of
continuing and reverberating homeostatic adjustments in other parts of the

system as they play back upon the given response system.
These consequences create an extraordinary range of possible

variability in autonomic effector function under natural conditions. There is a
considerable degree of unpredictability even between observations of steady
states and in response to even the most discrete and definable stimulation.
The variability is large both within the individual from one point in time to
the next and between individuals at any given time.
Some of the sources of variability can be minimized by the controls
which are possible in clinical laboratory investigation. However, very few

studies have been done with the highly desirable control, for example, of
extracellular fluid volume, which so affects cardiovascular regulation and
then indirectly many other functions. Diet, temperature, humidity, and the
activity of human experimental subjects, are arduous controls when they

must be maintained for days prior to an experiment.
If this were the extent of the interactions at work in the functional

control of the ANS, this section of the chapter would be shorter but less
interesting. There are, in addition to the homeostatic feedback characteristics
of the system, two major forms of servomechanism “override” exerted by the
CNS. The first of these are the regular, time-related processes of circadian
rhythms and of developmental changes. The second involve the irregularly
occurring events in response to which the balanced homeostatic organization
is overridden by central neural activity, apparently of higher priority, for

example, by responding to symbolic environmental stimuli, such as a signal
that an athletic contest is about to begin, before the physiological demands of

the event itself.
Man at Rest
No studies have been performed in which all or most of the
interconnected systems of the ANS described above have been measured

simultaneously in man even under basal conditions. Therefore, no complete
picture is available of the patterned functioning of the ANS. A few
investigators have been aware of the necessity of studying the pattern of

levels of functioning and have emphasized the importance of the relationship
of the level of activity in one function to that in another.
Sargent and Weinman, in an intensive study of army recruits,

simultaneously measured more than thirty physiological variables, half of
them directly reflecting autonomic neural activity and the others involving
water, electrolyte, and nutritional metabolic systems.
Repeated measurements were made at intervals over several-week
periods and repeated at a different season of the year. Because the subjects
were in the Army, they were under unusual control by the experimenters, so
that such factors as diet and activity could be strictly prescribed throughout
the experiments. The most striking finding in the observations made at rest
was the great individuality of the patterns exhibited by each subject. Like
fingerprints, the relationship of one autonomic effector system to another
was very different in one individual than in another. There seemed to be no
one characteristic pattern for the group. In the observations made on the
same individuals at a different season of the year (six months later), the
individual patterns had changed. Moreover, there did not seem to be any
regularity in the kinds of changes in the individual patterns.
The complex nature of the interrelationships between component parts
of the ANS, the extreme individuality of the patterns of ANS activity observed
between individuals in the resting state at one point in time, and the
inconstancy of a given pattern in the same individual with time (despite
rigorous efforts to reproduce an identical resting state) are all fundamental
characteristics of ANS organization.
These and other data are consistent with the conceptual scheme
outlined in the Introduction, in which multiple feedback relationships
between the widespread organ systems innervated determine a complex

pattern of balance, subject to a host of environmental factors as well as to
individual differences in relative set points. How certain environmental,
internal biological, and psychological processes come to exert predictable

control over this organization will be the focus of this chapter.
Circadian and Other Rhythms
So far we have examined the functioning of the ANS only in the resting
state and only at a single point in time. Repeated observations in man over a
period of days disclose pronounced regular, rhythmic fluctuations in all
autonomic functions studied. The previous chapter has described some of the
transduction mechanisms for altered neurotransmitter and enzyme levels.
Although individuals show slight differences in the timing and scope of these
fluctuations, everyone has daily high and low points in levels of functions,
many of these independent of environmental lighting, activity, posture, and
even of sleep. The low points generally occur during the time of darkness, and
the high points soon after dawn and awakening, although there are many
exceptions to this generalization.
Although these rhythms can be synchronized by such natural rhythmic
environmental events as light and temperature change, and can be caused to
cycle at slightly more or less than an exact twenty-four-hour period, they

retain their rhythmic behavior in the absence of external cues, thus indicating
the existence of an internal “clock” with rhythmic oscillations in set points of
ANS function. After prolonged deprivation of all usual daily cues (e.g.,
isolation in a cave)66 circadian rhythms become desynchronized, each

running at its own period, either slightly more or slightly less than twenty-
four hours in length, creating a steadily changing pattern of relationships
between individual functions.
Cyclic fluctuations of a shorter period, often approximating ninety
minutes in duration, have also been described for some functions and are
termed ultradian. More familiar are the annual, seasonal, and monthly
rhythms. Autonomic balance has been shown to alter in a rhythmic fashion in
time with the human menstrual cycle.
Developmental Changes
Circadian rhythms in autonomic function are not present at birth in the
human, with the exception of skin resistance. Most physiological functions
studied show an ultradian rhythm throughout the first postnatal months.

Heart rate becomes circadian in rhythmicity at four to twenty weeks but body
temperature requires twenty to forty weeks. The factors affecting the rate
and regularity of development of these rhythms in early life is an area of
current study. Both the inanimate and the social environment of the baby
during this early period have been shown to affect maturation of rhythmic
behavior.
In addition to the ultradian, circadian, and seasonal rhythms, the span of
an individual’s life exerts its own temporal patterning on ANS functioning.
Such levels of ANS functioning as heart rate and blood pressure are known to
vary systematically with age in man. Blood pressure rises with each decade
from birth onward. Resting-heart rate increases after birth during the first
few months, is maintained at relatively high rates in childhood, then shows a
pronounced decline, reaching a low plateau in adolescence, and rising again
slightly throughout adulthood. The pattern is very similar for at least one
animal species, the rat, in which it is possible to determine some of the factors
involved, Adolph has shown that the rat heart responds to neurotransmitters
from late stages in fetal life, and that developmental changes are neurally
mediated and not due to maturational changes in the myocardium itself.
Hofer’s work has demonstrated that the high rates during late infancy are the
result of high sympathetic tone and that this is, in turn, supported by the
mother through her milk which appears to act via a neural mechanism
involving the CNS. The subsequent decline of heart rate in late childhood in
both rat and man is the result of increasing vagal tone, which had not been
present earlier.
The existence of distinctly different patterns of autonomic organization
at different developmental stages and the interactions of environmental and
social factors in the development of adult patterns are areas with much
promise for future study (see below).
Autonomic Responses
We have developed a picture of the ANS in man at rest under basal
conditions as a dynamic system organized to maintain certain levels of
function by an elaborate network of checks and balances. These levels of
function, in turn, vary in a highly systematic rhythmic fashion around each
twenty-four-hour period, programmed by an internal clock which is
synchronized (“entrained”) by certain daily recurring environmental events.
The multiple interconnected feedback relationships described above and in

the preceding chapter may alter the intensity and even the direction of a
response to a given stimulus, depending on the status of these systems at the
time of stimulation. Partly as a result of these interactions, the resting or
prestimulus level in a single autonomic effector system can only be a rough

predictor of response according to the “initial value” effect. (By this empirical
rule, response magnitude should be inversely related to initial resting level.)
As indicated above, in evaluating autonomic responses in man we must
distinguish between (1) nonspecific or spontaneous activity bursts; (2) the

final level of function attained during the response; and (3) the magnitude of
change in level as a result of the response. Lacey has emphasized that these
parameters must be considered independently. He has also shown that

responses in different autonomic functions (e.g., heart rate, skin resistance or
blood pressure) to the same stimulus have a low correlation. As a result,

patterns of responses will be more meaningfully related to stimuli than single
variables. Nevertheless it is worth pointing out that a general relationship can

be demonstrated to exist between measures of intensity of physical
stimulation (e.g., touch or noise) and magnitude of response in autonomic
variables (e.g., skin conductance, heart rate, or finger volume). This simple
quantitative principle operates in addition to a number of more complex
qualitative determinants of direction and intensity of response which will be
discussed later in the chapter.
The autonomic system is organized to respond to a large variety of

environmental events in which the organism participates. These will be
discussed below, beginning with the simplest and leading to the complexity of
elicited emotional states.
Orienting Responses
A fairly uniform pattern of altered ANS activity follows a novel and
unexpected change in the environment. For example, a sudden sound, even a
weak one, or a sudden reduction in an ongoing level of sound, elicits cortical

alerting with characteristic EEG and evoked potential changes, accompanied
by a sudden increase in skin conductance, a fall in heart rate and in both
systolic and diastolic blood pressure, vasoconstriction in the extremities and

vasodilation in external cerebral vessels. This response pattern becomes
progressively less intense and finally disappears if the same stimulus is
repeated several times (habituation), but may at any time be elicited again by
a qualitatively different stimulus, for example, a tone of a different pitch.
If the stimulus which initially elicits an orienting response is repeatedly
followed by a task which the subject is motivated to perform, it continues to
elicit the same ANS pattern and fails to habituate. The stimulus now has
“signal properties,” continues to arouse attention, and may also arouse some
ANS preparatory adjustments appropriate to the task which is about to be
performed, e.g., tachycardia before exercise. The ANS pattern thus becomes
modified through a process of conditioning (see below, under Autonomic

Learning).
The Laceys have studied the relationship between the heart-rate
deceleration observed in response to a signal for a reaction-time test and the
subject’s performance on the test. They have found data to support the
hypothesis that the ANS adjustments of the orienting response serve the
purpose of increasing cortical vigilance via ANS afferent feedback to the CNS
(see below under Afferent Influences. )
It is apparent that even such a relatively simple psychophysiological
human response is in fact a pattern of great complexity. Real understanding
of its nature is a formidable analytic task. At present the barest descriptive

outline of the full pattern is possible.
Defense Responses
With more intense stimuli, the orienting response is discernible only
during the initial portion of the subject’s response to the first such stimulus
presented, and is rapidly overtaken by another pattern, the defense response.
Some of the physiological characteristics of the orienting response are
retained, (e.g., EEG activation, increased skin conductance and peripheral
vasoconstriction) in a prolonged and intensified form. Other autonomic
functions change in the opposite direction: heart rate and blood pressure are
generally increased and external cerebral blood vessels are constricted.
Muscle tone and respiratory frequency and amplitude are usually increased
in the moments following stimulation at near painful intensity. These
patterns and appropriate behavior have been elicited by brain-stimulation

studies as described in the preceding chapter. Another characteristic of
defense responses is that they do not cease to occur after the first one or two
repetitions of the stimulus (habituation) as do orienting responses. They do

undergo a complex series of changes in patterning with repetition, although
little systematic data are available on this point.
It is worth noting that the behavior of the organism is quite different in
response to weak as compared to strong stimuli (provided these stimuli have
not acquired special signal properties). Weak stimuli generally elicit a turning
of gaze and posture toward the stimulus and often result in approach of the
organism to the stimulus, associated with conscious experience which may be
described as curiosity or attention. Strong stimuli generally elicit withdrawal
or even generalized escape movements, movement away from the stimulus
and the experience of pain and fear.
There is evidence that some of the autonomic correlates of the defense
response (e.g., increases in heart rate and blood pressure) may activate
afferent ANS pathways serving to reduce cortical excitability and diminish or
attenuate the impact of the stimulus upon the CNS (see below under Afferent
Influences).
The autonomic responses cited may also be viewed as preparatory
mobilization of some of the characteristic physiological changes of physical
exertion, preparing the animal for fight or flight. Increased survival capability
of animals so prepared has presumably resulted in a selective process
favoring this form of ANS organization during evolution.
Exertion
We move now to a consideration of the functional organization of the
ANS during physical and mental activity which is sustained and organized
over a period of time. For many years, the alterations in cardiovascular

dynamics during exercise were explained as proceeding from increased
venous return due to the pumping action of active skeletal and respiratory
muscles and to vasodilation in muscle beds produced by the local
accumulation of metabolites. Hemodynamic principles discovered in isolated
heart-lung preparation were freely applied in unchanged form to the intact,
unanesthetized animal. The role of the ANS was thought to be entirely
reflexive, as in the Bainbridge reflex, whereby the increased cardiac rate

during exercise, although mediated by sympathetic nerves, was thought to be
reflexively dependent on increased venous filling.
Rushmer and Smith have summarized the large body of evidence which
reinstates the CNS and its autonomic cardiovascular connections as prime
movers in the cardiovascular as well as the behavioral patterns of exercise.

Some aspects of their work have been described in the previous chapter.
Central to this chapter is their finding that the cardiovascular changes
characteristic of physical exercise in the dog could be elicited either by

anticipation of treadmill exercise or by brain stimulation under anesthesia,
despite the fact that in these two situations no exercise occurred. Thus,
although the behavior and the characteristic ANS cardiovascular adjustment
pattern ordinarily occurred together and appeared to share common central

neural pathways, either could occur without the other. This demonstration of
the dissociability of behavioral and physiological events in the simple
situation of treadmill exercise illustrates a fundamental principle of ANS

function and of how it is organized in relation to behavior (and conscious
experience) which I will return to repeatedly in the subsequent sections.
The autonomic control of regional vascular tone, and of cardiac rate and
force of contraction during physical exertion, is brought into play with almost
exactly the same pattern of changes during the performance of mental tasks
such as mental arithmetic. Brod’s now classic studies show that the most
frequent pattern during serial subtractions was one of increased cardiac rate
and output, with a fall in total vascular resistance despite vasoconstriction in
skin and renal vascular beds. Muscle beds, such as the forearm, showed
increased flow and thus decreased vascular resistance. Blood pressure, both
systolic and diastolic, rose slightly.
These studies by Brod and Rushmer and Smith, and others employing
simultaneous measures of cardiac output and regional blood flow, permit
calculations of changes in vascular resistance by regions, and give a far more
complete understanding of ANS functioning than the usual
psychophysiological studies. For example, as Brod’s studies show, two

subjects with similar increases in blood pressure may nevertheless differ
remarkably in the balance between cardiac output and total peripheral
resistance. He was able to define a second pattern, occurring in a minority of

subjects in whom cardiac output actually fell during mental arithmetic. In
these people (four of eighteen studied), total peripheral resistance

consistently increased and this could be attributed to increases in extrarenal
vascular resistance exclusive of the muscular (forearm) vascular bed. All
subjects showed increases in blood pressure, so that Brod’s differentiation of
subjects into “output” and “resistance” types would have been impossible
without the multiple simultaneous measures.
Brod states that the test provoked “emotional stress,” and gives as
evidence that “subjects blushed, became tense and nervous and made
frequent mistakes which caused them great embarrassment.” Thus, even in
this very standardized task situation the subjects’ emotional response
became a major (uncontrolled) variable. One wonders whether the “output”
and “resistance” types of ANS pattern could have been differentiated in terms
of the emotions present while performing the task. The work of Funkenstein
and Wolf et al. in the 1950s suggests, on the basis of the very indirect
cardiovascular measures then available, that those who suppress hostility
and do not express their anger at the experimenters directly, give rise to the
“resistance” type of pattern. The vital importance of the relationship of the

subject to the experimenter will be considered further below.
Appetitive Behavior
Since the process of digestion is complex and the autonomic physiology
involved is adequately covered in standard physiology texts I will only

mention that a highly reproducible pattern of changes in motility, secretion,
and blood flow are set in motion by the ANS in response to digested food. The
degree of higher neural control over this process is illustrated by the
anticipatory changes in salivary secretion, gastric motility, and heart rate,
occasioned by signals prior to the appearance of the food itself and mediated
by ANS activity.
Sexual behavior is characterized by many responses organized through

the ANS, the central neural pathways which have been described in the
previous chapter. Some of these are similar to those occurring with any
exertion (greatly increased pulse and blood pressure) but many are quite
specific. There appears to be a shift of blood flow to the skin rather than away
from it as in ordinary exercise, and local vascular engorgement (e.g., lips, ear
lobes, nipples, and genitalia) is pronounced and unique to this form of

stimulation. Profound alteration in sweat and specialized glandular secretion,
and patterned changes in respiratory depth and rate, are also mediated over
autonomic pathways. The regular course of development of these changes

throughout an episode of sexual intercourse for both male and female has
been described by Masters and Johnson, as well as the variations in timing

and stages which occur. Despite the lack of sophisticated physiological
instrumentation, their observations have made clear the general outlines of

these patterned responses and opened up an area which had previously
never been studied systematically.
Special Situations
There are a number of additional life situations, less commonly
encountered than those previously described, which evoke pronounced

autonomic changes. These have been amply reviewed. Many of them may be
considered to be primarily physical stressors, such as heat, cold, and
centrifugal acceleration, but also arouse emotional responses and other

psychological processes which participate in the final autonomic response
patterns. Since many of the responses are quite similar to the defense and
exertional responses already described, I will deal with others which
exemplify a different sort of autonomic pattern, one in which marked

decreases in cardiac output and other adjustments occur which appear to
serve the function of conserving rather than mobilizing the resources of the
individual. Brain sites have been identified which give rise to behavioral and
autonomic patterns on stimulation which bear some resemblance to this class

of responses.
The most clear-cut example of this kind of response is the dive reflex.
Present in most mammals, this sudden and profound cardiovascular

adaptation occurs most clearly in sea mammals such as the seal, but also in
diving birds such as the duck. It has recently been studied in man and in dogs
by Eisner. When a man immerses his face in water, while holding his breath,
an immediate and profound vagal bradycardia occurs. Eisner recorded one
healthy young man who sustained an eighteen-second period of asystole. This
cardiac rate change is part of a complex pattern of readjustments. There is
massive peripheral vasoconstriction which shunts blood away from all areas
capable of anaerobic metabolism, such as muscle and the splanchnic area,

thus preserving blood oxygen stores for brain and myocardium. The cardiac
output accomodates to a much smaller functioning vascular bed by
decreasing markedly. Sensory stimuli capable of eliciting this response

include both tactile activation in the distribution of the trigeminal nerve, and
the pulmonary afferent stimulation involved in sudden breath holding. Anoxia
does not develop in time to play a role in these immediate responses.
Metabolic adjustments taking place during prolonged dives have been
reviewed by Andersen.
Forced—as contrasted with spontaneous— dives in seals have been
reported to elicit episodes of atrial fibrillation and ventricular tachycardia
and Wolf has suggested that some cases of unexplained sudden death in adult
and infant humans may involve the mechanism of the dive reflex.
A response which is less consistent among individuals, but which can be
elicited by a variety of stimuli is fainting or “vasovagal syncope.” Typically, the

early phases of this response are characterized by piloerection, dilation of the
pupils, cardiac acceleration, and decreased blood flow to the skin and viscera.
However, blood flow to the muscles is increased greatly. (This vascular
response is a critical element and can be largely blocked by intra-arterial
atropine, indicating the role played by cholinergic sympathetic vasodilator
fibers.) A fall in systemic vascular resistance occurs, accompanied by a
decrease in cardiac output rather than a compensatory increase. Blood

pressure falls, systolic before diastolic, and finally a vagal bradycardia occurs.
If the subject is erect, brain blood flow is seriously compromised and he loses
consciousness. The slowing of the heart is not a necessary part of the
phenomenon and syncope can occur without it. Muscular inaction may play a
necessary role in the development of the condition, since the fall in cardiac
output is partially due to lack of venous return from the muscular venous
pump.
A lack of ANS support for cardiac output in the face of decreased

peripheral resistance and muscle-bed vasodilation is the basic pattern of ANS
organization in this form of syncope. The stimulus situation which most
regularly provokes this ANS response is blood loss, and occurs in experienced
blood donors after 15-20 percent of blood volume is removed. Pooling of
blood and loss of effective blood volume by filtration of plasma into

dependent limbs during prolonged maintenance of the standing position can
lead to syncope, as it may occur on the parade ground. Cutaneous

vasodilation in a hot environment is an ANS response which predisposes to
the development of this more complex ANS response. Most interestingly,
syncope may be provoked by apparently trivial stimuli which have signal
properties (e.g., the sight of blood), or sometimes in association with physical
pain.
The response appears to be one in which musculoskeletal inaction is
superimposed upon peripheral ANS responses appropriate to vigorous

exertion. This in itself does not explain the fall in cardiac output or the
bradycardia. Graham emphasizes a sudden cessation of the hyperdynamic
state, and has found a subjective sense of relief just before syncope as, for
example, when an injection has been completed and the needle is withdrawn.
Engel has evidence from other situations which point to a cognitive and
emotional state of helplessness and “giving up” which immediately precedes
the syncopal episode.
Altered Central States
The relationship of central neural states to the functional organization
of the ANS is poorly understood. Only emotional states have received much
study, although they are vastly more difficult to reproduce and subject to
numerous methodological complications. As a result, they will be considered

in a separate section. Recent work on the state of sleep has made it clear that
the ANS is organized very differently during sleep and even according to the
subdivisions (stages) of the state of sleep. The fact that ANS response
characteristics can differ substantially according to changes in central neural
state has clear implications for our understanding of how the ANS operates in
the complex situations developing in natural life when emotions, physical
activity, sleep, mental tasks, cognitive processes, and psychological defenses

are all operating together.
Sleep
Rapid “flurries” of changes in respiratory rate, blood pressure, finger

blood flow and heart rate occur in close association with rapid eye
movements during stage “REM sleep.” In addition, it has recently been shown
that flurries of spontaneous fluctuations in skin resistance—“GSR (galvanic
skin response) storms,” occur predominantly in Stage 4, slow-wave sleep.
Heart-rate responses to an auditory stimulus (see Orienting Responses, p.
532) are found to be more pronounced and to have markedly different shape
and latency during Stage 2 and Stage REM than when the subject was awake
or in Stage 3-4 of sleep. Furthermore, there was no habituation of the heart-
rate response as long as the subject remained asleep! Another important
difference involves the thresholds for activation of responses in relation to
the threshold of arousal. In Stage 2, the EEG response (k-complex) first

appeared to tones 30 decibels (db.) below that required for arousal from
sleep. The finger-pulse response occurred 15 db. below arousal threshold, the
heart-rate response at 5 db., and the electrodermal response did not occur
until the subject was aroused from sleep sufficiently to show an awake EEG
and made a motor response.
These findings argue definitively against any concept of ANS function as
operating on a simple arousal continuum from low levels of function during

basal states in sleep to the highest levels during the heights of arousal in
response to maximal stimulation. Rather, the functional organization seems
to be reprogrammed during shifts in central neural state, so that specific
response characteristics, spontaneous activity levels, and thresholds are all

altered in a highly complex manner. Even such fundamental a characteristic
as habituation can be suspended during certain stages of sleep.
During the flurries of autonomic activity and inhibition in REM sleep,
patients with borderline cardiovascular adjustment may enter frank
pulmonary edema or life-threatening cardiac arrhythmia. It is out of slow-
wave sleep that classic night terrors arise. In these, profuse sweating and
violent tachycardia have been noted, indicating intense autonomic activation.
Mental content is usually fragmentary and indistinct, although intense anxiety
is usually described. In contrast, ordinary anxiety dreams occurring during

REM sleep may involve exceedingly vivid and specific hallucinatory
experiences, also with intense affects aroused, but this intense emotional
activation may occur without any alteration in autonomic variables recorded
at the time of the dream. Autonomic flurries are more regularly associated
with periodic REM than with dream content.
These observations raise an extremely important point to be kept in
mind throughout the remainder of this section. The ANS is not organized so
that there is any necessary relationship between feeling state and levels of
autonomic activation. Emotions, or indeed any consciously recognized states,

are not causally related to changes in the ANS and indeed the two are not
necessarily associated. Both conscious state and autonomic activity can vary
independently. It is this generally unrecognized fact which helps to explain
why efforts to use the measurement of autonomic variables as indicators of
mental state have generally been unsatisfactory or difficult to reproduce. In
the example given, the state of sleep appears to act to dissociate the emotions
from the autonomic responses. Our knowledge of how this is accomplished is
fragmentary but we know that other conditions may have the same effect
during other states. Research needs to be redirected toward analysis of the

processes responsible for full or partial dissociation between feeling state and
ANS activity.
Transcendental Meditation
Wallace and co-workers have obtained data on ANS function during a

relatively simple form of focused attention (transcendental meditation) and
have revealed a hypometabolic state with markedly decreased oxygen
consumption, decline in blood lactate, respiratory rate, and heart rate while
skin resistance markedly increased. Blood pressure remained unchanged. The
EEG showed increased quantity and amplitude of slow alpha rhythm at 8-9
hz. These changes were compared with changes in a few subjects who were
hypnotized or asleep; the oxygen consumption, in particular, was reduced far
more swiftly and more dramatically during meditation than during either of
the other altered CNS states.
Little systematic work has been done on ANS organization during
induced alterations of consciousness and this appears to be a fertile area for
future work.
Emotion
I have reviewed in some detail the organization of ANS function in a
variety of relatively well-defined conditions and in response to relatively

simple stimuli, in order to provide a base from which to move on to the welter
of data which has been collected on ANS function in emotional states. If we
view emotions as consisting of altered central states which interact with
numerous other processes (described in other sections of this chapter) in
determining autonomic response patterns, we will avoid much of the

difficulty which has beset the area of the autonomic nervous system and
emotion.
One of the major difficulties experienced by investigators in this area

has been in collecting and adequately describing the psychological data with
which they sought to correlate their physiological measurements. In fact, for a
time, some seemed to be attempting to describe and even quantify emotional
states in terms of measurements of ANS function. Other investigators,

convinced by the results of such attempts that this was the wrong approach,
adopted the position that qualitative differences in emotional state were of
little importance, but that degree of arousal determined the intensity of a
general ANS activation pattern consisting of heightened sympathetic activity
in all portions of the system. This position is still held by many workers
despite the considerable body of evidence which has accumulated against a

simple arousal model, some of it described above. Finally, much of the data
collected in experimental situations fails to take into account such facts as the
importance of the subject’s preconceived ideas about the experiment and his
relationship with the experimenters themselves. These variables have
repeatedly been shown to have a determining effect on the degree, direction,

and patterning of ANS response to the supposedly “standardized” emotional
experience under study. For example, Weiner et al. demonstrated that

maximal physiological responses often occur on the first exposure to the
laboratory and before the procedure for inducing emotional states was begun.
Then, when the subject made up a story in response to a thematic
apperception test (TAT) card but did not have to tell it to the experimenter,
the autonomic responses were a fraction of those observed during the verbal
report of similar mental content. Thus, the subject’s autonomic responses

were determined as much by his relationship with the experimenter as by the
psychological stimulus being studied (TAT cards).
Studies in animals are leading to an appreciation of the highly specific
autonomic patterning which is present during emotional states, and to an
understanding of the processes which determine these patterns. Zanchetti

has shown, for example, that whereas cats show a diffuse, prolonged, bilateral
cholinergic vasodilation during immobile alerting caused by the sight of a dog,
a localized, discrete cholinergic vasodilation occurs with attack movement,

limited to the moving limb only. Rats subjected to brief electric shock show
decreased blood pressure immediately afterwards when shocked in pairs but
increases after being shocked alone.
The old view that autonomic nervous regulation is governed simply by
homeostatic principles is no more erroneous than the more recent view that
autonomic responses in man are determined by emotions and can be simply

correlated with affects. To be sure, situations designed to arouse one
particular affect tend in general to arouse a pattern of autonomic response

which can be statistically differentiated from that occurring when a different
affect is provoked. However, simple tracking, tapping, or reaction-time tasks
with minimal affective arousal, evoke similar autonomic patterns which
likewise show a similar “situational stereotypy” as Lacey termed it. Also there
are the converse findings that some subjects show minimal or no response in
the autonomic systems monitored, despite the presence of affective arousal.
From this evidence we must conclude that the relationship between
emotional states and autonomic response patterns is far from simple. In fact,
there is new evidence that the two may be predictably dissociated by

manipulating the contingencies of the situation. Associations between
emotional behavior and the ANS may be the result of frequent concomitance,
rather than of a necessary functional relationship.
Brady studied monkeys which were anticipating electric shock during a

three-minute auditory signal immediately preceding the shock. The emotional
behavior studied was inhibition of a stable, previously conditioned, lever-
pressing response for food reward. The physiological variables recorded were
systolic and diastolic blood pressure and heart rate. Each of a series of
monkeys was followed through a long series of repetitions of this basic

paradigm, with variations being periodically introduced only in the
contingencies between signal and electric shock. These studies provide many
examples of clear-cut alterations in autonomic patterning without
concomitant detectable changes in emotional behavior. Likewise, changes in
emotional behavior were observed to occur without alteration in the
associated autonomic patterns. Furthermore, these experiments demonstrate
how environmental contingencies affect both autonomic pattern and
emotional behavior and suggest that the processes by which responses are
evoked in the two systems may be functionally independent.
We thus confront again one of the central unanswered questions in ANS
psychophysiology: what are the factors responsible for the maintenance and
disruption of correlated functioning of emotional experience, behavior, and
physiology by the CNS during life experience? Although other sections of this
chapter describe functional characteristics of the ANS which bear on this
question, there are several approaches dealing particularly with emotional
states which should be mentioned in this section.
Psychological defenses and general coping mechanisms involving
cognitive and behavioral processes intervene between stimulus and response
in the human, and have been shown to modify the relationship between the
situation and the affective and physiological responses. Although more work
has been done on this subject in the psychoendocrine than the autonomic
areas, there is ample evidence that classical intrapsychic defenses as well as

cognitive styles (“leveling-sharpening,” “field independence-dependence”)
may modify autonomic responses as well as mental experience. These

findings generally describe an interaction by which intensity of affect and of
autonomic reactivity are concurrently reduced by psychological processes
which tend to ward off, transform, avoid, or blunt the impact of the
potentially painful experience.
Another view, based primarily on clinical observations, describes the
converse relationship: the repression of affects (particularly anger) is held to
result in greater autonomic responses to a situation whereas affect

expression reduces the autonomic disturbance. This theory is sometimes
used as a hypothesis for the etiology of some psychosomatic illness. Oken has
specifically tested this notion and found little general support for it. In fact,
his data slightly suggest a contrary result. Systolic blood pressure, heart rate,
respiratory rate, skin resistance, and muscle-blood flow were all somewhat
more responsive in those subjects in the high extremes of affective range and
lability. The low affect group did, however, show a statistically insignificant
tendency toward greater responsiveness in three measures of peripheral
vasoconstriction.
The foregoing study used healthy volunteers and it has been shown that
patients with an illness involving the ANS (Raynaud’s Disease) were
physiologically more responsive in the organ system of their illness than

healthy people. In yet another study, Weiner found that young patients with
labile essential hypertension showed relatively reduced cardiovascular

responses to an emotionally arousing laboratory situation. They showed
reduced affective response and failed to show increased physiological
responses. A few individuals were notable exceptions to this generalization.
Until we can understand these and other contradictory findings, we must
remain aware that there is still a great deal to be learned about the
relationship between psychological functioning, affects, and autonomic
responses.
For example, we generally think of the autonomic system as an effector
system working on the internal environment, much as the musculoskeletal
system works on the external world. Autonomic responses are thus viewed as
regulatory, adaptive, or even pathogenic for viscera. And yet there is
mounting evidence that autonomic responses may play a role in regulating
central psychological processes and emotional states through afferent

feedback. This new role for the ANS may force modification of many of our
concepts regarding the role of autonomic responses and the emotions.
Autonomic responses may serve to temper, modulate, and shape central

emotional states.
Afferent Influences
Perhaps the most exciting and least appreciated aspect of how the ANS
works involves its function in conveying information from the internal organs
to the CNS. This topic has been surprisingly neglected during years of
research on the ANS and it is commonplace to find autonomic pathways
represented in textbooks as one-way effector pathways. It is almost as if the
collapse of the James-Lange theory of emotions (that they were caused by
visceral sensations) took with it all study of ANS afferent function. The
previous chapter has outlined the anatomy and neurophysiology of these
afferent pathways.
Russian work on classical conditioning involving “interoceptive
signaling” has continued over the years, however, and has demonstrated that
humans can make very fine discriminations among visceral sensations
previously thought to be diffuse and global. For example, a water jet at one
location along the small bowel mucosa can be distinguished from another
several inches away, after appropriate training. Recent experience with

biofeedback training suggests that information about internal states is
available to the CNS, but is ordinarily appreciated only in the most vague and
poorly differentiated manner. Training improves the clarity and

discrimination of the internal perceptions and may provide the basis for some
voluntary control over internal processes (see below under Autonomic

Learning.)
A second area which has exciting potential significance for our
understanding of ANS function, involves the role of afferents from

cardiovascular organs in controlling central neural functions, such as
attention, and perhaps in modulating affective states. The evidence for this
concept has been reviewed recently by the Laceys. Neurophysiological and
neuroanatomical studies have been reviewed in the previous chapter. The
most impressive direct behavioral evidence for the central effects of this
afferent feedback has been provided by Zanchetti and co-workers, who have
shown that the behavioral syndrome of “sham” rage in the decorticate cat can
be instantaneously halted by stimulating pressoreceptive afferent fibers from
aortic arch or carotid sinus.
Lacey has evidence from studies with humans, using reaction-time
measurements, that decreases in heart rate immediately before a task may
function to improve performance. This effect is presumed to be mediated
through cortical alerting via autonomic afferent pathways, the converse of the
inhibitory effects observed with increases in blood pressure. Obrist has
subsequently shown, however, that the decreases in chin electromyogram
(EMG) and respiratory rate are equally or even more closely related to
performance. His data suggest a more generalized and complex pattern of
preparatory adjustments capable of altering afferent feedback to the CNS

over a number of different pathways. These short-term effects, mediated over
afferent neural pathways, complement and/or counterbalance long-term

effects of ANS activation operating over hormonal pathways.
These findings suggest how autonomic responses, such as increases in
blood pressure, by stimulating baroreceptor nerves, may act to damp or even
block central neural responses to environmental stimulation. This suggestion
is a particularly interesting one because of the implications it has for
psychophysiological theory. The ANS response is no longer viewed as simply

deriving from or reflecting a central state but as having the function of
feedback control over the central neural state. Here is more evidence that
emotional behavior and autonomic responses may have to be studied as
organizationally distinct subunits capable of having important interactions,

rather than as components of a single integrated response pattern.
Individual Differences
In the preceding section I have described some of the organized
patterns of autonomic regulation which are characteristically found during

certain states, activities, and behaviors occurring in the course of natural life.
The complexity of the patterns possible, the interrelationships of the various
effector pathways, and their afferent feedback have already been introduced
as contributing to remarkable differences between individuals in the actual

ANS patterns shown under these conditions. Fortunately, we have some
fundamental data to answer the following questions: To what extent are
individual differences important? Is there consistency in these differences

when the individual is repeatedly observed in the same situation? To what
extent is a given individual consistent in his autonomic patterning in response
to different situations?
Lacey has found that the mean skin conductance and heart-rate changes
of a group of college-age, male subjects during a cold pressor test can be
reliably differentiated from the pattern of the group during a reaction-time

test or during attention to a tape-recorded story. Differences in mean
direction of heart-rate response, as well as differences in degree, characterize
each situation. However, if the individual data are examined, many deviations
from the mean group pattern can be found. Such individual patterns are not
simply the result of random variability with time due to the action of
interrelated variables such as temperature or fluid intake which may
influence ANS function. Lacey has shown that individual patterns are
maintained to a significant degree over intervals as long as four years and are
thus consistent modes of functioning. Here again, there are exceptions,
approximately one third of the subjects showing correlations between test

and retest below r = 0.30. Finally, if test situations are not too dissimilar,
correlation can be found in individual patterns across different situations,
although there are notable individual exceptions. In general, individuals show
a significant tendency to respond consistently in a pattern which is

characteristic for them. For example, one autonomic variable may be found to
be minimally reactive to a wide variety of situations and another, maximally
reactive. Interestingly there is some evidence that subjects with complaints in
a given system tend to be most responsive in that system, a fact with some
implication for pathological mechanism (see below). In addition, subjects who
are variable instead of consistent in their individual response patterns have

been studied and found to differ, for example, in cognitive style.
Thus we are faced with the fact that the ANS pattern is determined to a
significant degree both by the situation and by the characteristics of the
individual, as well as by uncontrolled factors productive of more random-
appearing variability. The attention to individual differences has been far

greater in psychophysiology than in other areas of biological study, where
they are obscured by analysis which emphasizes the central tendency of large
groups of subjects. The factors which correlate with these individual

differences appear to be almost limitless, and yet we have only fragmentary
information on the most obvious, the genetic determinants.
Most of the available genetic studies on autonomic function involve

blood-pressure regulation, reviewed by Pickering. Identical twins show
extremely high correlation in blood pressures from normal to hypertensive
range, fraternal twins less so. Rats can be bred to be hypertensive and so,
apparently, can humans, although there is disagreement as to the mode of
inheritance. No studies have been done on the extent of interindividual

variability in blood pressure which can be accounted for by genetic
determinants, for example by studying identical twins raised in separate
environments. Other aspects of autonomic functioning have been more
neglected, and no detailed study of autonomic response patterning in
identical and fraternal twins has been done, to my knowledge. Despite this
lack of real information, there is a strong tendency for genetic factors to be
taken for granted as important determinants of autonomic functional
organization.
Numerous investigators have attempted to understand the differences
between individuals in ANS response pattern to a given situation as a function
of their psychological response to the situation. Others have found that
enduring characterological or cognitive differences between individuals are
associated with ANS pattern differences. A focus on the transaction between

the subject and the experimenter or the patient and the therapist is preferred
by others, and here again significant associations can be demonstrated
between these interchanges and the pattern of ANS responses.
All this evidence leaves no doubt that the regulation of ANS function is
influenced by a range of neural systems serving a wide variety of affective and
cognitive functions. We lack any unifying hypothesis through which these

myriad influences can be logically arranged and we have no clear idea how
any of these influences may become so prepotent as to cause alterations of

pathological intensity which are not compensated by homeostatic regulation.
Some processes by which ANS organization can be altered or molded during
life experience will be discussed below.
Plasticity of Function
Throughout the discussion thus far, individual differences in ANS
functional organization have been repeatedly encountered. For the most part,
these individual characteristics are relatively stable, and are thought to be an
expression of the interaction between genetic and environmental
determinants in the previous life history of the subject.
In recent years, two kinds of research have begun to explore the
environmental contribution to the development of individual differences in

ANS response, the role of autonomic learning and the effects of early
experience on physiological development. Both of these kinds of
environmental interactions have already been shown to have the capacity to

alter psychophysiological function in consistent and systematic ways.
Knowledge of these processes may help us to understand the origin of
psychosomatic illness, to treat such conditions more effectively, and even to
prevent their occurrence.
Autonomic Learning
The ANS, in most of its effector systems, demonstrates the three basic
forms of short-term adaptation characteristic of the musculoskeletal nervous
system: (1) learning not to respond (habituation); (2) learning by association
(classical conditioning); and (3) learning by effect (instrumental
conditioning).
The simplest and, paradoxically, the least thoroughly studied form of
short-term adaptation is the phenomenon of habituation, the progressive
waning of response to a repeated stimulus. I have touched on this
phenomenon earlier when discussing the orienting response.
It must be distinguished from simple metabolic fatigue or adaptation of
peripheral sense organs, and this is done operationally by demonstrating that

after habituation, the effector system can be readily utilized for another
response or the response can be elicited by a qualitative change in the

stimulus used. Thus, habituation is a specific form of learning of immense
adaptive usefulness in coping, physiologically, with a situation of unavoidable,
repeated, or prolonged stimulation. This form of learning has been
demonstrated in most aspects of autonomic regulation and has been

reviewed at the behavioral, neuro-physiological (autonomic), and cellular
levels.
An intriguing and poorly understood aspect of habituation is its
duration. Obviously, if habituation were permanent, adult organisms would
be almost unresponsive except to stimuli never previously encountered.
Some responses, particularly to weak stimuli, return within minutes or hours
after the last stimulus presentation; others remain inhibited for days. If
habituation is carried out over a number of days, the specific effect can last
for weeks. Months later, after apparent recovery, some responses will
rehabituate in one or two trials, indicating prolonged residual effect. Very
painful and emotion-arousing stimuli or those related to the drives of hunger

and sex show little or no long-term habituation.
There is evidence that habituation of autonomic responses involves

central inhibitory systems and its rapidity is correlated with the rate of
extinction of classically conditioned responses.
The second form of autonomic learning, the “conditional reflex” of Ivan

P. Pavlov, has received more research attention than any other aspect of
autonomic functioning. In this form of plasticity, the kinds of autonomic
patterned responses described above (e.g., in exercise or digestion) come, at

least partially, under the control of previously neutral signal stimuli because
of repeated temporal association. The sign heralds the event and
subsequently comes to elicit the response which could previously be elicited

only by the event itself. The signal is generally termed the conditioned
stimulus and the event, the unconditioned stimulus. This simple learning
paradigm has served as a useful model for the study of psychophysiological
processes and even for the etiology of psychosomatic illness, wherein an
organism responds in accordance with past experience in preference to
current physical realities. To give a clinical example, classical conditioning

may be involved when the asthmatic child in the city begins to wheeze at the
sight of the car which usually takes him to the country, well before any rural
allergens have reached his respiratory system.
Unfortunately, it has rarely been possible to study classical conditioning
under the natural conditions of everyday life. The phenomenon remains a
laboratory model and there are no data to tell us the extent to which this form
of learning actually moulds specific autonomic responses in the individual
throughout his development.
The range and variety of classical conditioning phenomena involving
the ANS is truly impressive. Almost any stimulus which reaches the CNS,
including visceral sensation (“interoceptive” stimuli) can acquire the capacity

to activate almost any autonomic effector system, provided an unconditioned
stimulus can be found which acts through the CNS to produce a response in
the desired autonomic effector system. The signal (conditioned) stimulus

must precede the physiological (unconditioned) by an interval ranging from
less than half a second to as long as a minute for adequate conditioning to

take place. Centrally acting drugs serve as well as physical stimuli, such as
electric shock, and with interoceptive stimuli much longer pairing intervals
are effective. Generally, conditioned responses are small relative to the
unconditioned responses, may fluctuate in amplitude after being established,
and can even disappear after repeated elicitation. The timing of the
conditioned response (whether “anticipatory” to the unconditional stimulus
or coincident with it) and its magnitude are affected by: (1) the time interval
between the signal and the physiological stimulus; (2) the intensity and
nature of the physiological stimulus; the central state of the organism; and (4)
the frequency, timing, and number of previous associative pairings. Repeated
stimulation by a strong physiological stimulus may alter thresholds of
response to mild signal stimuli, irrespective of associative pairing. This is

often called “pseudoconditioning” and can be differentiated by the use of
appropriate experimental controls.
This form of physiological learning can be conceptualized as a
sophisticated extension of adaptive physiological organization. By this means

the organism can prepare in advance for an environmental demand, such as a
sudden burst of exertion, thus reducing the latency of appropriate

physiological alterations, e.g., increased blood flow to the muscles. Indeed,
some of the most elegant and complete descriptions of widespread classically

conditioned cardiovascular responses come from the work of Rushmer and
Smith on dogs repeatedly studied before treadmill-exercise tasks. Such
studies approximate natural conditions in which the signal stimuli are
complex, often involving a whole environment including other people, and
activate many sensory pathways. Likewise the unconditioned stimulus may
also involve all aspects of ANS regulation in an organized pattern. These

situations are very different from the excessively discrete stimuli used in the
laboratory and a great deal less is known about the properties of classical
conditioning under such circumstances. For instance, Hofer has shown that in
people who are currently undergoing classical conditioning experience,
naturally occurring life situations interact with the conditioned state to
release the specific conditioned physiological response well in advance of its
usual time of onset.
In the course of the exhaustive research conducted by Russian scientists

on classical conditioning, a phenomenon began to emerge which has greatly
extended the implications of learning for an understanding of ANS function in
health and disease. For example, Lisina (cited by Razran) noted that although
the usual classically conditioned vascular response to electrical shock was
vasoconstriction, occasional vasodilatory responses took place. If the shock
was made to terminate early whenever vasodilation occurred, there was little
effect. However, if the subject was allowed to watch his own plethysmogram,
he soon learned to vasodilate in response to the shock pairings and thus
escape some of the electric shock. This suggested that the ANS response could
be modified by an awareness of the consequences of the response, not simply
by previous association of stimuli.
For many years it was believed that autonomically mediated behavior
could be modified by classical but not by instrumental training methods. In
the last few years new data have appeared to demonstrate that the ANS may
also participate in the kind of learning which depends upon the consequences
of a given response.
In an impressive series of experiments, Miller, DiCara, and others have

demonstrated that salivation, heart rate, blood pressure, peripheral
vasomotor activity, intestinal motility, renal and gastric blood flow can be
either increased or decreased by a procedure of rewarding spontaneous

fluctuations in the desired direction. The desired autonomic response can be
progressively “shaped” to increasing magnitude by progressively altering the
criterion level for reward by either brain stimulation or shock avoidance.
These experiments were carried out under curare with controlled

positive pressure respiration as a control to rule out possible mediation of
autonomic changes via reflex responses to a primary musculoskeletal

maneuver, such as breath holding, carried out by the voluntary motor system.
Initially conceived as a necessary control, it was found that the learning effect
was much more readily obtained under curare than under natural conditions
and this has raised problems of interpretation of their results. Does the
explanation lie in the enormously simplified afferent feedback available to the
curarized animal, resulting in a relative amplification of visceral information
necessary for instrumental learning? Or is it that curare and positive pressure
respiration alter the central neural state so as to produce a unique functional

organization not available to the animal under normal conditions? If the ANS
is capable of instrumental learning during the natural state, why are the
changes produced in both animals and man so small in magnitude and

require so much training to achieve by present methods? These questions are
currently under intensive investigation.
Answers to these problems bear directly on the implications this form
of autonomic learning may have for the behavior of the ANS in health and
disease. If environmental rewards occur following an autonomic response

and if this “reinforcement” increases the likelihood and magnitude of the ANS
response when the situation recurs, this may be the way in which specific
autonomic responses, such as syncope or bronchoconstriction, become
unusually frequent and severe in some people. This idea will be enlarged
upon in the next section but it is clearly of considerable importance to
understand the conditions controlling the ease and rapidity of instrumental
learning in the ANS.
A major issue in our knowledge of how the ANS functions involves its
specificity. In the same way that the ANS was thought to be capable only of
classical conditioning, it was also, until recently, thought to be capable only of
diffuse discharge. We have noted the tendency for patterns of integrated
activity involving all effector systems to be a common mode of operation. By

differential reinforcement, again under curare, DiCara and Miller showed that
it was possible for the ANS to dilate blood vessels in one ear and not in the
other. Likewise, heart-rate increases could be produced without altering
blood pressure and, vice versa, the same with heart rate and intestinal
contraction. Clearly, discrete and specific alterations of ANS activity can be
predictably demonstrated.
DiCara and Goesling and Brener present evidence that a pattern of
musculoskeletal, respiratory, and cardiac activity is in fact conditioned under

curare, although the first two are not evident until the animal recovers from
the curare. Rats previously trained for high heart rates under curare are more
active, more emotional by various criteria, and have much higher respiratory
rates than those trained for low heart rates when the animals are replaced in
the training situation without curare. What is actually learned is a pattern

involving musculoskeletal, respiratory, and autonomic cardiac pathways.
Further training without curare can separate the cardiac from the other
physiological and behavioral changes, but no further increase in cardiac rate
change is accomplished. Brener has shown in another way that
musculoskeletal and cardiac changes are functionally interrelated and even
centrally interdependent. Animals trained to be active to avoid electric shock,
when subsequently trained to alter heart rate under curare, showed
increased heart rate regardless of which direction of change they were being
trained for under curare. Those trained to inactivity before heart-rate training
showed decreased heart rate, regardless of reinforcement contingencies
under curare. Thus, the direction of heart-rate change under curare was more
powerfully determined by their previous behavioral training than by the
more immediate autonomic training under curare. These experiments
suggest that there are important interactions between somatomotor and
autonomic learning experience. An understanding of these interactions may
take us a long way toward learning how these processes may determine
autonomic responses to environmental events in natural life situations.
The role of this form of plasticity in the internal economy of the
organism is also of considerable theoretical importance. For instance, to what

extent are homeostatic regulatory processes acquired through learning rather
than developed according to genetic plan? Miller et al. have shown that an
excess of extracellular water or salt can function as a drive and that a return
to normal water and electrolyte balance, accomplished by visceral hormonal

and autonomic responses, can function as a reward in an experimental
situation. The implication is that homeostatic autonomic responses may be
acquired and shaped by the action of reward in the form of a return of the
internal milieu to normal. Moreover, the imbalances caused by disease
processes are countered by autonomic readjustments which may be learned
in the same way through the effect of tending to return the internal state
toward status quo. This important new hypothesis on the origin and
maintenance of homeostatic functioning in health and disease urgently needs
experimental testing.
A parallel development accompanying the growth of interest in
autonomic reward learning has been the attempt to apply these training
techniques to the treatment of disturbed autonomic function, such as
arrhythmias of neural origin and hypertension. These techniques will be
reviewed in subsequent chapters on these disease states.
To return for a moment to the experiments described above the
subjects did not change their autonomic response when rewarded by shock
escape until they were provided with additional feedback over exteroceptive
pathways by being allowed to watch the plethys-mograph write-out. Brener
gave subjects an opportunity to hear their heart beat amplified and they were
eventually trained to be able to press a button every time they felt their heart
beat, in the absence of sound amplification. After this training in visceral
awareness, the subjects were able to increase or decrease heart rate

“voluntarily” to a significantly greater extent than control subjects.
By what strategies do subjects accomplish this “voluntary” control?
Some use respiratory or musculoskeletal intermediary behavior, others
attempt to create certain mental states, and still others cannot describe how it
is done. Contrived strategies are not always the most effective. In applying
biofeedback to the therapeutic situation, no other reward is necessary to the
patient than return of his biofeedback signal toward normal levels.
This work is in its infancy and requires a great deal more carefully
controlled investigation, but it promises to open up new links between
conscious experience and the autonomic nervous system.
Early Experience Effects
Mounting evidence over the past ten years has made it clear that
behavior, visceral responses, and even survival of the adult under stress can
be predictably influenced by alterations in early experience during

development of the organism. Of the visceral alterations produced in this way,
the pituitary adrenocortical system is the only one which has been
extensively studied. There is enough direct evidence however, to conclude

that autonomic responses can also be shaped by these long-term
developmental interactions. If autonomic neural regulation and response
patterning can be influenced by early experience, then knowledge about these
processes may help us to understand how a particular adult can have
acquired psychosomatic vulnerabilities.
In 1961, during John P. Scott’s classic studies on socialization in dogs,

his co-workers observed that if puppies were left in the company of other
dogs without human contact for the first twelve weeks of life, they showed
heart-rate responses to electric shock at fourteen weeks of age which were
significantly different from dogs which had had as little as one week
“socialization” experience with people when they were seven-week-old
puppies. If the week of socialization experience occurred either earlier or
later than seven weeks it was less effective in altering both cardiac response
and behavior. This age was thus described as a “critical” period for the effect
of socialization in the dog. The influence of restricted as opposed to increased
locomotor, sensory, and social experience on the development of heart-rate

regulation has been further documented by two independent studies. They
both showed higher heart rates in response to a variety of stimuli in adult rats
which had been raised in early environments with increased stimulation.

Restricted or isolated early living conditions, in contrast, predisposed to
bradycardia in response to stimulation by noise. Handling of neonatal rat

pups, known to produce an altered adrenocortical response to stress during
adulthood, has been shown to increase the level of heart rate and decrease its
variability during a period of stimulation of the adult rat by white noise.
These demonstrations make the importance of early experience in the
development of autonomic response tendencies clear but do not tell us how
the experience comes to affect autonomic regulation in later life. As yet we
cannot even say whether early handling works primarily by a direct
stimulating effect on the pups or through altering maternal behavior toward

those pups. Recent studies have shown that handling the mother can affect
adrenocortical reactivity of her offspring in later life and that separation of rat
pups from their mother, at two weeks of age, produces a marked alteration in
autonomic cardiac balance.
Studies have shown that the influence of early experience is not

confined to small differences in autonomic response pattern but can reliably
affect mortality rates from starvation, surgery, and metabolic derangement as
well as modify susceptibility to experimental gastric-ulcer formation. In all

these conditions, the ANS is known to play an important regulatory role and it
is reasonable to suppose that altered ANS function may mediate these early
experience effects.
Knowledge of the development of autonomic neural integration is just
beginning to accumulate and our understanding of how early experience and
its timing may shape the course of development is rudimentary. This is an

area of active research interest which should contribute significantly in the
next years to our understanding of the origin of psychosomatic illness.
Pathophysiological Mechanisms
Having outlined the functional characteristics of the ANS in relation to
both the internal and the external environment, I will conclude and
summarize by attempting to sketch how these characteristics may operate in
the exacerbation or production of disease states during interaction of the
organism with its environment. I would like to emphasize how tenuous the
links are between what we know of autonomic functioning and the
production of illness in the organism. The natural history of man is
characterized by repeated adaptive challenges posed by his social and
physical environment. The predominant function of the ANS is not only to

respond to the environment but to return to baseline, not only to react but to
repair. As Richards has so elegantly described, medical illness can be
characterized as disordered homeostatic balance. Yet little is known of the

factors which sustain imbalance or cause prolonged over- and
underresponse. New data suggest that homeostatic organization may be
acquired through physiological learning, rather than be dictated by genetic

mechanisms alone. If this is so, some individuals may acquire the potential for
prolonged disorders of homeostatic balance and thus a proclivity toward
illness. We do not yet have any clear idea of how or when such characteristics
might be acquired.
The ANS, through its central neural integration, is one of the prime
organizers of homeostasis, and we may justifiably examine its functional
properties in search for the mechanisms of disordered function and look to
the relationship of the organism with its environment as an important
contributor to the etiology of illness. But in our present state of knowledge we

must do so with the intent of generating testable ideas rather than outlining
established principles.
Although homeostatic regulation is organized to return function within
the ANS to a set level, priorities appear to exist so that homeostasis in one
area of the system may be maintained at the expense of severe disequilibrium
in another. The example was given of temperature homeostasis being
maintained at the expense of water and electrolyte balance during heat stress,
in order to illustrate the role of the ANS in determining the form of

physiological disruption following environmental stress. Since there appear
to be highly individual patterns of autonomic neural balance and integration
among the effector systems, certain individuals may be more susceptible and
others relatively resistant to disruption by an identical environmental stress.
These individual patterns may be predominantly determined by genetic

mechanisms or by previous environmental adaptations such as a high-salt
diet. Furthermore, autonomic functions fluctuate in regular rhythms leading

to a period during the twenty-four-hour cycle when susceptibility to under-
or overresponse to a given stressor is relatively increased. During the course
of development, autonomic balance changes markedly so that different life
stages are associated with a greater likelihood of certain pathological
responses. For example, clinicians are aware that autonomic responses to
manipulation of the upper gastrointestinal (GI) tract, such as salivation,

retching, and bradycardia are more intense during childhood and adolescence
than in later life.
Autonomic responses to environmental stimulation and to mental and
physical tasks appear to have some immediate adaptive function in preparing
the organism internally to function more effectively in its environment.

However, the repeated, frequent elicitation of defensive, alerting, and
exertional responses has been demonstrated to produce sustained
hypertension, vascular and renal lesions, and increased mortality in animal

colonies under specified conditions. Alterations of ANS function during
altered states of consciousness, such as REM sleep, may precipitate episodes
of congestive failure, arrhythmia or angina pectoris in cardiac patients

because of the “flurries” of tachycardia, and bradycardia and vasoconstriction
characteristic of the autonomic function during that state of sleep. Likewise,
transient emotional states are associated with a wide variety of autonomic
patterns and responses which may precipitate decompensation of chronic

disease states. Stroebel95 has found evidence that certain emotional states
cause a prolonged disruption of the organized patterns of circadian
rhythmicity. The resulting autonomic disorganization may increase disease
susceptibility. Avoidance learning contingencies may serve to perpetuate
such disorders of central neural homeostatic control.
None of these interactions account for the clinically observed fact that
some people are unusually prone to highly specific kinds of autonomic

responses of extreme intensity, for example asthma, in the absence of
allergenic stimulation. The facts on autonomic learning and early experience
effects allow us to build a theoretical model for the acquisition of such highly
specific autonomic pathophysiologic response tendencies. It seems possible

that a certain early experience occurring at a sensitive period may alter the
genetically programmed development of reactivity in autonomic function,
either through shifting baseline set point, variability, or the capacity to

habituate. Such early experience may at the same time elicit a characteristic
primitive emotional state. Then, through associative learning, a particular
physiological response may become conditioned to signal stimuli which, at

this development stage, characteristically precede physiological stimulation.
The response is thus more frequently elicited and by ordinarily trivial stimuli.
In addition, if the response tends to be followed by reward or by the
avoidance of unpleasant events, instrumental conditioning may gradually

strengthen and shape the autonomic response until a highly specific and
intense physiological response is produced in that particular individual.
One may exemplify such a series of processes in the hypothetical
development of bronchial asthma. A tendency toward respiratory
hyperactivity may be set in motion by an early experience, such as maternal
separation, which provokes repeated and prolonged crying, and a
concomitant emotional state which may be termed “separation anxiety.”
Subsequently, exposure to heavy concentrations of pollen precipitates asthma
in association with environmental cues which thereafter acquire the capacity

to elicit mild bronchoconstriction over autonomic pathways. The parents
respond to the mild wheezing elicited by these conditioned cues with
exaggerated attention, gifts, and permission to avoid unpleasant duties. They
may even cancel an intended departure from home. These rewards or

“reinforcement,” which may depend upon the emotional state generated by
threatened separation, increase the likelihood and intensity of asthmatic
episodes in the future. The child learns, perhaps without conscious

awareness, that he can get what he wants by asthmatic breathing.
At this point, the emotional state elicited in this person by threatened

separation has become associated (through classical and instrumental
learning processes) with a highly specific autonomic response pattern:
intense bronchospasm, mucous secretion, etc., that is, clinical asthma. Inborn
autonomic correlates of an emotional state thus may become specifically
modified by particular developmental experiences. The emotional state,
however, is subject to further modification by a number of other
psychological processes and experiences which may even disassemble this
organization and “cure the disease.”
The emotional states deriving from the early separation experience, and
the human relationships built upon them, thus may become interwoven with
the specific physiological effects of the experience on the development of the
child’s respiratory system. Both associative and instrumental learning may
function to stamp in and intensify what might otherwise be a mild and
transient period of childhood wheezing. Further learning and emotionally

trying human relationships may finally generate the severe reactive asthma
which has earned the term “psychosomatic.”
Bibliography
Ader, R. “Early Experiences Accelerate Maturation of the 24-hr. Adrenocortical Rhythm,” Science,
163 (1969), 1225-1226.
Adolph, E. R. “Ranges of Heart Rates and Their Regulations at Various Ages (Rat),” Am. J. Physiol.,
212 (1967), 595-602.
Alexander, R., T. M. French, and G. H. Pollock, eds., Psychosomatic Specificity, Vol. 1. Experimental
Study and Results. Chicago: University of Chicago Press, 1968.
Altman, P. L. and D. S. Dittmer. Biological Handbooks: Respiration and Circulation. Bethesda, Md.:
Fed. of Am. Soc. for Exptl. Biol., 1971.
Anderson, H. T. “Physiological Adaptations in Diving Vertebrates,” Physiol. Rev., 46 (1966), 212-
243.
Appley, M. and R. Trumbull, eds., Psychological Stress—Issues in Research. New York: Appleton-
Baccelli, G., M. Guazzi, A. Libretti, and A. Zanchetti. “Pressoreceptive and Chemoreceptive Aortic
Reflexes in Decorticate and in Decerebrate Cats,” Am. J. Physiol., 208 (1965), 708-
714.
Bernard, C. In J. Fulton, ed., Selected Readings in the History of Physiology, p. 307. Springfield, 111.:
Black, P., ed. Physiological Correlates of Emotion. New York: Academic, 1970.
Blizard, D. A. “Individual Differences in Autonomic Responsivity in the Adult Rat-Neonatal

Influences,” Psychosom. Med., 33 (1971), 445-457.
Bowlby, J. Attachment and Loss, Vol. 1, Attachment. New York: Basic Books, 1969.
Boyles, W. R., R. W. Black, and E. Furchtgott. “Early Experience and Cardiac Responsivity in the
Female Rat,” J. Comp. Physiol. Psychol., 59 (1965), 446-447.
Brady, J. V., D. Kelly, and L. Plumlee. “Autonomic and Behavioral Responses of the Rhesus Monkey
to Emotional Conditioning,” Ann. N.Y. Acad. Sci., 159 (1969), 959-975
Brener, J., R. A. Kleinman, and W. J. Goesling. “The Effects of Different Exposures to Augmented
Sensory Feedback on the Control of Heart Rate,” Psychophysiology, 5 (1969), 510-
516.
Brod, J., V. Fencl, Z. Hejl et al. “Circulatory Changes Underlying Blood Pressure Elevation during
Acute Emotional Stress (Mental Arithmetic) in Normotensive and Hypertensive
Subjects,” Clin. Sci., 18 (1959), 269-278.
Broughton, R., R. Poire, and C. Tassarini. “The Electroderm (Tarchanoff Effect) during Sleep,” EEG
Clin. Neurophysiol., 18 (1965), 691-708.
----. “Sleep Disorders: Disorders of Arousal?” Science, 159 (1968), 1070-1074.
Brown, C. C. “The Parotid Puzzle: A Review of the Literature on Human Salivation and Its
Application to Psychophysiology,” Psychophysiology, 7 (1970), 66-85.
Bykov, K. M. and W. H. Gantt. The Cerebral Cortex and the Internal Organs. New York: Chemical
Publishing, 1957.
Cannon, W. B. Bodily Changes in Pain, Hunger, Fear and Rage, 2nd ed. New York: Appleton, 1929.
Davis, R. C. and A. M. Buchwald. “An Exploration of Somatic Response Patterns: Stimulus and Sex
Differences,” J. Comp. Physiol. Psychol., 50 (1957), 44-52.
Davis, R. C., A. M. Buchwald, and R. W. Frankmann. “Autonomic and Muscular Responses and
Their Relation to Simple Stimuli,” Psychol. Monogr., Vol. 69, no. 20, 1955-
Dicara, L. “Heart Rate Learning in the Non-Curarized State, Transfer to the Curarized State and
Subsequent Retraining in the Non-Curarized State,” Physiol. Behav., 4 (1969), 621-
624.
----. “Learning of Cardiovascular Responses: A Review and a Description of Physiological and

Biochemical Consequences,” Trans. N.Y. Acad. Sci., (1971), 411-422.
Elsner, R., D. L. Franklin, R. L. Van Citters et al. “Cardiovascular Defense Against Asphyxia,”
Science, 153 (1966), 941-949-
Engel, G. L. Fainting-Physiological and Psychological Considerations, 2nd ed. Springfield, Ill.:

Folk, G. E. Introduction to Environmental Physiology-Environmental Extremes and Mammalian

Survival. Philadelphia: Lea & Febiger, 1966.
Freedman, D. G., J. A. King, and O. Elliot. “Critical Period in the Social Development of Dogs,”
Science, 133 (1961), 1016-1017.
Funkenstein, D. H., S. H. King, and M. E. Drolette. Mastery of Stress. Cambridge, Mass.: Harvard
Galen, C. De Usu Partium Corporis Humani, cited by D. Sheehan in “The Discovery of the
Autonomic Nervous System,” Arch. Neurol. Psychiatry, 35 (1936), 1081.
Gellhorn, E. Emotions and Emotional Disorders—A Neurophysiological Study. New York: Hoeber,
1963.
Glaser, E. M. The Physiological Basis of Habituation. London: Oxford University Press, 1966.
Glass, D. C., ed. Neurophysiology and Emotion. New York: Rockefeller University Press, 1967.
Goesling, W. J. and J. Brener. “Effects of Activity and Immobility Conditioning Upon Subsequent
Heart Rate Conditioning in Curarized Rats,” J. Comp. Physiol. Psychol, 81 (1972),
311-317.
Graham, D. T., J. D. Kabler, and L. Lunsford. “The Course of Vasovagal Fainting. A Diphasic
Response,” Psychosom. Med., 23 (1961).
Halbebg, F. “Chronobiology,” Ann. Rev. Physiol., 31 (1969), 675-725.
Heath, H. A. and D. Oken. “Change Scores as Related to Initial and Final Levels,” Ann. N.Y. Acad.
Sci., 98 (1962), 1242-1256.
Hein, D. L., S. I. Cohen, and B. M. Shmavonian. “Perceptual Mode and Cardiac Conditioning,”
Psychophysiology, 3 (1966), 101-107.
Hellbrugge, T., J. Lange, J. Rutenfranz et al. “Circadian Periodicity of Physiological Functions in

Different Stages of Infancy and Childhood,” Ann. N.Y. Acad. Sci., 117 (1964), 361-
373.
Henry, J. D., J. P. Meehan, and P. M. Stephens. “The Use of Psychosocial Stimuli to Induce
Prolonged Systolic Hypertension in Mice,” Psychosom. Med., 29 (1967), 408-432.
Hofer, M. A. “Regulation of Heart Rate by Nutritional Factor in Young Rats,” Science, 172 (1971),
1039-1041.
Hofer, M. A. and L. E. Hinkle. “Conditioned Diuresis in Man: Effects of Altered Environment,

Subjective State and Conditioning Experience,” Psychosom. Med., 26 (1964), 653-
660.
Hofer, M. A. and M. F. Reiser. “The Development of Cardiac Rate Regulation in Preweanling Rats,”
Psychosom. Med., 31 (1969), 372-388.
Hofer, M. A. and H. Weiner. “The Development and Mechanisms of Cardiorespiratory Response to

Maternal Deprivation in Rat Pups,” Psychosom. Med., 33 (1971), 353-362.
Hord, D. J., L. C. Johnson, and A. Lubin. “Differential Effect of the Law of Initial Value on Autonomic
Variables,” Psychophysiology, 1 (1964), 79-87.
Hutt, C. and S. J. Hutt. “The Neonatal Evoked Heart Rate Response and the Law of Initial Value,”
Israel, N. R. “Leveling-Sharpening and Anticipatory Cardiac Response,” Psychosom. Med., 31

(1969), 499-509.
Johnson, L. C. “A Psychophysiology for All States,” Psychophysiology, 6 (1970), 501-516.
Kandel, E. R. and W. A. Spencer. “Cellular Neurophysiological Approaches in the Study of

Learning,” Physiol. Rev., 48 (1968), 65-134.
Katin, E. S. and R. J. McCubbin. “Habituation of the Orienting Response as a Function of Individual

Differences in Anxiety and Autonomic Lability,” J. Abnorm. Psychol., 74 (1969), 54-
60.
Kimble, G. A. Hilgard and Marquis, Conditioning and Learning, 2nd ed., p. 100. New York:
Appleton-Century-Crofts, 1961.
Knapp, P. H. Expression of the Emotions in Man. New York: International Universities Press, 1963.
Kuntz, A. The Autonomic Nervous System. Philadelphia: Lea & Febiger, 1953.
Lacey, J. I. “Psychophysiological Approaches to Evaluation of Psychotherapeutic Process and

Outcome,” in E. A. Rubenstein et al., eds., Research in Psychotherapy, pp. 160-208.
Washington, D.C.: Am. Psychol. Assoc., 1959.
----. “Somatic Response Patterning and Stress: Some Revisions of Activation Theory,” in M. Appley
and R. Trumbull, eds., Psychological Stress, pp. 14-37. New York: Appleton-Century-
Crofts, 1967.
Lacey, J. I. and B. C. Lacey. “The Law of Initial Value in the Longitudinal Study of Autonomic
Constitution: Reproducibility of Autonomic Response and Response Patterns over
a Four-Year Interval,” Ann. N.Y. Acad. Sci., 98 (1962), 1257-1290.
----. “Some Autonomic-Central Nervous System Interrelationships,” in P. Black, ed., Physiological

Correlates of Emotion, pp. 205-207. New York: Academic, 1970.
Langley, J. N. “On the Union of Cranial Autonomic (Visceral) Fibers with the Nerve Cells in the
Superior Cervical Ganglion,” J. Physiol., 23 (1898), 240-270.
Lipton, E. L., A. Steinschneider, and J. B. Richmond. “The Autonomic Nervous System in Early
Life,” N. Engl. J. Med., 273 (1965 b 147-154> 201-208.
----. “Autonomic Function in the Neonate: VII-Maturational Changes in Cardiac Control,” Child
Dev., 37 (1966), 1-16.
Löfving, A. “Cardiovascular Adjustments Induced from the Rostral Cingulate GYRUS with Special
Reference to Sympatho-Inhibitory Mechanisms,” Acta. Physiol. Scand., 53, Suppl.
184 (1961), 1-79.
Luce, G. Biological Rhythms in Psychiatry and Medicine. Washington: U.S. Govt. Print. Off., 1970.
Masters, W. H. and V. E. Johnson. Human Sexual Response. Boston: Little, Brown, 1966.
Miller, N. “Learning of Visceral and Glandular Response,” Science, 163 (1969), 439-445-
Miller, N., L. V. Dicara, and G. Wolf. “Homeostasis and Reward: T-Maze Learning Induced by
Manipulating Antidiuretic Hormone,” Am. J. Physiol., 215 (1968), 684-686.
Mills, J. N. “Circadian Rhythms during and after Three Months in Solitude Underground,” J.
Physiol., 174 (1964), 217-231.
Mittelman, B. and H. G. Wolff. “Affective States and Skin Temperature: Experimental Study of
Subjects with ‘Cold Hands’ and Raynaud’s Syndrome,” Psychosom. Med., 4 (1942), 5-
61.
Murdaugh, H. V., J. C. Seabury, and W. L. Mitchell. “Electrocardiogram of the Diving Seal,” Circ. Res.,
9 (1961), 358-361.
Newton, G. and S. Levine. Early Experience and Behavior. Springfield, Ill.: Charles C. Thomas, 1968.
Obrist, P. A., R. A. Webb, and J. R. Sutterer. “Heart Rate and Somatic Changes during Aversive
Conditioning and Simple Reaction Time Task,” Psychophysiology, 5 (1968). 696-
723.
Oken, D. “Relation of Physiological Response to Affect Expression,” Arch. Gen. Psychiatry, 6

(1962), 336-351.
----. “The Role of Defense in Psychological Stress,” in R. Roessler and N. Greenfield, eds.,
Physiological Correlates of Psychological Disorders, pp. 193-210. Madison:
University of Wisconsin Press, 1962.
Paulev, P. “Cardiac Rhythm during Breath Holding and Water Immersion in Man,” Acta. Physiol.
Scand., 73 (1968), 139-150.
Pavlov, I. P. (1927) Conditioned Reflexes: An Investigation of the Physiological Activity of the

Cerebral Cortex. New York: Dover, 1960.
Pick, J. The Autonomic Nervous System Morphological Comparative, Clinical and Surgical Aspects.
Pickering, G. The Inheritance of Arterial Pressure in High Blood Pressure. New York: Grune &
Stratton, 1968.
Pribram, K. H. “Emotion: Steps toward a Neuropsychological Theory,” in D. C. Glass, ed.,

Neurophysiology and Emotion, pp. 3-40. New York: Rockefeller University Press,
1967.
Prokasky, W. F. Classical Conditioning. New York: Appleton-Century-Crofts, 1965.
Razran, G. “The Observable Unconscious and the Inferable Conscious, in Current Soviet
Psychophysiology: Interoceptive Conditioning, Semantic Conditioning and the
Orienting Reflex,” Psychol. Rev., 68 (1961), 81-147.
Reiser, M. F. “Reflections on Interpretations of Psychophysiologic Experiments,” Psychosom. Med.,

23 (1961), 430-439.
Richards, D. W. “Homeostasis: Its Dislocations and Perturbations,” Perspect. Biol. Med., 3 (1960),
238-251.
Richter, C. P. Biological Clocks in Medicine and Psychiatry. Springfield, Ill.: Charles C. Thomas,
1965.
Roessler, R. and N. Greenfield, eds. Physiological Correlates of Psychological Disorder. Madison:

Rushmer, R. F. and O. A. Smith. “Cardiac Control,” Physiol. Rev., 39 (1959), 41-69.
Sander, L., G. Stechler, H. Julia et al. “Continuous 24 Hour Interactional Monitoring in Infants in
Two Caretaking Environments,” Psychosom. Med., 34 (1972), 270-282.
Sargent, F. and K. P. Weinman. “Physiological Individuality,” Ann. N.Y. Acad. Sci., 134 (1966), 696-
719.
Schacter, S. and J. Singer. “Cognitive, Social and Physiological Determinants of Emotional State,”
Psychol. Rev., 69 (1962), 379-399.
Shapiro, D. and G. E. Schwartz. “Psychophysiological Contributions to Social Psychology,” Ann.
Rev. Psychol., 21 (1970), 87-112.
Snowdon, C. T., D. D. Bell, and N. D. Henderson. “Relationship between Heart Rate and Open Field
Behavior,” J. Comp. Physiol. Psychol., 58 (1964), 423-430.
Snyder, F., D. R. Morrison, and F. Gold-frank. “Changes in Respiration, Heart Rate and Systolic
Blood Pressure in Human Sleep,” J. Appl. Physiol., 19 (1964), 417-422.
Sokolov, Y. N. Perception and the Conditioned Reflex. New York: Macmillian, 1963.
Sollberger, A. Biological Rhythm Research. New York: Elsevier, 1965.
Stein, M. “Some Psychophysiological Considerations of the Relationship between the Autonomic

Nervous System and Behavior,” in D. C. Glass, ed., Neurophysiology and Emotion, pp.
145-154. New York: Rockefeller University Press, 1967.
Stellar, E. and J. Sprague, eds. Progress in Physiological Psychology, Vols. 1, 2, and 3. New York:
Academic, 1967-1970.
Stroebel, C. F. “The Importance of Biological Clocks in Mental Health,” in E. A. Rubinstein, and G. V.

Coelho, eds., Behavioral Sciences and Mental Health, pp. 286-314. Public Health
Service Publication 2064, Washington: Govt. Print. Off., 1971.
Thoman, E. B. and S. Levine. “The Role of Maternal Disturbance and Temperature Change in Early
Experience Studies,” Physiol. Behav., 4 (1969), 143-145.
Tobach, E., ed. “Experimental Approaches to the Study of Emotional Behavior,” Ann. N.Y. Acad.
Sci., 159 (1969), 621-1121.
Tobach, E., L. R. Aronson, and E. Shaw. The Biopsychology of Development. New York: Academic,
1971.
Von Bertalanffy, L. General System Theory. New York: George Braziller, 1968.
Wallace, R. K., H. Benson, and A. F. Wilson. “A Wakeful Hypometabolic Physiologic State,” Am. J.
Physiol., 221 (1971), 795-799.
Weiner, H. “Current Status and Future Prospects for Research in Psychosomatic Medicine,” J.
Psychiatr. Res., 8 (1971), 479-498.
Weiner, H., M. T. Singer, and M. F. Reiser. “Cardiovascular Responses and Their Psychological
Correlates. I: A Study of Healthy Young Adults and Patients with Peptic Ulcer and
Hypertension,” Psychosom. Med., 24 (1962), 477-488.
Weiss, T. and B. T. Engel. “Operant Conditioning of Heart Rate in Patients with Premature
Ventricular Contractions,” Psychosom. Med., 33 (1971), 301-322.
Weybrew, B. B. “Patterns of Psychophysiological Response to Military Stress,” in M. Appley and R.

Trumbull, eds., Psychological Stress, pp. 324-353. New York: Appleton-Century-
Crofts, 1967.
Wilder, J. “Modern Psychophysiology and the Law of Initial Value,” Am. J. Psychotherapy, 12
(1958), 199-221.
Williams, R. B. and B. Eichelman. “Social Setting: Influence on the Physiological Response to

Electric Shock in the Rat,” Science, 174 (1971), 613-614.
Wineman, E. W. “Autonomic Balance Changes during the Human Menstrual Cycle,”

Wolf, S. “The Bradycardia of the Dive Reflex—A Possible Mechanism of Sudden Death,” Trans. Am.
Clin. Climatol. Assoc., 76 (1964), 192-200.
Wolf, S., P. Cardon, E. Shepard et al. Life Stress and Essential Hypertension. Baltimore: Williams &
Wilkins, 1955.
Wolf, S. and H. Goodell, eds. Harold G. Wolff’s Stress and Disease. Springfield, Ill.: Charles C.
Thomas, 1967.
Wolf, W. “Rhythmic Functions in the Living System,” Ann. N.Y. Acad. Sci., 98 (1962), 753-1326.
Wolff, C. T., M. A. Hofer, S. Friedman et al. “Relationship between Psychological Defenses and
Mean Urinary 17—Hydroxycorticosteroid Excretion Rates, Parts I and II,”
Psychosom. Med., 26 (1964), 576-609.
Wolstenholme, G. E. W. and J. Knight, eds., Physiology, Emotions and Psychosomatic Illness, CIBA
Foundation Symposium. Amsterdam: Elsevier, 1972.
Zanchetti, A. “Emotion and the Cardiovascular System of the Cat,” in G. E. W. Wolstenholme and J.
Knight, eds., Physiology, Emotions and Psychosomatic Illness, pp. 201-219. CIBA
Foundation Symposium. Amsterdam: Elsevier, 1972.
Chapter 24
CLINICAL PSYCHOPHYSIOLOGY
Psychoendocrine Mechanisms
John W. Mason
Some Theoretical Implications of Psychoendocrinology
The recognition that endocrine systems are remarkably sensitive to
both acute and enduring psychological influences is a relatively recent and

notable historical development. Only since the 1950s have biochemical
methods for hormone measurement become sufficiently specific, sensitive,

and precise to permit reliable experimental exploration of the scope and
significance of psycho-endocrine relationships. As a result, it has now become

clear that, in viewing central nervous system organization, the endocrine
systems are properly regarded as representing a third effector or motor
system of the brain, along with the autonomic and skeletal-muscular systems.
The far-reaching implications of this new insight for biology, in general, and
for psychophysiology and psychosomatic medicine, in particular, are still only
beginning to be recognized and put to creative use.
Perhaps the broadest of these implications lies in the new and

strategically important leverage that recent knowledge of neuroendocrine
systems provides in gaining an understanding of the organization of central
mechanisms which integrate the internal environment. While the innervation

of smooth and cardiac muscle and exocrine glands by the autonomic nervous
system has been long recognized as a mediating link between the brain and
selected visceral structures, the discovery of neuroendocrine systems extends
the scope of central nervous system (CNS) coordination of the internal

environment to the level of virtually every body tissue and cell via the
circulatory distribution of hormones. In a historical perspective, then, it is
clear that lack of knowledge of this major mediating link between the brain
and peripheral bodily processes severely impeded earlier efforts to deal with
the important problem of how the many separate unit functions of the body
are integrated or coordinated in the overall fashion necessary to maintain the

exquisite homeostatic equilibrium of the organism as a whole. This problem
has long been regarded by biological theoreticians as one of the most
fundamental and crucial issues in biology. In general, the implications of
neuroendocrine linkages for psychosomatic medicine may be viewed in two

closely interrelated perspectives. First, hormonal responses may be viewed,
from principally a psychiatric orientation, as reflecting intrapsychic processes
and as providing a relatively objective approach to the qualitative and
quantitative study of psychological mechanisms. As knowledge develops that
particular psychological processes are determinants or correlates of
particular endocrine reactions, then the psychoendocrine approach can

become a very useful tool for the testing and development of psychiatric
theory, particularly in the elusive area of emotional and related intrapsychic
processes. Secondly, psychoendocrine reactions may be viewed, from

principally a medical orientation, in terms of their possible significance in the
mediation of the effects of psychopathological processes upon bodily tissues
in the pathogenesis of psychosomatic disorders. It may be possible from a
strategic standpoint, for example, to initiate an endocrinological search for
abnormal hormonal profiles or altered response patterns in patients with
psychosomatic illnesses, independently of psychological collaboration, if

necessary, in order to test the hypothesis that characteristic endocrine
abnormalities, reflecting integrative disorders, are regularly present in such

illnesses. If such endocrine imbalances can be demonstrated, then the second
phase, involving the more complicated and laborious work of defining the
relevant psychological concomitants, of evaluating the role of
nonpsychological factors, and of establishing criteria for evaluating the

pathogenetic significance of hormonal changes, could be undertaken with
greater confidence that this conceptual approach warrants such a large
investment of effort.
In the relatively brief span of two decades, there have been only a few
preliminary ventures in psychoendocrine research into the study of
psychosomatic patients, but psychoendocrinologists have been mainly
preoccupied with the basic psychophysiological exploration of the
significance of hormonal responses as reflections of intrapsychic processes.
To put it simply, the principal orientation has been, “what may be learned
about psychological processes by the measurement of blood and urinary

hormone levels”? As is often the case following the introduction of
revolutionary new methods, developments in the psychoendocrine field have
been rapid and wide ranging, with many probing attempts to test the relative
power and usefulness of new tools and to define the scope of their
application. While the total body of accumulated facts is already quite
substantial, the distribution of effort in psychoendocrine research has been
rather uneven, with a few areas receiving much attention, while other
important issues and approaches have barely been explored. Much necessary
attention has also been given to practical obstacles in research technique.
Particularly encouraging progress has been made in the developing and

refining of difficult new methods, the devising of effective, often novel,
strategic and tactical research approaches, and in beginning to solve some of
the formidable human and organizational problems hindering efforts to
achieve the interdisciplinary cooperation which is so essential to progress.
In summarizing the status of psychoendocrinology, therefore, the
general picture might be described as that of a young science emerging from
an initial period of considerable flux and preliminary exploration, but now
tending to move into a more stable period of consolidation and sharper
focusing of effort. A number of reviews provide detailed summaries of
research findings and dogma in the field, but also tend to present a somewhat
incomplete view of the scope of issues and approaches, because of the

disproportionate emphasis on a few selected research objectives and
endocrine systems in most early research efforts (see references 8, 45, 49-51,
and 83). Some principal aims in this chapter, therefore, are not only to outline
highlights of present knowledge in psychoendocrinology, but also to point out

gaps in knowledge, to present a more balanced theoretical perspective of the
evolution of issues and approaches in the field, and, hopefully, to convey
something of the historical sense of scientific adventure and breakthrough

which has pervaded psychoendocrine research in its infancy. In doing so, the
personal bias of the author will undoubtedly be evident, both in the
conceptual approach and in a predilection often to cite firsthand experimental

observations in preference to equally, or more, relevant observations of other
workers. It is hoped, however, that the sense of historical and conceptual
continuity and the broad overview of issues provided by this frankly personal
approach may compensate, in some measure, for the lack of a more eclectic
review of the field.
Basic Scientific Foundations of Clinical Psychoendocrinology
While this chapter is oriented primarily in terms of clinical aspects of
psychoendocrinology, it is important to recognize that interdisciplinary

cooperation between many basic neurosciences has established a solid
experimental foundation for the clinical field. Psychoendocrine research may,
indeed, be viewed as beginning with the pioneering experimental

observations reported in 1911 by Cannon and de la Paz that the adrenal
medulla releases hormone in the cat during the emotional arousal associated
with confrontation by a barking dog. The apparent utility of the multiple
physiological consequences of sympathetic-adrenal medullary response, in

terms of visceral preparation for the strenuous muscular exertion required
for flight or struggle or in preparation for injury, was brilliantly elaborated by
Walter Cannon. In 1936, Selye provided preliminary evidence that a second

endocrine system, the pituitary-adrenal cortical axis, also with extensive
influences on many metabolic functions, responded to “mere emotional
stimuli” in rats. It was not until about 1952, however, that the major
breakthroughs in hormone assay methodology, such as the chromatographic
Nelson-Samuel’s method for the determination of 17-hydroxycorticosteroid
(17-OHCS) levels in plasma, ushered in the modern era of psychoendocrine
research which has led to the realization that the scope of endocrine systems
involved in psychoendocrine relationships is extremely broad. In the 1970s,
in fact, we reach a point where it is difficult to exclude any endocrine system
as being entirely independent of psychological or neural influences.
Fortunately, the development of new hormone-assay methods during

the 1950s coincided with availability of a number of important new methods
and developments in the basic brain and behavioral sciences. The extensive
work of Harris and others in neuroendocrinology demonstrated the

functional significance of the hypothalamo-hypophyseal portal capillary
system as a neuro-humoral link between the hypothalamus and the anterior
pituitary gland. This finding greatly increased the scope of
neuroendocrinology, from concern with only the few hormones of the

posterior pituitary, sympathetic-adrenal medullary system, and, perhaps, the
vago-insulin system, to the inclusion of the many additional hormones of the
anterior pituitary gland and of the target endocrine glands of the pituitary
trophic hormones. Recognition of the hypothalamic-anterior pituitary linkage
as a major point of neuroendocrine articulation, thus, provided an anatomical
basis for exploring brain influences on secretion of growth hormone,

prolactin, adrenocorticotropin (ACTH) thyrotropin (TSH), luteinizing
hormone (LH), follicle-stimulating hormone (FSH), and, consequently,
cortisol, thyroxine, testosterone, estrogens, progesterone, and related adrenal
cortical, thyroid, and gonadal hormones, in addition to the hormones

representing previously recognized neuroendocrine linkages, such as
epinephrine, norepinephrine, vasopressin, oxytocin, and insulin.
A substantial science of neuroendocrinology has consequently
developed since the 1950s with the demonstration, by such
neurophysiological techniques as electrical stimulation or ablation of local
brain areas in laboratory animals, including primates, that not only the
hypothalamus but also such distant brain regions as the amygdaloid complex,
hippocampus, and midbrain exert modulating influences on hormone
secretion. Much of the work done so far on localization or mapping of neural

influences on hormone secretion, however, has been limited to
intrahypothalamic studies and to only a few hormones, particularly those of
the pituitary-adrenal cortical system. Modern neuroanatomical knowledge of
limbic system-midbrain circuitry and of direct and indirect projection

pathways to the hypothalamus presents a most inviting opportunity for
future systematic studies of the neural substratum for psychoendocrine
processes, which is still a largely unexplored area, particularly in relation to

such hormones as testosterone, thyroxine, insulin, and others for which
excellent assay methods have recently become available.
Another important series of experiments has been concerned with the
demonstration and characterization of neurosecretory releasing hormones in
the hypothalamus, which appear to be the specific humoral links between the
hypothalamus and anterior pituitary cells. Included are the corticotropin-
releasing hormone (CRH), thyrotropin-releasing hormone (TRH), luteinizing-
hormone releasing factor (LHRF), follicle-stimulating hormone-releasing
factor (FSHRF), growth hormone releasing factor (GHRF), and prolactin-
inhibiting factor (PIF). These hormones and factors are presumably secreted
by final common pathway neurones in the hypothalamus and then via the
hypothalamo-hypophyseal portal system act selectively to bring about
changes in the secretion rate of the various anterior pituitary hormones. The
hypothalamic final common pathway neurones, incidentally, not only

represent an anatomical boundary line, but appear also to define a boundary
line between scientific disciplines as well. In general, research at the
hypothalamic level and below has been largely in the field of endocrinology,
while research on higher brain influences on endocrine regulation has been
pursued largely in the central-nervous-system sciences.
The field of experimental psychology has also made important
contributions to the development of a basic science foundation for
psychoendocrinology. While naturalistic approaches to eliciting emotional

arousal in animals, such as by immobilization, crowding, etc., have been
fruitful, the use of behavioral conditioning methods has provided a
considerably more sophisticated and systematic approach to
psychoendocrine studies in animals. As an example, in a “conditioned

avoidance” procedure, during which a monkey must press a hand lever in the
presence of a red light in order to avoid an electric shock to the foot, an
organized and reproducible pattern of multiple psychoendocrine responses
has been observed. The contingencies of such conditioning procedures may
be arranged in a great variety of ways in order to vary the quality or intensity
of the emotional disturbance which is elicited.
While it is beyond the scope of this chapter to elaborate further on how

the basic brain disciplines may be useful, particularly in various
interdisciplinary combinations in the study of psychoendocrine mechanisms,
it is important for the clinician to keep in mind that a growing body of
knowledge, developing from neuroanatomical, electrophysiological,

experimental psychological, neurochemical, and neuropharmacological
approaches, is building a substantial basic science foundation which
complements, supplements, and illuminates related research in clinical

psychoendocrinology-
The Development of Issues and Approaches in Clinical Psychoendocrinology
The Sensitivity of the Pituitary-Adrenal Cortical System to Psychological Influences
While W. B. Cannon had laid the groundwork for psychoendocrinology

almost forty years earlier with his work on the sympathetic-adrenal
medullary system, it is a curious historical fact that modem psychoendocrine
research evolved largely out of a period of intensive, popular interest in the
pituitary-adrenal cortical system, following the publication of Selye’s
sweeping and provocative “stress” concepts in 1950. Selye’s “stress”
formulations, ascribing special importance to the apparent “non-specificity”
of the pituitary-adrenal cortical response to “nocuous” stimuli, had a

considerable impact not only on endocrinological research, but also intrigued
many behavioral scientists because of the implication of psychological stimuli
among the various “stressors” capable of eliciting ACTH release. The findings
of Selye and other workers prior to the early 1950s were based on relatively
indirect and crude indices of adrenal cortical activity, however, so that a
foremost objective in the psychoendocrine field, when the reliable,
chromatographic, microanalytical methods for 17-OHCS measurements in

blood and urine became available after 1952, was simply to see if the earlier
observations of corticosteroid responses to psychological stimuli could be
confirmed by more refined endocrinological and psychological methods.
Many endocrinologists were initially rather skeptical that psychological

factors would be found to play a significant role in pituitary-adrenal cortical
regulation in comparison with such drastic physical stimuli as trauma,

exercise, cold, fasting, hemorrhage, and so on. Considerable attention was,
therefore, devoted in early psychoendocrine experiments to the elimination

or control of physical stimuli as independent variables. The burden of proof,
in a sense, was on the psychoendocrinologist to rule out, in rigorous fashion,
any remote possibility that concomitant physical stimuli, particularly
muscular activity, might be causing corticosteroid changes attributed to
psychological influences.
Within several years, substantial and convincing evidence emerged
from many laboratories, using a variety of experimental approaches, which
established beyond any reasonable doubt the reality of pituitary-adrenal

cortical responsiveness to psychological influences. Particularly influential
among these early experiments were the rather captivating observations of
Thorn, Fox, and their coworkers, on Harvard oarsmen in relation to the
annual Harvard-Yale crew race. Indications of increased adrenal cortical
activity on the race day were observed, not only in the crew members, but in
the coach and coxswain as well. In 1956, a report of later extensions of these
studies indicated that psychological factors associated with competition or
with time-trial sessions were far more potent determinants of urinary 17-
OHCS elevations than muscular work alone. Also capitalizing on natural

stressful life situations, Bliss and his co-workers reported in 1956 that plasma
or urinary 17-OHCS increases were prevalent in medical students taking final

college examinations, in relatives of emergency room patients, and in subjects
exposed to a variety of other natural and contrived situations associated with
emotional reactions. Board et al. reported marked plasma 17-OHCS elevations

in acutely disturbed psychiatric patients, and correlations were observed
between the intensity of endocrine and psychological disturbances. The
demonstration by Mason et al. of consistent plasma 17-OHCS elevations in
rhesus monkeys during conditioned emotional disturbances permitted
systematic separation of psychological from physical factors as experimental
determinants of hormone release. Chair-restrained monkeys pressing a hand

lever to avoid an aversive stimulus during “conditioned avoidance” sessions,
as one example, showed marked plasma 17-OHCS responses, while the same
monkeys, pressing the lever at an equal or greater rate in order to obtain

food, showed no 17-OHCS elevations, thus militating against the variable of
muscular activity associated with lever pressing as a determinant of 17-OHCS
release in the “avoidance” situation. A host of other psychoendocrine studies
involving stressful life situations such as aircraft flight, anticipation of
surgery, military combat, hospital admission, etc., compiled overwhelming
and consistent evidence of pituitary-adrenal cortical response to emotional

stimuli in human subjects.
By the late 1950s, then, it was generally recognized not only that
psychoendocrinology rested on a solid experimental foundation, but that
psychological stimuli were, in fact, among the most potent of all natural
stimuli to the pituitary-adrenal cortical system. The potency of psychological
stimuli in ACTH regulation was evident not only in the marked 17-OHCS
elevations observed in severely stressful life situations in normal subjects and
in the even greater increases seen during some acute psychiatric
disturbances, but was perhaps most impressively demonstrated in the
striking sensitivity with which relatively subtle environmental or
psychological influences were often reflected in 17-OHCS levels. In the rhesus
monkey, for example, urinary 17-OHCS levels reflected the day-to-day level of
activity in the laboratory in which animals were housed, being highest on
Monday, fairly stable from Tuesday to Friday, and decreasing by 30 percent
during the weekend when people were absent. When the same monkeys were
transferred from a busy, active laboratory setting to a quiet, private room,
and screened visually from each other, their chronic, mean basal 17-OHCS
level consistently ran 50 percent lower than in the original setting. Many
workers were impressed by the sensitivity of 17-OHCS levels to such factors
as the “first experience” or novelty effect, population density, and various,
often seemingly minor, social influences. Studies of plasma 17-OHCS levels in

normal young adults viewing commercial motion pictures provided one
particularly striking demonstration of the sensitivity of this psychoendocrine

system. In the same group of subjects, 17-OHCS levels were observed to rise
during a distressing war movie, and then to decrease sharply on two other
occasions during the observation of Disney nature films, as shown in Figure
24-1. These and many other observations indicated not only great sensitivity
of hormonal response to psychosocial stimuli, but also suggested that the
concept of “tonicity,” similar to that in the autonomic and skeletal-muscular
effector systems, applies to the neuroendocrine systems as well. Rather than
to use the concept of a “normal,” absolute hormonal level,, it may be more
valid to think in terms of an ongoing “basal” or “tonic” 17-OHCS level in any
given individual which may be either raised or lowered on an acute or chronic
basis, depending upon environmental, psychological, or other factors.
Figure 24-1.
Elevation and suppression of plasma 17-OHCS levels in group of normal
young adults viewing commercial movies. (U.S. Army photo graph.)
The unequivocal and repeated demonstration of the sensitivity of the
pituitary-adrenal cortical system to psychological stimuli, isolated from
attendant physical stimuli by various experimental approaches, may be
viewed, then, as representing a historically important and decisive first phase
of psychoendocrine research which established the field as a viable science
and opened the way for future development. If there has been experimental
overemphasis in any phase of psychoendocrine research, it was probably in

these initial studies directed at the question “Does the pituitary-adrenal
cortical system respond to psychological stimuli or not”? For some time after
it was settled beyond any reasonable doubt that psychological stimuli elicited
ACTH release, there was a tendency for workers to continue to devote

considerable research effort to adding still more stressful situations to the list
of those in which ACTH-cortisol release occurs. It appears, in fact, that this
question was viewed by many as the principal, if not the sole, issue in the field
and that much general interest and participation was withdrawn at the
conclusion of this phase of psychoendocrine research.
As a smaller group of workers persisted in psychoendocrine research,
however, it became increasingly clear that many important issues and

approaches remained to be explored. A survey of some of these less well
recognized issues and approaches is a special objective of this chapter. It

should be borne in mind that, in the discussion of psychiatric theory, the
vantage point of the author is not that of a clinical psychiatrist, but rather of a
physiologist who has worked in close collaboration with research
psychiatrists for many years. It should also be emphasized that the major part
of the work on the development of concepts in psychoendocrinology up to the
present time is based upon research on the pituitary-adrenal cortical and
sympathetic-adrenal medullary systems. The resultant emphasis on these
systems in this chapter should not be construed necessarily as implying that

they have a preeminent role in the psychoendocrine apparatus as a whole.
Only similarly intensive future study of the pituitary-thyroid, pituitary-
gonadal, and other neuroendocrine systems can eventually provide a proper

perspective concerning the relative significance of individual systems in
psychoendocrinology.
Psychoendocrine Reflections of Emotional States
In the initial phase of psychoendrocrine research when primary
emphasis was largely on isolating psychological stimuli in “pure” form from

physical stimuli, and on evaluating the relative sensitivity of hormone levels
to psychological versus “physical” stimuli, only rather scattered and

preliminary efforts were made to define the nature of the psychological
mechanisms which were reflected in hormonal responses. The general and
plausible assumption was that hormonal levels were probably a rather direct
index of emotional state, particularly of the level of anxiety. Many early

studies simply employed situational criteria of threat, with the assumption
that a given situation would be anxiety-provoking to the subjects, but without
validating this assumption by objective psychological assessment of actual
emotional reactions in relation to hormonal responses in individual subjects.
A number of laboratories, however, began to deal with this difficult
issue directly and to develop or evaluate psychological methods which would
permit correlational studies, comparing hormonal levels with specific

emotional states. A principal approach was the development of relatively
objective and reproducible methods for clinical assessment of the levels of
anxiety, depression, and anger on a roughly quantitative rating scale. Special
care was taken to evaluate and develop intraobserver and interobserver

reliability in these methods. As was expected, such ratings did show
significant correlations with 17-OHCS levels under certain conditions. Persky
et al., for example, found that objective ratings of increase in anxiety,

depression, and anger were proportional to changes in plasma 17-OHCS
levels in anxious patients during stressful interviews.
Another approach was the use by Price et al. of projective tests to

evaluate affective state and 17-OHCS correlations in patients on the day
before elective cardiac surgery. In this study, significant correlations were not
observed between 17-OHCS levels and any specific affective state, such as
anxiety or anger, but rather with several measures such as the neutral
content, introversive tendencies, extended F+ percent and unpleasant

content, all of which may be regarded as reflecting emotionality in a more
general sense. As additional experience accumulated in the human, with such
techniques as estimates or ratings of affect based on psychiatric interview
and observation, clinical psychological testing, and self-reporting by subjects,
it was generally found that, while these techniques were useful in establishing
rather rough, general correlations between emotional reactions and 17-OHCS
levels, this hormonal system did not appear to be related to any one specific
affect, such as anxiety. Together with studies in experimental animals, the
clinical studies suggested the general conclusion, rather, that 17-OHCS levels
reflect a rather undifferentiated psychological state, for which such terms as
arousal, hyperalerting, involvement, or anticipation of coping activity might
be appropriate. In other words, while 17-OHCS levels may be a useful index of

the occurrence, intensity and perhaps duration of emotional arousal, the
pituitary-adrenal cortical system alone did not appear to provide leverage in
the study of the qualitative differentiation of affective states. It should be
emphasized, however, that more intensive, in-depth, psychodynamic studies

remain to be undertaken, particularly with regard to such questions, for
example, as the 17-OHCS reflections of anger and the various ways anger is
handled or expressed, or with regard to pleasant states of arousal. The work
of Levi and his co-workers has indicated that certain pleasant states, such as
sexual arousal, are associated with catecholamine elevations and suggests the
need for further systematic study of pleasant stimuli in psychoendocrine
research.
A rather promising approach to the issue of whether endocrine indices
may be used to differentiate emotional states, however, has emerged from
other studies of the sympathetic-adrenal medullary system. Although
chromatographic methods for measurement of plasma and urinary
catecholamines were available during the 1950s, considerably less attention
was devoted to the catecholamines than to the corticosteroids in
psychoendocrine research. One of the practical reasons for this, no doubt, was
the greater difficulty of the fluorimetric methods used for catecholamine
analysis, particularly in the plasma. Earlier psychophysiological studies by Ax
and by Funkenstein et al., based upon cardiovascular indices, had suggested
that epinephrine and norepinephrine might be differentially related to fear

and anger reactions. Funkenstein et al., for example, postulated that anger
directed “outwardly” is associated with norepinephrine predominance, while
anger direct “inwardly” is reflected in epinephrine predominance. Curiously,

these intriguing early leads have not yet been thoroughly evaluated with
modern psychoendocrine techniques, although a few more or less incidental
observations have been made in clinical studies of urinary catecholamine

levels which appear consistent with Funkenstein’s hypothesis. Some studies
of plasma corticosteroid and catecholamine patterns during acute emotional
disturbances in the monkey have also provided encouragement for further
exploration of the psychoendocrine differentiation of emotional states. In a

study of six different psychologically stressful situations, all associated with
plasma 17-OHCS and norepinephrine elevations in the monkey, significant
plasma epinephrine elevations were observed in only three of the situations.
Thus, two psychoendocrine reaction patterns were defined, pattern 1 with
17-OHCS and norepinephrine, but not epinephrine, elevation and pattern 2
with elevation of all three hormones. In general, the most striking distinction
between the situations associated with the two different hormonal response
patterns was apparently the presence of a high degree of unpredictability,

uncertainty, or ambiguity in the pattern-2 situations. Unpleasant elements
were present in all situations, but in the pattern-1 situations the animal knew
exactly what to expect, while in the pattern-2 situations the animal knew
threatening events were likely, but did not know exactly what they would be
or when to expect them. When one also considers that such hormones as
thyroxine, testosterone, insulin, growth hormone, and estrone can now be
determined quantitatively by reliable assays and have been shown to respond

to psychological stimuli, it is clear that the issue of psychoendocrine
differentiation of both acute and sustained emotional states remains largely
an open question, and there is a need for further resourceful and systematic
research along these lines, particularly in longitudinal studies of human
subjects.
Psychoendocrine Reflections of Psychological Defenses
One of the most fascinating and illuminating approaches in
psychoendocrinology has developed from recurrent observations of the
marked individual variations in psychoendocrine reactions between different
people exposed to the same stressful situation. In the face of a real, life-
threatening event, such as cardiac surgery, for example, some subjects
showed marked anticipatory 17-OHCS responses, while others showed little
or no 17-OHCS change. Although such observations were at first often

regarded with annoyance, since they diminished the significance of group-
mean levels in data analysis, it soon became clear that a fundamental and
intriguing question was raised concerning the psychological correlates of
these individual differences in endocrine response to a seriously threatening

event. The simple logic which emerged as this issue was faced, was that if 17-
OHCS levels provide a sensitive index of general emotional arousal, as had
already been established, by the same token they should provide a means of
studying the opposing psychological forces which prevent, minimize, or
counteract emotional arousal in the face of threat.
While a number of early workers recognized this issue, the emergence
of this approach is particularly well illustrated in the psychoendocrine studies
by Friedman et al., and Wolff et al., of “chronic psychological stress” in the

parents of children with leukemia. One of the most striking findings in these
parents was the persistence of characteristic individual differences between
subjects in chronic mean basal urinary 17-OHCS levels over periods of
months or years. Figure 24-2 summarizes the mean 17-OHCS levels and the
range of fluctuation, representing repeated sampling over many months, in a
group of mothers during the course of their child’s leukemic illness. While a
few subjects showed a substantial range of fluctuation, most of the mothers
maintained stable levels with a remarkably constricted range and could be
characterized with some confidence as individually falling into “high” (above

6 mg./day), “middle” (between 4-6 mg./day), and “low” (below 4 mg./day)
subgroups on the basis of chronic mean basal urinary 17-OHCS levels.
Considering the tragic and disruptive circumstances, the presence of average
or low mean 17-OHCS values in most subjects suggested the operation of
remarkably effective defensive psychological mechanisms. Injection of ACTH
and other observations indicated that adrenal exhaustion was not the
explanation. The fact that some individual subjects with the lowest chronic
mean 17-OHCS levels tended to suppress their levels even lower on days
when stressful or unpleasant events occurred, in contrast to “high” subjects
whose levels usually rose still higher on stressful occasions, as shown in

Figure 24-3, especially drew attention to the possibility of suppressive or
overcompensatory defensive psychological mechanisms as being reflected in

17-OHCS levels in the “low” group. An exploratory survey of defensive
organization revealed that several of the subjects with the lowest mean 17-
OHCS levels characteristically employed denial to a marked degree in coping
with the implications of their child’s illness. These and other preliminary
observations were sufficiently suggestive of the reflection of defensive styles
in chronic 17-OHCS levels that a predictive psychiatric study was done, in
which correlations between mean 17-OHCS level, as predicted by the
psychiatric assessment of the effectiveness of psychological defenses, and the
actual chronic mean basal level were examined and found to be significant
both for the fathers (r = 0.80) and the mothers (r = 0.59).
Figure 24-2.
Individual differences in chronic mean urinary 17-OHCS levels between

mothers of fatally ill children. (U.S. Army photograph.)
Figure 24-3.
Difference in direction of 17-OHCS response to superimposed acute

disturbance in some “high” versus “low” 17-OHCS excretors included in
Figure 24-2.47 (U.S. Army photograph.)
There were some particularly illuminating anecdotal observations in

certain parents in whom temporary relinquishment or ineffectiveness of
habitual defenses were associated with prompt and dramatic 17-OHCS
changes. Figure 24-4, for example, presents the case of a mother in whom the
predictive psychiatric interviews were associated inadvertently with the

undermining of her usual defenses of detachment and rationalization. During
the interviews, which represented her first experience with a psychiatrist,
there was an outpouring of suppressed, painful thoughts concerning personal
problems which she “had not talked to anyone about in years.” During and
immediately following this period, her urinary 17-OHCS level rose from the
“low” into the “middle” (shaded) range, but with the reestablishment of her
usual defenses, her 17-OHCS level declined and never again rose into this
range, even during the final days before the death of her child.
Figure 24-4.
Longitudinal study showing 17-OHCS response to relinquishment of

psychological defenses during psychiatric interviews. (U.S. Army
photograph.)
A second case presents an impressive example of the pitfalls of
assessing affect unilaterally without considering defensive organization in
psychoendocrine studies. This mother was by all overt appearances almost
constantly upset, as judged by the content and style of her speech, the
associated facial expressions, the tremulous actions, and so on. Accordingly,
the ward staff initially regarded her as among the most distressed parents in
the entire study. Figure 24-5, however, shows that her urinary 17-OHCS
levels were generally quite stable and low, ranging between only 2 to 4
mg./day during a two-month period when such overt signs of intense
affective distress were shown. Two days before her child’s death, observers
were struck with a sudden decrease in outward signs of affective distress, as
she attended quietly to her child’s needs, during which period her 17-OHCS
levels rose to nearly 6 mg./day. This type of dissociation between overt affect
ratings and 17-OHCS levels has since been observed in other subjects and
appears to reflect a defensive style in which the display of signs of affective

distress or frailty serves an effective coping function, perhaps from both an
intrapsychic and manipulative standpoint, i.e., in which affect display or
expression is employed as a “defense.” Psychiatric assessment involving
conventional affect ratings alone would, of course, have been misleading in

such cases and it is only in the deeper psychodynamic context of defensive
organization that the significance of the psychoendocrine data appear to be
clarified. The same general conclusion is suggested by other cases in which

the reverse relationship of marked 17-OHCS elevations, occurring in the
absence of overt evidence of affective distress, was observed in persons who
“suffer in silence,” or who subjectively are oblivious of inner distress.
Figure 24-5.
Figure 24-5.
Longitudinal study in which 17-OHCS levels reflect use of affective display as

a defensive style. (U.S. Army photograph.)
Confirmation of a relationship between chronic 17-OHCS levels and
defense effectiveness was reported by Rose et al., in a predictive study of
Army recruits during basic training patterned after the parent study. This
study, in addition, drew attention to some further methodological and

theoretical issues involved in this psychoendocrine approach. In assessing
effectiveness of defenses in individuals during basic training, it became

especially clear that a particular defensive style is not inevitably associated
with a particular characteristic 17-OHCS picture in all situations. The specific

demands of the current environmental or social setting must clearly be taken
into account in relation to the individual’s coping style. A defensive style
which might be quite effective in maintaining psychoendocrine stability
during basic training, for example, might be relatively ineffective in another
life setting where the environmental realities and demands are quite
different. An often overlooked methodological corollary of this conclusion,

then, is that one cannot expect a consistent correlation between any specific
behavioral trait or test score and hormone level to occur in all situations, but
must always view psychological-endocrine correlations in the context of the
specific social setting, and make accordingly careful observations and

assessment of the relevant social variables. This study made also clear that
certain non-psychological variables, such as body weight, environmental
variables such as temperature, and historic variables such as early parental

death may relate to chronic 17-OHCS level. These findings emphasize the
necessity to avoid simplistic methodological approaches and to deal with an
increasing range of interacting psychological, social, and nonpsychological
factors as multiple codeterminants of chronic 17-OHCS levels.
Still another issue in the psychoendocrine study of defensive
organization is illustrated by the work of Mattson et al., who made longterm

studies of 17-OHCS levels in hemophilic boys. In judging psychosocial
adaptation to the illness, he found that those patients regarded by the staff as
“good” adapters, being generally cooperative, controlled, and pleasant
showed high 17-OHCS levels, while the “poor” adapters, being often
uncooperative, irritable, and complaining tended to have low 17-OHCS levels.
A deeper psychodynamic analysis of the two subgroups, however, tended to
suggest that the organization of ego defenses in the “poor” adapters, although
associated with poor social adjustment, was more effective from an

intrapsychic standpoint in minimizing affective distress and maintaining low
17-OHCS levels than that in the socially “good” adapters. These observations
indicate the need to recognize that effectiveness of defenses, as viewed in

terms of social adaptation, may present quite a different picture than when
viewed in terms of internal or physiological homeostatic adaptation.
Finally, the psychodynamic implications of experimental observations
suggesting that common mental or psychomotor activities are reflected in 17-
OHCS levels should also perhaps be considered in the context of defensive

styles. The acute suppression of 17-OHCS levels during the viewing of Disney
nature movies, for example, raises the question of the likelihood that many
comparable everyday activities may be similarly reflected in psychoendocrine

adjustments. Levi has shown similar suppression of urinary catecholamine
levels in subjects viewing natural-scenery films. These findings suggest the
possibility that such seemingly similar everyday tension-relieving activities as
reading, television viewing, knitting, card games, hobbies, or other self-

selected recreational or diverting activities may also be reflected sensitively
in hormonal adjustments. This is still a largely undeveloped area in
psychoendocrine research, but even the limited information available
suggests that it is necessary to bear the role of tension-relieving activities in
mind as another variable to be considered in the assessment of the balance
between the arousal and antiarousal forces which operate as multiple

determinants of psychoendocrine reactions.
One may view the development of psychoendocrine research, then, as
providing a succession of insights into the nature and scope of the relevant
psychological factors which are codeterminants of hormonal levels. As
indicated previously, a broad basic generalization emerging from 17-OHCS

studies is that psychoendocrine state at any given point is a resultant of a
balance between two sets of opposing forces, those promoting arousal and
those defending against arousal. It is increasingly clear that the organization

of defensive or antiarousal mechanisms must be considered in a very broad
sense, as involving not only the classical intrapsychic defenses, but the full
range of mental processes and psychomotor activities which may counteract

the mechanisms promoting emotional arousal or involvement.
The practical implications of these generalizations for psychoendocrine
methodology relate to the necessity in future studies to assess an increasing

array of psychosocial factors concurrently, including quality and intensity of
affect, defensive or coping mechanisms in the broadest sense, and social

setting, all in the perspective of the dynamic factors operating in each
individual subject. This is a tall methodological order, to be sure, and
represents a major obstacle to future progress in psychoendocrinology. On
the other hand, there is already evidence that the feedback from
psychoendocrine experiments can facilitate the development of suitable

methods for psychiatric assessment of the above psychosocial factors, by
providing leverage and economy in several ways, particularly by virtue of the
highly objective indices hormone measurements afford in helping dissect out
of the maze of psychological and social variables those which bear the
greatest relevance to the psychoendocrine processes.
Once given the premise that 17-OHCS measurements provide an
objective index of the balance between arousal and antiarousal mechanisms,
it follows that the research psychiatrist is given a tool which may be applied
to the study of many issues in psychiatric theory, such as those concerned
with neurotic, psychotic, psychosomatic, social, and developmental processes,
insofar as these relate to emotional and defensive mechanisms. The

remainder of this chapter will deal mainly with illustrations of such
psychoendocrine approaches in diverse and overlapping areas of psychiatric

research.
Psychoendocrine Reflections of Neurotic Processes
One of the most striking paradoxes in this field, so far, is the very limited
degree to which psychoendocrine approaches have been applied to the study
of neurotic processes. Few, if any, studies have been expressly designed to
deal systematically with the testing of theoretical concepts of neurosis or
even with the descriptive psychoendocrine study of severely neurotic

patients. Most of the few available data suggesting the usefulness of this
approach have been incidentally derived from anecdotal observations of
individual neurotic patients encountered in “normal” groups or in groups of
patients with medical or psychosomatic illnesses.
One such example from the study of parents of leukemic children
involved a father with a long-standing neurotic hypersensitivity to rejection
by others. Normally, his urinary 17-OHCS level was about 10 mg./day, but one
weekend a remarkable elevation to 30 mg./day was noted. This elevation was

not attended by any readily evident outward signs or verbal expression of
distress, although the ward staff was well-trained and experienced in the
clinical rating of emotional behavior. Only a careful reconstruction of the

events of the weekend in the psychodynamic context of the patient’s neurotic
style appeared to clarify the psychoendocrine findings. During this weekend,

the subject had been forced by circumstances for the first time to spend many
hours in close contact with his ill child, a teen-age boy with whom the father
felt rejected and uncomfortable. Normally, the father on each weekend visit
would spend a few minutes with his son and then would busy himself with
other activities on the ward or elsewhere so as to avoid all but minimal
contact with the child, while the mother stayed in attendance. On the
weekend of the father’s marked 17-OHCS elevation, however, the mother was
absent from the hospital because of a family emergency at home, and the
father was unable to avoid involvement in the interpersonal situation which
apparently activated a strong neurotic reaction."
Another case history was that of a young man who volunteered as a
normal “control” subject and lived for many weeks in a hospital-ward setting
with other young healthy adults. This subject showed evidence of an

exaggerated, neurotic need for approval, low self-esteem, and fear of
rejection, and was constantly actively seeking out personal contacts with
other subjects and the ward staff. His chronic mean basal urinary 17-OHCS
level, established over a period of many weeks, was about 11 mg./day.
Following his success in becoming engaged to a young woman, also
participating in the project as a subject, his 17-OHCS levels sharply fell to a

new, stable plateau of about 5 mg./day for the period of several weeks that
the engagement lasted. While some mild behavioral changes appeared to
coincide with the changes in hormone level adjustment, they did not appear
commensurate in intensity with the degree of hormonal change.
A number of other similar observations have been made suggesting that

marked, psychologically induced 17-OHCS changes can occur in the absence
of overt clinical signs of associated emotional disturbance and with virtually
no subjective awareness of the person of any feelings of affective distress or
arousal. Since it is characteristic of many neurotic subjects, in the process of
self-alienation, to have unconsciously learned to lose or repress awareness of

certain unacceptable feelings, and since such repression of self-awareness can
be a major obstacle to rehabilitative efforts during therapy, the possibility
that psychoendocrine changes may objectively reflect intrapsychic processes
of the neurotic patient seems well worth further exploration. The discrepancy
between the striking magnitude of the somatic or psychoendocrine reaction
and the minimal clinical or subjective manifestation of intrapsychic
disturbance is the particularly impressive feature of the preliminary

observations suggesting this approach. Are neurotic defenses, strategies, or
conflicts particularly prone to lead to psychoendocrine or somatic reactions
or disorders? Are different patterns of neurotic trends or conflicts reflected in
characteristic psychoendocrine reaction patterns? Is there a characteristic

psychoendocrine reflection of neurotically repressed anger, as compared to
that for anger handled in other manners? These are random examples of
many similar questions which have not yet been approached directly and
systematically, although it now appears feasible to do so with the tools of

modern psychoendocrine research.
Initially, perhaps the most appropriate tactical approach for the
exploration of such questions would be the intensive, longitudinal, in-depth
psychodynamic study of individual neurotic patients during psychoanalysis,
with emphasis on the post hoc qualitative study of intrapsychic processes in
the light of recurrent psychoendocrine reaction patterns. Eventually, as this

approach yields pilot information and working hypotheses, more objective
and predictive methods could be introduced to test the validity of such
hypotheses in a more rigorous manner. Finally, because of the relatively high

incidence of neuroticism in patients with psychosomatic disorders, the
psychoendocrine reflections of neurotic processes in such patients may
provide not only objective indices of intrapsychic disorders but offer the
possibility of a three-way correlational study of psychological, endocrine and
somatic processes. Knapp and his co-workers have performed some valuable
pioneering work in the development of methodological guidelines for this

approach in their long-term studies of asthmatic patients. While the
usefulness of psychoendocrine approaches to the study of neurotic processes

is still largely speculative and unproven, there are compelling reasons to
regard it as one of the most potentially fruitful and powerful of all

psychoendocrine approaches to the testing of psychiatric theory, and
certainly so far one of the most unexplored and neglected.
Psychoendocrine Reflections of Psychotic Processes
Early psychoendocrine studies of schizophrenic patients between about
1945 and 1955 led to considerable confusion, largely because of
methodological limitations from biochemical, physiological, and psychiatric
standpoints. An early hypothesis that chronic schizophrenia was associated
with hypoadrenalism was not subsequently confirmed as methodological
approaches became more refined during the 1950s. It should be emphasized
that the conceptual approach in early psychoendocrine research on psychosis

evolved from the quest for a biochemical abnormality or deficiency which
might have pathogenetic significance in schizophrenia. In this respect, the
orientation is quite different from the mainstream of recent psychoendocrine
research, which has largely viewed hormonal responses as reflections, rather

than as determinants, of intrapsychic reactions, although both views are valid
and their relative importance remains to be elucidated, as will be discussed
later.
The classical study of acute schizophrenic patients by Sachar represents
one of the finest models of the application of psychoendocrine approaches to

the testing of psychiatric theory. Using a conceptual view of the natural
course of acute schizophrenic reactions as being divided into several clearly
defined phases of illness from initial breakdown to eventual recovery, he

studied endocrine correlates of such clinical phases. Figure 24-6 presents an
example of a case illustrating how closely such clinical phases correlate with
equally well-defined phases of endocrine change. During the initial turmoil
phase, when the patient’s characteristic defense mechanisms have been
overwhelmed, emotional distress and 17-OHCS and catecholamine levels are
very high. With the subsequent formation of a consoling psychotic delusional

system, becoming well established by about the eleventh day, hormone values
subside to a lower, more stable level. During this period of psychotic
equilibrium, the patient’s picture of himself and his style of interaction with
others is completely narcissistic, and affective distress is minimal. Then, as
the doctor and ward staff begin to challenge and undermine the patient’s
psychotic defenses during the 4th week, the patient reveals his true devalued
self-image, and the affective distress of anxiety and depression reappears
with associated increases in hormone levels. As the patient eventually arrives
at a more mature, clinically improved “equilibrium,” with minimal affective

distress, hormone levels stabilize in a range very close to that observed
during the earlier psychotic “equilibrium” phase. Similar correlations

between hormonal and psychological phases were observed in longitudinal
studies of additional patients of the same type.
These findings suggest that the psychotic system operates defensively
to minimize both emotional distress and associated endocrine disturbance.

Sachar’s observations were among the first to call attention to the important
role of psychological defenses in the maintenance of physiological as well as
psychological homeostasis. This work also points tion for the earlier
confusion and conflicting findings in psychoendocrine studies, when clinical
phases were often not evaluated in close relation to the period of hormone
sampling. Thus, it is not surprising that “contrast” studies of groups of normal

subjects versus patients in chronic psychotic equilibrium may show no
differences in group mean 17-OHCS out that it is essentially the effectiveness
of defenses, whether they be normal, neurotic or psychotic in character,

which is reflected in 17-OHCS levels, thus setting a pattern for later
psychoendocrine studies of defensive organization. It is also particularly
noteworthy that at the time the patient is the most severely psychotic and
withdrawn, emotional distress is often minimal, and 17-OHCS levels are
similar to those following eventual clinical recovery. This observation
provides a plausible explana-levels. Only when the dynamic factors involved

in defensive organization are viewed in relation to the life setting does the
significance of the psychoendocrine picture begin to become clarified. Finally,

Sachar suggests that endocrine measures may not only provide a form of
validation of theoretical classification of key phases in the course of a type of

psychosis, but may also provide helpful guidelines to the psychotherapist, as
he supports or challenges the patient’s psychological defenses.
Figure 24-6.
Figure 24-6.
Longitudinal study showing correlations between clinical and endocrine

phases during course of acute schizophrenic reaction. (U.S. Army
photograph.)
Another example of psychoendocrine evaluation of psychodynamic
issues is provided by studies of the manic state, which clinically has been
regarded by some observers as involving considerable intrapsychic distress,
and by others as a more comfortable, restitutive state. Longitudinal studies of

corticosteroid levels in manic patients have been reported by a number of
workers. Generally it has been found that pituitary-adrenal cortical activity is
relatively low during manic phases, in contrast to the higher levels during
depressed phases. These findings may be interpreted as providing
physiological support for the clinical hypothesis that mania, with its elements
of euphoria and denial, represents a counteracting, protective defense against
the painful distress associated with depression.
Psychoendocrine Reflections of Depressive Processes
Although a discussion of depressive syndromes obviously overlaps with
that in the previous sections on neurotic and psychotic processes, the
considerable emphasis on studies of depression in psychoendocrine research

merits special mention. In 1956, Board et al., reported marked plasma 17-
OHCS elevations in acutely depressed patients shortly after hospital
admission. While others confirmed these findings, it was subsequently found
in longitudinal studies which extended well beyond the hospital admission
period that 17-OHCS levels did not invariably correlate significantly with the
severity of depressive symptoms.
In a study by Bunney et al., for example, two general subgroups of

depressed patients could be distinguished on the basis of chronic urinary 17-
OHCS levels. One group, characterized by high and labile 17-OHCS levels,
appeared to be more aware of, and involved in, the struggle with their illness.
The second group, although also having high ratings on the depression scale,
had relatively low and stable 17-OHCS levels and appeared to have differently
organized defenses, often employing denial of their illness or related
problems.
This study indicated that the symptoms of depression alone are not
necessarily associated with 17-OHCS elevations, but that, again, a more
holistic, psychodynamic view of defensive organization must be taken,
particularly in view of the considerable heterogeneity of clinical depressive
syndromes.
The incisive studies of Sachar and his coworkers have, in particular,
contributed greatly to the clarification of psychoendocrine research on

depression. In a study designed to test the psychiatric hypothesis that certain
depressive reactions serve a defensive function against acknowledgment of
painful feelings of disappointment or anger, dynamic factors were carefully
assessed throughout the period of psychotherapy in a relatively
homogeneous group of patients with reactive depression. Elevated 17-OHCS
levels were generally not observed in those patients except during episodic
“confrontation” periods, when the painful losses which precipitated their

depressive reactions were being dealt with during therapy. Emphasis was
placed on distinguishing the affects associated with loss and mourning from
the organized syndrome of melancholia. Sachar also has presented a

penetrating critique of early psychoendocrine research on depression which
should be an important guide to future work in this field. The failure of many
studies to consider important control issues, such as the psychoendocrine
response to hospital admission, the social milieu throughout hospitalization,
the interference of certain central-acting medications, the criteria for control
data to be compared with illness data, as well as the failure to take
psychodynamic factors into account, are implicated as probable reasons for

inconsistencies and confusion in early psychoendocrine research on
depression.
At present, then, it appears that outward signs of depression are not
necessarily associated with 17-OHCS elevations, and that the intrapsychic
processes which are associated with the marked 17-OHCS changes often seen
in depressed patients remain to be qualitatively characterized in future
studies, which take into account dynamic factors as a basis for distinguishing
the many different syndromes in which signs of depression are a prominent

feature.
Psychoendocrine Approaches to the Study of Developmental Processes
It logically follows that insofar as endocrine measures reflect

intrapsychic processes, then such measures may be used to study experiential
and genetic influences on the development of those same intrapsychic
processes. The marked individual differences in psychoendocrine responses
observed between different subjects exposed to the same stressful situation

provides one point of departure for research along such developmental lines.
Under relatively highly standardized conditions, for example, six adult rhesus
monkeys were exposed to two-week sessions of a conditioned emotional
disturbance, conditioned “avoidance,” during which they were required to
press a hand lever at times in order to avoid an aversive stimulus. Of the six
monkeys exposed to this procedure, two showed marked 17-OHCS elevations,
two showed mild 17-OHCS elevations, and two animals actually showed
suppression of 17-OHCS levels, which was not, incidentally, associated with
elevated preexperimental 17-OHCS baselines. While no genetic or early

developmental data were available on these animals acquired as adults, it was
noteworthy that there appeared to be a close correlation between direction of
17-OHCS response and the extent of their prior laboratory experience and
handling. The monkeys showing marked 17-OHCS elevations were
laboratory-naive, while the monkeys showing suppression of 17-OIICS levels
were veterans of many laboratory experiments. While these studies of adult
monkeys may not be viewed as developmental in the usual sense, they did,
along with other observations in animals, suggest the possible importance of
even short-term experiential factors in the determination of psychoendocrine

reaction patterns and raised the issue of the need for systematic
developmental studies.
Some findings perhaps more directly related to this approach emerged
from studies by Poe et al. of childhood history in relation to individual
differences in chronic mean 17-OHCS levels in ninety-one Army recruits
studied during basic training. Of the fourteen men in this group who had lost
a parent by death, twelve had 17-OHCS levels in the upper or lower quartiles.
In the “high” 17-OHCS quartile, five of the six subjects had lost their mother,
while five of the six subjects in the “low” 17-OHCS quartile had lost their
father. So far, no subsequent attempts have apparently been made to pursue
this finding further or to search for possible psychological correlates of

endocrine differences in subjects who experienced parental deaths during
childhood.
More broadly, it appears that psychoendocrine reflections of emotional
and defensive mechanisms may provide useful adjuncts to the psychological
study of the early development of these intrapsychic mechanisms and

represent an objective basis for testing theories of developmental stages
based entirely on psychological observations. In addition to the well-
established usefulness of corticosteroid and catecholamine levels in defining

individual characterological differences, the recent availability of improved
methods for determination of testosterone and other sex hormones adds
even further interest to developmental approaches. At present, however,
there is a dearth of psychoendocrine data on virtually all phases of early

development, from the first year through adolescence and this approach
awaits further exploration.
Psychoendocrine Approaches to the Study of Social Processes
The social setting of psychoendocrine studies has already been
emphasized as an important variable to assess in relation to psychodynamic

factors and hormonal reaction patterns. Some of the specific examples of the
ways in which social influences may be reflected in hormonal levels suggest
in addition that psychoendocrine approaches may be useful to social

scientists in the systematic study of social interactions, particularly those
occurring in small groups.
One of the social phenomena apparently reflected in psychoendocrine
studies is what might be called the “emotional contagion effect.” An early
observation suggesting this interpretation was the close similarity of 17-

OHCS levels in crewmen of a B-52 bomber during a nonstop flight to
Argentina under unusually stressful conditions. The pilot had extremely high
urinary 17-OHCS levels of about 20 mg./day (compared with a mean normal
of about 7 mg./day in men). The other three crewmen, who were back in the
plane working closely together, all ran very similar elevated levels of about 13
mg./day. The rarity of 17-OHCS levels of 13 mg./day, even in large groups of

human subjects in stressful situations, suggested the possibility that a socially
communicated “13 mg./day atmosphere” prevailed in this aircraft on the

flight day.
Similar conclusions were suggested in the studies of other small,
closely-knit groups of five to six human subjects. In each of three different
groups of young men anticipating ninety-six-hour sleep-deprivation sessions,
mean plasma 17-OHCS levels differed appreciably from one group to the next.
Yet, within each group, the individual 17-OHCS values clustered very closely
around the particular group mean at the end of the control week during
which the men had been continuously in close social communication. The
tendency for 17-OHCS levels in most individual members of a group
anticipating a stressful experience to cluster around an “equilibrium level”
was also observed in normal young adults anticipating movie-viewing
experiences. In studies of normal young adults during hospitalization,

however, it was found that, while some groups had a very narrow range of
intragroup corticosteroid levels after the individuals lived together for a
while, other groups showed a much wider range of intragroup individual

variation in a similar setting. These observations suggest that certain group
dynamics may be reflected in psychoendocrine parameters, particularly when
the group is relatively small and the members have been together for some
time in a relatively intimate and stressful setting.
Many observations in animals have also indicated that such parameters

as population density and social hierarchy are reflected in endocrine activity.
Of particular interest are the elegant studies by Bose and his coworkers of
plasma testosterone levels in monkeys living in social groups. These studies
have shown correlations between plasma testosterone levels, dominance
rank, and various levels of agonistic behavior. Testosterone fluctuations in
individual male monkeys have also been observed in relation to such social or
sexual stimuli as defeat in combat or introduction to a colony of females.79 80
Similarly creative psychoendocrine approaches would appear to be
feasible in human groups, for example, in relation to various group-therapy
approaches, yet little has been done so far along these lines. The naturalistic
character of group interactions, as contrasted to the contrived laboratory

investigator-subject settings, seems rather promising as an experimental
approach for psychoendocrine studies in human subjects. Again, both the
potential and the limitations of this approach are defined by the rationale that
to the extent that hormonal reactions reflect emotional and defensive
organization, and to the extent which such intrapsychic processes are related
to social interactions, then psychoendocrine approaches should be useful to

the investigator of social processes.
Psychoendocrine Approaches to the Study of Occupational Activities
The sensitivity of corticosteroid and catecholamine levels to such
everyday activities as viewing motion pictures has already been mentioned. It

has been shown by Wadeson et al., and Levi that hormonal levels may rise
during the viewing of certain movies and fall during the viewing of other
movies. These experiments convey a rather dynamic sense of hormonal levels
shifting up or down from one short time segment to another during the day in
reaction to an experience not unlike many other common activities of

everyday life. The question naturally arises as to whether or not similar
hormonal reactions do occur in association with a much larger range of
everyday activities, including occupational as well as recreational pursuits,
even though we do not normally think of many of these activities as being

associated with appreciable changes in affective state.
In a series of resourceful studies, Levi and his co-workers have indeed
demonstrated that certain occupational tasks have psychoendocrine
reflections in the activity of the sympathetic-adrenal medullary system. He

found urinary catecholamine increases and hyperlipoproteinemia, for
example, in persons performing an exacting industrial task of sorting out four
slightly different sizes of steel balls in the presence of distracting noise and
lights. In another study, Levi found that conditions of everyday work, such as
whether it is performed on a piecework or salaried basis, were reflected in

urinary epinephrine and norepinephrine levels in young women who were
invoicing clerks. Frankenhaeuser et al., have also reported urinary

catecholamine changes in association with psychological tests involving
arithmetic and inductive tasks. In another study, it was found that individual
psychoendocrine differences associated with performance of mental activities
or tasks may, in turn, be correlated with individual differences in the
effectiveness of performance. Subjects showing the greatest improvement in
performance of proofreading or coding tasks in a stressful setting were also

those who showed the largest increase in norepinephrine excretion in
association with the task.
While we have as yet minimal data with which to evaluate this general
approach, it is certainly a provocative notion to consider that our daily
routines are composed of a sequence of episodic segments in which hormonal

increases and decreases reflect associated shifts in mental and psychomotor
activities, which may perhaps be divided into general classes, such as tension-
building or tension-relieving, on a psychological basis. The dynamic factors

involved in emotional and defensive organization of individual subjects
would, of course, have to be taken carefully into account in the interpretation
of findings emerging from this approach. Recent research with plasma

cortisol measurements at frequent intervals has shown some striking
periodic increases and decreases in hormonal levels over the course of the
day. One of the issues raised by these findings is whether such “ultradian”
fluctuations represent simply an “on and off” physiological mechanism of

glandular release of hormone in periodic bursts, or if the fluctuations are
largely a reflection of shifting inputs into the neuroendocrine machinery,
particularly perhaps a reflection of shifting intrapsychic functioning in
relation to moment-to-moment events, thoughts, and activities. While this is
certainly a technically difficult issue to approach experimentally, its practical
and theoretical implications for occupational stress research and

psychosomatic medicine provide a compelling basis for its further
exploration.
Psychological Reflections of Endocrine State
While recent psychoendocrine research has been oriented primarily in

terms of the influence of psychological factors upon hormone secretion, the
important fact should be kept in mind, of course, that interactions between
the brain and the endocrine glands operate in both directions. It is known
that many hormones exert influences on neural and psychological processes,
although our knowledge of such effects is still very limited, largely because of
the unusually difficult methodological problems involved in assessing the
affected CNS processes. The early work of Reiss and his associates in England
was directed at this “other side of the coin” in psychoendocrinology, i.e., the
possible clinical importance of the effects of abnormal hormone levels upon

the brain as a pathogenetic factor in various psychiatric disorders. The
psychiatric symptoms which often accompany certain clinical
endocrinopathies have long been recognized. The hypothesis that a deficiency
of gonadal hormone secretion, leading to an immature level of psychosexual
functioning, might be a pathogenetic factor in certain schizophrenic patients
was formulated many years ago, but could not, at that time, be rigorously
tested because of the lack of specific and reliable methods for gonadal
hormone measurement in blood and urine. Such methods, however, are now
available. The striking and regular fluctuations in mood state associated with
the menstrual cycle in many women provide another example of observations

which strongly suggest hormonal influences upon intrapsychic processes and
probably presents one of the best natural opportunities for the experimental
study of such correlations. The recent development of radioimmunoassay
methods for the measurement of the gonadotropins and of the individual
gonadal steroids now makes possible a highly refined endocrinological
approach to this clinical problem. The research of Rose and his co-workers,
involving the study of correlations between plasma testosterone and
agonistic behavior, presents another excellent model of how the general

problem of viewing psychoendocrine relationships in both directions may be
approached experimentally. It is clear that the study of hormonal feedback

upon the brain is another aspect of psychoendocrinology which is worthy of
greater attention in the future, particularly because of the recent availability

of many long-awaited, refined methods of hormone assay.
It should also be mentioned that there is a considerable body of
neurochemical and psychopharmacological research which indicates that
biogenic amines in the brain may be involved in the development of affective
disorders such as depression and mania. The possible role of various
hormones upon the metabolism and balance of the biogenic amines within
the CNS has, therefore, become yet another area of current interest in
psychoendocrine research. Some caution is probably well-advised in this
area, however, for several reasons, perhaps particularly with regard to the
pitfall of placing overemphasis prematurely on a single hormone before a
broader survey for possible multiple, interacting hormonal influences on the
biogenic amines is completed.
Psychoendocrine Approaches to the Study of Psychosomatic Disorders
Most of the psychoendocrine approaches discussed up to this point have

been oriented in terms of the study of hormonal changes as reflections of
psychological processes. The central issues have revolved around the use of
hormone measurements as sensitive, objective, roughly quantitative
reflections of the intrapsychic processes involved in emotional and defensive
organization. It has also been emphasized that the great bulk of

psychoendocrine research since the 1950s, furthermore, has been focused on
the pituitary-adrenal cortical and the sympathetic-adrenal medullary
systems.
In turning, finally, to the question of the implications of
psychoendocrine approaches for psychosomatic medicine, it is necessary to
broaden our conceptual approach to consider some fundamental facts of
endocrine physiology. The basic question now becomes, “Can psychologically
determined hormonal changes play a mediating, pathogenic role, along with
concurrent autonomic changes, in the development of somatic illnesses?” In
approaching this question, the modus operandi of hormones at the cellular

level becomes a highly relevant issue. A particularly crucial fact is that
hormones are now known to exert their effects upon metabolic or cellular
processes in a complex, interdependent way. In general, a given metabolic
process is regulated by numerous hormones which are aligned into a balance

of opposing and cooperating forces, with antagonistic, synergistic, additive,
and permissive relationships present between the hormones in relation to the
regulation of any particular cellular process. As a result, no single hormone

controls any single metabolic process, but there is always a balance between
interdependent forces. Thus, in considering the regulation of lipid metabolism,
for example, a substantial number of hormones must be taken into account,

including norepinephrine, insulin, cortisol, epinephrine, growth hormone,
thyroxine, and estrogens. Carried to its logical conclusion, then, this basic
feature of endocrine physiology dictates the conclusion that an understanding
of the regulation of the functional state of any given cellular process at any
given time can only be achieved by viewing the current overall hormonal
balance as the final, key determinant of the cellular activity in question. In
practical terms, this means that little success is to be expected in approaches
which attempt to relate psychological processes and somatic illnesses

through a view of any single mediating psychoendocrine system in isolation.
It means that an increasing number of concurrent hormonal measurements,
involving as many endocrine systems as possible, should be incorporated into
psychoendocrine studies of psychosomatic disorders.
Another body of evidence supports this conceptual approach in addition
to the reasoning based on cellular aspects of endocrine physiology. With the
recent, revolutionary advances in hormone-assay methodology, it has become
feasible to measure a large number of hormones concurrently and to test the
hypothesis that the many endocrine systems, which have anatomical contacts
with the brain, are responsive to psychological influences. Figure 24-7 shows
the pattern of multiple hormonal responses to a seventy-two-hour

conditioned emotional disturbance in a series of “conditioned avoidance”
experiments in monkeys. First of all, it is evident that every hormone

measured changed in reaction to this stressful situation, although the
dynamics of change differ considerably from one hormone to the next,
particularly with regard to temporal features. Two general hormone-

response subgroups may be distinguished on the basis of initial direction of
change. The levels of the corticosteroids, epinephrine, norepinephrine,
thyroxine or butanol-extractive iodine (BEI), and growth hormone all rise
initially, while the levels of insulin, androgens, and estrogens drop initially.
Following the session, the latter hormones tend to rebound above baseline
levels. The possibility that the organization of this acute psychoendocrine

response pattern represents a “catabolic-anabolic” sequence of coordinated
responses in preparation for muscular exertion, according to Cannon’s
formulation, fits well with our present knowledge of the role of each of these
hormones in relation to energy metabolism. The critical interpretation of
these experiments has been discussed at length elsewhere, but their general
relevance to psychosomatic studies seems clear. While this stereotyped
pattern of acute psychoendocrine response is demonstrable under certain
conditions in the monkey, how might the pattern of hormonal balance be
variously altered on an acute and chronic basis by the complex psychological

machinery which has already been demonstrated in corticosteroid and
catecholamine studies to exert such profound and varying effects on

endocrine function from one individual to the next? Are particular
characterological patterns of psychological organization reflected broadly in

the pattern of overall hormonal balance? If we view psychosomatic illnesses
as fundamentally integrative disorders, does the pattern of organization of

overall hormonal balance distinctively reflect the particular integrative
disorder involving emotional and defensive processes? If so, does the altered
pattern of hormone balance appear to constitute a pathogenetic link to the
associated somatic disorder? These questions represent the general lines
along which working hypotheses can be perhaps most logically developed in
the light of current psychoendocrine data and theory.
Figure 24-7.
Organization of multiple hormonal responses to sustained conditioned
emotional disturbance (conditioned avoidance) in rhesus monkeys. (U.S.
Army photograph.)
As yet, however, only the most preliminary efforts have been made to
test the usefulness of this broadly based, holistic psychoendocrine approach
to the study of psychosomatic disorders. Such efforts, while quite limited so
far, have provided some useful guidelines and leads for future work in this
area. In a study of hormonal patterns of recruits during basic training, for
example, several hormonal abnormalities were noted during the week prior
to onset of acute adenovirus respiratory illnesses. A gradual decline in

thyroid hormone levels, spiking corticosteroid and catecholamine elevations
several days before the onset of illness, and a high percentage of extremely
high or extremely low corticosteroid, thyroid hormone, or androgen levels
appeared to characterize the period preceding respiratory infections. These

findings suggest that it may be worthwhile to evaluate further the working
hypothesis that stress-related, preillness, multiple changes in overall
hormonal balance may play a pathogenetic role in altering host resistance to

infectious illnesses.
In a preliminary study of obese patients, Troyer et al. have observed

that two general classes of endocrine abnormalities should be considered.
First, the mean chronic profile of hormonal balance appears to be altered, with
the levels of certain hormones chronically higher or lower than those in

normal groups or other patient populations. Secondly, the pattern of acute
responsiveness reflected in changes in hormonal balance with psychological or
other stimuli may be distinctively altered in patients with psychosomatic
illnesses. A number of acute episodes were observed in obese patients, for
example, in which the anabolic hormones rose at the same time that the
catabolic hormones rose, a pattern quite different from that observed during
acute arousal in the normal monkey. It is also especially interesting,
incidentally, that these marked acute hormone responses apparently
occurred in the patients generally without overt expression or subjective

awareness of emotional distress. In two obese subjects studied earlier,
however, details of life events and some knowledge of dynamic factors in the
individual patient suggested that neurotic processes were suddenly activated
at the time of the hormonal changes. These pilot observations require
considerable further evaluation, but are mentioned here primarily to indicate
the kinds of methodological and theoretical issues which bear consideration

in the design of psychoendocrine studies of medical patients. Endocrine
sampling in long-term longitudinal studies of patients should yield both a

chronic mean hormonal profile and an acute psychoendocrine response
pattern so that both of these parameters, in turn, can be studied for possible
relationships to psychological and somatic parameters.
While the technical and organizational problems which make this

multidisciplinary approach difficult are substantial and require resourceful
and energetic efforts for their solution, historically it now appears within our
grasp. It is not often that a generation has suddenly new experimental
methods at its disposal which make possible the testing of a promising but
unproven concept of disease. While much of medicine, with the ever-
increasing trend towards specialization, continues to pursue the course of

viewing disease as a local or regional phenomenon, the opportunity is now
open to pursue, at a new level of sophistication, a view of many diseases as
disorders of integration. We have long thought of endocrine systems as largely

governed by relatively simple, humoral, nearly infallible self-regulatory
mechanisms. The new knowledge that highly complicated psychological
influences are superimposed upon the humoral machinery for endocrine
regulation raises the possibility that disorders of bodily function may result
when the more complex, and probably more fallible, psychological machinery
preempts, disrupts, or otherwise works at odds against the simpler, lower-

level, humoral machinery of endocrine regulation. Certainly, there are few, if
any, conceptual approaches to the genesis of disease presently envisioned in

medicine which are potentially more far-reaching, logically appealing, and
challenging.
Appendix: Some Control Issues and Experimental Tactics in Psychoendocrine

Research
While it is beyond the scope of this chapter to discuss in detail such

relevant research issues as nonpsychological determinants of endocrine
activity which may act as interfering independent variables in
psychoendocrine studies, control measures in experimental design, selection
and validation of hormone assay procedures, etc., it may be useful to review
briefly several of the problems which have most commonly proven pitfalls in
past psychoendocrine research.
Quality-Control Check System for Hormone-Assay Methods
Since hormone assay methods are generally quite delicate
microanalytical procedures, in which such subtle factors as minor variations
in day-to-day laboratory technique, fluctuations in environmental
temperature, variability in reagent batches, instrument malfunction,

glassware contamination, etc., can cause major errors in the accuracy of
results, it is essential that quality-control checks which are as rigorous and

comprehensive as possible be incorporated into every analytical run. Even in
the most experienced laboratories, such methods may suddenly give

unreliable results and days or even weeks of trouble-shooting may be
required in order to locate the source of error. A sound quality-control check
system cannot, of course, prevent such breakdowns of methods, nor the
associated loss of samples or time, but it has the all-important advantages of

providing the investigator with a highly reliable and objective basis for
accepting or rejecting biochemical results in each analytical run, and of
greatly reducing the chance of accepting erroneous results as valid. These
advantages apply equally whether the biochemical determinations are made
by the investigator himself, by a close colleague, or by a distant commercial
laboratory. The following system, outlined in a general way, can be applied to

most blood or urinary hormone-assay procedures with appropriate
modifications.
First, a large pool of plasma or urine should be obtained so as to provide
about 100 or more aliquots of the same volume as will be normally collected
for individual routine analyses of unknown samples from experimental

subjects. The number of aliquots is arbitrary and mainly decided by
convenience, in terms of providing a supply to last several months for the
method in question. If, for example, the method requires a x-ml. aliquot for
each determination, if two control samples are included in each analytical
run, and if three analytical runs are made each week, then 102 aliquots would
provide a seventeen-week supply of control samples. The concentration of

hormone in the original pool should be reasonably close to the concentration
range present in the samples from the subject population to be studied. The
original raw pool should be divided into three equal subpools, designated C1;
C2, and C3. Subpool C1 should remain untreated, as it was collected. To

subpool C2, a quantity of crystalline or highly purified hormone should be
added so as to increase the hormone concentration in each aliquot by an
amount just slightly greater than the standard deviation of the method. The
principle involved here is that C2 should be clearly distinguishable from C1 by

the analytical method, but just barely so. In other words, if aliquots from C1
and C2 are repeatedly analyzed in twenty or thirty successive runs, the
highest values obtained for C1 aliquots should only very rarely exceed the
lowest values obtained on C2 aliquots. If too much hormone is added to C2
and the concentration difference is too great between C1 and C2 so that they
are too easily distinguishable, then in some methods this may lead to
conscious or unconscious bias on the part of the technician. To subpool C3,
then, an amount of purified hormone, twice as great as that added to C2,
should be added so that C2 and C3 aliquots will be just comfortably
distinguishable by the method and values from the two subpools rarely
overlap.
Once the three subpools are thus prepared, and the added hormone in
subpools C3 well-mixed by shaking, each subpool should then be divided into

the small individual aliquots for individual analyses. Next comes the
important matter of coding the bottles with numbers in such a way as to give
no indication to the technician of which subpool is represented. A code sheet
is prepared listing numbers from 1 to 100, or whatever total number of

aliquots there may be, and samples are then numbered in order after they are
drawn at random from the three subpool groups. The code sheet might read,
for example, 1 (the only number actually on the tube) = C2, 2 = C1; 3 = C2, 4 =
C3, 5 = C3, 6 = C1, etc. The biochemist receives only the tubes with the
numbers 1, 2, 3, 4, 5, 6, etc. The responsible investigator should maintain
custody of the code sheet in such a way as to keep the procedure blind, but to
supply immediate feedback to the chemist or technician after each run is
completed. The control samples should be stored frozen, with a substantial
number of aliquots kept in the same freezer as the unknown samples from
experimental subjects. If the freezer should ever malfunction, the control
samples may provide some valuable indication as to whether serious damage
to hormone concentrations has resulted from high temperatures or not. For
most methods, at least two control samples should be included in each run,
preferably one at the beginning and one at the end of the series of tubes being
analyzed. Immediately after the control samples are initially prepared, six to
ten samples should be analyzed from each subpool so as to establish an
approximate mean value and standard deviation for each subpool before
proceeding with the analysis of unknown samples.
While this system provides a reliable check against the great majority of
sources of analytical error, it is not infallible and will not detect, for example,
an occasional random error caused by the contamination of a single tube. In

such an instance, the investigator can only ask for several replicate
determinations of any sample giving a value far away from the expected
range. In the main, however, the system is extremely valuable in monitoring
day-to-day accuracy and in providing reassurance to the investigator,
particularly when in search of psychological correlates, that the hormone
values are valid.
Choice of Blood- and Urine-Sample Collection Schedules
There are several guidelines for the design of hormone-sampling

schedules which have proven useful in promoting the interpretability of
psychoendocrine experiments. The first principle, perhaps, is that the sample-
collection times should be closely attuned to the dynamics of the endocrine
response and the stimulus under study. It is known, of course, that the levels
of some hormones such as epinephrine, norepinephrine, and growth
hormone are very labile, showing marked elevations or decreases within a

matter of minutes. Other hormones, such as cortisol, thyroxine, or
testosterone, apparently change more slowly. While some general guesses

about optimal sampling intervals can be made from previous work on various
hormones, it is desirable in any particular study, whenever possible, to carry
out a few pilot experiments with frequent enough samples so as to define
roughly the temporal configuration of hormonal-response curves. Once this is

established, a more economical collection design with fewer samples can be
devised with greater assurance that response peaks will not be missed
because of inappropriate sampling intervals.
Another extremely important practice is the obtaining of multiple

control or base-line samples before the onset of any experimental
manipulations on either an acute or prolonged basis. Because of the well-
known potency of anticipatory reactions, especially those involving novelty or

uncertainty, as stimuli to many endocrine systems, at least two, and
preferably more, preexperimental samples should always be obtained in
order to establish the slope of hormonal change against which experimental
stimuli are superimposed. It is probable that few factors have led to greater
confusion and error in the interpretation of experiments on endocrine
regulation than failure to obtain multiple base-line samples.
A number of other control and methodological issues, such as the
advantages of longterm “longitudinal” studies of individual patients over
“contrast” studies of large groups in the exploratory phases of
psychoendocrine research, the importance of social milieu during

hospitalization, the selection and validation of psychological methods, the
need to consider circadian and ultradian hormonal rhythms in experimental
design, and the role of nonpsychological determinants, such as age, sex,

medications, smoking, posture, bed rest, muscular activity, environmental
temperature, nutrition, etc., have all emerged as important considerations in

psychoendocrine research and are discussed in greater detail elsewhere
Bibliography
Ax, A. “The Physiological Differentiation between Fear and Anger in Humans,” Psychosom. Med.,
15 (1953), 433-442.
Berkeley, A. W. “Level of Aspiration in Relation to Adrenal Cortical Activity and the Concept of
Stress,” J. Comp. Physiol. Psychol, 45 (1952), 443-449.
Bernard, C. In A. Pi-Suner, ed., The Whole and the Parts: Classics of Biology, p. 313. New York:
Philosophical Library, 1955.
Bliss, E. L., C. J. Migeon, C. H. Branch et al. “Adrenocortical Function in Schizophrenia,” Am. J.

Physiol., 112 (1955), 358-365.
----. “Reaction of the Adrenal Cortex to Emotional Stress,” Psychosom. Med., 18 (1956), 56-76.
Board, F., H. Persky, and D. A. Hamburg. “Psychological Stress and Endocrine Functions. Blood
Levels of Adrenocortical and Thyroid Hormones in Acutely Disturbed Patients,”
Psychosom. Med., 18 (1956), 324-333.
----. “Psychological Stress and Endocrine Functions. Blood Levels of Adrenocortical and Thyroid
Hormones in Patients Suffering from Depressive Reactions,’’ Arch. Neurol.
Psychiatry, 78 (1957), 612-620.
Brown, G. M. and S. Reichlin. “Psychologic and Neural Regulations of Growth Hormone,”

Psychosom. Med., 34 (1972), 45-60.
Bunney, W. E., Jr., E. L. Hartmann, and J. W. Mason. “Study of a Patient with 48-Hour Manic-
Depressive Cycles: II. Strong Positive Correlation between Endocrine Factors and
Manic Defense Patterns,” Arch. Gen. Psychiatry, 12 (1965), 619-625.
Bunney, W. E., Jr., J. W. Mason, and D. A. Hamburg. “Correlations between Behavioral Variables
and Urinary 17-Hydroxycorticosteroids in Depressed Patients,” Psychosom. Med.,
27 (1965), 299-308.
Cannon, W. B. Bodily Changes in Pain, Hunger, Fear, and Rage. Boston: Branford, 1929.
Cannon, W. B. and D. de la Paz. “Emotional Stimulation of Adrenal Secretion,” Am. J. Physiol., 27

(1911), 64-70.
Christian, J. J. “Phenomena Associated with Population Density,” Proc. Natl. Acad. Sci., 47 (1961),
428-449.
Elmadjian, F., J. M. Hope, and E. T. Lamson. “Excretion of Epinephrine and Norepinephrine Under
Stress,” Recent Prog. Horm. Res., 14 (1958), 513-553.
Euler, U. S., V. Noradrenaline. Springfield, Ill : Charles C. Thomas, 1956.
----. “Quantitation of Stress by Catecholamine Analysis,” Clin. Pharmacol. Ther., 5 (1964), 398-404.
Euler, U. S., V., C. A. Gemzell, L. Levi et al. “Cortical and Medullary Adrenal Activity in Emotional
Stress,” Acta Endocrinol. (Kbh.), 30 (1959), 567-573-
Fox, H. M. “Effects of Psychophysiological Research on the Transference,” J. Am. Psychoanal.

Assoc., 6 (1958), 413-432.
Fox, H. M., S. Gifford, A. F. Valenstein et al. “Psychophysiological Correlation of 17-Ketosteroids

and 17-Hydroxycorticosteroids in 21 Pairs of Monozygotic Twins,” J. Psychosom.
Res., 14 (1970), 71-79.
Fox, H. M., B. J. Murawski, A. F. Bartholoway et al. “Adrenal Steroid Excretion Patterns in Eighteen
Healthy Subjects,” Psychosom. Med., 23 (1961), 33-40.
Fox, H. M., B. J. Murawski, G. W. Thorn et al. “Urinary 17-Hydroxycorticosteroid and Uropepsin

Levels with Psychological Data: A Three-Year Study of One Subject,” Arch. Intern.
Med., 10 (1958), 859-871.
Frankenhaeuser, M. and S. Kareby. “The Effect of Meprobamate on Catecholamine Excretion

during Mental Stress,” Percept. Mot. Skills, 15 (1962), 571-577.
Frankenhaeuser, M. and P. Patkai. “Catecholamine Excretion and Performance during Stress,”
Percept. Mot. Skills, 19 (1964), 13-14.
Frankenhaeuser, M. and B. Post. “Catecholamine Excretion during Mental Work as Modified by

Centrally Acting Drugs,” Acta. Physiol. Scand., 55 (1962), 74-81.
Friedman, S. B., J. W. Mason, and D. A. Hamburg. “Urinary 17-Hydroxycorticosteroid Levels in

Parents of Children with Neoplastic Disease,” Psychosom. Med., 25 (1963), 364-376.
Funkenstein, D. H., S. H. King, and M. E. Drolette. Mastery of Stress. Cambridge: Harvard University
Press, 1957.
Hamburg, D. A. “Plasma and Urinary Corticosteroid Levels in Normally Occurring Psychological

Stresses,” in S. Korey, ed., Ultrastructure and Metabolism of the Nervous System, pp.
426-452. Baltimore: Williams & Wilkins, 1962.
Harris, G. W. Neural Control of the Pituitary Gland. London: Arnold, 1955.
----.“Hypothalamic Control of the Anterior Lobe of the Hypophysis,” in W. S. Fields, B. Guillemin,

and C. A. Carton, eds., Hypothalamic-Hypophyseal Interrelationships, pp. 31-45.
Springfield, Ill.: Charles C. Thomas, 1956.
Hellman, L., F. Nakada, J. Curti et al. “Cortisol Is Secreted Episodically by Normal Man,” J. Clin.
Endocrinol. Metab., 30 (1970), 411-422.
Hill, S. R., Jr., F. C. Goetz, H. M. Fox et al. “Studies on Adrenocortical and Psychological Response to
Stress in Man,” Arch. Intern. Med., 97 (1956), 269-298.
Hoskins, R. G. The Biology of Schizophrenia. New York: Norton, 1946.
Hubble, D. “The Endocrine Orchestra,” Br. Med. J. 1 (1961), 523-528.
----. “The Psyche and the Endocrine System,” Lancet, 2 (1963), 209-214.
Ingle, D. J. “Parameters of Metabolic Problems,” Recent Prog. Horm. Res., 6 (1951). 159-194.
----. Principles of Research in Biology and Medicine. Philadelphia: Lippincott, 1958.
Johansson, S., L. Levi, and S. Lindstedt. Stress and the Thyroid Gland: A Review of Clinical and
Experimental Studies, and a Report of Own Data on Experimentally Induced PBI
Reactions in Man. Reports from the Laboratory for Clinical Stress Research, no. 17.
Stockholm, Nov. 1970.
Johns, M. W., T. J. A. Gay, J. P. Masterton et al. “Relationship between Sleep Habits, Adrenocortical
Activity, and Personality,” Psychosom. Med., 33 (1971), 499-503.
Katz, J. L., P. Ackman, Y. Rothwax et al. “Psychoendocrine Aspects of Cancer of the Breast,”
Psychosom. Med., 32 (1970), 1-18.
Knapp, P. H., C. Mushatt, S. J. Nemetz et al. “The Context of Reported Asthma during
Psychoanalysis,” Psychosom. Med., 32 (1970), 167-188.
Kreuz, L. E. and R. M. Rose. “Assessment of Aggressive Behavior and Plasma Testosterone in a

Young Criminal Population,” Psychosom. Med., 34 (1972), 321-332.
Kreuz, L. E., R. M. Rose, and J. R. Jennings. “Suppression of Plasma Testosterone Levels and
Psychological Stress: A Longitudinal Study of Young Men in Officer Candidate
School,” Arch. Gen. Psychiatry, 26 (197.2), 479-482.
Levi, L. “The Urinary Output of Adrenaline and Noradrenaline during Different Experimentally
Induced Pleasant and Unpleasant Emotional States: A Summary,” J. Psychosom. Res.,
8 (1964), 197-198.
----. “The Stress of Every Day Work as Reflected in Productiveness, Subjective Feelings, and
Urinary Output of Adrenaline and Noradrenaline Under Salaried and Piece-work
Conditions,” J. Psychosom. Res., 8 (1964), 199-202.
Levi, L., ed. “Stress and Distress in Response to Psychological Stimuli,” Acta. Med. Scand., 191,
Suppl. 528 (1972).
Mason, J. W. “Psychological Influences on the Pituitary-Adrenal Cortical System,” Recent Prog.

Horm. Res., 15 (1959), 345-389.
----. “Psychoendocrine Approaches in Stress Research,” in Symposium on Medical Aspects of Stress
in the Military Climate, pp. 375-419. Washington: Walter Reed Army Institute of
Research, 1964.
----. “The Scope of Psychoendocrine Research,” Psychosom. Med., 30 (1968), 565-575.
----. “A Review of Psychoendocrine Research on the Pituitary-Adrenal Cortical System,”

Psychosom. Med., 30 (1968), 576-607.
----. “A Review of Psychoendocrine Research on the Sympathetic-Adrenal Medullary System,”

Psychosom. Med., 30 (1968), 631-653
----. “A Review of Psychoendocrine Research on the Pituitary-Thyroid System,” Psychosom. Med.,

30 (1968), 666-681.
----. “Organization of the Multiple Endocrine Responses to Avoidance in the Monkey,” Psychosom.
Med., 30 (1968), 774-790.
----. “‘Over-all’ Hormonal Balance as a Key to Endocrine Organization,” Psychosom. Med., 30

(1968), 791-808.
----. “Strategy in Psychosomatic Research,” Psychosom. Med., 32 (1970), 427-439.
----. “A Re-evaluation of the Concept of ‘Non-Specificity’ in Stress Theory,” J. Psychiatr. Res., 8

(1971), 323-333.
Mason, J. W. and J. V. Brady. “The Sensitivity of Psychoendocrine Systems to Social and Physical
Environment,” in P. H. Liederman and D. Shapiro, eds., Psychobiological Approaches
to Social Behavior, pp. 4-23. Stanford: Stanford University Press, 1964.
Mason, J. W., J. V. Brady, and M. Sidman. “Plasma 17-Hydroxycorticosteroid Levels and

Conditioned Behavior in the Rhesus Monkey,” Endocrinology, 60 (1957), 741-752.
Mason, J. W., J. V. Brady, and W. W. Tolson. “Behavioral Adaptations and Endocrine Activity—
Psychoendocrine Differentiation of Emotional States,” in R. Levine, ed., Endocrines
and the Central Nervous System, pp. 227-250. Baltimore: Williams & Wilkins, 1966.
Mason, J. W., E. D. Buescher, M. L. Belfer et al. “Pre-illness Hormonal Changes in Army Recruits
with Acute Respiratory Infections,” (Abstract) Psychosom. Med., 29 (1967), 545.
Mason, J. W., C. C. Kenion, D. R. Collins et al. “Urinary Testosterone Responses to 72-Hour

Avoidance Sessions in the Monkey,” Psychosom. Med., 30 (1968), 721-732.
Mason, J. W., G. F. Mangan, Jr., J. V. Brady et al. “Concurrent Plasma Epinephrine, Norepinephrine,
and 17-Hydroxycorticosteroid Levels during Conditioned Emotional Disturbances
in Monkeys,” Psychosom. Med., 23 (1961), 344-353.
Mason, J. W., W. J. H. Nauta, J. V. Brady et al. “The Role of Limbic System Structures in the
Regulation of ACTH Secretion,” Acta. Neuroveget., 23 (1961), 4-14.
Mason, J. W., E. J. Sachar, J. R. Fishman et al. “Corticosteroid Responses to Hospital Admission,”

Arch. Gen. Psychiatry, 13 (1965). 1-8.
Mathe, A. A. and P. H. Knapp. “Emotional and Adrenal Reactions to Stress in Bronchial Asthma,”
Psychosom. Med., 33 (1970). 323-340.
Mattson, A., S. Gross, and T. W. Hall. “Psychoendocrine Study of Adaptation in Young

Hemophiliacs,” Psychosom. Med., 33 (1971), 215-225.
Michael, R. P. and J. L. Gibbons. “Interrelationships between the Endocrine System and

Neuropsychiatry,” Int. Rev. Neurobiol., 5 (1963), 243-292.
Miller, R. G., R. T. Rubin, B. R. Clark et al. “The Stress of Aircraft Carrier Landings. 1. Corticosteroid
Responses in Naval Aviators,” Psychosom. Med., 32 (1970), 581-588.
Nalbandov, A. V., ed. Advances in Neuroendocrinology. Urbana: University of Illinois Press, 1963.
Nauta, W. J. H. “Central Nervous Organization and the Endocrine Motor System,” in A. V.

Nalbandov, ed., Advances in Neuroendocrinology, pp. 5-21. Urbana: University of
Illinois Press, 1963.
Oken, D. “The Role of Defense in Psychological Stress,” in R. Roessler, ed., Physiological Correlates
of Psychological Disorder, pp. 193-210. Madison: University of Wisconsin Press,
1962.
Persky, H., D. A. Hamburg, H. Basowitz et al. “Relation of Emotional Responses and Changes in
Plasma Hydrocortisone Level after Stressful Interview,” Arch. Neurol. Physiol., 79
(1958), 434-447.
Pincus, G., H. Hoagland, H. Freeman et al. “A Study of Pituitary-Adrenocortical Function in Normal

and Psychotic Men,” Psychosom. Med., 11 (1949), 74-101.
Poe, R. O., R. M. Rose, and J. W. Mason. “Multiple Determinants of 17-Hydroxycorticosteroid

Excretion in Recruits during Basic Training,” Psychosom. Med., 32 (1968), 369-378.
Price, D. B., M. Thaler, and J. W. Mason. “Preoperative Emotional States and Adrenal Cortical
Activity: Studies on Cardiac and Pulmonary Surgery Patients,” Arch. Neurol.
Psychiatry, 77 (1957), 646-656.
Reiss, M., ed. Psychoendocrinology. New York: Grune & Stratton, 1958.
Rizzo, N. D., H. M. Fox, J. C. Laidlaw et al. “Concurrent Observations of Behavior Changes and of
Adrenocortical Variations in a Cyclothymic Patient during a Period of 12 Months,”
Ann. Intern. Med., 41 (1954) 798-815.
Rose, R. M. “Androgen Responses to Stress: Psychoendocrine Relationships and Assessment of

Androgen Activity,” Psychosom. Med., 31 (1969), 405-417.
----. “The Psychological Effects of Androgens and Estrogens—A Review,” in R. I. Shader, ed.,
Psychiatric Complications of Medical Drugs, pp. 251-293. New York: Raven Press,
1972.
Rose, R. M., T. P. Gordon, and I. S. Bernstein. “Sexual and Social Influences on Testosterone
Secretion in the Rhesus,” (Abstract) Psychosom. Med., 34 (1972), 473.
Rose. R. M., J. W. Holaday, and I. S. Bernstein. “Plasma Testosterone, Dominance Rank, and
Aggressive Behavior in Male Rhesus Monkeys,” Nature, 231 (1969), 366-368.
Rose, R. M., J. W. Mason, and J. V. Brady. “Adrenal Responses to Maternal Separation and Chair
Adaptation in Experimentally Raised Rhesus Monkeys (Macaca mulatta),” in C. R.
Carpenter, ed., Proc. 2nd. Int. Congr. Primates, Vol. 1, pp. 211-218. New York:
Karger, 1969.
Rose, R. M., R. O. Poe, and ]. W. Mason. “Psychological State and Body Size as Determinants of 17-
OHCS Excretion,” Arch. Intern. Med., 121 (1968), 406-413.
Rubin, R. T. and A. J. Mandell. “Adrenal Cortical Activity in Pathological Emotional States. A

Review.” Am. J. Psychiatry, 123 (1966), 387-400.
Sachar, E. J. “Corticosteroids in Depressive Illness: A Re-evaluation of Control Issues and the

Literature,” Arch. Gen. Psychiatry, 17 (1967), 544-553.
Sachar, E. J., J. M. Mackenzie, and W. A. Binstock. “Corticosteroid Responses to Psychotherapy of

Depressions: I. Evaluations during Confrontation of Loss,” Arch. Gen. Psychiatry, 16
(1967), 461-470.
Sachar, E. J., J. M. Mackenzie, W. A. Binstock et al. “Corticosteroid Responses to Psychotherapy of

Depressions: II. Further Clinical and Physiological Implications,” Psychosom. Med.,
30 (1968), 23-44.
Sachar, E. J., J. W. Mason, J. R. Fishman et al. “Corticosteroid Excretion in Normal Young Adults
Living under ‘Basal’ Conditions,” Psychosom. Med., 27 (1965), 435-445.
Sachar, E. J., J. W. Mason, H. S. Kolmer, Jr. et al. “Psychoendocrine Aspects of Acute Schizophrenic
Reactions,” Psychosom. Med., 25 (1963), 510-537.
Selye, H. “A Syndrome Produced by Diverse Nocuous Agents,” Nature, 138 (1936), 32.
----. Stress. Montreal: Acta, 1950.
Silverman, A. J., S. I. Cohen, B. M. Shmavonian et al. “Catecholamines in Psychophysiologic

Studies,” Recent Adv. Biol. Psychiatry, 3 (1961), 104-117.
Smith, C, K., J. Barish, J. Correa et al. “Psychiatric Disturbances in Endocrinologic Disease,”

Psychosom. Med., 34 (1972), 69-86.
Thorn, G. W., D. Jenkins, J. C. Laidlaw et al. “Response of the Adrenal Cortex to Stress in Man,”
Trans. Assoc. Am. Physicians, 66 (1953), 48-64.
Troyer, W., J. Mason, and J. Hirsch. “A Preliminary Psychoendocrine Study of Obese Patients,”
unpublished observations.
Von Bertalanffy, L. Modern Theories of Development. London: Oxford University Press, 1933.
Wadeson, R. W., J. W. Mason, D. A. Hamburg et al. “Plasma and Urinary 17-OHCS Responses to
Motion Pictures,” Arch. Gen. Psychiatry, 9 (1963), 146-156.
Willcox, D. R. “The Serial Study of Adrenal Steroid Excretion,” J. Psychosom. Res., 4 (1959), 106-
116.
Wolff, C. T., S. B. Friedman, M. A. Hofer et al. “Relationship between Psychological Defenses and
Mean Urinary 17-OHCS Excretion Rates. I. A Predictive Study of Parents of Fatally
111 Children,” Psychosom. Med., 26 (1964), 576-591.
Wolff, C. T., M. A. Hofer, and J. W. Mason. “Relationship between Psychological Defenses and Mean
Urinary 17-OHCS Excretion Rates: II. Methodological and Theoretical
Considerations,” Psychosom. Med., 26 (1964), 592-609.
Yates, F. E. and J. W. Maran. “Stimulation and Inhibition of Adrenocorticotropic (ACTH) Release,”

in W. Sawyer and E. Knobil, eds., Handbook of Physiology, Section on Endocrinology.
Washington: American Physiological Society, forthcoming.
Chapter 25
Psychosocial And Epidemiological Concepts In

Medicine
John J. Schwab
This chapter will present some of the concepts of psychosocial medicine
as they relate to psychosomatic disorders, particularly in groups. This will
involve an examination of the epidemiology of psychosomatic disorders, their
frequency and distribution, the demographic characteristics of the afflicted,
and changing patterns of susceptibility and illness. Then we will look at some
of the ideas about relationships between sociocultural processes and health
or illness. In this chapter, the term “psychosocial medicine” refers to the
health and illness of groups.
In any discussion of psychosocial medicine, we should be aware of

certain unanswerable questions. Can we attribute psychosomatic illnesses
and behavioral disorders to sociocultural processes? When a sufficient
number of individuals within a group becomes ill, should the entire group be
labeled a “sick society”? Can an entire group react, analogous to an individual,
in such a way that it becomes ill? Although we cannot find definitive answers
to these questions, we know that numbers of persons, groups, can display
similar reactions, that they may be predisposed to mental and psychosomatic

illnesses, possibly by learning and conditioning, and that certain illnesses may
become epidemic as a result of that predisposition, perhaps by conditions
leading to shared “definitions of the situation,” or even by contagion.
In his introduction to Psychosocial Medicine: A Study of the Sick Society,
Halliday states that:
A group, like an individual, may be viewed both physically and

psychologically. ... If [the physical] needs are not satisfied its “physical
health” declines and the group becomes a sick population characterized by
high rates of sickness and death due to reasons such as malnutrition,
infectious diseases, infestations, and so on. In its psychological aspects a
group appears as a society with psychological or social needs. If these
needs are not satisfied, its “psychological health,” which is also its “social
health” declines and the group becomes socially sick, that is, a sick society.
The medical approach to the study of the sick society is called
“psychosocial medicine.” [p. 10]
Our concepts of psychosocial medicine extend back to Hippocrates’ Airs,
Waters, and Places which deals specifically with the influence of the
environment on the organism—not only physical factors such as climate and
the character of the terrain, but also socioenvironmental factors such as the
habits and the child-rearing practices of various peoples as they relate to
health and disease. His treatise, therefore, may be considered as the first
essay on ecologic medicine.
Hippocrates described some specific psychosomatic afflictions and

associated their frequency with certain sociodemographic characteristics. For
example, in comparison to other peoples, the nomadic Scythians were an
infertile group. He attributed their infertility to their constitutions: “They are

stout and fleshy in appearance; they have ill-marked joints, and are flabby
and lacking in tone; their lower alimentary canals are moist beyond the
ordinary.” He related both their constitutional deficiencies and their infertility
to their habits and customs. Wealthy Scythians spent almost all of their lives
on horseback. The men developed edema and severe varicosities of their
lower extremities while the fat, indolent women had menstrual difficulties:
“The monthly cleansing process does not take place in proper fashion, but is
scanty and of short duration.” But the impotence and the menstrual
difficulties, Hippocrates noted, were diseases only of the wealthy who could
afford horses. The poor, who walked or ran while the tribes moved from place
to place, did not have these afflictions. Hippocrates stated that the wealthier
Scythians’ manner of life was one factor responsible for their infertility. As
further etiological evidence, he noted that: “an important proof of this is
furnished by their female servants; for no sooner do they have intercourse

with a man than they become pregnant, this being due to their lives of hard
toil and to the sparseness of their frames.”
In this classic, Hippocrates supplied us with an explanatory model for

examining populations and their illnesses in a psychosocial context. Life
styles, which were directly related to social class (in conjunction with
constitutional factors), affected both the men and the women in ways which
resulted in infertility in the upper classes. In addition to pointing out that the
frequency of infertility varied with social class, he noted that the child-rearing
practices were influential. In contrast to other peoples, the wealthy Scythians
did not swaddle their children, but instead, just allowed them to ride in
wagons. Although Hippocrates does not state explicitly that the children were
neglected by not being swaddled, he intimates that their life style was
conducive to the development of their constitutional deficiencies and thus

their infertility.
This ancient description of the relationship between sociocultural
processes and psychosomatic illness furnishes a background for looking at

the psychosocial aspects of psychosomatic disorders. A rationale for this
approach is provided by the studies which have shown repeatedly that
psychosomatic disorders are unequally distributed within and between

populations. Also, at times certain psychosomatic afflictions have been
epidemic; some examples are tarantism in the Middle Ages, fainting in the
Victorian Era, and coronary heart disease today.
In an editorial in Science, Stallones quotes Andrija Stampar: “No matter
what the number of physicians may be, they will never improve people’s
health by individual therapy.” Stallones does not minimize the importance of
direct medical care but he does assert that the major health benefits of the
last century “. . . have resulted from the operation of undirected, nonspecific
influences. Advances in medical knowledge and the decline of disease are
simultaneous results of a general improvement in the quality of life.” He

maintains that: “To define, explain, and gain control of the various and
extremely effective determinants of disease requires a deep appreciation of
the ecological systems of which they are a part.” He concludes that different
environmental experiences are responsible for differences in the frequency of

illness between different populations and that substantial improvements are
possible if “. . . we are able to understand and control the general
environmental factors contributing to disease.”
Both the unequal distribution of illnesses within a given population and
the significance of the social environment have been shown by Hinkle and
Wolffs prospective studies of health and disease over a period of more than
twenty years. Working initially with a healthy, homogeneous population, they
found that episodes of illness were not randomly distributed; instead, the
most frequently ill 10 percent of the subjects experienced 34 percent of the
total sickness disability in contrast to the healthiest 10 percent who
experienced only 1 percent of the total sickness disability. The ill group was
also found to be accident prone. A positive correlation was discovered
between what was characterized as a “good attitude and the ability to get
along with people” and a low frequency of illness. No differences in the

childhoods of the two groups were found but the group with the highest
frequency of illness was characterized as “unhappy, insecure, discontented,
and with a large number of interpersonal problems.” The difference in the

rates of absence from work was hypothetically explained by the correlation
between the frequency of illness and both unfulfilled expectations and
perceptions of a stressful life.
The results from their extended work with five different populations
(100 Chinese immigrants, 76 Hungarian refugees, 1527 skilled workmen,

1700 semiskilled women workers in New York City, and 132 recent college
graduates) were remarkably similar to their earlier findings. Episodes of
illness were not randomly distributed among the members of any of the
groups; in each of the groups, during twenty years of adult life, 25 percent of
the members experienced approximately 50 percent of all the episodes of
illness. The healthiest 25 percent in each group experienced less than 10
percent of the total number of illness episodes. Furthermore, differences in

susceptibility to illness were not limited to any specific syndromes:
In every group the members displayed a difference in their susceptibility
to illness in general, regardless of its type, or of the causal agents
apparently involved. Thus, as the number of episodes experienced by an
individual increased, the number of different types of disease syndromes
that he exhibited increased also. Although a great many of these
syndromes might involve one or two organ systems, episodes of illness
were not limited to a few systems; instead, as the number of episodes of
illness experienced by an individual increased, the number of his organ
systems involved in disease increased also. Likewise, as the number of
episodes he experienced increased, he exhibited illnesses of an increasing
variety of etiologies. He was likely to have more “major,” irreversible and
life-endangering illnesses, as well as more “minor,” reversible and
transient illnesses. Finally, as the number of his “bodily” illnesses
increased, the number of his “emotional disturbances” and
“psychoneurotic” and psychotic manifestations (here categorized as
“disturbances of mood, thought, and behavior”) usually increased also.
These findings have been obtained consistently in each of these five

groups, regardless of the sex, race, culture, economic or social background,
environment or life experiences of the people studied.
Then Hinkle and Wolff found that their subjects had peak periods in
which the number of illness episodes appeared as clusters of different

syndromes, of varying degrees of severity, and from several etiological
sources. They concluded that “efforts to adapt to the social environment are
to some degree involved in the majority of all of the illness episodes that
occur among the adult population.” They emphasize that the state of the host
is only one determinant of illness, that a man’s susceptibility to illness is
influenced by “his relation to the society in which he lives and the people in
it.” Their studies yielded no evidence for labeling any special category of
disease as psychosomatic; instead, they think that all forms of illness are
influenced by reactions to life situations and the patient’s relation to his
environment.
Table 25-1. Frequency and Distribution of Psychosomatic Illness

AUTHOR YEAR PERCENT OF SAMPLE WITH
PSYCHOPHYSIOLOGICAL SYMPTOMS
General Populations
Hollingshead and Redlich 1958 7-13
Leighton et al. (Stirling 1959 59

County Study)
Srole et al. (Midtown 1962 60

Manhattan Study)
Pasamanick 1962 3-65
Surveys of Medical
Practice
Watts 1962 26.5 (Great Britain)
Crombie 1963 40
Kessel and Munro 1964 1.68 (Scottish town)
Finn and Huston 1966 20
Mazer 1967 30
African and Aboriginal

Societies
Leighton et al. 1963 84 (Yoruba)
Kidson and Jones 1968 1.4 (Australian aborigines)
Hinkle and Wolff found, therefore, that illnesses were unequally
distributed within the five homogeneous groups they studied. A look at the
epidemiology of psychosomatic disorders and psychophysiological symptoms
in a number of different populations in various parts of the world reveals
varying frequencies in different populations.
Frequency and Distribution
It appears that the frequency of psychosomatic illness, and particularly

psychophysiological symptomatology, has been rising since World War II. As
shown in Table 25-1, both epidemiological studies and surveys of physicians’
practices have shown that psychophysiological illness is a common affliction
(see references). In the Stirling County Study, the psychophysiological
symptom pattern turned out to be the most common, present in 59 percent of
the total sample. Of the respondents in the Midtown Manhattan Study, 60
percent had somatic complaints. In their study of psychiatric treatment

patterns in New Haven, Hollingshead and Redlich reported psychosomatic
reactions in 7-13 percent of patients in various social classes. In a survey of
Baltimore households, conducted in 1961, Pasamanick found a prevalence
rate of 3.65 percent for psychophysiological disorders.
In our epidemiological study of a southeastern county which is in the

throes of social change, we are finding that large numbers of people are ill
with various types of diseases. In a preliminary random community sample of
322 adults, 31 percent were rated as impaired according to our criteria of
social psychiatric impairment; 42 percent reported psychophysiological
illnesses; and 42 percent were rated as having some degree of physical illness
(27 percent mild and 15 percent moderate or severe).
Of the more than 1600 respondents in our major community sample, 7

percent reported that they had had peptic ulcers, 3 percent asthma, and 8.6
percent reported having had hypertension at some time in their lives. About 6
percent reported having a “nervous stomach,” 8 percent symptoms of
indigestion, and almost 10 percent headaches at the present time.
Physicians’ surveys also attest to the high frequency of psychosomatic
illnesses and psychophysiological symptoms. Finn and Huston’s analysis of
medical practices in Iowa disclosed that about 20 percent of the adults
consulting physicians had psychosomatic illnesses. In a study of psychiatric
conditions in general practice, Mazer reports that 30 percent of the medical

patients were diagnosed as psychophysiologic. Kessel and Munro’s summary
of surveys from Scotland, Australia, and London, and Watts’ study of general
practitioners in Britain report a great variability in one-year-period

prevalence rates in various communities, ranging from 1.68 percent in a small
Scottish town to 26.5 percent in Britain. Maintaining that a strict enumeration

of psychosomatic disorders in medical practice is misleading, Crombie
concludes that 40 percent of patients going to practitioners had mixed
organic-emotional illnesses.
These findings, notwithstanding variations in methodology and results,
illustrate that the prevalence of psychophysiological illnesses is a health
problem of substantial magnitude. Furthermore, evidence of the increasing
frequency of psychosomatic disorders, e.g., peptic ulcer, diabetes, and

especially coronary heart disease, indicates that these illnesses can be
regarded as epidemic, at least in Western societies.
It may be argued that this increase is more apparent than real because
the population at risk is larger for a number of reasons; e.g., many would have
formerly died early deaths from infectious diseases before antibiotics were
discovered. Spain, however, concludes from an analysis of vital statistics that
there is considerably increased morbidity and mortality from psychosomatic
illness, and that the base has moved toward younger age groups.
Early investigators believed that psychophysiological illnesses were

unevenly distributed throughout the world, prevalent in industrialized
societies, but relatively rare among primitives. Studies by Kidson and Jones,
Leighton, et al., and Seguin, for example, found great variability in primitive
societies, ranging from 1.4 percent in Australian aborigines to 84 percent in
the Yoruba in Nigeria.
With increasing industrialization throughout the world, parity may be
reached in terms of distribution of psychosomatic illnesses. However, data
concerning this distribution and particularly transcultural comparisons, are
difficult to evaluate and are obviously subject to erroneous interpretations
because the epidemiological task is complex and social psychiatry is in its
infancy.
Demographic Characteristics of the Afflicted
Age
Table 25-2 summarizes the findings of major epidemiological studies

with reference to age and psychosomatic disorders. Although psychosomatic
disorders do occur in children, they are generally considered to be afflictions

of adult life. The authors of the Midtown Manhattan Study found that
psychosomatic symptoms increase with age. However, they did not sample
subjects aged sixty and older. In our preliminary community study, we also
found a linear relationship up to the age of sixty; psychophysiological illness
was present in 37 percent of those under the age of thirty, 41 percent in those
between thirty and forty-four years old, and 51 percent in the forty-five- to-
fifty-nine age group. But in those over the age of sixty, the percentage with
psychophysiological illnesses dropped to 43 percent. It should be noted,
however, that most of our respondents over the age of sixty, about 80
percent, had physical illnesses of some type; as the percentage with
psychophysiological illnesses among the elderly diminished, the percentage
with physical illnesses increased. The elderly, as a group, are more and more
plagued by ill health. Harrington, in discussing “the golden years,”

paraphrases Yeats, “(This) is no country for old men.”
Table 25-2. Relationship of Age and Psychosomatic Disorders

AUTHOR YEAR AGE RESULTS
GROUP
Leighton et al. (Stirling County 1959 30-70 Increase with age

Study)
Srole et al. (Midtown 1962 All ages Increase with age

Manhattan Study)
Finn and Huston 1966 15-64 Increase with age

-15, 65 + Prevalence diminished
Pasamanick 1957 -15, 65 + Prevalence diminished
U.S. National Health Survey 1960 35-54 Highest incidence of peptic ulcer
in men
Mazer 1967 45 + Fewer psychophysiological

disorders in men
Earlier, Halliday suggested that a rising frequency of

psychophysiological symptomatology in younger age groups was evidence of
greater incidence of psychosomatic illness. He found that peptic ulcer affected
increasingly larger numbers of young people in Britain in the 1930s. He

contended that these age shifts were due to the accumulation of persons who
were predisposed to psychosomatic illness because of changes of
conditioning during childhood. Studies found somewhat lower
psychophysiological illness rates for the adolescent-young adult group and
the elderly group. This may indicate an inverse relationship between

psychosomatic illness and depressive illness, since the latter appears to be
increasing in these groups.
Sex
The male-female ratio for psychophysiological symptoms in recent
times has been reported by various investigators as 1 to 1, 1 to 3, and 2 to 3.
In our research with medical patients we found that women expressed
significantly greater dissatisfaction with their bodily parts and functions than
men. Although we were not attempting to delineate psychosomatic entities,
we concluded that women tended to somatize while the men were more
stoical. In our recent community study, 47 percent of the women were found
to have psychophysiological illness in contrast to 32 percent of the men.
Certain illnesses such as peptic ulcer and asthma were more common in the
men than in the women, while hypertension, for example, was reported
almost twice as often in the women than in the men.
Marked shifts in the sex ratio were described by Halliday as being

characteristic of psychosomatic disorders. Surveying this point historically,
he notes that there was a reversal of the sex ratio for both diabetes and peptic
ulcer from the nineteenth to the twentieth century. In the nineteenth century,
peptic ulcer, which Dragstedt has called “the wound stripe of civilization,”
was a woman’s disease, but it became primarily an affliction of men in the

present century. Halliday notes that “the official Medical History of the (First)
Great War did not even mention the term ‘duodenal ulcer’.” In the United
States, although more men than women suffer from peptic ulcer, the ratio has
changed in the last few decades from at least 4 to 1 to 2.5 to 1.
In our community study, 10.3 percent of the white men and 5.6 percent
of the white women reported having had peptic ulcer at some time in their
lives, but in the blacks this large sex differential was not present, i.e., 5.7
percent of the men reported having had peptic ulcers, as compared to 4.5
percent of the women. Coronary heart disease is much more frequent in men
than in women, at least 2 to 1, but the sex difference diminishes with
increasing age.
Data concerning the disproportionate sex ratios of various
psychosomatic diseases have been given sociocultural interpretations by
Halliday, Jennings, and others. Fluctuations in sex ratio probably reflect the
fact that social change does not exert a uniform influence on both sexes
simultaneously. On the contemporary social scene, as women move out of

their traditional roles to participate more actively in the occupational and
social fields previously dominated by men, they are exposed to added
stresses. During this transition, there is greater role conflict and ambiguity,
particularly for women. In fact, the “identity crisis,” which is being
conceptualized as a discrete illness entity for youth, may also have to be

applied to many women, at least to the career women and working mothers.
As they are subjected to role strain, susceptibility to both well-known and
newer forms of psychosomatic illness is likely to increase. Perhaps we will see
some convergence of differential psychosomatic sex ratios. But genetic and

endocrine, as well as social factors, are influential in determining different
reactions; even with comparable social stresses on both men and women, it is
likely that some disorders will continue to be more frequent in one sex than
in the other.
Social Class
Although Karl Marx once said that: “It is not the consciousness of men
that determines their being, but, on the contrary, their social being that
determines their consciousness,” and novelists from Dickens to Steinbeck
have described the misery of lower-class status, Hollingshead and Redlich’s
work called our attention to the inverse relationship between social class and
the prevalence of psychiatric illness, including the psychosomatic. Their
lower-class patients somatized complaints to a greater extent than did the
upper-class patients. Crandell and Dohrenwend, reviewing both the Midtown
Manhattan and Stirling County Studies, concluded that there is “a distinct
tendency for lower-class groups to express psychological distress in
physiological terms.” Table 25-3 summarizes the findings regarding social

class from a number of studies.
Most observers of our social scene have found that the lower class is
afflicted with a greater frequency of illness of almost all types. We found that
psychophysiological illness was much more prevalent in lower-income
groups, i.e., present in 52 percent of those with annual family incomes of less
than $3000 per year, and in 66 percent of those with incomes between
$3000-5999 per year; but the figure dropped to 25-30 percent in the higher-
income groups. A larger percentage of our lower-income respondents than

those with higher annual family incomes had physical illness and also more
lower-than higher-income respondents were rated as having social
psychiatric impairment. For example, 67 percent of those with annual

incomes under $3000 and 45 percent of those with annual incomes of $3000-
5999 per year had physical illnesses, in contrast to 21-30 percent of those
with annual incomes above $10,000. And 49 percent of those with annual
incomes of less than $3000 and 42 percent of those with incomes from
$3000-5999 were rated as having some degree of social psychiatric
impairment, but impairment rates declined to about 15 percent in higher-
income groups.
Table 25-3. Relationship of Social Class to Psychosomatic Illness

AUTHOR YEAR RESULTS
Hollingshead and 1958 Frequency of psychophysiological reactions inversely

Redlich related to social class
Leighton et al. 1959 Psychophysiological disorders more common in poorly

integrated communities
Stamler et al. 1960 High frequency of coronary heart disease in males in all
socioeconomic groups
Srole et al. 1962

Inversely related to class
Arthritis
Hypertension
Neuralgia
Positively related to class
Colitis
Hives
Hay fever
Other illnesses showed only erratic relationships with
class
Bell-shaped curve for hypertension
Pasamanick 1963 U-shaped curve for hypertension
Just a few years ago, Coles reported that the physical health of migrant
laborers “deteriorates early in life.” Comparisons of certain illness rates in

families with incomes under $2000 and those over $7000 reveal that heart
disease, arthritis, mental and nervous conditions, hypertension, and some
physical impairments are two to four times more common in the lower-
income group.
Race
Prior to World War II psychosomatic illnesses were believed to be
relatively infrequent in Negroes. However, Rowntree’s evaluation of 13
million selective-service registrants in World War II showed a “marked
increase in incidence of psychosomatic disease in the Negro, who in

peacetime appeared relatively immune.” Halliday, in 1948, astutely
recognized that the Negroes have always been a “second nation” within the
United States and he also noted that the incidence of psychosomatic disorders
in Negroes was rising abruptly. Death from hypertension is seven times more
common in nonwhites than in whites. This variation may be due to genetic
differences but, as Stamler has indicated: “The patterns of discrimination and
segregation which Negroes experience in the United States may induce

psychologic stresses, strains, frustrations, etc. These primary central nervous
system effects may be responsible for the greater occurrence of hypertension
in this racial group.”
We found that fewer blacks than whites reported a history of peptic
ulcer, but more blacks, especially the women, reported hypertension. Certain
symptoms such as headaches and no appetite, were reported more frequently
by the blacks, complaints of headache were particularly common in the
younger black women.
The work of M. Schwab on hallucinations points to the difficulty in
evaluating certain symptoms in black groups. Our preliminary community
study showed that hallucinations were reported about twice as frequently by
blacks than whites. In a small, southern, black community, she found that
reports of hallucinations among the blacks were limited primarily to elderly
men and young women. The elderly men’s hallucinations could be interpreted
as coping mechanisms since the themes centered on peaceful, religious topics;
in contrast, the young women’s hallucinations, usually filled with terrifying
themes, were regarded as evidence of psychopathology and personal distress.
The facts showing that there are greater amounts of illness of all types
in the lower class point to the plight of the nonwhites in the United States
today who comprise the overwhelming majority of the low-income families.
In our countywide study, we found that the higher rates of social psychiatric
impairment and poor physical health in the blacks were correlated with
poverty and little education. This correlation between lower social status and
illness has been found consistently in other studies.
Although the physical and cultural deprivation associated with being
poor and uneducated is apparent to observers of our social scene, we found
that social structural factors, such as low incomes, did not account completely
for the high rates of social psychiatric impairment in the young blacks.
Strikingly, 52 percent of the younger blacks were found to be impaired, as
compared to 33 percent of the whites. Comparative analyses for sex, age,
education, and income revealed that the high impairment rate in the younger
blacks was not as strongly related to low income as was true for the older
group.
We suggest that the young black adults have been exposed, during their
formative years, to the sociocultural change that has taken place in the last
two decades. In their youth they witnessed the turbulence of America in the
1960s, and participated in the struggles accompanying desegregation. But
their opportunities were limited for sharing in the life styles and material
benefits of the wider society displayed by the media. At the same time the
protective traditional cultural patterns of the Southern blacks were being
assailed on two fronts, i.e., subordinated and exploited by the dominant white
society on one hand and challenged and repudiated on the other by groups
stressing African heritage and black power and scorning the former
accommodations to the caste system.
Some of the blacks, e.g., the younger age group, can be seen as
experiencing a conflict between competing sets of conditioned responses,
such as parental restraints on assertion and aggression versus growing
emphasis on pride in individuality and ethnicity. Such a situation produces
cognitive dissonance and the dilemmas of the “marginal man.” Marginality, a
concept developed by Park and elaborated by Stonequist, describes persons
caught between two different and often antagonistic cultures. Spiritual

instability, intensified self-consciousness, restlessness, and malaise were
noted by Stonequist as characteristic of the “marginal man.”
But some changes in the social position and the health of the blacks can
be expected as the nonwhites follow various paths to alleviate their distress.
Within the decade of the 1960s, the nonwhite social scene changed rapidly.
This group, once sociologically perceived as a homogeneous subcultural
entity, is composed now of diversified groups, socially stratifying within
themselves as they develop new ideologies and allegiances. We now see four
different patterns in the black population: (1) the militant separatists; (2) the
nonviolent protestors; (3) those moving toward middle-class status; and (4)
the poor, apathetic group. The Negro who is attempting to obtain a share of
the goods of middle-class America by adopting the dominant white value
system frequently becomes psychosomatically ill in following this path. The
apathetic group, analogous to Marx’s “Lum-penproletariat,” will probably

continue to have at least as much illness as always, unless the caretaking
functions of the government intervene. What will happen to those who are
expressing their current discontent—both the aggressive separatists and the
nonviolent protestors—remains to be seen.
The “second nation,” the nonwhites, therefore, is rapidly becoming one

composed of groups. We would expect, then, to begin to see differential
manifestations of psychosomatic disorders within these groups as they
become increasingly heterogeneous.
Changing Patterns of Susceptibility and Illness
Many observers of our medical scene have repeatedly maintained that

there are continuing changes in both individual and group susceptibility to
psychosomatic as well as to other diseases. These may be attributed in part to
sociocultural transformations. Many changes in types of disease have

occurred within our lifetime. For example, tuberculosis, once a scourge, has
declined drastically throughout the Western world. This decline paralleled
higher living standards. However, a rise in tuberculosis has been noted in the
ghetto population of New York in the last few years.
Some other infectious diseases, considered to be under control a few

years ago, are reappearing as public-health menaces. Recent outbreaks of
diphtheria, typhoid fever, and poliomyelitis can be traced to deteriorating
public-health standards and facilities relative to the increased population,
crowding, and migration, and to apathy resulting from overconfidence in the
belief that immunizations and other precautions are no longer necessary. But
the sharp rise in VD rates is probably one of the clearer examples of
psychosocial influences. The massive movement of young men to and from
Southeast Asia for a decade and the emergence of penicillin-resistant strains
of gonococci are only in part responsible for the increasing frequency of

gonorrhea in the United States today. Numerous complex social and cultural
processes have been converging to facilitate the spread of this disease. One of
the most noticeable is the change to freer sexual mores. But this is only one
aspect of a vast mosaic which includes the intergenerational conflict, with
protesting youth living in communes and at times openly practicing
polygamy, or even androgyny, as they reject the establishment’s values.
Moreover, promiscuity among adolescents and the large numbers of divorces

even among the middle-aged reflect the changing social structure. The
technological triumph represented by the pill may be the significant factor
underlying the changes on the social scene which are linked to the spread of
venereal disease.
Although changes in the incidence of carcinoma are still enigmatic, they

may be related to dietary and smoking habits. Carcinoma of the stomach is
now rare, while carcinoma of the lung has become prevalent. Quisenberry
believes that ethnic variations in distribution and types of carcinoma in

Hawaii are due to sociocultural forces, as well as genetic factors, but that with
increased intermarriage and integration, the epidemiological picture will
become more uniform.
Increased susceptibility to psychosomatic disease is taken for granted
as a hazard of urban and suburban living. Cities, of course, have been
regarded historically as sources of illness as well as social evil. In The Prelude,

Wordsworth described urban distress with the words: “Among the close and
overcrowded haunts/Of cities where the human heart is sick. . . .”
Today, psychosomatic illness may be considered one of the American

“crowd diseases,” particularly among the mobile population. Stamler points
out that hypertension is much more common in Negroes who have moved to
urban centers. In their epidemiological studies of hypertension, Geiger and

Scotch note a tendency toward high blood pressure in urban groups.
In many respects most of the world is being westernized, at least in

terms of urbanization and technological change. In Nigeria, for example,
Leighton et al. found a higher incidence of psychophysiological illness in

towns than in villages. Scotch’s comparative study of Zulus in rural and urban
settings confirms these findings. Seguin has described a marked increase in

psychosomatic illness among Peruvians who migrate from the Sierra to the
cities of the plain; according to him, they are undergoing “psychosomatic dis-
adaptation.”
Malzberg found that mental illness was more common among Negroes
who migrated from the South to the North, than among those born there. In
our preliminary county study in the Southeast, we found the highest rates of
social psychiatric impairment (including psychophysiological illnesses)
among the “hypermobile,” i.e., those who had moved nine or more times in
the last ten years. The lowest rates were found in those who had moved only
four to eight times during the last ten years.
More than a century ago, De Toqueville remarked that the Americans
were restless in the midst of their prosperity: “A man builds a house in which
to spend his old age, and he sells it before the roof is on ... he settles in a place,
which he soon afterwards leaves to carry his changeable longings elsewhere.”
(Italics ours.) That restlessness may be an American trait, but if so, it appears
to be intensifying with contemporary social change. We found that mobility
was associated with low rates of social psychiatric impairment when it was
not carried to the extreme of hypermobility. Geographic mobility demands
changing life styles affecting interactions with relatives and friends; especially
for whites, it involves minimizing if not severing reliance on kinship
networks. For our mobile, low-impairment group, it appears that the social
interaction necessary to maintain adequate mental health is provided by the

rapid acquisition of new friends whose life styles are similar or compatible.
Our initial findings on mobility are in keeping with Kantor’s conclusion
that there is no simple, direct relationship between migration and mental
illness. Adjustment to migration, she found, varies with: (1) the individual’s
social characteristics, attitudes toward moving, and preparedness; (2) with
the sociopsychological aspects of the situation; and (3) with the

characteristics of the sending and receiving communities. With the “National
Incorporation of the South,” the new elite is at home in Suburbia, U.S.A., in the
North, South, East, or West.
Not only are patterns of illness changing but new forms are emerging
and others are disappearing. Syncope, once an appropriate social response,
now occurs rarely. Of 1628 respondents in our community study, only eighty
stated that they had ever fainted and only seven men and one woman
reported that they had fainted during the preceding year. Schulte maintains
that fainting is not an adequate form of emotional discharge in our more
complex society in which a wide variety of psychophysiological
cardiovascular disorders occurs. With the widespread prevalence of coronary

heart disease, complaints of chest pain communicate distress and ensure that
the sufferer will receive sympathy and medical attention. We could view
syncope as a conditioned social response in the nineteenth century,
particularly in Victorian Britain, and chest pain as its equivalent in our

current era.
Accident proneness is an everyday phrase, understood by laymen as
well as professionals. Smart and Schmidt’s finding that ulcer patients had
more traffic accidents per capita than the general driving population supports
Halliday’s thesis regarding the association of psychosomatic affections. Also, a
rising frequency of posttraumatic neurosis, in Modlin’s terms, the

postaccident syndrome, appears to be directly related to our rapid social and
technological expansion. Modlin described the patients exhibiting this
syndrome in both social and medical terms; they are integrated into society
before the trauma but, in reality, they cannot adapt to the rate of
technological change. After the accident they cannot cope because of limited
“intrapsychic capacities which, in a crowded world of swift mobility,
precipitant crises, and incredibly intricate technological innovations, render

them disablingly vulnerable to the inevitable hazards of living in such a
world.”
The most common type of psychophysiological reaction that we see in
our Psychiatric Consultation Service at the University of Florida does not have
a label, indeed it is difficult to define as an entity. These are the “garden
variety” medical patients equivalent to those whom Von Mering and Earley
call the “problem patients” in medical practice. A typical patient complains of
numerous conventional and occasionally bizarre somatic complaints; his

diagnostic workup may reveal minor or borderline abnormalities; he appears
both anxious and depressed; and when questioned, he tells of interpersonal
difficulties, discontent, frustration, and despair. The patient’s personal
problems are often compounded by the effects of medications, drugs, and
alcohol which he has taken in an attempt to alleviate his distress with life and
enable him to cope with the complexities of everyday living. Such patients,
who, in von Mering and Earley’s words, display “undifferentiated health
aberrations,” are becoming more and more numerous throughout the
Western world.
Exotic diseases such as those produced by voodoo and hex, formerly
treated only in isolated areas by root workers and witch doctors, are now
seen in Negro migrants to ghetto areas. Ellul, in The Technological Society,
tells of a new disease, “brought on by modern city life . . . which might be
called urbanities.” During the 1960s, a number of reports of epidemic hysteria

appeared.
Relationships
The psychosocial relationship of social factors, such as income levels, or

cultural habits and customs, to health or illness is, of course, debatable. But
certain relationships between the social environment and either health or
illness have been established. In their review of more than forty different
studies, Dohrenwend and Dohrenwend conclude that “low socioeconomic

status within a community is consistently found to be associated with
relatively high overall rates of (psychological) disorder.”
Whether the high rate of illness in low-income groups is due mainly to

genetic factors, “drift” down the social scale, or causative social processes, is a
major unanswered question. But the climate of poverty does include
crowding, contact with the noxious and the infirm, nutritional deficiencies,
physical and cultural deprivations, and often a quality of despair, if not

desperation.
Sociocultural deprivation, as well as physical deprivation, appears to

influence health and illness. Thoroughman and Pascal showed by both
retrospective and prospective studies that ulcer patients with intractable
symptoms who scored high on a scale for environmental deprivation
responded poorly to surgical treatment. In East European countries,
deprivation is also a concern for research. For example, Mester and Mester
reported from Budapest that surgical success for the treatment of biliary
disease is less frequent in patients who come from large poor families.
Chertok et al. and Destounis concluded that economic difficulties were
possibly responsible for vomiting in pregnancy.
The frequency of object loss preceding many illnesses has been related
to socioeconomic changes. Mutter and Schleifer found that object loss
frequently preceded the onset of physical illnesses in children and that in
many, family disorganization was rampant. They concluded, “. . . changes in
the psychosocial setting interacting with the psychological and social
organization of the child and his family are relevant to the onset of somatic
illness in children.”
Animal studies show clear-cut relationships between the social
environment and various types of illness and disorder. Rats separated from
their mothers early in life were found by Ader and Friedman to have a higher
mortality rate from inoculated carcinosarcoma cells than did controls. Henry
et al. found that mice socially stressed by aggregating and mixing responded
with hypertension. Calhoun’s classic study of the overpopulation of rats in a

confined area demonstrated that crowding is associated with higher mortality
rates, prematurity, and massive disorganization.
Principles of psychosocial medicine hold that man and his environment

(which is now almost exclusively a social, man-made environment) are
inseparable, interacting, and mutually influential. Thus, sociocultural
processes, role functions and expectations, the personality and the self, with
its instinctual and social needs, comprise a mutable, complex system. From
this point of view, it is difficult to speak about exact etiological factors,
especially as constants over extended periods of time, since the entire system
is an interacting one, and we are always in the midst of social change and
culture lag. Moreover, the epidemiology of psychosomatic and mental
disorders is still in an embryonic, but developing, phase. In view of the lack of
sound, descriptive epidemiology, inferences about etiology may be
premature. Psychosocial medicine does consider that health and illness are
relative conditions on a continuum, that they reflect the social-self system and
that groups, as well as individuals, exist in varying states of health and illness.
Halliday developed the concept of a psychosomatic affection as an

illness produced by multiple etiological factors and also as one which is
characterized by “a synergy of causes” (italics ours). He proposed an
ontogenetic theory of psychosomatic affections which was grounded on the
“progressive unfolding of a ‘life’ in historical time in accordance with the
orderly mode of development characteristic of its species.” Particularly
during the stages of infancy both the physical and emotional development of
the child depend upon approval and disapproval by others, freedoms and
frustrations, adaptations, and defenses, which are eventually woven into
patterns of psychobiological reactivity that relate to health and illness.
In his Concept of a Sick Society, Ollendorff asserts that: “Society as a
whole is fundamentally responsible for the phenomena which are reproduced
in every human being.” He emphasizes, in Reichian terms, that character

formation occurring in infancy and childhood results from “. . . the endless
process of structuring as promoted by the impact of society as a whole.” Thus,

the influence of society is seen fundamentally as being much greater than that
of the immediate family, which can be viewed as just a more or less faithful
transmitter of the prevailing social forces. Ollendorff also notes that character
formation too frequently involves the development of character armor as a
result of the prolonged series of incessant bombardments to which the infant

and the child are exposed.
Brody notes that in Western cultures there is an oversocialization of

middle-class and undersocialization of lower-class children, particularly in
terms of expression of feelings, training for identity, and communication. He
thinks that the underprivileged group should be evaluated in terms of
“multiple impairment” and “cultural exclusion,” referring to those who do not
have the “opportunity to share fully in the symbolic experience of the
society.”
The child-rearing practices employed by groups may be the vital
determinants of psychosocial health or illness. Hippocrates’ observations on
the manner in which the Scythian children were reared and its relationship to
the sexual and menstrual disorders in adult life, therefore, presage the tenets
of modem social psychology and social psychiatry.
Halliday related the changes “in the worlds of the child and of the adult
that took place between the 1870s and the 1930s in Britain” to changes in the
incidence of various illnesses. Hysteria, common in Victorian England and
frequent among enlisted men in the British Army in World War I, was seen
much less often during World War II. Halliday describes the physical
environment of the infant in the 1870s as appallingly bad; lack of sanitation,
overcrowding, poverty, etc., led to high rates of bodily impairment and infant
mortality. But viewed psychologically, he emphasizes that infants and young

children were allowed a great deal of freedom; babies were breast fed, carried
in the arms or swaddled (the perambulator first appeared only in the 1880s
and was owned only by the wealthy); toilet training took place “in its own
good time.” The “vital drives” of early childhood were not inhibited; Halliday
associates these child-rearing practices with fewer physiological
dysfunctions. But he also notes that the frustrations imposed on the older
child during the Oedipal period, and the problems with the patriarchal father
were probably responsible for the high incidence of hysteria.
In contrast, the infants reared in the 1930s were fed from bottles
according to schedule; “the ‘infant in arms’ had become the ‘kid in the
carriage’ ”; bowel training was instituted early and thoroughly. Since there
were fewer children, they were more noticeable and thus more closely
watched and controlled. The family was based on the parental dyad.
Physically, the environment had improved so that the infant mortality rate
had fallen drastically. But psychologically, Halliday thinks that the imposed
system of conditioning in child-rearing practices was conducive to
physiological dysfunctions which became psychophysiological illnesses in
later life. Furthermore, he notes that the stern father of the 1870s became the
“daddy” in the 1930s, and that this also may be in part responsible for the
decline in the incidence of hysteria.
Presciently, Halliday pointed out that certain changes in the world of the
adults between the 1870s and the 1930s were also conducive to the
development of the obsessive character type who was afflicted with
numerous tensions and physiological dysfunctions. Many of these changes,
which Halliday described in the 1940s, became the cries of alarm heard in the
late 1960s. He described them as: (1) increasing separation from the outward
roots in Mother Earth; (2) increasing disregard of cosmic and biological
rhythms; (3) increasing frustration of manipulative creativity; (4) increasing

pace of change in the structure of society; (5) increasing standardization and
repression of individual expression; and (6) increasing absence of aim and
direction.
Halliday compared the indices of communal physical health (general
death rate, infant-mortality rate, and certain infectious disease rates), which
declined between 1900 and 1939, with indices of communal, psychological, or

social health (infertility rate, suicide rate, certain psychosomatic-illness
rates), which rose sharply between 1900 and 1939, and concluded that Great
Britain was a “sick society.” He attributed the psychosocial illness which
afflicted Great Britain and which was present elsewhere in Western societies
to the “failure of the integration of the social group (which) is attended by
failure of integration of the ‘psychoneuroendocrine system’ of its members.”
He stated that “the ‘causes’ of the weakening of those ‘psychological bonds

that enable the members of a community to live and work together’ are
therefore to be sought in the ‘causes’ that disintegrate social patterns in such
a manner and to such a degree that the social equilibrium of the community
cannot be restored.” He regarded social disequilibrium as the first stage of

functional breakdown which is succeeded by social disintegration with a
further weakening of the psychological bonds necessary for health.
As theorists of social change maintain, the causes of social
disintegration may be produced by external forces, e.g., defeat in war, or from

inner tensions, e.g., class conflict, or from decay as a natural phase of its life
cycle. Halliday believed that the accelerated changes concomitant with the
industrialization of Great Britain in the nineteenth century brought about

rapid changes in family, religious, cultural, occupational, and economic
patterns so that the “total social system became changed at an ever-

accelerating rate, until a point was reached when the national equilibrium
was so seriously upset that disintegration set in.” How social disintegration
affects individuals or groups to produce illness, of course, has never been
precisely determined. The Leightons correlated increased psychiatric illness
with community disintegration in the Stirling County Study. They postulate
that sentiments are a bridging concept for analyzing relationships between
the sociocultural environment and mental health or illness. Of particular
importance are the “essential striving sentiments” which concern physical

security, sexual expression, giving and receiving love, spontaneity, a sense of
orientation in relation to society, of belonging to a moral order, etc. Thus,
“sociocultural situations can be said to foster psychiatric illness if they

interfere with the development and functioning of these (striving) sentiments,
since the latter, in turn, affect the essential psychical condition.” Therefore, an
individual reacts to a disturbance in the essential psychical condition “. . . by
seeking to remove the disturbance. When the process of this removal is
inadequate (maladaptive to the personality), this fact is manifest in symptoms
and impairment. . . . Symptom formation, however, is not the inevitable

outcome.”
A number of models have been developed, but not tested, which relate
sociocultural processes to the self. As evidenced by the work of Parsons,
Goodenough, and Thomas and Bergen, these models emphasize the
importance of role theory and focus on the influence of role expectations, role
participation, and role strain as determinants of behavior which have

implications for psychosocial health and illness.
In Toward a General Theory of Action, Parsons proposes an overarching
series of constructs which embrace personality and society. He emphasizes
that the personality and society are systems and that role participation is at
the boundary, linking the individual personality and society: “One particular
crucial aspect of the articulation of personality with the social system is the
organized system of interaction between ego and ‘alter’ based upon role
expectations.” Parsons refers explicitly to the degree of integration or
disintegration being, in effect, located at the points of articulation of the
personality and social systems. Thus, role expectations and role participation
are subject to strain when there are sufficient dislocations in the social
systems or disturbances within the personality. Parsons’ concepts have
implications for health and illness, indeed, for societal conflicts. He states
that: “The group of problems centering around conformity, alienation, and
creativity are among the most crucial in the whole theory of action because of
their relevance to problems of social stability and change.”
In Rethinking Status and Role, Goodenough distinguishes between

personal identity and social identity. He insists upon flexible and dynamic
concepts of status and role which emphasize the importance of boundaries

and identities for the health of individuals and groups. In her book, Purity and
Danger, Mary Douglas describes, from an anthropological perspective, the

significance which certain groups have placed on boundaries as necessities
for ensuring societal integration and cohesion.
Thomas and Bergen propose a model which relates social change to
psychological malfunctioning. Social processes define roles and role
expectations; personality organization at several levels mediates between
role expectations and the instinctual and social needs of the self. Social roles,
particularly expectations, embody approval and disapproval in our
interpersonal relationships, and elaborated rewards and strains. Tensions
and strains become particularly visible when roles and barriers diffuse, when
values shift, and when the rate of social and culture change accelerates.
Furthermore, Thomas and Bergen maintain that social and culture change
affect the way an individual expresses the needs of the self, either by
approving or by limiting the number and the modes by which the needs of the
self are expressed. Either way, sociocultural processes require flexibility and
changes within the personality organization in order to reduce tension within
the group, within the social-self system, and/or within the individual.
At least implicitly, these schemata which attempt to explain how the
social environment influences health or illness equate illness with

maladaptation or see it as the result of stress. Equating illness with
maladaptation, basically a Darwinian concept applicable to evolution, runs
the risk of being tautological. Furthermore, we should be aware of

Kluckhohn’s appraisal of adaptation as applied to social man: “We require a
way of thinking that takes account of the pull of expectancies as well as the
push of tensions, that recognizes that growth and creativity come as much or
more from instability as from stability, and that emphasizes culturally created
values as well as the immediately observable external environment.”
The stress-strain model of illness, which uses a metaphor from a
simpler mechanistic era, suggests an essentially mechanical relationship

between man and the environment. As explained by Langner and Michael in
The Midtown Manhattan Study, noxious, or potentially noxious, factors
constitute stress, and the reaction to the stress is termed “strain.” They
compare to a situation in engineering, in which a structure is tested by

subjecting it to induced stress (e.g., tension, compression, etc.). The object
may become deformed under such stress. This reaction—the deformation—is
strain. Then, in reference to humans, they say: “We know that personality, the
sum of a person’s relatively reliable ways of acting and reacting, can become
deformed because of stress.”
Langner and Michael recognize the limitations of this model: “People

are not wooden beams or iron bars.” Instead, humans are unpredictable; they
symbolize, attach meanings to objects, situations, etc., and react to those
meanings or ideas. “It is primarily this capacity of man to symbolize that turns
a similar event into a catastrophe for one and a blessing for the other. If ‘one
man’s meat is another man’s poison,’ how can we define stress in terms of the
stimulus rather than the reaction? We can make some generalizations about
what stress is because there are cultural and societal uniformities of ‘meat’
and ‘poison’ that are somewhat broader than the individual variations.” Some
factors, constitutional, physical, and emotional, mediate between stress and
strain to determine whether the outcome for a given individual will be health
or illness. Socioeconomic status, for example, can be viewed either as a factor
which is potentially stressful (e.g., poverty) or as one which mediates
between other types of stress and strain (e.g., affluence).
In terms of the stress-strain model, illness, or simply symptoms, are
seen as reactions to noxious environmental forces. This is a useful frame of
reference, especially for the study of fairly large populations, i.e., symptoms
would be most common in the groups which are under the most stress,
subject, of course, to elaborate mediating factors.
During the last few years, scales have been developed which evaluate
the number, kinds, and significance of life events which are associated with
the onset of disease. These scales are based primarily on the work of Schmale
and others in the Rochester group which related object loss to the onset of
physical and/or mental illness. The theoretical construct is based on the
assumption that certain life events, usually considered to be adverse, are

stressful and thus require psychological and social readjustments.
The most widely used is The Social Readjustment Rating Scale of
Holmes and Rahe which contains forty-three items “indicative of the life style
or of the kinds of events occurring in the individual’s life . . . [which] involve
an adaptive response on the part of the person affected.” The forty-three
events range from death of spouse, divorce, and marital separation to a
change in eating habits, vacation, and minor violations of the law. Each item is
weighted in numerical Life Crisis Units (LCU)—death of spouse receives 100
LCU, while a minor violation of the law receives eleven LCU. Thus the subject
receives a total score; higher scores ostensibly reflect greater stress and have
been found to be associated with illness and presumably “high risk.”
Paykel and his colleagues at Yale have also developed a life-events scale
which contains thirty-three items which are comparable to those in The
Social Readjustment Rating Scale. In a controlled study, they found that
depressed patients had a general excess of life events before the onset of
depression. Moreover, the depressed patients had significantly more losses or
exits from the social field than the control group, who, in contrast, reported
more entrances into the social field.
Both of these scales are being standardized with minority groups and
used in cross-cultural epidemiological investigations. Their simplicity and
ease of scoring are attractive features. But, an event that is defined by one
individual as adverse, or even catastrophic, may be regarded by another as a
relatively minor, meaningless, or even fortunate occurrence, depending on his
“definition of the situation.” The common use of these scales, however, yields
precise information about the relationships of life events to illness and thus
adds to our knowledge about the stress-strain model and, particularly, the
significance of the social environment in health and disease.
The various models which relate psychosocial processes to illness in the
individual and the group can be criticized for the risk of being tautological,
because they are so all-inclusive that they cannot be adequately tested, or
because they ultimately fall back on Thomas’ definition of the situation. He
asserted that: “Preliminary to any self-determined act of behavior there is
always a . . . definition of the situation . . . gradually a whole life-policy and the
personality of the individual himself follow from a series of such definitions.”
This is a fundamental tenet of social psychology and how the situation is

defined accounts for individual variation. Moreover, Thomas emphasized that
there is “always a rivalry” between the individual’s spontaneous definitions
and the definitions of situations furnished him by society.
When carried to its logical extreme, this thesis, with its emphasis on the
individual, appears to contradict concepts of psychosocial medicine which
emphasize group reactivity in response to socioenvironmental stresses.

Moreover, the thesis cannot explain such undisputed facts as epidemics. But
we should not dismiss Thomas’ insights so quickly; particularly in our

contemporary era when we are witnessing sociopolitical polarization and
group coalescence, subject to the impact of instant visual communication, we
can postulate that shared definitions of a situation account for collective
behavior, epidemics, etc.
The studies of Hinkle and his colleagues of relatively large populations
demonstrate that the “reaction of a man to his life situation has an influence
on all forms of illness.”
Other studies have shown that even a single adverse event such as real,
threatened, or symbolic object loss, as presented by Schmale, Adamson, and

others, or bereavement as shown by the work of Parkes, is followed by illness
of various types and severity. Furthermore, in a theme that reminds us of
Halliday’s concept of a psychosomatic affection as one having multiple
etiological factors and one which is characterized by a synergy of causes,
Christenson and Hinkle state that the interactions between man and his
world are so complex “. . . that it is a gross oversimplification to attempt to
explain 1 or 2 of their categories of illness simply on the basis of the way that
they ate, how much they smoked, what happened to them in their childhood,
or the way that they react to their present occupations.” This point of view
about etiology is emphasized by Stallones in his editorial on community

health. He deplores a reductionist approach, advocates a “synthetic systems-
oriented approach” to the study of illness, and exhorts us to be concerned

with “clusters of causes and combinations of effects.”
A general systems approach, expressive of the metaphors of our
technological era, has become a fashionable way to view man and the
universe, to try to comprehend man and his ecosystems. Such an approach
states explicitly that the systems, biological, social, and even cosmic, are open
ones. But Abelson, in an editorial in Science commenting on D. H. Meadows et
al., The Limits to Growth, reminds us that to some extent, “the concept of earth
as a closed system is an appealing one, and in some respects it is valid.”
In addition to considering the evidence which indicates that we are
dealing with closed systems, e.g., the quantities of oxygen are limited, among
certain animals overpopulation leads to social disorganization or death, and
our cities decay after reaching a certain size, we should keep in mind Hinkle’s
statement about taking “a unitary view of the man-environment relationship”
and abandoning “the needless dichotomy of a ‘physical’ and a ‘social’
environment.” Moreover, in discussing the relationship between the internal

and external environments, he compares biological and social organizations.
Just as individual cells or organs are sacrificed to maintain the organism, “the
lives of individual men are subordinated to the requirements of the societies
of which they are members.” He points out that social groups behave “as if the
primary duty of the individual is to fulfill the various social roles in which he
finds himself.” Thus, Hinkle stresses the importance of role functions and
expectations in our modern society and he foretells that: “In the future we can
expect that no small part of human illness will be determined by the
interaction of men with other men, and by their adaptations to the social roles
that are thrust upon them.” This unitary concept of man and his environment,
the reaffirmation of Spencer and Durkheim’s view of society as a living

organism, and the focus on social roles as determinants of health and illness,
make a strong case for the increasing relevance of psychosocial medicine in
our contemporary era. Our epoch has already been described by Allen
Wheelis as The End of the Modern Age; with the discoveries in theoretical
science, dating from Niels Bohr’s work on the structure of the atom in 1917, it
appears that the principle of uncertainty is just as applicable to the movement
of an electron as it is to the vicissitudes of ordinary existence for human
beings. The dire conclusions drawn in The Limits to Growth indicate that we
are, indeed, creatures whose biological, social, and other systems are not only
closed ones but may be finite. This acknowledgment is implicit to the
concepts of psychosocial medicine.
This discussion of the relationships between social processes and
psychosomatic illnesses from a psychosocial point of view has centered on
many aspects of current social-science theories, particularly role functions
and expectations, and the stress-strain model of illness, as well as the concept
of adaptation. However, the presence of new epidemics such as coronary
heart disease and the recurrences of epidemic hysteria compel us to consider
contagion as a possible mechanism for transmitting psychosocial illnesses.
Contagion and Epidemics
In his classic work, The Epidemics of the Middle Ages, Hecker described
behavioral and psychosomatic disorders as well as diseases such as the black
death. He tells that the dancing mania “was propagated by the sight of the
sufferers, like a demoniacal epidemic over the whole of Germany and the
neighboring countries to the northwest, which were already prepared for its
reception by the prevailing opinions of the times.” This strange affliction,
characterized by wild dancing, screaming, bodily distortions, mental
aberrations, abdominal pain, and even convulsions, affected entire

communities between 1374 and the beginning of the seventeenth century.
Hecker reports that at one time it affected 500 inhabitants in Cologne and
that once the streets of Metz were filled with 1100 dancers. In discussing the
causes of this “mental plague,” he mentions that the wretched and oppressed
populace had been subjected to great natural disasters, famines, and the
“incessant feuds of the barons” which resulted in miserable conditions, club
law, and the corruption of morals. Furthermore, Hecker maintains that the
disposition of mind, peculiar to the Middle Ages, accounted for the long
duration of this “extraordinary mental disorder.”
In Italy, tarantism prevailed as a great epidemic in the fifteenth and
sixteenth centuries. The predominant symptoms were melancholia, weeping,
death resulting from paroxysms of laughter or tears, diarrhea, and a
sensitivity to music. In fact, dancing to the tarantella relieved the symptoms.
Hecker believed that these strange disorders, as well as the mass outbreaks of
hysteria which he described, spread by “morbid sympathy” until they became
real epidemics. He states that “imitation—compassion—sympathy, are
imperfect designations for a common bond of union among human beings—
for an instinct which connects individuals with the general body.” Thus, in the
midst of societal disintegration, these strange diseases were spread “on the
beams of light—on the wings of thought.”
Although we would like to explain psychosocial illness by scientific
theories, we cannot entirely dismiss the part played by sympathy and

contagion. There is some evidence that psychosomatic illnesses spread by
interpersonal contagion. Winkelstein, as cited by Spain, investigated the
household aggregates of hypertensive patients, composed of both blood-

related and nonrelated persons. The blood pressures of the nonrelated
persons in these “hypertensive” households were higher than those of

controls.
In 1955 an epidemic occurred at the Royal Free Hospital in London.
Over 300 staff members became ill with severe malaise, slight fever, the
subjective features of hyperventilation, and both evanescent and bizarre
neurological symptoms which often followed a glove and stocking
distribution. The term “benign myalgic encephalomyelitis” has been applied
as a diagnosis to about fifteen such outbreaks. McEvedy and Beard have
reviewed these epidemics and conclude that they are psychosocial

phenomena which should be termed “myalgia nervosa.”
In 1943 Schuler and Parenton, in reporting on an epidemic of hysteria in

a Louisiana high school, noted that descriptions of such phenomena were
abundant in the medical literature in the nineteenth century but that
publications on the subject had become rare; in fact, they could not find “a
single publication in the United States for over 40 years.” They concluded that
the “phenomenon of the ‘mental epidemic’ is not exclusively historical, nor is
it confined necessarily to ignorant and backward populations.” In 1958,

Taylor and Hunter described an epidemic of hysteria which occurred on an
open hospital ward among female patients who suffered mainly neurotic and
psychosomatic symptoms. Since then, mass hysteria associated with fears of

having been bitten by insects was reported among the workers in a textile
plant in South Carolina in 1963.14 This is reminiscent of the epidemics of

tarantism in Italy during the late Middle Ages, when the victims imagined
they had been bitten by tarantulas.
During the 1960s a number of outbreaks of epidemic hysteria were

reported in the United States and Britain, particularly among high school
students. Comparable epidemics have also been reported in nonwestern
nations such as Taipei and East Africa. In discussing these mass outbreaks,
Jacobs emphasizes that the “social and cultural contexts are most important
in defining why they take place when they do and where they do . . . .” Other
authors such as Kagwa refer to the basic similarity of such affections, “in man
at different psychosocial developmental levels regardless of race or locale.”
Redl has indicated that an occurrence of contagion does not occur
unless there are restraints to be reduced. This insight helps to explain that
epidemics occur not only at times when unfavorable social conditions are
conducive to the outbreaks, but also at times when repression is manifest.
From this point of view, the epidemics of hysteria in the Victorian Era can be
seen as miscarried revolts against the sexual repression of that time. We are
concerned about the increasing sociopolitical repression in the United States
today which may lead psychosocially to mass outbreaks of various mental
and behavioral phenomena.
Drawing on the works of these writers since Hecker’s day, we can also
note that, in addition to social restraints and repressive forces, adverse
conditions of life and a certain disposition of the mind are conducive to

epidemics. Taylor and Hunter explain that, “It often requires the adoption of a
particular idea by a pluralistically stirred group before the accumulated

emotions can be freely expressed. This idea will then appear to have been
‘infectious’ and to have aroused ‘collective’ emotions.”
The high acceptability ratings given by various study groups to illnesses

such as ulcer, arthritis, asthma, diabetes, and heart disease, relative to the low
acceptability ratings for tuberculosis, alcoholism, and mental illness in
Tringo’s study can be interpreted as evidence that we are a psychosomatically
oriented society. Moreover, it was explained that the psychosomatic illnesses

were acceptable because of their high frequency and “lessened shock value.”
The increasing incidence of coronary heart disease indicates that it has

now become an epidemic of immense proportions. Mathers and Eliot point
out that 500,000 Americans die every year from ischemic heart disease and
the latest figures indicate that 675,000 persons will die from coronary heart
disease in 1974. Harris states that: “We are again in the age of the great
pandemics. Our plague is cardiovascular.”
The shift of the age base to younger groups is further evidence that this
disease is now epidemic; for men between the ages of twenty-five and forty-
four, the death rate from coronary heart disease has risen from forty-six to
fifty-two per 100,000 between 1950 and 1972.
Ironically, Hinkle notes that this disease appears to be “the outgrowth of
several features of our society that we regard as most desirable.” These
include a high standard of living with an abundant diet which is rich in fat and
protein, a highly developed technology which reduces the demand for

physical labor, a longer life expectancy with continued exposure to the
abundant diet and lack of exercise, social mobility with its demands for
alertness, and cigarette smoking to relieve consequent anxieties and tensions.
In a comprehensive review of over 160 papers dealing with the
psychological and social precursors of coronary heart disease, Jenkins has

come to the following conclusions: Seven general categories of social
psychological factors can probably be considered as correlates of this illness.
Although no consistent relationship has been observed between a single

social-status index and coronary heart disease, status incongruity or
inconsistency (discrepant levels of occupation, education, and income for an
individual) appears to be associated prospectively with the disease. Although

the evidence about social mobility is not definite, a positive relationship has
been found between coronary heart disease and intergenerational mobility,
and for migration. Higher levels of anxiety and neuroticism seem to precede
coronary heart disease although the relationship between manifest anxiety

and denial may complicate these conclusions. Life dissatisfactions and
environmental stress are reported frequently by coronary heart disease
patients. The coronary-prone behavior pattern (Type A) is related to

increased risk. This pattern consists of the following traits: competitiveness,
striving for achievement, impatience, and other characteristics—“consistent
with the ‘Protestant Ethic,’ with urbanized Western civilization. . . ,”
The frequency and acceptability of diseases such as ulcer and coronary
heart disease, the prevalence of psychophysiological symptoms, and the mass
outbreaks of hysteriform illnesses with various somatic manifestations reflect

the social environment. Our contemporary scene is: “Swept with confused
alarms of struggle and flight/Where ignorant armies clash by night.” The
rampant aggression, internal as well as external, which is now a part of
everyday life, the lowered morale, and the national loss of confidence
(expressed by political leaders, liberal and conservative, Democrats and
Republicans) and the turbulent intergenerational conflict can occur only
when a society is undergoing disintegration or at a juncture in history when

an era is drawing to a close—when its forms are outworn and rejected, when
its ethic is obsolete.
Concepts of psychosocial medicine hold that societies or groups exist in

varying states of psychological health and illness; that sociocultural processes
determine the state of a society’s health; that the availability of the material
necessities of life is a requisite for health; that shared sentiments both

promote and reflect the health of the group; that through child-rearing
practices and learning, societal patterns are reproduced in individuals, and

that groups react like individuals. These concepts are extensions of Aristotle’s
statement that, “Man is by nature a social animal. . . . Society is something in
nature that precedes the individual. Anyone who either cannot lead the
common life or is so self-sufficient as not to need to, and therefore does not
partake of society, is either a beast or he is a god.”
Basic concepts of psychosocial medicine also affirm that man’s
environment, now almost exclusively a social and a man-made one, can be

pathogenic. Many of the indices of a society’s psychological or social health,
which Halliday used to characterize Great Britain as a “sick society” in the
1930s, are applicable to the United States in the late 1960s and early 1970s.
Particularly, the increasing incidence of coronary heart disease and the rising
suicide rate among the young show that our social environment can be lethal
as well as pathogenic.
Once a society has been diagnosed psychosocially as “sick,” Halliday
states the methodology for investigating the nature and the etiology of the
social sickness then calls for studying the three following questions:
1. What kind of social group is this, that is, what group characteristics
are relevant and causal?
2. Why did the community become sick when it did, that is, what are
the causal and environmental factors?
3. Why did the community take ill in the manner it did?
When we find answers to these questions, then we can develop “social
therapeutics— whose aim would be to alter etiologically relevant group
characteristics and etiologically relevant factors so that reintegration could
be secured and a sick society restored to health.”
Bibliography
Abelson, P. H. “The Limits to Growth,” Science, 175 (1972), 1197.
Acheson, E. D. “The Clinical Syndrome Variously Called Benign Myalgic Encephalomyelitis,

Iceland Disease and Epidemic Neuromyasthenia,” Am. J. Med., 26 (1959), 569-595.
Adamson, J. D. and A. H. Schmale. “Object Loss, Giving Up, and the Onset of Psychiatric Disease,”
Psychosom. Med., 27 (1964), 557-576.
Ader, R. and S. B. Friedman. “Social Factors Affecting Emotionality and Resistance to Disease in
Animals. V. Early Separation from the Mother and Response to a Transplanted
Tumor in the Rat,” Psychosom. Med., 27 (1965), 119-122.
Angrist, A. “Progress and Paradox in Pathology and Medicine,” Pharos, 32 (1969), 48-53.
Arnold, M. “Dover Beach,” in R. Aldington, ed., The Viking Book of Poetry of the English Speaking
World, Vol. 2, p. 972. New York: Viking, 1958.
Bennett, C. G. “Mayor’s Panel Finds TB on Rise Here,” New York Times, Dec. 18 (1968), 95.
Bertalanffy, L., Von. “General System Theory and Psychiatry,” in S. Arieti, ed., American Handbook
of Psychiatry, 1st ed., Vol. 3, pp. 705-721, New York: Basic Books, 1966.
Bleibtrau, H. K. “The Impact of Urbanization on Human Evolution,” unpublished paper.
Boyd, W. A Text-Book of Pathology, Chap. 1. Philadelphia: Lee & Febiger, 1953.
Brock, A. J. Greek Medicine. New York: Dutton, 1929.
Brody, E. B. “Transcultural Psychiatry, Human Similarities, and Socioeconomic Evolution,” Am. J.

Psychiatry, 124 (1967), 616-622.
Calhoun, J. B. “Population Density and Social Pathology,” in L. Duhl, ed., The Urban Condition, pp.
33-43. New York: Basic Books, 1963.
Champion, F. P. and R. Taylor. “Mass Hysteria Associated with Insect Bites,” J. So. Carolina Med.
Assoc., 59 (1963), 351-353.
Chertok, L., M. L. Mondazain, and M. Bonnand. “Psychological, Social, and Cultural Aspects of
Sickness during Pregnancy,” Activitas Nervosa Superior (Praha), 4 (1962), 394-401.
Christenson, W. N. and L. E. Hinkle. “Differences in Illness and Prognostic Signs in Two Groups of
Young Men,” JAMA, 177 (1961), 247-253.
Coles, R. “The Lives of Migrant Farmers,” Am. J. Psychiatry, 122 (1966), 271-285.
Crandell, D. L. and B. P. Dohrenwend. “Some Relations Among Psychiatric Symptoms, Organic

Illness, and Social Class,” Am. J. Psychiatry, 123 (1967), 1527-1538.
Crombie, D. L. “The Procrustean Bed of Medical Nomenclature,” Lancet, 1 (1963), 1205-1206.
Davis, K. “The Origin and Growth of Urbanization in the World,” Am. J. Sociol., 60 (1955). 429-437-
Department of Health, Education, and Welfare. Health Statistics from the U.S. National Health
Survey, Series B, no. 17. Washington: U.S. Govt. Print. Off., 1960.
Destounis, N. “Les Facteurs economiques, culturels, sociaux ayant retenti sur secteur donne sur
les complications de la grossesse—Une etude psychosomatique,” Bull. Off. Soc. Int.
Psycho-Prophylax. Obstetr., 6 (1964), 23-30.
Dohrenwend, B. P. and B. S. Dohrenwend. Social Status and Psychological Disorder: A Causal

Inquiry. New York: Wiley, 1969.
Douglas, M. Purity and Danger. New York: Praeger, 1966.
Dragstedt, L. R. “The Role of the Nervous System in the Pathogenesis of Duodenal Ulcer,” Surgery,
34 (1953), 902-903.
Dubos, R. Man Adapting. New Haven, Conn.: Yale University Press, 1965.
Ellul, J. The Technological Society. New York: Random House, 1967.
Engel, G. L. “The Concept of Psychosomatic Disorders,” J. Psychosom. Res., 11 (1967), 3-9.
Finn, R. and P. Huston. “Emotional and Mental Symptoms in Private Medical Practice,” J. Iowa St.
Med. Soc., 56 (1966), 138-143.
Friedman, I. T. “Methodological Considerations and Research Needs in the Study of Epidemic

Hysteria,” Am. J. Public Health, 57 (1967), 2009-2011.
Geiger, H. J. and N. A. Scotch. “The Epidemiology of Essential Hypertension,” J. Chronic Dis., 16

(1963), 1151-1182.
Goodenough, W. H. “Rethinking ‘Status’ and ‘Role,’ ” in S. A. Tyler, ed., Cognitive Anthropology, pp.
311-330. New York: Holt, Rinehart, & Winston, 1969.
Gordon, R. and K. K. Gordon. “Psychosomatic Problems in a Rapidly Growing Suburb,” JAMA, 170
(1959), 1757-1764.
Graham, S. “Socio-Economic Status, Illness, and the Use of Medical Services,” in E. J. Jaco, ed.,
Patients, Physicians, and Illness, pp. 129-134. Glencoe, Ill.: Free Press, 1958.
Halliday, J. L. Psychosocial Medicine: A Study of the Sick Society. New York: Norton, 1948.
Harmon, D. K., M. Masuda, and T. H. Holmes. “The Social Readjustment Rating Scale: A Cross-
Cultural Study of Western Europeans and Americans,” J. Psychosom. Res., 14 (1970),
391-400.
Harrington, M. The Other America. Baltimore: Penguin, 1963.
Harris, T. G. “Affluence, the Fifth Horseman of the Apocalypse: A Conversation with Jean Mayer,”
Psychol. Today, 3 (1970), 43.
Hecker, J. F. C. Epidemics of the Middle Ages. Translated by B. G. Babington. London: Woodfall,

1844.
Henry, J. P., J. P. Meehan, and P. M. Stephens. “The Use of Psychosocial Stimuli to Induce
Prolonged Systolic Hypertension in Mice,” Psychosom. Med., 29 (1967), 408-432.
Hinkle, L. E. “Relating Biochemical, Physiological, and Psychological Disorders to the Social

Environment,” Arch. Environ. Health, 16 (1968), 77-82.
Hinkle, L. E., R. H. Pinsky, I. D. J. Bross et al. “The Distribution of Sickness Disability in a

Homogeneous Group of ‘Healthy Adult Men,’” Am. J. Hygiene, 64 (1956), 220-242.
Hinkle, L. E. and H. G. Wolff. “Ecological Investigations of the Relationship between Illness, Life
Experiences, and the Social Environment,” Ann. Intern. Med., 49 (1958), 1373-1388.
Hippocrates. The Medical Works of Hippocrates. Translated by J. Chadwick and W. N. Mann.

Oxford: Blackwell Scientific Publications, 1950.
Hollingshead, A. B. and F. C. Redlich. Social Class and Mental Illness. New York: Wiley, 1958.
Holmes, T. H. and R. H. Rahe. “The Social Readjustment Rating Scale,” J. Psychosom. Res., 11
(1967), 213-218.
Hughes, C. C., M. Tremblay, R. N. Rapoport et al. The Stirling County Study of Psychiatric Disorder
and Sociocultural Environment. Vol. 2. The People of Cove and Woodlot. New York:
Basic Books, 1960.
Jacobs, N. “The Phantom Slasher of Taipei: Mass Hysteria in a Non-Western Society,” Soc.
Problems, 12 (1965), 318-328.
Jenkins, C. D. “Psychologic and Social Precursors of Coronary Disease (Part I),” N. Engl. J. Med.,
284 (1971), 244-255.
----. “Psychologic and Social Precursors of Coronary Disease (Part II),” N. Engl. J. Med., 284 (1971),
307-317-
Jennings, D. “Perforated Peptic Ulcer: Changes on Age, Incidence, and Sex-Distribution in the Last
150 Years,” Lancet, 1 (1940), 395-398.
Kagan, A., W. Kannel, T. Dawber et al. “The Coronary Profile,” Ann. N.Y. Acad. Sci., 97 (1963), 883-
894.
Kagwa, B. H. “The Problem of Mass Hysteria in East Africa,” East Afr. Med. J., 41 (1964), 560-566.
Kantor, M. B. “Internal Migration and Mental Illness,” in S. Plog and R. B. Edgerton, eds., Changing
Perspectives in Mental Illness. New York: Holt, Rinehart, & Winston, 1969.
Kardiner, A. and L. Ovesey. The Mark of Oppression. New York: World Publishing, 1951.
Kessel, N. and A. Munro. “Epidemiological Studies in Psychosomatic Medicine,” J. Psychosom. Res.,

8 (1964), 67-81.
Kidson, M. and T. Jones. “Psychiatric Disorders among Aborigines of the Australian Western
Desert,” Arch. Gen. Psychiatry, 19 (1968), 413-417.
Kissen, D. “Psychosocial Factors, Personality, and Lung Cancer in Men Aged 55-64,” Br. J. Med.
Psychol., 40 (1967), 29-43.
Kluckhohn, C. Culture and Behavior. New York: Free Press, 1962.
Knight, J. A., J. I. Friedman, and J. Sulianti. “Epidemic Hysteria: A Field Study,” Am. J. Public Health,
55 (1965), 858-865.
Langner, T. S. and S. T. Michael. The Midtown Manhattan Study. Vol. 2. Life, Stress and Mental
Health. New York: McGraw-Hill, 1963.
Leighton, A. H. The Stirling County Study of Psychiatric Disorder and Sociocultural Environment.
Vol. 1. My Name Is Legion: Foundations for a Theory of Man in Relation to Culture.
New York: Basic Books, 1959.
Leighton, A. H., T. A. Lambo, C. C. Hughes et al. “Psychiatric Disorder in West Africa,” Am. J.
Psychiatry, 120 (1963), 521-527.
Leighton, D. C. Personal communication, 1969.
Leighton, D. C., J. S. Harding, D. B. Macklin et al. The Stirling County Study of Psychiatric Disorder
and Sociocultural Environment. Vol. 3. The Character of Danger. New York: Basic
Books, 1963.
Leshan, L. “Cancer Mortality Rate: Some Statistical Evidence of the Effect of Psychological
Factors,” Arch. Gen. Psychiatry, 6 (1962), 333-335.
McEvedy, C. P. and A. W. Beard. “Royal Free Epidemic of 1955: A Reconsideration,” Br. Med. J., 1
(1970), 7-11.
----. “Concept of Benign Myalgic Encephalomyelitis,” Br. Med. J., 1 (1970), 11-15.
McKinney, J. C. and L. B. Bourque. “The Changing South: National Incorporation of a Region,” Am.
Sociol. Rev., 36 (1971), 399-412.
Malzberg, B. “Mental Disease among American Negroes: A Statistical Analysis,” in O. Klineberg,

ed., Characteristics of the American Negro, pp. 371-400. New York: Harper, 1944.
Marx, K. and F. Engels. “On Class,” in C. W. Mills, ed., Images of Man, pp. 101-New York: Braziller,
1960.
Mathers, D. H. and R. S. Eliot. “Predicting and Preventing Sudden Death,” in R. S. Eliot, ed., Acute
Cardiac Emergency, pp. 281-286. Mt. Kisca, New York: Futura Publishing, 1972.
Mazer, M. “Psychiatric Disorders in General Practice: The Experience of an Island Community,”

Am. J. Psychiatry, 124 (1967), 609-615.
Mering, O. Von. “The Diagnosis of Problem Patients,” Human Organ, 25 (1966), 20-23.
Mering, O., Von and L. W. Earley. “Major Changes in the Western Medical Environment,” Arch. Gen.
Psychiatry, 13 (1965), 195-201.
Mester, B. F. and Z. Mester. “Psychological Analysis of the Biographical Data of 83 Patients with
Biliary Disease,” Am. Med. Psychol., 119 (1961), 447.
Modlin, H. “The Postaccident Anxiety Syndrome: Psychological Aspects,” Am. J. Psychiatry, 123
(1967), 1008-1012.
Moss, P. D. and C. P. McEvedy. “An Epidemic of Overbreathing Among Schoolgirls,” Br. Med. J., 2
(1966), 1295-1300.
Mutter, A. and M. Schleifer. “The Role of Psychological and Social Factors in the Onset of Somatic
Illness in Children,” Psychosom. Med., 28 (1966), 333-343.
Newsweek. “Heart Attack: Curbing the Killer,” 79 (May 1, 1972), 73-74.
Newsweek. “VD: The Epidemic,” 79 (Jan. 24, 1972), 46-5°-
Ollendorff, R. H. V. “Concept of the Sick Society,” unpublished work.
Parens, H., B. J. McConville, and S. M. Kaplan. “The Prediction of Frequency of Illness from the
Response to Separation,” Psychosom. Med., 28 (1966), 162-176.
Park, R. E. “Human Migration and the Marginal Man,” Am. J. Sociol., 33 (1928), 881-893.
Parkes, C. M. “The Psychosomatic Effects of Bereavement,” in O. W. Hill, ed., Modern Trends in

Psychosomatic Medicine, Vol. 2. New York: Appleton-Century-Crofts, 1970.
Parsons, T. and E. A. Shils, eds. Toward a General Theory of Action. Cambridge, Mass.: Harvard
Pasamanick, B. “A Survey of Mental Disease in the Urban Population: An Approach to Total
Prevalence by Diagnosis and Sex,” J. Nerv. Ment. Dis., 133 (1961), 519-523.
Paul, J. R. Clinical Epidemiology. Chicago: University of Chicago Press, 1966.
Paykel, E. S., J. K. Meyers, M. N. Dienelt et al. “Life Events and Depression, a Controlled Study,”
Arch. Gen. Psychiatry, 21 (1969) 753-760.
Paykel, E. S. and E. H. Uhlenhuth. “Rating the Magnitude of Life Stress,” Can. Psychiatr. Assoc. J., 17,
Suppl. 2 (1972), SS93-100.
Peller, S. Quantitative Research in Human Biology and Medicine. Bristol, England: Wright, 1967.
Quisenberry, W. B. “Sociocultural Factors in Cancer in Hawaii,” Ann. N.Y. Acad. Sci., 84 (1960),
795-806.
Redl, R. “The Phenomenon of Contagion and ‘Shock Effect’ in Group Therapy,” in K. R. Eissler, ed.,
Searchlights on Delinquency, pp. 315-328. New York: International Universities
Press, 1949.
Rennie, T. A. C. and L. Srole. “Social Class Prevalence and Distribution of Psychosomatic

Conditions in an Urban Population,” Psychosom. Med., 18 (1956), 449-456.
Richardson, W. C. Dimensions of Economic Dependency, Health Administration Perspectives, no.

A4. Washington: U.S. Govt. Print. Off., 1967.
Richmond, J. B. “Toward a Developmental Psychosomatic Medicine,” Psychosom. Med., 25 (1963),

567-573.
Rosen, G. “The Evolution of Social Medicine,” in H. E. Freeman, S. Levine, and L. G. Reeder, eds.,
Handbook of Medical Sociology. Englewood Cliffs, N.J.: Prentice-Hall, 1963.
Rowntree, L. G. “Psychosomatic Disorders as Revealed by Thirteen Million Examinations of

Selective Service Registrants,” Psychosom. Med., 7 (1945), 27-30.
Sarvotham, T. G. and J. N. Berry. “Prevalence of Coronary Heart Disease in an Urban Population in
Northern India,” Circulation, 37 (1968), 939-953.
Schmale, A. H. “Relationship of Separation and Depression to Disease: A Report on a Hospitalized

Medical Population,” Psychosom. Med., 20 (1958), 259-277.
----. Object Loss, “Giving Up,” and Disease Onset: An Overview of Research in Progress. Washington:
Walter Reed Army Institute of Research, 1964.
Schmale, A. H., S. Meyerowitz, and D. C. Tilling. “Current Concepts of Psychosomatic Medicine,” in

O. W. Hill, ed., Modern Trends in Psychosomatic Medicine, Vol. 2, pp. 1-25. New York:
Schuler, E. A. and V. J. Parenton. “A Recent Epidemic of Hysteria in a Louisiana High School,” J. Soc.
Psychol., 17 (1943), 221-235.
Schulte, W. “Syncopal Attacks and Cardiac Phobias as Models of Psychosomatic Diseases, with a
Discussion of the Biographical and Sociological Correlations,” Klin. Wochenschr., 40
(1962), 1088-1093.
Schwab, J. J. “Psychosomatics and Consultation,” Psychosom., 13 (1972), 9-12.
Schwab, J. J., M. R. Bialow, J. M. Brown et al. “Sociocultural Aspects of Depression in Medical

Inpatients: II. Symptomatology and Class,” Arch. Gen. Psychiatry, 17 (1967), 539-
543.
Schwab, J. J., M. R. Bialow, C. E. Holzer et al. “Sociocultural Aspects of Depression in Medical

Inpatients: I. Frequency and Social Variables,” Arch. Gen. Psychiatry, 17 (1967),
533-538.
Schwab, J. J. and J. D. Harmeling. “Body Image and Medical Illness,” Psychosom. Med., 30 (1968),
51-61.
Schwab, J. J. and N. H. McGinnis. “Social Change, Cultural Change and Mental Health,” in Proc. 5th
World Congr. Psychiatry. Excerpta Medica International Congress Ser., no. 274, Part
1, Psychiatry, PP 703-709. Amsterdam: Excerpta Medica Foundation, 1973.
----. “Social Psychiatric Impairment: Racial Comparisons,” Am. J. Psychiatry, 130 (1973), 183-187.
Schwab, J. J., N. H. McGinnis, and J. D. Harmeling. “Anxiety, Self-Concept, and Body Image:
Psychosomatic Correlations,” in J. J. Lopez-Ibor, ed., Proc. 4th World Congr.
Psychiatry. Excerpta Medica International Congress Series, no. 150, Part 4, Free
Communications, pp. 2715-2717. Amsterdam: Excerpta Medica Foundation, 1968.
Schwab, J. J. and G. J. Warheit. “Evaluating Southern Mental Health Needs and Services: A
Preliminary Report,” J. Fla. Med. Assoc., 59 (1972), 17-20.
Schwab, J. J., G. J. Warheit, G. Spencer et al. “Concurrent Psychiatric and Medical Illness,” in J.
Bierer, V. Hudolin, and J. Masserman, eds., Proc. 3rd Int. Congr. Soc. Psychiatry, Vol.
4, pp. 157-163. Zagreb: Amali, 1970.
Schwab, M. “Hallucinatory Behavior in a Southern Negro Community,” in P. Adams, ed., Humane

Social Psychiatry, pp. 125. Gainesville, Fla.: Tree of Life Press.
Scotch, N. A. “A Preliminary Report on the Relation of Sociocultural Factors to Hypertension

Among the Zulu,” Ann. N.Y. Acad. Sci., 84 (1960), 1000-1009.
Seguin, C. A. “Migration and Psychosomatic Disadaptation,” Psychosom. Med., 18 (1956), 404-409.
Seldes, G. The Great Quotations, p. 67. New York: Lyle Stuart, 1960.
Smart, R. G. and W. S. Schmidt. “Psychosomatic Disorders and Traffic Accidents,” J. Psychosom.

Res., 6 (1962), 191-197.
Spain, D. M. “Discussion: Sociocultural Factors in Chronic Organic Disease,” Ami. N.Y. Acad. Sci., 84
(1960), 1031.
Srole, L., T. S. Langner, S. T. Michael et al. The Midtown Manhattan Study, Vol. 1. Mental Health in
the Metropolis. New York: McGraw-Hill, 1962.
Stallones, R. A. “Community Health,” Science, 175 (1972), 839.
Stamler, J., M. Kjelsberg, and Y. Hall. “Epidemiologic Studies on Cardiovascular-Renal Diseases: I.
Analysis of Mortality by Age-Race-Sex-Occupation,” J. Chronic Dis., 12 (1960), 440-
455.
Stonequist, E. V. The Marginal Man, pp. 139-158. New York: Scribners, 1937.
Taylor, F. K. and R. C. A. Hunter. “Observation of a Hysterical Epidemic in a Hospital Ward:

Thoughts on the Dynamics of Mental Epidemics,” Psychiatr. Q., 32 (1958), 821-829.
Taylor, I. and J. Knowelden. Principles of Epidemiology, 2nd ed. Boston: Little, Brown, 1964.
Thomas, C. S. and B. J. Bergen. “Social Psychiatric View of Psychological Malfunction and Role of
Psychiatry in Social Change,” Arch. Gen. Psychiatry, 12 (1965), 539-544.
Thomas, W. I. In H. Blumer, ed., An Appraisal of Thomas and Zanecki’s “The Polish Peasant in
Europe and America.” New York: Social Science Research Council, 1939.
Thoroughman, J. C., G. R. Pascal, W. O. Jenkins et al. “Psychological Factors Predictive of Surgical

Success in Patients with Intractable Duodenal Ulcer,” Psychosom. Med., 26 (1964),
618-624.
Tinling, D. C. “Voodoo, Root Work, and Medicine,” Psychosom. Med., 29 (1967), 483-490.
Toqueville, A., de. Democracy in America, Vol. 2. New York: Knopf, 1945.
Tringo, J. L. “The Hierarchy of Preference toward Disability Groups, J. Spec. Educ., 4 (1970), 295-
306.
Watts, C. A. H. “Psychiatric Disorders,” Stud. Med. Popul. Subj., 14 (1962), 35-52, 133.
Wheelis, A. The End of the Modern Age. New York: Basic Books, 1971.
Wordsworth, W. The Prelude, or Growth of a Poet’s Mind, E. de Selincourt, ed. London: Oxford
Chapter 26
Psychological Aspects Of Cardiovascular Disease1
Chase Patterson Kimball
Introduction
In considering the psychological aspects of cardiovascular disease four
areas are discussed: (1) coronary artery disease; (2)congestive heart failure;
(3) hypertension; and (4) special aspects of diagnosis and treatment.
Although the reader will note psychological variables common to each of

these processes, the emphasis is different in each situation. In coronary artery
disease, attention is given to the precursant behavioral factors and

concurrent social events. In congestive heart failure, emphasis is placed upon
the interrelationship of sociological, psychological, and physiological stress

factors in precipitating failure in the presence of structural myocardial or
valvular changes. In hypertension, the progressive nature of the disease is

considered in terms of effecting different psychosocial relationships for each
stage. The section on the psychological aspects of special procedures in
diagnosis and treatment discusses cardiac catheterization, cardiac
pacemakers, intensive care units, cardiovascular surgery, and the new
operant conditioning techniques.
The psychological aspects are discussed in terms of three phases: (1)
preillness behavior patterns and personality; (2) the psychological state of

the individual at the time of onset; and (3) the emotional and psychological
reaction to illness. In each of these phases, the reader will find that it is
difficult to separate strictly psychological phenomenon from the
physioanatomic on one hand or from the socioenvironmental on the other.

Wherever possible, the interaction of these variables with one another is
stressed, rather than an implied linear or causal relationship between them.
The literature is identified in considerable detail not only to provide current

and historical reference sources for the interested student, but also to convey
the complex interrelationships that prevail. At the same time, the significance
of the findings presented are discussed in terms of their relevance and

applicability to clinical problems. For example, the section on Psychological
Aspects of Diagnosis and Treatment identifies the increasing attention that
investigators have given to the adaptational responses of patients with
catastrophic illness and the significance of these in their care.
Coronary Artery Disease Epidemiological Precursors
Epidemiological Precursors
A discussion of psychosocial factors, precursant, concurrent, or
consequent to the development and onset of cardiovascular and coronary

artery disease begins with the work of epidemiologists. Specific factors
implicated by epidemiological study are diet—including caffeine—serum
lipids, elevated blood pressure, smoking, diabetes, obesity, and cultural and
genetic traits. To date, almost all of these studies have been of men. The
Framingham studies conducted during the 1960s correlated cholesterol
levels, elevated blood pressure and smoking with atherosclerosis. Heavy
cigarette smokers experienced a three-fold increase in incidence of

myocardial infarction and death from any cause over noncigarette, i.e., pipe
and cigar, and former smokers. Although the study failed to demonstrate a
relationship with angina pectoris, it did show a correlation of the latter with
weight gain after the age of twenty-five. Other investigators have verified
these relationships and suggested that smoking may act both as an
independent factor and in association with other risk factors.
Paffenbarger and his colleagues have reviewed the college health

records of individuals who subsequently developed cardiovascular disease,
identifying eight precursors for victims of coronary disease: heavy cigarette

smoking, higher blood pressure levels, excess body weight, shortness of
stature, nonparticipation in athletics, early parental death, only-child status
and “sociopsychological exhaustion”. Thomas, in a prospective study of
medical students has found similar correlations. More recently the lower
incidence of atherosclerotic heart disease in some areas of the United States
has been related to the increased Lithium content in the water supply. A
similar correlation has been suggested for mental illness, which is made more
interesting by at least one study which suggests that patients with
cardiovascular disease often have cyclothymic personalities. In a study of

young men with coronary artery disease, Hatch et al. have found that
overnutrition and heavy smoking may interact with hereditary factors to
accelerate the progress of coronary atherosclerosis. Among the genetic
factors cited are short stature, vascular defects, and abnormalities in the
intermediary metabolism of lipoproteins and carbohydrates.
Psychosocial Precursors
In a review of the psychosocial precursors of coronary artery disease,

Jenkins cites and evaluates 162 studies. He sees the need for larger
prospective studies to examine the psychosocial variables: behavior patterns,
crisis-related disease-onset situations, and social incongruity. He suggests
that these studies address themselves to four patterns of coronary artery

disease: (1) survivors vs. (2) nonsurvivors of myocardial infarctions; (3)
individuals with silent infarctions; and (4) patients with angina pectoris. Such
studies, he anticipates, will identify relative importance for each of the
psychosocial variables as related to different disease patterns. The following
discussion identifies some of the correlations between psychosocial variables
and coronary artery disease.
Social
Hinkle, on the basis of an earlier review of the social and biological
correlates of coronary artery disease, hypothesized that diet, activity
patterns, increased latitude for social mobility, and striving behavior foster,
via neuronal and hormonal mechanisms, a biochemical environment in the
blood stream that accelerates atherosclerosis, facilitating occlusion of
coronary arteries, impairing blood supply to the heart muscle, and making
arrhythmias and death more likely. He believes that social and behavioral
variables cannot be dealt with in broad general categories such as “stress”
and “mobility” but must be studied as discrete, carefully limited, vigorously
defined concepts or entities. Coronary artery disease is the outcome of a

complex interaction of many variables in which no single one predominates.
In an examination of the variables occupation and education, Hinkle and his
colleagues executed a five-year survey of 270,000 Bell System employees

establishing that: (1) men attaining the highest levels of management do not
have a higher risk of coronary artery disease than men at the lowest levels;
(2) there was no added risk for men elevated quickly or transferred; (3) men
who had college degrees on entering the company had a lower attack rate,
lower death rate, and lower disability rate at every age, in every part of the
country, and in all departments; (4) the difference in risks exists at the time of
employment; and (5) may be the result of biological differences in noncollege

as opposed to college men related to social and economic background and
resulting habits, e.g., smoking, diet, childhood health care.
Other investigators have studied the relationship of social class to the
incidence of coronary artery disease. Friedman and Hellerstein examined this
incidence in four groups of lawyers presumably divided on the basis of
economic and ethnic background. Lawyers in the highest and lowest groups
had a lower incidence than those falling in the middle groups. Bruhn et al.
related a lower incidence of death from myocardial infarction with the

stability of the community in the comparison of a mixed ethnic town with one
composed primarily of lower socioeconomic Italians. In a study of major
significance, Shekelle et ah, on the basis of a prospective study of 1472

middle-aged male Caucasians free of coronary heart disease, concluded that
the incongruities in social status are associated with the risk of coronary
heart disease. They demonstrated that the incidence increased as the number
of incongruities per subject increased. Men with four to five incongruities had
six times the risk compared to men with no incongruities. This finding was
not explained by correlations with serum cholesterol, arterial pressure, blood
glucose, age, educational status, weight, or cigarette smoking. An interesting
relationship was observed between level of education and manifestation of
cardiac symptoms with men in the highest and lowest strata manifesting
angina pectoris as opposed to the middle strata where symptoms and signs of
myocardial infarction prevailed.
Caffrey, in a retrospective study of monks with myocardial infarctions,
emphasized that a profile of scores relative to a number of factors is of
greater significance in ascribing possible etiogenicity than single factors. For
monks, he suggests that such a profile including behavior pattern type A, i.e., a
moderately high level of responsibility, a family background of lower
socioeconomic status, a fairly sedentary occupation in one who has
previously enjoyed a good deal of exercise, related to a greater likelihood of

myocardial infarction. Cassel et al. comparing a prevalence vs. an incidence
study among rural Georgians concluded that the previous high association of
coronary artery disease in higher social class white men as opposed to lower
rates for lower-class blacks was gradually disappearing presumably because
of the increasing behavioral similarities in the two groups, especially among
the younger men.
Behavioral
Since 1958, Friedman and Bosenman and their associates have
published extensive retrospective and prospective surveys relating a
behavior pattern, identified as type A, to coronary artery disease. In their
initial studies, they correlated behavioral factors including intense ambition,
competitiveness, constant preoccupation, the stress of occupational
deadlines, and a sense of urgency with elevated serum cholesterol, increased

blood clotting, arcus senilis and clinical coronary artery disease. Subsequently,
they have measured the physiological reactions of subjects listening to a
specially designed tape recording of two monologues, noting that individuals

designated as type A manifested greater respiratory excursions, more
frequent clenching of fists and body movement on listening to a dull, hesitant,
monotonous, repetitive monologue as compared to individuals identified as
having a type-B behavior pattern. In a later, retrospective analysis of

prospectively obtained data, 80 of 113 men who developed coronary heart
disease or higher serum alpha lipoproteins had been rated as exhibiting
behavior pattern type A. In a two year follow-up study, 70 of 3524 employees

developed coronary heart disease as demonstrated by infarction or angina.
All of these had initially shown an abnormal lipoprotein pattern,
hypertension and/or type-A behavior pattern. Of the three, the latter was the
single most constant factor. In contrast to the high risk of coronary artery
disease identified for type-A behavior, they established a substantially lower
risk for a type-B behavior pattern, presumably the converse of type A. A man
with type B was considered to be essentially immune to the development of
clinical coronary heart disease if he exhibited a serum cholesterol level less
than 226 μg./100 ml., a serum triglyceride level less than 126 μg./100 ml. or a
serum B/ 00 lipoprotein ratio less than 2.01 singly or in combination. On a
study of the vasculature of type A and type B succumbing to death for
whatever cause, they identified that the former exhibited severe coronary
atherosclerosis six times more frequently than the latter. In a recent review
article of their findings, a more graphic description for the individual with
type-A behavior is suggested as a coat of arms showing a clenched fist
wearing a stop-watch. The association of coronary artery disease and type-A
behavior is associated with parental coronary artery disease, elevated
cholesterol, cigarette smoking, and elevated diastolic blood pressure. The

possible role of the hypothalamus is suggested. Electrical stimulation of the
diencephalon and lesions in the fornix, medial portion of the lateral
hypothalamus and either ventromedial or dorsomedial nucleus have

produced transient and persistent elevations in plasma cholesterol levels in
rats. These elevations have also been associated with more active behavior
patterns. Pursuing their search for a more objective identification of

individuals with behavior pattern type A, the Friedman group has developed
a twenty-item questionnaire and a voice analysis method of taped interviews
which, they report, have achieved this objective. Jenkins, in a computerized
analysis of the questionnaire reports an astounding 73 percent correlation

with interview assessment of type-A pattern.
Bahnson has suggested another personality type for men with coronary
artery disease in which passive and dependent traits rather than assertive
and dominant ones are manifested. This more “passive” pattern is
hypothesized as developing from unresolved attachments to mothers as
opposed to fathers which is suggested for type A.
The work of Friedman and Rosenman is in some ways a refinement of
that pioneered by Flanders Dunbar in the 1930s and 1940s. Based on an
extensive review of the literature until that time and the intensive
examination of 1600 hospital admissions, she identified personality profiles
for patients with a variety of illnesses, including coronary occlusion,
hypertensive cardiovascular disease, angina, rheumatic heart disease, and
arrhythmias. Her profiles included not only obsessive-compulsive personality
traits, but also passive-aggressive defenses for the expression of hostility and
anger, rigid middle-class social patterns, and involved symbiotic family

relationships. For each of these illnesses she delineated one or more features
in several areas of the individual’s psychosocial field that was characteristic

for the group as a whole. These early identifications have spurred other
investigators toward more specific examinations using more sophisticated
methodologies.
More thorough studies, such as those of Storment, have failed to confirm

an overall personality type for cardiovascular illness, although accord
sometimes has been reached for selected traits, such as stability of mood in
patients with coronary occlusion and overcriticalness in hypertensives. Other
studies continued to investigate the possible correlations between
personality and cardiovascular disease. More often than not, it seems that
what is considered as personality is poorly defined and refers rather to one or
several specific traits. Besides this difficulty, as several critics suggest, many
of the studies have been retrospective and as such are more suggestive of
types of responses to coronary disease rather than of common psychological

precursors. Studies have included highly selected survivors, ignoring the 30
percent who died before inclusion, as well as those with “silent” infarctions
who are rarely identified. Prospective studies, focusing on more objective

measurements and larger numbers may overcome some of these deficits. The
few prospective studies that have been executed have attempted to answer
some of these criticisms. Lebovits et al. noted that individuals who died of
coronary artery disease had higher Minnesota Multiphase Personality

Inventory (MMPI) scores on several testings as compared with those who
survived. Among survivors there had been a worsening of MMPI scores

between the first and second examinations prior to infarction as compared to
individuals who did not subsequently develop heart disease. Brozek followed
258 business and professional men between the ages of forty-five and fifty-
five, over fourteen years, subsequently comparing thirty-one who developed
coronary disease with 138 who did not. The former showed higher
hypochondriasis scores on the MMPI, were more “aggressive” in their
interests, and had higher scores on the Activity Drive Scale of the Thurstone
Temperament Schedule.
Of studies that have been retrospective, Ibrahim et al. have suggested
that the similarities in characteristics that they and others have identified
probably are related to the reaction of patients to the disease." They studied
hypertension and elevated serum cholesterol in a coronary group and
compared it with two at-risk groups, noting that two-thirds of the coronary
group as opposed to one-fifth of the noncoronary group showed low-level
manifest hostility and elevated levels of anxiety and regression. However,
Shekelle et ah, based on cross-sectional and longitudinal observations of
middle-aged men, conclude that a psychological pattern is not related to
either the risk of coronary heart disease nor is its occurrence related to the
loss or acquisition of psychological patterns.
Other retrospective studies have contrasted victims of cardiac disease
with other populations. Bendian and Groen found patients with myocardial
infarctions to be extroverts and suggested a cyclothymic personality for

coronary patients. Mine et ah, found cardiac patients to show a greater degree
of rational control. Their patients showed greater inhibition both in behavior
as measured by standard psychological tests and in cerebral cortical

functioning as measured by alpha-wave frequency, critical frequency flicker,
and reaction time. Cohen and Parsons contributed a negative correlation
showing that there was no difference in time perception in coronary patients
as opposed to others, and hypothesized that what previous investigators had
identified in this regard related to socioeconomic variables. Dreyfuss et ah,

observed that victims of myocardial infarction viewed the environment as
more conflict-laden, the outcome of their actions as more unclear and with
less certainty of success. They felt their study supported Cleveland’s and
Johnson’s hypothesis of weak ego boundaries based on the identification of

chronic restlessness, underlying passivity, suppressed hostility, and sexual
conflicts. Subsequently Dreyfuss noted that infarction frequently occurred in
depressed patients. Wolff described compulsivity, repressed hostility, strong

repressive superegos, and unfulfilled oral needs for psychiatric patients with
angina pectoris. Bruhn et ah, contrasted survivors with nonsurvivors noting
greater depression as determined by the MMPI for the latter.
In summary of the psychosocial aspects of coronary artery disease

during the past decade on the basis of carefully constructed hypotheses and
methods, several conceptual approaches to the study of the precursors of

coronary artery disease have emerged. Paffenbarger, Thomas, and the
Framingham group have noted the association of such risk factors as

smoking, hypertension, cholesterol levels, early parental death, and activity
patterns with the subsequent development of coronary artery disease.
Hinkle has produced striking evidence suggesting that higher education
at the time of employment is the signal variable correlating with a lower
incidence of coronary artery disease. He suggests that this may be related to
social and economic factors. Shekelle et al. have introduced the intriguing
observation that social incongruity is related to increasing risk for coronary
artery disease. Friedman, Rosenman, and their associates have repeatedly
identified the type-A behavior pattern as the single most frequent variable
correlating with the development of coronary artery disease. Jenkins through
a computerized analysis of interview and questionnaire data has verified this.
The social, behavioral, and physiological interrelationships remain to be
elucidated. To what extent these are mutually independent or dependent,

genetically or epigenetically determined or cumulative remain for present
and future investigators to unravel.
Stress and Illness Onset Precursors
In recent years, attention of investigators has turned increasingly to the
environmental situation in which cardiovascular disease is first experienced.

The stress researchers, while not ignoring the importance of genetic and
previous behavior patterns, identify catastrophic events occurring in
temporal proximity to the first symptoms and signs of cardiac disease. Harold
Wolff, a father of modern stress research, in a number of carefully designed
and executed studies demonstrated a relationship between stressful
situations and such physical factors as circulatory efficiency, faulty exercise
tolerance, hemodynamic response, cardiac arrhythmias, renal blood flow,
electrocardiogram, and blood-pressure changes in patients with and without

structural heart disease. He identified that stress occurring concurrently with
physical activity delayed return of cardiovascular factors to the resting state
following cessation of activity. Noting that individuals responded

cardiovascularly to stressful situations either hyper- or hypodynamically, he
offered as an explanation that the type of response depended on the symbolic
significance (often learned) of the stress to the perceiver. Only in this way and
for the individual was stress specific for a specific cardiovascular response.
Fisher noted that patients with cardiovascular disease frequently presented a
history of working excessively under self-imposed and environmental

pressure, and reported a gradual increase in the number and intensity of
stressful situations prior to the onset of manifest heart disease. Van der Valk
and Groen emphasized the occurrence of myocardial infarction in a work
situation as a result of interpersonal conflict precipitating an exaggeration of

aggressive behavior. Liljefors and Rahe, in a study of identical twins
correlated life dissatisfactions as the single most consistent factor with the
severity of coronary heart disease, as distinguished from smoking, obesity,
hypercholesterolemia, the medical history and the physical examination.
Raab reviewing 305 studies relating stress factors to coronary artery disease
suggested that emotional and sensory stresses resulted in central nervous
system arousal of the pituitary-adrenal and sympathoadrenomedullary
systems resulting in the overproduction of adrenocortical steroids and
sympathomimetic catecholamines leading to a depletion of myocardial
potassium, elevation of blood pressure, and local myocardial hypoxia. He
included fear, anxiety, anger, frustration, and optical, accoustical, and thermal
percepts among precipitating stimuli. Wolf, studying sudden death from

myocardial infarction and cardiac arrhythmias attributed these to
undampened autonomic discharges in response to either afferent information
from below or impulses resulting from integrative processes in the brain
involved in adaptation to stressful life experiences or both. He suggested that

triggering stimuli were effective in situations of weary dissatisfaction,
frustration, feelings of abandonment and dejection, especially at times when
emotional reactions were not forthcoming from others. Engel emphasized

both inhibitory and excitatory parasympathetic responses in association with
stressful situations as leading to sudden death, the determinants of the
response depending upon individual psychobiologic perception and reaction

to stress. Paul identified the epidemiologic and prodromal causes of sudden
death relating these to arrhythmias and abnormal free fatty acid metabolism.
Rees and Lutkins found a six-fold increase over the expected mortality in
deaths from myocardial infarction in London widowers within a six-month

period following the death of their spouses. Critics such as Horvath view
present research as imprecise because of the failure to carefully identify and
measure stress. Mine sees coronary artery disease as a disease of civilization,
and as a consequence of an attempt at intellectual control over feeling and
subsequent behavior conditioned by a social environment that disallows
emotional response to stress, resulting in an arousal of the autonomic
nervous system. Werko suggests that attention to the changing social
structure in the community may be of the greatest importance in the

prevention of ischemic heart disease. These speculations lead into
metaphysical contemplations regarding the relationship of the disease and
civilizations which go beyond our present knowledge and our methods of
research.
In summary, the situation in which myocardial infarction, physiological
decompensation, or sudden death occurs has been the subject of several
investigations. The illness onset situation, whether of the initial process or a

recurrence, is seen as a stressful one leading to psychological and
physiological changes. Stressful situations are frequently associated with loss

and bereavement which in the vulnerable or sensitized individual may lead to
psychological and physiological decompensation. The particular stress
eliciting a reaction may be nonspecific and is dependent on other factors

predilecting the individual to a vulnerable physiological state. The reaction of
individuals are variable, both psychologically and physiologically. Since
different individuals may react hyper- or hypodynamically to the same
stressful situation, it is not possible to universally associate specific stresses
with specific patterns of response. Individual variation of response depends
on how the individual perceives the stress symbolically, and on innate or

learned patterns of physiological response associated with that percept.
Reactions to Coronary Artery Disease
Perhaps of more immediate application and reward in the field of the
psychological aspects of cardiac disease are the investigations of the
individual’s reactions to the symptoms, signs, and diagnosis of cardiovascular
disease, for it is at these points that specific and often life-threatening

emotions and the defenses against these may be precipitated. Examples are
the studies of Hackett and Cassem and Olin, who identified denial in subjects
with chest pain at the time of myocardial infarctions as causing delay in
seeking medical attention. Their subjects, many of whom were sophisticated

in the various meanings of chest pain, attributed their discomfort to more
benign conditions than myocardial infarction. Although some subjects had
previous infarctions, these too tended to use the expression, “I thought it
couldn’t happen to me,” in describing their reaction to substernal pain. If this

occurs in survivors and repeat victims, the question may be asked how often
this or a similar response occurs in subjects who die before seeking medical
help. If this pattern occurs in as many individuals as some epidemiologists
believe, then a study of this reaction may be a crucial consideration for
psychiatrists and other workers in preventive cardiology. Although most
subjects studied have been observed to use denial at one or more points in
their reaction to cardiac disease, observers have noted that, whereas in the
early phase of illness it is simply a denial of the symptoms as a way of
contending with anxiety over the possibility of death, this early denial is a
fragile and brittle defense which subsequently is replaced by more
characterological mechanisms in which the denial of illness and of its
significance may become manifest by inappropriate behavior, also
threatening to the recovery of the individual. Arlow has noted that the
manifestation of anxiety in anginal patients depends upon the defenses the
individual erects to cope with this anxiety which, in turn, are determined by
the individual’s previous experience as well as his current emotional state. He
sees overwhelming panic leading to the use of repression and denial. Ideation
encountered in these patients includes fear of dying, fantasied loss of love,
abandonment, and at times aggressive and homosexual impulses as means of

coping with this fear. Croog et ah, identified greater denial in postinfarction
patients of Jewish or Italian background than in those patients of British or

Irish descent. They demonstrated the persistence of denial in 20 percent of
their subjects over a year’s time. Bakker, contrasting individuals with
arteriosclerotic heart disease with anginal patients, identified more emotional
lability, tenseness, conflict, and compulsivity in the latter. Cleveland and
Johnson compared postcoronary with presurgical patients, noting chronic
restlessness, underlying passivity, and suppressed hostility in the former.
Rosen and Bibring related behavioral reaction to myocardial infarction to age
and social status. Depression and scrupulous cooperation were greater in
older patients, whereas cheerfulness and active defiance were seen in
younger ones. Anxiety was more prevalent in white-collar workers, while

casualness prevailed in blue-collar workers. Croog and Levine, studying
reactions of patients between the age of thirty and sixty to myocardial
infarction, found that higher-status individuals showed a greater awareness
of emotional stress as an etiological factor than lower-status patients who

were less inclined to talk about their reaction to illness. Rodda et al., also
identified greater anxiety in younger patients, and depression in older
patients. Druss and Kornfeld following survivors of cardiac arrest described

the defense mechanisms invoked to control anxiety precipitated by this
experience. Subjects reported violent and frightening dreams, and identified
various theories and explanations in order to integrate the experience of

having been dead and reborn. Residual problems included insomnia,
irritability, and restriction of activities beyond what was medically
appropriate.
Treatment and Management
The recognition of chronic anxiety and persistent depressive states in
patients with coronary artery disease has led a number of investigators
toward examining models of therapeutic intervention. Pelser emphasizes that
many patients experience myocardial infarction at a time when they are
already under emotional strain and that in the course of treatment they
should be given permission to ventilate and discuss their frustration about
the broader emotional field. Noting that these patients frequently manifest
behavior pattern type A and do poorly in passive situations, he stresses the
need for the physician to seek the active cooperation of the patient in his
recovery. He suggests that the patient who has usually repressed hostile
feelings be encouraged to complain and make demands on his environment,

now that he is ill as a means of giving expression to his pent-up frustrations.
Bilodeau and Hackett investigated the reaction of postmyocardial infarction
patients meeting together with a psychiatric nurse over a three-month

period. Subjects that came under discussion in this group process included:
current and future states of health, effects of illness on one’s life, the role of
the patient and its effect on the family, the history of the illness, and medical
care following discharge. Adsett and Bruhn have written about the
advantages of short-term group psychotherapy for postmyocardial infarction
patients and their wives. Hellerstein and Friedman finding unnecessarily
limited sexual activity among patients with arteriosclerotic heart disease

emphasized the need for counselling patients and their spouses about this
important function. Wishnie et al., describing the anxiety and depression in
infarction patients after returning home emphasized the need to prepare the
patient for the weak, fearful, uncertain feelings he may experience. Among the
recommendations they make to the medical team caring for these patients
are: regular telephone contact during early convalescence, establishment of a
program of mental and physical activity, avoidance of vague advice,
prescription of drugs for sleep and of tranquilizers for anxiety, and assisting
the patient in altering his lifetime habits in order to adapt to coronary
disease. Walter et ah, describe the effect that arrhythmias have on patients
with coronary disease, leading to symptoms of cerebral ischemia including
dizziness, giddiness and syncope. These reactions may be both a cause of and
a reaction to anxiety and may be allayed by working with the patient’s
chronic anxiety. Patients with symptoms of angina pectoris frequently
experience this distress at times of stressful environmental situations leading

to emotional conflict. At other times, some of these patients are subject to
conversion reactions imitative of their anginal disease. Conversion reactions
frequently occur in patients with underlying anxiety and covert depression

relating to their illness. These patients may become increasingly
hypochondriacal and develop what has been called a cardiac neurosis
superimposed on their cardiac disease. Psychiatric intervention in the form of
relaxation techniques has been employed in these situations by Rifkin.

Wincott and Caird identify two phases of concern regarding the return of
cardiac patients to work. In the first phase, the individual is concerned with
employment and finances. Later, after returning to work, he is concerned
about increased dependence, invalidism, and performance. Williamson et al.,
followed seventy-four patients admitted with congestive heart failure to a
coronary care unit finding that only two were asymptomatic and functioning
normally after a year. Twenty-four had returned to work but were
symptomatic. Another nineteen, although ambulatory, were unable to assume

life activity. Seven remained bed-ridden and twenty-two had died. Concerned
about the staggering morbidity and mortality, they saw this as a critical area
for further research. Wells finds physicians and employers partly responsible
for patient failures to return to work and sees the need to educate employers
and insurance companies and for employee retraining programs. Perlman et
al., contrasted 105 patients with congestive heart failure with fifty controls,
finding long-standing emotional problems, difficulty in accepting illness, overt

denial, and major problems concerning living arrangements. Rosenberg found
that patients with congestive heart failure showed improved function and a
lower hospital-read-mission rate after participation in a group-education

program.
Finally Riseman suggesting that few of the injunctions about activity,

food, blood pressure, smoking, alcohol, anticoagulants, and vasodilators are
proven, believes that the best course for the patient to follow is moderation in
all things, gradually returning to normal activity and moderate exercise. He
should reduce weight, limit intake of saturated fats, control blood pressure,
and eliminate or reduce cigarette smoking. Psychotherapy may be necessary
to achieve moderation for the coronary patient with type A behavior.
Conclusions
A summary of the studies that have been cited herein suggests that
coronary artery disease is more likely to occur in the individual who: (x) has a
family history of cardiovascular disease; (2) lives in a family or social

structure in which genetic determination and/or sociocultural values foster a
particular behavior pattern; (3) lives in a physical environment in which
cardiotoxic factors are present; (4) engages in an aggressive, competitive,

upward-mobile culture without resolving internal conflicts about
dependency, passivity, and sexuality; (5) becomes involved in nonspecific
stressful situations in which these unresolved conflicts are aggravated,
leading to a psycho-biological decompensation elaborated through the
stimulation of the hypothalamus from above and below with an excitation of
both autonomic and adrenal cortical activity; and (6) develops, in the face of
morphological change and physical decompensation, behavioral patterns that
are predicted by the direct effect of those changes on the central nervous
system and the psychological defenses erected to contend with vulnerability
and chronic illness. The elaboration and identification of all of these factors in
a particular patient will lead the physician to an identification of those for
which help can be sought, as well as to a greater awareness of and empathy
for the affected individual.
A review of the psychological aspects of cardiovascular disease as

presented above commences with the limited genetic and environmental
factors that are known. Genetic factors may include either a single genetic
substrata that determines predisposition to both a behavior pattern such as
Type A and coronary artery disease, or the two independent factors closely
linked may be inherited separately but usually together. On the other hand,
the association between cardiovascular disease and particular psychological
patterns may result from the occurrence of heart disease such as rheumatic
fever at a vulnerable time in development, resulting in psychological fixation
at that stage and subsequent distorted development. In the case of the
individual with congenital heart disease, the structuring of personality and

behavior patterns may also result from the effects of the disease on the
intellectual development and/or the limitations imposed by parents and
society on the individual with heart disease. Other patterns are identified in
terms of the reactions of individuals to acquired heart disease, their

emotional responses, and the defenses erected to contain these. An
interesting theoretical consideration is that the early association of
cardiovascular response to environmental events with repetition becomes
conditioned and reinforced. In time the environmental stimulus triggering the
cardiovascular response may be replaced and internalized as a symbolic
stimulus which no longer needs the same external event for activation. With
constant repetition and under the appropriate environmental milieu (internal
or external) secondary changes such as atherosclerosis and cardiomyopathies
develop. An extensive review of the literature suggests that the relationship is

not a linear and unidirectional one between two variables but is more likely a
cyclical process including multiple variables that may be stimulated at
various points in the cycle. Hence, personality variables may lead to behavior
which is cardiotoxic, but cardiovascular disease may also lead to behavior or
reactions that are neurotogenic. For either of these reactions to take place,
the simultaneous occurrence of other variables including genetic,

psychosocial and environmental may need to be present. For the individual
patient, an examination of the individual’s psychological and physical

development, the psychosocial field in which the illness is exacerbated or
precipitated, and the reaction of the patient, his family, and society to his
illness is necessary in order to assist the patient and his family in the very
arduous and circuitous road to maximum rehabilitation.
Psychophysiological and Psychodynamic
Problems of the Patient with Structural Heart
Disease2
Morton F. Reiser and Hyman Bakst
Congestive Heart Failure
Physiological Considerations
The basic physiological problems involved in structural heart disease
that leads to congestive failure can be understood as one of supply and
demand. With the progressive decrease in cardiac reserve that results from
the heart lesion, there ensues progressive difficulty in maintaining adequate
cardiac output in response to varying functional demands.
Congestive heart failure will develop whenever myocardial capacity is

inadequate to meet the metabolic demands of the body. Certain events then
occur which lead to the classical picture of congestive failure, and chief among
them is the impairment of normal renal mechanisms with the resultant
retention of salt and water. The ultimate responsibility for this fluid and
electrolyte imbalance must be assigned to circulatory inadequacy, but the
immediate and crucial mechanism is altered renal function. Consideration of
congestive failure must therefore be concerned not only with disordered
circulatory dynamics but with the physiological factors controlling the
disposition of sodium chloride and water by the kidney.
The balance between tissue needs and the ability of the heart muscle to
meet them may be disrupted by increasing the demand or by reducing the
functional cardiac reserve. Infection, exertion, increase in blood volume,

certain paroxysmal arrhythmias, and emotional stress are all factors which
may lead to a relatively abrupt increase in the demand for cardiac work.
Diminution in coronary blood supply, inflammation (myocarditis,
myocardosis), arrhythmias which reduce efficiency of cardiac function and
emotional stress are factors which may lead to relatively rapid decrease in
the heart’s capacity to perform work. Increased demand and decreased

capacity may occur in combination, and as reserve decreases with time and
advancing disease, progressively smaller loads determine the limits of
compensation.
There is a direct relationship between cardiac output and effective
renal-plasma flow; diminished cardiac output lowers the glomerular filtration
rate, thereby producing a decrease in salt and water excretion. This is not the
sole regulating mechanism however, and it has been established that the
renal tubule may operate independently of the glomerulus in this respect. The
renal tubule is the second discrete regulator of sodium chloride and water
balance. For purposes of simplification, the glomerulus may be considered to
be affected primarily by hemodynamic changes. Tubular function, on the
other hand, is modified chiefly by humoral agents.
The humoral agents which affect tubular function include the
antidiuretic hormone (ADH) of the neurohypophysis, which promotes water
reabsorption, and the adrenal corticosteroids, which promote sodium

retention. Of the latter, the most potent is aldosterone, but other steroids
(hydrocortisone, corticosterone) also exert an appreciable effect.
Norepinephrine can also cause marked change in sodium excretion. Both
adrenal activity and altered circulatory dynamics are necessary for the
development of edema, the prime feature of congestive failure. There are
many factors which evoke increased aldosterone activity in congestive failure,

including dietary restriction of sodium, impaired hormone degradation due to
hepatic congestion, and elevated serum potassium levels. In addition, those
adrenal steroids which are under ACTH (adrenocorticotrophic hormone )

control all have sodium-retaining activity and can, at times, tip the balance in
the direction of failure. The role of emotional stress in increasing adrenal

cortical activity is well known and will be referred to more fully in the
following section when the emotional factors in congestive failure are

discussed.
In attempting to clarify the mechanisms underlying the clinical
phenomena which concern us, it is pertinent to consider the ways in which
psychological stress may affect circulatory equilibrium, either by increasing
current demand or by decreasing available supply, and/or by altering renal
function.
Psychophysiological Changes Leading to Increased Cardiac Work Demand
It has been repeatedly demonstrated that “emotional stress” may be
accompanied by measurable changes in arterial blood pressure, heart rate,

stroke volume, cardiac output, and peripheral resistance. Perhaps the most
carefully and extensively documented study from a physiological point of
view is that of Hickam and co-workers who utilized a spontaneous,
nonspecific stress situation—an important academic exam—in order to
demonstrate differences in measurements reflecting circulatory dynamics
obtained during “emotional tension” from measurements obtained during
relative relaxation. The subjects were twenty-three healthy medical students.

Each student was examined just before the critical exam and then again a day
or two later, after having been informed that he had passed. The average
cardiac index (volume output of the heart l./min per m.2 body-surface area)
before the exam was 2 l./min. per m.2 greater than that measured during
relative relaxation. When this figure was converted to “work load,” it
corresponded to a load which would be demanded by increasing oxygen
consumption by an amount equal to the basal metabolism.
In Hickam’s work, as well as in that of other authors cited in the

footnote on this page, the meaning of the psychological stress and the nature
of the reaction to it were not specifically studied in the individual subjects.
Hickam noted that the pattern of mobilization varied in his subjects, and
described three patterns. For the largest part of the group, anxiety was
accompanied by an increase in cardiac index, decrease in peripheral
resistance, and relatively small rise in mean arterial pressure. In a smaller
second group, the “anxious state” was associated with a slight to moderate
rise in peripheral resistance, with a rise in mean blood pressure and no
change or a slight decrease in the cardiac index. In three subjects there were
rises in cardiac index but large moment-to-moment fluctuations in stroke

volume and heart rate.
Much research has been done in an effort to determine whether specific
differences in pattern of circulatory response may be related to specific

differences in the concomitant emotion involved. The investigative group
headed by H. Wolff at Cornell, through the use of structured stimuli
(introduction of conflictual topics during interview), have described

relationships between different directly observed (and subjectively reported)
affects and different patterns of circulatory mobilization. Funkenstein et al.,

working with groups of healthy subjects under a specified stressful task, have
described three patterns of emotional response which they designate: “anger-
in,” “anger-out,” and “anxiety.” On the basis of ballistocardiographic, heart-
rate, and blood-pressure recordings taken simultaneously, they reported that
subjects showing the “anger-out” pattern developed circulatory changes

similar to changes produced by the administration of noradrenalin. (This
resembles the second pattern described by Hickarn, see above.) Subjects
showing “anxiety” and “anger-in” reactions demonstrated changes similar to
those that would be produced by injection of adrenalin (resembling the first

pattern described by Hickarn). Ax and Schachter, working on subjects who
were exposed to laboratory situations deliberately staged to evoke either
anxiety or hostility, reported differences in pattern of circulatory changes

similar to those described by Funkenstein.
The implication of this is that outwardly displayed anger is
accompanied by a release of norepinephrine, whereas anxiety and anger
directed inward are accompanied by the release of epinephrine. It should be

noted that these implications have been drawn by indirect inference from
measurement of circulatory functions, and the studies did not include assays
of the hormone levels in the blood. The inferences drawn are also open to
criticism, since they were based upon quantitative amplitude measurements

of ballistocardiographic tracings obtained by the use of direct-body pickup
instruments which cannot be satisfactorily calibrated. The issue may be more
complicated than this, since Lacey and coworkers have advanced definite
evidence to show that individual differences in pattern of response may be
largely reflections of constitutional differences, and only partly reflect specific
connections between specific affects and particular patterns of response.

Reiser, Weiner, and Thaler, in recording circulatory functions during
projective psychological testing, observed the first two patterns reported by
Hickarn, as well as an intermediate group which, like Hickam’s, seemed too

variable from moment to moment for adequate qualitative classification. In all
subjects, brisk responses (of the same magnitude as those reported by
Hickarn and others) occurred in association with little directly observable or
subjectively reportable evidence of affect. The amount of affect which could
be identified in this way was not sufficient for classification. Differential
patterning of the circulatory responses appeared to be related more to

differential attitudes toward the examiner, but the experiment did not allow
for adequate exploration of the unconscious aspects of this relationship.

Although the question of specific relationships between affects and
physiological patterns of circulatory response is left open, these studies singly

and collectively demonstrate that emotion is accompanied by circulatory
changes which may greatly increase the amount of work required of the
heart. Stevenson et al., have demonstrated that the circulation recovers from
the effects of exercise slowly and inefficiently during states of emotional
tension, thus prolonging the strain upon the heart.
Most of the studies referred to above deal with changes in healthy
subjects whose circulatory systems were presumably normal. The studies of
Hickarn, Wolff, and others were extended to patients with valvular disease
and limited cardiac reserve, with similar results. Striking is Hickam’s
demonstration in a patient with severely limited cardiac reserve that the
effects of exercise and anxiety were similar and were in the direction of
developing congestive failure. Cardiac index and pulmonary arterial pressure

were determined by cardiac catheterization. With anxiety as well as with
exercise, there was a failure of the cardiac index to rise, accompanied by an
increase in pulmonary arterial pressure.
Psychophysiological Changes Leading to Decreased Myocardial Capacity
Diminution in functional cardiac reserve during tension may occur as a
result of interference with intrinsic cardiac mechanisms governing heart rate

and rhythm. Changes in the electrocardiogram reflecting such interference
with cardiac mechanisms have been repeatedly demonstrated by numerous
workers, including Katz et al., Mainzer and Krause, and Wendkos. This
literature has been reviewed by Weiss.
Psychophysiological Changes Altering Renal Function
There have been only a few studies which bear directly on the role of
emotional factors as they affect renal function. Diuresis has been reported in
both animals and man following emotional stress, and investigations have
been conducted on the effect of specific emotions on fluid and electrolyte
balance. Schottstaedt and his co-workers have reported a series of such

studies, and indicated a direct correlation of certain emotional response
patterns with specific types of alteration of water and sodium excretion. They
found that feelings of anger, uneasiness, and apprehension produced
increased rates of water and sodium excretion, whereas feelings of

depression were associated with decreased rates.
Confirmation of these findings by other investigators has not been
reported and further research on these psychophysiological relationships is
needed. Other evidence bears directly on the relationship between emotions

and adrenal cortical activity and between adrenal cortical activity and renal
tubular function. Thus, by inferential reasoning, one may hypothesize a
sequential psycho-adreno-renal pathway as an important factor in the clinical

manifestations of congestive failure.
Clinical Observations
In view of the psychophysiological findings summarized above, it is not
surprising to find that stressful events often precede the development of

episodes of congestive failure in patients with established cardiac disease and
limited reserve. This expectation can be affirmed readily on the medical
wards of any hospital. Chambers and Reiser interviewed twenty-five
consecutive patients who were admitted to the wards of the Cincinnati
General Hospital because of congestive heart failure. An acute emotionally

stressful experience had immediately preceded the development of
congestive failure in 76 percent. In each instance these events seemed to have
highly specific meaning for the patient in relation to his previous life
experiences and conflicts, and in most they were superimposed upon a

chronic state of sustained emotional tension. An important aspect of these
findings lies in the fact that most of these patients had been through similar
conflictual crises previously without having developed congestive heart

failure, that is, similarly stressful experiences occurring before the critical
limitation of cardiac reserve had developed, had not resulted in clinical
disturbance of the patients’ circulatory equilibrium. It was only after the
underlying progressive heart disease had resulted in serious loss of cardiac

reserve that the stressful events assumed clinical importance in respect to
circulation. All of the patients in this series were seriously ill and exhibited
advanced forms of heart disease and serious degrees of cardiac
decompensation. They were the type of patient in whom the extent of

underlying cardiac pathology might so impress the physician that he might
well not feel it necessary to search for a specific precipitating factor. It is
important to recognize that the extent of the underlying heart damage does
not ordinarily account for the nature of the forces immediately responsible
for the abrupt onset or worsening of congestive failure. In the' same study it
was noted that marked improvement in clinical status coincided with
providing the patient an opportunity to share and discuss his difficult life
with the physician. It was further observed that a continuing supportive
relationship with the physician aided in avoiding further unresolved
emotional crises and stabilized the clinical course to a great extent (without,
of course, effecting any change in the extent of the underlying heart damage).
In summary, the tenuous balance between work load and cardiac
reserve in patients with structural heart disease and diminished cardiac
reserve may be seriously disturbed by the various circulatory responses that
accompany psychological stress. In this fashion, serious episodes of
congestive heart failure may be precipitated and sustained by emotionally
stressful situations.
Somatopsychic Problems
In a discussion of the somatopsychic problems in patients with

structural heart disease, it is useful to identify those factors intrinsic to
cardiac disease which may operate as stressful agents in the psychological
sphere, and thus demand attempts at adjustment on the part of the patient.
The clinical effects of each of them stem from the fact that they act as sources
of anxiety. The end results may come about in two ways, either as the result
of untoward effects of free anxiety and other affects upon the tenuous
circulatory balance, or as the result of indirect consequences of anxiety,
namely behavior which stems from maladaptive use of ego defenses against
anxiety. These maladaptive behavioral phenomena, in turn, may complicate
or aggravate the circulatory problem. They may lead to behavior which
interferes with the patient’s ability to utilize a prescribed medical regimen,
for example, refusal to take digitalis. They may also be reflected in more
general aspects of the patient’s personality adjustment and lead to psychiatric
problems (e.g., depression) which may not immediately affect circulation but
may require therapeutic attention in their own right. The complexity of these
direct and indirect consequences, and the manner in which they may in
themselves lead to mobilization of additional anxiety (thus completing
feedback cycles), is schematically illustrated in Figure 26-1.
Figure 26-1.
Figure 26-1.
Psychophysiological relationships in patients with structural heart disease.
The psychological burden imposed by the onset and/or diagnosis of
heart disease may stem from any or all of three general sources. The first
source is constituted by the symptoms themselves. The abrupt onset of
sensations, such as breathlessness, severe precordial pain, palpitation,
dizziness, etc., is anxiety provoking. The initial anxiety generated at the onset
of an acute episode may impose considerable additional burden upon the
already compromised circulation.
The second source is the threat inherent in the diagnosis of heart
disease. Any illness may cause anxiety because of actual or threatened
damage to bodily integrity. In the case of the heart anxiety is exquisitely
exaggerated. The reasons for this are general and universal. The central
indispensable role of the heart in maintaining life provides an appropriate
background for the use of its mental representation as a symbolic object of
awesome unconscious fears. Ample reinforcement comes from folklore,
symbolic language conventions, and a vast popular literature. It is probable

that the diagnosis of heart disease activates fears of sudden, unexpected, and
catastrophic death. The danger implied by the diagnosis is not to be
minimized here, but it should be pointed out that fears may exaggerate and
amplify it out of proportion. For example, the unconscious threat may be no
less intense to the patient who is informed of the discovery of a functional
cardiac murmur than it is to the patient confronted by a diagnosis of serious
advanced rheumatic heart disease. In addition to these fears stemming from

the diagnosis, there may be specific additional factors causing conflict. For
example, a patient who has had a highly charged ambivalent relationship with
a relative or close friend who died of heart disease may have unresolved
problems of identification and guilt.
The third source of anxiety stems from the fact that the patient
experiences (or can anticipate) a real limitation of his physical capacity, and
knows that this will be progressive. The adaptive task imposed upon the
patient cannot be underestimated. Successful or ideal adjustment necessitates

realistic acceptance of the loss and the attendant limitations which it imposes.
It also necessitates rearrangement of living patterns which take these
limitations into account and at the same time make maximal utilization of
residual capacities. Many factors influence the degree to which the patient
succeeds in meeting this challenge. The most important are: (1) the severity
of the specific emotional impact of heart disease; (2) the strength of his
personality; (3) reactions and attitudes of medical personnel, particularly his
doctor; and (4) the reactions of people close to him. The psychological trauma
inherent in the development of a cardiac disorder may severely aggravate a
preexistent psychiatric problem. In some instances it serves as a precipitant
for the development of major psychiatric difficulties in a previously
satisfactorily integrated personality.
There are a number of ways in which the handling of anxiety may lead
to unsatisfactory responses. Inadequately resolved anxiety may worsen the
medical condition, as described above. In addition, psychological
mechanisms, which ordinarily have the function of defending against anxiety,

may be inappropriately and maladaptively mobilized in the patients attempt
to defend against the threat. For example, specific ego defenses such as denial
(for example, of illness) and reaction-formation (for example, against
dependent wishes) may lead to open, unrealistic, and rebellious

unwillingness to adhere to a prescribed medical regimen. This is a problem
frequently encountered in middle-aged men with coronary disease, and such
behavior may unwittingly be self-destructive. So far as it contributes to
progression and aggravation of symptoms and further actual constriction of
the patient’s physical capacity, it creates new anxiety, and in this indirect way
another type of vicious cycle is established.
Disturbances in the sphere of behavior may not be restricted to issues

centering on the physical disorder and its care. Profound changes may
develop in the basic functional organization of the personality. Extensive
reliance upon defenses, such as projection and displacement, may lead to
drastic changes in the patient’s view of the world and his reactions to specific
people. Unconsciously determined changes in significant and important
relationships may result—for example, dissolution of business associations,
divorce, etc. These too may represent fresh sources of tension and conflict
which lead to still another type of feedback cycle. Even without this,
symptomatic behavior of this magnitude represents major
psychopathological development and demands therapeutic attention in its

own right.
As the situation progresses, more far-reaching long-term changes may
become evident. As in any major illness, strong regressive tendencies

develop, and when these are added to and combined with the kinds of
developments described above, a process is instituted which may eventuate

in serious constriction of all aspects of ego-function in general, and, in
particular, in restriction of the defensive operations of the ego to relatively
few mechanisms that are for the most part maladaptively utilized. The cardiac
status becomes part of the self-image, and the personality becomes
constricted, rigid, brittle, and fragile. The cardiac status may become a
nuclear part of the patient’s style of conducting interpersonal relationships,
and this is most often manifested by behavior which exploits the physical
condition in the service of secondary gains which may acquire considerable
value.
One additional mechanism should be mentioned, which can be
described as a form of “binding of anxiety.” Whenever serious physical
disease (or a physical condition which can be treated as “serious”) develops
during a period when the patient is grappling with a serious unconscious

psychological conflict, the physical disease may be seized upon as a way of
resolving the conflict. For example, the illness may provide a way of avoiding
the issue by precluding the conflictual activity and may thus reduce the
importance of the conflict to a state where it is of academic interest only. Two
typical and frequently seen examples of this mechanism can be cited. The first
is the example of the patient in early adolescence who has not yet reached a
satisfactory resolution of problems centering on issues of sexuality and

independence; chronic invalidism for such a patient may provide a very
convenient way out. The second example is that of the overtly aggressive and
ambitious man who harbors unresolved problems about success. Here again,
even early manifestations of cardiac disease may offer a face-saving occasion
for retrenchment and retreat from vocational growth. In other words, the
status of illness may acquire a powerful psychic value because it offers

opportunity for “acceptable” avoidance of serious conflicts that would be
activated in a fuller life sphere.
Essential Hypertension
Introduction
The concept of essential hypertension remains variable and imprecise

despite increasingly sophisticated techniques for correlating physiological
and biochemical processes with elevated blood pressure. An etiological and
physiological explanation for more than 90 percent of hypertension remains

undeveloped.
Essential hypertension is generally identified by blood-pressure

readings of greater than 140/90 mm. Hg. for which an etiology has not been
identified. Its incidence is usually higher for each advancing decade. Its
prevalence is greater in some geographical areas and sociocultural groups
than in others. The readings themselves may be associated with progressive
symptoms and signs. The former includes “top-of-head” headaches, dizziness,
ringing in the ears, and irritability. Signs include epistaxis, elevated blood-
pressure readings, and retinal changes. Secondary symptoms and signs are
associated with pathophysio-anatomic changes occurring in organ systems,
especially the heart, kidneys, and brain.
The course of the disease may be benign or malignant. Recent statistics
suggest that even in benign situations, the course is relentlessly progressive

despite a slower development of secondary organ involvement. What governs
the differences between a benign and a malignant course remains essentially
unknown, although a recent study has suggested different renin and
aldosterone patterns in patients with hypertension which seem to have
prognostic value in terms of myocardial infarcts and cerebrovascular
accidents. Nevertheless, we are left with a poorly defined phenomenon which

undoubtedly groups together symptoms, signs, and secondary patho-
physioanatomic manifestations for which future research may establish one
or more precise etiological factors.
Epidemiological Considerations
Before considering the psychological aspects of essential hypertension,
some attention needs to be given to epidemiological findings. Similar to
coronary artery disease, epidemiological considerations are fragmentary and

for the most part supply only limited impressions upon which derivative
formulations are based. The picture is further complicated by the seemingly
conflicting findings often reported from the epidemiological field. Studies in
the United States have demonstrated that hypertension is higher among
urban than among rural dwellers, among lower than upper classes, among
blacks than whites, and in men than women. It is also noted that the
development of hypertension is more frequently observed and of greater
severity in the rural dweller who moves to the city than in the individual who
has always lived in the city.
Donaldson, studying changes in disease incidence and prevalence
among rural Africans undergoing acculturation, noted that hypertension was
greater in the more acculturated urban groups. Obvious correlates of
acculturation are changes in life style which include food, housing, work, and
interpersonal relations. The changes in disease patterns are probably more
complex than the apparent associations suggest. For example, the changes
observed may be related to an unmasking of a latent genetic predisposition in

a population that rarely became manifest in the less sophisticated and more
socially supporting tribal state where infectious disease and starvation

frequently lead to early death. Other relative factors may be considered,
although supporting data are lacking. Blood-pressure levels identified as

falling in the hypertensive range in one geographical area and biocultural
population are not necessarily equivalent to identical values for another area
and group. These studies suggest that both genetic and environmental factors
are related in the pathogenesis of essential hypertension.
Psychobiological variables
The ensuing discussion examines genetic and environmental variables

in terms of their interrelationships with psychological ones in individuals
developing hypertension. In considering these interactions, several
hypotheses are entertained: (1) the psychological and social aspects of
behavior related to hypertension may be independent derivatives of the same

or a different (though inherited together) genetic factor as the physiological
component; (2) the psychological and physiological components may become
associated during the course of development; and (3) the psychological

component may be a reaction to the disease process.
Longitudinal Studies
Thomas is the most prominent among recent investigators of
hypertension. For more than twenty years, she has studied prospectively the
development of hypertension and associated diseases in medical students. In
the course of her investigations, she has made the following correlations: (x)
the proportion of students in graduating classes manifesting clinical
hypertension was three times that in younger classes; the proportion
showing transitory hypertension was double; (2) in the former group, 62.5
percent gave a history of parental hypertension compared with 36.0 percent

in the latter; (3) the “at-risk” groups also tended initially to manifest higher
resting blood pressures, elevated cholesterol levels, and more intense
reactions to stress behaviorally; (4) psychologically, she noted apparent
submissiveness of the predisposed individual under the domination of a
parent; and (5) the onset of hypertension occurring as an anniversary
reaction or in the setting of an unrealistic marriage. She suggested that the
observed hypercholesterolemia represented an inborn metabolic defect; that

the inheritance of the deficit might be governed by a single locus, although
modifying genes and environmental factors were important in determining
clinical expression; and that the total behavioral pattern developing under
stress might also reflect an inborn predisposition.
Paffenbarger and his associates have also made correlations between
characteristics observed in college students and subsequent disease.
Undergraduate patterns of cigarette smoking, elevated blood pressure,
increased body weight, shorter body stature, early parental death, heart
consciousness, and nonparticipation in varsity sports were associated with
the occurrence of subarachnoid hemorrhage and occlusive stroke, pathology
frequently resulting from chronic hypertension. Associated with heart

consciousness and cigarette smoking, Paffenbarger noted emotional distress
in terms of anxiety and irritability.
Some Biological Correlates with Behavior
Specific biological variables have been identified in patients with
hypertension. Similar to some of the psychological variables discussed below,

these are as likely to be secondary to the development of hypertension as
they are to be precursors. Renin, angiotensin I and II, and aldosterone may
also be considered in this light. Through the accumulation of data via
longitudinal studies such as those cited above it may be possible for an

eventual distinction to be made.
Schneider and Zangari noted an association of anxiety, tension, fear,
anger, and hostility with decreased clotting time, increased viscosity, and
elevated blood pressure. With feelings of depression, dejection, and of being
overwhelmed, they noted prolonged clotting time, normal viscosity, and

normal blood pressure. Hypertensive as opposed to normotensive subjects
demonstrated decreased clotting time to the stress of the pressor test.
Testosterone and estrogen have been cited as affecting blood-pressure
levels in addition to hormones of the pituitary-adrenal axis. Susceptible male

mice developed marked hypertension and aggressive behavior when
subjected to social stress, whereas susceptible castrated male mice under the
same circumstances remained normotensive and nonaggressive. However,
when the latter mice were given testosterone, blood pressures rose and
aggressive behavior developed. In some lower sociocultural groups,
premenopausal women tend to manifest higher blood pressure than men; the
reverse pattern prevails following menopause. Among upper sociocultural
groups, the reverse pattern has been observed. These findings suggest that
age, sex, and other variables are more than biological but interact with
sociocultural roles and the personalities and life situations involved with
these. Women who have family histories of hypertension and personal

histories of toxemia of pregnancy appear more sensitive to the hypertensive
effects of estrogen preparations. They also appear more likely to experience a
depressive response to these preparations.
Von Eiff suggests that hereditary factors prime the pressor center of the
hypothalamus to respond hyperactively to environmental stresses leading to
increased blood pressure. Yamori et ah, have found lower concentrations of
norepinephrine in the lower brain stem and hypothalamus of spontaneously
hypertensive rats as compared to normotensive ones. This was associated

with a lower concentration of L-amino acid decarboxylase, but not of tyrosine
hydrogenase, suggesting that abnormal metabolism of ergotrophic hormones
may be related to hypertension. Sjoerdsma has noted that monoamine

oxidase inhibitors lead to a decarboxylation of alpha dopamine, resulting in
what is in effect a medical sympathectomy. This is of interest, inasmuch as
clinical observations have frequently suggested a correlation between
depression and hypertension, and that the latter tends to improve with the
treatment of the former with antidepressants. These fragmentary findings are

identified in order to suggest the direction of neurophysiological research in
seeking a central mechanism affecting blood pressure. These and others have
yet to be woven into an integrated formulation. The actual regulation of blood

pressure is a highly complex phenomenon and, as Penaz has noted, depends
also on the mechanical parts of the system such as the heart as well as central
nervous control.
Psychiatric Relationships
As long ago as 1902, Alexander noted that blood pressure was
frequently elevated in patients suffering from acute melancholia, as opposed
to chronic melancholia or mania. Altschule corroborated this observation,
finding that elevation of blood pressure was the rule in patients with
involutional depression whereas patients with schizophrenic states more
often showed blood pressure readings below the normal range. Readings in
patients displaying manic behavior were only occasionally elevated.

Vanderhoof et al., demonstrated a lower blood flow in patients with
schizophrenic states as opposed to those with affective psychoses. Heine et

al., studying hypertension in severely depressed patients, observed a
decrease in blood pressure for the agitated patients following improvement
in their mental status. However, those patients manifesting less agitation and
having a history of more frequent depressive episodes were less likely to
demonstrate a change in blood pressure following treatment. They suggest

that chronicity of emotional stress correlates with irreversible changes in the
regulation of blood pressure.
Overview of Psychophysiological Relationships
Several reviews are first briefly identified and discussed to serve as

reference for the student interested in further pursuit of this subject.
Alexander was one of the first investigators to consider hypertension as
a progressive sequence of psychopathophysiological changes. Not ruling out
the possibility of a constitutional instability of the vasomotor system, he
observed that the specific neurotic handling of excessive and inhibited hostile
impulses precipitated by a conflictual situation was associated with extreme
fluctuations of the blood pressure. In time, with repetition of the conflictual

episode, he suggested that these patterns tended to become fixed leading to
chronic neurotic states associated with elevated blood pressure and still later
to the organic consequences of this condition. Much of the work of
subsequent investigators has elaborated on data that have been interpreted
as supporting this hypothesis. However, Binger in 1951, reviewing more than
200 articles, suggested that no one had “hit the mark” in establishing a
relationship between psychological influences in the etiology of hypertension.
Despite the enormous growth of the literature in the intervening decades, it is
still possible to make a similar assessment. Nevertheless, many of the
variables that have been identified have assisted the clinician in approaching
and attempting to understand the patient with hypertension.
Brod conceptualizes hypertension as an intensified and extended
normal hemodynamic response to an acute emotional stress, consisting of a
redistribution of cardiac output, with blood shifted from the viscera and skin
to the skeletal muscles, myocardium, and brain, advantageous for the

performance of strenuous muscle work. The increased blood supply to the
muscles is in part secondary to the release of epinephrine and is partly
related to a reflex involving cholinergic fibers. This pattern is analogous to the

circulatory response produced in animals by electrical stimulation of the
hypothalamus, which is accompanied by apprehensive and rage behavior
identified as “defense system.” Brod hypothesizes that this is an old
phylogenetic reaction which has been transferred from a threatening external

situation to a symbolic internalized stimulus. Whereas, phylogenetically, the
reaction would cease with the removal of the provoking stimulus, in the
human situation the internalized symbol remains as a constant stimulus to

the vascular and rage reaction, resulting in eventual pathophysiological and
pathoanatomic changes. Levi suggests that emotional stress triggers
sympatho-adreno-medullary and related physiological changes of relatively
short duration. If repeated often enough over lengthy periods and of
increasing intensity, he sees these as etiological in the development of

essential hypertension.
Geiger and Scotch in 1963 reviewed the biological, epidemiological,
psychological, and sociocultural factors relating to the etiology of
hypertension. In concluding, these authors found ample room for further
research. Essential hypertension as a pathological entity with a well-

established etiological and physiochemical mechanism still required
clarification. They questioned to what extent essential hypertension was
related to one or more primary disease processes yet to be identified, and

also whether it might not represent a variation on a norm. More research was
required in establishing a hereditary basis for hypertension through the study
of first-degree relatives and controls. Longitudinal studies were necessary to

establish the natural history and progress of the disease. These authors saw
the implication of sociocultural factors as an open question. They noted that
age, sex, and other variables were more than biological, inasmuch as they
served as the bases for personal interaction in a culture and family and
consequently were precursors of sociocultural and personality factors, which
assumed possible significance in their own right. They raised the still
intriguing question whether many of the psychological variables associated
with hypertension might not be more directly related to the lability of blood
pressure frequently observed in the prehypertensive individual. Finally, they
considered the stress factors relating to the onset of hypertension and the
adaptive behavior of individuals to these and to the subsequent disease
course.
Groen, following Page’s Mosaic theory of essential hypertension,
suggests that the reactivity of the central nervous system under the influence
of genetic and environmental influences is the main causal factor in a

constellation of multiple factors associated with the development of
hypertension. He cites the following: (1) Hypertension is an exaggeration and
intensification of normal reaction patterns of the organism; (2) It follows in

the wake of repeated and prolonged conflicts; (3) It occurs in individuals
predisposed to react to conflicts with key persons in certain ways, a pattern
which is both genetically determined and environmentally conditioned; (4)

These individuals demonstrate personality traits which include compulsivity,
rigidity, sensitivity, a need for love, a fear of losing love, a tendency to
dominate, a tendency toward aggression, and a tendency to inhibit the acting
out of aggressive impulses; (5) Hypertension is precipitated in a conflict

situation in which active aggression is inhibited; (6) Exacerbations of conflict
lead to exacerbation of blood-pressure response; (7) The more severe the
personality disorder and the more intense the conflict situation, the more
malignant is the course of hypertension; and (8) The greater the sensitivity
and the greater the reactivity associated with a greater tendency to inhibit
motor discharges, the more likely will the reaction be channelled through the
limbic system, the hypothalamic vasomotor center, the sympathetic nervous
system, the heart, and the smooth muscles of the renal and splanchnic
arterioles, leading to increased peripheral resistance. Groen sees this in terms

equivalent to a displacement phenomenon in which the organism reacts to a
symbolic stress via a neurovisceral route as opposed to reacting to a physical
stress via a neuromuscular route. He indicates that changes in the
environmental conditions, the use of central-acting tranquilizers, and
peripheral-acting blocking agents together with supportive psychotherapy
have ameliorating effects on hypertension.
Figure 26-2.
Figure 26-2.
Psychophysiological relationships in patients with essential hypertension.
Reiser, in reviewing his own and others’ work, identifies three phases of
hypertension; Phase 1; preceding the manifestation of the clinical disease;
Phase 2: the onset of the disorder; and Phase 3: the continuing course of the
disease once it has become established (see Figure 26-2). For each of the
phases, he suggests that the underlying pathophysiological mechanisms may

differ. For example, the importance and relative influence of variables, such as
sodium metabolism, emotional influences, neurogenic and hormonal
mechanisms in the mediation of the psychophysiological process may change
as the disease progresses. With his associates, he has recorded the difference
in the labile blood-pressure responsivity of normotensives and patients
labelled prehypertensive, as contrasted to the limited responsivity of blood
pressure to a structured experimental interpersonal stress in patients with
well-established essential hypertension. In the pre-dispositional phase, Reiser

considers both genetic factors and experiential constitutional factors
(deriving from the conditioning of the organism during its prenatal, perinatal,
and early neonatal experience through the shaping and reinforcement of
visceral functions) as contributing to the establishment of a latent but

potentially pathogenic hypertensive pressor mechanism. For example, he
cites the infant’s crying reaction to nonspecific stress as involving a Valsalva
response causing an increased intrathoracic pressure, a decreased ventricular

filling, a decreased cardiac output, an increased heart rate, and an increased
peripheral resistance in order to maintain the perfusion pressure of vital
organs. Behavioral shaping of such a response pattern might occur through
chance experiences affecting the organism in which emotions and their

defenses become annealed with specific physiological patterns at “critical”
phases of development. The defense pattern itself may also be learned from
familial patterns of reactivity to stress. With repetition of stressful events, the
relationship between the psychological and physiological reactions becomes

reinforced. On the other hand, presence of an inherent hyperreactive pressor
mechanism may also directly influence the development of psychological
traits, such as ego defenses, that would protect against its activation by
attenuating closeness of interpersonal relationships (insulating defenses)
(see also Chapter 28, Introduction). This vascular hyperreactivity in and of
itself, or as a reflection of total central-nervous-system hyperreactivity, may
then be associated with independently observed emotional and psychological
patterns of response in individuals identified as prehypertensive or
hypertensive.
In Phase 2, Reiser hypothesizes the breakdown of the critical ego-
defensive systems in reaction to stress. With the failure of ego defenses,
changes occur in the autonomic outflow tracts, including sympatho-adreno-
medullary mechanisms and the hypothalamic anteropituitary adrenal cortical
axis. Affect and regressive changes occur in a large number of ego functions
including attention, perception, cognition, and intellectual functions. These
also influence and are in turn influenced by autonomic and/or hormonal
reactions. At this point, cyclical interactions are recognized in which not only
do psychological processes influence physiological ones but the changes in
the latter directly affect and compromise the former.
In Phase 3, the process developed during Phase 2 becomes fixed

resulting in an individual who is different both physiologically and
psychologically from what he was in Phase 1. In this Phase entirely new
patterns of behavior and reactions prevail.
Emotions
Rennie identified that blood-pressure elevation related to anxiety and
depression in patients. Later Ax associated increased diastolic blood pressure

with decreased heart rate, increased skin conductance, and increased muscle
potential with anger. In contradistinction, fear, while associated with
increases in the latter two variables as well as with respiratory rate, did not
produce an elevation in blood pressure. On the basis of these observations, he
related anger to a discharge of epinephrine and norepinephrine as opposed to
fear which he saw as producing an epinephrine response. Funkenstein
recorded similar observations, suggesting anger-out related to

norepinephrine while anger-in and anxiety related to epinephrine. However,
specific biochemical correlates have never been measured for these states.
Saul identified hostility as the essential component in patients with

hypertension. He described this as arising from an unresolved relationship
with the mother resulting in conflicts over passivity-activity, dependence-
independence, and sexuality. Miller suggested that repression of hostile

emotion was the core factor in hypertension. Moses observed both rage and
resentment as the psychic correlates of elevated blood pressure related to
increased peripheral resistance, in distinction to blood-pressure elevations
secondary to anxiety and related to increased stroke volume and heart rate
without a change in peripheral resistance. Both Schachter and Van der Valk
identified fear, anger, and hostility as more intense and associated with
greater elevations in hypertensives as compared with normotensive controls.
Kaplan et al. extended these observations by demonstrating hostile content in
samples of verbal productions and hypnotic dreams of patients with

hypertension. Using Rorschach factors, Brower correlated higher diastolic
blood pressures in relationship to lower adjustment to reality. Graham and
coworkers related elevations in blood pressure in hypertensive subjects with
the attitude of having to be on guard against bodily assault. Moos and Engel,
studying response specificity to stress in hypertensives vs. arthritics,
demonstrated sustained elevation in blood pressure in the former and greater
muscle reactivity in the latter. In addition, they showed that arthritics could
adapt for blood pressure but not muscle tension where the reverse prevailed
for hypertensives. Weiner et al. studying cardiovascular responses in
hypertensive and peptic-ulcer patients to TAT (Thematic apperception test)
cards noted that these related to the interaction of the subject and
experimenter. Subjects with essential hypertension were remarkably
unreactive as a group and this lack of physiological responsiveness was

related to the nature of the interaction. McKegney and Williams showed that
patients with hypertension, as opposed to those without, had greater

increases in blood pressure during a personal discussion phase of the
interview. Williams et al. in further work suggested that blood-pressure
elevation during an interview was related to the intensity of interviewer-
subject interaction. Silverstone and Kissin demonstrated that patients with
essential hypertension tended to be more field dependent than patients with
peptic ulcer. Goldstein et al. showed that field-dependent subjects have higher
GSRs (Galvanic Skin Response) at rest, and do not discriminate on a
physiological level as well between conditional and other similar stimuli.
Sapira et al. in showing films of “good” and “bad” doctor-patient relationships
to hypertensive and normotensive subjects, found that the hypertensives

tended to deny seeing any difference between the two doctors. These studies
suggest that the hypertensive patient may be more vulnerable to external
threats and therefore perceptually tend to screen out potentially noxious
stimuli as a behavioral response protecting his hyperactive pressor system.
Personality
Dunbar pioneered the work in relating personality styles to specific

illness constellations. She identified lifelong patterns of anxiety,
perfectionism, compulsivity, and difficulty with authority figures as the
psychological components of the individual with hypertensive disease.
Gressell et al. and Saslow et al. identified obsessive-compulsive behavior and

subnormal assertiveness. They also noted that this correlation prevailed
regardless of the type of hypertension. Ostfeld and Lebovits, using Rorschach
and MMPI tests, also found no difference between patients with renal and
essential hypertension. Noting that blood-pressure responses during periods
of life stress were also similar in the two diseases they concluded that
personality and attitude factors were etiologically not related to essential
hypertension. On the other hand, Koster, emphasizing differences found
among patients with essential hypertension, suggested that it is basically

several different diseases, each with its own peculiar physiology and
psychology. Davies, using the Eysenck Personality Inventory, found no
correlations with neurotic traits among patients with hypertension, although
he found correlations with body weight, arm circumference, body build, and a
family history of cardiovascular disease.
To summarize these studies, it is suggested that individuals with
hypertension cope with stresses likely to precipitate emotional feelings
(anger, anxiety, sadness) with repressive and protective psychological

defenses leading to behavior patterns that include altered perception,
especially in the area of interpersonal relationships. When stress factors
break through these defenses, aggravation and exacerbation of hypertension

occurs.
Environmental Factors
Investigators have been concerned with the identification of
environmental stress and its relationship to the development and/or
exacerbation of hypertension. Wolf et al. studied fifty-eight patients with
hypertension and reported that they met day-to-day threats and challenges
with restrained aggression, simultaneously displaying a vascular reaction
characterized by elevated blood pressure and vasoconstriction of both
afferent and efferent renal glomerular arterioles. Even after sympathectomy,
they observed that hypertensives continued to respond to threatening

situations with constriction of the afferent arteriole although the efferent
arteriolar reaction was abolished. Reiser et al. associated emotionally charged
life situations with the course of the disease and the precipitation of
malignant hypertension. Harris et al., studying “prehypertensives” (patients
with labile blood-pressure responses) and matched controls, found that the
former were less well-controlled, more impulsive, more egocentric, and less
adaptable in stressful situations. Henry et al., using an ingenious

intercommunicating box system, studied the social response of two groups of
mice, differently raised, to the effect of crowding and competition. Mice
isolated from weaning to maturity showed profound physical signs and

pathology in addition to markedly elevated blood pressure. In addition, the
deprived mice demonstrated an inability to respect each others need for
territory and to control aggression. Subsequently, they observed that

susceptible mice subjected to psychosocial stimulation showed increases in
catecholamine-forming enzymes. They suggest that the increase in these
enzymes may be neuronally mediated and that unlike epinephrine and
norepinephrine, enzyme changes may take a long time to develop. Henry and
Cassel in a review article suggested that repeated arousal of the defense
alarm response may be one mechanism for elevated blood pressure. In man,
such arousal may occur when previous socially sanctioned patterns of
behavior, to which the organism has become adapted during critical early
learning periods, can no longer be used to express normal behavioral urges.
Difficulties in adaptation and status ambiguity may result in years of repeated
arousals of vascular, autonomic, and hormonal function due to the organism’s

perception of events as threatening. This may lead to progressive and
irreversible disturbances.
Kasl and Cobb reported that blood-pressure levels were higher among
workers during an anticipation of job loss, unemployment, and probationary
reemployment than after later stabilization. Men, whose blood pressure
remained higher for a longer time, were subject to greater unemployment,
manifested lower ego resilience, and reported longer-lasting subjective

stress. Harburg, Schull, et al. in a pilot study, identified that the proportions of
persons with hypertensive levels were significantly greater in a high-stress

area than in a low-stress one. The stresses identified included: ecological,
personal-interpersonal (making a living, marital, early family life,
neighborhood, race relations, life situations, status striving, resentment, self-

esteem), and health risks (family history of cardiovascular disease, weight,
smoking, infrequent use of medical aids). Sokolow et al. studied blood
pressure responses automatically recorded every thirty minutes in
hypertensives who concurrently kept a log of events and completed mood
checklists. The highest systolic and disastolic levels correlated with times of
reported anxiety, time pressure, and alertness.
Although some workers have identified specific environmental stresses

as directly affecting blood-pressure responses, a current interpretation is that
hypertension develops as a consequence of the manner in which a genetically
vulnerable individual perceives an environmental threat, and the defensive
patterns that he gradually adopts determine the complex somatopsychosocial

relationships.
Therapy
Shapiro, working in the field of hypertension for the past thirty years,
has been, perhaps, the most important pioneer in therapeutic developments.

Advocating supportive psychotherapy, together with the use of
antihypertensive agents, he has achieved an amelioration of symptoms and a

slowing of disease progression by assisting the patient in identifying and
avoiding noxious stimuli and learning how to adjust to his environment and
the limitations of disease. He has found therapy to be most effective when it is
transmitted in a supportive, nonthreatening, and nonauthoritative doctor-
patient relationship. Wolff and Lindeman, and Sokolow and Perloff have
reviewed the pharmaceutical agents used in the control of hypertension.
Relaxation methods have enjoyed limited popularity from time to time.
Jacobson and Raab have been proponents of these, both noting beneficial
results for patients with cardiovascular disease. Gantt has advocated therapy
through conditioning techniques. Most recently Miller, DiCara, and their co-
workers at Rockefeller University have demonstrated effective conditioning
of blood pressure in laboratory animals. More limited success has been
obtained with human subjects. The relationships of these techniques to the

control of hypertension by meditational experiences remains to be
elucidated.
Conclusions
During the past thirty years, workers in the field have adopted a multi-
factorial genesis for the ill-defined condition called “essential hypertension.”
First and foremost, a primary genetic predisposition on the basis of
geographic, racial, and family studies has been suggested as necessary, but
not sufficient, for the development of hypertension. Environmental studies
have implicated early developmental factors, especially those relating to

mother-child interaction. Of considerable interest has been the observation of
the alterations in perception that seem to occur in patients with hypertension
in the course of the disease, suggesting that these may represent an attempt
to protect a vulnerable hyperreactive pressor mechanism. Increasing
attention is presently directed at the early conditioning of autonomic
responses in an attempt to explain the repeated association of emotional and
psychological traits with hypertension. The emotions most often identified

have been those of anxiety and hostility or anger, where expression is
frequently repressed. Obsessive and compulsive personality patterns have
also been identified. Depressive reactions have frequently been observed to

correlate with the development and/or exacerbation of hypertension.
Secondary to the development of the disease, altered physiological and
behavioral patterns have been hypothesized and attributed to secondary
effects of the process, especially on the heart, brain, and kidneys. Such effects
may include deterioration of perceptual and cognitive functions. Stress
relative to specific environmental factors has been identified as relating to the

development and/or exacerbation of hypertension in genetically and
psychologically vulnerable individuals. Therapeutic approaches include the

combination of peripheral antihypertensive agents and psychotherapy.
Several investigators have suggested the possible benefit of antidepressants

when depression coexists. There is considerable excitement about the
potential use of operant conditioning in modifying autonomic activity.

Whether these will prove effective for all phases of the illness remains
questionable.
Special Psychological Aspects of Diagnosis and Treatment
The investigation and treatment of cardiovascular disorders frequently
involves specialized procedures and approaches which, in themselves,

contribute to the precipitation of emotions and the erection of defenses
against them. Catheterization, implantation of a pacemaker, intensive care
units, and cardiac surgery are among these.
Cardiac Catheterization
Greene et al. have observed that patients undergoing cardiac
catheterization exhibit four behavioral patterns: (1) anxious-engaged; (2)
anxious not-engaged; (3) depressed; and (4) calm. All of these conditions
showed elevated free fatty acids. Cortisol was elevated in both anxious
groups, whereas growth hormone was elevated only in the anxious not-
engaged group. Neither the depressed nor the calm group demonstrated
elevations in cortisol or growth hormone. A follow-up study of twenty-two
patients indicated significantly greater mortality among the anxious not-
engaged and depressed groups. These observations indicate the stress that
catheterization has for patients and how reaction patterns may be

characterized by both psychological and physiological measures. They also
suggest the possible prognostic value of the identification of patients’
reactions to catheterization in terms of subsequent survival.
Pacemakers
Several investigators have studied reactions of patients requiring the
implantation of cardiac pacemakers (see references 17, 39, 47, 77, and 225).
Noting the initial anxieties of patients relative to the underlying cardiac
disease and arrhythmias, they have delineated the concerns of these patients
about relying on an artificial mechanical instrument, its unpleasant side

effects, the possibility that batteries run out, and possible complications
resulting from implantation. Blacher and Basch have identified three phases
in the acceptance of pacemakers by patients: (1) the preoperative,
characterized by concern with life and death, confrontation with the mystique
of medical technology, fear of dependence on an artificial device that could
fail, guilt, and pessimism; (2) the immediate posthospital phase characterized
by depression; and (3) a later phase in which there has been acceptance of
the pacemaker and the pursuance of normal activities, control and mastery of
feelings, and preoccupation with physical sensations, fantasies, and denial.
Crisp and Stonehill, comparing patients with external and internal
pacemakers, noted that the former exhibited greater distress, and suggested
that patients with implanted pacemakers were able to make greater use of
denial as a defense mechanism in coping with an incurable disease.
The Intensive Care Unit (ICU)
As hospitals are absorbing the technological advances that applied
scientific research and methodology brought to medicine, specialized units
have been established to cope with acute and specific problems. These
intensive care units (ICU) and coronary care units (CCU) have evolved from
hospital wards or recovery rooms into highly complex and specially
constructed acute emergency units, requiring skilled nursing and medical
technicians to operate the monitors, defibrillators, respiratory and suction

apparatuses, and hypothermia units. In many ways, these units have become
the symbol of the new frontier in medicine, its technological coming of age. As
such they present a new unknown for the patient, his family, and the medical
staff. Simultaneous with the development of these units, the hospital staff has
noted an increasing incidence of behavioral disturbances among patients
admitted to them, a phenomenon that Nahum has aptly identified as one of
the “new diseases of medical progress.” Consequently, the ICUs and CCUs
have become foci of interest for the behavioral scientist in observing and
identifying possible explanations for these syndromes that are estimated to
occur 40-60 percent of the time. Kornfeld has developed four categories for
the behavior observed in these units:
1. Behavioral reactions associated with the medical and surgical

illness and/or arising from metabolic, circulatory, or toxic factors.
Hackett and his group, who have compiled extensive observations of
patients in CCUs, emphasize the psychological reactions to illness of the
patients admitted to the CCU.33, 34,82,83 Noting that one-third of patients
admitted to CCUs were referred for psychiatric consultation, Cassem and
Hackett classified the reactions as anxiety, depression, and behavior disorder

(see Figure 26-3). Anxiety was related to impending death or death heralds of
pain, breathlessness, weakness, and new complications. Anxiety was most
manifest in the first two CCU days. Depression was seen as representing
injuries to the self-esteem and was observed on the third to fourth CCU day,
whereas behavioral disorders had a bimodal distribution during the whole
CCU period, with the primitive defense of denial most present on the second
day and more sophisticated defenses, appropriate to the patient’s personality

style, emerging after the fourth day. The defensive behavior described
included denial of illness, inappropriate euphoric or sexual responses, and
projection of hostile dependent conflicts. These observations raise interesting
questions about the protective role of denial. In the days following the
catastrophic onset, denial of anxiety would seem to serve a protective
function for the patient. Later, as his physiological course has stabilized,
denial of illness may keep him from accepting and conforming to medical and
rehabilitative routines. Cassem and Hackett specify psychiatric intervention

in the CCU as including medication to diminish anxiety, explanatory
clarification, environmental manipulations, bolstering of optimism,
elaborating on the patient’s anticipations, confrontation, and hypnosis. That
these techniques may be of value is proved by their finding of three times less
mortality in the referred group as compared with nonreferred CCU groups.
Figure 26-3.
Psychological responses in a coronary care unit.
Organic brain syndromes, usually acute, may be associated with the

cardiac dysfunction and present with symptoms and signs of impairment in
the cognitive functions. These may also result from drugs administered to the
patient. Occasionally withdrawal states from alcohol, barbiturates, or other
drugs are observed three to five days following admission of a patient to the
ICU.
2. Psychiatric reactions to the unique and unfamiliar environment of
the ICU.
McKegney has studied the emotional reaction of the patient to acute and
catastrophic illness in the ICU setting. Identifying the initial anxiety and
subsequent depression experienced by these patients, he stressed not only
deficits in the physical environment, but also emphasized problems relating
to the medical personnel, and the interactions between these and the patient
and his family. Crucial for the patient’s adjustment in the ICU is the
relationship established with the medical and nursing attendants and the
acceptance by the relatives of the ICU environment and the patient’s

condition.
Not least among the hazards of the ICU environment are emergency
situations and their associated procedures. Arrhythmias are not uncommon
and often demand dramatic intervention of cardioversion either by drugs or

electrical defibrillation. For the patient, this means additional medications
with their potential untoward effects and/or the preparation for light
anesthesia and electrical shock. At least some of the arrhythmias developing
in ICUs are directly associated with high-anxiety states, suggesting that on the
basis of a possible causal relationship, attention to the symptoms of anxiety

may be equal in importance to attention to the arrhythmia.
Margolis, in studying psychotic reactions in patients in ICUs,
emphasized the lack of privacy at a time when many desired privacy most.
For these patients, he noted a diminution of psychotic symptoms on transfer
to private rooms. Studies of patients witnessing deaths of other patients in
the ICU by Bruhn et al. demonstrated elevated systolic blood pressures and
symptoms of anxiety. Leigh et al. compared open vs. closed ICUs,

corroborating the observations of other workers. They found that closed
units provided privacy at the expense of human interactions, resulting in
increased feelings of loneliness and displacement of hostile feelings. The open

unit was observed as providing greater social contact with associated
freedom of expression of hostile feelings, while the lack of privacy resulted in
higher levels of “shame” anxiety. On the basis of these and other observations,
they suggested that some individuals will do better in one setting and/or that
an ideal CCU could be designed to provide for both togetherness and privacy.
Some units have already incorporated this plan with folding partitions that
can be closed at the time of nursing procedures, and open at other times to
provide for communication with other patients.
3. Psychiatric reactions produced by the ICU environment and

experience that manifest themselves after discharge from the unit.
Klein et al., and Dominian and Dobson have found heightened anxiety,
associated with cardiovascular distress, in patients at the time of and
following discharge from the ICU. Correlating these emotional changes with
increased urinary catecholamines, Klein subsequently demonstrated that
cardiovascular complications were reduced in patients prepared for transfer
and followed by the same nurse and physician throughout hospitalization.
Kimball has observed that many patients experiencing delirium with
hallucinations and delusions during the ICU period continue to have
obsessional preoccupations with this experience as part of an acute

depression following sudden hospitalization.
4. Emotional reactions of the ICU staff.
Not the least of considerations found by Kornfeld is the emotional

reactions of the staff. If the stresses and strains of the ICU are burdensome to
the patient and his family, they are equally so for the ICU staff, attending
simultaneously to a number of patients, each of whom is critically ill, and
physiologically and psychologically labile to any one of a number of potential

complications demanding immediate recognition and intervention. Vreeland
and Ellis, Cassem et al., and Hay and Oken, have described the pivotal role of
the nurse in the ICU. They have compared the nurse’s objective role, i.e., the
need for technical competence, decisive and controlled response to a chronic

state of emergency, and constant vigilance, with her subjective one, i.e.,
interacting with patients and relatives, handling the fatigue and brusqueness
of physicians, and containing her own emotions. They have proposed that
these factors be considered in the training and scheduling of nurses. Some
hospitals now arrange for intermittent rotation of ICU nurses to general-
nursing floors and for the opportunity to ventilate feelings in group
discussion with nurses and administrators within their own hospital as well
as from other centers.
Attention to these environmental and personnel factors is needed as a

crucial prelude for the patient’s hospitalization and eventual rehabilitation
and adjustment.
Cardiovascular Surgery
Since cardiac surgery was first performed, severe behavioral

postoperative states have been observed. Blachly and Starr have given the
name postcardiotomy delirium to these states. This condition is described as
occurring suddenly three to five days following surgery after an untoward

early postoperative period. The delirium is marked by increasing confusion,
progressing to delusions and hallucinations. Blachly and associates attribute
this condition to an abnormal metabolic state and postulate the presence of
psychotoxic metabolites.
Studies have suggested that not only the physical condition but the
psychological condition of the individual faced with surgery strongly
influences the success or failure of cardiac surgery in terms of morbidity and
mortality. Attempts to gain a clearer understanding of these conditions have
focused on various aspects of the patient’s hospital and surgical course. Janis
has observed that the way in which a patient handles anxiety before an
operation affects his postoperative course. Patients who denied or showed

little or no anxiety and those who manifested overwhelming anxiety
sustained greater postoperative morbidity than those patients who admitted
to anxiety and demonstrated moderately intact and mature defenses in

coping with it.
Abram has verified that patients with high anxiety preoperatively are
more likely to experience a postcardiotomy delirium. He explains the
occurrence of this psychoticlike state as a defense against the anxiety over the
possibility of death. Meyer et al. have suggested that this condition arises out
of the patient’s misperceptions in the early postoperative period, occurring
while he is still under the influence of anesthesia and adjunctive agents such
as the anticholinergics. They also postulate that in his semidrugged state the
individual misperceives what is going on in an unfamiliar environment,

picking up fragments from this which he may subsequently attempt to fit
together in what is projected as an unreal delusional sequence.
Kornfeld et al. emphasized the possible contributing effects of the
recovery room (RR) or ICU.123,124 Here was an environment of
simultaneous sensory overstimulation and monotony in terms of the
repetitive beeping sounds of cardiac monitors, the hissing of oxygen and
suction apparatuses, the intermittent clacking of automatic blood-pressure
recordings. The patient was constantly aroused by nursing staff carrying out
necessary medical observations and procedures. Sleep was only possible in
short sequences. The patient’s communication was disrupted because of
oxygen masks, tracheotomies, and the suppression of cognitive processes
(orientation, memory, concentration, and abstraction) associated with

analgesics and sedatives. In the case of cardiac surgery, the environment
becomes further distorted by the introduction of hypothermia, and, for the
coronary patient in rarer instances, by the use of hyperbaric chambers. Not

only was the patient estranged from those in the immediate environment by
machines and sounds, but in a large measure, the ICU was similarly isolated
from the rest of the world. Windows in these units were rare. Lights were
kept on at all times obliterating day-night sequences, distorting circadian

rhythms, and ultimately the patient’s time sense and orientation. Clocks and
calendars were absent. Regular meal times were not observed. Familiar
objects were nowhere to be seen. The personnel was strangely garbed and
masked. Other patients were perceived as moaning heaps of white, while

physically close enough at hand to compromise privacy, frequently far distant
in a communicative sense. No wonder then that patients admitted to these
units often experienced confusion, disorientation, misperceptions, and, less
frequently, manifested delusional and hallucinatory behavior associated with
agitation interfering with medical care. In rarer instances, the disruptive
behavior resulted in patients’ ripping off intravenous and monitor
attachments and fleeing from the unit followed by a mélange of attendants to
the startled attention of the other patients. Komfeld’s vivid description went
beyond mere observation. He suggested a number of remediable factors
which have since been introduced into the ICU that presumably have led to
the reduction in the incidence of these behavioral states.
Kimball et al. following patients undergoing cardiac surgery, observed
that the delirium identified by Blachly and others is almost always preceded
by symptoms and signs suggesting progressive cognitive dysfunction from
the first postoperative day, and is most frequent in individuals who reported
prior compromise of cerebral functions. Early symptoms and signs included
restlessness, agitation, mild confusion, complaints, and little or no sleep.

These occurred in patients whose operative experience and postoperative
course had been more severe. In other studies, Kimball found that patients
who preoperatively denied anxiety and yet manifested considerable agitation,
and those with marked depression were more likely to experience
adjustment difficulties in the postoperative period and sustained greater

morbidity and mortality. These patients responded to cognitive deficits with
heightened anxiety and depression which further compromised their ability
to cope with the stresses of the postoperative environment. With increasing
sleep deficits and the not infrequent complications, mild confusion became
gross disorientation with increasing agitation, which, if left untreated,
resulted in delusional and hallucinatory states (see Figure 26-4). Patients

who had fairly successful life patterns before surgery enjoyed lower
mortality, although those who had used illness as a means of adjusting to life
situations showed greater morbidity postoperatively and had poorer overall

results.
Figure 26-4.
Figure 26-4.
Course of mental status of patients undergoing heart surgery.
Kennedy and Bakst identified six groupings of patients preoperatively

as having predictive significance in terms of postoperative adjustment and
outcome. Focusing on patients’ expectations of surgery, they observed that

patients with a long history of unsatisfactory life conditions approached
surgery consciously expressing a death wish. On the other hand, patients with
congenital cardiac defects expressed optimism, viewing the repair as
something owed to them and that correction would make them rightfully
healthy. Patients who had used their illness in making life adjustments feared
and later experienced profound readjustment problems when they no longer
had severe disability to rely upon in negotiating their demands. Knox’s
experience with patients he classified as neurotics or hysterics on the basis of
interviews and performance on the M-R section of the Cornell Medical Index
showed similar poor postoperative adjustment.
Tufo et al. have correlated aberrant postoperative behavior with

demonstrated neurological deficits and neuropathological lesions.
Furthermore, they have shown that patients who had long intervals on extra-
corporeal circulation and who had sustained blood pressures below 60 mm.
Hg. were more vulnerable to postoperative delirium. Heller et al.
demonstrated that patients with longer bypass times were more vulnerable
to developing delirium, raising the interesting hypothesis of the possible role

of the lung in metabolizing substances that, when accumulated, are “toxic to
brain function.
Precise explanation for the various correlations are still in the process
of evolution based upon more intensive research. Efforts are in progress to
identify biological correlates of the emotional and behavioral states. Such
studies suggest, but do not conclusively prove, that the manner in which
individuals confront experiences influence their subsequent psychological
and physiological behavior in identical ways. For instance, a possible

explanation why depressed patients are more likely to die is that the
depressed state prevents them from augmenting sufficient physiological
defenses to sustain the stress of the operative procedure. However, it is
possible that depressed states and their biological correlates vary
considerably from one individual to another.
Identifying in vulnerable patients preoperatively signs and symptoms of
organicity, overwhelming anxiety and/or depression, and considering

appropriate preoperative and/or postoperative intervention may help to
diminish postoperative morbidity. Attention to the individual’s expectations
may be all important in whether or not he makes a satisfactory response. If
expectations are unrealistic, if the patient expects rebirth and rejuvenation,
and discovers in its place continued limitation and restriction, recovery and
rehabilitation will be retarded. The preoperative and rehabilitative efforts of

the staff need to include the family, especially the spouse. Attention to
vocational, social, and domestic (including marital) expectations of the
patient and his family is their responsibility. Without such attention, the
social reintegration of the patient will be less than ideal and fraught with
superimposed frustrations. The efforts of the staff do not cease with the event
of successful surgery. The long road to recovery has only just begun, twists,
turns, and detours are many and can only be approached and overcome by
the continued support, understanding, and foresight of the team.
Lazarus and Hagens have demonstrated the that patients who
underwent a preoperative interview with a psychiatrist had lower mortality
and morbidity than matched patients who were not afforded this experience.
This observation has recently been substantiated by Layne and Yudofsky.
Kimball noted in his original series of fifty-four patients that there was no
occurrence of post-cardiotomy delirium at a time when other authors were
reporting incidences as high as 40 percent. He attributed this finding to the
manner in which patients had been prepared for surgery by the team. This
included a week’s hospitalization before surgery which provided an

equilibration period during which the patient was seen daily, acquainted with
the details of the procedure to be performed, exposed to the recovery room,
instructed in several techniques to be used postoperatively, and talked with a

psychiatrist.
Attention to the postoperative environment and an amelioration of the
disruptive factors identified by Kornfeld, Heller et al., and McKegney, will go
far in diminishing the incidence of postoperative delirium. Instructing the

nursing staff in the ICU in the use of a scale similar to the Eleven Item
Behavioral Rating Scale will lead to the early detection of cognitive deficits
and will prevent gross behavioral disturbance through the appropriate
intervention. Judicious and cautious use of phenothiazines to diminish the

anxiety underlying or associated with aberrant behavior, whatever its cause,
has helped greatly in controlling behavior and bringing relief to the disturbed
patient. Preparation of the patient for release as well as admission to the ICU,
as stressed by Klein, will help prevent the occurrence of transfer anxiety,
when the patient suddenly feels abandoned and on his own.
Lastly, for the physician and the team that works with these patients
and wishes to sensitize himself to the subjective concerns of the patient

undergoing cardiac surgery, reading of Rachel MacKenzie’s Risk is essential.
Behavior and Conditioning Techniques
During the past decade, innovative research, based on new laboratory
techniques, has led to renewed interest in the potential role of conditioning in

the understanding and treatment of autonomic dysfunctions. Although this
research is in its infancy and still of more theoretical interest than of practical
application, enough experimental work has been accomplished to suggest

that an extension of these techniques may become one of the major
developments in medicine during this century.
Relaxation methods, often under conditions of hypersuggestibility or
hypnosis, have from time to time been employed in the treatment of patients
with chronic illness in which psychological factors have been implicated.

These methods, given emphasis by Jacobson in the 1930s, and Raab in the
1960s, have been derived in part from behavior therapy. Such methods
remain in limited use. Raab emphasized the use of “retreats” by patients with
cardiovascular problems in which somatic and autonomic relaxation could be
effected through “regressive” individual and group experiences, including
mud baths.
Gantt, and more recently Rifkin (after Wolpe), have emphasized
classical conditioning methods in their work with patients with cardiac

problems. Aiken and Henrichs have demonstrated relaxation techniques in
patients following open-heart surgery. Although in limited use, partly because
of little contact of students and physicians with them during training, the use
of specific and more general conditioning methods have an important place in

the rehabilitation of patients enduring disease processes in which changes in
habits are deemed essential to their continued effectiveness and survival.
Most exciting is the work performed by Miller and his colleagues,

Banuazizi, Carmona, and DiCara in operant conditioning or instrumental
learning. In instrumental, as opposed to classical conditioning, reinforcement
or reward may strengthen any immediately preceding response. In classical

conditioning the reward achieves its desired effect only when the response to
be learned is already elicited by an unconditional stimulus. Miller explains the
relationship between these methods as different manifestations of the same

basic phenomenon under different conditions. He identifies similar laws as
effecting both types of learning and assumes that there is essentially only one
kind of learning.
Using curarized rats in order to ablate the affect of skeletal on visceral

responses to be conditioned by instrumental learning, Miller and Trowill
were able to demonstrate that increases or decreases in heart rate could be
effected, using as a reward direct stimulation of the rewarding areas of the
brain or as punishment a mild pain stimulus to the tail. Subsequently Miller

and DiCara were able to effect greater changes in these responses through the
techniques of shaping and to demonstrate that learning can be both brought
under the control of a discriminative stimulus and retained. They were then
able to show that operantly learned behavior under the influence of curare
could be carried over to the noncurarized state, supporting the contention
that this learning is effected directly through the visceral system rather than
indirectly through the effect of learned motor behavior on visceral functions
as summarized by Katkin and Murray. Such learning was also demonstrated
to be specific for the condition rewarded and not generalized to other

autonomic functions. In other words, cardiovascular functions such as blood
pressure and heart rate could be independently conditioned in either

direction. However, DiCara has observed greater “emotionality” occurring in
animals conditioned to increase their heart rate, as compared to those

conditioned to decelerate their heart rate following instrumental
conditioning. To date, operant learning, while it occurs, has been poorer in
the noncurarized state than the curarized one, a phenomenon explained by
Miller on the basis that the later state eliminates sources of distractability and
variability. Because of initial success in effecting brain wave activity and
associated behavior through instrumental learning techniques, Miller and his

colleagues are at present attempting to modify the activity of a specific part of
the vagal nucleus directly which holds potential for the instrumental
regulation of cardiac activity.
The implications of this work are several. Understanding the individual
specificity with which organisms react to similar stresses through their

autonomic nervous system may be tentatively explained on the basis of the at
first casual juxtaposition of a chance stress with such a response at a
particularly vulnerable time in the development or structuring of that

autonomic function under a specific environmental situation in which the
gross behavior associated with the autonomic response was wittingly or
unwittingly rewarded (reinforced).
With improvement and perfection of these techniques, their theoretical
potential for use in altering visceral dysfunctions is viewed as unlimited. This
has especial potential for cardiovascular disorders such as cardiac

arrhythmias and hypertension, where preliminary human trials have
suggested their applicability. Frazier et al. have shown that discriminative

avoidance conditioning leads to changes in the rate of response, the speed of
the detection response, and the probability of signal detection, noting
associated changes in heart rate, pulse pressure, skin resistance, and 17-
hydroxycorticosteroid, epinephrine, and norepinephrine excretions. Headrick
et al., with augmented sensory feedback techniques, effected heart-rate

increases. They cited three dependent factors: (1) amount of training time
required; (2) feedback; and (3) motivation. Weiss and Engel have reported
success in using operant techniques in treating cardiac arrhythmias, work
that has yet to be replicated by others. Plumlee has described increases in

blood pressure under operant learning and Benson et al., and Shapiro et al.,
have achieved significant decreases in systolic blood pressures with these
methods used on patients with essential hypertension. Whether these

techniques will achieve long-term results awaits further trials and
observations. In concluding this brief discussion, the authors are reminded of
the long-observed changes in autonomic responses occurring in
transcendental meditation or yoga.
Bibliography
Abram, H. S. and B. F. Gill. “Predictions of Postoperative Psychiatric Complications,” N. Engl. J.

Med., 265 (1961), 1123-1128.
Adams, F. H. and A. J. Moss. “Physical Activity of Children with Congenital Heart Disease,” Am. J.
Cardiol., 24 (1969), 605-606.
Adsett, C. A. and J. G. Bruhn. “Short term Group Psychotherapy for Post-myocardial Infarction
Patients and Their Wives,” Can. Med. Assoc. J., 99 (1968), 577-584.
Aiken, L. H. and T. F. Henrichs. “Systematic Relaxation as a Nursing Intervention Technique with

Open Heart Surgery Patients,” Nurs. Res., 20 (1971), 212-217.
Alexander, F. “Emotional Factors in Essential Hypertension,” Psychosom. Med., 1 (1939), 173-179.
Alexander, H., de M. “A Few Observations on the Blood Pressure in Mental Disease,” Lancet (July
5, 1902), 18-20.
Altschule, M. D. Bodily Physiology in Mental and Emotional Disorders, pp. 23-24 New York: Grune
& Stratton, 1953.
Arlow, J. A. “Anxiety Patterns in Angina Pectoris,” Psychosom. Med., 14 (1952), 461-468.
Ax, A. F. “The Physiological Differentiation between Fear and Anger in Humans,” Psychosom. Med.,
15 (1953), 433-442.
Bahnson, C. B. and W. I. Wardwell. “Parent Constellation and Psychosexual Identification in Male

Patients with Myocardial Infarction,” Psychol. Rep., 10, 3-V10 (Monograph Suppl.)
(1962), 831-852.
Bakker, C. B. and R. M. Levenson. “Determinants of Angina Pectoris,” Psychosom. Med., 29 (1967),

621-633.
Barnes, R. and W. Schottstaedt. “The Relation of Emotional State to Renal Excretion of Fluids and
Electrolytes in Patients with Congestive Heart Failure,” Clin. Res., 6 (1958), 224.
Bendian, J. and J. Groen. “A Psychological-Statistical Study of Neuroticism and Extraversion in

Patients with Myocardial Infarction,” J. Psychosom. Res., 7 (1963), 11-14.
Benson, H., D. Shaprio, B. Tursky et al. “Decreased Systolic Blood Pressure through Operant
Conditioning Techniques in Patients with Essential Hypertension,” Science, 173
(1971), 740-741.
Bilodeau, C. B. and T. P. Hackett. “Issues Raised in a Group Setting by Patients Recovering from
Myocardial Infarction,” Am. J. Psychiatry, 128 (1971), 73-78.
Binger, C. “On So-called Psychogenic Influences in Essential Hypertension,” Psychosom. Med., 13

(1951), 273-276.
Blacher, R. S. and S. H. Basch. “Psychological Aspects of Pacemaker Implantation,” Arch. Gen.

Psychiatry, 22 (1970), 319-323.
Blachly, P. H. “Open Heart Surgery: Physiological Variables of Mental Functioning,” Int. Psychiatry
Clin., 4 (1967), 133-155-
Blachly, P. H. and A. Starr. “Post-cardiotomy Delirium,” Am. J. Psychiatry, 121 (1964), 317-375.
----. “Treatment of Delirium with Phenothiazine Drugs following Open Heart Surgery,” Dis. Nerv.
Syst., 27 (1966), 107-110.
Bolt, W., M. F. Bell, and J. R. Harnes. “A Study of Mortality in Moderate and Severe Hypertension,”
Trans. Assoc. Life Ins. Med. Dir. Am., 41 (1958), 61.
Boyle, E., Jr. “Biological Patterns in Hypertension by Race, Sex, Body Weight, and Skin Color,”
JAMA, 213 (1970), 1637-1643.
Brod, J. “Haemodynamics and Emotional Stress,” Bibl. Psychiatr., 144 (1970), 13-33.
Brower, D. “The Relation between Certain Rorschach Factors and Cardiovascular Activity before
and after Visuo-Motor Conflict,” J. Gen. Psychiatry, 37 (1947), 93-95.
Brozek, J. “Personality Differences between Potential Coronary and Noncoronary Subjects,” Ann.
N.Y. Acad. Sci, 134 (1966), 1057-1064.
Bruhn, J. G., B. Chandler, M. C. Miller et al. “Social Aspects of Coronary Heart Disease in Two
Adjacent Ethnically Different Communities,” Am. J. Public Health, 57 (1966), 1493-
1506.
Bruhn, J. G., B. Chandler, and S. Wolf. “A Psychological Study of Survivors and Nonsurvivors of
Myocardial Infarction,” Psychosom. Med., 31 (1969), 8-19.
Bruhn, J. G., A. E. Thurman, Jr., B. C. Chandler et al. “Patients’ Reactions to Death in a Coronary
Care Unit,” J. Psychosom. Res., 14 (1970), 65-70.
Brunner, H. R., J. H. Laragh, L. Baer et al. “Essential Hypertension: Renin and Aldosterone, Heart
Attack and Stroke,” N. Engl. J. Med., 286 (1972), 441-449.
Caffrey, B. “A Multivariate Analysis of Sociopsychological Factors in Monks with Myocardial

Infarctions,” Am. J. Public Health, 60 (1970), 452-458.
Cassel, J., S. Heyden, A. G. Bartel et al. “Incidence of Coronary Heart Disease by Ethnic Groups,
Social Class, and Sex,” Arch. Intern. Med., 128 (1971), 901-906.
Cassem, N. H. and T. P. Hackett. “Psychiatric Consultation in a Coronary Care Unit,” Ann. Intern.
Med., 75 (1971), 9-14.
Cassem, N. H., T. P. Hackett, C. Bascom et al. “Reactions of Coronary Patients to the Coronary Care
Unit Nurse,” Am. J. Nursing, 70 (1970), 319-324.
Cassem, N. H., H. A. Wishnie, and T. P. Hackett. “Response of Coronary Patients to Last Rites,”
Postgrad. Med., 45 (1969), 147-152.
Chagan, M., T. Hanes, D. O’Neill et al. “The Intellectual and Emotional Development of Children
with Congenital Heart Disease,” Guys Hosp. Rep., 100 (1951), 331-341.
Chambers, W. N. and M. F. Reiser. “Emotional Stress in the Precipitation of Congestive Heart

Failure,” Psychosom. Med., 15 (1953), 38-60.
Cleveland, S. E. and D. L. Johnson. “Personality Patterns in Young Males with Coronary Disease,”
Psychosom. Med., 24 (1962), 600-610.
Cohen, S. and O. A. Parsons. “The Perception of Time in Patients with Coronary Artery Disease,” J.
Psychosom. Res., 8 (1964), 1-7.
Crisp, A. H. and E. Stonehill. “Aspects of the Psychological Status of Patients Treated with Cardiac
Pacemakers,” Postgrad. Med., 45 (1969), 423-427.
Croog, S. H. and S. Levine. “Social Status and Subjective Perceptions of 250 Men after Myocardial
Infarction,” Public Health Rep., 84 (1969), 989-997.
Croog, S. H., D. Shapiro, and S. Levine. “Denial among Male Heart Patients: An Empirical Study,”
Psychosom. Med., 33 (1971), 385-397.
Datey, K. K., S. N. Deshmukh, C. P. Dalvi et al. “ ‘Sahvasan’: A Yogic Exercise in the Management of
Hypertension,” Angiology, 20 (1969), 325-333.
Davies, M. “Blood Pressure and Personality,” J. Psychosom. Res., 14 (1970), 89-104.
Dawber, T. R. and W. B. Kannel. “Atherosclerosis and You: Pathogenic Implications from

Epidemiologic Observations,” J. Am. Geriatr. Soc., 10 (1962), 805-821.
DiCara, L. V. and N. E. Miller. “Instrumental Learning of Systolic Blood Pressure Responses by

Curarized Rats; Dissociation of Cardiac and Vascular Changes,” Psychosom. Med., 30
(1968), 489-494.
----. “Long-Term Retention of Instrumentally Learned Heart-Rate Changes in the Curarized Rat,”
Comment. Behav. Biol., 2 (1968), 19-23.
Dlin, B. M. and H. K. Fischer. “Psychologic Adaptation to Pacemaker and Open Heart Surgery,”
Dominian, J. and M. Dobson. “Study of Patients’ Psychological Attitudes to a Coronary Care Unit,”
Br. Med. J., 4 (1969), 795-798.
Donaldson, J. F. “Patterns of Disease in Rhodesia Central Africa,” J. Med., 17 (1971), 51-53.
Doyle, J. T., T. R. Dawber, W. B. Kannel et al. “Cigarette Smoking and Coronary Heart Disease,” N.
Engl. J. Med., 266 (1962), 796-801.
Dreyfuss, F., H. Dasberg, and M. I. Assael. “The Relationship of Myocardial Infarction to
Depressive Illness,” Psychother. Psychosom., 17 (1969), 73-81.
Dreyfuss, F., J. Shanan, and M. Sharon. “Some Personality Characteristics of Middle-Aged Men
with Coronary Artery Disease,” Psychother. Psychosom., 14 (1966), 1-16.
Druss, R. G. and D. S. Kornfeld. “The Survivors of Cardiac Arrest,” JAMA, 201 (1967), 291-296.
Dunbar, F. Emotions and Bodily Changes, pp. 331-361. New York: Columbia University Press,
1954.
Eliasson, S., B. Folkow, P. Linogren et al. “Activation of Sympathetic Vasodilator Nerves to the
Skeletal Muscle in the Cat by Hypothalamic Stimulation,” Acta Physiol. Scand., 27
(1953), 18-37.
Engel, G. L. “Sudden and Rapid Death during Psychological Stress,” Ann. Intern. Med., 74 (1971),
771-782.
Epstein, F. H. “Epidemiologic Aspects of Atherosclerosis,” Atherosclerosis, 14 (1971), 1-11.
Erikson, E. Childhood and Society, pp. 274. New York: Norton, 1963.
Fisher, S. H. “Psychological Factors and Heart Disease,” Circulation, 27 (1963), 113-117.
Fox, H. M. “Physiological Response of the Adrenal to Psychological Influences as Indicated by

Changes in the 17-Hydroxycorticosteroid Excretion Pattern,” in G. E. W.
Walstenholme, ed., Ciba Foundation Colloquia on Endocrinology, Vol. 8, p. 612.
London: Churchill, 1955.
Fox, H. M., B. J. Murawski, G. W. Thorn et al. “Urinary 17-Hydroxycorticoid and Uropepsin Levels
with Psychological Data. A Three-Year Study of One Subject,” Arch. Intern. Med., 101
(1958), 859-871.
Frazier, T. W., H. Weil-Malherbe, and H. S. Lipscomb. “Psychophysiology of Conditioned

Emotional Disturbances in Humans,” Psychophysiology, 5 (1969), 478-503.
Friedman, E. H. and H. K. Hellerstein. “Occupational Stress, Law School Hierarchy, and Coronary
Artery Disease in Cleveland Attorneys,” Psychosom. Med., 30 (1968), 72-86.
Friedman, M., S. O. Byers, R. H. Rosenman et al. “Coronary-Prone Individuals (Type A Behavioral

Pattern) Growth Hormone Response,” JAMA, 217 (1971), 929-932.
Friedman, M. and R. H. Rosenman. “Association of Specific Overt Behavior Pattern with Blood and
Cardiovascular Findings,” JAMA, 169 (1959), 1286-1296.
----. “Overt Behavior Pattern in Coronary Disease: Detection of Overt Behavior Pattern A in
Patients with Coronary Disease by a New Psychophysiological Procedure,” JAMA,
173 1960), 1320-1325.
Friedman, M., R. H. Rosenman, R. Straus et al. “The Relationship of Behavior Pattern A to the State
of the Coronary Vasculature,” Am. J. Med., 44 (1968), 525-537.
Funkenstein, D. H., S. H. King et al. “The Experimental Evocation of Stress,” in Symposium on

Stress, p. 304. Washington: Army Medical Service Graduate School, 1953.
Gantt, W. H. “The Meaning of the Cardiac Conditioned Reflex,” Cond. Reflex, 1 (1966), 139-143.
Garfinkel, L. “The Association between Cigarette Smoking and Coronary Heart Disease and Other
Vascular Diseases,” Bull. N.Y. Acad. Med., 44 (1968), 1495-1501.
Garner, H. H. and M. A. Falk. “Recognizing the Patient with Pseudoangina,” Geriatrics, 25 (1970),
87-92.
Geiger, H. J. and N. A. Scotch. “The Epidemiology of Essential Hypertension. I. Biologic

Mechanisms and Descriptive Epidemiology,” J. Chronic Dis., 16 (1963), 1151-1182.
Goldstein, H. S., H. Pardes, A. M. Small et al. “Psychological Differentiation and Specificity of

Response,” J. Nerv. Ment. Dis., 151 (1970), 97-103.
Gordon, T. “Mortality Experience among Japanese in the United States, Hawaii, and Japan,” Public
Health Rep., 72 (1957), 543-553.
Graham, D. T., J. D. Kabler, and F. K. Graham. “Physiological Response to the Suggestion of
Attitudes Specific for Hives and Hypertension,” Psychosom. Med., 24 (1962), 159-
169.
Greene. W. A., G. Conron, D. S. Schalch et al. “Psychological Reactions with Changes in Growth
Hormone and Cortisol Levels: A Study of Patients Undergoing Cardiac
Catheterization,” Psychosom. Med., 32 (1970), 599-614.
Greene, W. A. and A. J. Moss. “Psychosocial Factors in the Adjustment of Patients with

Permanently Implanted Cardiac Pacemakers,” Ann. Intern. Med., 5 (1969), 897-902.
Gressel, G. C., F. O. Shobe, G. Sallow et al. “Personality Factors in Arterial Hypertension,” JAMA,
140 (1949), 265-272.
Groen, J. J., J. M. Van der Valk, A. Welner et al. “Psychobiological Factors in the Pathogenesis of
Essential Hypertension,” Psychother. Psychosom., 19 (1971), 1-26.
Grollman, A. “Effect of Psychic Disturbances on the Cardiac Output, Blood Pressure, and Oxygen
Consumption in Man,” Am. J. Physiol., 89 (1929), 584-593.
Hackett, T. P. and N. H. Cassem. “Factors Contributing to Delay in Responding to Signs and

Symptoms of Acute Myocardial Infarction,” Am. J. Cardiol., 24 (1969), 651-658.
Hackett, T. P., N. H. Cassem, and H. A. Wishnie. “The Coronary Care Unit: An Appraisal of Its
Psychological Hazards,” N. Engl. J. Med., 279 (1968), 1365-1370.
----. “Detection and Treatment of Anxiety in the Coronary Care Unit,” Am. Heart J., 78 (1969), 727-
730.
Harburg, E., W. J. Schull, J. C. Erfurt et al. “A Family Set Method for Estimating Heredity and Stress.
I. A Pilot Study of Blood Pressure Among Negroes in High and Low Stress Areas.
Detroit 1966-1967,” J. Chronic Dis., 23 (1970), 69-81.
Harris, R. E., M. Sokolow, L. G. Carpenter, Jr. et al. “Response to Psychologic Stress in Persons Who
Are Potentially Hypertensive,” Circulation, 7 (1953), 874-879.
Hatch, F. T., P. K. Reissell, T. M. W. Poon-King et al. “A Study of Coronary Heart Disease in Young
Men. Characteristics and Metabolic Studies of the Patients and Comparison with
Age-Matched Healthy Men,” Circulation, 33 (1966), 679-703.
Hay, D. and D. Oken. “The Psychological Stresses of Intensive Care Unit Nursing,” Psychosom. Med.,
34 (1972), 109-118.
Headrich, M. W., B. W. Feather, and D. T. Wells. “Unidirectional and Large Magnitude Heart Rate
Changes with Augmented Sensory Feedback,” Psychophysiology, 8 (1971), 132-142.
Heine, B. E., P. Sainsbury, and R. C. Chynoweth. “Hypertension and Emotional Disturbance,” J.

Psychiatr. Res., 7 (1969), 119-130.
Heller, S. S., K. A. Frank, J. R. Malm et al. “Psychiatric Complications of Open-Heart Surgery,” N.

Engl. J. Med., 283 (1970), 1015-1020.
Hellerstein, H. K. and E. H. Friedman. “Sexual Activity and the Post-Coronary Patient,” Arch.
Intern. Med., 125 (1970), 987-999.
Henry, J. P. and J. C. Cassel. “Psychosocial Factors in Essential Hypertension. Recent Epidemiologic

and Animal Experimental Evidence,” Am. J. Epidemiol., 90 (1969). 171-200.
Henry, J. P., J. P. Meehan, and P. M. Stephans. “The Use of Psychosocial Stimuli to Induce
Prolonged Hypertension in Mice,” Psychosom. Med., 29 (1967), 408-432.
Henry, J. P., P. M. Stephans, J. Axelrod et al. “Effect of Psychosocial Stimulation on the Enzymes
Psychosom. Med., 33 (1971), 227-237.
Hickam, J. B., W. H. Cargill, and A. Golden. “Cardiovascular Reactions to Emotional Stimuli: Effect
on Cardiac Output, Arteriovenous Oxygen Difference, Arterial Pressure, and
Peripheral Resistance,” J. Clin. Invest., 27 (1948), 290-323.
Hinkle, L. E. “Some Social and Biological Correlates of Coronary Artery Disease,” Soc. Sci. Med., 1
(1967), 129-139.
Hinkle, L. E., L. H. Whitney, E. W. Lehman et al. “Occupation, Education and Coronary Heart
Disease,” Science, 161 (1968), 238-246.
Hovarth, S. M. “Cardiac Disease in the Context of the Future Environment,” Environ. Res., 2 (1969),
470-475.
Ibrahim, M. A., C. D. Jenkins, J. C. Cassel et al. “Personality Traits and Coronary Heart Disease,” J.
Chronic Dis., 10 (1955), 255-271.
Itil, T. and M. Fink. “Anticholinergic Drug-Induced Delirium: Experimental Modification,

Quantitative EEG, and Behavioral Correlations,” J. Nerv. Ment. Dis., 142 (1966), 492-
507.
Jacobson, E. Progressive Relaxation. Chicago: University of Chicago Press, 1938.
Janis, I. L. Psychological Stress. Psychoanalytic and Behavioral Studies of Surgical Patients. New
York: Wiley, 1958.
Jenkins, C. D. “Psychologic and Social Precursors of Coronary Artery Disease (Part 1),” N. Engl. J.
Med., 284 (1971), 244-255.
----. “Psychologic and Social Precursors of Coronary Artery Disease (Concluded),” N. Engl. J. Med.,
284 (1971), 307-317.
Jenkins, C. D., S. J. Zyzanski, and R. H. Rosenman. “Progress toward Validation of a Computer-

Scored Test for the Type A Coronary-Prone Behavior Pattern,” Psychosom. Med., 33
(1971), 193-202.
Jenkins, C. D., S. J. Zyzanski, R. H. Rosenman et al. “Association of Coronary-Prone Behavior Scores

with Recurrence of Coronary Heart Disease,” J. Chronic Dis., 24 (1971), 601-611.
Kannel, W. B., J. LeBauer, T. R. Dawber et al. “Obesity and Coronary Heart Disease,” Circulation, 35
(1967), 734-744.
Kaplan, S. M., L. A. Gottschalk, E. B. Magliocco et al. “Hostility in Verbal Productions and Hypnotic
Dreams of Hypertensive Patients,” Psychosom. Med., 23 (1961), 311-322.
Kasl, S. V. and S. Cobb. “Blood Pressure Changes in Men Undergoing Job Loss: A Preliminary
Report,” Psychosom. Med., 32 (1970), 19-38.
Katkin, E. S. and N. E. Murray. “Instrumental Conditioning of Autonomically Mediated Behavior:

Theoretical and Methodological Issues,” Psychol. Bull., 70 (1968), 52-68.
Katz, L. N. “The Mechanism of Cardiac Failure,” Circulation, 10 (1954), 663-679.
Katz, L. N., S. S. Winton, and R. Megibow. “Psychosomatic Aspects of Cardiac Arrhythmias,” Ann.
Intern. Med., 27 (1947), 261-274.
Keith, R. A. “Personality and Coronary Heart Disease: A Review,” J. Chronic Dis., 19 (1966), 1231-
1243.
Kennedy, J. A. and H. Bakst. “The Influence of Emotions on the Outcome of Cardiac Surgery: A
Predictive Study,” Bull. N.Y. Acad. Med., 42 (1966), 811-849.
Keys, A. “Diet and the Epidemiology of Coronary Heart Disease,” JAMA, 164 (1957), 1912.
Kimball, C. P. “Psychological Responses to the Experience of Open-Heart Surgery. I,” Am. J.

Psychiatry, 125 (1969), 348-359.
----. “The Experience of Open-Heart Surgery. II. Determinants of Post-operative Behavior,” Proc.
8th Europ. Conf. Psychosom. Med., 1970. Psychother. Psychosom., 18 (1970), 259-
274.
----. “The Experience of Open-Heart Surgery. III. Toward a Definition and Understanding of Post-
cardiotomy Delirium,” Arch. Gen. Psychiatry, 27 (1972), 57-63.
Kimball, C. P., D. M. Quinlan, F. Osborne et al. “The Experience of Cardiac Surgery. V. Psychological
Patterns and Prediction of Outcome,” Proc. 9th Europ. Conf. Psychosom. Med.,
Vienna, 1972. Psychother. Psychosom., 22 (1973), 310-319.
Kimball, C. P. and J. V. Magnuson. “Depression and Contraception,” in P. Zuspan and M. D.

Lindeheimer, eds., Medical Complications of Pregnancy. New York: Lea & Feiber,
forthcoming.
Klein, R. F., V. A. Kliner, D. P. Zipes et al. “Transfer from a Coronary Care Unit,” Arch. Intern. Med.,
122 (1968), 104-108.
Knox, S. J. “Psychiatric Aspects of Mitral Valvotomy,” Br. J. Psychiatry, 109 (1963), 656-668.
Kornfeld, D. S. “Psychiatric Problems of an Intensive Care Unit,” Med. Clin. North Am., 55 (1971),
1353-1363.
Kornfeld, D. S., S. Zimberg, and J. R. Malm. “Psychiatric Complications of Open-Heart Surgery,” N.

Engl. J. Med., 273 (1965). 287-292.
Koster, M. “Patterns of Hypertension,” Bihl. Psychiatr., 144 (1970), 1-8.
Lacey, J. I., D. E. Bateman, and R. Van Lehn. “Autonomic Response Specificity: An Experimental
Study,” Psychosom. Med., 15 (1953), 8-21.
Lacey, J. I. and R. Van Lehn. “Differential Emphasis in Somatic Response to Stress,” Psychosom.
Med., 14 (1952), 71-81.
Laragh, J. H. “The Pill, Hypertension, and the Toxemias of Pregnancy,” Am. J. Obstet. Gynec., 109
(1971), 210-213.
----. “Mechanisms of Edema Formation and Principles of Management,” Am. J. Med., 21 (1956),
423.
Layne, O. L., Jr. and S. C. Yudofsky. “Post-operative Psychosis in Cardiotomy Patients,” N. Engl. J.
Med., 284 (1971), 518-520.
Lazarus, H. R. and J. H. Hagens. “Prevention of Psychosis following Open-Heart Surgery,” Am. J.

Psychiatry, 124 (1968), 1190-1195.
Lebovits, B. Z., R. B. Schkelle, A. M. Ostfeld et al. “Prospective and Retrospective Psychological

Studies of Coronary Heart Disease,” Psychosom. Med., 29 (1967), 265-272.
Leigh, H., M. Hofer, J. Cooper et al. “A Psychological Comparison of Patients in ‘Open’ and ‘Closed’
Coronary Care Units,” (Am. Psychosom. Ann. Meet., Abstract), Psychosom. Med., 33
(1971), 476.
Leon, A. S. and W. B. Abrams. “The Role of Catecholamines in Producing Arrhythmias,” Am. J. Med.
Sci., 262 (1971), 9-13.
Leutscher, J. A. and B. B. Johnson. “Observations on the Sodium-Retaining Corticoid (Aldosterone)

in the Urine of Children and Adults in Relation to Sodium Balance and Edema,” J.
Clin. Invest., 33 (1954), 1441-1446.
Levi, L. “Emotional Stress and Sympatho-Adrenomedullary and Related Physiological Reactions

with Particular Reference to Cardiovascular Pathology,” Bibl. Psychiatr., 144
(1970), 38-51.
Liljefors, I. and R. H. Rahe. “An Identical Twin Study of Psychosocial Factors in Coronary Heart
Disease in Sweden,” Psychosom. Med., 32 (1970), 523-542.
Lynn, D. B., H. H. Glaser, and G. S. Harrison. “Comprehensive Medical Care for Handicapped
Children: III. Concepts of Illness in Children with Rheumatic Fever,” Am. J. Dis. Child,
103 (1962), 120.
McKegney, F. P. “The Intensive Care Syndrome. The Definition, Treatment and Prevention of a
New ‘Disease of Medical Progress’,” Conn. Med., 30 (1966), 633-636.
----. “After the Coronary Care Unit: Three Transitions,” in M. A. F. Pranulis, ed., After the Coronary
Care Unit—Then What?, pp. 3-13. Proceedings of a symposium sponsored by the
Greater Bridgeport Heart Association, December 3, 1969. Bridgeport, Conn.:
Connecticut Regional Medical Program.
McKegney, F. P. and R. B. Williams. “Psychological Aspects of Hypertension. II. The Differential

Influence of Interview Variables on Blood Pressure,” Am. J. Psychiatry, 123 (1967),
1539-1545.
MacKenzie, R. Risk. New York: Viking, 1971
Mai, F. M. M. “Personality and Stress in Coronary Disease,” J. Psychosom. Res., 12 (1968), 275-287.
Mainzer, F. and M. Krause. “Influence of Fear on Electrocardiogram,” Br. Heart J., 2 (1940), 221-
230.
Margolis, G. J. “Postoperative Psychosis on the Intensive Care Unit,” Compr. Psychiatry, 8 (1967),
227-232.
Marriott, H. J. L. and P. M. Nizet. “Physiological Stimuli Simulating Ischemic Heart Disease,” JAMA,
200 (1967), 139.
Merrill, A. J. “Edema and Decreased Renal Blood Flow in Patients with Chronic Congestive Heart
Failure,” J. Clin. Invest., 25 (1946), 389-400.
Meyer, B. C., R. S. Blacher, and F. Brown. “A Clinical Study of Psychiatric and Psychological Aspects
of Mitral Surgery,” Psychosom. Med., 23 (1961), 194-218.
Miller, M. L. “Blood Pressure Findings in Relation to Inhibited Aggressions in Psychotics,”

Psychosom. Med., 1 (1939), 162-172.
Miller, N. E. “Learning of Visceral and Glandular Responses,” Science, 163 (1969), 434-445.
Miller, N. E. and A. Banuazizi. “Instrumental Learning by Curarized Rats of a Specific Visceral

Response, Intestinal or Cardiac,” J. Compr. Physiol. Psychol., 65 (1968), 1-7.
Miller, N. E. and A. Carmona. “Modification of a Visceral Response, Salivation in Thirsty Dogs by

Instrumental Training with Water Reward,” J. Compr. Physiol. Psychol., 63 (1967), 1-
6.
Minc, S. “Psychological Factors in Coronary Heart Disease,” Geriatrics, 20 (1965), 747-755
Minc, S., G. Sinclair, and R. Taft. “Some Psychological Factors in Coronary Heart Disease,”
Psychosom. Med., 25 (1963), 133-139
Moos, R. H. and B. T. Engel. “Psychophysiological Reactions in Hypertensive and Arthritic

Patients,” J. Psychosom. Res., 6 (1962), 227-241.
Mordkoff, A. M. and O. A. Parsons. “The Coronary Personality: A Critique,” Psychosom. Med., 29
(1967), 1-14.
Moses, L., G. E. Daniels, and J. L. Nicker son. “Psychogenic Factors in Essential Hypertension:
Methodology and Preliminary Report,” Psychosom. Med., 18 (1956), 471-485.
Nahum, L. H. “Madness in the Recovery Room from Open Heart Surgery or ‘They Kept Waking Me
Up’,” Conn. Med., 29 (1966), 771-772.
Olin, H. S. and T. P. Hackett. “The Denial of Chest Pain in 32 Patients with Acute Myocardial
Infarction,” JAMA, 190 (1964), 977-981.
Ostfeld, A. M. and B. Z. Lebovits. “Personality Factors and Pressor Mechanisms in Renal and
Essential Hypertension,” Arch. Intern. Med., 104 (1959), 59-68.
Paffenbarger, R. S., Jr. “Chronic Disease in Former College Students. VI. Implications for College
Health Programs,” J. Am. Coll. Health Assoc., 16 (1967), 51-55.
Paffenbarger, R. S., Jr., J. Notkin, D. E. Krueger et al. “Chronic Disease in Former College Students.
II. Methods of Study and Observations on Mortality from Coronary Heart Disease,”
Am. J. Public Health, 56 (1966), 962.
Paffenbarger, R. S., Jr., P. A. Wolf, J. Notkin et al. “Chronic Disease in Former College Students. I.
Early Precursors of Fatal Coronary Heart Disease,” Am. J. Epidemiol., 83 (1966),
314-328.
Page, I. H. In Ciba Symposium, Hypertension. Berlin: Springer, 1966.
Paul, O. “Myocardial Infarction and Sudden Death,” Hosp. Practice, 6 (1971), 91-108.
Paulk, E. A., Jr. “Clinical Problems of Cardioversion,” Am. Heart J., 70 (1965), 248-274.
Pelser, H. E. “Psychological Aspects of the Treatment of Patients with Coronary Infarct,” J.

Psychosom. Res., 11 (1967), 47-49
Penaz, J. “The Blood Pressure Control System: A Critical and Methodological Introduction,” Bibl.
Psychiatr., 144 (1970), 125-150.
Perlman, L. V., S. Ferguson, K. Bergum et al. “Precipitation of Congestive Heart Failure: Social and
Emotional Factors,” Ann. Intern. Med., 75 (1971), 1-7.
Peters, J. P. “The Problem of Cardiac Edema,” Am. J. Med., 12 (1952), 66-76.
Pickering, G. The Nature of Essential Hypertension. London: Churchill, 1961.
Pinderhughes, C. A. and C. A. Perlman. “Psychiatric Aspects of Idiopathic Cardiomyopathy,”

Psychosom. Med., 31 (1969), 57-67.
Pitts, R. F. “Some Reflections on Mechanisms of Action of Diuretics,” Am. J. Med., 24 (1958), 745-
763
Plumlee, L. A. “Operant Conditioning of Increases in Blood Pressure,” Psychophysiology, 6 (1969),

283-290.
Price, D. B., M. Thaler, and J. W. Mason. “Preoperative Emotional States and Adrenal Cortical
Activity,” Arch. Neurol. Psychiatry, 77 (1957), 646-656.
Quinlan, D. M., C. P. Kimball, and F. Osborne. “The Experience of Open Heart Surgery. IV.
Assessment of Disorientation and Dysphoria Following Cardiac Surgery,” Arch. Gen.
Psychiatry, 31 (1974), 241-244.
Raab, W. Organized Prevention of Degenerative Heart Disease: A Challenge to American Medicine

and Economy. Burlington, Vt.: Queens City Press, 1962.
----. “Emotional and Sensory Stress Factors in Myocardial Pathology,” Am. Heart J., 72 (1966),
538-564.
----. “The Preventable Neurogenic Causes of Hypoxic Myocardial Disease,” Med. Psicosomatica
(Rome), 11 (1966), 1-30.
----. “Correlated Cardiovascular Adrenergic and Adrenocortical Responses to Sensory and Mental
Annoyances in Man: A Potential Accessory Cardiac Risk Factor,” Psychosom. Med.,
30 (1968), 809-818.
Rees, W. D. and S. G. Lutkins. “Mortality of Bereavement,” Br. Med. J., 4 (1967), 13-16.
Reiser, M. F. “Theoretical Considerations of the Role of Psychological Factors in Pathogenesis and

Etiology of Essential Hypertension,” Bibl. Psychiatr., 144 (1970), 117-124.
Reiser, M. F., A. A. Brust, and E. Ferris. “Life Situations, Emotions and the Course of Patients with
Arterial Hypertension,” Psychosom. Med., 13 (1951), 133-139,
Reiser, M. F., R. B. Reeves, and J. Armington. “The Effect of Variations in Laboratory Procedure
and Experimenter upon the Ballistocardiogram, Heart Rate, and Blood Pressure of
Healthy Young Men,” Psychosom. Med., 17 (1955), 185-199.
Reiser, M. F., M. Rosenbaum, and E. B. Ferris. “Psychologic Mechanisms in Malignant

Reiser, M. F., M. Thaler, and H. Weiner. “The Experimental Manipulation of Projective Stimuli in
the Study of Psychophysiological Responses,” Psychosom. Med., 17 (1955), 480.
Reiser, M. F., H. Weiner, and M. Thaler. “Patterns of Object Relationships and Cardiovascular
Responsiveness in Healthy Young Adults and Patients with Peptic Ulcer and
Hypertension,” Psychosom. Med., 19 (1957), 498.
Rennie, T. A. “Personality in Hypertensive States,” N. Engl. J. Med., 221 (1939), 448-456.
Rifkin, B. F. “The Treatment of Cardiac Neurosis Using Systematic Desensitization,” Behav. Res.
Ther., 6 (1968), 239-241.
Riseman, J. E. F. “Management after the Acute Coronary Attack,” Vase. Dis., 3 (1966), 315-319.
Rodda, B. E., M. C. Miller, 3RD, and J. G. Bruhn. “Prediction of Anxiety and Depression Patterns
among Coronary Patients Using a Markov Process Analysis,” Behav. Set., 16 (1971),
482-489.
Rosen, J. L. and G. J. Bibring. “Psychological Reactions of Hospitalized Male Patients to Heart
Attacks,” Psychosom. Med., 28 (1966), 808-821.
Rosenberg, S. G. “Patient Education Leads to Better Care for Heart Patients,” HSMHA Health Rep.,
86 (1971), 793-802.
Rosenman, R. H. and M. Friedman. “The Central Nervous System and Coronary Heart Disease,”
Hosp. Practice, 5 (1971), 87-97.
Rosenman, R. H., M. Friedman, and S. O. Byers. “Glucose Metabolism in Subjects with Behavior
Pattern A and Hyperlipemia,” Circulation, 33 (1966), 704-707.
Rosenman, R. H., M. Friedman, C. D. Jenkins et al. “The Prediction of Immunity to Coronary Heart
Disease,” JAMA, 198 (1966), 137-140.
Sachdev, N. S., C. C. Carter, R. L. Swank et al. “Relationship between Post-Cardiotomy Delirium,

Clinical Neurological Changes and EEG Abnormalities,” J. Thorac. Cardiovasc. Surg.,
54 (1967), 557-563.
Sapira, J. D., E. T. Scheilp, R. Moriarty et al. “Differences in Perception between Hypertensive and
Normotensive Populations,” Psychosom. Med., 33 (1971), 239-250.
Saslow, G., G. C. Gressel, F. O. Shobe et al. “Possible Etiologic Relevance of Personality Factors in
Arterial Hypertension,” Psychosom. Med., 12 (1950), 292-302.
Saul, L. J. “Hostility in Cases of Essential Hypertension,” Psychosom. Med., 1 (1939), 153-161.
Saul, L. J., E. Sheppard, D. Selby et al. “The Quantification of Hostility in Dreams with Reference to
Essential Hypertension,” Science, 119 (1954),382-383.
Schacter, J. “Pain, Fear, and Anger in Hypertensives and Normotensives,” Psychosom. Med., 19
(1957), 17-29.
Schneider, D. E. The Image of the Heart. New York: International Universities Press, 1956.
Schneider, R. A. and V. M. Zangari. “Variations in Clotting Time, Relative Viscosity and other
Physiochemical Properties of the Blood Accompanying Physical and Emotional
Stress in the Normotensive and Hypertensive Subject,” Psychosom. Med., 13 (1951),
289-303.
Schottstaedt, W. W., W. J. Grace, and G. Wolff. “Life Situations, Behaviour, Attitudes, Emotions, and
Renal Excretion of Fluid and Electrolytes, I-V,” J. Psychosom. Res., 1 (1956), 75-83.
Schull, W. J., E. Harburg, J. C. Erfurt et al. “A Family Set Method for Estimating Heredity and Stress:
II. Preliminary Results of the Genetic Methodology in a Pilot Survey of Negro Blood
Pressure, Detroit, 1966, 1967,” J. Chronic Dis., 23 (1970), 83-92.
Scotch, N. A. and H. J. Geiger. “The Epidemiology of Essential Hypertension. II. Psychological and
Sociocultural Factors in Etiology,” J. Chronic Dis., 16 (1963), 1183-1213.
Selye, H. The Stress of Life, pp. 128-148. New York: McGraw-Hill, 1956.
Shapiro, A. P. “Psychophysiologic Pressor Mechanisms and Their Role in Therapy,” Mod. Treat., 3
(1966), 108-117.
Shapiro, A. P., M. Rosenbaum, and E. B. Ferris. “Relationship Therapy in Essential Hypertension,”

Psychosom. Med., 13 (1951). 140-146.
Shapiro, D., B. Tursky, E. Gershon et al. “Effects of Feedback and Reinforcement on the Control of
Human Systolic Blood Pressure,” Science, 163 (1969), 588-590.
Shapiro, D., B. Tursky, and G. E. Schwartz. “Control of Blood Pressure in Man by Operant
Conditioning,” Circ. Res., 27, Suppl. 1 (1970), 27-41.
Shekelle, R. B., A. M. Ostfeld, B. Z. Lebovits et al. “Personality Traits and Coronary Heart Disease: A
Re-examination of Ibrahim’s Hypothesis Using Longitudinal Data,” J. Chronic Dis.,
23 (1970), 33-38.
Shekelle, R. B., A. M. Ostfeld, and O. Paul. “Social Status and Incidence of Coronary Heart Disease,”
J. Chronic Dis., 22 (1969). 381-394.
Silverman, A. J., S. I. Cohen, and G. D. Zuidiman. “Psychophysiological Investigations in
Cardiovascular Stress,” Am. J. Psychiatry, 113 (1957), 691-693.
Silverstone, S. and B. Kissin. “Field Dependence in Essential Hypertension and Peptic Ulcer,” J.
Psychosom. Res., 12 (1968), 157-161.
Silverstone, J. T., M. M. Tannahill, and J. A. Ireland. “Psychiatric Aspects of Profound Hypothermia

in Open-Heart Surgery,” J. Thorac. Cardiovasc. Surg., 59 (1970), 193-200.
Sjoerdsma, A. “Relationships between Alterations in Amine Metabolism and Blood Pressure,”

Society of Actuaries. The Build and Blood Pressure Study, 1959. Circ. Res., 9 (1961),
734-745.
Sokolow, M. and D. Perloff. “The Choice of Drugs and the Management of Essential Hypertension,”
Prog. Cardiovasc. Dis., 8 (1965), 253-277.
Sokolow, M., D. Werdegar, D. B. Perloff et al. “Preliminary Studies Relating Portably Recorded
Blood Pressures to Daily Life Events in Patients with Essential Hypertension,” Bibl.
Psychiatr., 144 (1970), 164-189.
Stamler, J. “Cigarette Smoking and Atherosclerotic Coronary Heart Disease,” Bull. N.Y. Acad. Med.,
44 (1968), 1476-1494.
----. The Primary Prevention of Coronary Heart Disease,” Hosp. Practice, 6 (1971), 49-61.
Stead, E. A., Jr., J. V. Warren, A. J. Merrill et al. “Cardiac Output in Male Subjects as Measured by
Technique of Right Atrial Catheterization. Normal Values with Observations on the
Effect of Anxiety and Tilting,” J. Clin. Invest., 24 (1945). 326-331.
Stevenson, I. P., C. H. Duncan, and H. G. Wolff. “Circulatory Dynamics before and after Exercise in
Subjects With and Without Structural Heart Disease during Anxiety and
Relaxation,” J. Clin. Invest., 28 (1949), 1534-1543.
Stonehill, E. “The Role of Denial in Incurable Disease: Psychological Adaptation to Long-term

Cardiac Pacemakers,” Bibl. Psychiatr., 144 (1970), 151-163.
Storment, C. T. “Personality and Heart Disease,” Psychosom. Med., 13 (1951), 304-313.
Syme, S. L. “Psychological Factors and Coronary Heart Disease,” Int. J. Psychiatry, 5 (1968), 429-
433.
Thaler, M., H. Weiner, and M. F. Reiser. “Exploration of the Doctor—Patient Relationship through
Projective Techniques. Their Use in Psychosomatic Illness,” Psychosom. Med., 19
(1957), 228-239.
Thomas, C. B. “Observations on Some Possible Precursors of Essential Hypertension and

Coronary Artery Disease,” Bull. Johns Hopkins Hosp., 89 (1951), 419-441.
----. “Characteristics of the Individual as Guideposts to the Prevention of Heart Disease,” Ann.
Intern. Med., 47 (1957), 389-401.
----. “Characteristics of Smokers Compared with Nonsmokers in a Population of Healthy Young

Adults, Including Observations on Family History, Blood Pressure, Heart Rate, Body
Weight, Cholesterol and Certain Psychologic Traits,” Ann. Intern. Med., 53 (1960),
697-718.
----. “The Precursors of Hypertension,” Med. Clin. North Am., 45 (1961), 259.
----. “Psychophysiologic Aspects of Blood Pressure Regulation: The Clinician’s View,” Psychosom.
Med., 26 (1964), 454-461.
----. “Psychophysiological Aspects of Blood Pressure Regulation: A Clinician’s View,” J. Chronic

Dis., 17 (1964), 599-607.
----. “The Precursors of Hypertension and Coronary Artery Disease: Insights from Studies of
Biological Variation,” Ann. N.Y. Acad, of Sci., 134 (1966), 1028-1040.
----. “Developmental Patterns in Hypertensive Cardiovascular Disease: Fact or Fiction?” Bull. N.Y.
Acad, of Med., 45 (1969), 831-850.
Thomas, C. B. and B. H. Cohen. “The Familial Occurrence of Hypertension and Coronary Artery
Disease with Observations Concerning Obesity and Diabetes,” Ann. Intern. Med., 42
(1955), 90-126.
Thurston, J. G. B. “A Controlled Trial of Hyperbaric Oxygen in Acute Myocardial Infarction—

Preliminary Results,” Am. Heart Assoc. (Abstract in circulation), 40 Suppl. 3 (1969),
203.
Trowill, J. A. “Instrumental Conditioning of the Heart Rate in the Curarized Rat,” J. Compr. Physiol.
Psychol., 63 (1967), 7-11.
Tufo, H. M., A. M. Ostfeld, and R. Shekelle. “Central Nervous System Dysfunctioning following
Open-Heart Surgery,” J. Am. Heart Assoc., 212 (1970), 1333-1340.
Vanderhoof, E., J. Clancy, and R. S. Engelhart. “Relationship of a Physiological Variable to

Psychiatric Diagnoses and Personality Characteristics,” Dis. Nerv. Syst., 27 (1966),
171-177.
Van der Valk, J. M. “Blood-Pressure Changes under Emotional Influences in Patients with
Essential Hypertension and Control Subjects,” J. Psychosom. Res., 2 (1957). 134-144.
Van der Valk, J. M., and J. J. Groen. “Personality Structure and Conflict Situation in Patients with
Myocardial Infarction,” J. Psychosom. Res., 11 (1967), 41-46.
von Eiff, A. W. “The Role of the Autonomic Nervous System in the Etiology and Pathogenesis of
Essential Hypertension,” Jap. Circ. J., 34 (1970), 147-153.
Voors, A. W. “Lithium in the Drinking Water and Atherosclerotic Heart Death: Epidemiologic
Argument for Protective Effect,” Am. J. Epidemiol., 92 (1970), 164-171.
Vreeland, R. and G. L. Ellis. “Stresses on the Nurse in an Intensive Care Unit,” JAMA, 208 (1969),
332-334.
Walter, P. F., S. D. Reid, and N. K. Wenger. “Transient Cerebral Ischemia Due to Arrhythmia,” Ann.
Intern. Med., 72 (1970), 471-473.
Weinberger, M. H., R. D. Collins, A. J. Dowdy et al. “Hypertension Induced by Oral Contraceptives

Containing Estrogen and Gestragen,” Ann. Intern. Med., 71 (1969). 891-902.
Weiner, H., M. T. Singer, and M. F. Reiser. “Cardiovascular Responses and Their Psychological
Correlates. I. A Study in Healthy Young Adults and Patients with Peptic Ulcer and
Weiss, B. “Electrocardiographic Indices of Emotional Stress,” Am. J. Psychiatry, 113 (1956), 348-
351.
Weiss, T. and B. F. Engel. “Operant Conditioning of Heart Rate in Patients with Premature
Ventricular Contractions,” Psychosom. Med., 33 (1971), 301-321.
Wells, R. L. “The ‘Unemployable’ Cardiac Patient,” JAMA, 218 (1971), 247.
Wendkos, M. H. “The Influence of Autonomic Imbalance on the Human Electrocardiogram. I.

Unstable T-Waves in Precordial Leads from Emotionally Unstable Persons without
Organic Heart Disease,” Am. Heart J., 28 (1944), 549-567.
Wendkos, M. H. and R. Logue. “Unstable T-Waves in Leads II and III in Persons with
Neurocirculatory Asthenia,” Am. Heart J., 31 (1946), 711-723.
Werko, L. “Can We Prevent Heart Disease? Multifactorial Physical, Environmental, Hereditary,

Clinical Factors Are Identified,” Ann. Intern. Med., 74 (1971), 278-288.
White, K. “Angina Pectoris and Angina Innocens,” Psychosom. Med., 17 (1955), 128-138.
Williams, R. B., Jr., C. P. Kimball, and N. Willard. “The Influence of Interpersonal Interaction Upon
Diastolic Blood Pressure,” Psychosom. Med., 32 (1972), 194-198.
Williams, R. B., Jr., and F. P. McKegney. “Psychologic Aspects of Hypertension. I. The Influence of
Experimental Interview Variables on Blood Pressure,” Yale J. Biol. Med., 38 (1965),
265-273.
Williamson, J., J. Mitchell, S. Kreider et al. “Assessing End Results for Heart Failure Patients
Selected from a Coronary Care Unit,” Am. Fed. Clin. Res. Natl. Meet., May 1968,
Abstract. Clin. Res., 16 (1968), 367.
Wincott, E. A. and F. I. Caird. “Return to Work after Myocardial Infarction,” Br. Med. J., 2 (1966),
1302-1304.
Wishnie, H. A., T. P. Hackett, and N. H. Cassem. “Psychological Hazards following Coronary

Infarct,” JAMA, 215 (1971), 1292-1296.
Wolf, G. A. and H. G. Wolff. “Studies on the Nature of Certain Symptoms Associated with
Cardiovascular Disorders,” Psychosom. Med., 8 (1946), 293-319.
Wolf, S. “Psychosocial Forces in Myocardial Infarction and Sudden Death,” Circulation, 39, Suppl. 4
(1969), 74-83.
Wolf, S., P. V. Cardon, Jr., E. M. Shepard et al. Life Stress and Essential Hypertension: A Study of
Circulatory Adjustment in Men. Baltimore: Williams & Wilkins, 1955.
Wolf, S., J. B. Pfeiffer, H. S. Fipley et al. “Hypertension as a Reaction Pattern to Stress: Summary of
Experimental Data in Variations in Blood Pressure and Renal Blood Flow,” Ann.
Intern. Med., 29 (1948), 1056-1076.
Wolf, S. and E. Shepard. “An Appraisal of Factors that Evoke and Modify the Hypertensive
Reaction Pattern,” Assoc. Res. Nerv. Ment. Dis. Proc., 29 (1950), 976-984.
Wolff, F. W. and R. D. Lindeman. “Effects of Treatment in Hypertension. Results of a Controlled

Study,” J. Chronic Dis., 19 (1966), 227-240.
Wolff, H. G. “Life Stress and Cardiovascular Disorders,” Circulation, 1 (1949), 187-203.
Wolff, K. “Angina Pectoris and Emotional Disturbances,” Dis. New. Syst., 30 (1969), 401-404.
Wolpe, J. Psychotherapy by Reciprocal Inhibition, pp. 139-165. Stanford: Stanford University Press,
1958.
Yamori, Y., W. Lovenberg, and A. Sjoerdsma. “Norepinephrine Metabolism in Brainstem of

Spontaneously Hypertensive Rats,” Science, 170 (1970), 544-546.
Ziskind, E. and T. Augsburg. “Hallucinations in Sensory Deprivation,” Dis. Nerv. Syst., 28 (1967),
721-726.
Notes
1This chapter has a subsection on Psychophysiological and Psychodynamic Problems of the Patient
with Structural Heart Disease by Morton F. Reiser and Hyman Bakst.
2This section through is modified from the corresponding section in Chapter 33, Psychology of
Cardiovascular Disorders by Morton F. Reiser and Hyman Bakst, appearing in the 1st ed.
of the American Handbook of Psychiatry, Vol. 1, New York: Basic Books, 1959.
Chapter 27
Psychological Aspects Of Gastrointestinal

Disorders1
George L. Engel
Introduction
This chapter is intended to summarize the present status of our
knowledge with respect to the interrelationships of psychic and somatic

processes as they affect gastrointestinal activity. Furthermore, it offers a
clinical classification of the varieties of gastrointestinal disturbances which

may result directly or indirectly from psychological influences.
Historically, there have been two major approaches to psychosomatic
research. The psychoanalytic approach, exemplified by the work of Franz

Alexander, by elucidating the nature of unconscious mental processes,
identified specific psychodynamic tendencies that are intimately related to
gastrointestinal activity in a developmental as well as functional sense. While
such data originated in the course of the psychoanalytic treatment of
neurotics and led to the now familiar concepts of the oral and anal phases of
psychosexual development, the application of the same method to patients
with gastrointestinal disorders served to highlight more explicit etiological

relationships between such unconscious psychodynamic influences and
gastrointestinal symptoms (see references 7, 20, 94, 96, and 158).
Furthermore, psychoanalytic theory and method have made the development
of other techniques possible, such as the various projective and other testing
instruments of the clinical psychologist, whereby the unconscious psychic
processes can be identified and studied.
During the same period, Harold Wolff, Stewart Wolf, and others at
Cornell University approached the problem through direct observation and

measurement of physiological change in the exposed gut of fistulous subjects
and related these changes to concomitant psychological states. These
correlative psychophysiological and biochemical studies have provided a

basis for delineating the somatic parameters more precisely in terms which
can be related to concurrent psychological and behavioral variables. Some

efforts have been made to combine the two approaches, that is, to make
physiological or biochemical measurements in the course of psychoanalysis,

but these have involved such technical and theoretical difficulties as to
seriously limit the value of the results so obtained. In addition to these
approaches, careful clinical—-including epidemiological—studies of
individuals and populations of patients correlating the course of disease with
psychological and social factors, continue to be an indispensable source of
new knowledge in this area. Less distinction between the approaches is made
today than two decades ago, and the student of gastrointestinal disorders
draws upon multiple perspectives and overlapping approaches.
Specific Relationships Between Psychological Processes and the

Gastrointestinal Tract
The most significant contribution of psychoanalysis to gastroenterology
was the demonstration of the role of feeding and elimination in the

psychological and social development of the child. The relevant points may be
summarized as follows:
The newborn infant’s cycle of hunger→ crying → nursing → satiation →

sleep → hunger→ and so on, constitutes an important, biological influence
regulating the first establishment of a relationship between the neonate and
its mother. In the course of mounting hunger and then nursing, the infant
periodically achieves relief of tension in the mother’s arms, laying the basis
for the ultimate association in the nervous system of an intrinsic drive
(hunger) and its relief through an environmental influence (mother). This is a
reciprocal process, the mother being required to recognize and respond
appropriately to the infant’s cues indicating hunger and the infant being
required to fit into the mother’s particular patterns of nursing. If successful, it
is a source of mutual gratification; if unsuccessful, it becomes a source of
tension and frustration for both infant and mother. The consequence of this
dependence on the feeding cycle for the psychobiological unit of mother and
child is that for the infant many of the first learning experiences, i.e., the first
awareness of the mother as part of an outer environment, and the early
associations of comfort and discomfort, may be experienced in the oral

intaking terms of the nursing experience. This is responsible for the fact that
one prominent psychological perspective of the young infant is an oral one,
namely, that which is perceived as good or desirable is taken in, while that
which is felt as bad is spit out or refused. Evident in infancy in such literal
behavioral terms as mouthing, sucking, and tasting everything in reach, this is
also manifest in later life as a general psychodynamic tendency which is
capable of influencing the content of thought and the nature of behavior, if not
the actual activity of the gastrointestinal tract itself. This is revealed in the
oral mannerisms of sucking, mouthing, and chewing pencils, pipes, cigarettes,

knuckles, gum, and what not, in such familiar oral terms of endearment and
pleasure as “How sweet!”, “I could eat you up,” or of displeasure (distaste!) as,
“You make me sick (to my stomach),” “I can’t stomach that,” as well as in the
language used to designate certain personality traits, as “sour,” “greedy,”
“sweet,” etc. In a broader context, the feeding experiences of infancy also
provide a nidus around which may cluster a whole complex of associations
related to such fundamental human needs as to be taken care of, supported,
and nurtured, the so-called dependency needs, and hence the classical
psychodynamic association, “oral-dependent.”
With the eruption of teeth and the transition from sucking to chewing
comes another contribution of a body activity to psychic development,
namely, the expression of aggression and hostility in oral terms, namely,
biting, tearing, and even consuming cannibalistically. Again, human behavior
and language amply attest to the universality of such psychodynamic
tendencies. “Gnashing the teeth,” or “clenching the jaw with rage,” or “biting
sarcasm” (from the Greek, “sarkazo,” to tear flesh), and many other
expressions may be cited. Characteristically, the thwarting of oral needs,
literally or figuratively, may elicit aggressive impulses, to take by force that
which is not given, or to force the others to give, expressed literally by the
child (and symbolically by the adult) through grabbing, tearing, biting, or
holding firmly with the teeth. Greed, envy, possessiveness, spite, bitterness,
sarcasm, vindictiveness, all are words that convey such oral aggressive
meaning.
Since the infant cannot survive or develop without food and cannot feed
in the absence of a nurturing person (mother), it is clear that these oral-

dependent and oral-aggressive tendencies must be present and operative in
all individuals. But what originally was essential for survival, eventually loses
such imperative qualities and the associated patterns of behavior must give
way to other patterns more acceptable to society. Critical for the course of
such developmental achievements are the strength or the driving quality of

the original feeding impulses, the degree to which the mother succeeds or
fails in gratifying the primary oral needs, the range of other biological and
psychological gratifications that are available to or provided for the
developing infant, and the environment’s standards and expectations as to

manner, degree, and circumstance of oral expression and behavior (the
interpersonal and social forces). The child in time internalizes these external
demands, expectations, and standards and he learns, so to speak, the

conditions under which he can prosper and be loved and those under which
he is frustrated or rejected. In brief, through the processes of socialization he
not only learns that the reality of his particular life situation requires
compromises, delays, and the weighing of the consequences of his wishes,

impulses, and acts, but in so doing he is repeatedly subject to intrapsychic as
well as interpersonal conflict.
The presence of a legacy of past as well as of current conflict is a fact of
psychic life. It is a fundamental premise of psychoanalysis that those

psychodynamic tendencies which must be denied expression for any reason,
may nonetheless continue as unconscious forces to exert an influence on
mentation and behavior, an influence which may be reflected in various bits
of derived behavior, including changes in gastrointestinal function. It is
assumed that unconscious oral-dependent or oral-aggressive impulses, if not
successfully gratified by psychological or social devices may be accompanied

by physiological changes in the stomach appropriate to preparing to take food
into the stomach. Evidence that such indeed is the case in infancy, when
affection and aggression are literally expressed in oral terms, is found in the
results of a study of concomitant behavior and gastric secretion in a fifteen to
eighteen-month-old infant with a gastric fistula. When this baby was relating
to a familiar experimenter either with affection and pleasure or with rage, the
rate of hydrochloric acid secretion by the stomach was high. On the other
hand, when the experimenter was a stranger from whom she typically
withdrew and whom she ignored completely, becoming totally inactive,

sometimes to the point of falling asleep, the secretion of gastric acid virtually
ceased, even remaining unresponsive to histamine. When the familiar

experimenter reappeared, she characteristically exhibited signs of exuberant
joyful recognition, and a copious secretion of gastric juice ensued. The

maximum rates of acid secretion during a sustained joyfully affectionate
relationship, or during intense rage approached those observed during sham

feeding. In brief, this study appeared to establish that at the level of
development characteristic of this child (actually closer to ten to twelve
months in development than to her chronologic age of fifteen to eighteen
months) active relating patterns, whether affectionate or hostile, were
accompanied by the increments in gastric secretion comparable to what
occurred when the stomach was preparing to receive food; in the absence of
both food and meaningful human relationship, stomach activity virtually
ceased. Similar findings have been reported in a pair of twins a year and a half
old, one with a gastric fistula and the other normal.
Comparable psychophysiological studies of a four-year-old child
demonstrated the dissociation between behavior and gastric secretion that
takes place upon the development of more sophisticated mental means of
relating and communicating, including language. This child showed a low
basal level of secretion of acid and pepsin when she was relating comfortably
and happily with the experimenter withdrawing gastric juice. This contrasts
with the high secretion found in the younger infant under such circumstances.
On the other hand, when the four-year-old had to make an effort to relate, as
with a new experimenter, gastric secretion rose, as it did also when she was
angry or anxious. Secretion was low when she became detached or

withdrawn.
Studies of adults with a gastric fistula also indicate rise in gastric
secretion during rage, both expressed and suppressed, and a fall during
dejection and withdrawal. Depression and “giving up” experimentally induced

through hypnosis in adult volunteers also has been found to be associated
with a decline in the rate of gastric acid secretion.
Like feeding, elimination constitutes another physiological pattern, the

development and control of which eventually involves a reciprocal
relationship between mother and child. In earliest infancy defecation is
controlled by an innate reflex which automatically empties the bowel when it
reaches a critical degree of fullness. Presumably the infant has no psychic

engagement in this process other than in terms of what pleasant or
unpleasant sensations may accompany such peristaltic activity. However,
toward the end of the first year and for a variable period thereafter, most
infants not only appear to experience pleasure in the act of defecation but
may also come to regard their feces with interest, if not decided pleasure.
Certainly they manifest no disgust. Ultimately, however, the child must learn
to control defecation and restrict his pleasure in feces in a manner prescribed
by the child-rearing practices of his particular group, which may range from
highly exacting to excessively lenient. Ultimately feces become objects of

loathing and disgust, though this attitude is more pronounced toward
another’s bowel movements than one’s own. This constitutes another

important reciprocal relation between mother and child that is geared closely
to an intrinsic biological rhythm in the child. To aid her child to achieve bowel
control, the mother must learn the physiological cues that the child emits and
which indicate his readiness to defecate, while the child must learn from the
mother’s response that his physiologically derived sensations call for a
specific toileting action. As with nursing, this reciprocal situation is mutually
gratifying when successful but fraught with complications when mother or
infant fail to respond properly to each other. The latter incompatibility may
range from the mother who misses all the cues and fails to put the baby on
the pot to the mother who interprets the wrong cues and puts the baby on the
pot at the wrong times. The tensions which may develop between mother and
child with such stressful learning failures constitute the basis for explicit
psychophysiological relationships between behavior on the one hand and
variations in bowel activity on the other. In addition, the failure to resolve
successfully the inevitable incompatibility between the wishes to enjoy feces
and the bowel movement, and the necessity to conform to parental
requirements may perpetuate such underlying psychodynamic pressures and

exert a distinctive influence on personality development, contributing to the
development of the so-called “anal traits” of exaggerated orderliness,

perfectionism, punctuality, and pedantry. These are seen as defenses against
a persistent unconscious wish to be free to soil. Once again, the persistence of

unconscious psychodynamic tendencies must be emphasized, exerting an
influence on mentation and behavior, and sometimes on bowel function as

well. As will be discussed later, bowel symptoms are common in persons with
these characteristics, called “anal” in psychoanalytic terminology.
The utilization of concepts of bowel activity as a vehicle for the
expression of aggression is amply attested to by familiar anal and fecal swear
words and gestures. Increased physiologic activity of lower bowel has been
noted during expression of anger in fistula subjects.
By virtue of the pleasurable sensations which originate during sucking,

eating, and defecation, and the intimate role of feeding and excremental
activities in the development of affectual relationships, it should not be
surprising that both ends of the gastrointestinal tract are capable of being
endowed by the child with sexual meaning. Concepts of oral or anal
intercourse and oral or anal pregnancy and birth are a common part of the
fantasy life or misinterpretation of children. How such ideas, when
unresolved, may serve to provoke gastrointestinal symptoms, will be
discussed later2.
Classification of Psychological Phenomena in Relation to the Gastrointestinal

Tract
Psychogenic Disorders
These include two groups of disorders. One refers explicitly to
symptoms ascribed by the patient to the abdomen or gastrointestinal tract

which, in fact, constitute psychic phenomena involving intrapsychic
representations of gastrointestinal function and process. In such disorders,
the gastrointestinal tract per se either is not primarily involved, or is
responding in a normal manner to a stimulus, as for example, nausea or
vomiting in response to a disgusting idea. Within this category are conversion

reactions, somatic delusions, and hypochondriacal phenomena.
The second group comprises bizarre and inappropriate patterns of

feeding or elimination which represent either inadequate or undifferentiated
behavior patterns and/or are the logical consequences of bizarre (psychotic)
ideation. These include anorexia nervosa, pica, food faddism, encopresis,
psychogenic megacolon, compulsive use of laxatives or enemas, and other
bizarre feeding or bowel behavior. Some persons in this group are psychotic.
Psychophysiological Disorders
These involve mainly the physiological concomitants of affects, e.g.,
rage, anxiety, shame, guilt, etc. The involvement of the gastrointestinal tract
may be direct, through its innervations, or indirect, through other general
physiological or biochemical processes. Important here is that in the presence
of preexisting organic vulnerabilities or latent defects such physiological or
biochemical processes may serve to precipitate manifest organic disease.
Somatopsychic-Psychosomatic Disorders
These are organic disorders, the predisposing conditions for which not
only are present or acquired early in infancy but also have influenced
psychological development in specific ways. Such disorders may become
manifest any time in life but the individual bearing the predisposing
biological factor, though always vulnerable, will only develop the manifest
disorder if certain environmental—including psychological—stresses occur.
Included in this category are the conditions classically considered in the past
as psychosomatic, i.e., duodenal ulcer and ulcerative colitis, as well as others
such as coeliac (malabsorption) syndrome, regional enteritis, and achalasia.
Psychogenic Disorders
The psychogenic disorders contribute disproportionately to the number
of patients presenting with complaints presumably originating from the
gastrointestinal tract. Anorexia, bulimia, nausea, vomiting, dysphagia,
abdominal pain, bloating, aerophagia, rectal incontinence, diarrhea,

constipation, and pruritus ani all are symptoms which may be psychogenic in
origin rather than the consequences of intrinsic disorder of the
gastrointestinal system. Before discussing specific syndromes and symptoms,
however, it is necessary to elucidate some underlying psychic mechanisms,

including conversion and delusion, and to relate these to the syndromes of
hysteria, hypochondriasis, and schizophrenia.
Conversion Reactions
Conversion reactions comprise a major category of psychogenic
disturbances, experienced or manifested in somatic terms. As a psychological

process, conversion represents a means of dealing with stress which makes
use of the fact that it is possible to express ideas symbolically through body
activities or sensations. The gesture is a familiar example of how a body

movement may be used to communicate an idea or a wish and to relieve
tension. The typical conversion reaction, however, occurs when the wish,
idea, or fantasy in question not only cannot be consciously expressed, but
cannot even be consciously acknowledged. Under such circumstances the

idea may achieve expression in the form of a sensation or a body activity
which symbolically represents the idea in question, and yet at the same time
effectively prevents it from being acted upon. As a means of dealing with
psychological stress and resolving intrapsychic conflict, such symbolic use of

the body replaces both acting on the wish and consciously entertaining it as a
thought or fantasy, both of which are felt as threatening. By this means,
psychological compensation is maintained although at the expense of some

abnormal utilization of the body part selected for this purpose. The result is a
somatic symptom based on psychological misuse of the body part, not on
disease of the part so involved. Physical examination, therefore, demonstrates
no organic defect directly related to the symptom.
The common conversion reactions involve a great variety of body parts
and functions, all of which share the following: (1) they are accessible to
voluntary control (motor) or awareness (sensation); (2) they had been
involved in some way in human relationships in the course of development;
and (3) they are capable of being imagined in the form of some concepts of
the body image or a function thereof. Each conversion manifestation
characteristically is overdetermined, meaning that multiple factors are

involved in determining the choice of the particular bodily expression used.
The expression which proves to be the most satisfactory psychologically is
the one which can most economically symbolize these multiple determinants.
We may best illustrate conversion by a hypothetical example. As
pointed out earlier, circumstances may encourage some children excessively
to endow the act of eating or swallowing with sexual or aggressive fantasies
or wishes which then become a source of conflict. When later in life some
provoking circumstance serves to activate such an unconscious impulse, as,
for example, the equating of the act of eating with an infantile primitive wish
to bite aggressively or to use the mouth for sexual purposes, the conflict
evoked may serve to block the impulse from coming to consciousness as a
thought or a wish, as well as prevent the overt act. Instead, it may appear in
its symbolic form as a conversion symptom, as anorexia, dysphagia, nausea,
vomiting, or pain. In such a case the disturbing wish or fear, namely, to bite, to
perform fellatio, to be bitten or be sucked on, has been effectively disposed of
and has been “converted” to a bodily activity which symbolically means, “I
can’t eat (swallow),” or “I throw up what I swallow.” This forms one basis for
such conversion symptoms as anorexia, dysphagia, nausea, or vomiting. Such

an inhibition of the processes of eating, swallowing, or retaining that
swallowed is a symbolic substitute for the forbidden idea, an idea which in
fact had originally related not to food in its literal sense but rather to some
unacceptable sexual or aggressive wish which, in the course of development,
acquired a link to the act of eating or swallowing. The person so afflicted not
only keeps the forbidden idea from conscious awareness by literally not
eating, swallowing, or retaining, but he also broadcasts to the world that he
does not take anything into his mouth; when he does do so, he has difficulty
swallowing it or he regurgitates it. In this symptomatic act the disturbing

motivation is contained as “I wish to bite, to take the penis in the mouth, to
swallow the loved (or hated) person,” etc., implementation of which is

blocked. Thus he simultaneously expresses the wish symbolically, yet makes
it impossible for the wish to be acted upon.
How the conversion is experienced by the patient and communicated to
others is in part determined by the characteristics of the society in which the

patient lives and in part by the nature of his thought processes and capacity
for reality testing. “Styles” of conversion reactions change with changing
times and attitudes, so that certain patterns common in a past generation
now are rare. The Victorian swoon is a good example. Modern health and
medical consciousness contributor to a tendency to manifest conversion
symptoms in keeping with the popular concepts of what physicians expect of

physically sick patients. The more capable the patient is of retaining accurate
reality orientation, the more likely will the conversion symptom be
communicated in such terms. In contrast, the psychotic patient whose

thought processes and reality capacities are defective is more likely to
experience and communicate conversion symptoms in bizarre terms,
approaching true somatic delusions, and to offer bizarre explanations for the
symptoms.
The positive identification of a bodily symptom as a conversion reaction

requires considerable diagnostic skill. The common practice of depending
solely upon the ruling out of organic factors as the means of diagnosing
conversion is hazardous. Not only may some organic defects be extremely

difficult to demonstrate but also conversion symptoms and organic processes
may coexist. In the absence of positive psychological criteria, conversion cannot
be invoked as the explanation of a symptom, even when all other data indicating
organic defect are negative.
The conversion symptom always has its sources in the history of the
individual’s past human relationships and in the types of bodily activities or
experiences which had been involved in the gratifications and conflicts that
marked these relationships. A skillfully conducted interview is the keystone
to the diagnosis of conversion.
Conversion reactions may occur under a wide variety of stressful
circumstances and in persons of the most varied psychological
characteristics, from the essentially healthy individual to the psychotic. They

are most common in and characteristic of hysteria, a condition in which there
is a predilection toward use of the body for expression of feelings, wishes, and
ideas. But it is not correct to assume that conversion reactions occur only
among hysterics.
A less common syndrome than hysteria is hypochondriasis, marked by
the occurrence of unpleasant bodily sensations, as itch, formication, crawling,
pulling, fullness, pain, and other peculiar sensations or by the persistent idea
of the presence of an organic disease, as cancer, tuberculosis, syphilis, etc. The
latter represent disturbed ideas but may include as well symptoms related to
the disease in question, as, for example, fullness, bloating, anorexia, etc.,
associated with the idea of stomach cancer. Hypochondriacal symptoms
characteristically have an insistent, demanding, nagging, torturing, and even

persecuting quality and are the source of great distress to the patient, who
pleads for relief. They involve especially the skin, abdomen, nose, rectum, and
genitals. Peculiar and persistent sensations in the rectum are especially
characteristic. At times hypochondriacal symptoms assume the quality of
somatic delusions. Thus, the patient may experience or interpret sensations
to mean that something is growing inside, that his insides are rotting away,
that a body part is changing shape, that bugs are crawling under the skin, etc.
Specific gastrointestinal conversion symptoms have their origins in the
psychodynamic factors discussed earlier. They include the whole range of

oral and anal, aggressive and sexual fantasies of which the child is capable.
Thus anorexia, bulimia, hypophagia, nausea, vomiting, and bloating may
relate to conflicts over unacceptable wishes to be nursed like a baby, to bite
or swallow aggressively, to use the mouth for sexual purposes, concepts of
oral pregnancy or birth, and many others.
Some general clinical characteristics of individual conversion symptoms
that are manifest as gastrointestinal symptoms follow.
Anorexia
As a conversion symptom, anorexia is likely to be described in complex

terms and to be expressed as an active distaste for food, or dislike of eating
rather than merely as an absence of appetite. It may be directed toward

certain foods and not others, especially foods capable of symbolic meaning,
such as liquid egg white, scum on milk, rare meat, etc. There may be a
preference for “baby” foods. It may occur only in certain settings or with
certain people and be totally absent at other times or under different

circumstances. Occasionally the complaint of anorexia does not correspond
with the observed nutritional status, the patient maintaining or even gaining
weight by virtue of eating more than he realizes. Appetite may be present,
even ravenous, only to disappear upon the sight or odor of food, or at the time
when meals are served, returning when the meal is over.
Bulimia
Certain types of sporadic overeating, often followed by self-induced

vomiting, may be regarded as conversion reactions. In these cases the act of
gorging, the manner of biting, chewing, and swallowing the food, and even the
choice of food so consumed are determined by their symbolic defensive
function in dealing with threatening aggressive or sexual wishes. The

induction of vomiting sometimes represents an attempt to undo the symbolic
act.
Dry Mouth, Burning or Painful Tongue
Such symptoms are occasionally brought about through the conversion
mechanisms. On examination mouth moisture is seen to be ample and no

changes in the tongue are evident. Such a sensation of dry mouth may
symbolize fear or may be a defense against an oral sexual wish. The
conversion symptom, burning tongue, may reflect a conflict either about the
use of the tongue in speaking, such as to utter burning, sharp, or acid words of
attack, or about its use as a sexual organ. The common expression, to be
“burnt” refers to being caught and hurt or punished for committing a
forbidden act. Pain in the tongue may reflect symbolically the notion “I will
bite my tongue rather than say that.”
Nausea and Vomiting
As conversion symptoms these share many of the characteristics

already described for anorexia. The symptom may be unrelated to eating, and
may either precede or follow food intake. The vomiting may be relatively
unproductive, yielding only mucus or a small amount of bile-stained gastric
juice. Retching and gagging may be prominent, at times occurring merely on

the sight of food or when food enters the mouth or posterior pharynx. Food
may be taken into the mouth gingerly, in small morsels, and kept in the
forepart of the mouth for a long time, the act of swallowing evoking a gag.
Morning nausea, gagging, and vomiting may indicate unconscious pregnancy

fantasies in men as well as women. Similar symptoms at night may reflect an
unconscious wish for or fear of an oral sexual experience.
Dysphagia
The idea as well as the act of swallowing is discomforting. It may include
the feeling that the food cannot be taken into the mouth, cannot be passed
into the pharynx, and, if it is swallowed, that it will stick in the gullet.
Observed eating, the patient may pucker his face, chew very slowly and
gingerly, keep the bolus in the forepart of the mouth, and act as if it is very
difficult to move it into the vault. Indeed, he may spit it out. Here an inhibition
of the volitional part of swallowing is quite evident. Food is experienced as

sticking high in the gullet. The difficulty in swallowing may be restricted to
particular items of food or may include everything swallowed, liquid as well
as solid. Conversion dysphagia may involve all consistencies of food rather
than showing the usual progression of difficulty, from solid to soft, and then
liquid that is more characteristic of organic obstructions. Achalasia is
classified as a somatopsychic-psychosomatic disorder and will be discussed
later.
Globus Hystericus
This conversion reaction, a sensation of a lump in the throat usually at
the suprasternal notch, is unrelated to eating and usually does not interfere
with swallowing, though the patient may fear that it will.
Abdominal Bloating
This term covers a number of entities. Some patients complain that the
abdomen is enlarged, but this is not confirmed upon examination. This false
perception of abdominal distention usually is accompanied by unpleasant
abdominal sensations, sometimes specified as gurgling or movement and
sometimes interpreted by the patient as indicating a cancer. Complaints of
belching, flatus, and indigestion are common. Such persons are usually
blatantly hysterical or hypochondriacal. Evidence for an underlying

pregnancy fantasy is usually not hard to come by.
The second type is called nongaseous abdominal bloating and is
produced by simultaneously thrusting the lumbar spine forward and relaxing
the abdominal musculature. The lumbar lordosis is often so great that the
hand may easily be passed beneath the spine of the reclining patient. This
type of muscular bloating typically appears and disappears rapidly, often
within seconds. It characteristically disappears during sleep. These patients,

almost always women, also are obviously hysterical, with unconscious
pregnancy fantasies, intense longing to be pregnant, or actual delusions of

pregnancy.
Air swallowing (aerophagia) is a third mechanism of bloating and will
be discussed under Psychophysiological Disorders.
Constipation and Diarrhea
As conversion symptoms these are concerned mainly with that segment
of lower bowel which is under more or less voluntary control. Conversion
constipation is secondary to an inhibition of the act of defecation rather than
to an intrinsic disturbance in bowel motility, though the latter may develop in
time as well. The history generally will reveal considerable variability in
bowel behavior, with an inability to defecate at certain times or in certain
settings, as in strange and unclean bathrooms, in the presence of others, etc.

Its sporadic appearance may be correlated with the threatening emergence of
anal soiling or sexual impulse.
Diarrhea as a conversion symptom most often consists merely of the
complaint of several stools a day, but these are usually relatively formed. It is
uncertain whether true diarrheal stools ever result from a conversion
mechanism.
Pruritus Ani
As a conversion reaction, this symptom is more common among men

than women (who are more likely to complain of pruritus vulvae). It rather
typically reflects unconscious erotic anal fantasies, including a wish for anal
masturbation. In some instances the unconscious latent homosexual
implications contribute to a paranoid attitude, a fear of anal attack, or the

delusion that another man threatens such an attack. The existence of such
paranoid tendencies must always be carefully searched for before the male
patient with pruritus ani is subjected to rectal examination or proctoscopy.
Pain
Probably the most common conversion symptom encountered in
medical practice is pain. Conversion pain may be experienced in any part of

the body and therefore must be distinguished from pain that indicates
organic disorder. The topic of pain is treated fully in Chapter 34 of this
volume.
In differentiating conversion pain from pain of other origin, it is
necessary to explore the patient’s background not only for the specific
psychodynamic factors which are especially conducive for the choice of pain,
rather than some other symptom, but also to determine that it is in fact
conversion pain. A careful description of the pain is of high importance in

differentiating the two varieties of pain. In general, the conversion pain
differs from the pain of a discrete organic process in respect to its quality,
timing, location, radiation, and the nature of the provoking and alleviating
factors. The latter reflect the characteristics of the neural input as determined
by the pathophysiological processes at the periphery and confer upon the
pain experience those distinctive qualities which enable one to differentiate
the pain of biliary colic, for example, from that of peptic ulcer. This may be
referred to as “the peripheral signature” and it is the deviation from such
discrete patterns which usually first alerts the physician to the possibility that
the pain is not originating from a peripheral site. Occasionally, however, the
patient with a conversion pain, having been subjected to pointed and
directive interview experiences, may present a description indistinguishable

from some classical organic syndrome. The same may hold true of the patient
whose conversion pain actually was preceded by some painful illness, as
biliary colic or duodenal ulcer, or of the patient who has an intimate

knowledge of such syndromes through close contact with another patient, or
through the familiarity that results when the patient is a physician or nurse.
Ordinarily, conversion pain is described either with vivid imagery or very
vaguely. Such complex pain descriptions as “burning like a fire,” “like being
stabbed with a knife,” “like being tied in a knot,” “wrung like a mop,” reflect
the idiosyncratic psychological meaning of the pain to the sufferer and are of
value in suggesting the diagnosis.
Disorders of Eating and Elimination Secondary to Psychopathological States
There are a variety of patients who exhibit inappropriate or bizarre
patterns of eating or elimination which are secondary to psycho-pathological
states. These differ from conversion reactions as described above in that they
represent more complex disturbances in the behavior associated with eating
and elimination rather than involving the use of a body part or function in a
symbolic and defensive manner. Such disturbances may range from
inadequate or undifferentiated eating or elimination behavior to behavior
which is determined by bizarre (psychotic) ideation but is logical in the

framework of that ideation though inappropriate or strange by ordinary
standards. For the most part, this group of patients make themselves evident
by the obvious peculiarity of their ideas about or manner of eating or moving

their bowels, though these may easily be overlooked if the examining
physician neglects to obtain a precise description of these acts or to explore
the patient’s explanation for his complaint of “no appetite,” “sick to the
stomach,” “constipation,” or “diarrhea.”
Anorexia Nervosa
Typically a disorder of young people, usually beginning during
adolescence, and far more common among girls than boys, anorexia nervosa
generally presents as profound weight loss and emaciation secondary to a
failure to eat. This syndrome is described fully in Chapter 32 of this volume.
Pica, Food Faddisms, and Other Peculiar Dietary Habits; Laxative and Enema
Addiction
This group ranges from children (and a rare adult) who exhibit a defect
or perversion in the ability to discriminate the edible from the inedible to
persons whose food habits are determined by bizarre or peculiar modes of
thinking. As a whole these patients have not been very extensively studied.
The first group includes the childhood syndrome of pica and those who
habitually consume hair and other items, leading to bezoar formation. By and
large these are grossly disturbed people.
Food faddism, vegetarianism, addiction to peculiar diets, morbid
concern over contamination of food, harmful ingredients, artificial additives,
etc., and excessive use of laxatives or enemas may present as thoroughly
rationalized behavior, or in relationship to some gastrointestinal complaint
which the patient usually explains in terms of his idiosyncratic concepts. Such
patients are unlikely to consult physicians about their theories of diet or

digestion. Indeed, they commonly have a low regard for the medical
profession and may withhold such information. More often they offer such
traditional complaints as lack of appetite, nausea, vomiting, eructation,

bloating, abdominal rumbling, “indigestion,” excessive gas, diarrhea, or
constipation, but a less directed inquiry which permits the patient to

elaborate his own ideas about his difficulty quickly reveals these to be
expressions of more complex and pathological ideation. In brief, they reflect

morbid psychological concepts of something “bad” or destructive within the
body, which in actuality represent displacements of “bad” or disturbing
thoughts or fantasies. Accordingly, the patient sees certain foods or the
contents of the bowel as positively bad or dangerous, not simply as
disagreeing with him—a contrast to patients with specific food intolerances.
Instead, they espouse complex and bizarre theories as to the mode of action
of the food on the body or mind, and sharply divide foods into beneficial and
harmful categories. Some may indulge in compulsive and excessive catharsis,
or use of enemas or colonic irrigation as means of getting rid of the “bad” that
is inside. Secondary nutritional deficiencies and electrolyte imbalances may
result from such self-imposed dietary restrictions or excessive purging.
More detailed psychological inquiry usually establishes that these
strange notions are not restricted to the functions of the gastrointestinal
system but extend to many other spheres as well. Thus these people may also
exhibit eccentricities in dress, manner, behavior, and belief systems, and
belong to crank or fringe groups. Some are obviously schizophrenic, while
most reveal at least an inclination toward the persecutory delusional attitude

of the paranoid. In general, they feel strongly about their theories, which are
not easily modified by any argument no matter how sound.
Encopresis and Psychogenic Megacolon
Encopresis, or “fecal soiling,” like its urinary counterpart, enuresis, with

which it is occasionally associated, represents a complex psychologically
determined failure or lapse in toileting. It consists of the passage of stools of
normal or near-normal consistency into clothes, bed clothes, or any
receptacle not intended for such purposes. It typically begins in childhood
either as a failure to achieve proper toileting or as a loss of previously

achieved bowel control. Less frequently it extends into adulthood, unless one
includes in this category patients who become incontinent in the course of
organic brain disease. Severely withdrawn, catatonic schizophrenics and
other disturbed psychotics may also relinquish normal standards.
Among children encopresis may take the form either of the
promiscuous and casual expulsion of feces whenever the impulse so moves or
of prolonged retention of stool, with leakage of feces or periodic huge
movements. The latter may be associated with enormous distention of the

colon, sometimes designated as psychogenic megacolon. This may be
distinguished from aganglionic megacolon (Hirschsprung’s disease) by the
following characteristics. It begins at an age when neuromuscular control is

to be expected; the child is encopretic (as defined above); there are periodic
voluminous bowel movements either spontaneously or after an enema;

defecation may occur in supine and standing positions; the rectum commonly
is packed with feces; episodes of intestinal obstruction do not occur; the

course is relatively benign; and the spastic rectal segment characteristic of
Hirschsprung’s disease does not occur.
Of the many variables involved in the genesis of encopresis, toilet
training and possibly some intrinsic factors enhancing the meaning of the
bowel movement for the child appear to be the most important. The reader is
referred to pp. 656-657 for a discussion of such factors in child development.
Giant megacolon or megasigmoid may occur in chronically

institutionalized psychotic, mentally deficient, or brain-damaged patients. It is
thought to reflect a neglect to respond to defecation stimuli, leading to the
accumulation of enormous fecal masses. Major complications include sigmoid
volvulus, secondary toxemia, and perforation of a stercoraceous ulcer.
Subtotal colectomy may be necessary.
Feeding and Bowel Disorders with Psychosis
Reference already has been made to the role of psychotic ideation in the
genesis of some of these disorders. It suffices to add here only that such occur
most commonly in the syndromes of paranoid schizophrenia and endogenous
depression where delusions of internal persecutors are not uncommon. The
paranoid may complain of bowel symptoms, including bizarre rectal

sensations, while the depressed person typically suffers with anorexia and
constipation which at times may be considerable.
Psychophysiological Disorders
Psychophysiological gastrointestinal disorders include concomitants of
affect, local defense reactions, or the expressions of drive patterns.
Interactions between such physiological processes and other preexisting or
concurrent somatic processes may result in organic pathology.
Physiological Concomitants of Affects
It has been known for centuries that intense or prolonged unpleasant

emotions may be accompanied by gastrointestinal symptoms associated with
changes in gastrointestinal function. Changes in secretory patterns, blood
flow, and motility have been demonstrated in the esophagus, stomach, small
bowel, and colon during spontaneous as well as evoked emotions, but so far
there is little information as to how to relate such physiological changes to the
symptoms experienced during affect experience. Hence, at the present time
little is known about the clinical significance of such physiological changes, at

least as they involve otherwise normal gut. The story may be different in the
presence of preexisting defect or abnormality, as will be discussed below.
Be that as it may, it is important from the practical clinical point of view

to appreciate that the patient who presents with such gastrointestinal
complaints as change in appetite, nausea, vomiting, cramps, diarrhea, or
constipation may be undergoing psychological stress, and be experiencing
anxiety, shame, guilt, depression, or anger. When consulting a physician, some
patients place the major emphasis on their physical symptoms rather than on
their emotional state. At times this is a way of avoiding having to face the
underlying psychological issues, while at other times it reflects the patient’s
expectation that the physician will be more attentive to somatic than to

psychological complaints. By conducting a more thorough interview, the
physician will usually be able to establish that the patient is experiencing a
significant psychological stress, such as a frustrating life situation, a recent or
impending loss, or an interpersonal conflict, and that he is also exhibiting

other psychological or physiological expressions of affect. Thus, the patient
experiencing realistic or neurotic anxiety is likely, at the same time, to reveal
some of the usual circulatory and respiratory concomitants of anxiety, such as

palpitation, tachycardia, cold moist hands, sighing respiration, etc., as well as
to be beset with anxious or phobic concerns of one sort or another. The
depressed patient may appear lethargic, inactive, burdened, slowed down,
and may acknowledge feeling blue, discouraged, pessimistic, helpless, or

hopeless.
In general, it is not difficult to identify the patient whose

gastrointestinal symptoms are reflections of the physiological concomitants
of an affective response to psychological stress. However, it cannot be

emphasized too strongly that a direct cause-and-effect relationship is not
necessarily justified when gastrointestinal symptoms follow a psychological
stress, for it is also entirely possible for an organic gastrointestinal disorder
to develop under quite the same circumstances. For this reason, the most
meticulous care must be taken in the study and examination of the patient
whose gastrointestinal symptoms appear during or after a period of obvious

psychological stress, so as not to overlook these occasions when a somatic
lesion develops as well. Awareness of this possibility is generally sufficient to
alert the physician to be comprehensive in his inquiry. One should be

especially wary of patients who are insistent on ascribing their symptoms to
psychological stress, for just as some patients emphasize somatic processes in
order to avoid facing their psychological problems, so, too, may patients
fearful of organic disease, especially cancer, set up the smoke screen of
alleged psychological causes to hide from themselves and their physician the
organic state they fear more.
Another potential source of error in the differential diagnosis of
gastrointestinal disturbances accompanying affects and psychological

distress concerns the patient who is experiencing an affective response to an
occult organic process. A notorious offender in this regard is carcinoma of the
body or tail of the pancreas, though other types of intraabdominal neoplasm
may also be responsible. Prominent complaints among patients with such

occult disorders are irritability, anxiety, depression, or hypochondriacal
concern, as well as the gastrointestinal complaints commonly associated with
such affective states. The high frequency with which abdominal or back pain
eventually occurs in pancreatic cancer is the most important clue to the
correct diagnosis. In all likelihood, the important factors in the prominence of
psychological symptoms in pancreatic carcinoma and other occult disorders

are the vagueness and intractability of the symptoms, and the difficulty in
reaching a definitive diagnosis. Diagnostic or therapeutic uncertainty on the
part of the physician is another potent source of psychological stress to such

patients.
Local Defense Reactions
In addition to the more or less nonspecific physiological patterns of

affects already referred to, there are also local defense patterns involving the
surfaces and the portals of entry into the body, such as upper gastrointestinal
tract, respiratory passages, lower bowel, lower urinary tract, skin, and
conjunctivae. All of these local reactions constitute well-defined riddance

patterns designed to cope with noxious agents, be they irritating chemical
substances, poisons, foreign bodies, or microorganisms. However, identical
responses may also be provoked by a learned stimulus that indicates the
threat of such a noxious agent, as well as by a stimulus that is symbolic of a

past danger. It has now been suggested experimentally that specific visceral
and glandular responses can be learned. Such local responses to learned or
symbolic stimuli include surface changes, to dilute, wash away, neutralize, or
digest the noxious material, and motor activity to keep out or expel the
noxious agent. Surface charges include edema, vascular engorgement, and
hypersecretion and may involve the skin, the conjunctivae, and the mucous
membranes of nasal and upper respiratory passage, bronchi, esophagus,
stomach, and colon. Motor activity includes spasm, hyperperistalsis or
reverse peristalsis of the smooth muscles of esophagus, stomach, bronchial

tree, sigmoid, and rectum. Accordingly, individuals may respond to certain
symbolic stimuli with such manifestations as engorgement and congestion of
the nasal passages, nausea and vomiting, esophageal spasm, pylorospasm,
diarrhea, etc. Presumably the stimulus is symbolically experienced as
justifying such local defense reactions, either because it is capable of being so
represented mentally or because it was in some way in the past associated

with a situation in which such reactions had been activated by a noxious
agent. For example, nausea and vomiting may ensue upon eating
contaminated fish, on the sight or odor of fish, at the thought of eating fish in
the same setting where the fish was first eaten, or upon the anniversary of the
original experience. Such gastrointestinal reactions may occur in response to
foods that fall under cultural, religious, or family taboos, unfamiliar foods,
foods from filthy sources, foods with disagreeable sensory properties, and
foods simply with unpleasurable associations.
The psychological mechanisms involved in such reactions are closely
related to the conversion reactions involving the same systems and in some
instances the two cannot be distinguished. The example of nausea and
vomiting just cited does not, strictly speaking, constitute a conversion
reaction as we have defined it. But were fish, be it the animal, the word, or the
idea, to be equated symbolically with an unconscious conflict (e.g., a conflict
over a wish to take the penis in the mouth), then the reaction pattern more
properly constitutes a conversion.
Displaced or Incomplete Drive Patterns
Some somatic reactions do not constitute expressions of defense but of

incomplete or substitute drive activities where the full expression of drive is
blocked by conflict or by external restraints. Thus, increased secretory and
motor activity of the stomach or of the bowel may reflect oral or anal drive
activity which for some reason cannot adequately be expressed in
psychological or behavioral terms. It is uncertain how often such processes
are productive of symptoms in a person with a normal gastrointestinal tract.

Presumably, prolonged tension of such origin could contribute to hyperemia,
hypersecretion, or hypermotility with consequent symptoms of dyspepsia,
heart burn, gas cramps, constipation, or diarrhea. It is also conceivable, but as
yet unproven, that such psychophysiological influences may play a role,
directly or indirectly, in the variations in symptomatology of such conditions
as esophagitis, hiatus hernia, diverticulosis, and even tumors. For example, in
the presence of a hiatus hernia, hypersecretion of gastric acid so induced may
contribute to the symptoms of peptic esophagitis; with a bowel tumor,

increased motor activity may give rise to the first symptoms of the developing
bowel obstruction.
Some disturbances are due to the inhibition of a drive action after the
physiological process has been initiated. This is exemplified in the
gastrointestinal tract by “air swallowing” or aerophagia (with bloating and

eructation). The syndrome may occur in some individuals when a strong need
to discharge feelings by speaking has to be suppressed. Normally during
speaking a small amount of air is taken into the esophagus at the beginning of
inspiration and this is used for phonation during the balance of inspiration. If
some of the motor actions of speaking are carried out at the same time that
actual phonation is inhibited, then the air may be swallowed instead of

expelled. Clinically one notes audible swallowing of air and frequent belching
during periods when the patient remains silent while struggling to keep from
exploding with a verbal torrent. Once encouraged to vocalize what is being
held back, the episode may quickly subside.
Complications of Affect Concomitants
Reference has already been made to some of the complications which
may develop when psychophysiological reactions involve gut which already is
the site of structural abnormalities. For completeness, mention must also be
made of the role of psychological stress responses acting in a nonspecific way
to alter resistance of the body to physical stressors or latent intrinsic
metabolic or cellular defects. Empirically, it has been noted that a wide
variety of organic disorders become manifest in settings in which individuals

psychologically “give up” upon encountering some life situation with which
they are unable to cope. The corresponding affect states are best described as
“helplessness” and “hopelessness.” Infections, neoplasia, metabolic disorders,
and degenerative changes all have been noted to emerge under such
circumstances. It is hypothesized that some biological changes occurring
during the psychobiological state of “giving up” may, in as yet unidentified
ways, constitute conditions permissive or precipitating for the onset of the

somatic disease, so long as the necessary predisposing organic factors already
exist. On the other hand, in the absence of such somatic determinants, no
somatic disorder develops, though the psychological state is nonetheless

manifest in terms of affects and behavior, often experienced by the patient as
depressive. Sometimes more discrete psychopathological states develop
instead of somatic disorder.
Such relationships, while as yet unexplained, underscore again the
practical necessity to deal with somatic and psychological phenomena in a
unified fashion. All persons experiencing psychological decompensation in
response to stress must be considered also as potentially having organic
disease, rather than solely as being candidates for psychophysiological

disorder. Accordingly, somatic symptoms occurring under such
circumstances must be carefully evaluated. Gastric or bowel cancer, benign
gastric ulcer, intestinal tuberculosis, active amoebic colitis in a chronic

carrier, acute pancreatitis and even appendicitis have been reported under
such circumstances.
Somatopsychic-Psychosomatic Disorders
In this grouping belong certain conditions which in the past have been
designated as “psychosomatic diseases,” as well as some not heretofore so
considered. This sequence of terms is intended to convey two basic notions as
to the etiopathogenesis of these disorders. The first is that the primary factor
in the genesis of the disorder is a somatic process which not only is
responsible for the nature of the final organic state, e.g., duodenal ulcer, but
also is capable of contributing directly or indirectly to the development of

specific psychological characteristics. Some of the ways in which
gastrointestinal processes may influence psychic development have already
been discussed. The second is that these psychological features define, in a
more or less specific way, the circumstances which prove psychologically
stressful for the individual, and hence the psychodynamic conditions under
which the organic process may become activated. The sequence of the term
“somatopsychic-psychosomatic,” thus has developmental and chronological

implications. It specifies the primacy and the necessity of the somatic factor in
the genesis of the ultimate lesion as well as its influence on psychic
development. At the same time it specifies the influence of psychic factors on

the ultimate emergence of the somatic lesion. To fulfill these requirements,
the somatic factor must be present and exerting an influence from very early
in life, placing it in the category of a genic, congenital, or early acquired defect.
This formulation gives due emphasis to the evidence that a somatic
factor (the constitutional factor of Franz Alexander) is necessary before a

particular psychodynamic complex can give rise to a particular disease. But it
goes further than the classical psychosomatic concept in that it proposes that
the demonstrated psychological similarities of patients with each of these

disorders reflects in addition a contribution of the somatic factor to
psychological development as well. It is in these regards that these disorders
differ from those designated more simply as psychogenic and
psychophysiological. The following clinical features characterize the

disorders which are classified as somatopsychic-psychosomatic:
The disease may make its first appearance at any age, from earliest
infancy to old age. Its occurrence in the neonatal period, though rare, may be
regarded as evidence for the overriding importance of the somatic factor in
these cases. Ordinarily, the peak incidence of first attacks is during
adolescence and early adulthood.
Once initiated, the disorder is characteristically chronic or recurring.
Though some remissions may be complete, with no evidence of residual

structural change, the capacity for relapse is ever present, provided the
appropriate pathogenic conditions recur.
Psychological stress is an important contributing factor for the
development of the manifest disorder. Furthermore, careful clinical
psychological study reveals for each illness an impressive consistency, not
only in respect to the psychological characteristics of the patients so afflicted
but also in the particular psychodynamic settings that are stressful in
provoking, as well as helpful in relieving, attacks.
The following gastrointestinal disorders are here classified as

somatopsychic-psychosomatic, though the data justifying such a
categorization are more complete for the first three than the others: duodenal
ulcer, ulcerative colitis, celiac-sprue syndrome, regional enteritis and colitis
(Crohn’s disease), irritable bowel syndrome (spastic colon, mucous colitis),
and achalasia.
Duodenal Ulcer3
The work and ideas of Mirsky elucidating the pathogenesis of duodenal
ulcer provides the paradigm for the somatopsychic-psychosomatic concept.
Pathogenesis
Most patients with duodenal ulcer characteristically have large and
chronically hyper-secreting stomachs. Some active ulcer patients show a low
secretory capacity, ascribed by some to accompanying gastritis. But while
duodenal ulcer will not develop in the absence of acid and pepsin,
hypersecretion alone is not sufficient for ulcer formation. Thus, while
duodenal ulcer patients are relatively high acid and pepsin secretors, not all
hypersecretors have ulcers. Yet, as Mirsky has shown, those persons with
consistently higher gastric secretory capacities, as evidenced by plasma
pepsinogen values above the median for the total population, constitute the
subgroup from which the bulk of actual and potential duodenal ulcer patients
are drawn. In addition, the same distribution of plasma pepsinogen levels
holds for children as for adults, suggesting that the tendency toward higher
secretory patterns is established early and presumably maintained into adult
life.
These findings identify at least one of the somatic factors in the genesis
of duodenal ulcer. Whether the large stomach with its big parietal cell mass
and its generally increased secretory potential is a genetically determined
anatomical characteristic, or whether the stomach hypertrophies in response
to some primary central nervous system influences operating from birth,
cannot be answered. There is a significantly higher concordance of ulcer

disease among monozygotic than dizygotic twins and a highly significant
excess of ulcers among close relatives. Relatives without ulcer show a highly
significant increase in hydrochloric acid response to maximal histamine

stimulation when compared with controls. Individuals who are blood group O
and nonsecretors of blood group antigens are much more liable to duodenal
ulcer. While such findings indicate a genetic factor, Pearl et al. have produced
a marked and sustained increase in the parietal cell mass in cats by

continuing anterior hypothalamic stimulation for four to six weeks. This
suggests that increased functional demand, for whatever reason, may also
contribute to the development of a hypersecretory capacity. Whichever

factors may be operating it is known that infants differ in their patterns of
feeding activity, but whether those with the more active gastric secretory
potential are also the ones with a more vigorous drive to nurse has not yet
been studied. Be that as it may, such a possibility provides the basis for an
attractive hypothesis relating ulcer predisposition with incompatibilities
between mother and infant in the early nursing relationship. As has already
been discussed, the repetitive sequences of hunger crying → feeding by
mother → satiation → sleep reflect one parameter of a rising and falling
psychic tension, regulation of which is achieved in relationship with another
human being, the nursing adult. The drive aspect of this has been designated
as oral, since the tension can be relieved only by oral activities, namely
nursing and related processes. The hypothesis suggests that the infant with
the more active gastric secretory pattern behaves more of the time like a
hungry infant than does the normo-or hyposecreting infant. Furthermore, it

proposes not only that infants differ in the vigor of this oral drive but also that
mothers differ in their ability and capacity to satisfy the oral drive. Thus, one
may postulate a range of possible mother-infant relationships as shown in
Table 27-1.
Table 27-1. Relationship of Infant’s Oral Drive to Mother’s Ability to Gratify It

INFANT’S ORAL DRIVE MOTHER’S ABILITY TO INFANT’S ORAL SATISFACTION
GRATIFY ORAL NEEDS
1. High High May be achieved

Medium High Will be achieved
Low
High Will be achieved
2. High Medium Will not be achieved
3.Medium Medium May be achieved

Low Medium Will be achieved
4. High Low Will not be achieved

Medium Low Will not be achieved
5.Low Low May be achieved
According to this schema, when the mother’s ability to gratify oral needs
matches or exceeds that of the infant, then the infant will have a good chance
of satisfaction and hence a better opportunity to gain confidence that oral
tensions will not become intolerable or remain unrelieved. On the other hand,
when the ability of the mother to satisfy the oral drive is relatively lower than
the need of the infant, the latter repetitively or chronically will be exposed to
periods of oral tension and will have difficulty gaining confidence that the
environment can be depended upon to fulfill these needs. Furthermore, this

schema allows for the possibility that even a mother with an excellent
integrative capacity and without any basic hostile or rejecting attitudes
toward her infant may not succeed in satisfying the physiological and
psychological needs of an excessively orally demanding hypersecreting infant.
Such failure on the part of the mother may also prove to be frustrating to her
and hence may provoke in her a hostile or rejecting attitude toward her
infant. Thus, relative incompatibilities between infant needs and maternal
capacities may serve to intensify and entrench in the developing child strong
oral-dependent wishes, expressed ultimately as a lack of confidence in the
ability or willingness of the environment to provide and in a corresponding
need in one way or another to compensate for this. Such tensions, projected
over the entire developmental span of the child, may be expected to exert a
significant influence on the ultimate psychic structure of the adult.
This hypothesis corresponds closely to what has long been known

psychologically about the ulcer and ulcer-prone patient. So-called oral
character traits and conflicts around the dependent-independent axis, though
expressed in many different ways, are prominent characteristics of duodenal
ulcer patients. But not all persons with such psychological characteristics
develop ulcer or are ulcer prone. Whether or not a duodenal ulcer develops
later in life is dependent upon still another factor, namely, the secretory
capacity of the stomach, the greatest potential for ulcer formation being
among those who are hyper-secretors and were orally frustrated in infancy.
In this way we can understand how some hypersecretors, by virtue of
adequate nurturing, may develop neither noticeable psychological distortions

nor duodenal ulcer; how hypersecretors and some normosecretors with
adequate mothering may be highly ulcer prone; and how other
normosecretors with inadequate mothering may develop psychological traits

indistinguishable from those found among ulcer patients, yet never develop
ulcer. It is not the gastric hypersecretion alone which is the decisive

determinant in the psychological development but the success or failure of
the transaction between mother and child around this need-frustration cycle.
If the infant with hypersecreting stomach is adequately satisfied, his
psychological development will be less influenced by the kinds of distortions
which result when such oral needs are chronically or recurrently unsatisfied.
Hence he will be less ready in later life to experience situations as threatening
his inner sense of security or his confidence in the environment as a source of
support. On the other hand, hypersecreting infants less adequately handled

may suffer on both scores and hence be more vulnerable to ulcer formation.
This would explain not only the occurrence of hypersecretors (as determined
by plasma pepsinogen) without ulcer, but also the occurrence of ulcer among
those with pepsinogen levels more near the median.
While the secretory capacity of the stomach and the psychological

status together determine the individual’s vulnerability to duodenal ulcer
formation, these do not determine whether or when an ulcer will develop.
This is dependent on current psychosocial factors and the degree to which

they are psychologically stressful for the particular individual. Thus it is
possible for one individual with relatively high ulcer vulnerability to go
through life without ever developing an ulcer, while another, who may even
have a lesser vulnerability, may experience repeated bouts of ulcer activity.
The psychosocial situations specifically stressful for each individual make up
the precipitating circumstances determining the point in time at which an
ulcer ultimately forms in the ulcer-prone person.
Strong support for this formulation comes from a study in which it was
possible to distinguish, by purely psychological means, the hypersecretors
from the hyposecretors and to predict among whom peptic ulcer developed in
a stressful situation. From a group of over 2000 army inductees, sixty-three
were selected with high serum-pepsinogen values and fifty-seven with low
pepsinogen levels. Not only could these two populations be distinguished by

psychological criteria (without prior knowledge of the pepsinogen values),
but also the three soldiers who subsequently were found to have evidence of
healed ulcer, and the six who developed active ulcer during the induction
period, all fell in the upper 15 percent, eight in the upper 5 percent of
pepsinogen values.4 Of relevance to these findings are the experiments of

Ader on gastric erosions in the acid-secreting portion of the stomach
provoked by subjecting rats to physical restraint for six hours. These studies
demonstrated that, while animals with high plasma pepsinogen were more
likely to develop erosions than were those with low levels, high pepsinogen
was neither necessary nor sufficient. Taking advantage of the known twenty-
four-hour activity cycle of rats, it was hypothesized that restraint instituted

during a period of activity would be more “stressful” than during a period of
quiescence. When rats were restrained under these two conditions it was
found that all the rats who developed erosions had high pepsinogen levels
and had been restrained during a period of activity.
Psychological Characteristics of the Gastric Hypersecretor and Duodenal-Ulcer

Population
The classical psychodynamic formulation of the peptic ulcer patient was
developed by Alexander and has been confirmed and elaborated by others.
Mirsky has shown that comparable psychological features characterized
about 85 percent of the hypersecretor group whether or not they had had
active ulcer to the time he examined them. As has already been stated, similar
features may be expected as well among some individuals who are neither
hypersecretors nor have ulcers. Among identical twins discordant for ulcer,
the twin with the peptic ulcer displays these psychological features more
prominently than the twin without ulcer.
The basic psychodynamic trends in the hypersecretor-duodenal ulcer
group cluster around strong needs to be taken care of, to lean on others, to be
fed, to be nurtured, to have close body contact of a succoring type. Many
developmental factors serve to determine how such a central organizing
psychodynamic tendency is eventually expressed. By way of emphasis,

several caricatures of hyper-secretor ulcer-prone patients may be drawn to
indicate how these underlying dependent wishes may be organized.
The Pseudoindependent. His underlying dependent needs may be

largely or completely denied and an opposite facade presented. These
patients then appear as highly independent, self-reliant, aggressive,
controlling, and overactive. Men present a caricatured “hypermasculine”

facade, while the women show strong “masculine”5 identifications. Such
persons ridicule the necessity for rest, relaxation, or vacations, and are
contemptuous of those they consider weak and dependent. In Western
society these characteristics are peculiarly in keeping with success in the
business and professional world. The interpersonal relationships of these

patients are controlling rather than warm. By dominating or controlling
behavior they force others to provide their wants and in this way succeed in
keeping unconscious the gratification of their dependent needs. The spouse,
for example, is likely to be the long-suffering, self-denying provider, while the

patient sees himself as powerful and self-sufficient. The following case
illustrates this situation. They are vulnerable to ulcer disease early in life and
vascular disease later on.
Mr. D., a forty-eight-year-old consulting engineer, had ulcer symptoms

on and off since age twenty.6 The twelfth of fourteen children born of
immigrant parents, he was a completely self-made man. With a harsh,
exacting father and an overburdened mother, his childhood was marked by

premature assumption of work responsibilities and denial of the usual
childhood gratifications. He early strove for and achieved a status of such
social and occupational independence that he could claim he was beholden to

no one. His greatest success was as a consultant who “cured sick industries,” a
situation in which he could feel that the entire organization depended upon
him. Indeed, he only accepted such consulting positions under the condition
that he take orders from no one. Aggressive, dominating, constantly on the go,
involved in many ventures at a time, he never rested or took vacations.
Indeed, when a well-intentioned physician advised that he buy a farm as a
means of relaxation, he converted it into a successful business venture.
Supporting this facade of ruthless independence were a coterie of

assistants, secretaries, and sycophants who were kept on the go doing his
bidding, and a wife to whom he cynically assigned the task of catering to his
needs at home and toward whom he felt no affection. He divorced his first
wife and left his children when she became too preoccupied with their care,
marrying a second woman who would devote herself to gratifying his needs.
The intense drive to be cared for and supported, a need of which he was
completely oblivious, was revealed not only by the efficient machinery he set
up to assure this, as described above, but also by numerous side remarks and
slips of the tongue. He repeatedly spoke of what a good cook his mother was
and made invidious comparisons with his two wives. Of one he said, “She just
puts on a God-damn salad with a couple of leaves.” He derived much pleasure
from feeding and caring for the farm animals, saying, “I treated them better
than myself,” but quickly philosophized that “there is danger in taking care of
someone so well that they never take care of themselves.”
Ulcer symptoms first developed soon after being drafted into the Army
in World War I when he could not control his environment. Subsequently,
symptoms occurred when his wife or his staff failed him, when threatened by
reverses beyond his control, and between jobs. As he grew older, he subtly
shifted toward a more obviously dependent relationship with an older
business executive in whose organization he, for the first time, took a
permanent position. His most severe ulcer symptoms occurred after this man
died and was succeeded by his son, who deprecated our patient.
The Passive-Dependent. The underlying dependent needs are overtly
expressed and to a considerable degree are conscious as well. These persons,
some of whom may be fairly successful, are outwardly compliant, passive,

ingratiating, eager to perform for others; yet they are also clinging,
dependent, and may even be demanding in a passive-aggressive way. They
tend to get into social and interpersonal relationships in which they can
depend on a nurturing figure or a paternal, supportive social organization.
The men may show strong feminine identifications.7
The patient was a fifty-two-year-old black laborer born and raised on a
farm in the South, the middle child of thirteen children. He was much attached
to his mother, but felt discriminated against by his father and brothers. He
was the hardest working and most conscientious of all the children. At
twenty-one years of age he married a motherly, dependable type of girl. Mild,
transient epigastric distress first developed when the patient became worried
over his wife’s frequent pregnancies. Because of lack of economic opportunity
in the South, the patient moved his family to Cincinnati and obtained work in
a railroad roundhouse, where he remained twenty years. His bosses gradually
entrusted him with more responsibilities without commensurate salary

increase. Fellow workers soon came to know that he would finish the work
that they had left undone. This caused the patient to feel resentful toward
them, but he was not able to summon up enough aggressiveness to object. By
hard work and careful saving he and his wife built their own home and
successfully raised a family of five children. When this house burned to the
ground, his wife was badly injured, and two grandchildren were burned to
death. He struggled to reaccumulate his fortune, but was discouraged by

increased responsibilities at his job without a raise and by the failure of his
wife to recover from her injuries. During this period, symptoms of a duodenal
ulcer started. Epigastric pain was experienced at work when he felt imposed
upon by his boss or fellow workers, and it was accentuated at home when his
wife was forced to take to bed. A rather meek, effeminate individual, he
became quite dependent on the therapist and was never able to express any
aggression toward his doctors, illustrated by the fact that he was unable to
interrupt his visits to his former doctor, “because I don’t want to hurt his
feelings.”
The Acting Out. In this group the dependent needs are taken care of by
blatant acting out and/or by insistent demanding. These are, psychologically
speaking, the most immature patients; their character is marked by the
infantile trait of “I want what I want when I want it,” even if this involves
asocial, antisocial, or criminal behavior that disregards the needs and rights
of others and of society. Irresponsible, with little investment in achievement,
they may drift from job to job and are often unemployed. Addiction to
tobacco, alcohol, and drugs is common. In their relationships they are

parasitic and without consideration of others.
The patient was a thirty-eight-year-old man whose childhood was

unhappy and deprived. Before he was three years old his parents separated
and he was placed in an orphanage. Later, he never got a permanent job or
settled down, but drifted around the country working spasmodically as a

peddler or dishwasher. His first marriage was unhappy. Ulcer symptoms and
chronic alcoholism developed in conjunction with economic difficulties and
incompatibility with his wife. He married a second time to a motherly type of

wife, but his ulcer was reactivated and later perforated while she was
pregnant. Following an operation it was quiescent for a short period during
which he obtained a temporary job as a cook. When his employer, in
desperation over the manpower shortage, made the patient night manager of
the restaurant the ulcer began to bleed.
These caricatures serve to highlight the extremes of the types that are
most vulnerable psychologically and hence most likely to develop active ulcer.
While all share the same underlying psychodynamic tendencies, among many
these are much more subtly manifest or defended against. Indeed, some
hypersecretors even have evolved such effective and socially acceptable

psychological and social devices to assure satisfaction of needs, and are so
well buffered against stress, that they may never develop an ulcer or do so
only during some extreme stress, as the death of the beloved spouse or the
threatened loss of a business. On the other hand, there are extreme

hypersecretors who, though psychologically fairly well adjusted, have such a
low threshold for ulcer formation that ulcer symptoms occur in response to
relatively minor variations in their life situations.
The Nature of the Pathogenic Psychological Stress
Effective frustration of dependent needs is the common denominator of
the psychological stresses leading to activation of duodenal ulcer. This may
include any of the vicissitudes of life which result in brief or prolonged

periods of deprivation. It may be a feeling revived by virtue of passing
through the anniversary of a previous frustration. It may also be brought on
by some symbolic stimulus and the development of an intrapsychic conflict

evocative of such frustration. In brief, the precipitating events are
characterized by their capacity to mobilize fears of loss of love or security

through intensification or frustration of persistent infantile, passive
dependent wishes, usually with feelings of helplessness and anger.
Awareness of the psychological and social devices characteristically

utilized by these patients to assure gratification of dependency needs is useful
to the physician in anticipating what will be stressful for any particular
hypersecretor ulcer-prone patient. Thus, as illustrated in the preceding
examples, the pseudoindependent person is likely to have ulcer activity when

his own efforts no longer succeed in forcing others to provide, or when
external circumstances beyond his control become frustrating. The passive-
dependent person may develop ulcer symptoms when the person or
organization upon whom or which he is dependent refuses or fails to satisfy
his needs. The acting-out or demanding person will get symptoms when he is
forcibly restrained from acting out, as when jailed, or when supplies of his
needs simply are not forthcoming. Groen suggests that the rising incidence of
peptic ulcer among men in the twentieth century may be related to the fact
that the specific conflict situation is linked with the social structure of
twentieth-century Western society. Only in this culture is work so important
as a way to obtain recognition and increase self-esteem, while the

emancipation of women renders them less available to some men for
gratification of dependent needs.
In most cases the sequence of events in response to such a psychological

stress is for the patient: (1) to intensify the psychological and social devices
that he characteristically utilizes to assure gratification of needs; (2) when
these fail, to experience increasing anger, which, however, usually must be
suppressed or denied if it threatens the sources of supply still further; (3)
then, to turn on to the self or internalize the aggressive impulse, with the
development of corresponding feelings of guilt; and finally (4) when he no
longer feels able to cope, to give up, with feelings of helplessness in some,
hopelessness in others. Once symptoms begin, this sequence may be
terminated or reversed by the altered expectation from the self and the
changed behavior of the environment toward the patient. The exact point in
this sequence when ulcer activity begins has not yet been clearly delineated.
Relation Between Psychological Stress and Ulcer Activation
Little is known concerning this relation. While there is considerable
support for the thesis of Alexander that both increased dependent needs and
aggression are accompanied by increased gastric secretions (as if the need for
support is to be satisfied symbolically by preparation for eating and the

aggression acted out by a symbolic cannibalism of the loved and hated
object), as yet there has been no definite demonstration that actual ulcer
formation is indeed preceded by a significant increase in gastric secretion. In

general, basal acid secretion is alleged to be the same during periods of ulcer
activity as during quiescence, though in some subjects healing following a

severe, protracted episode may be accompanied by a fall in the high
hydrochloric acid output." Basal hydrochloric acid secretion is said to be
more variable among duodenal ulcer patients than nonulcer patients, but
whether gastric secretion of ulcer patients is more responsive to stress is a
matter of disagreement. Clearly, the Alexander thesis requires that the

specific psychodynamic situation be associated with increased gastric
secretion and that both regularly precede ulcer activation. No appropriate
test of this assumption has yet been accomplished.
Garma has introduced another psychological construct which may have
relevant pathophysiological implications. He invokes a primitive, infantile
fantasy, namely that in the face of oral frustration the archaic concept of the
frustrating provider (mother) is revived as a bad object inside, to be extruded
or destroyed. This view evolves purely from psychoanalytic data, but it does
suggest the possibility of an underlying physiological process, namely,
forceful gastric contractions periodically subjecting the duodenum to jets of
highly acid gastric juice which cannot be neutralized by available enteric

juice. Wolf reports such forceful gastric contractions up to the point of tetany,
along with increased secretion in an ulcer patient during a stress interview

Smith et al. showed a marked increase in gastric and duodenal motor activity
occurred upon administration of an acid-barium meal among ulcer patients,

but not among normal subjects. Rhodes demonstrated that the duodenal
mucosa of patients with high levels of gastric secretion is exposed to much
longer and more profound fluctuations in acidity than is that of normals,
further indicating that alternation between spasm and rapid emptying may be
a significant variable.
Some alteration in the mucous barrier or in other determinants of tissue
resistance or of vascularity as nonspecific biological concomitants of the

affects of giving up cannot be excluded. The roles of newly identified
hormones, such as vasoactive intestinal hormone, gastric inhibitory hormone,
motilitin, and others in the pathogenesis of ulcer is a new chapter yet to be
considered by psychosomatic investigators.
Implications for Treatment
From the discussion just presented, it should be evident that any

activity on the part of the physician (or others) which assures gratification of
the patient’s dependent needs without, at the same time, undermining his
pride and self-respect, such as it is, should have a salutary effect in reversing
the conditions which led to ulcer activation. Clearly this requires an

understanding by the physician of the psychological and social resources
peculiar to each patient. He must know, for example, to what extent and
under what circumstances the pseudoindependent patient will permit himself
to be controlled by the physician. The clinician must know who in the family
or among friends is acceptable to and capable of supporting the patient. He
must recognize that for the pseudoindependent patient, respite may not be
achieved by rest or inactivity but by permission to engage in some other
activity, to escape temporarily. He must know that the passive-dependent
patient may need a much longer period of babying and indulgence, but also
that a few of these patients are insatiable in their needs to be taken care of. He
must recognize that the excessively passive-dependent patient may respond
to surgery by prolonged invalidism even though the ulcer heals, while the
guilt-ridden patient may have intractable pain long after the ulcer is healed.
Attention to such details will greatly widen the range of effectiveness of drugs
and diet beyond that achieved by neutralization of gastric acid.
The somatopsychic-psychosomatic concept also should make it evident
that no form of psychotherapy can be expected to eliminate the underlying
somatic determinants, that is, the life-long chronic hypersecretion and the as
yet unidentified factors determining the vulnerability of the duodenal
mucosa. On the other hand, psychotherapy, including psychoanalysis, may be
expected to improve in some individuals significantly the capability of the
individual to manage his life, to deal with unconscious conflicts, and to gratify
needs in personally and socially acceptable ways. None of these, however, can
be expected to protect him from the vicissitudes of life and hence it is possible
that even the best adjusted hyper-secretor may under sufficient provocation
develop a duodenal ulcer.
Nonspecific Inflammatory Bowel Disease
Ulcerative Colitis
As a chronic or remitting disorder involving primarily the mucosa and
submucosa of the large bowel—and occasionally of the small bowel as well—
ulcerative colitis fulfills all the criteria of a somatopsychic-psychosomatic

disorder as outlined above. Clinically, there is evidence that the capacity to
develop the disorder is present early in life, though as yet no biological index,
corresponding to the hypersecretory state so characteristic of the duodenal
ulcer-prone population, has been identified. A significant familial occurrence

supports the view of a genetic relationship, probably involving a polygenic
inheritance with the interaction of several genes. Dick et al. demonstrated
persistence of mucosal abnormality even during symptom free periods; it
would be interesting to know whether such changes antedate the onset of

symptoms. Burch suggests that extrinsic factors, including psychological
stress, disturb an endogenous defense mechanism directed against a
forbidden clone derived from a gene mutation, and thereby bring about
activation of the disease. Shorter et al. propose that the inflammatory reaction
results from the establishment early in life of a state of hypersensitivity to
antigens of bacteria normally present in the individual’s gastrointestinal tract
and that the pathological and clinical features of inflammatory bowel disease
then result from a predominantly cell-mediated hypersensitivity reaction to
the bowel wall. They discuss how various factors, including psychic insult,
may trigger the breakdown of defenses in such “immunologically primed”
patients to produce the overt disease. Engel had suggested earlier from
clinical, psychological, and pathological data that the disease may result from
“unidentified changes which alter relationships in the colon so that it
responds to its own flora as pathogens.” Spontaneous occurrence of
ulcerative colitislike lesions in gibbons in response to psychological stress has
recently been reported.
The manifest disease may develop at any age, including neonatally, and
once initiated may be marked by remissions and relapses, or by a chronic
unremitting course. When one carefully studies the setting in which
symptoms develop and remit, there is a clear-cut chronological relationship

between psychological stress and onset or exacerbation on the one hand, and
psychological support and remission on the other. Furthermore, there is a
consistency not only in the nature of the circumstances which are likely to be
psychologically stressful or helpful, but also in the psychological
characteristics of ulcerative colitis patients as a group. For the most part,

these characteristics antedate the development of the active disease, though
they may, in certain respects, also become exaggerated in the presence of the
symptomatic bowel disorder. To what extent the as yet unidentified biological
preconditions for the bowel disease contribute distinctively to the
psychological development of the patients can, at present, only be
conjectured.
Summary of Psychological Data. In 1955 we summarized the available
knowledge about the psychological features of ulcerative colitis patients
beginning with the first study by Murray in 1930.41 Since then numerous
clinical reports have largely confirmed those formulations; so too has
psychological testing using projective techniques. On the other hand, studies
comparing ulcerative colitis patients with “controls” (usually other
gastroenterology or general medical patients) using MMPI (Minnesota

Multiphase Personality Inventory), or various ratings of psychological
abnormality have failed to reveal differences; indeed, one group using such an
approach pronounced colitis patients to be “supernormal”! For the most part

such studies can be criticized on the basis of a naive conceptualization, that
ulcerative colitis is a “psychogenic disease” caused by psychic disturbances,
and therefore should demonstrate more rampant psychopathology than the

control patients. Furthermore, the psychological procedures used have not
been sufficiently specific to detect the personality features reported by
clinicians to characterize ulcerative colitis patients. These characteristics, as
described below, may differ in degree from patient to patient but still provide
a reliable overview of what to expect upon the psychological study of such
patients. Among the more important variables accounting for differences
between patients are the sex and age at which the colitis began.
Personality Structure. A high proportion of ulcerative colitis patients are

described as manifesting so-called obsessive-compulsive character traits,
including neatness, orderliness, punctuality, conscientiousness, indecision,
obstinacy, and conformity. A few are conspicuously messy and dirty. Along
with these are often noted a guarding of affectivity, overintellectualization,
rigid attitudes toward morality and standards of behavior, meticulousness of
speech, avoidance of “dirty” language, defective sense of humor, obsessive
worrying, and timidity. Some are petulant, querulous, demanding, and

provocative, but by and large well-directed aggressive action and clear-cut
expressions of anger are uncommon. Many investigators have been
impressed with the extreme sensitivity of these patients, their almost

uncanny perception of hostile or rejecting attitudes in others. They are easily
hurt, constantly alert to the attitudes and behavior of others toward them,
and they tend to brood and withdraw. Much activity is devoted to warding off
or avoiding rebuffs, manifest in some patients by placating attitudes,
submission, politeness, attempts to please and conform, in other patients by
attempts to deny or ignore by remaining proud, nonchalant, haughty, and
aloof.
Some patients give an outward appearance of energy, ambition, and

efficiency, but this often proves to cover feelings of inferiority, an acute sense
of obligation, a need to experience some sense of security. By and large they
avoid chances and do not deal daringly with their environment. Such people
are often admired for their virtue, morality, and high standards. They are
more likely to seek achievements in the intellectual sphere and to eschew

modes of life demanding vigorous physical activity. It must be emphasized
that such characteristics are entirely compatible with effective
accomplishment, and indeed some noted scientists, artists, writers and even a
few athletes have been numbered among ulcerative colitis victims. While
good statistical data are not available, it is a clinical impression that the
disorder is relatively less common in the lower socioeconomic bracket and in
the intellectually less well endowed.
Relationship with People. The patient with ulcerative colitis reveals a

rather consistent pattern of interpersonal relationship, a pattern which
originates in the relationship with the mother (see below). On the one hand,
he appears to have a quite “dependent” relationship with one or two key

persons, usually a parent or parent figure; on the other hand, he has a limited
capacity to establish warm, genuine friendships with others.
Close scrutiny reveals that the patient often lives through a key figure
who at the same time lives through him. Often this is the mother or a mother
substitute. The patient appears to use the key figure as though a part of his
equipment for dealing with the external world. He leans on the key figure for
guidance, advice, and direction; he is reluctant to take initiative or to plan
independent action, and he tends to act out the wishes, conscious and
unconscious, of the key figure. At the same time this is a highly ambivalent
relationship, one within which overt expressions of hostility are fraught with
great danger, for to be rejected may induce overwhelming feelings of
helplessness. This type of relating reflects a fixation at a symbiotic level of
object relationship and is a recurring feature in the majority of patients. The
quality of expectation from the key figure (mother) is magical, imperious, and
omnipotent. In most cases it is clear that it is not only the patient but the
maternal figure who needs the mutual symbiosis.
This pattern of relating may be carried over into the relationship with
the physician. Ordinarily, the patient either becomes very “dependent” upon
his physician or establishes no relationship or, at best, a very superficial one.
Further, the patients who do develop a “dependent” relationship in general
fare better than those who do not. Once established, it is difficult for the
patient to relinquish the relationship and remain in good health. A disruption
of the doctor-patient contact is not infrequently followed by some relapse of

symptoms.
Mothers: Psychological Characteristics and the Symbiotic Relationship.
The nature of the relationship with the mother is of decisive importance in

understanding the psychology of the ulcerative colitis patient. There is also an
impressive consistency in the description of the mothers of patients with
ulcerative colitis, although women patients describe their mothers differently
from the way men do. This consistency is confirmed by direct observation of
the mothers and by projective testing of the children. In general, the mothers
are described as controlling and dominating. Women patients are likely to see
their mothers as powerful and overwhelming figures, who make them feel
helpless and dependent. They often describe their mothers as cold,
unaffectionate, punitive, rigid, strict, and judgmental. The men, although

describing similar domination, are more likely to find this acceptable and to
portray their mothers as kind, considerate women who worry constantly
about their well-being.
Women more often portray themselves as in competition or combat

with the mother, while the men more readily capitulate and give in. Despite
these different attitudes of the men and women toward their mothers, one
readily finds many similarities among the mothers. In general they are either
unhappy, pleasureless, gloomy women with no great zest or enjoyment in life,
or hard-driving, businesslike, perfectionistic women who are active and

concerned with many outside interests but often dissatisfied with their own
or others’ accomplishments. They tend to be worrisome, complaining,

pessimistic, and often hypochondriacal. Expression of genuine warmth,
affection, and understanding comes with difficulty. A high proportion show
moderate to severe obsessive-compulsive traits; a smaller proportion show
pathologically disordered behavior or eccentric preoccupation with
collections of odds and ends. A few are psychotic characters or frankly
psychotic, usually paranoid. Many of these mothers are described as

depressive.
A prominent feature is the mother’s propensity to assume the role of a
martyr, often mobilizing thereby guilty reactions from the patient.
The persisting symbiotic nature of the patient’s relationship with the

mother is reflected in the patient’s exquisite sensitivity to the mother’s
feelings and behavior. The patient often behaves as if he cannot distinguish
his own feelings from his mother’s. Patients comment on their sensitivity to
mother’s sigh, disapproving look, or change in posture or facial expression, as
well as to verbal expressions of distress. Some patients, especially the men,
submit passively and obediently to the mother’s domination. Others, while
submitting, do so with the complaint that mother won’t permit them to do

otherwise or that they can’t stand mother being upset. In general, the patient
feels under great pressure from the mother to perform, whether it be in the
sense of general social achievement or in ways peculiarly designed to meet

the mother’s emotional needs or alleviate her guilt, shame, or anxiety. This
may lead the patient to manipulate others so that mother will be spared
distress. In other words, the patient “learns” the conditions under which he
will be spared rejection. Mother’s love is conditional on his fulfilling her
requirements. In the mutual symbiosis the patient may unconsciously act on
the underlying wishes or needs of the mother, even to the extent of remaining
ill.
Notable is the need of these mothers to be in control of their children
even after they are grown up. Many insist on taking care of their ill adult sons
or daughters even when spouses are willing and available.
Fathers. In general, the woman patient is inclined to portray her father

as a gentle, kind, passive, usually ineffective man to whom she is quite
attached, while the male patient is likely to describe his father either as
brutal, punitive, threatening, coarse, and very masculine, or occasionally as
passive and weak, and unable to stand up to the mother. The man may see his
father as threatening and abusive to the mother, in which case he becomes
excessively submissive to both parents. Not uncommonly the male patient
feels that his father compared him unfavorably to a more masculine brother
who more adequately fulfilled the father’s ideal. The woman, on the other
hand, often complains that the father did not adequately protect her from
mother’s aggression, that he let her down.
We have seen two men patients whose symbiotic object relationship
was with the father and not the mother. In both cases the son was attempting
to fulfill the ambition for physical accomplishment of a father who was
frustrated by crippling in adolescence. Superficially these two patients
presented as very active, even adventurous men. In both the disease began
when they disappointed the father by failing in an important competitive
sport event.
Family Dynamics. A study of families with children with ulcerative colitis

has characterized these families as “restricted.” They reveal a marked
inability to engage in or even recognize opportunities for behavior outside
the pattern of their own immediate lives. They are limited in the range of
interaction, careful in dealing with each other, and they handle a variety of
situations in a similar fashion. This was seen as a false solidarity or
pseudomutuality. More family studies are needed.
Sexual and Marital Adjustment. In general, these patients tend toward

inadequate sexual development. Interest and participation in sexual activity
tend to be relatively low. Most of the women are frigid, and even those who
experience orgasm do so infrequently. A few patients engage in little or no

heterosexual activity even when married. Many acknowledge a preference to
being fondled or cuddled, more like a child, and largely reject any genital
approach. They are prone to regard sexual activity in anal terms, using such
terms as “dirty,” “soiling,” “disgusting,” “unclean,” etc., and are squeamish
about body contact, secretions, and odors. Excessive bathing, use of
deodorants, concern about being malodorous or dirty may be present even in
the absence of bowel symptoms, and may be used as rationalization to avoid
sexual contact. In the marital relationship the spouse commonly fulfills the
role of the succoring, sustaining mother or takes a role subordinate to the

mother. Sometimes it is a mother-in-law, who closely resembles the mother,
who is the real object for the patient. Under such circumstances the spouse
often is related to more like a sibling than a marital partner.
The Nature of the Significant Psychological Stress. In establishing
exactly the time of onset of the disease, it is necessary to establish the first
clear deviations from usual bowel activity. Many patients are found to have
had rectal bleeding or abrupt severe constipation for days, weeks, or even
months before diarrhea begins. When the onset of disease is accurately

established, it is often found that the time interval between a psychologically
stressful circumstance and the onset of the first symptom of the colitis is a
matter of hours or a day or two. On the other hand, there are cases where the
onset is rather gradual and not easily timed. Here one deals not with a well-
defined stressful experience but rather with a gradually changing psychic

status during which symptoms gradually and sometimes intermittently
develop. The latter is typical of colitis developing during adolescence. In

general, psychologically stressful events are likely to fall into the following
categories: (1) real, fantasied, or threatened interruption of a key
relationship; (2) demands for performance which the patient feels incapable
of fulfilling, especially when support had already been withdrawn or when
disapproved activities are involved; and (3) overwhelming threat from or
disapproval by a parental figure. As a rule hostility and rage toward the

disappointing figure is repressed. Common to all these circumstances is an
acute or gradually developing feeling on the part of the patient that he has
become helpless to cope with what is happening. The disease becomes active
in the course of “giving up” psychologically, which is marked by the affect of
helplessness. Patients verbalize giving up in such terms as “too much,”
“despair,” “nothing left I could do,” “helpless,” “overwhelmed,” etc.
The following vignettes illustrate patterns of onset and typical
precipitating, psychological stress.
Case 1. Constipation and Bleeding. A thirty-one-year-old married woman
became pregnant a few months after the birth of her first baby. The first
pregnancy had been a deliberate and successful attempt to hold her husband,
who had become interested in another woman. To have two babies so close
together, however, seemed more than she could cope with. Shortly after she
missed her first period she became constipated and noted the passage of
bright red blood. For the next six months she continued to pass fresh blood,
with and without feces, one to three times a day. Stools remained formed and
somewhat constipated, often with fresh blood on the surface. True diarrhea
developed six months after the bleeding began, as the inevitability of the
second baby became undeniable and the implications overwhelming.
Case 2. Acute Constipation. A twenty-one-year-old married woman was
awaiting the return from overseas of her soldier husband, whose train
reached the city that day. After keeping her waiting four to five hours while
he visited his mother, he appeared at the door, and without further

elaboration announced that he wished a divorce. On this note he left. The
same day she was seized with terrific cramplike pain in the left lower
quadrant of the abdomen and an urge to defecate, but she was unable to do
so. She was admitted to a hospital where she was given eight enemas in two
days before any relief was achieved. Following this she had formed stools,
three to four times a day, for a month, when small amounts of blood were first
noted. Thereafter she passed blood and mucus four to five times a day, stools
became semiformed, then grossly diarrheal and bloody.
Case 3. Bloody Diarrhea. A twenty-nine-year-old woman married when

she discovered she was two months pregnant. She hoped to hide the
premarital conception from her puritanical mother by saying the baby was
born prematurely. Gestation actually was seven months, so the baby was born
five months after the marriage. Two days after the baby was brought home
and her mother arrived to help, she had abrupt onset of chills, fever, and
diarrhea which became grossly bloody in a few days.
Case 4. Insidious Diarrhea. A fifteen-year-old girl noted over a period of
two months a gradual increase in the frequency of her bowel movements,
which remained, however, formed but soft. This coincided with the first
emergence of the typical conflicts of adolescence. She was then in an
automobile accident, which involved no serious injury but did bring up some
problems of adolescent acting out. Immediately after the accident her bowel
movements became watery and frankly bloody.
Case 5. Tenesmus and Cramps. Immediately following the death of her
brother, a thirty-one-year-old unmarried woman developed postprandial
distention, belching, mild lower abdominal cramps, and tenesmus associated
with the passage of small amounts of blood, mucus, and flatus. Her stool
remained formed and hard, and she was constipated for a month. Thereafter
she had one to three semisolid fecal movements with blood.
In general, the older the patient at the time of onset of the disease the
more likely is the precipitating circumstance to be a major external event.
Thus, a fifty-year-old chairman of a university department experienced his
first attack, which was fatal, soon after the death of both his parents in a fire.
His wife, who would have been his source of support, lost her mother around
the same time.
At the present time there is no information as to why this
psychobiological state of giving up and helplessness is associated with
activation of the ulcerative colitis process. Of interest is the fact that if the
patient becomes angry and aggressive, and does not give up, but instead feels
guilty, he is more prone to develop headache than activation of colitis. Indeed,
the appearance of headaches in a heretofore acutely ill colitis patient is a good

prognostic sign.
Three incidents from Case 1 (above) illustrate this:
October 31, 1947—headache: The patient had been free of bowel
symptoms for three months. Her two-and-a-half-year-old son defecated in his

crib and smeared the feces. “I was awfully mad and gave him a spanking. That
night I had a migraine attack. The next morning I still had a headache. Then I
realized how guilty I was feeling for spanking him. Shortly thereafter my
headache disappeared.”
August 20, 1934—-bleeding: The patient and her husband bought a
building lot, but it turned out that the real estate man tricked them. The
patient became very angry with him and told him how she felt. He was
unmoved. “I got so mad, and there was absolutely nothing I could do about it.”
Now they faced the loss of their precarious financial reserves. By that evening
she was bleeding.
March 28, 1951-—headache terminating attack of colitis: The patient
began to bleed on February 20, 1951, when she realized a business venture of
her husband was going to fail. She had increasing bleeding and diarrhea and
after a couple of weeks it became necessary to confine her to bed at home. At
my suggestion another doctor saw her at home, but she had the feeling, “you
are leaving me flat.” I called her by phone daily, but she was apathetic and
relatively uncommunicative. The other internist and I considered

hospitalization but decided to delay it as long as possible to keep the financial
burden at a minimum. On March 28, 1951, she called me for the first time and
said firmly and belligerently, “You must put me in the hospital; I am too sick.”
On admission I was astonished to discover that she was not suffering

primarily from diarrhea but from a severe, left-sided migraine headache, with
nausea and vomiting. Her opening remark was an unprecedented: “I don’t like
you.” Her headache subsided by noon and within two days she had formed
stools without blood.
In general patients who are good at differentiating their feelings have

little difficulty in identifying the affective state most conducive to relapse.
Thus one woman claimed the anxiety associated with long-standing phobic
symptoms never precipitated colitis symptoms; nor did bursts of rage

expressed to her estranged husband. The dangerous period was when she
ceased trying to cope actively with these stresses and gave up, sometimes
taking to her bed to “sleep it off” only to awaken with cramps or bleeding.
Implications for Treatment. The physician who understands the basic

psychological processes operating in these patients is much better equipped
to do what is helpful and to avoid doing what is harmful.
The first step in the treatment of an acutely ill patient is to establish a
relationship. This is best achieved through the sensitive quality of the
physician’s first inquiry and his prompt attention to relief of discomfort.
Thereafter, constant awareness of the patient’s needs and of his characteristic

ways of functioning is of the utmost importance in enabling the patient to
utilize the relationship with his physician as a means of reestablishing his
psychological equilibrium and health. In many respects, this is the keystone of

the whole treatment program, and if the initial step is unsuccessful, the whole
treatment program may fail.
The physician who undertakes the care of the patient with ulcerative
colitis assumes a very complex responsibility, for if he succeeds in this first

step of establishing a relationship with the patient, he must be aware that in
so doing he is, in part at least, taking over the role of the key figure. This
means that while this relationship may be a powerful factor in initiating
recovery, its disruption may carry with it the equally great danger of
precipitating a relapse. The patient, for some time at least, remains just as
vulnerable to a disturbance in his relationship with his physician as he was to
a disturbance in his original key relationship. He quickly comes to endow his
physician with omniscient and omnipotent qualities. He literally expects the
physician to know more of his needs and wants than he himself reveals.
Therefore, the doctor must attend closely and respond appropriately to the
patient’s communications of needs and of sources of discomfort, even when
these are not verbally conveyed. This demands patience, a willingness to
devote time to the patient, and, most important, the capacity to appreciate
and accept the patient’s need to have tangible demonstration of the
physician’s reliability, even in respect to such seemingly minor details as
punctuality, following through on promises, and availability for help. Simply
the assurance that the physician can be reached at any time can be a powerful
source of help, even if this resource is never actually used. It is difficult to
overemphasize the importance of these small details, which are perceived by
the patient as indices of the doctor’s successful and effective participation in

his care.
A patient (Case 1, above) had a serious relapse when she had called her
physician to check on her medication schedule only to discover that he was
out of town and unavailable for a week. When she became my patient we had
a standing arrangement whereby she could call me anytime day or night, even
when I was away from the city. She called infrequently and then only to
report some considerable symptom or a disturbing situation. A relapse
occurred following a remission of almost a year when the patient moved into
a house in a new suburban tract only to discover that the phone company had
not yet laid the cables and hence she would be without a phone for an
uncertain period. Symptoms promptly subsided when I was able to prevail
upon the phone company to put in an emergency line and she once again
knew she could reach me.
The management of the family is another important consideration.
Awareness of the kind of relationship that exists with other members of the
family, especially with the mother or the spouse, prepares the physician for
the kinds of difficulties which may arise. Usually the important other figure is
experiencing a considerable amount of guilt concerning the illness of the

patient and may have a strong need to reassert her control both over herself
and the patient. It is important that the physician not take a retaliative or a
punitive attitude toward the other members of the family. On the other hand,
to the patient he must appear stronger than any member of the family.
Occasionally, for example, we find the patient making demands, such as to
leave the hospital or change medication, which, in fact, reflect not the
patient’s needs or concerns but rather those of some other family figure. For
the physician not to accede to such requests may be a great relief to the
patient, for by asserting his medical authority the physician protects the
patient from what actually may have been a frightening prospect.
While this approach is predicated on a psychotherapeutically oriented

perspective, it is well to recognize that some patients can profit from more
systematic psychotherapy in the hands of a skilled therapist. The capacity of a
patient to so benefit must be evaluated by the psychiatrist, but care must be

exercised that the referral to a psychiatrist, even when initiated by the
patient, is not interpreted by the patient as a rejection by the internist or
gastroenterologist. The latter, by all means, should maintain an active
involvement with the patient so that beginning psychotherapy is seen as an

addition, not a replacement.
In one study, in which patients receiving psychotherapy in addition to

medical therapy were matched with patients receiving medical therapy alone,
pretreatment criteria favoring good response to psychotherapy were
identified. These included: (1) the presence of an obvious precipitating event,
especially if recognized by the patient; (2) depression traceable to loss, as

compared to depressive apathy; (3) the unconscious use of diarrhea and
bleeding as substitutes for rage and as means of punishment, in contrast to
regarding the illness without shame or guilt as a justification to remain

helpless and make demands on others; and (4) a wish to become
independent.
In recognizing the role of psychotherapy in the treatment of these
patients, one should also have very clearly in mind what psychotherapy can
and what it cannot be expected to accomplish. There is no evidence at the
present time that psychotherapy, no matter how intensive, can eliminate the
biological defect underlying colitis. Therefore, an expectation of complete
cure is unjustified. While remission and complete healing are common,
psychotherapy cannot ensure against recurrence in the face of sufficient

stress. The major contribution that psychotherapy can make is the
modification of the basic psychological structure so as to render the
individual less vulnerable to the types of situations in which the disease
becomes manifest. These particularly concern the capacity of the patient to

develop human relationships and to tolerate their loss or the threat of their
loss. Successful psychotherapy usually brings about a significant
improvement in the patient’s techniques of dealing with the early parental

figures, as well as some resolution of early conflicts. With this one generally
sees a gradual emancipation from parental figures and an increasing capacity
to establish satisfying and enduring relationships with others. But, as with

any person, there may still occur events with which the patient feels he has no
effective means of coping and under such circumstances the disease may
resume. In general, however, we find that the patient who has achieved some
successful psychotherapeutic response has more chance of maintaining a

remission. But it is of the utmost importance that the patient, embarking on
psychotherapy, clearly understands that psychotherapy cannot eliminate the
potential for colitis, otherwise even a mild relapse may be felt as a personal
failure or destroy the patient’s confidence in the therapist, thereby
constituting a major stress capable of provoking a massive recurrence. Many
of the serious relapses during or upon termination of psychotherapy or

psychoanalysis have been of this nature and have led to an unjustified
pessimism as to the effectiveness of this approach.
As to modalities of psychotherapy, insight therapy is more useful with
the relatively more active, independent patients, while patients who are
strongly symbiotic or transitional are helped more by support, catharsis and
suggestions than interpretation. Best results are obtained by therapists who
rate high in interest in the patient, empathic understanding, and optimism
about results, and with patients who are most hopeful about being helped and
who can develop a warm trusting working alliance with the therapist. The
ability of the therapist to “fit” or match himself to the fluctuating dependency
needs of the patient is important. Symbiotic patients improve when their

therapists are able to tolerate their infantile dependent needs without
rejection, impatience, or arbitrary corrective attitudes. The papers by Karush
et al., and by Groen et al. are excellent sources of information about the
psychotherapy of ulcerative colitis patients.
In considering the usual indications for ileostomy and colectomy,
namely, intractable diarrhea, recurring fistulae or abscesses, massive
hemorrhage, rectal incontinence, and threat of cancer, it is important to
appreciate how stressful it is for these patients not to have complete control
over their bowel activity, whether it be in the form of unpredictable bleeding,

diarrhea, or cramps. With his great need to maintain control over his
thoughts, acts, and body, and to perform well, incapacity on this score is often
felt as a true inadequacy, for which the patient often inappropriately assumes
responsibility. Hence the removal of the offending colon and the construction
of an artificial anus (ileostomy) over which the patient generally has much
better control often has a more salutary effect psychologically than had been
anticipated by the patient, his family or physician, all of whom tend to view
the procedure primarily in terms of its mutilating effect. Hence the
psychotherapist is well advised to keep in mind not only these indications for
surgery, but also the contribution he can make in preparing the patient for
operation and the postoperative adjustment. Above all must he appreciate

that recourse to surgery does not constitute a failure of psychotherapy or
grounds for relinquishing his therapeutic role. There is great advantage for
the prospective ileostomy patient to meet a successful ileostomy patient and
to learn at first hand the gains as well as the realistic problems of ileostomy.
Additional help may be provided through participation in the activities of the
Ileostomy Clubs, which constitute a resource not only for practical
information but also for group activity which is psychologically sound for
these patients. Their slogan HELP (Help, Encouragement, Learning,
Participation) clearly reflects an intuitive grasp of the basic human and
psychological needs of the ulcerative colitis patients.
Ulcerative Enteritis. That the same pathological process may also
involve the terminal ileum has been known for a long time. Less well known
is that it may develop in a previously healthy ileum after colectomy and
ileostomy have been performed, and under the same types of psychologically
stressful situations as had previously led to the activation of the ulcerative
colitis. The entire small bowel may rarely be so involved. Swelling of the
stoma with partial obstruction, profuse watery drainage, or perforation may
ensue. Edema, petechial hemorrhages, and ulceration of the protruded
mucous membrane may be noted.
The risk of this complication provides further reason why a continuing

supportive or psychotherapeutic approach is called for, even after colectomy
and ileostomy, especially with the patient who has been in psychotherapy.
Regional Enteritis and Colitis

( Crohn’s Disease )
While not the subject of as extensive psychological inquiry as ulcerative
colitis, the available data indicate many similarities between patients with
regional enteritis and those with ulcerative colitis. This is not surprising,
considering the fact that although clearly differentiated on pathological
grounds, there is nonetheless a tendency for the two diseases to occur in the
same family suggesting a common genetic factor. Furthermore, now that it is
being appreciated that a similar pathological process may affect the large
bowel (granulomatous colitis, Crohn’s disease of the colon), it is clear that at
least some of the colitis patients studied psychologically in the past actually
belonged in this category. The several patients that this writer has studied
who later proved to have the granulomatous form of colitis did not appear to
differ psychologically from those who had classical ulcerative colitis. The
resemblance is greatest in respect to the prominence of obsessive-
compulsiveness, the patterns of relating, and the vulnerability to object loss
and subsequent development of giving up as the setting in which onset or

relapse of active disease occurs. Compared to ulcerative colitis patients, some
authors feel patients with Crohn’s disease are relatively more flexible and
more active, but the only systematic comparative study suggests no

differences. Hence, until more information is available, it seems warranted to
use the data on ulcerative colitis as a rough guide for the management of
these patients as well. More detailed study is called for.
Possible Somatopsychic-Psychosomatic Conditions
There are a number of other conditions which possibly can be classified
under the heading of somatopsychic-psychosomatic disorders but which have
not yet been sufficiently studied to justify the claim.
Celiac Sprue
It is currently believed that celiac disease of childhood and many

instances of so-called idiopathic steatorrhea of adulthood represent the same
disorder, hence the term “celiac sprue.” In both diseases identical and to a
large extent reversible damage to the small intestinal mucosa is produced by
low-molecular-weight glutamine-rich polypeptides, isolated from the

breakdown products of gluten, the water-insoluble protein moiety of wheat.
Many adult patients give a history of celiac disorder early in childhood, while
proven childhood celiacs, allegedly recovered, may as adults still show

absorption defects, typical histopathological changes, and reactivity to gluten,
with intermittent mild symptoms of malabsorption. Evidence for a genetic
determinant has been brought forth, leading to the suggestion of an inborn
deficiency in the intestinal mucosa of a peptidase that hydrolyzes the

peptides of gluten.
The natural history of spontaneous remissions despite the presence of

dietary gluten in the childhood form of the disease, and the poor correlation
between symptoms and the presence of typical histopathological changes
suggests that the underlying mucosal defect and the presence of gluten in the
diet may be necessary but not sufficient for the development of the
malabsorption syndrome. Individuals appear to differ in sensitivity to gluten,
and symptoms may also correlate more with the extent of the intestine
involved than with the severity of the lesion on biopsy. The effects of gluten
are more marked on proximal than on distal intestine, presumably a

reflection of declining concentration of the noxious polypeptides. The great
majority of patients show prompt marked clinical improvement on strict
glutenfree diets with reversal of epithelial changes more complete distally

than proximally. But returning gluten to the diet does not necessarily
reactivate symptoms even though biopsy evidence of damage may be
demonstrated. Hence some have suggested that psychological stress may be a
contributing factor. Among children a disturbance in the mother-child

relationship, including changes in patterns of handling and feeding, appear to
be associated with exacerbations, while remissions have been brought about
through improving the mother-child relationship, even without removing

gluten from the diet. Among adults, with and without a childhood history,
onset or recurrences are noted in settings in which real or threatened loss of
support eventuates in psychological “giving up” with feelings of sadness,

despair, and helplessness. These are psychological states in which Sadler and
Orton have demonstrated decreased absorption of amino acids in a surgically
isolated loop of ileum in a man who did not have celiac-sprue syndrome.
Suggestive data on this interrelationship between the intrinsic intestinal
defect, dietary gluten, and psychological factors have been provided by
Grant’s double-blind study of eight patients with adult celiac disease, four of
whom were known to have had childhood celiac disease and three of whom
had a history compatible with childhood celiac disease. Placed on a gluten-
free diet, all patients showed remission of symptoms and improvement in
absorption. Then, in a double-blind fashion they were given capsules

containing either gliadin (a derivative of gluten containing the glutamine-rich
polypeptides) or an inactive material. The occurrence of symptoms was noted
and the psychological state evaluated. Gliadin capsules were administered a
total of thirty-one periods during five of which typical malabsorption

symptoms developed. All of these occurred within days of the onset of a
psychological upset, generally characterized by some loss, defeat,
discouragement, or helplessness. On no occasion did gliadin alone induce

symptoms in a patient who otherwise was emotionally composed. On the
other hand, bowel symptoms also occurred during periods when the patient
was similarly upset but was not receiving gliadin. Notable, however, was the
fact that under such conditions the symptoms were those of a nonspecific,
nonfoul watery diarrhea, sometimes with mucus, and did not include the
typical bloating or the foul smelling, pale, copious stools typical of
malabsorption. These observations suggest an interaction between at least

three factors in the production of the full-blown malabsorption syndrome: (1)
an intrinsic intestinal defect; (2) gliadin in the diet; and (3) some effect
mediated through psychophysiological or neurogenic influences.
The data available are insufficient to justify any statement concerning
distinctive psychological characteristics of this group of patients. Paulley
emphasizes querulousness and extreme rigidity among the more disturbed

patients and perhaps a higher incidence of psychotic, often delusional and
paranoid features. We have been impressed with the immaturity and
dependency of the adults with a childhood history of celiac disorder as well as
their unusual vulnerability to loss of love objects. Prugh, in his study of
children, emphasizes the prominence of obsessive-compulsive traits, and the
controlling and ambivalent nature of the mother’s relation with her child, and
points to evidence that such attitudes of the mother antedated the birth of the
child. He describes the children on the surface to be passive, often withdrawn,
inhibited personalities, with a tendency toward obsessive-compulsive

features. Overt expressions of aggression or self-assertion seem to be difficult
for these children. As infants, they were fussy, irritable, and cried a great deal,
even before the onset of the celiac symptoms. Somatic effects of multiple
nutritional deficiencies as well as of the psychological responses to diarrhea
and other debilities must not be underestimated in evaluating some of these

descriptions.
Irritable Bowel Syndrome
This is the classical “functional” bowel disorder, characterized by
alternating diarrhea and constipation, abdominal cramps, flatulence, and at
times increased mucus in the stools. Some investigators differentiate two
groups, i.e., spastic colon and functional diarrhea. Those with spastic colon
have lower abdominal pain and cramps as their main symptom, and in
addition have constipation which alternates with diarrhea or with periods of
normal bowel movements. Patients with functional diarrhea have little or no

abdominal pain, their chief symptom being constant or intermittent diarrhea.
Many are overtly anxious and their symptoms may more properly be
classified as instances of diarrhea as a physiological concomitant of affect,
though it remains obscure why some anxious people have diarrhea and
others do not. Both neural and hormonal mechanisms have been postulated.
Accelerated transport of intestinal contents, through increased peristalsis
induced by increased sensitivity to cholecystikinin, by gastro-ileal or gastro-

colic reflexes or by higher neurogenic effects may induce diarrhea simply by
overloading the absorptive capacity of the colon. Both with spastic colon and
with functional diarrhea it has been claimed that the colon reacts excessively
to parasympathetic stimulation as compared to the colon of patients without
bowel disorder or with ulcerative colitis, but some writers disagree. They
point out that the increase in intraluminal pressure is a function of the
mechanics of intraabdominal pressure recording, important factors being

resistance to expulsion and the consistency of the stools. While pressures are
low with diarrhea and high with constipation, the increased activity in
painless diarrhea may reflect a control mechanism for handling excessive
intestinal contents by segmentation rather than by inhibition. Such findings
give further reason to regard patients with painless diarrhea as belonging to a
different group from the rest of those with irritable colon syndrome.
Be that as it may, there is virtually universal acceptance of the view that
bowel symptoms in both types are somehow brought about by psychological
influences. This has led to the classification of irritable colon syndrome as a
“psychogenic” or “psychophysiological” disorder, the inference being that the
bowel disorder can be accounted for by chronic and excessive
parasympathetic stimulation psychophysiologically determined. This is
almost certainly an oversimplification. The virtually lifelong symptomatic
history of many of these patients suggests that there may be as yet
unidentified organic factors influencing the bowel response to psychological

stress. Until more definitive data are available, it seems prudent not to
exclude such primary organic determinants; hence its classification here as a

“somatopsychic-psychosomatic” rather than psychophysiological disorder.
Because there is no clear organic criterion for the diagnosis of irritable
bowel syndrome, which even gastroenterologists make largely by exclusion,
existing data on the psychological characteristics of patients with this

syndrome are highly dependent upon the population utilized. In general they
have been patients referred to a psychiatrist after the gastroenterologist has
ruled out other explanations of the symptoms, and often because he has been
impressed by evidence of neurotic difficulties. Early published series may
well have included patients who now would be recognized as suffering from
lactase deficiency or adult celiac syndrome. Hence it is likely that patients so
far reported on have been selected to begin with because of manifest
emotional problems, and are neither a representative population nor even
necessarily all have irritable bowel syndrome. With this caveat it is claimed
that patients with spastic colon are more inclined to be rigid, obsessional, and
compulsive individuals while those with functional diarrhea may show more
diffuse free-floating or phobic anxiety as well. Many tend to be orderly,

methodical, conscientious, precise, preoccupied with cleanliness, tidiness,
regularity, punctuality, and schedules, and it is not surprising that some
gravitate to work roles in which such qualities are valued as accounting,
bookkeeping, filing, library work, etc. Such patients place a high premium on
intellectual control and performance and are very restrained in expression of
emotions, be they pleasurable or unpleasurable. By the same token, they tend,

on the one hand, to maintain a cold, intellectual almost impervious air toward
the emotional turmoil of others, while, on the other, to be extremely sensitive

to hostile or rejecting behavior, or emotional outbursts when directed toward
them. In the latter respect they appear as hypersensitive and easily hurt to
the point at times of paranoid suspiciousness. Important in the underlying
psychodynamics are conflicts about giving and receiving, and the control of
aggression. Distrustful and fearful of rejection, especially if aggressive or
sexual impulses are displayed, they tend to hold on to what they possess, not
to give. Some are stingy, stubborn, and parsimonious, while others overdo the
guise of generosity (reaction formation) but as a result constantly feel
unappreciated and disappointed that the recipient is not more grateful.
Feelings of depression are common, and there is a relatively high incidence of

significant clinical depression.
It has been suggested that the alternations between constipation and
diarrhea characteristic of these patients reflect shifts between psychologically
holding back and maintaining control, on the one hand, and letting go in an
unconscious, aggressively soiling or depreciatingly giving way on the other. It
is of interest that headaches commonly accompany the controlled,
constipated phase, which is marked not only by guilt-determined inhibition of

action but also by the use of the head (intellect). In general, diarrhea is most
prominent at times when emotional tension is most evident.
Achalasia ( Cardiospasm )
Though not accepted by all, the association between psychological
stress and onset or exacerbation of cardiospasm has been proposed for many
years. However, the disorder is relatively uncommon and hence the
information available is insufficient to document more than the fact of a high
incidence of psychological disturbances among the sufferers and a
chronological correlation between psychological stress and episodes of the
disorder. The fact that the disease may have its onset at any age, though it is
rare in infancy and childhood, that it most commonly develops in early adult
life, that there is a familial incidence, and that there is evidence of a
disturbance in the intrinsic parasympathetic innervation of the esophagus all
favor some intrinsic organic process present or acquired early in life. Patients
with achalasia have an elevated level of resting lower esophageal sphincter
pressure and incomplete sphincter relaxation with swallowing. The available
evidence indicates that this is caused by the loss of β-adrenergic inhibitory
activity and that denervation of the sphincteric muscle is of primary

importance. The difficulty in swallowing is accentuated during emotional
upset but as yet too few patients have been studied in detail to provide any
general psychological characterization as a group.
Bibliography
Acheson, E. D. and M. D. Nefzger. “Ulcerative Colitis in the United States Army in 1944.
Epidemiology: Comparisons between Patients and Controls,” Gastroenterology, 44
(1963), 7-19.
Adamson, J. D. and A. H. Schmale. “Object Loss, Giving Up and the Onset of Psychiatric Disease,”
Psychosom. Med., 27 (1965), 557-576.
Ader, R. “Plasma Pepsinogen Level as a Predictor of Susceptibility to Gastric Erosions in the Rat,”
Psychosom. Med., 25 (1963), 221-232.
----. “Gastric Erosions in the Rat. Effects of Immobilization at Different Points in the Activity
Cycle,” Science, 145 (1964), 406-407.
----. “Behavioral and Physiological Rhythms and the Development of Gastric Erosions in the Rat,”
Psychosom. Med., 29 (1967), 345-353.
Ader, R., C. C. Beels, and R. Tatum. “Blood Pepsinogen and Gastric Erosions in the Rat,” Psychosom.
Med., 22 (1960), 1-12.
Alexander, F. “The Influence of Psychologic Factors upon Gastrointestinal Disturbances: General

Principles, Objectives and Preliminary Results,” Psychoanal. Q., 3 (1934), 501-539.
----. “Gastrointestinal Neuroses,” in S. Portis, ed., Diseases of the Digestive System, 1st ed., pp. 206-
226. Philadelphia: Lea & Febiger, 1941.
----. Psychosomatic Medicine. New York: Norton, 1950.
----. “Emotional Factors in Gastrointestinal Disturbances,” in S. Portis, ed., Diseases of the Digestive
System, 3rd ed., pp. 228-252. Philadelphia: Lea & Febiger, 1953.
Almy, T. P., F. K. Abbot, and L. E. Hinkle. “Alterations in Colonic Function in Man under Stress: IV.
Hypomotility of the Sigmoid Colon and Its Relationship to the Mechanism of
Functional Diarrheas,” Gastroenterology, 15 (1950), 95-113.
Almy, T. P., L. E. Hinkle, B. Berle et al. “Alterations in Colonic Function in Man under Stress. III.
Experimental Production of Sigmoid Spasm in Patients with Spastic Constipation,”
Gastroenterology, 12 (1949), 437-449.
Almy, T. P., F. Kern, and M. Tulin. “Alterations in Colonic Function in Man under Stress. II.
Experimental Production of Sigmoid Spasm in Healthy Persons,” Gastroenterology,
12 (1949), 425-436.
Almy, T. P. and P. Sherlock. “Genetic Aspects of Ulcerative Colitis and Regional Enteritis,”
Almy, T. P. and M. Tulin. “Alterations in Colonic Function in Man under Stress: I. Experimental
Production of Changes Simulating the ‘Irritable Colon’,” Gastroenterology, 8 (1947),
616-626.
Alvarez, W. C. “Hysterical Type of Non-Gaseous Abdominal Bloating,” Arch. Intern. Med., 84

(1949), 217-245.
Anthony, E. J. “An Experimental Approach to the Psychopathology of Childhood; Encopresis,” Br. J.

Med. Psychol., 30 (1957), 146-175.
Arthur, B. “Role Perceptions of Children with Ulcerative Colitis,” Arch. Gen. Psychiatry, 8 (1963),
536-545.
Askevold, F. “Studies in Ulcerative Colitis,” J. Psychosom. Res., 8 (1964), 89-100.
Bacon, C. “Typical Personality Trends and Conflicts in Cases of Gastric Disturbances,” Psychoanal.
Q., 3 (1934), 540-557.
Barker, W. F. “Family History of Patients with Ulcerative Colitis,” Am. J. Surg., 103 (1962), 25-26.
Boyer, P. H. and D. H. Anderson. “A Genetic Study of Celiac Disease,” Am. J. Dis. Child., 91 (1956),
131-136.
Burch, P. R. J., F. T. deDombal, and Watkinson. “Aetiology of Ulcerative Colitis. II. A New
Hypothesis,” Gut, 10 (1969), 277-284.
Card, W. L. and I. N. Marks. “The Relationship between the Acid Output of the Stomach following
‘Maximal’ Histamine Stimulation of the Parietal Cell Mass,” Clin. Sci., 19 (1960),
147-163.
Chaudhary, N. A. and S. C. Truelove. “Human Colonic Motility: A Comparative Study of Normal

Subjects, Patients with Ulcerative Colitis, and Patients with Irritable Bowel
Syndrome,” Gastroenterology, 40 (1961), 1-17.
----. “The Irritable Colon Syndrome,” Q. J. Med., 31 (1962), 307-316.
Coddington, D. “Study of an Infant with a Gastric Fistula and Her Normal Twin,” Psychosom. Med.,
30 (1968), 172-192.
Cohen, S. and Z. W. Lipshut. “Lower Esophageal Sphincter Dysfunction in Achalasia,”

Cox, A. S. “Stomach Size and Its Relation to Chronic Peptic Ulcer,” Arch. Pathol., 54 (1952), 407-
422.
Crocket, R. W. “Psychiatric Findings in Crohn’s Disease,” Lancet, 1 (1952), 946-949.
Daniels, G. E., J. F. O’Connor, A. Karush et al. “Three Decades in the Observation and Treatment of
Ulcerative Colitis,” Psychosom. Med., 24 (1962), 85-93.
DeGraff, J. and M. A. M. Schuurs. “Severe Potassium Depletion Caused by Abuse of Laxatives,” Acta
Med. Scand., 166 (1960), 407-422.
Dick, A. P., L. P. Holt, and E. R. Dalton. “Persistence of Mucosal Abnormality in Ulcerative Colitis,”
Gut, 7 (1966), 355-360.
Doll, R. and J. Buch. “Hereditary Factors in Peptic Ulcer,” Ann. Eugen., 15 (1950), 135-146.
Eberhard, G. “Peptic Ulcer in Twins. A Study in Personality Heredity and Environment,” Acta
Psychiatr. Scand., 44, Suppl. 205 (1968), 7-118.
Edwards, H. H. “The Meaning of the Associations between Blood Groups and Disease,” Ann. Hum.
Genet., 29 (1965), 77-83.
Ehrentheil, O. F. and E. P. Wells. “Megacolon in Psychotic Patients,” Gastroenterology, 29 (1955),

285-294.
Eisenman, B. and R. L. Heyman. “Stress Ulcers—A Continuing Challenge,” N. Engl. J. Med., 282
(1970), 372-374.
Engel, G. L. “Studies of Ulcerative Colitis. II. The Nature of the Somatic Processes and the
Adequacy of Psychosomatic Hypotheses,” Am. J. Med., 16 (1954), 416-433.
----. “Studies of Ulcerative Colitis. III. The Nature of the Psychologic Processes,” Am. J. Med., 19
(1955), 231-256.
----. “Studies of Ulcerative Colitis. IV. The Significance of Headaches,” Psychosom. Med., 18 (1956),
334-346.
----. “Studies of Ulcerative Colitis. V. Psychological Aspects and Their Implications for Treatment,”
Am. J. Dig. Dis., 3 (1958), 315-337.
----. “Review of A. Garma, ‘Peptic Ulcer and Psychoanalysis’,” Nerv. Ment. Dis. Monograph no. 85.
Am. J. Dig. Dis., 4 (1959), 829-831.
----. “Psychogenic Pain and the Pain-Prone Patient,” Am. J. Med., 26 (1959), 899-918.
----. “Biologic and Psychologic Features of the Ulcerative Colitis Patient,” Gastroenterology, 40
(1961), 313-317.
----. “Guilt, Pain and Success. Success Facilitated by the Pain of a Glomus Tumor and Peptic Ulcer,”
Psychosom. Med., 24 (1962), 37-48.
----. Psychological Development in Health and Disease, pp. 29-104. Philadelphia: Saunders, 1962.
----. Psychological Development in Health and Disease, pp. 364-380. Philadelphia: Saunders,
1962.
----. Psychological Development in Health and Disease, pp. 381-401. Philadelphia: Saunders,
1962.
----. “A Reconsideration of the Role of Conversion in Somatic Disease,” Compr. Psychiatry, 9

(1968), 316-326.
----. “Psychological Factors in Ulcerative Colitis in Man and Gibbon,” Gastroenterology, 57 (1969),
362-365.
----. “Pain” in C. M. MacBryde and R. S. Blacklow, eds., Signs and Symptoms: Applied Pathologic
Physiology and Clinical Interpretation. 5th ed., pp. 44-61. Philadelphia: Lippincott,
1970.
----. “Conversion Symptoms,” in C. M. MacBryde and R. S. Blacklow, eds., Signs and Symptoms:
Applied Pathologic Physiology and Clinical Interpretation. 5th ed., pp. 650-668.
Engel, G. L., F. Reichsman, and D. Anderson. “Behavior and Gastric Secretion. III. Cognitive
Development and Gastric Secretion in Children with Gastric Fistula,” Psychosom.
Med., 33 (1971), 472-473.
Engel, G. L., F. Reichsman, and H. Segal. “A Study of an Infant with a Gastric Fistula. I. Behavior and
the Rate of Total Hydrochloric Acid Secretion,” Psychosom. Med., 18, (1956), 374-
398.
Feldman, F., D. Cantor, S. Soll et al. “Psychiatric Study of a Consecutive Series of 34 Patients with
Ulcerative Colitis,” Br. Med. J., 1 (1967), 14-17.
Finch, S. M. and J. N. Hess. “Ulcerative Colitis in Children,” Am. J. Psychiatry, 118 (1962), 819-826.
Fodor, O., S. Vestea, S. Urcan et al. “Hydrochloric Acid Secretion Capacity of the Stomach as an
Inherited Factor in the Pathogenesis of Duodenal Ulcer,” Am. J. Dig. Dis., 13 (1968),
260-265.
Ford, C. V., G. A. Glober, and P. Castelnuovo-Tedesco. “A Psychiatric Study of Patients with

Regional Enteritis,” JAMA, 208 (1969), 311-315.
Frazer, A. C. “The Present State of Knowledge of the Celiac Syndrome,” J. Pediatr. 57 (1960), 262-
276.
French, J. M., C. F. Hawkins, and W. T. Cooke. “Clinical Experience with the Gluten-Free Diet in
Idiopathic Steatorrhea,” Gastroenterology, 38 (1960), 592-595.
Freyberger, H. “The Doctor-Patient Relationship in Ulcerative Colitis,” Psychother. Psychosom., 18
(1970), 80-89.
Fullerton, D. T., E. J. Kollar, and A. B. Caldwell. “A Clinical Study of Ulcerative Colitis,” JAMA, 181
(1962),463-471.
Garma, A. Peptic Ulcer and Psychoanalysis. Nerv. Ment. Dis. Monograph no. 85, 1958.
Goldman, M. C. “Gastric Secretion during a Medical Interview,” Psychosom. Med., 25 (1963), 351-
356.
Grace, W. J. “Life Stress and Regional Enteritis,” Gastroenterology, 23 (1953), 542-553.
Grace, W. J., S. Wolf, and H. G. Wolff. The Human Colon. New York: Hoeber, 1951.
Grant, J. M. “Studies on Celiac Disease. I. The Interrelationship between Gliadin, Psychological

Factors, and Symptom Formation,” Psychosom. Med., 21 (1959), 431-432.
Groen, J. J. “The Psychosomatic Specificity Hypothesis for the Etiology of Peptic Ulcer,” Psychother.
Psychosom., 19 (1971), 295-305.
Groen, J. J. and D. Birnbaum. “Conservative (Supportive) Treatment of Severe Ulcerative Colitis.

Methods and Results,” Israel J. Med. Sci., 4 (1968), 130-139.
Gullick, H. D. “Carcinoma of the Pancreas. A Review and Critical Study of 100 Cases,” Medicine, 38
(1959), 47-84.
Gundry, R. K., R. M. Donaldson, C. A. Pinderhughes et al. “Patterns of Gastric Acid Secretion in

Patients with Duodenal Ulcer: Correlations with Clinical and Personality Features,”
Harvey, R. F. and A. E. Read. “Effects of Cholecystokinin on Colonic Motility and Symptoms in

Patients with the Irritable Bowel Syndrome,” Gut, 13 (1972), 837-838.
Hislop, I. G. and A. K. Grant. “Genetic Tendency in Crohn’s Disease,” Gut, 10 (1969), 994-995.
Hoffman, H. N., E. E. Wolleager, and E. Greenberg. “Discordance for Non-Tropical Sprue (Adult
Celiac Disease) in a Monozygotic Twin Pair,” Gastroenterology, 51 (1966), 36-42.
Hunt, J. N. “Inhibition of Gastric Emptying and Secretion in Patients with Duodenal Ulcer,” Lancet,
1 (1957), 132-134.
----. “The Influence of Hydrochloric Acid on Gastric Secretion and Emptying in Patients with
Duodenal Ulcer,” Br. Med. J., 1 (1957), 681-684.
----. “Some Notes on the Pathogenesis of Duodenal Ulcer,” Am. J. Dig. Dis., 2 (1957), 445-453.
Jackson, D. and I. Yalom. “Family Research in the Problem of Ulcerative Colitis,” Arch. Gen.
Psychiatry, 15 (1966), 410-418.
Kaplan, H. “The Psychosomatic Concept of Peptic Ulcer,” J. Nerv. Ment. Dis., 123 (1956), 93-111.
Kapp, F., M. Rosenbaum, and J. Romano. “Psychological Factors in Men with Peptic Ulcers,” Am. J.
Psychiatry, 103 (1947), 700-704.
Karush, A., G. E. Daniels, G. F. O’Connor et al. “The Response to Psychotherapy in Chronic

Ulcerative Colitis. I. Pretreatment Factors,” Psychosom. Med., 30 (1968), 255-276.
----. “The Response to Psychotherapy in Chronic Ulcerative Colitis. II. Factors Arising from the
Therapeutic Situation,” Psychosom. Med., 31 (1969), 201-226.
Kaufman, W. “Some Emotional Uses of Food,” Conn. Med., 23 (1959), 158-161.
Kehoe, M. and W. Ironside. “Studies on the Experimental Evocation of Depressive Responses

Using Hypnosis. II. The Influence of Depressive Responses upon the Secretion of
Gastric Acid,” Psychosom. Med., 25 (1963), 403-419.
Kezur, E., F. Kapp, and M. Rosenbaum. “Psychological Factors in Women with Peptic Ulcers,” Am.
J. Psychiatry, 108 (1951), 368-373.
Kirsner, J. B. “Ulcerative Colitis, Mysterious, Multiplex and Menacing,” J. Chronic Dis., 23 (1971),
681-684.
Kirsner, J. B. and W. L. Palmer. “The Irritable Colon,” Gastroenterology, 34 (1958), 491-501.
Kirsner, J. B. and }. A. Spencer. “Family Occurrence of Ulcerative Colitis. Regional Enteritis and
Ileocolitis,” Ann. Intern. Med., 59 (1963), 133-144.
Kohn, L. “The Behavior of Patients with Cancer of the Pancreas,” Cancer, 5 (1952), 328-330.
Kollar, E. J., D. T. Fullerton, R. Dicenso et al. “Stress Specificity in Ulcerative Colitis,” Compr.
Psychiatry, 5 (1964), 101-112.
Kraft, E., N. Finby, P. T. Egidio et al. “The Megasigmoid Syndrome in Psychotic Patients,” JAMA,
195 (1966), 1099-1101.
Levey, H. B. “Oral Trends and Oral Conflicts in a Case of Duodenal Ulcer,” Psychoanal. Q., 3 (1934),
574-582.
Levin, E., J. B. Kirsner, and W. L. Palmer. “Twelve-Hour Nocturnal Gastric Secretion in

Uncomplicated Duodenal Ulcer Patients: before and after Healing,” Proc. Soc. Exp.
Biol. Med., 69 (1948), 153-157.
Levine, M. “Pregenital Trends in a Case of Chronic Diarrhea and Vomiting,” Psychoanal. Q., 3
(1934), 583-588.
Lieberman, M. A., D. Stock, and R. Whitman. “Self-Perceptual Patterns among Ulcer Patients,”
Lindsay, M. K. M., B. E. C. Nordin, and A. P. Norman. “Late Prognosis in Celiac Disease,” Br. Med. J.,
2 (1956), 14-18.
Littman, A. “Basal Gastric Secretion in Patients with Duodenal Ulcer: A Long-Term Study of
Variations in Relation to Ulcer Activity,” Gastroenterology, 43 (1962), 166.
MacDonald, W. C., L. L. Brandborg, A. L. Flick et al. “Studies of Celiac Sprue. IV. The Response of
the Whole Length of the Small Bowel to Gluten-Free Diet,” Gastroenterology, 47
(1964), 573-589.
MacDonald, W. C., W. O. Dobbins, and C. E. Rubin. “Studies of the Familial Nature of Celiac Sprue
Using Biopsy of the Small Intestine,” N. Engl. J. Med., 272 (1965), 448-456.
McKegney, F. P., R. O. Gordon, and S. M. Levine. “A Psychosomatic Comparison of Patients with

Ulcerative Colitis and Crohn’s Disease,” Psychosom. Med., 32 (1970), 153-166.
McMahon, J. M., F. I. Braceland, and J. Moersch. “The Psychosomatic Aspects of Cardiospasm,” Ann.
Intern. Med., 34 (1951), 608-631.
Margolin, S. G. “The Behavior of the Stomach during Psychoanalysis,” Psychoanal. Q., 20 (1951),
349-369.
Menguy, R. “Acute Gastric Mucosal Bleeding,” Ann. Rev. Med., 23 (1972), 297-312.
Miller, N. “Learning of Visceral and Glandular Responses,” Science, 163 (1969), 434-445.
Mirsky, I. A. “Psychoanalysis in the Biological Sciences,” in F. Alexander and Ross, eds., Twenty
Years of Psychoanalysis, pp. 155-176. New York: Norton, 1953.
----. “Physiologic, Psychologic and Social Determinants in the Etiology of Duodenal Ulcer,” Am. J.
Dig. Dis., 3 (1958), 285-314.
Misiewicz, J. J., S. L. Waller, P. P. Anthony et al. “Achalasia of the Cardia: Pharmacology and
Histopathology of Isolated Careiac Sphincteric Muscle from Patients with and
without Achalasia,” Q. J. Med., 38 (1969), 17-30.
Mittleman, B. and H. G. Wolff. “Emotions and Gastrointestinal Function,” Psychosom. Med., 4

(1942), 5-61.
Mohr, G. J., I. M. Josselyn, J. Spurlock et al. “Studies in Ulcerative Colitis,” Am. J. Psychiatry, 114
(1958), 1067-1076.
Monson, R. R. “Familial Factors in Peptic Ulcer. I. The Occurrence of Ulcer in Relatives,” Am. J.
Epidemiol., 91 (1970), 453-459.
Morris, P. J. “Familial Ulcerative Colitis,” Gut, 6 (1965), 176-178.
Noordenbos, W. Pain. Amsterdam: Elsevier, 1959.
Paulley, J. W. “Regional Ileitis,” Lancet, 1 (1948), 923.
----. “Chronic Diarrhoea,” Proc. R. Soc. Med., 42 (1949), 241-244.
----. “Psychosomatic Factors in the Aetiology of Acute Appendicitis,” Arch. Middlesex Hosp., 5
(1955), 35-41.
----. “Emotion and Personality in the Etiology of Steatorrhea,” Am. J. Dig. Dis., 4 (1959). 352-360.
----. “Crohn’s Disease,” Psychother. Psychosom., 19 (1971), 111-117.
Pearl, J. M., W. P. Ritchie, R. B. Gilsdorf et al. “Hypothalamic Stimulation. Feline Gastric Mucosa
Cellular Populations,” JAMA, 195 (1966), 281-284.
Pilot, M. L., A. Muggia, and H. M. Spiro. “Duodenal Ulcer in Women,” Psychosom. Med., 29 (1967),
586-597.
Poser, E. G. and S. G. Lee. “Thematic Content Associated with Two Gastrointestinal Disorders,”
Psychosom. Med., 25 (1963), 162-173.
Prugh, D. G. “A Preliminary Report on the Role of Emotional Factors in Idiopathic Celiac Disease,”
Psychosom. Med., 13 (1951). 220-241.
Reinhart, J. B. and R. A. Succop. “Regional Enteritis in Pediatric Practice,” J. Am. Acad. Child
Psychiatry, 7 (1968), 252-281.
Rhodes, J., H. T. Apsimon, and J. H. Lawrie. “pH of the Contents of the Duodenal Bulb in Relation to
Duodenal Ulcer,” Gut, 7 (1966), 502-508.
Richmond, J. B., E. J. Eddy, and S. D. Garrard. “The Syndrome of Fecal Soiling and Megacolon,” Am.
J. Orthopsychiatry, 24 (1954), 391-401.
Riemer, M. D. “Ileitis—Underlying Aggressive Conflicts,” N.Y. State J. Med., 60 (1960), 552-557
Ritchie, J. A. and M. S. Tuckey. “Intraluminal Pressure Studies at Different Distances from the Anus
in Normal Subjects and in Patients with Irritable Colon Syndrome,” Am. J. Dig. Dis.,
14 (1969), 96-106.
Rosenbaum, M. “Psychosomatic Aspects of Patients with Peptic Ulcer,” in E. Wittkower and R. A.

Cleghorn, eds., Recent Developments in Psychosomatic Medicine, pp. 326-344.
Rubin, J., R. Nagler, H. N. Spiro et al. “Measuring the Effect of Emotions on Esophageal Motility,”
Psychosom. Med., 24 (1962), 170-176.
Sadler, H. H. and A. V. Orten. “The Complementary Relationship between the Emotional State and
the Function of the Ileum in a Human Subject,” Am. J. Psychiatry, 124 (1968), 1375-
1384.
Schmale, A. H. “Giving Up as a Final Common Pathway to Changes in Health,” Adv. Psychosom.

Med., 8 (1972), 20-41.
Shorter, R. G., K. H. Hinzenga, and R. J. Spencer. “A Working Hypothesis for the Etiology and
Pathogenesis of Nonspecific Inflammatory Bowel Disease,” Am. J. Dig. Dis., 17
(1972), 1024-1032.
Sifneos, P. E. Ascent from Chaos. A Psychosomatic Case Study. Cambridge: Harvard University
Press, 1964.
Singer, H. C., J. G. D. Anderson, H. Frischer et al. “Familial Aspects of Inflammatory Bowel Disease,”
Slesinger, M. H., M. Davidson, J. H. Pert et al. “Recent Advances in the Physiology of the
Esophagus,” N.Y. State J. Med., 55 (1955), 2747-2754.
Smith, H. W., E. C. Texter, J. H. Stickley et al. “Intraluminal Pressures from the Upper
Gastrointestinal Tract. II. Correlations with Gastroduodenal Motor Activity in
Normal Subjects and Patients with Ulcer Distress,” Gastroenterology, 32 (1957),
1025-1047.
Stein, A., M. R. Kaufman, H. D. Janowitz et al. “Changes in Hydrochloric Acid Secretion in a Patient
with a Gastric Fistula during Intensive Psychotherapy,” Psychosom. Med., 24 (1962),
427-458.
Stewart, W. A. “Psychosomatic Aspects of Regional Ileitis,” N.Y. State J. Med., 49 (1949), 2820-
2824.
Stout, G. and R. L. Synder. “Ulcerative Colitis-like Lesion in Siamang Gibbons,” Gastroenterology,

57 (1969), 256-261.
Sun, O. C. H., H. Shay, B. Dlin et al. “Conditioned Secretory Response of the Stomach Following
Repeated Emotional Stress in a Case of Duodenal Ulcer,” Gastroenterology, 35
(1958), 155-165.
Sundby, H. S. and A. M. Auestad. “Ulcerative Colitis in Children. A Follow-Up Study with Special
Reference to Psychosomatic Aspects,” Acta Psychiatr. Scand., 43 (1967), 410-423.
Szasz, T. S. Pain and Pleasure. New York: Basic Books, 1957.
Szasz, T. S., E. Levin, J. B. Kiksner et al. “The Role of Hostility in the Pathogenesis of Peptic Ulcer,”
Psychosom. Med., 9 (1947), 331-336.
Thompson, M. W. “Heredity, Maternal Age and Birth Order in Aetiology of Celiac Disease,” Am. J.
Hum. Genet., 3 (1951), 159-166.
Tripp, L. E. and D. P. Agle. “Acute Pancreatitis as a Psychophysiologic Response: A Case Study,”

Am. J. Psychiatry, 124 (1968), 1253-1260.
Truelove, S. C. “Movements of the Large Intestines,” Physiol. Rev., 46 (1966), 457-512.
Wangel, A. G. and D. J. Deller. “Intestinal Motility in Man. III. Mechanisms of Constipation and
Diarrhea with Particular Reference to the Irritable Colon Syndrome,”
Watkins, G. L. and G. A. Oliver. “Giant Megacolon in the Insane,” Gastroenterology, 48 (1965), 718-
727.
Weiner, H., M. Thaler, M. F. Reiser et al. “Etiology of Duodenal Ulcer. I. Relation of Specific
Psychological Characteristics to Rate of Gastric Secretion (Serum Pepsinogen),”
Psychosom. Med., 19(1957), 1-10.
Weisman, A. D. “A Study of the Psychodynamics of Duodenal Ulcer Exacerbations,” Psychosom.

Med., 18 (1956), 2-42.
----. “The Psychiatric Management of Duodenal Ulcer,” Int. Record Med., 170 (1957), 568-575.
Weiss, E. “Cardiospasm,” Am. J. Dig. Dis., 3 (1958), 275-284.
West, K. L. “MMPI Correlates of Ulcerative Colitis,” J. Clin. Psychol., 26 (1970), 214-219.
White, B. V., S. Cobb, and C. Jones. Mucous Colitis. A Psychological Medical Study of 50 Cases,
Psychosom. Med. Monograph, NRC, 1939.
Whybrow, P. C., F. J. Kane, and M. A. Lipton. “Regional Ileitis and Psychiatric Disorder,” Psychosom.
Med., 30 (1968), 209-221.
Wijsenbeek, H., B. Maoz, I. Nitzan et al. “Ulcerative Colitis, Psychiatric and Psychologic Study of 22
Patients,” Psychiatr. Neurol. Neurochir., 71 (1968), 409-420.
Wilson, G. “Typical Personality Trends and Conflicts in Cases of Spastic Colitis,” Psychoanal. Q., 3
(1934), 558-573.
Winkelstein, A. “Psychogenic Factors in Cardiospasm,” Am. J. Surg., 12 (1931), 135-138.
Wlodek, G. K. “Gastric Mucosal Competence and Its Role in the Etiology of Peptic Ulcers,” Can.
Med. Assoc. J., 99 (1968), 483-488.
Wolf, S. “Physiology of the Mucous Membranes and Direct Observations on Gastric and Colonic
Function in Man,” in S. Portis, ed., Diseases of the Digestive System, 3rd ed., pp. 183-
208. Philadelphia: Lea & Fe' iger, 1953.
Wolf, S. and H. G. Wolff. Human Gastric Function. London: Oxford University Press, 1947.
Wolff, H. G. “Stress and Adaptive Patterns Resulting in Tissue Damage in Man,” Med. Clin. North
Am., 39 (1955), 783-797.
----. “The Mind-Body Relationship,” in L. Bryson, ed., An Outline of Man’s Knowledge, pp. 41-72.
New York: Doubleday, 1960.
Wolff, P. and J. Levine. “Nocturnal Gastric Secretion of Ulcer and Non-Ulcer Patients under Stress,”
Psychosom. Med., 17 (1955), 218-226.
Wolowitz, H. M. and S. Wagonfeld. “Oral Derivatives in the Food Preferences of Peptic Ulcer
Patients. An Experimental Study of Alexander’s Psychoanalytic Hypothesis,” J. Nerv.
Ment. Dis., 146 (1968), 18-23.
Wormsley, K. G. and M. I. Grossman. “Maximal Histalog Test in Control Subjects and Patients with
Peptic Ulcer,” Gut, 6 (1965), 427-432.
Yessler, P. G., M. F. Reiser, and D. M. Rioch. “Etiology of Duodenal Ulcer. II. Serum Pepsinogen and
Peptic Ulcer in Inductees,” JAMA, 169 (1959), 451-456.
Notes
1 This chapter is a revised version of the author’s chapter “Psychological Processes and
Gastrointestinal Disorders” which appeared in M. Paulson, ed., Gastroenterologic
Medicine, Philadelphia: Lea & Febiger, 1969. It is used here by permission.
2 For a more detailed consideration of these concepts, the reader is referred to reference 48.
3 Comparable physiological and psychological data are not available concerning benign gastric ulcer
and hence this discussion is limited to duodenal ulcer. While the presence of acid gastric
juice apparently is necessary for gastric-ulcer formation, chronic hypersecretion is not
characteristic of gastric ulcers, except for those occurring in the immediate prepyloric
region. Rather there is evidence that factors decreasing the competence of gastric
mucosa to contain an acid solution are implicated. The same probably holds true for so
called stress ulcers, or acute gastric mucosal bleeding, associated with bums or trauma,
though ulcers occurring after head trauma sometimes are accompanied by a sharp rise in
acid secretion.
4 The fact that the hyposecretors also fall into a discrete group in terms of psychological characteristics
is of theoretical interest. Furthermore, not only are these characteristics essentially the
same as those that have been noted among patients with pernicious anemia but also the
extreme hyposecretors (achylia gastrica) constitute the population in which pernicious
anemia ultimately may develop.
5 By culturally bound definitions.
6 The role of pain from a glomus tumor was a variable in this case not discussed in this summary.
7 By culturally bound definitions.
Chapter 28
Psychosomatic Aspects Of Bronchial Asthma1
Peter H. Knapp
Introduction
Observations bearing on the role of psychological factors in bronchial
asthma have a long history. Hippocrates allegedly said “The asthmatic must
guard against anger.” Distinguished clinicians in the 18th century contributed
anecdotal evidence about the role of emotions in precipitating or aggravating

the disorder. As recently as 1971 a critical review of respiratory function in
asthma remarked that “many asthmatic persons are somewhat unstable and
it is admitted that the course of the disease may be affected by emotional or
environmental factors.” In the late 1930s, a group of psychiatric clinicians,

most of them psychoanalytically inspired, along with physiologists and other
basic scientists, turned their attention to a group of chronic diseases of

unknown etiology. Bronchial asthma was an early object of this
psychosomatic scrutiny. The monograph on asthma by French and Alexander
reported a series of twenty-six cases treated by psychoanalysis, and surveyed
the psychosomatic evidence then extant. Since that time the continuously
expanding number of reports has been reviewed by Leigh, Freeman et al., and
Kelly.
Various psychosomatic theories have been proposed, the best known of

which is the thesis that asthma represents a “suppressed cry for the mother,”
originally stated by E. Weiss and elaborated by French and Alexander. Such
views have seldom been rigorously tested, and still less solidly confirmed, al-
though a thorough experiment in blind diagnosis from edited protocols,

designed by Alexander and his colleagues to put his theories to test, did yield
support for his original hypothesis about asthma. Most of the reported studies
have involved clinical and predominantly psychotherapeutic approaches, the

ultimate effects of which could only be ascertained by painstaking
investigation over a long time. They have also frequently failed to explain
their conceptual basis, and to specify by just what means and to what extent
events in the psychological-social sphere are conceived as interacting with
pulmonary processes. Finally they have often neglected to encompass
knowledge about the complex pathophysiological aspects of asthma itself,
which has undergone remarkable growth in the past decade.
This chapter will survey relatively recent work in four areas: (1)
Biological observations which have thrown light on the pathogenesis of
bronchial asthma and on pathways leading from brain to peripheral
pulmonary tissues, in other words on potential psychosomatic mechanisms;
(2) psychophysiological studies, offering evidence that short-term psy-
chological influences, possibly utilizing such pathways, may contribute to

acute exacerbations and remissions in asthmatic subjects; (3) psychosocial
studies, suggesting that certain personality constellations, possibly extending
short-range influences into chronic states of readiness, may correlate with the
disorder; and (4) studies of therapy, examining various psychotherapeutic

approaches to asthma, their limitations, and potential future directions.
Biological Observations
The basic pathophysiological defect in bronchial asthma is reversible
obstruction of the small airways. Presumably it results from smooth muscle

spasm, edema of bronchiolar mucosa, hypersecretion, or possibly all three. A
consequence of such obstruction is heightened resistance to the flow of air.
Increase in airway resistance—or decrease in its reciprocal, airway
conductance—is an essential index of asthmatic dysfunction. Without

evidence about air flow, which many clinical reports lack, it is difficult to
make meaningful statements about physical changes in an asthmatic patient.
Methods of assessing respiratory function have advanced rapidly in the
past two decades. Relatively simple and easily applied techniques for
estimating air flow, i.e. the timed vital capacity tracing and the peak-flow
meter, suffer from some inaccuracy and are to a large extent dependent on
voluntary effort. Since 1956 they have gradually been replaced by the whole-
body plethysmograph which yields a rapid accurate sampling of airway

conductance, corrected for lung volume, largely independent of effort. This
was first applied to the study of psychiatric patients by Ottenberg and Stein,
later by Heim et al., Luparello, and others. The instrument is cumbersome,
expensive and requires some skilled cooperation. Additional techniques

provide greater flexibility, i.e., flow-volume measurement, and the recently
introduced respiratory resistance unit, which allows breath-by-breath
assessment of total respiratory resistance.
Studies of gas exchange and of total, as well as regional ventilation have

also thrown light on asthma. Dudley and Martin and their colleagues, working
with normal subjects, have demonstrated marked sensitivity of numerous
respiratory indices to hypnotically induced emotion and pain.
Their techniques and the previously mentioned measures of airway
resistance all interfere with free bodily movement and occlude the mouth. As
yet there is no satisfactory noninvasive way of monitoring the respiratory

functions crucial to asthma. Useful approximations can be obtained by
pneumograph tracings of external chest movement, calibrated against other

respiratory indices. Heim et al. have applied this approach to speaking
subjects, and a number of groups are working with still greater refinements,
integrating thoracic and abdominal tracings and using a sensitive magnetic
pneumograph.
Taken as a whole, these physiological methods have clarified the
enormous range in severity of pulmonary dysfunction in asthma, which may
or may not correlate with a patient’s subjective impressions. They have

shown complex impairments of elasticity and regional ventilation, the clinical
significance of which is not entirely clear. Exercise also has a puzzling
relationship to asthma, at times alleviating and at times aggravating the dis-
order. Of great importance is the remarkably protracted and persistent
impairment of pulmonary function following a severe attack. Equally
important is the well-established phenomenon of impaired gas exchange in

asthma of more than mild degree. Decrease in arterial oxygen concentration
appears early in severe attacks and requires careful monitoring; the
concentration of CO2 rises as a late manifestation when attacks continue and

worsen. It can increase alarmingly, adding a marked respiratory acidosis to
the effects of hypoxia, dehydration, and exhaustion, with which the patient is
struggling; it may require correction by administration of bicarbonate.
Despite recent advances in pharmacotherapy, such severe episodes of status

asthmaticus remain a frequent, life-threatening complication of the disease,
calling for competent and vigilant therapeutic management.
The factors initiating all of these pulmonary changes are still obscure.
Two pathogenetic views exist, each supported by a body of evidence and
often zealous, if not myopic, proponents: the allergic-immunologic and the
neurogenic.
The view of asthma as basically an allergic disorder has been

paramount during most of this century. Clinically it is well known that
asthmatics tend to have a family history of allergic sensitivity. Careful
epidemiological studies support the concept of an hereditary predisposition,
although a recent study of 7000 twin pairs in Sweden by Edfors, indicated
that concordance for asthma in identical twins is only 18 percent, a
surprisingly low figure which suggests a far greater role for environmental
factors than had been thought previously.
In so-called “extrinsic” asthma, comprising possibly 40-60 percent of

cases, a specific antibody, reagin, is demonstrable in the blood serum and is
also present in the bronchial tissue of the predisposed individual. Binding of
antigen to this specific antibody (immediate hypersensitivity, type I) results
in the release of several substances, or mediators. These are still not fully
understood. Histamine, serotonin, and bradykinin have been implicated, as
has a less clearly identified, slow reacting substance probably released from
polymorphonuclear leucocytes. So, more recently, have prostaglandins. Mathe

and his colleagues, measuring airway conductance, found that ten asthmatic
subjects were almost 8000 times more sensitive to prostaglandin F2a than
were ten matched control subjects.
Factors governing the release and activity of such substances have also
not been completely elucidated, particularly in the substantial proportion of
cases where no extrinsic allergens can be demonstrated. Pulmonary
infections are frequently associated with asthma, but it is not always known
whether these constitute specific or nonspecific precipitants, or
complications developing after the asthmatic process is already underway.
A crucial question for our purposes is whether the immunologic-allergic
responses of the body are independent of influences from the brain. There is
evidence to indicate a connection. Hypothalamic lesions or electrical
stimulation of hypothalamic areas can induce changes not only in the
autonomic nervous system but in immunologic reactivity. Tuberal lesions
have proved capable of protecting the rat against fatal anaphylactic shock. An-
terior, but not posterior, hypothalamic lesions have had similar protective
effects in the guinea pig. In that species they have led to a significant decrease
in circulating antibodies. It may thus, in Szentivanyi’s words, “be possible to
profoundly alter the anaphylactic reactivity” of various animal species.
Immunological and allergic factors may thus interact with
neurophysiological and neurochemical influences on the pulmonary tree. The
latter are complex in their own right. The role of the parasympathetic nervous
system is a case in point. Vagal stimulation and parasympathomimetic agents
produce an asthmalike response of the bronchial tree. Vachon et al. have
elicited a short-lived and mild but definite decrease in airway conductance in
normal subjects by sudden immersion of their heads in water, apparently

eliciting a vagal response via a central link, the so-called “diving reflex.”
These more or less pure parasympathetic nervous effects tend to be
transient and relatively mild. Airway-conductance deficits of from 15 to 20
percent are the rule. (We shall see that this holds also for effects of simple
suggestion, which may also be vagally mediated.) Moreover, pharmacological

blockade of the parasympathetic nervous system, or even vagotomy, have not
proved effective in treating asthma. The theory that asthma represents a
“vagotonic” disorder, prevalent at the turn of the century, was largely eclipsed
in succeeding years by immunological advance.
However, careful experiments by Gold and his colleagues have forced a
reconsideration of the role of the vagus. Using dogs allergic to known

antigens, they demonstrated that vagal blockade, both afferent and efferent,
could eliminate the experimentally induced sharp rise in airway resistance.
They showed furthermore, that unilateral challenge of one lung with antigen
resulted in bilateral bronchoconstriction, also inhibited by vagal blockade on
the challenged side. They concluded that “vagally mediated reflex broncho
constriction, possibly arising from epithelial irritant receptors, is a major
component of acute, antigen-induced canine asthma.” Only further
investigation can tell whether these striking findings will be applicable in
human asthmatic disease.
Advancing knowledge about the sympathetic nervous system adds to
this picture of intricately balanced adaptive regulation of airway caliber.

Ahlquist’s formulation of alpha- and beta-adrenergic receptors, as two
systems which have both overlapping and antagonistic functions, has drawn
attention to the role of these receptors in asthma. Some evidence has been
offered that the human lung has alpha adrenergic receptors, stimulation of
which, contrary to usual thinking about adrenergic activity, can induce mild
broncho constriction, although other evidence is contradictory on this point.

What is unequivocal is the fact that beta-adrenergic agents have maximal
bronchodilating action, tending to override parasympathetic activity. The
most widely used, potent, short-range agent, having predominantly beta-

adrenergic activity, is isoproterenol.
These facts have led to another line of investigation. Szentivanyi,
working with mice, which usually show little allergic reactivity, exposed them
to Bordetella pertussis and found that they then developed marked sensitivity
to histamine and to various antigens. He suggested that this altered state was
an animal model of “beta-adrenergic blockade” and proposed a sweeping
hypothesis: namely, that the key feature in human asthma was such a
“blockade” of beta receptors, leaving the lungs prey to bronchoconstrictive
reaction upon exposure to allergens, as well as to other noxious stimuli,
including cold, infection, and emotional arousal.
Human studies yield some support for the clinical importance of this
concept. It is well known that asthmatics are dangerously sensitive to the

beta-adrenergic blocking agent, propranolol. Although earlier investigations
using relatively insensitive methods failed to show a pulmonary effect in
normal subjects, McNeil and Ingram, using the body plethysmograph to
measure five normal subjects, produced beta blockade by propranolol and
found marked increase in airway resistance, varying from 40 to over 100
percent. These findings in normal subjects of responses which approached

the asthmatic range are unusual. They support the possibility, which is
though by no means a certainty, that deficient beta- adrenergic responsivity
could play a part in asthma. If so, we should note, it would not necessarily
represent a fixed receptor lesion, but might equally well result from a
reversible deficiency of circulating catecholamines (as suggested by Mathe.)

Conceivably this could play a role in the nocturnal incidence of many
asthmatic attacks, although evidence is unclear on this point.
Understanding is still incomplete of the additional steps mediating

cellular responses following the action of catecholamines at receptor sites.
The second messenger system, adenosine monophosphate (cyclic AMP), is
probably involved; and other messenger systems may play various roles (as
indicated in the earlier reference to prostaglandins). For present purposes it
is important to indicate the existing pathways that link brain processes with
those occurring at the peripheral cellular level.
Obviously all these facts have important pharmacological implications.

As noted, atropine and antihistamine drugs have only limited influence on the
asthmatic process, in contrast to the powerful short-term effects of beta-
adrenergic agents, notably isoproterenol. In severe asthma, one encounters
limits posed by excitatory adrenergic side effects, particularly cardiovascular
ones, as well as by the still puzzling phenomenon of “fastness” to adrenergic
agents. Other drugs, such as aminophylline and especially corticoid

substances, have important bronchodilatory action. The latter, as we shall see
later, have their own complications, although so far no satisfactory substitute
has been found for them.
An intriguing speculation is that tricyclic antidepressant drugs, thought
to mobilize catecholamine stores in the brain, might have some beneficial
central and also peripheral effect in asthma; preliminary evidence supports

such a possibility, though the putative mode of action is obscure.
To summarize: Physiological regulation of lung function represents a
complex adaptive balance; its accurate study is necessary to provide precise
knowledge about the wide range of pathophysiological respiratory function
encountered in asthma.
Immunologic-allergic reactions can lead to a broncho obstructive
asthmatic response. However, it seems unlikely that they are the sole cause of
asthma, particularly in the substantial number of chronic asthmatics without

clear evidence of extrinsic allergy. There is reason to believe that
immunological systems may be integrated with the parasympathetic nervous
system centrally or peripherally or both. Nervous influences may augment or
decrease the final broncho obstructive process.
The sympathetic nervous system may also be important in the etiology
of asthma. Relative deficiency of beta-adrenergic function may aggravate the
disorder because of failure to counteract persistence of basic immunologic

and/or parasympathetic nervous activity. A second, radical hypothesis is that
some sort of “beta-adrenergic deficit” is fundamental in asthma, allowing
allergic as well as other noxious influences to produce the disorder. A third,

more general possibility is that there is a reciprocal balance between
bronchodilating (beta-adrenergic) and bronchoconstrictive (immunologic
and parasympathetic) influences, both having links to the brain; and that
asthma may represent an acute or chronic imbalance between the two.
Clearly mechanisms are available permitting psychological factors to
play a role in asthma, either in conjunction with allergy or possibly at times
by themselves. We next must ask what is the psychophysiological and psy-
chosocial evidence for their activity.
Psychophysiological Observations
Acute Exacerbation and Remission
The physiological considerations just mentioned may throw light on a
paradox that has puzzled students of asthma. Acute attacks often occur in a
setting of turmoil and anxiety, both in adults and children. Hahn found
elevations in both heart rate and skin temperature in asthmatic, as compared
with normal, children and concluded that there was sustained activation of
some parts of the sympathetic nervous system. One is faced with the
troublesome question of why the asthmatic patient, in a state of turmoil and

arousal, does not “cure himself.”
Experimental stress should throw some light on this matter. Mathe and
Knapp used as stressful stimuli a film and a mathematical task carried out
under negative criticism. No effort was made to differentiate the “first-day”
stress from these experimental stimuli. Their subjects were eight mild
asthmatics free of symptoms and not requiring medicine, and eight
comparison subjects matched for age and socioeconomic status. All dietary
and activity factors relevant to catecholamine excretion were controlled.
Asthmatics and normals alike responded with increase in heart rate, blood
pressure, and circulating corticoids under stress as compared to the control

day. As expected, asthmatics differed significantly in their respiratory
responses, showing a decrease in airway conductance, as well as slowing of
respiration. In addition they showed a highly significant difference in free
fatty acid response and epinephrine excretion. Both of these measures were
elevated in the control subjects under stress but remained strikingly constant
in the asthmatic subjects. Subjectively the asthmatics also reported increases
in anxiety and in overall affect but differed on one emotional dimension: they
reported significantly less anger in the provoking experimental
circumstances. A partial repetition of this work, confirming the faulty
mobilization of epinephrine excretion, has been recorded by Bernstein and
Greenland. These findings are consistent with the view that some kind of
adrenergic defect does play a role in acute asthma.
Physiological considerations are also important in evaluating studies of

learning in bronchial asthma. Classical conditioning of asthma was reported
by Noelpp-Eschenhagen and Noelpp who exposed guinea pigs to an allergic

stimulus, provoking a dyspneic asthmalike response; later this was obtained
merely by introducing the animals to the experimental chamber. More
recently Justesen, Braun, et al. described similar conditioned “asthma” in
guinea pigs and used a variety of pharmacological influences to affect this
response. Both of these studies must be questioned, however, in the light of
the careful work of Ottenberg and Stein and of Stein and Schiavi. These
authors showed that the preponderant effect observed in attempts at
conditioning is hyperventilation, presumably as part of a diffuse stress
reaction. By careful measurement of airway resistance they were able to

identify an apparently true asthmatic response and to obtain this in a small
number of animals as a true learned response. However, it readily
extinguished, and extrapolation to the human disorder is difficult.
In humans, Dekker, Pelser, and Groen attempted to show conditioning.
However, their results were inconstant and their measurement technique, the
timed vital capacity, was relatively crude. Effects of suggestion or pseudo-
conditioning could not be excluded in those cases who did show some
increase in timed vital capacity. Sloanaker and Luminet used a classical

paradigm, exposing subjects in a closed-breathing circuit to a parasympatho-
mimetic stimulus (mecholyl) preceded by a tone. In a small number of
instances they obtained a possible conditional asthmalike response, but,
again, chance or suggestive effect could not be excluded. We must conclude

that there is no convincing evidence for classical conditioning in the strict
sense as a cause of bronchial asthma in the human. The possibility remains
that classical sequences, such as strong emotions associated with prior
asthma, may serve as conditional triggering stimuli for subsequent attacks.
An alternative approach is found in the operant paradigm. Vachon used
the respiratory resistance unit, which gives a breath-by- breath feedback of
information; this was computer processed and fed back to subjects. He

worked with two groups of mild asymptomatic asthmatics, fifteen in one and
thirteen in another. They were instructed to keep a red light on, programmed
to flash when their resistance fell below a critical level. They were also given a
monetary reward. The result was a “learned” drop in airway resistance in

both groups of experimental subjects. They differed significantly from control
subjects exposed to the same situation but given purely random
reinforcement. The decrease in resistance was modest, about 15 percent.

How reproducible and lasting, in short, how clinically significant the change
was, remains to be determined, as does the question of whether its extent can
be increased.
Suggestion (which perhaps should be regarded as a variant of learning,
capitalizing on either acquired associations, or implied reinforcement, or
both) has also intrigued students of asthma ever since Sir James McKenzie’s
vivid description in 1886 of “rose asthma” (that is, acute coryza and
respiratory congestion accompanied by wheezing) induced in a young woman

by the sight of a paper rose. Dekker and Groen reported a number of attacks
in subjects, which followed exposure to pictorial or verbal suggestions of
objects or substances to which they were sensitive. Their results were not
uniform; the extent and mechanism of the asthmalike response remain
unclear. Luparello et al. and McFadden, Luparello, and Lyons carried out body
plethysmographic studies of forty subjects exposed to saline aerosol,
suggesting that it was either an allergenic precipitant to which they had been
found sensitive, or a bronchodilator. In approximately half of their subjects
they found clear-cut changes in airway conductance in the suggested

direction. The effect was blocked by atropine, pointing to an acute vagal
influence. Weiss was unable to confirm this suggestive effect in children,
possibly because he used less sensitive measures. White also, using the less
sensitive timed vital capacity, attempted by hypnosis to influence asthmatics
suffering from clinical disease. As a group they reported subjective relief, but
gave no objective evidence of improved pulmonary function.
Environmental change has played a time-honored role with asthmatics,

particularly children. Many clinical observations have indicated that when a
child is sent away from his family, whether to a hospital, school, or camp, his
asthma improves, at least initially. The suspicion followed that one might be
removing the child from noxious interaction with family members, especially
his mother. Abramson and Peshkin have even talked of the beneficial effects
of “parentectomy.”
An obvious question is whether social or allergenic factors were
changed. Lamont and his collaborators hospitalized children allegedly
sensitive to house dust in their homes. The investigators then secured house
dust from each home and distributed it copiously in each child’s hospital
room. In nineteen of twenty cases no asthma ensued. Purcell et al. carried out
an even more rigorous experiment with thirty-five children. They paid their
parents to take a vacation away from home, and brought in an experienced

nurse to make daily measurements of medication, respiratory symptoms, and
peak air flow. Though some children seemed to have mild anticipatory
anxiety, at times accompanied by symptoms, the main effect was, as
predicted, improvement in their asthmatic status in the absence of their

parents. Again this was modest in scope and occurred in about half of their
subjects. It was of further interest that, on the basis of a brief specially
designed diagnostic interview, the authors were able to predict with a high
degree of success which children would show improvement and which would
not.
Such observations on separation from the home environment fit with
earlier reports of Purcell, Bernstein, and Bukantz, indicating that two types of
children appeared to be admitted to the Children’s Asthma Research Hospital

in Denver. They labelled these rapid remitters and steroid dependent,
respectively. The former cleared up rapidly; the latter had persistent
intractable symptoms and required continued steroid medication. The
authors found more obvious neurotic difficulties, both in the children and in
their families, in the rapid remitters. They postulated two distinct types of
asthma, one more psychosocial in origin, the other more biological. However,
one cannot be sure that they ruled out more subtle emotional conflicts,
perhaps deep-seated and masked by denial, nor that they excluded a possible
physiological chain of events which kept children bound to maintenance

steroids, partly on an iatrogenic basis. We will see a similar debate about
long-term personality trends in asthmatics. It is worth noting that Kinsman,
Luparello, and their colleagues, studying acute symptom patterns in adults,
rather than finding simple dichotomous distribution, noted a complex
patterning of subjective symptomatology, based around five clusters of
symptoms: panic-fear, irritability, hyperventilation-hypercapnia,

bronchoconstriction, and fatigue.
To summarize: Acute changes in airway conductance can occur in

response to psychosocial stimuli in certain subjects. Presumably these are
mediated by the parasympathetic nervous system, that is, vagal influences on
the upper airways.
Somewhat more sustained changes in airway conductance, probably
involving altered neuroendocrine balance, may be related to specific

impairment of epinephrine mobilization. Conceivably this may be a function
of altered patterns of arousal, in particular partial mobilization of aggressive
impulses along with inhibition of their full expression.
These findings point to avenues whereby learning may influence
moment-to-moment airway patency. Classical conditioning has yet to be
demonstrated to play a significant role in human asthma, although its
participation in triggering attacks cannot be excluded. Possibly more

important is the role of operant learning, in which subjects achieve change to
gain reinforcement. Preliminary evidence suggests that this can influence
airway resistance, though the extent and lasting nature of the effect remains
to be shown.
Regardless of the exact nature of mediating pathways, there is strong
evidence that remission of asthma may be brought about in certain subjects
by interruption of on-going pathogenic interaction, especially with parental
figures. The assertion remains open, but not proved, that these subjects
represent a distinct subgroup, comprising about 50 percent of severe

perennial asthmatics; they may have prominent “neurotic” elements in their
exacerbations, in contrast to other patients with a more permanent “organic”
basis.
Psychosocial Observations
Long-term Factors in Bronchial Asthma
It seems wise to return to the assumption stated earlier that asthma as a
long-term disorder almost invariably requires some biological vulnerability,

hereditary or (conceivably in some instances) acquired in early years. The
classical life history is that of a child with a positive family history who
develops allergic manifestations, usually eczema, in his first year of life,

followed by respiratory difficulty, coming on gradually in the second or third
year, often associated with infection, which then develops into typical
periodic obstructive disease running its complex fluctuating course.
Although the predisposition is probably always lifelong, many major
variations occur in its course. Approximately half of the children with

infantile eczema do not develop asthma. A crucial study of family differences
among those who do and those who do not has been undertaken, but not yet
completed, by Meijer. Asthmatics change with chronological age. There is
allegedly a preponderance of males among asthmatic children, and of females

among adults, though recent accurate studies bearing on this distribution are
not available. We do know that some children “grow out” of asthma in

adolescence. While they are growing out, others are “growing in.” Asthma in
midlife seems to have special features. It may run an acute, even fatal course;
often it seems to resemble a midlife depression, as illustrated in cases
described by Knapp and Nemetz. Recovery, when it takes place, may seem
relatively complete. Often in such cases a strong family history is absent. As
with many chronic diseases, a sudden onset relatively late in life may carry an
improved prognosis, providing the patient weathers the acute phase
successfully.
Other specific features have been sought in populations of asthmatic

patients. Studies purporting to show EEG abnormality have been reviewed by
Leigh and Pond, who conclude that asthmatics are not different from other
“psychiatric” patients; the authors explicitly leave open the rather tenuous
possibility that all such patients may differ from “normals.”
The incidence among different cultural groups is unclear. Anecdotal
reports have suggested a higher frequency of asthma among Puerto Rican

immigrants to large inner cities, such as New York and Boston. However, valid
epidemiologic evidence has not been forthcoming; and the relative role of
sociocultural stress, as against air pollution, inadequate heating, infection,
dietary deficiency, and other factors, cannot be ascertained.
The family structure of asthmatics has been a focus of much attention. A
number of studies have dealt with mother and child. The early notion of a
“rejecting” mother yielded to that of an “engulfing” one. An investigation by
Block et al. suggests that clinicians working with asthma are not in complete
agreement about maternal characteristics, raising the possibility of more than
one subgroup of mothers and children. Freeman and her colleagues bring
evidence that there may be a reciprocal relationship between the allergic
potential of a child and psychopathology in the mother. The authors suggest
two types of disease, one primarily biogenic, the other sociogenic. This and
other efforts to dichotomize the population of asthmatic mothers and chil-

dren—as in the work of Purcell, Bernstein and Buchantz already mentioned—
risk overlooking the role of denial. Some mothers may have a powerful need
to overemphasize putative biological contributions to the children’s illness

and to minimize psychosocial conflict. Jacobs and his colleagues in two
studies tested young adult males with hay fever and mild asthma, using
selected indices of biological reactivity, along with a battery of projective tests
administered on a “blind basis.” The subjects perceived their mothers

retrospectively as controlling or rejecting or both; their feelings in this
respect differentiated them from the healthy comparison group. It was
possible, on a basis of both “allergic potential” alone and “psychologic

potential” alone, for blind judges successfully to select individuals who
showed actual manifestations of allergic disease. Jacobs’ hypothesis was
additive: that both psychological and biological factors are widely distributed
in the allergic population and that their combined strength determines the
severity of the disorder.
We are entering an area which requires complex estimates of family
constellations and inner psychological processes. Surface factors may directly
contradict and mask hidden elements. Objective methods to measure such
balanced forces are not available, and we must rely on more subjective
clinical judgments. These have come chiefly from psychoanalytically

oriented investigations of a small number of cases. Some of these are sum-
marized below, recognizing their limitations but feeling that their insight
cannot be ignored. It remains to be seen whether future large-scale,

methodologically more refined, studies will verify them.
Examining a small number of children in psychoanalytically oriented

psychotherapy and in psychoanalysis, Jessner and her associates found
evidence of continuing oscillation between attempts on the part of the
asthmatic patient to separate from the mother and to achieve intense erotized
closeness. Sperling elaborated this pattern, underlining the existence of faulty
differentiation between mother and child. She felt that mothers of asthmatic
children, like those of young patients with other psychosomatic diseases,

could tolerate their child only when ill. This viewpoint, phrased in other
terms, suggests that the mother may inadvertently provide powerful
sustained reinforcement of the asthmatic process.
Fathers may play an important auxiliary role. Jacobs’ retrospective
studies with allergic subjects suggest that fathers of asthmatics tend to be

absent in one or another way, either physically out of the home, aloof, or in-
effective, so that they fail to correct the imbalance between mother and child.
These findings might lead one to expect consistent characterological

features in patients suffering from asthma, and there is clinical evidence that
these do exist. Some of them center around conflictual concerns which are
relatively specific and perhaps have a somatopsychic basis: sensitivity to
odors, concern about water, sleep, crying, and use of the voice. Stein and
Ottenberg and Herbert offer evidence that asthmatics as a group have a
heightened sensitivity to odors, which at times antedates the onset of
asthmatic symptoms. McDermott and Cobb reported that fears of water or of
drowning were more common and intense in asthmatics than in comparison
subjects, thus partially confirming what a number of clinicians, for example
Deutsch reported. Excessive secretion in the respiratory tract can lead to a

state in which the individual feels close to drowning in his own fluids, and
such experiences could well mold the anxieties of the asthmatic.
Asthmatic attacks tend to develop at night, often waking the sufferer

from sleep, frequently being interwoven with bizarre sleep patterns. It has
not been possible to identify asthma clearly with the REM phase of sleep, nor
with variations of the diurnal cycle of catecholamine or cortisol secretion,

although all of these features may play some role.
Early studies of asthmatics suggested that weeping, crying, and related
vocalization were often stirred up, yet were conflictual and not easily
expressed. Such “suppressed crying,” as French and Alexander put it in their
familiar formulation, might be part of the acute process of asthma, though
obviously not specific for that disorder alone. Concern with the voice and the
process of speech itself seems at times to be closely related to asthmatic

symptoms, possibly connected with inhibition of powerful primitive
aggressive impulses, as Bacon speculates. Knapp and Nemetz reported a
number of cases in which episodes of aphonia were strikingly interwoven

with asthmatic symptomatology. They discussed the possibility, raised by
earlier clinicians, that sensitizing life experiences, including close
interpersonal experiences with an individual suffering from respiratory
disease, might contribute to the later development of asthma as a form of

primitive or “pregenital” conversion symptom. Occasional reports keep this
possibility alive; for example, a striking case mentioned by Lofgren, in which a
patient had been nearly strangled in childhood, and an example of Coolidge’s

of asthma in three successive mother-daughter generations.
These reported conflicts influence other habitual character traits.

Alternation of asthmatic symptoms with overt psychotic manifestations may
occur, although this appears to be the exception, not the rule. Chessick et al.
reported that the most frequent chronic disease among narcotic addicts at the
U. S. Public Health Hospital, Lexington, Kentucky was asthma.
Other clinical observations have suggested that asthmatics as a group
have unusually strong passive and dependent personality traits, reflecting
needs to maintain gratification and support from key persons in their envi-
ronment. This form of personality organization is obviously not unique to
asthmatics. At times, furthermore, it appears to be subjected to a kind of
personality “counterrevolution” in which a surface picture of marked
assertiveness becomes dominant, perhaps assisting the individual in some

way to overcome his illness. Frequent anecdotal reports describe children
hospitalized for asthma, recovering symptomatically from their disorder and
becoming aggressive behavior problems. The more frequent finding is that
hints of hidden aggressive impulses, appearing only briefly, are followed by

intensification of asthma, often with evidence of guilty depressive feeling. In a
study of psychoanalytic material from one patient, two psychoanalysts using
a model of primitive impulse-arousal plus failure of psychological defenses,

studied notes of sessions immediately before twenty-five exacerbations of
asthma and twenty-five comparison sessions from the same period of the
treatment. Notes were edited to remove medical cues; as a further control

they were given to two allergist-internists who attempted the same task. The
psychoanalysts were able to select “asthmatic” contexts from neutral com-
parison contexts with significant success, whereas the allergists’ results were
only at a chance level.
A clinical hypothesis to account for these observations is that many
asthmatics have a deep and early developmental personality defect, which
leaves them both attached to a parental figure and subject to powerful ag-
gressive impulses of an early infantile type. Some of these may have a
particularly sadistic flavor. The hidden sadistic components have been
striking in a series of our patients studied psychoanalytically. Full emergence
of such impulses would threaten their “partial symbiotic” attachment, so that

when aggression is aroused it is in some way “switched off” and results in
asthma. (One is tempted to speculate about connections with a possible
parallel defect in adrenergic catecholamine mobilization mentioned earlier.)
It is interesting that detailed biographical material of a famous asthmatic,

Marcel Proust, supports this picture of a passive loving son attached to and
deeply identified with his mother. He showed unmistakable evidence of
hidden sadistic perverse impulses.
To summarize: Long-term psychological or social patterns associated
with asthma can be defined only tentatively. There appears to be an

interaction between hereditary vulnerability and the early environment. The
exact nature of their respective roles is uncertain; so is the question of
whether we are dealing with a simple dichotomy of allergic versus sociopsy-

chologic cases, as advocated by some, or with a more variable spectrum.
Concerns with odors and water, and conflicts over crying and over use
of the voice may be partly related to heightened somatic responsivity in a
somatic subject. Other characterological features, although colored by
somatic illness, often antedate it and appear related to early experience with
the human environment. These pertain to fears of separation from the

mother, and to primitive impulses often of a sadistic destructive nature,
deeply hidden and defended against by passive, dependent, and masochistic
personality organization. Such traits are not unique for asthmatics but may
interact with other factors localizing a somatic process in the pulmonary

system, and thus contribute to the overall picture of the disease.
Therapeutic Considerations
If, indeed, we are dealing with a lifelong, often life-threatening disorder,
having multiple etiologic factors and running a fluctuating course, the

problem of evaluating therapy is inevitably difficult.
These considerations apply to all therapy in bronchial asthma, including
reports of medical measures. As Bates, Macklem, and Christie remark: “In no
other common disorder have so many different therapeutic approaches been
adopted and it is suspicious that many of these are credited with improving
the condition.” They add that “spontaneous improvement and remission are
common, often occurring independently of any change in treatment,” though
one must add that a careful search for any change in life situation must be
conducted before one can be sure change is entirely “spontaneous.” If there is
any truth to the assertion that asthmatics are sensitive to personal
relationships, the influence of these must be considered in reports of success
with allergic or other measures. In all assessments of therapeutic results the

severity of cases treated must be carefully specified, as well as the amount
and kind of all modalities of treatment. Therapy which produces amelioration
must be distinguished from therapy which approaches long-range cure. As a
rule, ethical considerations demand, at least in patients with asthma of any

severity, that some medical allergic management go along with psy-
chotherapy.
A particular problem is posed by steroid medications. In the short run
these have changed the picture of the management. Terrifying episodes of

status asthmaticus can be brought under control and immediate dangers to
life greatly diminished. However, the longterm effects are far from clear.
Schneer cites evidence that mortality in children with asthma is as great a

decade after the introduction of steroids as it was before their advent.
Certainly the persistent complications and side effects, i.e., electrolyte

imbalance, hypertension, or tendency to peptic ulcer, present hazards. They
are compounded by the states of dependence which patients develop. These

appear to have a clearly physiological basis. Removal of steroids leads to a
characteristic state of lassitude and weakness, and in asthmatics, a proneness
to explosive and drastic exacerbation, sometimes itself fatal. Yet occasionally
in our experience, possibly aided by a variety of therapeutic modalities,
including careful medical weaning, also with psychotherapeutic support,
patients who have been receiving large amounts of steroid medication do

recover and function without the need for medication.
Antidepressive Measures
These have been tried in a sporadic fashion with asthmatics. In sudden
late-life asthma, electric shock has been occasionally used, although there are
no systematic evaluations of its effect. Experimental evidence of possible
bronchodilatory effects of antidepressant medication has led to clinical

reports of their use, though these are scattered and inconclusive.
Suggestive Measures, Hypnosis
Although hypnosis may be unable to affect the fully established
pathophysiological process, it is possible that hypnotherapy may have long-

term benefits. Falliers studied 120 asthmatic patients, using 115 control
subjects, also suffering from asthma. The experimental group was treated
with brief rapid-induction hypnosis at weekly intervals. Control subjects were
treated with body relaxation. Both groups showed improvement, the females
significantly more with hypnosis. By the end of a year in the hypnotized group
59 percent were better and 8 percent worse; the control-group figures were
43 percent better and 17 percent worse; the difference between the groups
was significant at the 5-percent level. One patient in each group was dead.
One cannot exclude a general “physician-interest” effect, and it would be

interesting to know more about the exact characteristics of the patients
involved. Nevertheless, a beginning in the study of an important treatment
modality is represented here.
Relaxation
This form of quasisuggestive therapy has also been tried, mostly with
children. A study by Alexander et al. shows some effects, mostly in mild cases,
of relaxation instructions, relayed to the subjects in different ways. The
approach has a certain logic. Clinically many asthmatics state that if they can
only “relax,” their tightness, wheezing, and congestion seem to improve. It
will be necessary to await further results before we can fully assess the
clinical importance of this approach.
Behavior Modification
There are only a few systematic studies of this form of treatment.
Walton used Wolpe’s method of “reciprocal inhibition” successfully with one

case. Moore extended his observations in a controlled study, comparing
systematic “desensitization” with two other treatment modalities, simple
suggestion and a relaxation therapy. She studied twelve subjects, half of them
children, in a balanced incomplete block design so that two forms of
treatment were given to every patient, and each of the three treatments could
be compared in eight subjects. All three forms of treatment led to some
subjectively reported improvement. Significantly more improvement in peak
air flow, the physiological measure used, was found in the group which had
reciprocal inhibition. The strength of this study lies in the fact that the
patients were their own controls. However, the numbers were small. A major
share of the variance was contributed by two subjects who received recip-
rocal inhibition as their first treatment, and had a rather marked effect from
it. It is possible that individual differences in such a small group of subjects
still played a major role. Few details were given about the initial status of the
patients and the severity of their illness. The study needs replication, but is
nevertheless a model for systematically controlled investigation of

therapeutic approaches in this area.
Operant Conditioning
This method, using the biofeedback model, is technically available after

the initial studies of Vachon, but it has not yet been systematically applied as
a therapy.
Group Therapy
Groen reports an intensive group-therapy experience in the
Netherlands. It involved weekly meetings with patients and an extensive

supportive medical and milieu regime. Results were positive, but the large
number of variables involved makes definitive assessment difficult.
Long-term Psychoanalytically Oriented Psychotherapy
This method was applied to the original series of twenty-six adults and
children reported by French and Alexander. They described substantial
improvement in their series but did not give detailed physiological or other
follow- up data. The approach has also been applied to severely incapacitated
patients by Knapp, Sperling, and others. One can argue logically that such a
long-term approach is indicated if one accepts the evidence of early

disturbance in mother-child relationships and deep, primitive personality
disorganization in many asthmatic patients. The classical analytic approach
must be modified, most observers state, as many individuals suffer from se-
vere personality disturbances. It is necessary to think of severe asthmatics as

suffering from “borderline” or “narcissistic” disturbance, though this may be
masked by many effective areas of functioning. Different strategies are
possible within this general psychoanalytic framework, such as the more

egonurturant empathic approach advocated by some, or a more confrontative
and active attack on the defensive and gratifying “use” of symptoms by a
subject, as advocated by Sperling. No real evidence can decide between these,
considering the lack of definitive long-term assessment of all therapeutic
results with asthma.
In conclusion: Given the tentative nature of therapeutic evidence, what

should a psychiatrist advise for an asthmatic? He is probably wisest if he
approaches patients with this “psychosomatic” disorder on the basis of their
obvious psychopathology. As with all forms of psychiatric treatment at this
time, he must be guided by his own beliefs and experience, and must try to
carry out therapy systematically with the hope that time and the
accumulation of clinical knowledge will make it possible to sort the wheat of
results from the chaff of claims.
Two contrasting cautions are important: the psychiatrist should respect
the potential seriousness of the biological process and utilize sophisticated
medical knowledge, which in most cases means a sophisticated medical col-

league, as part of the total treatment plan. Yet he should respect the
remarkable capacity of psychological conflict to lurk behind a screen of “real”
physiological symptoms; he must be prepared to stick to his insight when he

senses such conflict, though the patient, the family, and even the attending
physician may rationalize it away as an unfortunate by-product of physical

suffering. Time-limited and controlled approaches are valuable for purposes
of comparative study, particularly of mild cases; but in severe asthma one
faces a complicated problem of long-term management, and a long-term
relationship with an individual whose somatic and psychic difficulties are
extraordinarily intertwined.
Bibliography
Abbasy, A. S., M. S. Fahmy, and M. M. Kantoush. “The Adrenal Glucocorticoid Function in

Asthmatic Children,” Acta Paediatr. Scand., 56 (1967), 593-600.
Abramson, H. A. “Evaluation of Maternal Rejection Theory in Allergy,” Ann. Allergy, 12 (1954),

129.
Abramson, H. A. and M. M. Peshkin. “Group Psychotherapy of the Parents of Intractably Asthmatic

Children,” J. Childr. Asthma Res. Inst. Hosp., 1 (1961), 77.
Ahlquist, R. P. “The Adrenergic Receptors,” J. Pharm. Sci., 55 (1966), 359-67.
Alexander, B. “Systematic Relaxation in Asthmatic Children,” Psychosom. Med., 34 (1972), 389.
Alexander, F., T. M. French and G. Pollock. Psychosomatic Specificity, Vol. 1, Experimental Study
and Results. Chicago: University of Chicago Press, 1968.
Anthracite, R. F., L. Vachon, and P. H. Knapp. “Alpha-adrenergic Receptors in the Human Lung,”
Psychosom. Med., 33 (1971), 481-489.
Avni, J. and I. Bruderman. “The Effect of Amitryptymine on Pulmonary Ventilation and the
Mechanics of Breathing,” Pharmacologic, 14 (1969), 184-192.
Bacon, C. “The Role of Aggression in the Asthmatic Attack,” Psychoanal. Q., 25 (1955), 309-324.
Bates, D. V., P. T. Macklem, and R. V. Christie. Respiratory Function in Disease, Philadelphia:
Saunders, 1971.
Bernstein, I. L. and R. Greenland. “Catechol Excretion in Asthma,” (Abstract), Fed. Proc., 32 (1973),
813.
Block, J., E. Harvey, P. H. Jenning et al. “Clinicians’ Conceptions of the Asthmatogenic Mother,”
Arch. Gen. Psychiatry, 15 (1965), 610.
Chessick, R. D., M. D. Kurland, R. M. Husted et al. “The Asthmatic Narcotic Addict,” Psychosomatics,
1 (1960), 346.
Coolidge, J. C. “Asthma in Mother and Child as a Special Type of Intercommunication,” Am. J.

Orthopsychiatry, 26 (1956), 165.
Dekker, F. and J. Groen. “Reproducible Psychogenic Attacks of Asthma,” J. Psychosom. Res., 1

(1956), 58-67.
Dekker, F., H. E. Pelser, and J. Groen. “Conditioning as a Cause of Asthmatic Attacks,” J. Psychosom.
Res., 2 (1957), 96.
Deutsch, F. “Basic Psychoanalytic Principles in Psychosomatic Disorders,” Acta Ther., 1 (1953):

102-111.
Dudley, D. L., T. H. Holmes, C. J. Martin et al. “Changes in Respiration Associated with Hypnotically
Induced Emotion Pain and Exercise,” Psychosom. Med., 26 (1964), 46-57.
Edfors-Lubs, M. L. “Allergy in 7000 Twin Pairs,” Acta Allergol. 26 (1971), 249-285.
Falliers, C. J. “Hypnosis for Asthma—A Controlled Study,” Br. Med. J., 31 (1968), 476-479.
Freeman, E. H., B. F. Feingold, K. Schlesninger et al. “Psychological Factors in Allergy: A Review,”

Psychosom. Med., 26 (1964), 543-575.
Freeman, E. H., F. J. Gorman, M. T. Singer et al. “Personality Variables and Allergic Skin Reactions:
A Cross Validation Study,” Psychosom. Med., 29 (1967), 312-332.
French, T. M. and F. Alexander. “Psychogenic Factors in Bronchial Asthma,” Psychosom. Med.
Monogr., 4 (1941), 2-94.
Gold, W. M., G. R. Kessler, and D. Y. C. Yu. “Role of Vagus Nerves in Experimental Asthma in
Allergic Dogs,” ]. Appl. Physiol, 33 (1972), 719-725.
Goldman, M., R. J. Knudson, J. Mead et al. “A Simplified Measurement of Respiratory Resistance by

Forced Oscillation,” J. Appl. Physiol., 28 (1970), 113.
Grieco, M. H., R. N. Pierson, and F. X. Pi Sunyer. “Comparison of the Circulatory and Metabolic
Effects of Isoproterenol, Epinephrine and Methoxamine in Normal and Asthmatic
Subjects,” Am. J. Med., 44 (1967), 863.
Groen, J. “Experience with and Results of Group Therapy with Bronchial Asthma,” J. Psychosom.
Res., 4 (1960), 191.
Hahn, W. “Automatic Responses of Asthmatic Children,” Psychosom. Med., 28 (1965), 323.
Hartman, E. The Biology of Dreaming. Springfield, Ill.: Charles C. Thomas, 1967.
Heim, E., H. Constantine, P. H. Knapp et al. “Airway Resistance and Emotional States in Bronchial
Asthma,” Psychosom. Med., 29 (1967), 450-467.
Heim, E., P. H. Knapp, L. Vachon et al. “Emotion, Breathing and Speech,” J. Psychosom. Res., 12
(1968), 261-274.
Herbert, M., R. Glick, and H. Black. “Olfactory Precipitants of Bronchial Asthma,” J. Psychosom. Res.,
11 (1967), 195-202.
Jacobs, M. A. et al. “Incidence of Psychosomatic Predisposing Factors in Allergic Disorders,”

Psychosom. Med., 28 (1966), 679-695.
Jacobs, M. A., L. S. Anderson, H. D. Eisman et al. “Interaction of Psychologic and Biologic

Predisposing Factors in Allergic Disorders,” Psychosom. Med., 29 (1967), 572-585.
Jessner, L. “The Psychoanalysis of an Eight-Year-Old Boy with Asthma,” in H. I. Schneer, ed., The
Asthmatic Child, pp. 118-137. New York: Harper & Row, 1963.
Jessner, L., J. Lamont et al. “Emotional Impact of Nearness and Separation for the Asthmatic Child
and His Mother,” in The Psychoanalytic Study of the Child, Vol. 10, p. 353—375. New
York: International Universities Press, 1955.
Justesen, D. R., E. W. Braun, R. G. Garrison et al. “Pharmacologic Differentiation of Allergic and

Classically Conditioned Asthma in the Guinea Pig,” Science, 170 (1969), 864-866.
Kelly, E. “Asthma and Psychiatry,” J. Psychosom. Res., 13 (1969), 377.
Kinsman, R. A., T. J. Luparello, K. O’Banion et al. “Multidimensional Analysis of the Subjective

Symptomatology of Asthma,” Psychosom. Med., 35 (1973), 250- 266.
Knapp, P. H. “The Asthmatic Child and the Psychosomatic Problem of Asthma,” in H I. Schneer, ed.,
The Asthmatic Child, pp. 234-255. New York: Harper & Row, 1963.
----. “The Asthmatic and His Environment,” J. Nerv. Ment. Dis., 149 (1969), 133.
Knapp, P. H., C. Mushatt, and S. J. Nemetz. “The Context of Reported Asthma during
Psychoanalysis,” Psychosom. Med., 32 (1970), 167-188.
Knapp, P. H. and S. J. Nemetz. “Personality Variations in Bronchial Asthma: A Study of 40 Patients:

Notes on the Relationship to Psychosis and the Problem of Measuring Maturity,”
Psychosom. Med., 19 (1957), 443-465.
----. “Sources of Tension in Bronchia Asthma,” Psychosom. Med., 19 (1957), 443.
----. “Acute Bronchial Asthma: 1. Concomitant Depression and Excitement and Varied Antecedent
Patterns in 406 Attacks,” Psychosom. Med., 22 (1960), 42-56.
Lamont, J. “Psychosomatic Study of Asthma,” Am. J. Psychiatry, 114 (1958), 890.
Leigh, D. “Asthma and the Psychiatrist. A Critical Review,” Int. Arch. Allergy, 4 (1953). 227.
Leigh, D. and D. A. Pond. “The Electroencephalogram in Cases of Bronchia Asthma,” J. Psychosom.
Res., 1 (1956), 120.
Lofgren, J. B. “A Case of Bronchial Asthma with Unusual Dynamic Factors Treated by

Psychotherapy and Psychoanalysis,” Int. J. Psycho-anal., 42 (1961), 414-423.
Luparello, T. J., H. A. Lyons, E. R. Bleecker et al. “Influences of Suggestion on Airway Reactivity in

Asthmatic Subjects,” Psychosom. Med., 30 (1968), 819- 825.
Luparello, T. J., M. Stein, and C. D. Park. “Effect of Hypothalamic Lesions on Rat Anaphylaxis,” Am.
J. Physiol., 207 (1964), 911-914.
McDermott, N. T. and S. Cobb. “A Psychiatric Survey of 50 Cases of Bronchial Asthma,” Psychosom.

Med., 1 (1939), 203-244.
McFadden, E. R., Jr., R. Kiser, and W. J. DeGroot. “Acute Bronchial Asthma,” N. Engl. J. Med., 288
(1973), 221-225.
McFadden, E. R. Jr., T. Luparello, H. A. Lyons et al. “The Mechanisms of Action of Suggestion in the
Induction of Acute Asthma Attacks,” Psychosom. Med., 31 (1967), 134-43.
MacKenzie, J. N. “The Production of ‘Rose Asthma’ by an Artificial Rose,” Am. J. Med. Sci., 91
(1886), 45.
McNeil, R. S. and C. G. Ingram. “Effect of Propanolol on Ventilatory Function,” Am. J. Cardiol., 18

(1966), 473-475.
Mathe, A. A. “Decreased Circulating Epinephrine Possibly Secondary to Decreased Hypothalamic

Adrenomedullary Discharge; A Supplementary Hypothesis of Bronchial Asthma
Pathogenesis,” J. Psychosom. Res., 15 (1971), 349-359.
Mathé, A. A., P. Hedqvist, A. Holmgken et al. “Bronchial Hyperactivity to Prostoglandin F2 and

Histamine in Patients with Asthma,” Br. Med. J., 36 (1973), 193- 196.
Mathe, A. A. and P. H. Knapp. “Decreased Plasma Free Fatty Acids and Urinary Epinephrine in
Bronchial Asthma,” N. Engl. J. Med., 281 (1969), 234-238.
----. “Emotional and Adrenal Reactions to Stress in Bronchial Asthma,” Psychosom. Med., 33
(1971), 323.
Mead, J., N. Peterson, and G. Brimby. “Pulmonary Ventilation Measured from Body Surface
Movements,” Science, 156 (1967), 1383.
Meares, R. A., J. E. Mills, T. B. Horvath et al. “Amitryptillene and Asthma,” Med. J. Aust., 2 (1971),
25-28.
Meijer, A., and P. H. Knapp. “Asthma Predictors in Infantile Atopic Dermatitis,” J. Psychosom. Res.,
in press.
Miller, H. and D. W. Baruch. “Psychiatric Studies of Children with Allergic Manifestations. I.

Maternal Rejection: A Study of 63 Cases,” Psychosom. Med., 10 (1948), 275-278.
Mithoefer, J. C., R. H. Runser, and M. S. Karetzky. “Use of Sodium Bicarbonate in the Treatment of
Acute Bronchial Asthma,” N. Engl. J. Med., 272 (1965), 1200- 1203.
Moore, N. “Behavior Therapy in Bronchial Asthma—A Controlled Study,” ]. Psychosom. Res., 9

(1967), 257-77.
Morris, H. G., G. Roche, and M. R. Earle. “Urinary Excretion of Epinephrine and Norepinephrine in
Asthmatic Children,” J. Allergy Clin. Immunol., 50 (1972), 138-145.
Noelpp-Eschenhagen, I. and B. Noelpp. “New Contributions to Experimental Asthma,” Progr.

Allergy, 4 (1954), 361.
Oberndorf, C. P. “The Psychogenic Factors in Asthma,” N.Y. J. Med., 35 (1935), 41-48.
Orange, R. P., M. D. Valentine, and K. F. Austen. “Release of Slow-Reacting Substance of

Anaphylaxis in the Rat: Polymorphonuclear Leukocyte,” Science, 157 (1967), 318-
319.
Ottenberg, P. and M. Stein. “Psychological Determinants in Asthma,” Trans. Acad. Psychosom. Med.,
(5th Annual Meeting) (1957), 122.
----. “Learned Asthma in the Guinea Pig,” Psychosom. Med., 20 (1958), 395.
Purcell, K., L. Bernstein, and S. Bukantz. “A Preliminary Comparison of Rapidly Remitting and
Persistently Steroid Dependent Asthmatic Children,” Psychosom. Med., 23 (1961),
305.
Purcell, K., K. Brady et al. “Effect on Asthma in Children of Experimental Separation from the
Family,” Psychosom. Med., 31 (1969), 144-164'
Schiavi, R. C., M. Stein, and B. B. Sethi. “Respiratory Variables in Response to a Pain-Fear Stimulus
and in Experimental Asthma,” Psychosom. Med., 23 (1961), 485.
Schneer, H. I., ed. The Asthmatic Child. New York: Harper & Row, 1963.
Scholander, P. F. “The Master Switch of Life,” Sci. Am., 209 (1963), 92-107.
Schwartz, M. “Heredity in Bronchial Asthma: A Clinical and Genetic Study of 191 Asthma
Probands and 50 Probands with Baker’s Asthma,” Acta Allergol. 5, Suppl. 2 (1952),
1.
Sloanaker, J. and D. Luminet. “Classical Conditioning in Bronchial Asthma.” Unpublished Ph.D.

dissertation, Boston University, 1961.
Sperling, M. “A Psychoanalytic Study of Bronchial Asthma in Children,” in H. I. Schneer, ed., The

Asthmatic Child. New York: Harper & Row, 1963.
Stein, M. and P. Ottenberg. “The Role of Odors in Asthma,” Psychosom. Med., 20 (1958), 60.
Stein, M. and R. Schiavi. “Respiratory Disorders,” in A. M. Freedman, and H. I. Kaplan, eds.,

Comprehensive Textbook of Psychiatry, pp. 1068-1071. Baltimore: Williams &
Wilkins, 1967.
Szentivanyi, A. “The Beta Adrenergic Theory of the Atopic Abnormality in Bronchial Asthma,” J.
Allergy, 42 (1968), 203-232.
----. “Effect of Bacterial Products and Adrenergic Blocking Agents on Allergic Reactions,” in M.
Samter, ed., Immunologic Disease, pp. 356-374. Boston: Little Brown, 1971.
Szentivanyi, A. and G. Fillip. “Anaphylaxis and the Nervous System: 2,” Ann. Allergy, 16 (1958),
143-151.
Vachon, L. “Visceral Learning of Respiratory Resistance,” (Abstract), Psychosom. Med., 34 (1972),

471-472.
Vachon, L., C. J. Brotman, and P. H. Knapp. “Bronchial Tree Response to the Diving Reflex,”
(Abstract), Psychosom. Med., 31 (1969), 447.
Walton, D. “Application of Learning Theory to a Case of Bronchial Asthma,” in H. Eyesenck, ed.,

Behavior Therapy and the Neuroses., pp. 188-189. Oxford: Pergamon, 1960.
Weiss, E. “Psychoanalyse eines Falles von Nervosen Asthma,” Int. Z. Psychoanal., 8 (1922), 440-
445.
Weiss, J. H. “Effects of Suggestion on Respiration in Asthmatic Children,” Psychosom. Med., 32

(1970), 409-415.
Widdicombe, J. G. “Regulation of Tracheobronchial Smooth Muscle,” Physiol. Rev., 43 (1963), 1.
White, H. “Hypnosis in Bronchial Asthma,” Psychosom. Res., 5 (1961), 272.
Zaid, G. and G. N. Beall. “Bronchial Response to Beta Adrenergic Blockade,” N. Engl. J. Med., 275
(1966), 580-584.
Notes
1 Supported in part by Grant MH 11299-05. Grateful acknowledgment is made of the criticism and
assistance of A. A. Mathe, and L. Vachon.
Chapter 29
Disorders Of Immune Mechanisms
Raul C. Schiavi and Marvin Stein
In recent years immunology has progressed from description of the

immune reaction to cellular and molecular analysis of the underlying
mechanisms. The fields of microbiology, biochemistry, and biophysics as well
as other biological disciplines have developed and applied specialized
quantitative techniques which have led to the understanding of immune
processes at the organ, tissue, cellular, and subcellular levels. Immune

phenomena were initially considered in relation to infectious diseases, and as
having a protective and adaptive function. As more knowledge was gathered,
it appeared that immune mechanisms may also be involved in the

development of various pathological states. Allergic disorders were among
the first to be considered as pathological manifestations of immune

processes. Since 1950, with the explosive expansion of information and
techniques in the field of immunology, considerable data has been acquired,
indicating that immune processes are involved in a wide range of pathological
and clinical disorders, including autoimmune diseases, neoplasia, and organ
transplants. Although clinicians now have an increased understanding of the
immunological basis of a variety of illnesses, little attention has been paid to
the psychophysiological aspects of immune processes. The immune system,

similar to the nervous and endocrine systems, plays an important role in
biological adaptation, contributing to the maintenance of homeostasis and to
the establishment of body integrity. The similarity between the function of

the immune and central nervous systems maintaining the integrity of the
organism in relation to the external environment has recently been pointed
out by Salk.
The observation that emotions modify host resistance to infection and
that they may influence the development and course of some hypersensitive
reactions and autoimmune and neoplastic diseases have led some
investigators to propose that immune processes play a significant role in the
mediation of psychological influences in some physical illnesses. This chapter

will review clinical and experimental findings concerned with the influence of
psychosocial processes on immunological reactions. There is an extensive
literature in the area of serum proteins and immunological responsivity in
psychiatric disorders which has been recently reviewed; these data will not
be presented here.
Immune Response
Before considering specific immune disorders, it is important to have an
understanding of the concepts of immune response. The immune response

may be thought of as a complex specialized reaction developed against
foreign proteins or polysaccharide substances known as antigens. The
response is specific for each antigen and usually becomes more intense and
highly specific with each repeated exposure to the specific antigen.
Immune responses consist of an afferent phase, a central phase, and an
effector phase. The borders between these various phases are not clearly
delineated. During the afferent phase antigen is processed and identified as
foreign; during the central phase various processes occur primarily in the
lymphoid tissues which amplify the recognition signal; and in the effector
phase appropriate cells are mobilized to react against the antigen. The
response may be recognized at the effector level either as specific humoral
antibodies elaborated by lymphoid cells, or by an action of specific cells (e.g.,
lymphocytes or macrophages) on the relevant antigen. Circulating antibodies

are usually produced in response to a soluble antigen, whereas cell-mediated
immunity develops in response to an antigen fixed in the tissue. The humoral
antibody response and the cell-mediated response will be briefly reviewed.
Humoral Antibody Response
Soluble antigen passes to the medulla of lymph nodes or the red pulp of
the spleen where it is taken up by macrophages. These cells then appear to
send a message to plasma cell precursors, which lie in close proximity to the
macrophages at the cortico-medullary junction of lymph nodes and in the red
pulp of the spleen. The plasma-cell precursor, probably lymphocytes,
proliferate into antibody-producing cells (plasma cells). Plasma cells contain
all of the systems required for the synthesis and secretion of proteins. This
class of proteins produced by plasma cells is known as antibodies since they
react directly with antigens. They are primarily 7 globulins and, because of
their immunological function, are referred to as immunoglobulins. There are
at least five classes and several subclasses of immunoglobulins in man. The

three major classes are designated IgM, IgG, and IgA.
The IgM antibodies are extremely efficient in binding to particulate
antigens such as bacteria and erythocytes, but not as efficient in binding to

particulate antigens, such as toxins. The IgG system can bind to soluble
antigens, and antibodies are produced for long periods of time. The cells of
the IgA, and perhaps of the IgE system, produce molecules capable of binding
to skin and mucous membranes. Reagins which have been classified as IgE
antibodies are associated with anaphylactic phenomena such as hay fever and
asthma. After the interaction of antigen and IgA or IgE antibodies, histamine
and other pharmacological agents are locally released.
Cell-Mediated Immune Response
If antigen is fixed in tissues, such as a tissue homograft, or in a modified
part of the body’s own tissues, such as skin treated with a simple chemical
sensitizing agent, the response is of a different type than that of the humoral
antibody response. It appears that small lymphocytes passing through the
tissues are sensitized peripherally and then pass down to a local lymph node
where they enter the free area of the cortex follicles. The small lymphocytes
proliferate at this point and become differentiated into large cells with easily
identifiable characteristics. After a few days some of the lymphocytes become
immunologically active leaving the local lymphoid tissue to go to other lymph

nodes where other immunologically active lymphocytes are propagated. At
this point, the immunologically active cells can be found in the peripheral
blood and pass to the graft where they can initiate the process of graft
rejection or react with an antigen deposit in peripheral tissue to produce an

inflammatory response such as that which occurs in chemical contact
sensitivity or the tuberculin reaction. Immunological responses carried out by
sensitized cells in the absence of circulating antibody include delayed

sensitivity, transplantation immune reactions, and various autoimmune
phenomena. The cellular systems capable of carrying out these processes may
form part of a surveillance system the function of which may be to eliminate
cells arising as a result of mutation, e.g., neoplastic cells.
Infectious Diseases
The concept of multiple causation of disease is well illustrated by the
observation that colonization of an organism by bacteria does not necessarily

result in illness. Clinically, it has been noted for many years that infectious
diseases are the result of host-microorganism interaction. In order to
understand the disease process, it is necessary to investigate the aspects

which determine the capability of the microorganism to initiate infection and
those which influence the host response to the infection. A great deal of
attention has been devoted clinically and in the laboratory to the
identification of microorganisms involved in infectious diseases and there has

been growing interest in the factors which modify host resistance. Among
these, psychosocial influences have been shown to play a role in infectious
diseases. For example, several studies have shown that psychological

variables influence the rate of recovery from infectious mononucleosis and
influenza, and the development of lesions due to herpes simplex virus.
Psychological factors have also been demonstrated to modify the onset and
course of pulmonary tuberculosis and experimentally it has been shown that
the tuberculin reaction can be inhibited by means of hypnosis.
There are, however, few data regarding the physiological mechanisms
involved in the mediation of psychological factors on host resistance in man.

The study of Meyer and Haggerty represents one of the few attempts to
consider immune variables in relation to psychological influences on
infectious diseases. They studied prospectively members of sixteen families
for a one-year period with systematic throat cultures for β hemolytic
streptococci, periodic measurement of anti-streptolysin-O-antibody titers,

and clinical evaluation of illness. It was found that acute or chronic family
stresses not only were important factors determining whether the individual
became a host for the streptococcus, or became ill following colonization, but
also that psychological stress influenced the proportion of persons in whom

there was a rise of antistreptolysin O following infection.
In addition to clinical observations, there is a growing body of
experimental data supporting the hypothesis that psychosocial factors play a
role in infectious diseases. Rasmussen and collaborators, in an extensive

series of studies, have primarily employed avoidance-learning procedures as
the experimental model for investigating the effects of psychological stress.
This procedure requires mice to jump a barrier once every five minutes at the
presentation of a signal to avoid an electric shock delivered to their paws, a
response the animals quickly learn to perform. Daily exposure for six-hour
periods to these conditions resulted in an increased susceptibility to herpes
simplex virus, poliomyelitis virus, coxsackie B, and polyoma virus infection.

Physical restraint also was found to increase the susceptibility of mice to
herpes simplex virus," while high-intensity sound stress resulted in a
transient diphasic susceptibility pattern in mice inoculated intranasally with
vesicular stomatitis virus. In monkeys acute avoidance stress was found to
decrease their susceptibility to poliomyelitis. Social factors such as the effect
of differential housing have been studied, and it has been shown that mice
housed alone were significantly more susceptible to encephalomyocarditis
virus and less susceptible to Plasmodium berghei than animals housed in
groups.
In summary, both clinical and experimental observations demonstrate
that psychosocial factors influence infectious diseases. The experimental

procedures which have demonstrated psychosocial influences on host
response to infection have also been shown to modify a variety of immune
processes. These studies will be reviewed in a later section.
Allergic Disorders
Hypersensitivity refers to a state of enhanced reactivity to a foreign
substance acquired by previous exposure to the same or a related substance.
Allergy is frequently used synonymously with hypersensitivity and has come
to be considered a clinical state in which individuals react in an intense and

frequently injurious manner to a substance that usually has no effect on most
people. A wide range of antigens are capable of inducing the hypersensitive
response and the term allergen is used generically. Hypersensitive reactions
are of two major types. Immediate hypersensitivity in which the response
takes place within seconds or moments after exposure to the allergen and is
always associated with humoral antibodies. This type of reaction occurs in
anaphylaxis and in various allergic clinical states such as asthma, hay fever,
eczema, and urticaria.
The other type of hypersensitive reaction occurs two to three days after
exposure to the antigen and is referred to as delayed hypersensitivity. In this
reaction there are no humoral antibodies, and it is a cell-mediated immune
response. As mentioned earlier, the tuberculin reaction typifies delayed
hypersensitivity. Clinically, contact allergy occurring in response to poison
ivy, poison oak, or contact with certain drugs is a manifestation of a delayed
hypersensitive reaction.
Considerable clinical evidence suggests that psychological factors are
related to the precipitation of many allergic disorders including bronchial
asthma. The literature on the role of psychological influences on bronchial

asthma is reviewed in Chapter 28 of this volume and the present discussion
will focus only on the relationship of emotional factors to allergic processes in
general.
It has been repeatedly demonstrated that periods of life change and
stress antedate the onset of many allergic episodes and that a variety of
emotional states may trigger the onset of symptoms. Sensitivity to allergens
has not been demonstrated to be quantitatively stable with time and in a
number of instances it has been demonstrated to increase in association with
emotional distress. More than twenty years ago, Holmes et al. demonstrated
that naturally occurring and experimentally induced emotional distress

enhanced the intensity of allergic rhinitis and the magnitude of the response
of the nasal mucosa of patients with hay fever exposed to a standard amount
of pollen. The evidence suggested that parasympathetic activity mediated the

psychological influences in the nasal mucous membranes. Since that time, a
body of information has been gathered from the fields of pharmacology,
immunology, and pulmonary physiology, substantiating the influence of the
autonomic nervous system on vascular, mucosal, and muscular changes

occurring in target organs during the hypersensitive reaction. Mediating
mechanisms involved in the precipitation of at least some allergic and
asthmatic episodes probably include the autonomic and endocrine systems

interacting with allergic inflammatory processes. It has been postulated that
increased parasympathetic activity leading to broncho-constriction and to an
increase in bronchial mucous secretion mediates behavioral influences in the

precipitation of asthmatic attacks.
Several investigators studied the relationship between psychological

factors and biological susceptibility as two sets of independent variables
predisposing to allergic illnesses. The results have shown that both emotions
and immune mechanisms contribute to the development of susceptibility to
allergy although the mode of interaction is still unclear. The findings have also
suggested that failure to take into account the immunological heterogeneity

of allergic patients may have been one important source of inconsistency in
earlier psychosomatic investigations.
Implicit in a number of psychological studies of hypersensitive patients
is the possibility that emotional factors not only interact with an already
established allergic substrate, but that they may also directly influence the
development of an allergic diathesis. There is, at present, no solid clinical
evidence; limited experimental data will be reviewed later.
Autoimmune Diseases
It is well known that antibodies are not usually developed against an

individual’s own tissues. Burnet and Fenner emphasized this phenomenon
when they discussed the concept of self-recognition, i.e., the ability of the
mechanisms responsible for antibody production to distinguish “self” from
“not self.” In view of the previous discussion of the immune response, the
formation of antibodies which would react with the body’s own tissues would
be extremely destructive. Usually a substance is only antigenic when foreign
to a specific organism. In rare instances cells are antigenic in the organism
from which they arise. The antibodies which develop are known as
autoantibodies and the immunizing process is referred to as
autoimmunization. Autoimmune disease is defined as an illness in which
autoantibodies or a sensitized lymphocyte reacts with host tissue. It is

important to note that there is no conclusive evidence indicating that the
autoantibody or lymphocyte is the causative agent. Autoantibodies could be
causative, a result of autoimmune disease, or only a concomitant part of the
illness.
It has been suggested that autoimmunity is a result of immunologic
hyperactivity in response to the release of a sequestered antigen or due to
proliferation of “forbidden clones” of antibody-producing cells. Both of these
theories have been thoroughly discussed. Another hypothesis is that

autoimmune disease is a result of a state of immunological deficiency, and
several theories have been proposed to explain the pathogenic mechanism of
the deficient state. Among these is the suggestion that a latent virus,
mycoplasma, or bacterium may become pathogenic and alter the
immunological mechanism resulting in the production of autoantibodies. The

autoantibody may be an attempt of the organism to protect itself and may not
represent the primary pathogen.
A number of clinical entities in man are now considered to be

autoimmune diseases and include systemic lupus erythematosus, rheumatoid
arthritis, chronic glomerulonephritis, thyroiditis, and hemolytic anemia. In
addition, autoimmunity has been implicated in the pathogenesis of
scleroderma, myasthenia gravis, and ulcerative colitis. There is evidence
strongly suggesting that the tissue in rheumatoid arthritis is involved in a

chronic immune response. The profuse lymphocytic infiltration of synovial
tissue in rheumatoid arthritis and the immune complexes found in the
synovial fluid support this hypothesis. The specific aspects of the altered
cellular antigen have not as yet been demonstrated, but a chronic viral
infection is one of the major possibilities. It is likely that one of the many
viruses capable of slow atypical infection may modify the antigenicity of the
synovial cells and result in an immune reaction. It has been speculated that a
similar immune process is involved in other collagen vascular diseases such
as scleroderma, dermatomyositis, and systemic lupus erythematosus.
Solomon has reviewed the extensive literature concerned with the
psychophysiological aspects of autoimmune diseases. Among autoimmune

diseases, rheumatoid arthritis has been the disorder most frequently
considered in psychosomatic investigations. Several investigators have

studied the influences of psychosocial factors in relation to rheumatoid
arthritis and have assessed personality traits in arthritic patients. Although

no consistent personality pattern in rheumatoid patients emerges from these
studies, the findings convincingly document the importance of emotional
factors in the course of the disease. Patients have been described as
predominantly perfectionistic, self-conscious, introverted, and inhibited in
relation to various comparison groups. Moos and Solomon in a controlled
study found that patients with rheumatoid arthritis were significantly more
masochistic and self-sacrificing and showed difficulties in recognizing and
expressing hostility. They also studied the relation between psychological
factors and rapidity of progression of the disease, and functional incapacity

and response to medical treatment. Patients with poor prognosis and less
satisfactory response were significantly more anxious and depressed, and
demonstrated more social alienation and less adequate coping and adaptive
mechanisms.
Several authors have drawn attention to similarities in the role of

psychological factors in patients with rheumatoid arthritis and patients with
other autoimmune disorders. Stressful life events, such as the loss or
threatened loss of a significant relationship, were reported to precede not

only the onset of rheumatoid arthritis, but also of systemic lupus
erythematosus. Furthermore, similarities were found in the personality
characteristics of patients with these two disorders. Patients with ulcerative
colitis, a disease in which anticolon antibodies have been demonstrated, have

also been described as showing certain obsessive-compulsive traits which
resemble to some degree the personality factors described in arthritic
patients. The meaning of personality factors in the various autoimmune
disorders is, however, not certain and requires further study.
Solomon has advanced the theory that the central-nervous-system
control of immune mechanisms plays an important role in the mediation of
the effect of psychological factors in autoimmune disease. This theory rests on

evidence that autoimmune diseases are the result of a state of immunological
incompetence, and it has been proposed that the immune deficient state may
be the consequence of the activation of the adrenocortical system due to
emotional influences. A deficient immunological state may prevent

elimination of self-reacting immunologic competent cells, or it may permit the
formation of soluble antigen-antibody complexes resulting in the production
of tissue injury and inflammation.
Organ Transplants
In the 1960s, considerable progress has been made in the area of organ
transplantation and there are a number of excellent reviews which consider
the immunological aspects. The greatest success has been with the kidney,
while transplantation of other organs e.g., liver, heart, or lungs, has been far
less successful. A great deal of attention has been paid to the mechanisms
responsible for failures in the acceptance of grafted organs. Peter B. Medawar
and his co-workers were the first to demonstrate that the homograft reaction
is mediated by immune mechanisms. It has been demonstrated that skin
homografts are rejected by the cell-mediated immune response as described
earlier. The rejection of other grafts such as the kidney involves both humoral
and cellular immune mechanisms. Hume has described the mechanism of

primary acute rejection of the kidney. Antigens migrate from the donor
kidney to local lymph nodes where they encounter immunocompetent plasma
cells. In the lymph node humoral antibodies and sensitized lymphocytes are
produced and migrate back to the donor kidney. The sensitized lymphocytes
and humoral antibodies react to the kidney cells resulting in the
characteristic pathological features of the rejection crisis. Progress has been
made in the use of immunosuppressive agents which inhibit the immune

mechanisms involved in organ rejection while leaving all other immune
responses intact.
Attention has also been drawn to the role of psychosocial factors in
relation to organ transplantation. It has been shown experimentally that in

mice subjected to chronic avoidance learning, there is a prolongation of skin
homograft survival time. This effect is probably mediated by a modification of

immune mechanisms as a result of the psychological stress produced by the
avoidance learning.
Clinically, some investigators have reported that stressful life events,

intense anxiety and depression precede some rejection crisis following renal
homo-transplantation. Patients who died following kidney transplantation
were observed to experience feelings of abandonment, emotional tensions,
and grief to a degree not evidenced among patients who survived. Various
pathophysiological processes may be directly responsible for the patient’s

death, including disturbances in electrolyte balance, hemorrhage,
cardiovascular complications, and infection. The possibility that immune
processes may participate in some rejection crises associated with
psychological trauma deserves consideration. At present, however, there are

no data reported in this regard.
Cancer
The natural history of neoplastic diseases is in many ways similar to the
interaction between host and microorganisms in infectious diseases. The

genetic characteristics of both participants, as well as a variety of internal and
external factors, determine the outcome of the relation between the host and
living pathogenic cells. There is a growing body of knowledge that immune
mechanisms may be involved in both the development and outcome of

neoplasia. It has been shown that many experimental cancers in animals
contain new antigens. In addition, it has also been demonstrated that the
majority of carcinogenic agents decrease the overall immunological capacity

before the onset of cancer. There are many reports suggesting immunological
deficiency in man as a prerequisite for progressive neoplasia. It is of interest
that the relation of immunological mechanisms to cancer has been further
supported by some observations on immunosuppressive techniques utilized
in organ transplants. It has been found that there is a marked increase in the
incidence of tumors in approximately 6-8 percent of transplant patients
maintained on immunosuppressive drugs. Furthermore, it appears that in
some instances when the immunosuppressive treatment is stopped, the

tumors that developed while on immunosuppression rapidly regress.
As pointed out above, a variety of internal and external host factors

appear to play a role in the development, course, and outcome of neoplastic
disorders. Among these factors psychosocial influences have been shown,
both experimentally and clinically, to be determinants in neoplasia.
Experimentally, considerable evidence demonstrates that early
experiential factors not only have a profound influence on behavior and on
the endocrine and immunological responsiveness of small mammals, but that

they also influence the development and course of experimentally induced
cancer. Furthermore, the findings show that the outcome of the relation
between the host and the neoplastic process depends upon the species and
the nature of the experimental intervention. Brief daily handling and mild
electric shock administered early in life, for instance, modify the rate of tumor
development and the survival of rats injected with Walker-256 sarcoma.
Infantile stimulation also shortens the survival time of mice after
transplantation of lymphoid leukemia, but does not modify the mortality rate
of murine leukemia virus. Similarly, differential housing and sex-segregated
groupings modify the incidence of mammary carcinomas in mice, decrease

the survival time to injections of subcellular leukemia material, but do not
influence the development of Walker sarcoma tumors.
Clinically, a number of investigators have reported a relationship
between certain premorbid factors and personality types, and the
development of cancer. Kissen and collaborators, for example, have
conducted an extensive series of studies on the role of personality factors in
lung cancer. They have repeatedly observed that lung cancer patients have
less ability for emotional discharge than noncancer patients, as assessed

clinically and measured by the Maudsley Personality Inventory. In addition,
they have found significant differences between the same lung-cancer
patients and controls in the reported incidence of certain environmental

factors such as adverse episodes in childhood and adulthood. Bahnson and
Bahnson also have claimed that certain features such as depression, denial,
and repression exist to a pathological extent as premorbid characteristics in
patients with cancer.
By and large, the studies concerned with premorbid factors in cancer

are retrospective in nature and, therefore, are limited by the inability to
control for distortions due to the effect of immediate precipitating factors and
the psychological impact of the disease. Some investigators have focused on
the role of emotional factors during the immediate premorbid phase. Their
findings have demonstrated that depression, hopelessness, inability to

express hostile feelings, and object loss may play an important role in
influencing the onset of the neoplasia or the course and outcome of the
disease. An illustrative example is given by an interesting predictive study
conducted by Schmale and Iker on fifty-one females with cervical cellular

cytology, indicating suspicion of cervical cancer identified during routine
screening procedures. The investigators were able to make a significantly
high number of correct predictions regarding the diagnostic outcome of cone

biopsy of the cervix, based on the clinical assessment of feelings of
hopelessness during the previous six months. Assuming that a causal
relationship exists between emotional factors and the onset and development
of neoplasia, a question that has attracted considerable interest is concerned

with the nature of the physiological processes involved. The growing
information on the immunological aspects of cancer raises the possibility that

immunological mechanisms play an important role in the mediation of
emotional influences on susceptibility to neoplastic disease. The extensive

literature on the psychophysiological aspects of cancer has been thoroughly
reviewed.
Psychosocial Factors and Immune Processes
It is of considerable interest that some of the psychosocial situations,
which have been demonstrated to modify the susceptibility to infection and

the development of neoplasia, have also been found to have a profound
influence on immune processes. Avoidance learning, for example, decreases
the susceptibility of mice to passive anaphylaxis. Overcrowding, but not the

stress of electric shock, initiated prior to immunization of rats with flagellin, a
bacterial antigen, reduced both the primary and secondary antibody
response. Vessey found that grouped mice have significantly lower titers of
circulating antibodies than isolated mice and, by identifying social rank, he

demonstrated that dominant mice had higher titers than the other mice in
their groups. In primates, exposure to a complex pattern of visual, auditory,
and somasthetic stimulation was observed to increase plasma cortisol levels

markedly and to decrease the circulating antibody response to immunization
with bovine serum albumin. A number of reports in the Russian literature
have considered the effect of psychological mechanisms on antibody titers.

Petrovskii, for example, studied changes in agglutinin titers associated with
behavioral disturbances induced in immunized dogs and baboons by stressful
stimuli or by conflict-conditioning techniques. He observed a parallelism
between the intensity and duration of the behavioral disturbances and the fall
in circulating antibody titers. It is to be noted that under certain conditions
psychological stimulation can enhance the immune response. Brief handling
of rats, for instance, during the preweaning period was found to increase both
the primary and secondary antibody response to flagellin immunization.
The physiological mechanisms which mediate the psychosocial
influences on host resistance are complex and in need of further clarification.
It seems reasonable to speculate that the demonstrated effect of psychosocial

stress on the modified susceptibility to some viral infections and neoplastic
processes may be due to the suppression of immediate and delayed
hypersensitive mechanisms.
There is evidence that the hormonal and reticuloendothelial systems
are involved in the mediation of psychological influences. Avoidance learning
or confinement is accompanied by adrenal hypertrophy, lymphocytopenia

and a slowly developing involution of the thymus and spleen occurring in
temporal relation with the increase in susceptibility to viral infection. The
pituitary-adrenocortical system which is known to be altered by psychosocial
stimulation, has been the focus of considerable attention because of evidence

primarily derived from pharmacological studies that adrenal steroids may
modify susceptibility to infectious disease, alter immune reactions, or depress
inflammatory responses. In addition, both psychological stress and

adrenocortical steroids have been reported by some investigators, although
not by others, to suppress interferon production, a nonspecific protein

directly involved in host resistance to viral infection.
Whether changes in endogenous adrenal hormones, occurring in
response to environmental stimulation, are responsible for some of the
effects of host resistance and immune processes requires further analysis in
the context of the different experimental models investigated. Based on
studies conducted with stressed, adrenalectomized animals, it appears that
adrenal steroids are responsible for the increased resistance to passive
anaphylaxis, while the retarded rate of disappearance of vesicular stomatitis

virus from the site of inoculation and the increased susceptibility to this viral
agent seems independent of adrenal activity. These findings clearly
demonstrate the complexity of the field.
Little information is available on the role played by other hormonal
systems and physiological processes in the mediation of psychological and
environmental stimulation. Probably only after careful elucidation of the
physiological correlates of psychosocial intervention and their interaction

with the pathophysiological processes underlying a given pathogenic
stimulus, will it be possible to predict the response of an organism to specific

experimental conditions.
The Central Nervous System and Immune Processes
Recently the neurophysiological mechanisms that might mediate the

psychosocial influences on immunological reactions have been
experimentally studied. At the turn of the century the central nervous system
(CNS) was considered to be involved in the development of immune
phenomena. The brain was thought to be the target organ initiating the
anaphylactic reaction. A series of studies conducted between 1910 and 1920

demonstrated, however, that the characteristic signs of anaphylaxis could
occur in decerebrated guinea pigs and dogs. With the development of
immunological and biochemical techniques, an impressive amount of
knowledge on the cellular and chemical aspects of immune processes was

acquired, and the participation of the CNS was largely overlooked. The
consideration of the integrative capacity of the CNS on a variety of
physiological processes has stimulated a renewed interest in the role of the

CNS in immune processes.
Studies of the effect of sectioning the spinal cord on immunogenesis
have shown changes such as decreased antibody formation following
sensitization and lowered histamine sensitivity. These findings may be the

secondary result, however, of peripheral disturbances in temperature control
and blood circulation.
The effect of midbrain lesions on the course of anaphylaxis in the guinea

pig has been investigated by Freedman and Fenichel. Bilateral electrolytic
lesions at the level of the superior colliculus involving the reticulo-thalamic

tracts and deep tegmental nuclei inhibited anaphylactic death. Szentivanyi
and Filipp were among the first to study the role of the hypothalamus on
anaphylaxis. They demonstrated that lethal anaphylactic shock in the guinea
pig and the rabbit can be prevented by bilateral focal lesions in the tuberal
region of the hypothalamus. Luparello, Stein, and Park investigated the effect
of hypothalamic lesions on rat anaphylaxis and found that anterior, but not
posterior, hypothalamic lesions inhibited development of lethal anaphylaxis
in the rat. In a recent study reported by Macris, Schiavi, et al., it has been
shown that lesions in the anterior hypothalamus of actively immunized

guinea pigs afforded significant protection against lethal anaphylaxis. Lesions
in the median and posterior basal hypothalamus did not modify anaphylactic
reactions.
Little is known about the mechanisms involved in the antianaphylactic

effect of hypothalamic lesions. Filipp and Szentivanyi have reported that
circulating as well as tissue-fixed antibodies were markedly reduced in
guinea pigs injured in the tuberal region. Low precipitin levels were observed
in sensitized animals following hypothalamic lesions as evidenced by the Ring
test. Korneva and Khai also found that lesions in the posterior ventral
hypothalamus of rabbits completely suppressed the production of
complement-fixing antibodies and induced a prolonged retention of the

antigen in the blood. In cases where the areas of destruction were localized in
other parts of the hypothalamus, the thalamic structure, the caudate nucleus,
and the posterior commissure, the course of immune processes was similar to
that in control animals. It has been found that anterior hypothalamic lesions
in the guinea pig were associated with significantly lower circulating antibody
titers.
The significance of the low-circulating antibodies in the decreased

anaphylactic response remains to be determined. If the antianaphylactic
effect was due solely to diminished antibody production, then no protection
would be expected in animals passively immunized with antibody levels that
are sufficient to produce lethal anaphylaxis. Szentivanyi and Filipp have

reported that guinea pigs passively sensitized with homologous as well as
with heterologous (rabbit) serum are protected by hypothalamic lesions.
These investigators did not identify the hypothalamic structures damaged by

the lesions nor did they quantify the amount of antibodies injected to the
animals. Macris, Schiavi, et al. investigated the effect of hypothalamic lesions
in guinea pigs passively immunized with heterologous (rabbit)

antiovalbumin. Significant protection against passive lethal anaphylaxis was
found in the animals with anterior but not with posterior hypothalamic
lesions.
There are several mechanisms that may be involved in the protective
action of anterior hypothalamic lesions in addition to their effect on

circulating antibodies. The lesions may interfere with antibody binding to
host tissues; they may alter the content and release of histamine and other
mediator substances by the tissues; or they may diminish the responsiveness
of the target tissue to the pharmacological agents liberated by the antigen-
antibody reaction. Several studies have reported that the CNS modified the
susceptibility of animals to histamine which, in the guinea pig, is the main
agent responsible for the acute anaphylactic reaction. Whittier and Orr found
that bilateral lesions of the caudate nuclei of rats were associated with a
significant increase in survival time following the intraperitoneal

administration of histamine phosphate; sham operations and lesions in the
cerebral cortex did not modify the time of survival. Przbylski investigated the
effect of the removal of the region of quadrigeminal bodies and of the cerebral
cortex on histamine toxicity in guinea pigs. The animals in which the
quadrigeminal bodies were removed showed a decreased susceptibility to
histamine when administered either intravenously or by the inhalation of an
aerosol. Removal of the cerebral cortex did not modify the reactivity of the
animals.
Schiavi, Adams, and Stein studied the effect of bilateral electrolytic

lesions in the anterior and posterior medial hypothalamus of guinea pigs on
histamine toxicity as measured by dose-mortality curves and the LD50. The

animals with anterior lesions were afforded significant protection against
histamine toxicity. The mechanism by which anterior hypothalamic lesions
modifies the susceptibility of the animals to exogenous histamine is not
apparent from this study. Maslinski and Karczewski extensively investigated
the effect of electrical stimulation of the brain of guinea pigs with current
intensities above and below the seizure threshold on the susceptibility of the
animals to histamine. They found that electrical stimulation of guinea pigs
through temporal electrodes with a 50-100 Hz. current at levels between 8
and 10 milli amp. has a marked protective effect against lethal histamine
shock. These investigators demonstrated that the decrease in histamine
susceptibility was transitory and was associated with a marked decrease in
the bronchospastic effect of histamine. Karczewski found that the parameters
of electrical stimulation effective against lethal histamine shock also induced
a marked depression of the electrical activity of the afferent and efferent
fibers of the vagus. This and other observations led him to postulate that the
modified histamine susceptibility following brain stimulation could be due to
a reduced physiological tone of the airways leading to a reduced response to

the constricting stimuli. A study by Mills and Widdicombe conducted on
vagotomized guinea pigs provided evidence that a vagal reflex is partially

responsible for the bronchoconstriction occurring in anaphylaxis and
following intravenous administration of histamine. A decreased response to

broncho-constricting agents due to an autonomic imbalance induced by the
anterior hypothalamic lesions deserves further consideration.
Extensive work has demonstrated that the hypothalamus is intimately
involved with autonomic nervous activity. Several lines of evidence indicate
that bronchomotor tone is the result of a balance between parasympathetic
and sympathetic influences. Damage to the region of the anterior
hypothalamus, which is thought to mediate primarily parasympathetic
responses may decrease vagal bronchoconstrictor tone resulting in the
predominance of bronchial adrenergic β-receptor activity. In keeping with

this hypothesis, inhibition of vagal activity or β-adrenergic stimulation
decrease histamine induced bronchoconstriction while blockage of β-
receptors potentiate histamine broncho-spasm.
Szentivanyi has postulated that the hyperreactivity observed in
bronchial asthma may be due to the reduced functioning of the β-adrenergic
system leading to α-adrenergic dominance and the consequent increase in
bronchial responsiveness to the various pharmacological mediators. Orange

and Austen have reported that increased intracellular levels of cyclic
adenosine-3'5'-mono-phosphate (cyclic AMP) following activation of β-

adrenergic receptors inhibit the IgE mediated immunological release of
histamine and “slow reactive substance” (SRS-A) from lung tissues.
Hypothalamic lesions may produce a functional imbalance in the two

adrenergic effector systems or increase the levels of cyclic AMP resulting in
an inhibition of release of histamine and SRS-A; at present, however, there are
no data to support these possibilities.
The influence of the CNS on immune mechanisms may be due, at least in

part, to changes in neuroendocrine function induced by the destruction of
specific hypothalamic structures. It has been shown in the rat that the
anterior medial hypothalamus is involved in the regulation of the secretion of

thyroid stimulating hormone (TSH) by the hypophysis. Electrolytic lesions in
this area induce low plasma levels of TSH and decreased thyroid function. A
number of investigators have demonstrated in the rat and guinea pig a
relationship between thyroid physiology and immune processes. It has been

noted that the resistance to the anaphylactic reaction is increased in
thyroidectomized rats. Similar findings were observed by Nilzen in the guinea
pig following thyroidectomy or administration of I. Suppression of thyroid

activity inhibits local and systemic anaphylaxis, abolishes circulating
precipitins, and decreases the susceptibility of the animals to exogenous
histamine. Little is known about the effect of anterior hypothalamic lesions on

thyroid function in the guinea pig.
Hypothalamic lesions can also modify ACTH secretion and blood
corticoid levels. Adrenal steroids have been found to have a protective effect
against anaphylactic shock in the rat and an inhibitory effect on antibody
formation in rats and guinea pigs. Adrenocortical hormones (ACTH) also have
a profound action on the metabolism and effects of histamine. They have
inhibitory effects on histamine decarboxylase activity, tissue binding of newly
formed histamine and on the amount of histamine released by the tissues.
Although adrenal steroids have a protective effect against histamine toxicity
in mice and rats, they do not appear to modify significantly the susceptibility
of guinea pigs to anaphylaxis and to exogenous histamine.
It has been suggested that the protective effect of anterior lesions may
also be due to simultaneous changes in thyroid and adrenocortical function.
Filipp and Mess reported that exogenous administration of thyroxin partially
restored the sensitivity to anaphylaxis of actively immunized guinea pigs with
lesions in the tuberal area of the hypothalamus. In another study the same
authors investigated the combined effect of thyroxin and metopirone, an
inhibitor of adrenocorticol hormone synthesis, on the anaphylactic response

of sensitized guinea pigs with lesions in the tuberal region. The observation
that the administration of both substances completely abolished the
protective effect of the lesions led the investigators to postulate that the anti-
anaphylactic effect of hypothalamic damage is due to the combined effect of
decreased thyroid function and increased adrenocortical activity. There have

been very few studies concerned with the neuroendocrine effects of localized
hypothalamic damage in guinea pigs. Additional information is necessary on

plasma levels of thyroid, adrenocortical, and adrenomedullary hormones in
guinea pigs with well defined hypothalamic lesions effective in decreasing
anaphylactic reactivity.
Concluding Remarks
This chapter has reviewed the effect of psychosocial influences on
infectious diseases, allergic disorders, autoimmune diseases, organ

transplantation, and cancer. Clinical and experimental data have been
presented which suggest that the effect of psychosocial factors on these
disorders is due at least in part to an alteration in immunological
mechanisms. The role of the CNS in relation to immune processes has also
been discussed. The complexity of the psychophysiological processes
involved in the role of psychosocial factors on immune disorders has been
emphasized.
Bibliography
Abramoff, P. and M. LaVia. Biology of the Immune Response. New York: McGraw-Hill, 1970.
Ader, R. and S. B. Friedman. “Differential Early Experiences and Susceptibility to Transplanted

Tumor in the Rat,” J. Comp. Physiol. Psychol., 59 (1965), 361-364.
Aviado, D. M. “Antiasthmatic Action of Sympathomimetics: A Review of the Literature on Their

Bronchopulmonary Effects,” J. Clin. Pharmacol., 10 (1970), 217-221.
Bahnson, C. B. “Second Conference on Psychophysiological Aspects of Cancer,” Ann. N.Y. Acad. Sci.,
164 (1969), 307-634.
Bahnson, C. B. and M. B. Bahnson. “Role of the Ego Defenses: Denial and Repression in the
Etiology of Malignant Neoplasia,” Ann. N.Y. Acad. Sci., 125 (1966), 827-845.
Basch, S. H. “The Intrapsychic Integration of a New Organ: A Clinical Study of Kidney

Transplantation,” Psychoanal. Q., 42 (1973), 364-384.
Berenbaum, M. C. “Effects of Carcinogens on Immune Processes,” Br. Med. Bull., 20 (1964), 159-
164.
Black, S., J. H. Humphrey, and J. S. F. Niven. “Inhibition of Mantoux Reaction by Direct Suggestion
under Hypnosis,” Br. Med. J., 1 (1963), 1649-1652. g. Block, J. “Further
Consideration of Psychosomatic Predisposing Factors in Allergy,” Psychosom. Med.,
30 (1968), 202-208.
Bock, E., B. Weeke, and O. J. Rafaelsen. “Serum Proteins in Acutely Psychotic Patients,” J. Psychiatr.
Res., 9 (1971), 1-9.
Bogendorfer, L. “Uber den Einfluss des Zentralnervensystems auf Immunitatsvor-gange:

Beziehungen des Sympathicus zum Zustandekommen der Agglutination,” Arch. Exp.
Pathol. Pharmakol., 133 (1928), 107-no.
Burnet, F. M. The Clonal Selection Theory of Acquired Immunity. Nashville, Tenn.: Vanderbilt
Burnet, F. M. and F. Fenner. The Production of Antibodies. Melbourne: McMillan, 1941.
Castelnuovo-Tedesco, P., ed. Psychiatric Aspects of Organ Transplantation. New York: Grune &
Stratton, 1971.
Chang, S. S. and A. F. Rasmussen. “Stress-Induced Suppression of Interferon Production in Virus

Infected Mice,” Nature, 205 (1965), 623-624.
Cooper, I. S. “Neurological Evaluation of Cutaneous Histamine Reaction,” J. Clin. Invest., 29 (1950),

465-469.
Crisp, A. H. “Some Psychosomatic Aspects of Neoplasia,” Br. J. Med. Psychol., 13 (1970), 313-331.
DeJong, W. and J. Moll. “Differential Effects of Hypothalamic Lesions on Pituitary-Thyroid Activity
in the Rat,” Acta Endocrinol. (Kbh.), 48 (1965), 522-535.
Dews, P. B. and C. F. Code. “Effect of Cortisone on Anaphylactic Shock in Adrenalectomized Rats,”

J. Pharmacol. Exp. Therap., 101 (1951), 9.
----. “Anaphylactic Reactions and Concentrations of Antibodies in Rats and Rabbits. Effect of
Adrenalectomy and of Administration of Cortisone,” J. Immunol., 70 (1953), 199-
206.
Dzhumkhade, A. P. “Role of Conditioned Reflexes in Production of Antibodies,” Zh. Vyssh. Nerv.

Deiat., 10 (1960), 599-601.
Ebresen, P. and R. Rask-Nielsen. “Influence of Sex-Segregated Grouping and of Inoculation with

Subcellular Leukemic Material on Development of Non-Leukemic Lesions in
DBA/2, BALB/C and CBA Mice,” J. Natl. Cancer Inst., 39 (1967), 917-925’
Eisendrath, R. M. “The Role of Grief and Fear in the Death of Kidney Transplant Patients,” Am. J.
Psychiatry, 126 (1969), 129-135.
Filipp, G. and B. Mess. “Role of the Thyroid Hormone System in Suppression of Anaphylaxis Due
to Electrolytic Lesion of the Tuberal Region of the Hypothalamus,” Ann. Allergy, 27
(1969), 500-505.
----. “Role of the Adrenocortical System in Suppressing Anaphylaxis after Hypothalamic Lesion,”
Ann. Allergy, 27 (1969), 607-610.
Filipp, G. and A. Szentivanyi. “Anaphylaxis and the Nervous System, Part III,” Ann. Allergy, 16
(1958), 306-311.
Fisherman, E. “Does the Allergic Diathesis Influence Malignancy?” J. Allergy, 31 (1960), 74-78.
Florsheim, W. H. “The Effect of Anterior Hypothalamic Lesions on Thyroid Function and Goiter
Development in the Rat,” Endocrinol., 62 (1958), 783-789.
Freedman, D. X. and G. Fenichel. “Effect of Midbrain Lesions on Experimental Allergy,” Arch.
Freeman, E. H., B. F. Feingold, K. Schlesinger et al. “Psychological Variables in Allergic Disorders:

A Review,” Psychosom. Med., 26 (1964), 543-575.
Freeman, E. H., F. J. Gorman, M. T. Singer et al. “Personality Variables and Allergic Skin Reactivity,”
Psychosom. Med., 29 (1967), 312-322.
Friedman, S. B. and L. A. Glasgow. “Psychologic Factors and Resistance to Infectious Disease,”

Pediatr. Clin. North Am., 13 (1966), 315-335.
Friedman, S. B., L. A. Glasgow, and R. Ader. “Psychosocial Factors Modifying Host Resistance to
Experimental Infections,” in C. B. Balmson, ed., Second Conference on
Psychophysiological Aspects of Cancer. Ann. N.Y. Acad. Sci., 164 (1969), 381-393.
Fudenberg, H. H. “Immunologic Deficiency, Lymphoma and Autoimmune Diseases: Observations,

Implications, Speculations,” Arthritis Rheum., 9 (1966), 464-472.
----. “Are Autoimmune Diseases Immunologic Deficiency States?” in R. A. Good and D. W. Fisher,
eds., Immunobiology, PP-175-183. Stamford, Conn.: Sinauer Associates, 1971.
Gellhorn, E. Autonomic Imbalance and the Hypothalamus. Minneapolis: University of Minnesota

Press, 1957.
Gellhorn, E., H. Nakao, and E. S. Regate. “The Influence of Lesions in the Anterior and Posterior
Hypothalamus on Tonic and Phasic Autonomic Reactions,” J. Physiol., 131 (1956),
402-423.
Geocaris, K. “Circumoral Herpes Simplex and Separation Experiences in Psychotherapy,”

Psychosom. Med., 23 (1961), 41-47.
Gold, E. R. and D. B. Peacock. Basic Immunology. Bristol, England: John Wright, 1970.
Greenfield, N. S., R. Roessler, and A. P. Crosley. “Ego Strength and Length of Recovery from
Infectious Mononucleosis,” J. Nerv. Ment. Dis., 128 (1959), 125-128.
Hagnell, O. “The Premorbid Personality of Persons Who Develop Cancer in a Total Population
Investigated in 1947 and 1957,” Ann. N.Y. Acad. Sci., 125 (1966), 846-855.
Hasek, M., A. Lengerova, and T. Hraba. “Transplantation Immunity and Tolerance,” Adv. Immunol.,
1 (1961), 1-56.
Hawkins, N. G., R. Davies, and T. H. Holmes. “Evidence of Psychosocial Factors in the Development
of Pulmonary Tuberculosis,” Am. Rev. Tuberc. Pulmon. Dis., 75 (1957), 5-10.
Herxheimer, H. “Bronchoconstrictor Agents and Their Antagonists in the Intact Guinea Pig,” Arch.
Int. Pharmacodyn. Ther., 106 (1956), 371-380.
Hicks, R. “The Effects of Drug-Induced Adrenocortical Deficiency and of Mineralocorticoid Drugs

on Anaphylaxis in the Guinea Pig,” J. Pharm. Pharmacol., 20 (1968), 497-504.
Hill, C. W., W. E. Greer, and O. Felsenfeld. “Psychological Stress, Early Response to Foreign Protein
and Blood Cortisol in Vervets,” Psychosom. Med., 29 (1967), 279-283.
Holmes, T. H., T. Treuting, and H. G. Wolff. “Life Situations, Emotions and Nasal Disease,”
Psychosom. Med., 13 (1951). 71-82.
Hume, D. M. “Immunological Consequences of Organ Homotransplantation in Man,” Harvey Led.,

64 (1968-1969), 261-388.
----. “Organ Transplants and Immunity,” in R. A. Good and D. W. Fisher, eds., Immunobiology, pp.
185-194. Stamford, Conn.: Sinauer Associates, 1971.
Imboden, J. B., A. Carter, and E. C. Leighton. “Convalescence from Influenza: A Study of the
Psychological and Clinical Determinants,” Arch. Intern. Med., 108 (1961), 115-123.
Jacobs, M. A., L. S. Anderson, H. D. Eisman et al. “Interaction of Psychologic and Biologic

Predisposing Factors in Allergic Disorders,” Psychosom. Med., 29 (1967), 572-585.
Jensen, M. M., and A. F. Rasmussen, Jr. “Stress and Susceptibility to Viral Infections: II. Sound
Stress and Susceptibility to Vesicular Stomatitis Virus,” J. Immunol., 90 (1963), 21-
23.
Johnson, T., J. F. Lavender, E. Hullin et al. “The Influence of Avoidance-Learning Stress on
Resistance to Coxsackie B. Virus in Mice,” J. Immunol., 91 (1963), 569-575.
Johnson, T. and A. F. Rasmussen, Jr. “Emotional Stress and Susceptibility to Poliomyelitis Virus
Infection in Mice,” Arch. Gesamte Virusforsch., 18 (1965), 392-398.
Karczewski, W. “The Electrical Activity of the Vagus Nerve After an ‘Antianaphylactic’ Stimulation
of the Brain,” Ada. Allergol. (Kbh), 19 (1964), 229-235.
Karczewski, W., P. S. Richardson, and J. G. Widdicombe . “The Role of the Vagus Nerves in
Determining Total Lung Resistance and Histamine-Induced Bronchoconstriction in
Rabbits,” J. Physiol., 181 (1965), 20P.
Kass, E. H. “Hormones and Host Resistance to Infection,” Baderiol. Rev., 24 (1960), 177-185.
Kemph, J. P. “Renal Failure, Artificial Kidney and Kidney Transplant,” Am. J. Psychiatry, 122
(1966), 1270-1274.
Kissen, D. M. “Relationship between Lung Cancer, Cigarette Smoking, Inhalation, and Personality,”
Br. J. Med. Psychol., 37 (1964), 203-216.
----. “Psychosocial Factors, Personality and Lung Cancer in Men Aged 55-64,” Br. J. Med. Psychol.,
40 (1967), 29-43.
Kissen, D. M. and L. L. LeShan, eds. Psychosomatic Aspeds of Neoplastic Disease. London: Pitman,
1964.
Knapp, P. H. and S. J. Nemetz. “Acute Bronchial Asthma: I. Concomitant Depression and

Excitement and Varied Antecedent Patterns in 406 Attacks,” Psychosom. Med., 22
(1960), 42-56.
Korneva, E. A. and L. M. Khai. “Effect of Destruction of Hypothalamic Areas on Immunogenesis,”

Fed. Proc. Transl. Suppl.), 23 (1964), T88-92.
Leger, J. and G. Masson. “Factors Influencing an Anaphylactoid Reaction in the Rat,” Fed. Proc., 6
(1947), 150-151.
LeShan, L. L. “An Emotional Life-History Pattern Associated with Neoplastic Disease,” Ann. N.Y.
Acad. Sci., 125 (1966), 780-793.
Levine, S. and C. Cohen. “Differential Survival to Leukemia as a Function of Infantile Stimulation

in DB A/Z Mice,” Proc. Soc. Exp. Biol. Med., 102 (1959), 53-54.
Lukyanenko, V. L. “The Conditioned Reflex Regulation of Immunological Reactions,” Zh. Mikrobiol.

Epidemiol. Immunobiol., 30 (1959). 53-59.
Luparello, T. J., M. Stein, and D. C. Park. “Effect of Hypothalamic Lesions on Rat Anaphylaxis,” Am.
J. Physiol., 207 (1964), 911-914.
McClary, A. R., E. Meyer, and D. J. Weitzman. “Observations on the Role of Mechanism of

Depression in Some Patients with Disseminated Lupus Erythermatosus,”
Psychosom. Med., 17 (1955), 311-321.
McCulloch, M. W., C. Proctor, and M. J. Rand. “Evidence for an Adrenergic Homeostatic

Bronchodilator Reflex Mechanism,” Europ. J. Pharmacol., 2 (1967), 214-223.
McFadden, E. R., Jr., T. Luparello, H. A. Lyons et al. “The Mechanism of Action of Suggestion in the
Induction of Acute Asthma Attacks,” Psychosom. Med., 31 (1969), 134-143.
Macris, N. T., R. C. Schiavi, M. D. Camerino et al. “Effect of Hypothalamic Lesions on Immune

Processes in the Guinea Pig,” Am. J. Physiol., 219 (1970), 1205-1209.
----. “Effect of Hypothalamic Lesions on Passive Anaphylaxis in the Guinea Pig,” Am. J. Physiol., 222
(1972), 1054-1057.
Marchant, J. “The Effects of Different Social Conditions on Breast Cancer Induction in Three
Genetic Types of Mice by Dibenz (A,H) Anthracene and a Comparison with Breast
Carcinogenesis by 3-Methylcholanthrene,” Br. J. Cancer, 21 (1967), 576-585.
Marsh, J. T., J. F. Lavender, S. S. Chang et al. “Poliomyelitis in Monkeys: Decreased Susceptibility

after Avoidance Stress,” Science, 140 (1963), 1414-1415.
Marsh, J. T. and A. F. Rasmussen, Jr. “Response of Adrenal, Thymus, Spleen and Leucocytes to
Shuttle Box and Confinement Stress,” Proc. Soc. Exp. Biol. Med., 104 (1960), 180-
183.
Maslinski, C. and W. Karczewski. “Prevention of So-Called Histamine Shock by Stimulation of the

Brain with Electric Current: Preliminary Communication,” Acta. Physiol. Pol., 6
(1955), 372-376.
----. “The Protective Influences of Brain Stimulation by Electric Current on Histamine Shock in
Guinea Pigs,” Bull. Acad. Pol. Sci., 5 (1957), 57-62.
Meyer, R. J. and R. J. Haggerty. “Streptococcal Infections in Families: Factors Altering Individual

Susceptibility,” Pediatrics, 29 (1962), 539-549.
Miescher, P. A. and H. J. Muller-Eberhard, eds. Textbook of Immunolopathology. New York: Grune

& Stratton, 1968.
Mills, J. E. and J. G. Widdicombe. “Role of the Vagus Nerves in Anaphylaxis and Histamine-Induced
Bronchoconstrictions in Guinea Pigs,” Br. J. Pharmacol., 39 (1970), 724-731.
Moos, R. H. “Personality Factors Associated with Rheumatoid Arthritis: A Review,” J. Chronic Dis.,
17 (1963), 41.
Moos, R. H. and G. F. Solomon. “Personality Correlates of the Rapidity of Progression of

Rheumatoid Arthritis,” Am. Rheum. Dis., 23 (1964), 145-151.
----. “Psychologic Comparisons between Women with Rheumatoid Arthritis and Their Non-
Arthritic Sisters: I. Personality Test and Interview Rating Data,” Psychosom. Med.,
27 (1965), 135-149.
Arthritic Sisters: II. Content Analysis of Interviews,” Psychosom. Med., 27 (1965),
150-164.
----. “Personality Correlates of the Degree of Functional Incapacity of Patients with Physical
Disease,” J. Chronic Dis., 18 (1965), 1019-1038.
Monaenkov, A. M. “The Influence of Changes in the Activity of the Cerebral Hemispheres in
Immunological Reactions,” Zh. Mikrobiol. Epidemiol. Immunobiol., 12 (1956), 88-89.
Movat, H. Z. Inflammation, Immunity and Hypersensitivity. New York: Harper & Row, 1971.
Nilzen, A. “The Influence of the Thyroid Gland on Hypersensitivity Reactions in Animals: I,” Acta
Allergol. (Kbh), 7 (1955), 231-234.
----. “The Influence of the Thyroid Gland on Hypersensitivity Reactions in Animals: II,” Acta
Allergol. (Kbh), 8 (1955). 57-60.
----. “The Influence of the Thyroid Gland on Hypersensitivity Reactions in Animals: III,” Acta
Altergol. (Kbh), 8 (1955), 103-111.
Orange, R. P. and F. Austen. “Chemical Mediators of Immediate Hypersensitivity,” in R. A. Good

and D. W. Fisher, eds., Immunobiology, pp. 115-121. Stamford, Conn.: Sinauer
Associates, 1971.
Otto, R. and I. P. Mackay. “Psychosocial and Emotional Disturbance in Systemic Lupus

Erythematosus,” Med. J. Aust., 2 (1967), 488-491.
Parrot, J. L. and C. Laborde. “Inhibition d’histidine-decarboxylase par la cortisone et par le

salicylate de sodium,” J. Physiol., 53 (1955), 441-442.
Petrovskii, I. N. “Problems of Nervous Control in Immunity Reactions: II. The Influence of

Experimental Neurosis on Immunity Reactions,” ZH. Mikrobiol. Epidemiol.
Immunobiol., 32 (1961), 1451-1458.
Porter, J. C. “Secretion of Corticosterone in Rats with Anterior Hypothalamic Lesions,” Am. J.

Physiol., 204 (1963), 715-718.
Przbylski, A. “Effect of the Removal of Cortex Cerebri and the Quadrigeminal Bodies Region on
Histamine Susceptibility of Guinea Pigs,” Acta. Physiol. Pol., 13 (1962), 535-541.
Rasmussen, A. F. Jr. “Emotions and Immunity,” in C. B. Bahnson, ed., Second Conference on

Psychophysiological Aspects of Cancer. Ann. N.Y. Acad. Sci., 164 (1969), 458-462.
Rasmussen, A. F. Jr., J. T. Marsh, and N. Q. Brill. “Increased Susceptibility to Herpes Simplex in
Mice Subjected to Avoidance-Learning Stress or Restraint,” Proc. Soc. Exp. Biol.
Med., 96 (1957), 183-189.
Rasmussen, A. F., Jr., E. T. Spencer, and J. T. Marsh. “Decrease in Susceptibility of Mice to Passive
Anaphylaxis Following Avoidance-Learning Stress,” Proc. Soc. Exp. Biol. Med., 100
(1959), 878-879.
Rees, W. L. “Physical and Emotional Factors in Bronchial Asthma,” J. Psychosom. Res., 1 (1956),
98-114.
----. “The Role of the Autonomic Nervous System in Asthma and Allied Disorders,” J. Psychosom.
Res., 9 (1965), 159-163.
Rose, B. “Hormones and Allergic Responses,” in J. H. Shaffer, G. A. LoGrippo, and M. W. Chase, eds.,
International Symposium on Mechanisms of Hypersensitivity, PP 599-634, London:
Churchill, 1959.
Russell, P. S. and A. P. Monaco. “The Biology of Tissue Transplantation,” N. Engl. J. Med., 271
(1964), 502, 553, 610, 664, 718, 776.
Rytel, M. W. and E. D. Kilbourne. “The Influence of Cortisone on Experimental Viral Infection,” J.

Exp. Med., 123 (1966), 767-775.
Salk, J. “Theoretical Psychophysiological Considerations,” in Bahnson, C. B., ed., Second

Conference on Psychophysiological Aspects of Cancer. Ann. N.Y. Acad. Sci., 164
(1969), 590-610.
Savchuk, O. Y. “The Reflex Mechanism of the Formation of Antibodies,” Zh. Mikrobiol. Epidemiol.
Immunobiol., 29 (1958), 123-131.
Schayer, R. W., J. K. Davis, and R. L. Smiley. “Binding of Histamine in Vitro and Its Inhibition by
Cortisone,” Am. J. Physiol., 182 (1955), 54-56.
Schiavi, R. C., J. Adams, and M. Stein. “Effect of Hypothalamic Lesions on Histamine Toxicity in the
Guinea Pig,” Am. J. Physiol., 211 (1966), 1269-1273.
Schmale, A. H. and H. P. Iker. “The Affect of Hopelessness in the Development of Cancer: I. The
Prediction of Uterine Cervical Cancer in Women with Atypical Cytology,”
Psychosom. Med., 26 (1964), 634-635.
Schwartz, R. S. and Y. Borel. “Principles of Immunosuppressive Drug Action,” in P. A. Miescher and

H. J. Müller-Eberhard, eds., Textbook of Immunopathology, Vol. 1, pp. 227-235. New
York: Grune & Stratton, 1968.
Solomon, G. F. “Stress and Antibody Response in Rats,” Arch. Allergy, 35 (1969), 97-104.
----. “Emotion, Stress, the Central Nervous System and Immunity,” in C. B. Bahnson, ed., Second
Conference on Psychophysiological Aspects of Cancer. Ann. N.Y. Acad. Sci., 164
(1969), 335-343.
----. “Psychophysiological Aspects of Rheumatoid Arthritis and Autoimmune Disease,” in O. W.

Hill, ed., Modern Trends in Psychosomatic Medicine, pp. 189-216. New York:
Solomon, G. F., S. Levine, and J. K. Kraft. “Early Experience and Immunity,” Nature, 220 (1968),
821-822.
Solomon, G. F., T. Merigan, and S. Levine. “Variation in Adrenal Cortical Hormones within
Physiological Ranges, Stress and Interferon Production in Mice,” Proc. Soc. Exp. Biol.
Med,., 126 (1967), 74-79.
Solomon, G. F. and R. H. Moos. “Psychologic Aspects of Response to Treatment in Rheumatoid

Arthritis,” Gen. Pract., 32 (1965), 113-115.
Stjernsward, J. “Age-Dependent Tumor Host Barrier and Effect of Carcinogen-Induced

Immunodepression on Rejection of Isografted Methylcholanthrene-Induced
Sarcoma Cells,” J. Natl. Cancer Inst., 37 (1966), 505-512.
Szentivanyi, A. “The Beta Adrenergic Theory of the Atopic Abnormality in Bronchial Asthma,” J.
Allergy, 42 (1968), 203-232.
Szentivanyi, A. and G. Filipp. “Anaphylaxis and the Nervous System, Part II,” Ann. Allergy, 16
(1958), 143-151.
Treadwell, P. E. and A. F. Rasmussen, Jr. “Role of the Adrenals in Stress-Induced Resistance to

Anaphylactic Shock,” J. Immunol., 87 (1961), 492-497.
Turk, J. L. Immunology in Clinical Medicine. New York: Appleton-Century-Crofts, 1969.
Vessey, S. H. “Effects of Grouping on Levels of Circulating Antibodies in Mice,” Proc. Soc. Exp. Biol.,
115 (1964), 252-255.
Wan, W. C. and M. Stein. “Effect of Vagal Stimulation on the Mechanical Properties of the Lungs in
Guinea Pigs,” Psychosom. Med., 30 (1968), 846-852.
Weil-Malherbe, H. and S. I. Szara. The Biochemistry of Functional and Experimental Psychoses.

Springfield, Ill.: Charles C. Thomas, 1971.
Whittier, J. R. and A. Orr. “Hyperkinesia and Other Physiologic Effects of Caudate Deficit in the
Adult Albino Rat,” Neurology, 12 (1962), 529-539.
Widdicombe, J. G. “Regulation of Tracheobronchial Smooth Muscle,” Physiol. Rev., 43 (1963), 1-37.
Wistar, R. T. and W. H. Hildermann. “Effect of Stress on Skin Transplantation Immunity in Mice,”

Science, 131 (1960), 159-160.
Wollcock, A. J., P. T. Macklem, J. C. Hogg et al. “Influence of Autonomic Nervous System on Airway
Resistance and Elastic Recoil,” J. Appl. Physiol., 26 (1969), 814-818.
Wollcock, A. J., P. T. Macklem, J. C. Hogg et al. “Effect of Vagal Stimulation on Central and
Peripheral Airways in Dogs,” J. Appl. Physiol., 26 (1969), 806-813.
Wyatt, R. J., B. A. Termini, and J. Davis. Biochemical and Sleep Studies of Schizophrenia: A Review of
the Literature— 1960-1970. Schizophrenia Bulletin, Issue no. 4. Washington, D.C.:
Natl. Clearinghouse for Mental Health Information, Fall 1971.
Yamada, A., M. Jensen, and A. F. Rasmussen, Jr. “Stress and Susceptibility to Viral Infections: III.
Antibody Response and Viral Retention during Avoidance Learning Stress,” Proc.
Soc. Exp. Biol. Med., 116 (1964), 677-680.
Yamasaki, H. and T. Yamamoto. “Inhibitory Effect of Adrenal Glucocorticoids on Histamine

Release,” Jap. J. Pharmacol., 13 (1963), 223-224.
Chapter 30
Musculoskeletal Disorders
Donald Oken
Introduction
This chapter will discuss five clinical disorders: psychogenic
rheumatism, occupational cramp, rheumatoid arthritis, parkinsonism, and
gout. It is immediately apparent, therefore, that its title is a misnomer in one

important sense. The basic pathophysiological processes involved in at least
three of these disorders almost certainly lie outside the musculoskeletal

system. A more accurate title might have referred to disorders with
predominant musculoskeletal manifestations. The logic of their selection

based on common symptomatic features is reinforced by a significant
resemblance among the psychological factors that have been found associated
with each.
The fact that the psychological findings reported for these disorders
overlap poses questions about their precision, if not their validity. The
similarities, however, may be quite real. If so, this raises a suspicion that the
findings are similar for the same reason that the disorders are, i.e., their
shared manifestations. The presence of any disease that causes severe

limitation of motility, as well as pain and related symptoms in the muscles
and joints, will produce psychological reactions to these symptoms. Perhaps
the greatest problem in obtaining and interpreting data on patients with
musculoskeletal disorders lies in separating these consequences of disease

from factors which are antecedent. Some of the data does bear on factors
antedating onset and these are of particular interest. But the entire subject
area contains a wealth of findings that merit interest, and illustrate both the
successes and difficulties of the psychosomatic approach.
Prior to the consideration of the disorders themselves is a section which
reviews the available data in the area of basic psychophysiology most
relevant to the musculoskeletal system, i.e., muscle tension. The rationale for
this choice can be questioned for the very reason and to the same degree that
the chapter may be mislabeled. Nevertheless, muscle tension does seem to

have direct relevance to two of the disorders, and indirect relevance to at
least two others. It also represents an important area of psychophysiology in

its own right. Other relevant areas of psychophysiology will not be neglected,
but will be considered in direct relation to the disorders in which they may be
implicated.
Basic Psychophysiology
It hardly needs to be pointed out that posture, gait, facial expression,
and gestures represent basic characteristics of the personality. Individuals

have their own relatively unique styles of motor expression which are readily
recognizable both to themselves and those who know them. The style of a
person’s motor activity also provides revealing manifestations of his
psychological attributes. Many studies (reviewed by Plutchik) are unanimous

in showing that motor expression reliably communicates characteristic
attitudes.
Freud pioneered our understanding of the significance of “meaningless”
motor acts as manifestations of specific unconscious motivational forces.
Psychoanalysts who followed have provided further insights about the

meanings behind various movements and postures. The individualized nature
of these activities makes an ideographic clinical approach such as
psychoanalysis the most appropriate method for their psychological study.
No comparable method existed on the motor side for a long time. Now an
ingenious beginning toward a science of “Kinesics” has been launched by
Birdwhistell.
Expressive behavior has obvious relevance to both normal personality
and psychopathology, the domain of psychiatry. The psychosomatic approach
requires a focus on psychophysiological mechanisms, rather than motor
behavior. Within this framework, our interest is in muscle tension.
Muscle Tension
The term “tension,” with its inherent dual meaning of a psychological as

well as muscular phenomenon, implies the existence of a psychosomatic
relationship. While this may be revealing in a very general sense, a scientific
understanding of that relationship requires specific, precise definition of both
its psychological and somatic components. The vagueness of the term tension
to represent a psychological phenomenon is obvious. It may be less evident
that there has been considerable variation in its use on the somatic side as
well. The common feature which appears to underlie these various usages is
skeletal muscle contraction; and it seems most sensible to define muscle
tension simply in that way. In so doing we bypass issues of central
neurophysiological states, and ignore the highly unlikely possibility that

differing types of contraction exist.
This still leaves the problem of operational definition. The methods
used to measure muscle tension have varied widely. As early as 1942, R. C.
Davis catalogued six different modes of measurement, each including multiple
differing techniques. Davis’ careful analysis led him to conclude that the best
method is the electronically integrated electromyogram (EMG) recorded from
electrodes on the skin. There is now general agreement with his viewpoint
that the surface EMG represents the most definite, sensitive, reliable, and
practically useful method of measuring muscle tension. A manual providing a
detailed description of the technique is available. Care must be exerted to
choose electronic components with appropriate characteristics. With such
equipment, the EMG is a direct, linear correlate of isometric skeletal muscle

contraction over most of its range. It appears also to correlate with subjective
feelings of muscle tension.
Nevertheless other methods continue to be used. Among these are a
resonance technique which records combined motion and tension; eye-blink

rate; the speed and accuracy of fine psychomotor activity; the after
contraction phenomenon; several techniques for quantifying movement,
including a “motility bed”; and many others. All may have value. But they are
measuring different phenomena than the muscle action potentials which the
EMG detects. They cannot be considered equivalent either to the EMG or to

one another.
Another problem lies in the choice of the muscle groups to be measured.
Factor analyses applied to data from several independent studies show

convincingly that a general factor of muscle tension does exist. This indicates
that there is a tendency for tension to occur to a similar degree in muscles
throughout the body. However, this tendency is limited. The general factor
neither includes all muscles nor does it represent close to all the variance of
those it does include. Additional factor clusters also emerge from the analyses
that represent more localized patterning of tension. Moreover, it has been
demonstrated that response specificity occurs for the muscles as well as
autonomic variables. This phenomenon, originally identified by Lacey,
represents the tendency for individuals to react physiologically to differing

stimuli in a preferential fashion, with maximum response in a particular,
differing response system. The determinants, or even correlates, of the
“choice” of a specific site of muscular responsivity remain unknown. Stimulus

specificity, the patterning of responses due to the specific effects of a given
stimulus, also seems to occur. The study by Voas also indicated that muscle
tension measured in seven separate sites varied not only for different
individuals but within the same individual during different conditions. In any
single research, therefore, confidence can be placed on the findings only as
they apply to those muscles specifically measured. Very few studies have
included EMG’s from multiple sites. Yet the results from one or two sites are
frequently interpreted as if they represented a valid index of generalized

tension. One of the favored sites is the frontalis. Here the dangers of
erroneous extrapolation are especially great, for this muscle seems to be one
of those least related to the general tension factor. In a few instances there
are several studies focused on a given research question which together
include sufficient sites to permit a reasonable capacity to infer that
generalized tension has been demonstrated. There are also, of course,
questions for which measurement of tension in only a single site is relevant.
If, for example, one wishes to know if a symptom arises from muscle tension,
then the tension at its locus represents the only relevant measure.
Additional methodological problems arise about the selection of
variables for analysis. Is the variable of choice the resting EMG level, or that
reached after stimulation? Is it the mean response or the peak? Is duration of
response more important than its magnitude, or, returning to the matter of
the locus of response, is it better to know when tension involves a greater
number of muscle areas or the body as a whole? There are no a priori
answers. All these indices have been used. Any of them may be valid (i.e.,
relevant) to a given problem. At times, the use of several adds up to a broader

understanding. But the lesson is clear; each study must be examined carefully
to learn precisely what was measured and how, and the results interpreted in
those terms.
Muscle Tension and Personality
Systematic attempts to understand the relation of specific personality
traits to muscle tension began to develop around the turn of the century. One
of the first was provided by William James, who divided people into hyper-
and hypoactive types; the former being excitable, hypermotile, and tense, and
the latter phlegmatic, calm and relaxed. Many other observers have suggested
a similar dichotomy, often emphasizing that hyperactivity occurred at times

of emotional stimulation. These and related studies have been the subject of
an extensive review by Iris Balshan Goldstein.
It seems likely that emotional “excitability” corresponds closely to what
we would now term “trait anxiety.” To be distinguished from the state of
anxiety, this term refers to the characterological tendency to respond with
anxiety to many situations, including those of low threat, i.e., a chronic
proneness to anxiety. The threshold may be so low that anxiety is
experienced even at seeming rest. Using this better defined concept, Balshan
Goldstein found that normal women, scoring high on trait anxiety scales, had
higher levels of tension (in sixteen muscles) during noise stimulation than did
those with low scores. This greater responsiveness was negatively related to
scores for restraint, and positively to scores for general activity in the
Guilford-Zimmerman Temperament Survey, but not to any of its other trait

variables. In a later very similar study, this time using a patient group,
Balshan Goldstein found the same relationship between EMG-measured

tension and trait anxiety. Rossi also demonstrated a relation between these
two variables. Trait anxiety has also been related to eye-blink rate, a measure
that has been proposed as an index of overall tension.
In both of Balshan Goldstein’s studies, tension levels at rest were very

low for all groups. Malmo also believes that stressful stimulation usually is
required to bring out the higher tension levels of more anxious people. Others
have suggested that anxious individuals will have significantly greater tension
even at rest. The explanation for the discrepancy may lie in the degree of
success in creating sufficiently non-stimulating conditions. The anxiety-
inducing effects of exposure to the psychosomatic laboratory itself makes it
difficult to achieve truly basal conditions.
Trait anxiety would be expected to be associated with evidences of
maladjustment. This too has been shown to relate to muscle tension. Duffy
found that children with lower ratings of adjustment in nursery school
manifested higher pressure in squeezing a hand dynamometer. Adults with
increased EMG tension (in the arm, shoulder and back) have been noted to
react to minor environmental changes with anger and irritation. Similarly,

Wenger found that boys judged to be most tense physically tended to be
emotional, irritable, aggressive, and unstable, and that ratings of tension in
children correlated with emotionality, carelessness, distractibility, and

impulsiveness. There is evidence of the same relationship in laboratory
settings as well.
Lacey has reported data suggesting that impulsivity and hyperkinetic
traits are associated with tendencies to exhibit bursts of sympathetic-like
activity, or continuous oscillatory changes, in autonomic variables. Although
he did not measure muscle tension, its correlation with these behaviors has
just been indicated. Lacey’s interesting idea remains conjectural, however,
since the only attempt at replication has proved negative.
The interrelationships among autonomic variables, muscle tension, and
personality represents a barely touched-upon subject that may have
considerable significance. One interesting possibility is opened by the study
of Kempe. This revealed contrasting traits between individuals whose stress
response was primarily autonomic and those who tended to develop
generalized muscle tension. Those with tension responses tended to be aloof,
to deny emotion, and to intellectualize easily. The autonomic responders
were emotional, insecure, and prone to worry. Although stress does have
some tendency to result in a generalized “activation” of all physiological
responses (as will be considered shortly), there is also evidence that the
autonomic and muscle systems may have a reciprocal relationship under
some circumstances. Malmo and Shagass noted this reciprocity between heart
rate, and both motor responses and EMG levels in the arm in a group of
psychiatric patients exposed to a painful stimulus.
In this latter study, some of the motor responses were “defensive,” i.e.,
they served to terminate the painful stimulus. This raises the issue of the role
of psychological defense in producing muscle tension. The traits reported by
Kempe to characterize those who respond to stress with generalized muscle
tension suggest a personality in which defenses against affects are

predominant. This is an issue of great importance. The control of affect,
particularly anger, has been postulated as a major pathogenic mechanism in
several of the musculoskeletal disorders to be discussed in subsequent
sections.
This relationship has been suggested by many psychoanalytic
observations. Abraham reported in 1913 that “during analysis patients show
inhibitions of those bodily movements which derive from a repressed [my
emphasis] erotic pleasure in movement.” Ferenczi noted the frequent

reciprocity between thought and action, and observed that many patients
exhibit stiffness of the limbs during a state of resistance, which disappears
following its resolution. The tendency for the affect-controlled compulsive

character to manifest generalized muscular rigidity was explored in detail by
Reich, who clarified its ties to the rigidity of defense in the important term
“character armor.” He pointed out how physical relaxation can result in a
loosening of defenses and freeing of affective expression. Similarly, Barlow

reported that following relaxation “one may see uncontrollable reactions,
such as laughter and weeping.” Fenichel comments that “pathogenic defense
always means the blocking of certain movements.” He reported that a patient
“who can no longer avoid seeing an interpretation is correct, but nevertheless
tries to, frequently shows cramping of his entire muscular system or of
certain parts of it.” The most detailed psychoanalytic studies were carried out
by Felix Deutsch who reported on the presence of individually characteristic
infantile postures and movements associated with the regressive nature of
the psychoanalytic situation. A portion of what he observed were defensive

movements, e.g., rigidity related to the suppression of thoughts, a point also
emphasized by Ascher. In sum, these observations focus on the role of muscle
tension in relation to defense, and often specifically in relation to control of
affective expression. Plutchik summarizes the implication of these and other
studies in much the same way. He comments also on the ubiquity of reference
to this connection in everyday language (being rigid, keeping one’s chin up,
etc.). There is, in addition, the familiar observation that being self-protectively
“on guard” in the face of danger is associated with muscular tenseness. Also
consistent with the reciprocity noted by Kempe are Kepecs’ psychoanalytic
observations of a reciprocity between muscle and secretory activity, including

weeping and exudation into the skin. He suggests that when the muscles are
about to be activated during rage but this undergoes inhibition, the result
may be actual weeping or weeping lesions of the skin.
An attempt was made by the Michael Reese group to obtain
experimental verification of the relationship between muscle tension and
“control.” In the initial study a series of hospitalized depressed patients were
selected for study because of the motoric disturbances found in this type of
disorder. These patients were exposed to a stressful situation, and one

designed to stimulate efforts at self-control, while EMG recordings were
obtained from seven muscles. The temporary activation of efforts at self-
control did not elevate muscle tension. However, there were a number of
significant correlations between tension in four muscles (frontalis, trapezius,
quadriceps, and particularly the biceps) and several personality trait
measures that seem consistent with the postulated relationship. Tension in
these muscles was greater in the patients who were characterologically less
emotional, less anxious, more prone to use fantasy than action, and who had a
more rigid definition of their body boundaries. An attempt to replicate these

findings on a different study population, a mixed group of psychiatric
outpatients, failed. A careful analysis of the discrepancies suggests that their

major source lay in the differences between the psychological characteristics
of the patients in the two studies. Whatever the explanation, one can only
conclude that the clinical observation that defensive character armoring is
reflected in elevated levels of muscle tension remains unverified in the

laboratory.
The basis for selection of a measure of body boundary definiteness
stemmed from the work of Fisher and Cleveland. These researchers have
conducted a number of studies of body image focused on the degree to which
an individual conceives of his body boundary as representing a distinct
barrier between internal and external interchanges. They developed the

hypothesis that a high “barrier” measure is associated with exterior
psychosomatic disorders, including arthritis, and with greater reactivity of
the physiological systems nearer the surface of the body. In several studies, it
was found that subjects with a high barrier score developed greater levels of
muscle tension in response to stressful stimulation than did those with a low
barrier score. Details of their work and that of others on this subject are
available in two books.
Stress, Arousal, Emotion, and Defense
There is solid evidence that the psychological stress response is
accompanied by an increase in muscle tension in most people. In Duffy’s

studies, the greatest rises in tension occurred with emotional stress. It has
been repeatedly demonstrated that when elevations of muscle tension occur
during interviews, specifically stressful material is being discussed. In one
interesting study, jaw muscle tension was high following criticism by the
therapist, but fell after praise, in both the patient and therapist.
Not only does tension increase under stress, it spreads to involve larger
areas of the body. There is a tendency for an individual to lose his ability to
discretely utilize specific muscles required for appropriate action, and for
tension to spread progressively from that site. Luria’s classical studies
demonstrated that affectively meaningful stimuli produced a disorganization

of purposeful responses in the hand, which became impulsive and tremulous;
there was “overflow” of tension to the muscles of the nonactive hand. Factor
analyses of the data collected in the Michael Reese studies mentioned above
also revealed that muscle responses became more diffuse as stress

intensified.
There is a school of thought which asserts that there are no real
physiological differences among the various states of affect associated with
stress, nor indeed among these and other states of heightened motivation and
mental effort. All such states are seen as representing points of elevation
along a single continuum. Their qualitative differences are ascribed to added
cognitive elements and components of “directionality” (approach avoidance).

The central underlying phenomenon has been termed “arousal” or
“activation,” the former emphasizing its behavioral properties, the latter its
neurophysiological ones. A detailed consideration of this theory and the
evidence upon which it is based is available, and does not concern us here.
What we do need to note is that the theory postulates that the level of
muscle tension (along with manifestations of sympathetic nervous system
activity) parallels the level of activation. Consistent with this are the findings
of increased tension associated with learning, motivation, difficulty of mental
work, reaction time, attention, thinking, etc. (References to this work can be
found in Balshan Goldstein’s review.) Certainly emotional stresses of

essentially every kind have been demonstrated to be associated with
increased muscle tension. One interesting exception is the occurrence of a
precipitous drop in tension, to the point of physical collapse, associated with
sudden surges of intense emotion, the phenomenon known as tonusverlust.
Levels of activation may be applied not only to classify stimuli (stronger
stimuli being more activating) but to characterize individuals as well. There is
a tendency for people to retain their respective ranks in their levels of muscle
tension across a variety of stimulus situations. Individuals at the poles of such

a ranking would presumably be the same ones identified by the hyper- vs.
hypoactive personality typology already described.
While activation theory may have value in understanding states of

affective arousal in general, there are sound reasons for looking beyond it to
more specific issues. As Lacey has so well clarified for autonomic responses,
specific “fractionation” of the general response occurs, with variations

ascribable to the stimulus, to the individual, and probably to the quality of the
internal response state evoked. It has been indicated already that the
tendency for muscles to react in a generalized fashion is not a strong one, and
that there is distinct evidence that more discrete response patterns occur. It is
now a commonplace laboratory observation that rises in muscle tension
during arousal often can be demonstrated if the “correct” muscle is found, but
this site will vary among individuals.
Whatever activation theory does explain, it necessarily begs questions
relevant to the occurrence of specific sites of tension in specific people under

specific circumstances, compelling us to look further.
Anxiety plays a special role in the psychological stress response, being

both an indicator of its presence and a precursor of further response. Hence it
is not surprising that anxiety is the affect most clearly implicated in stress-
associated rises in muscle tension. Motor hyperactivity and “nervous”
mannerisms are widely accepted as evidence of everyday anxiety. Tremor,
purposeless movements, restlessness, and other motor symptoms are regular
features of clinical states of anxiety. Cameron’s systematic analysis of
symptoms occurring in patients with anxiety revealed that the “skeletal

muscle pattern” represented the largest subgroup. Balshan Goldstein
concluded from her extensive review that muscle tension tends to be high,
“particularly in disorders in which anxiety is the major concomitant.” In

studies of the stress responses of psychiatric patients belonging to several
diagnostic categories, Malmo and Shagass found that the degree of anxiety
paralleled the extent of the rise in muscle tension, regardless of the diagnosis
(with some exceptions among chronic schizophrenics). Two separate studies
of hypnotically induced emotions demonstrated that rises in muscle tension
were greater following an anxiety or fear suggestion than one for depression.
A detailed laboratory study of muscle tension in psychiatric outpatients by

the Michael Reese group, involving multiple psychological variables, revealed
that the increases in muscle tension occurring with stress were related most
closely to ratings of anxiety. Both Jacobson and Wolpe consider muscle
tension as an inherent component of the state of anxiety, so that their anxiety

treatment techniques are based on tension reduction.
Anxiety also causes a prolongation of the muscle-tension response to
stressful stimulation. The exaggerated startle reaction so typical of anxiety
seems to be due to this rather than an increased magnitude of response.

Anxious patients manifested a continuing rise in tension following a sudden
noise stimulus at a time when the responses in normals were falling and had
almost disappeared.
Anger also is relevant. The subjective sense of increased tension
associated with rising anger is a familiar experience. A specific attempt to
differentiate the physiological patterns specifically characteristic of fear vs.

anger revealed that both were associated with elevated frontalis tension, with
the levels during anger exceeding those for fear.
The state of frustration may not be identical to that of anger, but it is
certainly one closely akin. In his thoughtful review, Plutchik marshalled a
substantial body of evidence linking frustration and conflict to muscle
tension. He cites a variety of studies which confirm the observable link
between frustration, anger, and hypermotility, and of tension arising in
situations where internal conflicts block action. From these and other data he
concludes that chronic muscular tensions represent “a continuous state of

readiness, indicating present day conflict or frustrations” that “reflect
attitudes which are usually verbally unexpressed.” Freeman also felt
frustration and conflict were central to the development of muscle tension.
If we take a second look at the studies of stress, maladjustment and trait
anxiety, it becomes apparent that irritation, irritability, impatience, and
similar states are frequently part of the reported affective reactions. Given the
complexity of human beings, states in which a single “pure” affect develop are
rare. Experience in the psychosomatic laboratory confirms this; even with the
specific attempt to stimulate a given affect, mixed states occur. Certainly the
physiological features of anxiety, anger, and other affects overlap, requiring
great sophistication in research methodology to delineate their minor,
quantitative differences. It may be that each affect is associated with a

somewhat specific patterning of tension, i.e., with prediliction for certain
muscle groups. Bull has suggested that feeling states arise secondarily as the
perception of the patterned muscular responses which, she feels, represent
the primary emotional state, a derivative of the James-Lange theory. The term
she uses for emotional states is “attitude,” one that has both affective and
positional connotations.
But in every situation of stress and affect arousal it is equally certain

that the reaction also will include elements of ego defense. It is impossible to
conceive of a state of stress in human beings unaccompanied by the
mobilization of defenses and coping mechanisms. The states of frustration and
conflict, discussed above, also include a component of defense. Even simpler

demands for performance, problem solving, attention, etc., necessarily call
forth adaptive efforts. Thus we are brought back again to the possible role of
control and defense mechanisms in the production of muscle tension,

especially when it is sustained. It is possible that it is these processes, rather
than the affect, that is the crucial factor in stress-induced tension.
The two studies which attempted specifically to identify the role of

control were, as indicated, negative. The focus of these was on relatively
conscious and immediate exertions of control efforts, i.e., self-control.
Perhaps a better definition of control related to more automatic processes, or

a focus on other defense and coping mechanisms, especially those linked to
character, might have better payoff. One report, which touches on this
subject, linked the responsiveness of frontalis muscle tension to ego strength,
as measured by the MMPI (Minnesota Multiphasic Personality Inventory).
Given the known inverse relationship of ego strength to such factors as trait
anxiety, which correlate with muscle tension, this seems puzzling. The
explanation may lie in the greater defensive response of the high ego-strength
subjects. Unfortunately the design of the study included no observations of
this dimension.
Any stressful situation will inevitably tend to cause rises in all these
factors concomitantly, i.e., a mixture of various affects, defenses, and coping
maneuvers. A researcher will therefore find the explanatory variables he
happens to look for. The present state of our knowledge suggests that all
these factors may bear a relationship to muscle tension. It seems sensible to
view tension as representing a final common pathway of peripheral response

which is related to a variety of central psychological states. Within this very
general situation, it may be that differential patterning of muscle response
occurs in relation to specific states. To determine if this is so requires more

sophisticated research which can examine a variety of psychological factors
simultaneously, each in relation to tension measures taken from many

muscles. Until then, we are left with many interesting conjectures but only a
few dependable conclusions.
Psychiatric Disorders
There is one direction in which many findings do converge. Every one of
the aforementioned factors suggests that elevated muscle tension should be
found in psychiatric patients. Who, if not psychiatric patients, are prone to
manifest anxiety, conflict, stress sensitivity, etc.? The verification of this is
ample. The overall picture shows that patients with essentially every disorder
exhibit a heightened muscle tension under many conditions. In fact, several of
the studies already discussed have used patient groups precisely for this
reason. Therein lies the problem. In such instances it is difficult to discern if
the findings bear a relationship to the disorder per se. The burden of proof
must rest in the other direction, given the widespread presence of elevated
tension across diagnostic groups.
Several of Malmo’s studies have specifically suggested that anxiety is the
primary significant factor. Also consistent is Martin’s finding that “dysthymic”
(anxious, depressed, and/or obsessional) neurotics displayed significantly

more forearm and frontalis-tension at rest than did hysterics. A similar
comparison by Balshan Goldstein revealed like differences which, however,

were small and not statistically significant. There seems little point, therefore,
in discussing the many studies in which mixed, nonspecified or anxious
patient groups have been studied.
Several studies focusing on schizophrenia have pointed to elevated

levels of tension in these patients, at least under “resting” conditions.
Whatmore and Ellis found resting EMG tension recorded from four areas
(forehead, jaw, forearm, and leg) to be higher in a group of twenty-one
schizophrenics than in ten normal controls. The nature of the patient group
was not specified beyond statements that they had “clear-cut” diagnoses, and
were “without signs of deterioration.” Malmo and his coworkers compared
neck and forearm EMG levels in seventeen chronic schizophrenics, with
groups of “acute psychotics,” neurotics, and normal controls. All patient
groups had high levels of tension at rest, whereas the normals did not.
Stressful stimulation produced an increase in tension for all groups, but the
rise was significantly lower for the chronic schizophrenics than the other
patient groups, with the normals falling between. The schizophrenics were
especially less responsive if the stimulus was brief. Very similar results to
those of Malmo were obtained by Williams using a resonance (non-EMG)
technique.
In a previous study from the same laboratory, “early” schizophrenics

were found to be similar to very anxious neurotics. Both showed high levels of
neck tension in response to painful stimulation. The schizophrenics, however,

manifested poor discrimination among the various levels of stimulus
intensity. Martin also reported that early schizophrenics were significantly

more tense (frontalis and forearm EMG) than normals. But the difference was
present at rest and disappeared following stimulation.
In a complex and methodologically sophisticated study, Balshan
Goldstein compared muscle tension in psychotics, neurotics, patients with
character disorders, and normal controls. All groups included contained
fifteen subjects, and both sexes. The psychotics were not chronic and included
ten schizophrenics. The EMG records were obtained from seven muscles at
rest and in response to a noise stimulus. The psychotics had generally higher
tension levels at rest, and distinctly greater responses to the noise. The
differences were significant for the sternocleidomastoid, frontalis, biceps, and
forearm extensor muscles, especially the forearm. Both the normals and
patients with character disorders had low levels and responses, while the
neurotics fell between. This study incorporated a unique feature in that the
neurotic and psychotic groups were equated for their levels of anxiety on the
Taylor MAS scale (manifest anxiety scale). Thus their differences in tension
seem reliably related to the diagnostic difference itself. This is the only study
about which such a statement can be made with confidence.
Whatmore and Ellis also conducted studies of depression. In their initial

project, six severely retarded patients, as well as thirteen patients with
agitated or mixed pictures, were compared with matched controls. All were
female. Resting EMG recordings (forehead, jaw, forearm, and leg) revealed
high tension in all areas, with the greatest differences in the jaw muscles, and
the least in the frontalis. The highest levels occurred in the retarded
depressives. On the basis of these data Whatmore and Ellis formulated a
theory that persistent muscular hypertension at rest, which they termed
“hyperponesis,” reflected a central neurophysiological state that was an
inherent aspect of the depressive disorder. This formulation, however, is not

only vague but loses some credibility from their own previous similar
findings in schizophrenics, of which they make no mention. Nevertheless
their data, particularly those in retarded patients, are of great interest.
In their second project, five previously studied severely retarded
depressed patients were followed with the same measures longitudinally

through remissions and relapses. Increased tension was again demonstrated
during periods of depression. Although the levels decreased temporarily
during successful treatment, they soon returned to the previous high levels
which persisted “indefinitely.” In one patient, a relapse was just preceded by
an increase above the already elevated level. Whatmore and Ellis interpret
these data as further support for their concept of “hyperponesis.”
Martin and Rees found increased forearm tension in female depressives
during a reaction-time test, compared to controls. While patients’ mean
reaction times were slower, some of their responses were as fast as the
normals, suggesting that the difference may have been due to reduced
motivation.
The degree of elevation in forearm tension was found to correlate with
the severity of depression in a group of patients (of both sexes) studied by
Noble and Lader. Tension correlated also with the level of anxiety. In contrast
to Whatmore and Ellis’ findings, the elevated resting level dropped
significantly following electroconvulsive therapy (ECT). Mental arithmetic
produced an increase in tension to about the same levels both before and
after ECT, the extent of the change being greater afterwards because of the
lower resting level. A positive relationship between the intensity of
depression and the level of resting tension in the forearm, and to some extent
the frontalis, was found also in another study of depressed patients, by Rimon
et al. This was more certain for males than females. Jaw tension however,
which Whatmore and Ellis reported as showing the highest levels, had a
negative relationship with the severity of depression in both sexes. The
posttreatment data are confusing. Patients who made a good recovery

showed an increase in tension, while those who had a poor recovery had a
decrease.
Data on depressives was obtained also in the aforementioned study by
Balshan Goldstein. Tension levels were recorded from seven muscles in
nonpsycliotic depressed patients and matched groups of nondepressed

neurotics and controls. Each contained thirteen women and eight men.
Following a stimulus, the depressed patients had significantly higher levels of
tension in the trapezius and frontalis; in the forearm the difference fell just
short of significance. Similar, but insignificant, differences were present at
rest. No differences in jaw tension were found, a result in accord with the
findings of Rimon but directly contrary to those of Whatmore and Ellis. It

seems likely that Goldstein’s subjects were less severely depressed than those
in either of these two studies, which had included psychotic patients.
Whatmore and Ellis’ patients also were older, a factor which Rimon found to
be associated with higher levels of tension.
The problem of relating specific sites of tension to specific disorders is

illustrated by the data on the forearm extensors. Elevated tension in these
muscles is the most reliable finding in depressives, having been reported in
all the studies discussed above. However, it has also been reported to occur in
schizophrenics in three separate studies.
A recent study has demonstrated a decrease in the postural reflex
activity of the shoulder (supraspinatus) in depressed patients. This

correlated, in general, with the level of depression. These findings fit with the
commonly observable slumped posture of depressives. An essential point is
that this interesting technique is entirely different from that used in the other
studies considered above.
It might be mentioned also that psychotics of all types are said to differ
from neurotics in having significant disturbances of fine psychomotor activity.
Finally, it should be noted that characteristic microscopic muscle lesions and
an elevation in circulating levels of certain muscle enzymes have been
reported to occur in patients with a variety of acute psychoses.
Conclusions
It seems possible to come to a few general conclusions despite the
differing and somewhat confusing nature of this array of data:
1. There is a tendency for individuals to be characterized by different
levels of muscle tension and to maintain this relative level in various
situations. Perhaps the best personality correlate of higher levels of tension is
the tendency to experience anxiety and to manifest other forms of emotional

hyperreactivity.
2. Individuals have a proclivity to develop tension, when stimulated,

primarily in specific sites characteristic for themselves. Under conditions of
increased arousal, tension tends to become progressively more generalized,
and the differences among individuals thus tend to disappear.
3. Under stressful conditions, particularly those which induce anxiety,
muscle tension rises. At high anxiety levels this increase in response is likely
to be accompanied by its prolongation in time, and by its spread, leading to
disruption of motor coordination. The relationship of stress-induced tension

with heightened anxiety is clearest, but it may be related also to anger and
other affects, to the mobilization of certain defenses, to the state of conflict or
frustration, or to all of these.
4. Patients with psychiatric disorders of every type are likely to exhibit
high levels of muscle tension, especially after stressful stimulation. It is

uncertain if this relates to the disorders themselves or is merely a reflection
of anxiety and the other factors just mentioned. Increased tension may be
especially characteristic of two disorders, schizophrenia and the depressions,

above and beyond the presence of anxiety. For the depressions, where the
evidence seems particularly strong, the level of tension seems to parallel the
severity of the disorder, even in the presence of overt psychomotor

retardation.
5. No convincing evidence yet exists to relate specific patterns or sites of
muscle tension to specific affect states or to specific psychiatric diagnostic
entities, despite several interesting suggestions. This state of knowledge may

be partly a product of the fact that few studies have obtained tension
measures from more than a limited number of sites.
6. Clarification of many of these problems seems amenable to research
embodying now existing technical and methodological knowledge.
These conclusions reflect the substantial body of research on the basic
psychophysiology of muscle tension. None of them bears directly on the role

of muscle tension in the musculoskeletal disorders. They do, however, have
some relevance to the psychological characteristics which have been
suggested as playing a significant role in these disorders, as will be seen.

There are also a few studies in which tension measures have been made
directly in patients with given disorders. These will be considered, as
appropriate, within the following sections which deal with each disorder.
Psychogenic Rheumatism
While the term “rheumatism” lacks precise meaning, that very quality
may have a particular aptness in grouping together a grab bag of disabilities
which have common underlying features. The complaints may include a
variety of aches, pains, weakness, stiffness, and other uncomfortable
sensations in the muscles or joints, as well as subjective swelling, tenderness,

and limitation of motion. These may involve a single area, several, or occur
“all over” the body, and they may be migratory. The diagnosis of psychogenic
rheumatism is applied to such disorders in which the symptoms and

disability occur in the absence of established “organic” disease or are
significantly out of proportion to its extent. Clinically, the complaints often
have a vague or odd quality, may not conform to expected anatomic
distributions, and may be unrelieved by analgesics or physical therapies.
Abnormal, sometimes bizarre, posture and movements may develop.
However, the symptoms can closely mimic known organic diseases.
The overall incidence of minor isolated rheumatic symptoms must be
100 percent. (Who has not had unexplainable aches and pains?) But there are
no clear figures for the prevalence of disability significant enough to require
diagnostic labeling. It is established that this disorder occurs frequently
enough to comprise a major portion of the patients with diagnosed rheumatic
disease. In several large series, reviewed by Boland, it consistently ranked
among the top three causes of rheumatic disease, along with rheumatoid and
osteoarthritis. The incidence seems to be particularly high in military

personnel, where figures as high as 34 and 42 percent of the admissions to
special rheumatic centers have been reported. In this setting, its onset is
especially common just prior to overseas or combat duty.
Some further idea of the vast extent of rheumatic disease and its
disability, particularly in the military, is provided by data on veterans’
pensions. In 1931 (an era when the number of veterans was far fewer than it
is today and their care was far less complete) the Federal government was
providing pensions to more than 35,000 disabled veterans in this category, at

an annual cost exceeding 10 million dollars!
Classification and Mechanisms
Boland, who provides one of the best general reviews of the subject,
refers to the disorder also as “psychoneurotic musculoskeletal complaints.”

He does so to emphasize the very high incidence of coexisting neurotic
symptoms and predisposing “neurotic traits” he finds to be characteristic.
Ehrlich also describes it as a form of psychoneurosis. The studies on which

this impression is based, however, lacked adequate controls, and the ubiquity
of psychiatric symptoms when these are skillfully sought after makes one
cautious about this viewpoint. It seems likely that many cases of lesser
severity which do not require referral to a rheumatologist or psychiatrist will

fail to demonstrate overt psychopathology.
Boland classifies psychogenic rheumatism into three subtypes: (1) pure;
(2) superimposed (functional overlay); and (3) residual (functional
prolongation).22 The last most often follows trauma, while the superimposed
type is usually associated with more minor rheumatic diseases, rather than
with a serious articular disease such as rheumatoid arthritis. Fibrositis is
traditionally included as one minor condition particularly prone to

psychogenic overlay. But there is good reason to question whether this entity
exists at all. Its diagnosis is based on subjective complaints. Though nodules

are sometimes palpable, Halliday has pointed out that these can be found
(as?) often, if sought for, in asymptomatic individuals. In one study cited by
Boland, 70 percent of cases labeled as fibrositis showed “significant
psychiatric disorders.” Although acknowledging the difficulties in diagnosis,
Hench and Boland suggest that, with care, the two can be differentiated
clinically. They characterize fibrositis as having more localized and definite

symptoms which are highly responsive to external temperature and humidity
(rather than to mood, distraction, or emotional stress), as having a better
response to the usual therapies, as associated with less disability, and as

occurring in less neurotic patients who are more calm and cooperative during
examination, and who may evidence a more “objective” attitude about their
illness.
Halliday, the earliest serious student of the problem, classified fibrositis
as one of three types of psychogenic rheumatism. The others were hysterical

pains, seen most often in people in hazardous occupations, and symptoms
arising as manifestations of a psychoneurotic anxiety state or psychotic
depression. Paul, who studied back pain, divided that condition into four
categories. These included: (1) pain due to muscle tension “of conversion
origin;” (2) pain of conversion origin without increased muscle tension; (3)
pain due to muscle tension of “anxiety-tension origin;” and (4) any of these
with associated back disease or injury.
Each of these classifications has some heuristic value, but a fully

satisfactory taxonomy remains to be developed. One problem centers around
symptoms arising from conversion (hysterical) mechanisms. Because they
represent psychogenic rather than psychophysiological disturbances,
conventionally these are excluded from the “psychosomatic” category. This
may be entirely appropriate for such curious and blatant examples of hysteria
as camptocormia, or the “stiff-man” syndrome. But it is likely that more minor
conversion mechanisms are involved in some of the ordinary disorders
diagnosed as psychogenic rheumatism. This may occur as a secondary
elaboration of symptoms which initially developed on a psychophysiological

basis. Faulty postural compensations also can add a significant element to
symptoms which arose originally on a psychological basis.
Nevertheless in most instances the major pathogenic mechanism seems
to be a psychophysiological one, i.e., elevated muscle tension. Of the several

major clinical disorders considered in this chapter in which increased muscle
tension has been hypothesized to be the significant mechanism, the evidence
seems by far most dependable for psychogenic rheumatism. Clear signs of

localized muscle tension are often readily apparent in the physical
examination of patients with the symptoms of psychogenic rheumatism. This

clinical finding has been confirmed by EMG measures. Particularly relevant is
the phenomenon termed “symptom specificity,” elucidated by the excellent

research of Malmo and Shagass. Symptom specificity refers to the fact that the
stress response of some individuals is characterized by a distinct predilection
for hyperactivity in a given muscle (or autonomic variable) leading to
symptoms directly referable to that increased activity. Thus, patients with a
history of head and neck pains responded to psychological stress with greater
rises in neck-muscle tension than did controls or patients with cardiovascular

symptoms, while the latter patients had the greatest cardiovascular changes.
In longitudinal studies, several headache patients manifested periods of
increased head and neck tension occurring during stress, and it was at such
times that episodes of their typical pain occurred.
Rinehart, disciple of Jacobson’s “progressive relaxation,” also identifies

elevated muscle tension as the primary issue in psychogenic rheumatism. His
entirely anecdotal report loses all credibility, however, by lumping together
all rheumatic disease (including rheumatoid and osteoarthritis) as having the

identical pathophysiology and pathogenesis, as does the entire school of
“progressive relaxation” by its indiscriminate implication of muscular
hypertension as being the central defect in a large array of disease processes.
Psychogenesis
There are few disorders in which patients’ use of symbolic organ
language is as conspicuous as in psychogenic rheumatism. One is struck, as
were Halliday, Weiss, and Paul, by these patients’ references to themselves,

their reactions, and their world in terms replete with musculoskeletal
connotations. They are people who “wouldn’t stoop” to certain behavior, even
when they meet “stiff’ situations, as might a “spineless” person; they manage
somehow to “limp along” and “not buckle,” even when things are a “pain in
the neck,” etc.
Two themes are especially prominent in their expressions: anger and its
control. These same issues were identified by Weiss as the characteristic

feature of forty patients with varied rheumatic symptoms. His interviews
revealed “chronic resentment” and “smoldering discontent” to be their
“special emotional problem.” They were “burned up” and “aching to” express
their hostility, but were unable to do so because of repressing forces. Weiss
went on to comment that muscles “serve as the means for defense and attack
in the struggle for existence,” and that chronic muscle tension arises when the
expression of aggression is inhibited.
The very careful study of seventy-five diverse backache patients led
Holmes and Wolff to quite similar conclusions, despite their different

(nonpsychoanalytic) frame of reference. They were able to discern a common
“basic personality” characterized by an “action orientation” going back to
childhood, and by a “basic insecurity” which had led to a wary, tentative, “on-
guard” approach to people and life situations. These patients had many
obsessive-compulsive character traits and a strong need to “keep the peace.”

Episodes of back pain occurred in life situations in which they felt
disapproved, unreceiving of deserved praise, or criticized despite their
efforts, and thus felt “anger and resentment” over being taken advantage of,
but could not take action without increasing their insecurity. They dealt with
this conflict by being even more “on guard.” Support for this formulation
came from EMG measures taken during interviews. Striking increases in
muscle tension occurred during the discussion of stressful events of the
specific type noted, which were especially prone to occur when the current
life situation was of the same nature.
Something very like the “on-guard” attitude seems to characterize the
response of these patients during medical examinations. Hench and Boland
describe the attitude of “touch me not” as being sufficiently typical to
constitute a clue to diagnosis. The obsessive-compulsive traits also were

noted by both Halliday and by Rinehart. This makes sense, given the
psychodynamic relationships of such defenses to the control of anger, and
their common “anal” genetic origin—a shorthand designation for a

developmental period in which the main issue is the mastery and control of
muscular activity.
However, the clinical descriptions provided in these and several other

reports include some patients who have manifest anxiety. This was the major
quality communicated in Boland’s descriptions, as already noted. The

question therefore exists whether it is the anger, its control, or anxiety over
that or other conflicts, which is the relevant factor. Basic research, as I have
noted in an earlier section, leaves this matter open. Perhaps the wisest
present position that can be taken is that one must determine individually for
each patient the psychological factors that are involved in his increased
muscle tension.
Chapman makes the interesting observation that these disorders occur

mainly in muscles that have important uses in animals, but are of lesser
importance in man. Just why a given site is involved in a given person is not
always clear. What psychological factors contribute to the “symptom
specificity”? Sometimes the specific symbolic meanings of the part seem to be
involved. These may become apparent in the organ language used to describe
the symptoms. One interesting lead is provided by experimental findings

which suggest that hostility is related to tension in the arm, and that, in
women, sexual problems are related to leg tension. Further work of this type
is needed.
Treatment
As always, good treatment rests on accurate diagnosis. Little can be
added to Halliday’s advice that this requires establishing what kind of a
person this is, why did he take ill when he did, and in the manner that he did.
In many mild cases, the kind of doctor-patient relationship inherent in this
approach itself leads to a reduction in the intensity of conflicts, allowing for
recovery. At an early stage the usual simpler techniques of symptomatic
relief, reassurance, support, ventilation, and environmental manipulation
usually suffice. Muscle relaxants may be very useful for the anxious patient,
especially if these also have “tranquilizer” effects. These agents require more
cautious use in rigidly controlled patients, who suffer from generalized
muscle tension. “Relaxation” may have a paradoxical effect by threatening
such patients with an inability to maintain their defenses.
Major and prolonged illnesses represent a far more difficult problem.
There is great value in early intervention before symptoms have become fixed
and elements of secondary gain are superimposed. As Hench and Boland
understate it: “Our pleasure at being able to reassure soldiers . . . that they do
not have arthritis . . . and need not fear the presence of a crippling disease is
tempered by the difficulty in helping them develop insight and to accept the
diagnosis.” Physical and pharmacological therapies specifically associated

with “organic” forms of arthritis should be avoided, since the patient uses
these to reinforce his denial of the psychogenic nature of his illness. The
physician’s firmness in this regard does not require being argumentative and
must be combined with an accepting open attitude to the patient. The

treatment of persistent symptoms in its further details merges into the entire
body of techniques of psychotherapy.
Special therapeutic techniques designed specifically to reduce muscle
tension promise usefulness in those many instances where muscular
hypertension can be implicated. These include “autogenic training,”
“progressive relaxation,” hypnosis, and the “reciprocal inhibition,” associated
with behavior therapies. All of these techniques have been reported to
produce significant immediate relaxation in selected individual instances
during training sessions. This has been confirmed by EMG measures. But it is
yet far from clear how much generalization occurs to situations outside
sessions, whether reports of outside subjective improvement are also
associated with demonstrable reductions in EMG levels, or how widely
applicable such methods are to different patients. The body of literature on

these techniques is very large, but almost none of the “research” reports can
be said to embody even the most minimal principles of scientific
methodology, though beginnings are being made.
Occupational Cramp
The occupational cramps include a large number of functional disorders
characterized by the impairment of a specific learned occupational motor
skill. The dysfunction typically is associated with muscle spasm, and pain or
severe discomfort of the involved part, although the specific clinical features
vary. An excellent brief review of the subject is available.
The varieties of cramp are apparently as numerous as there are
occupational motor acts. Some thirty-four varieties affecting the upper
extremity alone have been delineated, ranging from telegraphist’s, to cigar
maker’s, to violinist’s cramp! The various forms seem to have much in
common. The incidence of each seems merely to reflect the prevalence of the
skill. For this reason writing is by far most often affected.
Writers cramp is well known and certainly the best studied of these
disorders. Crisp and Moldofsky have reviewed the subject extensively. It
exists essentially in all cultures. Its incidence is reported as being 0.1 percent
of “neuropsychiatric cases,” though the meaning of this figure is obscure,
given the impossibility of defining the base. Mild cases are probably quite
numerous. As with the other occupational cramps, its psychogenic nature is
evident from the fact that a specific skill is involved, while unrelated activities
involving the same muscles and movements are spared or minimally affected.
The disability tends to increase with stress, and concomitant neurotic
symptoms are usually found.
Many psychologists would formulate the origins of the disorder as a

“faulty learning experience.” This viewpoint has become more attractive
because of the resurgent interest in the application of learning models to
behavioral disorders. But the idea is not new, and corresponds closely to that
held by Pierre Janet. Techniques of “reeducation” have, indeed, proved
somewhat efficacious. This is more likely to be the case when they are
combined with other techniques of effective psychotherapy. Partly, such
reeducation may be required because of the superimposition of secondary
maladaptive compensatory positions and movements, which do represent a

form of erroneous learning. Frustration and anxiety over anticipated failure
play a role in this development. In any event, the faulty-learning-habit
explanation begs the questions of why the learning was deviant, and why the
disorder developed when it did.
Psychiatrists have tended generally to classify writer’s cramp as a
psychoneurotic symptom, though most formulations have been vague. Most
writers have tended to view it as an hysterical symptom, though noting that it
might occur in conjunction with an obsessional state. Cameron viewed it as an

hysterical symptom related to ambivalence over the writing activity, and
Glover felt it represented an hysterical conversion mechanism.
Crisp and Moldofsky present compelling arguments for placing it

instead in the psychosomatic (psychophysiological) category. Careful study
revealed that their patients lacked the classical hysterical features, i.e., they
were neither bland nor manipulative. In fact, obsessive-compulsive traits

were usual. Secondary gain played a minimal role; the actual inability to write
was rare. Instead, there was a “continuing unresolved ambivalence” over

writing, with expressed resentment over having to do so. Symptomatic
exacerbations corresponded closely with periods of intensified resentment.
Thus, the disorder seems to represent a concomitant of affective disturbance,
rather than a neurotic defense against it. Finally, a physiological disturbance
of the motor system does seem to be present and to extend beyond the
symptom. Von Reis has provided EMG evidence of widespread muscle tension
throughout the arm of the involved hand, occurring even at rest.
Crisp and Moldofsky’s experience also underlines the value of an overall
treatment program which combines psychotherapy with both relaxation
exercises and reeducation. They emphasize that the transference relationship
plays a key role in the effectiveness of treatment, sufficiently so that it can be
used as a predictor of therapeutic success.
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an inflammatory disorder of connective

tissue, with polyarthritis as its most characteristic feature. The arthritis has a
predilection for the more peripheral and smaller joints, and is typically
symmetrical. The pathological process in the joints is one of acute
proliferative inflammation which attacks the synovial membrane. This results

in the formation of a granulomatous pannus, with damage and destruction of
the underlying cartilage. Adhesions and scar formation tend to occur,
eventuating in disability and deformity which may be crippling. Any of the
connective tissues throughout the body may be involved in a similar
inflammatory process. Constitutional symptoms are common. The typical
course of the disease is dominated by unexplained exacerbations and
remissions, which may be total. Attacks may vary greatly in the severity of the
arthritis and other symptoms, and there are marked differences in the long-
term course of those afflicted.
The disease is worldwide, though it may be less common in the tropics.
It occurs at all ages, the most common onset being the mid-30s. Females are
affected about two and one half times more frequently than men, with onset
in middle age not uncommon. It is generally said to occur in approximately 3
percent of the population. Precise figures, however, are uncertain because of
its episodic and varying course, even with the arduous development of
standard diagnostic criteria. It has been suggested that RA may be a much
more common and benign disorder overall than is generally believed.
Rheumatoid arthritis is classified as one of the collagen or connective

tissue diseases, grouped together because of their common histopathological
features, symptoms, therapeutic response to steroids, and other similarities.
The etiology of all these disorders is unknown. There are strong indications
that alterations in the immune response are involved. Even if this is
confirmed, the causative factors that initiate and underlie this immunological
disturbance require clarification.
Genetic factors also have been implicated, since RA has a high familial
incidence; but such a finding can arise from environmental as well as genetic
factors, and definitive data are lacking. Genetic explanations are inadequate
to explain certain peculiarities of its familial incidence, for example its
increased frequency in spouses.
Psychosomatic Correlations; the “RA Personality”
The notion that RA might be a psychosomatic disorder is an ancient one.
Paulus Aegineta, who lived in the sixth or seventh century, ascribed attacks to
“sorrow, care, watchfulness and other passions of the mind.” In modem times,
well over 100 papers and books have appeared which have linked
psychological and social factors to the disease. The bulk of this work has been
examined in several thoughtful and comprehensive reviews (see references
133, 179, 187, 236, and 267). The book by Prick and Van de Loo, published in
1964, contains summaries of most of the then available studies, including
many by European workers not included in other sources. Further
information is provided by the Annual Rheumatism Review, published since

1935.
The vast preponderance of reports which deal directly with the role of
psychological factors in RA are in agreement that stress is associated with
attacks, if not the origin of the disease. Much of this material, unfortunately, is
anecdotal and impressionistic. It is little different from what has been
reported for innumerable other disease states. Seemingly every type of
stressful situation has been implicated. On the other hand, the most extensive
clinical epidemiological study of arthritis thus far carried out, reported a

failure to find evidence of stressful situations associated with the onset of RA.
It is difficult to place much reliance on this report either, however, because of
the grossly superficial methods used to collect the psychological data.
Some studies have attempted to go beyond this level of generality to
identify personality features that might characterize the RA patient. This
work has provided descriptions of these patients as shy, leading quiet lives,
and feeling inadequate and inferior; as self-sacrificing and needing to serve
others; as conscientious, dutiful and compulsive; as having a strict, rigid,

moralistic conscience; and as manifesting a tendency to depression. This
offers too much diversity to indicate that there is any one simple overt “RA
personality type.”
Still other studies have probed deeper to attempt to identify underlying
conflicts and defenses. These suggest that there may well be specific
psychological attributes which characterize RA patients at this deeper level. A

preponderance of this work suggests in a variety of ways that the central
issue for these patients relates to the control or containment of anger (see
references 20, 39, 47, 123, 125, 150, and 222) Thus, RA patients are felt to
have a great deal of unconscious or unexpressed anger (see references 20,
125, 149, 150, and 172); but they sharply restrict their overt expressions of
hostility (and other emotions) (see references 20, 39, 47, 104, 125, 150, and
172); and avoid situations likely to result in disagreement; because anger,

they report, “is likely to make their joints worse.” Swaim links the recovery
from RA to the patient’s capacity to develop a satisfactory overall philosophy
of life leading to a state of spiritual harmony. It would be easy to dismiss this
as unscientific and irrelevant, were it not for the fact that this author is a
renowned rheumatologist, and that his approach involves persuading his
patients to “give their resentments to God.” (My emphasis.)
RA patients also have been reported to engage in a great deal of physical
activity in the form of sports and hard work. The preference for these
activities is reported to go back to childhood, and has been interpreted as
representing a preferred method for safely discharging aggression (see
references 15, 25, 38, 47, 125, 150, and 172). Thus it has been suggested that
RA may be precipitated when this channel for discharge becomes blocked.
Arthritics of both sexes have been reported also to suffer from disturbances
in sexual identification (see references 15, 25, 125, 147, 172, and 253). In the
females, this has been described as having the features of a classical

masculine protest reaction, which seems linked to their involvement in active
physical sports as girls.
Perhaps fears of disagreements and the need to maintain tight
emotional control explain their reported difficulty in establishing close
relationships, and also their shy, quiet attributes already mentioned. Most of
the other overt personality traits noted (being compulsive, self-sacrificing and
depressed, having a strict conscience, etc.) are equally consistent with
conflicts over hostility and aggression, as these can be understood within a
psychoanalytic framework. The seemingly diverse overt personality traits,

therefore, exhibit psychodynamic coherence.
Another reported finding is a frequent history of separation or loss of a
parent figure during childhood (see references 15, 20, 25, 36, 146, 150, 222,
and 243). It has been suggested that grief and separation are important
antecedent stresses in relation to the development of an attack. In two
studies, however, the control groups showed an equal or higher incidence of
early parental loss.
All these trends were noted by King in his 1955 review. Justifiably, he
was critical of methodological deficiencies in all the studies then available.
Most were impressionistic and lacked control for bias; almost none used
comparison groups; diagnosis was loose; and all were retrospective and thus
potentially interpretable in terms of the consequences of RA, etc. Yet, as King
indicated, there is an impressive consistency to this work, especially in the

prominence of problems related to aggression.
The attempt to develop a comprehensive, coherent schema, that utilized
psychoanalytic insights, in order to explain the genesis of RA and other
psychosomatic diseases reached its acme in the work of Franz Alexander and
his co-workers. For over thirty years this group carried out a series of
intensive studies of patients with several psychosomatic disorders to elicit a
“specific dynamic configuration” characterizing each. It was their view that
such a configuration, in combination with certain equally specific but

unknown somatic factors, led to susceptibility to the disease. The disorder
would then appear in situations whose nature was specifically such as to
severely aggravate the conflict nuclear to the configuration.
The formulation developed for RA indicated that these patients: (1) had
overprotective, restrictive parents who stimulated rebellious feelings
together with heightened anxiety over the expression of these; (2) the
rebellion was discharged in childhood via sports and physical activity,

associated in women with a masculine protest reaction; (3) progressively in
later life hostility was expressed through masochistic self-sacrifice which

served to control the environment while denying hostility (benevolent
tyranny); (4) an interruption in the availability or success of this pattern led
to rising anger and increased conflict over its expression; (5) this led to
simultaneous increased tension in both sets of opposing (because of the
conflict) muscles; and (6) this led somehow to arthritis.
Methodological considerations momentarily aside, the formulation has
an elegant quality in its internal consistency and its integration of diverse
observational data. Its correctness, moreover, need not be limited by its
etiological implications. There is no reason why this formulation cannot be
correct at the descriptive level, even if it proves inadequate at the explanatory
level. The two are separable. The former requires merely establishing that the
postulated psychodynamic features are characteristic of RA patients.

Validation of the latter requires additional data demonstrating that these
characteristics existed prior to the onset of the disease, and represented
necessary and/or sufficient factors for its occurrence. Whether this
formulation will be acceptable even in this limited descriptive sense depends

ultimately on one’s willingness to accept conceptualizations of human
behavior in psychoanalytic terms. One can only note that for clinicians with
this orientation who have actual experience working with arthritics, the
formulation does seem remarkably applicable to many RA patients.
The study on which it is based does, of course, exhibit grave

methodological faults. The patients were interviewed with full knowledge of
their diagnosis and of the personality traits reported by previous
investigators, and no control groups were used. Some reassurance is

provided by a later systematic validation study conducted by the Alexander
group. Using eighty-three patients representing seven major psychosomatic
disorders for which formulations had been developed, “blind” diagnoses were
made on case records from which medical diagnostic clues were deleted.
Psychoanalytic judges were able to make the correct diagnosis significantly
more often than at chance expectancy, and also significantly better than could
a group of internists judging the same data. The degree of success in
identifying the RA patients was particularly high.
Additional confirmation comes from studies carried out by Cleveland
and Fisher utilizing psychological test data. They compared RA patients with
a matched control group of patients suffering from back pain, utilizing a

battery of projective tests, such as Rorschach, TAT (thematic apperception
test), and DAP (draw-a-person), to elicit unconscious fantasies. The fantasies
of the RA patient “were so unique that three psychologists were able to

differentiate with only one error” the RA patients from the controls. During
interviews the RA patient was noted to be an “overtly calm” person who
“rarely expresses or feels anger.” But the test data revealed that “covertly he
seems to be containing a large amount of hostile feelings.” The RA patients
displayed evidence of a relatively unique body image, characterized “as a kind
of hollow container filled with uncontrolled fluid material and surrounded by
a hard, unpenetrable surface.” This external “barrier” quality was

conceptualized as playing a major role in the defense against hostile
expression.
Cleveland and Fisher also compared RA with ulcer patients. Both groups
evidenced strong hostility. But the RA patients were distinctive in their use of
physical activity as a technique for handling this, and they more frequently
gave a history of greater participation in rugged physical activity during early
life. Subsequent studies utilizing similar test data have confirmed the findings
with regard both to body image and contained hostility. The general nature of
these findings is also remarkably consistent with the early, less systematic
Rorschach studies of Booth.
Further information has been provided by the series of careful
psychosocial studies carried out by Cobb, King, and their associates, using
sophisticated survey research methods. These data confirmed previous
observations that RA is more prevalent in the lower classes. (As one observer
has put it, “RA seems to be a disease of losers ... all evidences of the disease
were commoner in those with low incomes or little education.”) Discrepancy

between income and education, which King and Cobb point to as an indicator
of social-status stress, was especially associated with RA. Other indices of

social stress also were more common.
Certain factors appeared prevalent specifically in women with RA. They
had come from parental homes with high social-status stress; they reported
mother’s authority and discipline as more arbitrary and controlling; their

recalled reaction to this was high covert hostility but very low overt
resistance and aggressiveness; and they evidenced strong identification with
mother despite her negative image. As adults, the conflicts over the control of
anger remained in evidence, and they manifested evidence of poorer mental
health functioning. Their own marriages too were likely to be with husbands
of incongruent social status, and to be characterized by much hostility. Men
married to these women are more likely to have peptic ulcers. Taken all
together, these data on women are in remarkable agreement with the
psychoanalytically derived formulation of the Alexander group. The

information regarding the families of origin is of special interest in that it
represents reasonably objective evidence of stress antecedent to the disease
onset.
Cobb and his associates also report that RA patients had a higher
incidence of divorce but put up with an unsatisfactory marriage longer than
those free of the disease. They interpret this as evidence of the suppression of
hostility. A Swedish study failed to confirm the higher divorce rate for RA
patients. The implication that this represents refutation, however, is
incorrect, pointing up an important methodological clarification about this

type of research. Divorce and similar social indices represent culture-bound
phenomena with multiple determinants. Within any one society, divorce can
be interpreted as an evidence of interpersonal disturbance. The fact that it
does not occur differentially in another society may merely mean that other
cultural determinants there make it sufficiently accessible or inaccessible to
its members, so that psychological factors become irrelevant. In such a
culture interpersonal difficulties, when present, will be evidenced in
alternative aspects of social behavior. The data of Cobb et al. deserve the test
of replication within the United States; but this would represent their only
valid test.
It seems appropriate at this point to mention the reported relationship
of RA to schizophrenia. Two studies have suggested that the disorders rarely
occur simultaneously. In one study, not a single case of arthritis was found
among 2200 patients at a mental hospital. In another, only twenty arthritics
were found among more than 15,000 hospitalized psychotics. Both studies
exhibit serious methodological deficiencies. Yet, the magnitude of these

findings is impressive. If they are correct, it is difficult to interpret their
meaning. Some observers have suggested that RA patients are, underneath,
seriously disturbed psychologically, and that RA may thus constitute an

organismic defense against psychosis.
Objective Tests
The aforementioned studies by Cobb, King, et al. and by Cleveland and
Fisher represented a major advance in methodological sophistication.

Nevertheless, these too had shortcomings that have been pointed out by
Scotch and Geiger. In an effort to introduce greater precision, a number of
investigators have carried out a series of studies using better defined samples
and better control groups, and relying on objective psychological tests,
usually the MMPI.
The choice of such tests deserves comment. They can be easily and
directly scored, have well-established baseline data on large normal and

other samples, and provide concrete quantifiable data. They can provide
measures of static traits or trait clusters, including nomothetic expressions of
underlying motivational forces (e.g., hostility, dependency) one at a time.
These data are important, valid and reliable. But they are simply not relevant
to every problem. These tests do not provide information about dynamic
relationships among motivational forces and defenses, nor their ideographic

expressions. They cannot provide any direct information about the presence
of a complex psychodynamic configuration of the type proposed by
Alexander. Some reviewers have reacted to “projective” psychological tests as

if that adjective represented the converse of objective, i.e., as if data derived
from such instruments lacks validity. Projective tests are, of course, less
precise and quantifiable. But, in fact, the concern of such critics with the
validity of projective methods seems to reflect their skepticism about the

acceptability of psychodynamic conceptualizations per se. Both types of tests
are valid. Each has its disadvantages as well as advantages, and the
appropriateness of each varies with the purposes for which they are used.
A number of studies have utilized the MMPI. An almost universal finding

is elevation of the “neurotic triad” of the hypochondriasis, hysteria, and
depression scales (see references 29, 81, 189, 197, 209, 262, and 268). It
seems clear that the RA patient describes himself as characterized by neurotic

trends. On the other hand, the scale elevations are less than those found in
neurotic patients, and the picture is inconsistent with the view that RA
patients are seriously disturbed and near psychotic. The fact that these
findings are indistinguishable from those in neurotic patients has been

interpreted as running counter to the expectation that a specific RA
personality pattern exists. A question also can be raised as to whether these
abnormal MMPI findings merely reflect the presence of the symptoms and
disability which RA produces. To get more information on this, several
investigators have carried out item analyses to determine if the scale
elevations result entirely from responses which reflect these manifestations

of the disease. The results have been conflicting.
Bourestom and Howard described similarities in the MMPI-scale
elevations among patients with RA, multiple sclerosis, and spinal-cord

injuries. They also found overall differences which “support the hypothesis of
some specific personality correlates associated with the three disabilities.” In

addition, sex-linked differences were found within each group, and the male
arthritics seemed somewhat different from all other groups. Nalven analyzed
MMPI responses in terms of hostility, and also obtained scores on three
special hostility scales. The data failed to provide evidence of increased
hostility in RA patients but did suggest that they had the problem of
overcontrol of hostility. Geist used projective tests and a questionnaire
battery as well as the MMPI. His MMPI data indicated neurotic trends similar
to the earlier studies. The other instruments revealed signs of inhibited
chronic aggression in the RA patients. They also indicated the presence of

obsessive compulsive defenses, participation and interest in sports prior to
disease onset, and a suggestion that the families of origin were characterized
by matriarchal discipline. Unfortunately his sample was relatively small

(twenty-two), and his questionnaire lacked external validation.
Robinson and his co-workers used Catells’ 16 Personality Factor
Inventory (16PF) to study patients with recent (“new”) as well as long-
standing (“old”) RA, and similar matched groups of tuberculosis, diabetes, and
hypertension patients. The new RA patients differed little from the other new
disease groups, but did show deviations from the test norms indicating
neurotic trends similar to that revealed by the MMPI. In contrast to the other
illness groups, the new and old RA patients were significantly similar to one
another, which these authors interpreted as evidence supporting the
existence of an RA personality type. As a whole, the RA patients manifested
emotional instability, introversion, guilt, and depression proneness,
exaggerated dependency needs, and trends toward compulsivity and tension.
This combination, they concluded, reflects “a person who restricts his
emotional expression, including expression of aggression.”
The 16PF was used also by Moldofsky and Rothman in a complex study
of symptoms, treatment and personality in a group of RA patients. The
patients as a group had test scores which, compared to norms, revealed low
ego strength, emotional instability, dependency, and conformity, i.e., again,
similar findings to the MMPI studies. The investigators concluded from this
that there was no specific RA personality. The personality traits did not show
any relationship to disease activity, but patients on steroids manifested more
severe emotional symptoms. Wolff comments that “the results obtained in

these two 16PF studies differed considerably, strongly suggesting that large
variations in personality patterns exist in RA.” Here again, the nature of the
data does not seem to be considered sufficiently.
The most creatively designed studies utilizing the MMPI were carried
out by Moos and Solomon. They scored the MMPI on a variety of derived
scales developed to reveal underlying personality traits, as well as on the

conventional scales, and also utilized ratings and content analyses of
interviews. Women with RA were compared with their healthy sisters, and
with other female relatives. The patients displayed more compliance-
subservience, depression, conservatism-security, and sensitivity to anger
than did their sisters. They also manifested clear and striking differences
from their sisters in their self-descriptions, in the extent of their masochism,
self-sacrifice, and denial of hostility, in their perceptions of the amount of

rejection they perceived from their mothers and of the strictness of their
fathers. Compared with female relatives in general, the patients scored higher
on scales reflecting physical symptoms, depression and apathy, psychological
rigidity, and neurotic symptoms indicative of anxiety, masochism, self-

alienation and over-compliance. No clear differences in physical interests or
activity could be elicited. The RA patients also displayed some similarities to
patients with other psychosomatic conditions. As the authors note, this

finding cannot be interpreted merely as lack of specificity, for it was not
general. There were similarities to both ulcer and hypertension patients, but
in entirely different ways. The point is that the dynamic formulations for
different disorders do overlap, not merely because they lack precision but
also because each is a constellation of transacting traits which include some
common elements.
This work provides meaningful information about personality in RA
that goes well beyond the earlier, less sophisticated MMPI studies. At the
same time, it is entirely consistent with that work in revealing the general
pattern of nonspecific neurotic symptoms characteristic of the RA patient. As
did some earlier workers, Moos and Solomon carried out a careful item
analysis to see if this was explainable on the basis of RA symptoms alone,
which substantiated the impression that it was not. (They also cite an
unpublished study by D. Cohen that provided a similar result.) Moos and

Solomon take pains to point out, however, that this tendency of the RA patient
to display neurotic symptoms could be a nonspecific consequence of the
presence of a painful, disabling disease. They reaffirm the point, made by

every serious student of the problem, that the interpretation of reported
distinctive personality findings requires longitudinal studies to determine if
these existed antecedent to the onset, and there are absolutely no such data
as of 1972.
A later study carried out by Meyerowitz, Jacox, and Hess is of special

interest because of its methodological approach. Detailed psychological test
and clinical studies were carried out on eight sets of female monozygotic
twins, discordant for RA. No consistent differences in personality could be

found. There was nothing distinctive about the patients’ conflicts or handling
of hostility. Both groups showed a conspicuous preference for physical
activity, and a need to serve and take responsibility for others. The single
consistent difference pertained to the involvement of the ultimately affected

twin, prior to disease onset, in events experienced as “demanding and
restricting.” To these, the patients responded “with their characteristic
heightened activity, but increasing stress was experienced to the point of
being unable to cope.”
In a subsequent review, Meyerowitz points to the importance of
distinguishing such contributions to disease onset from those purporting to
explain etiology, as well as from those which merely delineate the effects of
psychological factors upon the course of the disease. Nevertheless, this
finding is strongly reminiscent of the etiological specificity hypothesis
proposed for RA by Graham and Grace. These latter investigators proposed
that psychosomatic disorders are characterized by the presence of a

distinctive “attitude” prior to the disease onset. The latter was defined as a
feeling state combined with a disposition towards some action. A concomitant
specific physiological state is proposed, which is implicated in the

pathogenesis of the given disorder. For RA, the attitude is defined as follows:
“Felt tied down and wanted to get free (felt restrained, restricted, confined,
and wanted to be able to move around).” The problems of evaluating the

retrospective report of this particular attitude provided by a patient currently
affected by the characteristic effects of RA are too obvious to detail.
Subgroups
An apposite criticism of many of the reported studies is their failure to

provide a detailed description of the particular patients studied. The specific
characteristics of a given sample can affect the data in significant ways.
Findings may derive from characteristics of the sample entirely extraneous to
the presence of RA. As well as being misleading, these may obscure the
manifestations of factors that are specific to the disorder. There is also the
possibility that seeming discrepancies among studies may reflect the
existence of variants of the disorder (subgroups), each of which has differing
psychological characteristics. The most obvious example of this relates to the
sex of the patients studied. Most studies have been restricted to a single sex,
or have failed to consider the male and female patients separately. Yet in two
instances already mentioned, where both sexes were included and their data
were compared, differences were found. One would hardly expect otherwise.
If psychological factors are involved in RA, their role is complex and related to
deeper layers of the personality where sex-linked motivations and
characteristics exist. At the least, similar dynamic forces will manifest
themselves differently within the total psychological economies of men and

women. It is possible also that the relevant factors themselves differ for the
two sexes.
The importance of elucidating characteristics to identify still other
possible subgroups is well illustrated by the careful study of Rimon. This

Finnish researcher conducted detailed physical and psychiatric examinations
of 100 female clinic patients with RA, and compared them to the same
number with other “somatic diseases.” He identified fifty-five of the RA
patients in whom there was a correlation between emotional conflict
situations and the disease onset, and thirty-three in whom there was no such
correlation. (The balance represented an inbetween situation.) There were

significant differences between the two. In the group where the disease onset
followed a significant conflict, recurrences also tended to follow similar
conflict situations, and the course of the disease was one of sudden onset with
distinct and often acute symptoms and a much more rapid progression. The
patients had few affected relatives. In the group without conflict correlation,
the onset was slow and the progression of symptoms delayed, and these
patients had a relatively high family incidence of RA. This latter group had an
evident incapability of expressing hostile feelings. (For the whole group,
“problems in aggression dynamics were of minor incidence” at the “rational”

level, again suggesting the irrelevance of data at this level.) A detailed look at
ten patients, whose disease had a malignant progression, revealed that half
had an exceptionally heavy genetic predisposition, while the other half
manifested a great “psychic vulnerability.” The latter was indicated by

evidence of ego disorganization with overt depression. This research,
therefore, suggests that two separate groups of people have a predilection to

develop RA. In one, heredity plays the major role, whereas for the other
psychological stress is the significant factor; the disease progresses
differently for each.
Additional confirmation will be required before we can accept Rimon’s
findings as generally valid. There are data available from an earlier study by
King and Cobb which furnish indirect support for some of Rimon’s findings.
They compared thirty-two severe RA patients, 25 percent of them
hospitalized, with a group of normal controls, and also with data obtained
previously on a group of normals and twenty-one patients diagnosed as
having mild RA. The severe cases showed poorer maternal identification and
felt a lack of a positive relationship with their mothers, perceiving her as
giving insufficient attention and affection. They viewed both parents as
having been strict and uncompromising. In contrast, the mild cases were like
the controls. If we assume that these psychosocial variables parallel

psychological stress proneness, then their more severe disease seems to
match the more acute and rapid disease progression in Rimon’s comparable
group.
Also somewhat confirmatory is a study by Moos and Solomon which
found that patients with greater functional incapacity from their disease had
poorer ego strength and evidences of a variety of abnormal personality traits,
as measured by the MMPI.192 These researchers took pains to match the two
groups on many variables, but their efforts failed on one. The more
incapacitated group had a shorter duration of illness, and since the groups
were matched for the stage of disease, this means the rate of progression had
been more rapid in that group. The greater psychopathology which they
manifested is thus consistent with Rimon’s data. Another study by the same
investigators indirectly points in a different direction. In asymptomatic
relatives of RA patients, those who lacked the serum rheumatic factor had
greater evidence of emotional disturbance on the MMPI. This led the
investigators to conclude that only those individuals who have the hereditary
predisposition and experience emotional distress are likely to develop RA.
Regardless of the plausibility of that suggestion, the important issue is
the need for further studies like that of Rimon which attempt to delineate
subgroups. A further illustration of this approach, as well as the use of an
anteriospective design, is provided by the work of Moldofsky and Chester
who observed two contrasting pain patterns in a group of sixteen RA patients.

In patients manifesting the “synchronous” pattern, changes in arthritic
symptoms occurred concomitantly with, or just after, mood changes,
primarily those of anxiety or hostility. Patients with the “paradoxical” pattern

were characterized by an inverse relationship between joint symptoms and
feelings of hopelessness. No clinical or socioeconomic variables differentiated
the two groups. However, the paradoxical group demonstrated a less
favorable outcome when followed longitudinally.
Studies which focus on treatment outcome can contribute to the same

end. Factors which are discovered to predict differential responsiveness to
differing therapies may serve as clues to subgroups basic to the disorder
itself. McGlaughlin et al. found personality differences between patients who
responded well to ACTH (adrenocorticotropic hormone) and those who do
not. Those who had good dream recall, indicating a higher level of ego
function, responded better. Apropos of the point made earlier, there also
were differences between the findings for the male and female patients. The
characteristic conflict in both was between hostility and dependency; but the
males dealt with this by compulsive defenses and withdrawal, whereas the
females relied more on physical activity and on the control of others through
self-sacrifice.
A study carried out by Wolff is also of interest in its predictive design, as
well as its use of a measure of “pain sensitivity range” he developed. Lower

preoperative pain sensitivity served to predict a more favorable outcome to
surgical rehabilitative procedures. It seems likely, however, that this variable
is more relevant to rehabilitation potential in general than to RA or any

subtypes which it may include.
Mechanisms
Any theory which postulates that psychological factors play an
etiological role in RA must account for a psychophysiological mechanism

through which these factors produce its characteristic joint lesions. The
psychoanalytically oriented investigators of RA typically have suggested that
conflict over the expression of hostility causes increased muscle tension, and
that this leads somehow to the joint pathology. Studies were conducted by
two of these research groups dealing with the first part of this proposed chain
of events, i.e., the psychophysiology of muscle tension in RA patients.
Morrison, Short, Ludwig, et al. studied thirty-four RA patients, using both
surface and needle EMG.193 Half of the RA patients evidenced inconstant
spontaneous spiking in some muscles adjacent to the affected joints, when

they were apparently relaxed. The normals showed no such activity.
Gottschalk and his co-workers, associates of Alexander, carried out two
studies. In the first, multiple handwriting variables were measured in RA
patients, in a mixed group of fifteen psychiatric patients that contained nine

hypertensives, and in fifteen normal subjects. Both patient groups exhibited
greater variability on several measures than did the normal subjects. These
data were interpreted as evidence of a disturbance in the synergistic use of

muscles related to neurotic conflict or pent-up aggression. In their second
study, EMG records were obtained on groups of equal size (six) of RA

patients, RA patients in psychoanalysis, hypertensives, and normal subjects.
Initially, measures were taken from the forearm muscles at rest, and during
actual and imagined movements. The RA patients in analysis and the controls
showed generally lower tension than the medically treated RA patients and
the hypertensives. It was concluded that both RA and hypertension are
associated with increased muscle tension and that this may be reduced by
psychoanalysis. The second part of this study recorded arm and leg tension in
the patients in analysis before and after emotional stress. There were marked
reactions “partly predictable” from knowledge of the analysis. “In general,”
when defenses allowed expression of hostile impulses the tension decreased,
and when there was inadequate means of coping with these impulses, the
tension rose.
Surprisingly, there seem to be but two subsequent studies on this issue.

Southworth obtained surface EMG recordings from the trapezius and frontalis
in patients with RA and those with peptic ulcer before and after a stressful
word association test. The only difference was in a more prolonged elevation
subsequent to the stress in the RA group, confined to the trapezius. (Moos and
Engel interpreted this as a “lack of adaptation,” i.e., perseveration, in the
muscle responses of arthritics, and suggest that findings might have been
enhanced had “symptomatic” muscles been selected for study.) The word
association data failed to indicate conflicts over aggression in either group;
conflicts over dependency were equally present in both. However, a
computed overall “emotional disturbance score” correlated negatively with

trapezius tension, which Southworth interprets as evidence that discharge via
emotional and muscular tension are inversely related.
Moos and Engel carried out a study of their own. They attempted to
determine if hypertensives and RA patients would demonstrate “response
specificity” (see p. 728). A complex conditioning technique was used to study
twelve female patients in each group. No conditioning occurred. The RA
patients showed generally higher tension in their symptomatic muscles, and
greater reactivity in both symptomatic and asymptomatic muscles, as
measured by EMG. They also demonstrated a failure to “adapt” (i.e., a

persisting response) in their muscle responses, although their blood pressure
responses did adapt; hypertensives displayed the reverse.
Even if we accept these findings, major problems arise with regard to
their interpretation. First, the presence of acute arthritis or any painful
process is associated with splinting of the involved part by increased muscle
tension. Hence increased tension, specifically around a symptomatic joint,
may be a consequence rather than a cause of arthritis. The only finding that
even partly confronts this issue is a mention by Morrison et al. of a single
instance in which occasional spikes recorded from a resting muscle preceded

by one week the appearance of arthritis in the adjacent joint. Second, and
more important, among the various extra-arthritic manifestations of RA is a
myositis associated with round-cell infiltration, indistinguishable from that

found in the other collagen diseases. There is at least as much reason to
implicate this as the basis for increased muscle tension as a
psychophysiological mechanism.
To clarify the relationship of conflicts over the expression of anger to

muscle tension in RA will require studies made during periods of total
remission or, better still, prior to the initial onset of the disease. (Data from
normal subjects who do not develop RA may not be adequate, since RA

patients could differ in the presence of just such a relationship.) A
longitudinal approach allowing for observations antecedent to onset will also
answer the question as to whether the psychological findings arise as the
result of the disorder or precede it. Every thoughtful student of the field has
emphasized the need for such longitudinal studies, while recognizing the
immense practical problems which have precluded their accomplishment
thus far.
The hypothesis that muscle tension represented the pathogenic link
between psychological factors and arthritis seemed plausible at the time it
was proposed. Since then, our knowledge of RA has vastly increased. If RA is a

systemic disease of collagen tissue, as we now believe, that hypothesis no
longer seems adequate. An acceptable psychosomatic theory must account for
the specific pathogenic process central to a disease, as Engel has pointed out
so beautifully. This viewpoint in no way affects the validity of any of the above
mentioned psychological findings per se, which either may play no etiological
role, or may do so via another pathogenic mechanism.
One such alternative mechanism has, in fact, been proposed. There is
accumulating evidence strongly suggesting that all of the collagen disorders,
RA among them, represent “autoimmune” diseases. Although the initiating
mechanism remains obscure, a hypersensitivity mechanism seems to be
involved in their pathogenesis. Consistent with this, the serum of RA patients
typically (though not invariably) contains a macroglobulin “rheumatoid
factor.” This has been identified as a complex of an unknown 19S

macroglobulin with normal gamma globulin, suggesting that it represents an
immune reaction to the patient’s own serum protein. Solomon and Moos have
suggested that RA may arise via stress-induced alterations of immunological
mechanisms. They have marshalled data from a large variety of studies which
suggest that emotional factors can alter immune mechanisms. Among these
was Fessel’s work demonstrating elevated 19S protein in stressed prisoners,
and their own demonstration of elevated immunoglobulins in psychiatric

patients. Hendrie et al. also found elevated gamma globulin levels in female
psychiatric patients, but not in males, and confirmed Solomon’s finding that
this bore no specific relation to schizophrenia. The relevance of this body of

research to RA is entirely indirect. Thus Solomon and Moos label their
hypothesis a “speculative theoretical interpretation.” However it clearly
merits further pursuit, using both RA patients and experimental animals.
This new approach, as well as the whole thread of the discussion in this
section, tells us a good deal about the present state of the field. The evolution
of psychosomatic research on RA has reached the stage of progress which
provides a clear guideline for its future direction. The major focus of future
research must be on the painstaking clarification of mechanisms through

which psychological and somatic processes interface. These must be chosen
in terms of their relevance to the best available knowledge of the pathogenic
processes centrally involved in the disorder.
Parkinsonism
The parkinsonian syndrome is a progressive neurological disorder
manifested by muscular tremor, weakness, and rigidity, often associated with
autonomic symptoms, that arises from abnormalities of the basal ganglia. In

some instances, lesions result from an attack of encephalitis, and, less
commonly, trauma, toxins, neurosyphilis, and possibly arteriosclerosis have
been implicated. But there remain a large group of patients, most likely a
majority, in whom no such specific cause is found, and where the disorder is
ascribed to ideopathic degeneration of the basal ganglia. Under these
circumstances it has been suggested that the disorder may belong to the
psychosomatic category. The basis for this viewpoint came from a number of
observations that: (1) the onset followed emotional stress; (2) that those
afflicted had a characteristic personality configuration; and (3) that
psychiatric symptomatology is frequently exhibited.
An early impetus for this viewpoint came from Jeliffe, who described the
“obvious resemblances” between parkinsonians and catatonics. He indicated
that, in both, the motility disturbances served to bind unconscious hostility;
and likened the parkinsonian posture to that of a boxer.
Jackson and his co-workers, although taking a more traditional organic
stance regarding etiology, observed that “the direct exciting causes are as a
rule psychogenic.” They called attention to the great frequency and variety of
psychiatric symptoms found in the disorder, noting that often these preceded
the neurological signs. Depression was by far the commonest finding in their
large series of patients, but many other symptoms were noted, including
delusions, hallucinations, and agitation. It seems likely that some of the
striking nature of these findings resulted from sampling bias, i.e., the authors
were located at a state hospital. A more recent and conservative study carried
out by Schwab, Fabing, and Prichard also emphasized the number and variety
of psychiatric symptoms to be found in parkinsonians. These neurologists
grouped the psychiatric disturbances into four categories: (1) unrelated, e.g.,
antedating the disorder; (2) reactive; (3) secondary to medication; and (4)
paroxysmal, often associated with oculogyric crises and attributed to the CNS
(central nervous system) pathology. The latter included episodes of anxiety,

depression, compulsive acts, agitation, paranoia, and other symptom clusters.
The Parkinsonian Personality
The first major systematic studies of psychogenesis were carried out by
Booth. Several series of patients, both here and in Germany, were studied by
clinical interviews as well as the Rorschach. For the first time, control groups
were utilized. From these data Booth concluded definitely that a “specific
personality type” was to be found. He described this as characterized by an

“urge to action” through motor activity and industriousness, and by a
“striving for independence, authority and success within a rigid, usually
moralistic, behavior pattern.” He adds that “the balance between success,
aggression, and morals appears to be unusually delicate.” Of special interest

to us, Booth’s controls included a group of patients with rheumatoid arthritis.
He was struck by their many similarities to parkinsonians. Both disorders, he
concluded, are dominated by an urge for independent action in which
“obstacles are likely to provoke aggressiveness,” and both are subject to

conflicts between these feelings and a strict rigid conscience. The difference
lay in their emotional relationships. Whereas the arthritics had a “defensive
attitude against emotional involvement and outside influences,” the

parkinsonians were “activated by emotional experience coming from the
environment” (my emphases). Booth’s work represents one of the rare
instances in which subtle psychological differences among given
“psychosomatic” diseases have been dissected from their similarities. (These
studies also included hypertensives, and delineated a different personality
constellation for that disorder which will not be considered here).
Unfortunately, methodological flaws open all of Booth’s work to question, i.e.,
the patients were interviewed and tested by him alone, and his
interpretations were made with full foreknowledge of the nature of the
diagnoses.
Three clinical studies provided additional data that coincide with
Booth’s findings. Unfortunately, all are mere anecdotal reports devoid of
controls. Mitscherlich reported on the presence of chronic emotional tension
in relation to aggression, leading to “readiness to motor activity without the
possibility to realize it,” resulting in a personality presenting as “coolness.”
Shaskan et al. regarded the needs for conformity and “virtuousness” to be so
great as to produce an “unusually satisfactory” adjustment to the disease (a
finding that seems at considerable variance from that of most observers).

Sands considered these needs as sufficiently striking to characterize
parkinsonians as having a “masked personality.” The last two investigators

emphasized that intense anxiety, anger, and conflict lay beneath the
superficial calm and conformity.
Machover, who like Booth utilized Rorschach data, failed to confirm
these observations. He found no evidence of any consistent personality

picture. What little homogeneity he did elicit was limited to signs of cognitive
interference, dependence, affective instability, inertia, and passivity—data at
considerable variance with the industriousness and striving for independence
reported by Booth. These were related to the duration of the disease and
were explained as the consequences of living with a disabling disease that

severely constrained activity. Unfortunately, he failed to use controls.
Stronger support for these negative findings have come from the
program of well-designed studies of Riklan, Differ, and their associates. Their
findings, together with a comprehensive review of the background of the
problem, have been collected in an excellent monograph. Extensive data were
derived from systematic interviews with both patients and family members;
from detailed clinical observations and examinations; and from a battery of
psychological tests, both objective and projective, which tapped cognitive as

well as personality attributes; and from controls. These data led to the
conclusion that parkinsonians do not reveal distinctive behavioral features.
Neither a “parkinsonian personality,” nor even a typical reaction to the

disease (such as reported by Machover) was found. Impairment in
perceptual-cognitive functions was sometimes present but this covaried with

the severity of the neurological impairment, not its duration. The investigators
tend to view it as due to the disease process itself, not its symptoms.
Support for the findings in the cognitive area comes from a study by
Talland. On the basis of a specially selected group of cognitive tests “No
definite signs of impairment could be established.” Patients off medication
generally did better on all tests, suggesting that some of the defects observed
clinically might be due to drug effects. Talland was by no means unaware of
the existence of patients with severe intellectual impairment. But he

differentiates these few from parkinsonians generally, and suggests that they
may represent an etiologically distinct subgroup in which the pathological
process directly disrupts brain functions. Riklan and his co-workers extended
this line of thinking even further. The diversity of their findings led them to
conclude that “parkinsonism refers to a number of complex and composite
neurological syndromes,” and, “it would be theoretically inconsistent and
practically useless to propose that parkinsonian patients define an entity

generalizing its own behavioral characteristics.” Here precisely lies the nub of
a problem in accepting their negative findings as the final word on the
question of a parkinsonian personality. Each subtype of the disorder has
special features which act to obscure any held in common. If a specific

personality configuration should exist, its presence can only be determined
by eliminating these extraneous sources of variance. This requires the

selection of uniform subgroups for study. The first task is to exclude patients
whose disease arises from known exogenous factors, as well as all those in
whom there is any evidence of intellectual or other diffuse neurological
impairment. Demographic variables should then be used to create still more
homogeneous subgroups. Even then, problems remain. One is left with
patients whose impairment varies in extent and locus, and whose
psychological reactions to these differ. Perhaps the question will only be
answered when longitudinal prospective studies can be done. In any event,
the present weight of the evidence favors caution about the existence of a
parkinson-specific personality.
In contrast, the influence of psychological factors on parkinsonian
symptoms, is an established fact. Symptoms frequently are increased in the
presence of strong emotion, stress, and fatigue. This tells us nothing about
etiology, since all diseases necessarily are responsive to psychological
influence. A disorder of the CNS itself would seem especially likely to exhibit a
sensitivity to emotional arousal. The CNS is characterized by rich
interconnections among its parts, and the hypothalamic and limbic structures
which subserve emotion have known effects upon the musculature. Clinically
this is apparent in the familiar extrapyramidal side effects of the

phenothiazines. Nor can we make any etiological inferences from the
symptomatic improvement that can result from psychotherapy.
However it is difficult indeed to explain away the careful report by

Grinker and Spiegel of the development of the full-blown parkinsonian
syndrome in cases of combat exhaustion, These patients were
indistinguishable from typical “organic” parkinsonians, except that the entire

picture rapidly disappeared with psychiatric treatment. A report also has
appeared in which parkinsonian symptoms developed during the course of a
schizophrenic illness, and disappeared following a lobotomy concomitant
with symptomatic recovery from the psychosis. Psychodynamic study of this
patient suggested that “the parkinson syndrome may have developed as a

defense against the patient’s violent hostility” (reminiscent of the
aforementioned formulations of Jeliffe and Booth) as well as serving
regressive needs.
Somatopsychic Correlations
Cooper’s development of a stereotactic neurosurgical approach to
parkinsonism which involves the production of lesions in the thalamus and
corpus pallidum, provides a new avenue for increasing our understanding of
the functions of these parts of the brain. This work has been the subject of an
excellent review by Crown, (which also considers some of the material
covered above). In the cognitive sphere the findings are reasonably definite.
There are transient losses postoperatively, which seem more related to verbal
skills with left-sided lesions, and to performance and visual-motor skills with
those on the right side. More important, no permanent cognitive defects can
be ascertained.
A detailed clinico-pathological correlational study is available which

clarifies some of the subtle language and speech effects of thalamic surgery.
Some interesting findings emerge with regard to personality effects
following surgery, though these are far from clear. Riklan and Levita mention
only two changes which seemed to be persistent. These were a defect in body
image and a reduction in perceptual integration and nonspecific drive or
energy. The latter, according to these workers, may reflect reduced
kinesthetic feedback to the reticular activating system, a kind of relative
sensory deprivation. This intriguing hypothesis receives some support from

another of their studies. In a group of parkinsonians, a negative correlation
was demonstrated between “activation level” (as measured by skin
resistance) and the degree of voluntary motor impairment.
The reports of mood changes after surgery are somewhat conflicting.
McFie comments on the “improved emotional reactions following the
alleviation of symptoms” (my emphasis), and on the frequency of overt
euphoria which he linked to right-sided surgery. He likens the reaction to that

found with leukotomy. Hays also found euphoria to be the commonest
affective reaction. However he attributed this to the specific CNS effects of the
surgery, and found that it was not related to the degree of improvement. In
contrast, Asso found that most affective changes were those of anxiety or
depression, and that euphoria was rare. Unfortunately, there is no direct way
to compare these studies. Uniform rating scales were not used, nor is it clear
if there were equivalent preoperative levels of depression or expectancies of
benefit from the surgery in the three groups.
Obviously, we have still much to learn about the role of these brain
structures in personality and mood.
Gout
Gout is a disorder of uric acid metabolism in which symptoms arise
from the formation of urate deposits in various body areas. The usual site for
deposition is one or more of the joints, producing an acute, often exquisitely
painful arthritis. Chronic joint deformities occasionally eventuate. The other
major sites are the subcutaneous tissues, giving rise to the development of
nodular tophi, and the kidneys, resulting in nephritis and stone formation.
The metabolic dyscrasia is ordinarily manifested by an elevated
concentration of uric acid in the blood and other body fluids, but may only be
evident in other subtler but measurable abnormalities (e.g., an increased size

of the uric acid pool). Most research has identified the major metabolic defect
as being an overproduction of uric acid, though its decreased conversion or
excretion, or both, may also play a role.
Dietary overindulgence (increased purine intake), alcohol, exercise, and
certain drugs can increase uric acid levels transiently to precipitate an acute
attack. (The classically ascribed causative role of venery, however, seems
dubious!) Trauma, infection, surgery, and other physical stressors also may
act as precipitants. So can acute emotional stress. Sydenham, himself a victim,
as quoted by Talbott, advised gout sufferers to “keep the mind quiet.”
However, it is now well substantiated that these factors have relevance only
to the precipitation of acute attacks, and only to a small minority of these,

whereas the pertinent issue for the disorder is a metabolic fault, in which
such factors play no important role.
The disease was known as early as the fifth century B.C., when it was
described by Heiron, a resident of ancient Syracuse. Its hereditary nature has
been recognized nearly as long. Modern studies, while confirming the genetic
factor, have amplified our understanding of it in important ways. It is likely
that multiple genes are involved, and that their effects are simply additive
rather than interactive. The heritability factor has been quantified as ranging
from approximately one fifth to one third, and being distinctly less important
for males than females. Twin studies together with those of family incidence
suggest strongly that, for males, environmental influences may outweigh the
genetic as determinants of uric acid levels.
The relevance of this sex difference becomes apparent in the fact that
more than 95 percent of gout occurs in men. Mean uric acid levels in males
are approximately 5 mg. percent, a value about 1 mg. percent higher than that
for women beginning from puberty. The difference converges somewhat in
late life because of a rise in the level for women at menopause. The
precipitation of uric acid in the tissues is, of course, a function of its
concentration. As levels progressively exceed its solubility (ca. 6.4 mg.
percent) there is a parallel increase in the probability that crystallization and

deposition will occur.
The observation that the disease is more common among the affluent,
eminent, and successful also goes back to antiquity. With the clarification of
the role of uric acid, it has become possible to examine this relationship more
closely. A substantial number of modern studies have provided both
confirmation of its general validity, and a clarification that the crucial issue is
not socioeconomic status per se, but the psychological characteristics of drive
achievement and leadership. The latter, of course, build the path to success
and prominence. Mueller and his associates have provided an extensive
review of this work.
The relationship with social status has been demonstrated in a variety

of groups. Uric acid levels were found to be higher in executives than both
craftsmen and normal controls, and higher in medical than high school
students. Within a single plant, Oak Ridge, the highest mean values were
found in the Ph.D. scientists and the lowest in craftsmen, with the supervisors
and inspectors falling in between. Dodge and Mikkelson, as cited by Mueller,

found the age corrected urate levels of professionals and executives to be
higher than those of workers in unskilled jobs and farmers. State white-collar
employees had a higher mean level than the general population.
By comparing subsamples within some of these and similar groups, it
has become possible to delineate the role of achievement-related behavior
from overall socioeconomic characteristics, since each group is more-or-less
homogeneous with regard to the latter. Thus, in a Scottish study, the top
executives had urate levels exceeding those found in those of lower rank.
Executives enrolled in a summer Executive Development Program, and thus
presumably of greater ambition, had uric acid levels exceeding those of an
unselected group of executives. Among the state employees, those with the
greatest number of job changes (considered to be an index of upward
mobility) had the higher levels. In a study of a group of men anticipating job
termination, those with high uric acid levels were more likely to resign early
to find another job.
Even closer to the point, within a sample of university professors,

interview ratings of achievement motivation were found to correlate at a level
of r = 66 with serum uric acid values. Similarly, Jenkins et al. found significant
correlations, within a large group of supermarket employees, between serum

urate levels and test items related to drive, competitiveness and challenging
life circumstances, as cited by Mueller from a personal communication.

Further confirmation is provided by a pilot study that utilized a measure of
the motivational trait free from overt achievement behavior. Patients with
gout and hyperuricemia had measurably higher levels of need achievement
than did a control group of social work students.
The relationship holds also in regard to educational variables. The uric
acid levels of high school and college students were positively related to the
extent of their extra curricular activities, including those of a social and

nonathletic type, and with test measures of achievement motivation. There
does not appear to be any simple relationship of uric acid to grades. However,
high school students with poor grades turned out to be more likely to go to
college if they had high uric acid levels than if they did not, and within this
group, uric acid levels correlated with the length of time they remained in
college. Approached from the other side, students attending or planning to

attend college had higher uric acid values than those without such plans,
above and beyond any association with grades.
A few reports have appeared that fail to demonstrate relationships

between uric acid and social class. But, as of 1971, the weight of the evidence
is so preponderant, both in numbers of studies and their meaningful
consistencies, that it is difficult to be skeptical. It should be emphasized,

however, that, with a single exception, all the findings involve studies done
exclusively on men. Given the sex incidence of hyperuricemia and gout, this is
not surprising. Moreover, the apparently greater role of genetic factors in
women may dilute the effect of other variables, including those related to
achievement. The one study done on women did show a suggestive
relationship. In nursing students, a positive association was found between
uric acid and extracurricular activities. It will be important to learn if this

relationship does indeed hold true also for women.
In one of the aforementioned studies, uric acid measures were taken

also on a group of women, the subjects’ spouses. Because achievement indices
were recorded only for their husbands, this study provides no contribution to
the question of the relationship of this variable in women. These data are
helpful in another way. The uric acid levels of the executives’ and
professionals’ wives did not exceed that of the wives of the less skilled
workers. Thus, there is further support for believing that it is not their living
styles (dietary and drinking habits etc.), nor other aspects of social class per
se which are involved in the elevated uric acid levels found in their husbands.
It might be added that various details of design in several of the other studies
mentioned above lead to further confidence that such exogenous factors are
not responsible for the findings.
There is one additional facet of this whole body of research that is of

unique significance. Because the subjects had hyperuricemia but not gout, the
psychological findings cannot be ascribed to any secondary effects of

suffering from that disease. In this sense, this is prospective research, free
from the potential error inherent in the retrospective method.
Assuming that the relationship between uric acid and achievement

behavior and/or motivation does exist, how are we to understand it? The
possibility arises that uric acid overproduction is a concomitant of chronic
stress arising from the drive to success and the effort attendant upon its
achievement. There are two studies which provide direct evidence that short-
term psychological stress is associated with a rise in uric acid. In a group of
Navy frogmen during training, Bahe and his co-workers found uric acid
elevations just prior to the start of training (the familiar pre-experimental
anticipation effect that occurs in many stress variables.) Bises in uric acid also
occurred during periods when the trainees approached demanding tasks with
an “optimistic” attitude, while drops were noted during a period when they
felt “overburdened” and less assured of success. Similar findings occurred in a
study of stably employed men experiencing job loss because of a plant closing.
Anticipation of job loss was associated with elevations of uric acid which
dropped following new employment. The duration of the rise tended to
parallel the length of time it had taken to find the new job. Of special interest,
those men who resigned prior to termination to obtain a new job had stable
higher uric acid levels. This latter behavior not only implies greater
achievement drive, it also suggests a greater degree of optimism.
Furthermore, for a small subgroup in which psychological measures could be
made reliably, a combined rating of sadness, low self-esteem, and anxiety
correlated negatively with uric acid levels.
Thus, these studies contribute to the understanding of the relationship
of uric acid to transient emotional states, as well as to the larger body of work
on its relationship to enduring personality traits. They also provide an

intriguing lead for better delineating achievement drive in terms of the
attitude associated with it. Additional confirmation of this lead can be found
in closer scrutiny of some of the previously mentioned studies of the
achievement trait. More frequent job change seems interpretable in terms of

optimism and a sense of active mastery, as well as of upward mobility. So
does the willingness to attempt college. Moreover the uric acid levels in
college professors, which were positively correlated with ratings of

achievement motivation, were concomitantly negatively correlated with
reported feelings of being overburdened and worried about their jobs. Also
consistent with this point is the finding that high school students with lower
uric acid levels had more unrealistic vocational expectations and aspirations
than those with high levels (the degree to which such goals are unrealistic
being a concomitant of achievement avoidance) .
It would be difficult to overestimate the importance of this type of
clarification. Such traits as drive, achievement, and leadership represent global

qualities which may subsume or even obscure more narrowly and precisely
defined personality attributes. It is essential to separate the latter from the
grosser traits within which they are imbedded. (An excellent example of such
an endeavor is to be found in Jenkin’s delineation of the separate traits
included within the coronary-prone personality.) The justification for this

viewpoint comes not only from considerations of logic but from its
demonstrated payoff. Thus, in several of the studies reported, cholesterol
levels were measured also and showed a very different relationship with the
psychological variables than did uric acid. In general the relation of

cholesterol to the personality continuum of the optimism sense of mastery vs.
less assured overburdened was just opposite to that for uric acid. Since
coronary disease is accompanied by elevation in the mean levels both of

cholesterol and uric acid, the clarification of the differential personality
correlates of the two substances is of considerable interest.
The correlation between personality traits and biochemical or
physiological variables does not, of course, indicate a causal relationship.

Either or both may be mere derivative products of other, more central factors.
Even if the relationship were causal, the psychological variable need not be
the primary factor. As a matter of fact, Orowan has offered the interesting
converse hypothesis that uric acid acts as an endogenous cortical stimulant.

Consistent with this is the positive relationship between uric acid and IQ
levels. However, this correlation, albeit statistically significant, is very low (r
≅ 0.1), and, in any event, this hardly constitutes validation of the hypothesis.
Clearly there remains much work to be done. In this instance such a

statement is no mere cliche. Rather it reflects an existing stage of
accomplishment, important not merely in itself but in the clear directions it
provides for further research. The elucidation of the relationship of uric acid
and personality represents one of the brighter areas of psychosomatic
research.
Bibliography
Abraham, K. (1913) “A Constitutional Basis of Locomotor Anxiety,” in Selected Papers on

Psychoanalysis, pp. 235-243. London: Hogarth, 1949.
Acheson, R. M. and W. O’Brien. “Some Factors Associated with Serum Uric Acid in the New Haven
Survey of Joint Disease,” in P. H. Bennett and P. Wood, eds., Population Studies of the
Rheumatic Diseases, pp. 365-370. Amsterdam: Excerpta Medica Foundation, 1968.
Alexander, F. Psychosomatic Medicine. New York: Norton, 1950.
Alexander, F., T. French, and G. H. Pollock. Psychosomatic Specificity. Chicago: University of

Chicago Press, 1968.
Allport, G. W. and P. Vernon. Studies in Expressive Movement. New York: Macmillan, 1933.
Amkraut, A. A., F. Solomon, and C. Kraemer. “Stress, Early Experience and Adjuvant-Induced
Arthritis in the Rat,” Psychosom. Med., 33 (1971), 203-214.
Anumonye, A., J. Dobson, S. Oppenheim et al. “Plasma Uric Acid Concentrations among Edinburgh
Business Executives,” JAMA, 208 (1969), 1141-1148.
Ascher, E. “Motor Attitudes and Psychotherapy,” Psychosom. Med., 11 (1949), 228-234.
Asso, D., S. Crown, J. A. Russell et al. “Psychological Aspects of the Stereotactic

Treatment of Parkinsonism,” Br. J. Psychiatry, 115 (1969), 541-553.
Avni, J. and J. Chaco. “Objective Measurements of Postural Changes in Depression.” Paper

presented at the Annual Meeting of the American Psychosomatic Society, Boston,
April 1972. Unpublished.
Ax, A. F. “The Physiological Differentiation between Fear and Anger in Humans,” Psychosom. Med.,
15 (1953), 433-442.
Ax, A. F., J. Bamford et al. “Autonomic Response Patterning of Chronic Schizophrenics,”

Psychosom. Med., 31 (1969), 353-364.
Balshan, I. D. “Muscle Tension and Personality in Women,” Arch. Gen. Psychiatry, 7 (1962), 436-
448.
Barlow, W. “Anxiety and Muscle Tension,” in D. O’Neill, ed., Modern Trends in Psychosomatic
Medicine. New York: Hoeber, 1955.
Bennett, L. A. “The Personality of the Rheumatoid Arthritis Patient.” Master’s thesis, McGill
University, Montreal, 1952. Unpublished.
Bennett, P. and P. H. N. Wood, eds., Population Studies of the Rheumatic Diseases, International
Congress Series no. 148. Amsterdam: Excerpta Medica Foundation, 1968.
Birdwhistell, R. L. Introduction to Kinesics. Louisville: University of Louisville Press, 1952.
---- . Kinesics and Context. Philadelphia: University of Pennsylvania Press, 1970.
Bland, J. H., ed. “Symposium on Rheumatoid Arthritis,” Med. Clin. North Am., 52 (1968), 477-769.
Blom, G. E. and G. Nicholls. “Emotional Factors in Children with Rheumatoid Arthritis,” Am. J.
Orthopsychiatry, 24 (1954), 588-600.
Boland, E. W. “Psychogenic Rheumatism: The Musculoskeletal Expression of Psychoneurosis,”
Calif. Med., 68 (1948), 273-279.
----. “Psychogenic Factors in Rheumatic Disease,” in J. L. Hollander, ed., Arthritis and Allied
Conditions, 6th ed. Philadelphia: Lea & Febiger, 1960.
Boland, E. W. and W. P. Corr. “Psychogenic Rheumatism,” JAMA, 123 (1943), 805-809.
Boman, K. “Effect of Emotional Stress on Spasticity and Rigidity,” J. Psychosom. Res., 15 (1971),
107-112.
Booth, G. “Personality and Chronic Arthritis,” J. Nerv. Ment. Dis., 85 (1937), 637-662.
----. “Objective Techniques in Personality Testing,” Arch. Neurol. Psychiatry, 42 (1939), 514-530.
----. “Organ Function and Form Perception,” Psychosom. Med., 8 (1946), 367-385.
----. “Psychodynamics in Parkinsonism,” Psychosom. Med., 10 (1948), 1-14.
Bourestom, N. C. and M. T. Howard. Personality Characteristics of Three Disability Groups,” Arch.

Phys. Med. Rehahil., 46 (1965). 626-632.
Brooks, G. W. and E. Mueller. “Serum Urate Concentrations among University Professors,” JAMA,
195 (1966), 415-418.
Bull, N. The Attitude Theory of Emotion. New York: Coolidge Foundation, 1951.
Cameron, D. E. “Observations on the Patterns of Anxiety,” Am. J. Psychiatry, 101 (1944), 36-41.
Cameron, N. The Psychology of Behavior Disorders. Boston: Houghton Mifflin, 1947.
Chapman, A. H. Management of Emotional Disorders: A Manual for Physicians. Philadelphia:

Lippincott, 1962.
Christian, C., ed. “Nineteenth Rheumatism Review,” Arthritis Rheum., 13 (1970), 474-711.
Cleveland, S. and S. Fisher. “Behavior and Unconscious Fantasies of Patients with Rheumatoid
Arthritis,” Psychosom. Med., 16 (1954), 327-333.
----. “A Comparison of Psychological Characteristics and Physiological Reactivity in Ulcer and

Rheumatoid Arthritis Groups: I. Psychological Measures,” Psychosom. Med., 22
(1960), 283-289.
Cleveland, S., E. E. Reitman, and E. J. Brewer, Jr. “Psychological Factors in Juvenile Rheumatoid
Arthritis,” Arthritis Rheum., 8 (1965), 1152-1158.
Cobb, Sidney. “Contained Hostility in Rheumatoid Arthritis,” Arthritis Rheum., 2 (1959), 419-425.
----. “Hyperuricemia in Executives,” in J. H. Kellgren, ed., The Epidemiology of
Chronic Rheumatism, pp. 182-196. Philadelphia: Davis, 1963.
----. The Frequency of Rheumatic Diseases. Cambridge, Mass.: Harvard University Press, 1969.
Cobb, Sidney and T. Lincoln. “On the Frequency of Individuals Who Suffer Occasional Attacks of
Rheumatoid Arthritis,” Arthritis Rheum., 3 (1960), 48.
Cobb, Sidney, M. Miller, and M. Wieland. “On the Relationship between Divorce and Rheumatoid
Cobb, Sidney, W. J. Schull, E. Harburg et al. “The Intrafamilial Transmission of Rheumatoid

Arthritis,” J. Chronic Dis., 22 (1968), 195-296.
Cobb, Stanley, W. Bauer, and I. Whiting. “Environmental Factors in Rheumatoid Arthritis,” JAMA,
113 (1939), 668-670.
Cooper, I. S. The Neurosurgical Alleviation of Parkinsonism. Springfield, Ill.: Charles C. Thomas,

1956.
Cormier, B. M. and E. Wittkower. “Psychological Aspects of Rheumatoid Arthritis,” Can. Med.

Assoc. J., 77 (1957), 533-541.
Crisp, A. H. and H. Moldofsky. “A Psychosomatic Study of Writer’s Cramp,” Br. J. Psychiatry, 111
(1965), 841-858.
Crown, S. “Psychosomatic Aspects of Parkinsonism,” J. Psychosom. Res., 15 (1971), 451-459.
Damaser, E. C., R. Shor, and M. Orne. “Physiological Effects during Hypnotically Requested
Emotions,” Psychosom. Med., 25 (1963), 334-343.
Davidowitz, J., A. N. Brown-MAYERS, R. Kohl et al. “An Electromyographic Study of Muscular

Tension,” J. Psychol., 40 (1955), 85-94.
Davis, F. H. and R. B. Malmo. “Electromyographic Recording during Interview,” Am. J. Psychiatry,

107 (1951), 908-915.
Davis, J. F. Manual of Surface Electromyography. Montreal: Allan Memorial Institute of Psychiatry,

1952.
Davis, J. F., R. B. Malmo, and C. Shagass. “Electromyographic Reaction to Strong Auditory

Stimulation in Psychiatric Patients,” Can. J. Psychol., 8 (1954), 177-186.
Davis, R. C. “Methods of Measuring Muscular Tension,” Psychol. Bull., 39 (1942), 329-346.
Decker, J. L. “The Epidemiology of Hyperuricemia: A Summary,” in G. Katona and J. R. Gill, eds.,

Panamerican Rheumatology, pp. 74-75. Amsterdam: Excerpta Medica Foundation,
1969.
Deutsch, F. “Analysis of Postural Behavior,” Psychoanal. Q., 16 (1947), 195-213.
Duffy, E. “The Measurement of Muscular Tension as a Technique for the Study of Emotional
Tendencies,” Am. J. Psychol., 44 (1932), 146-162.
----. “The Relation between Muscular Tension and Quality of Performance,” Am. J. Psychol., 44
(1932), 535-546.
----. “Level of Muscular Tension as an Aspect of Personality,” J. Gen. Psychol., 35 (1946), 161-171.
----. Activation and Behavior. New York: Wiley, 1962.
Dunbar, H. F. Emotions and Bodily Changes. New York: Columbia University Press, 1954.
Dunn, j., W. G. Brooks, J. Mausner et al. “Social Class Gradient of Serum Uric Acid Levels in Males,”
JAMA, 185 (1963), 431-436.
Ehrlich, G. E. “Psychosomatic Aspects of Musculoskeletal Disorders,” Postgrad. Med., 38 (1965),

614-619.
Eleftheriou, B. and J. P. Scott. The Physiology of Aggression and Defeat. New York: Plenum, 1971.
Engel, G. L. “Studies of Ulcerative Colitis: I Clinical Data Bearing on the Nature of the Somatic
Process,” Psychosom. Med., 16 (1954), 496-501.
----. “Studies of Ulcerative Colitis: II. The Nature of the Somatic Processes and the Adequacy of
Psychosomatic Hypotheses,” Am. J. Med., 16 (1954), 416-433.
----. “Studies of Ulcerative Colitis: III. The Nature of the Psychologic Processes,” Am. J. Med., 19
(1955), 231-256.
Fenichel, O. The Psychoanalytic Theory of Neurosis. New York: Norton, 1945.
Ferenczi, S. (1919) “Thinking and Muscle Innervation,” in J. Rickman, ed. Further Contributions to
the Theory and Technique of Psychoanalysis, pp. 230-232. New York: Basic Books,
1952.
Fessel, W. J. “Mental Stress, Blood Proteins and the Hypothalamus,” Arch. Gen. Psychiatry, 7
(1962), 427-435.
Fischman, D. A., H. Meltzer, and R. Poppei. “Disruption of Myofibrils in the Skeletal Muscle of
Psychotic Patients,” Arch. Gen. Psychiatry, 23 (1970), 503-513.
Fisher, S. Body Experience in Fantasy and Behavior. New York: Appleton-Century-Crofts, 1970.
Fisher, S. and S. E. Cleveland. “A Comparison of Psychological Characteristics and Physiological
Reactivity in Ulcer and Rheumatoid Arthritis Groups: II. Differences in
Physiological Reactivity,” Psychosom. Med., 22 (1960), 290-293.
----. Body Image and Personality, 2nd ed. New York: Dover, 1968.
Freeman, G. L. “Postural Tensions and the Conflict Situation,” Psychol. Rev., 46 (1939). 226-240.
French, J. G., H. J. Dodge, M. O. Kjelsberg et al. “A Study of Familial Aggregation of Serum Uric Acid
Levels in the Population of Tecumseh, Michigan, 1959-60,” Am. J. Epidemiol., 86
(1967), 214-224.
French, T. and L. Shapiro. “The Use of Dream Analysis in Psychosomatic Research,” Psychosom.
Med., 11 (1949), 110-112.
Freud, S. The Problem of Anxiety. New York: Norton, 1936.
----. (1901) The Psychopathology of Everyday Life, in J. Strachey, ed., Standard Edition, Vol. 6.
Geist, H. The Psychological Aspects of Rheumatoid Arthritis. Springfield, Ill.: Charles C. Thomas,
1966.
Gellhorn, E. Physiological Foundations of Neurology and Psychiatry. Minneapolis: University of

Minnesota Press, 1953.
Gertler, M. M., S. M. Garn, and S. A. Levine. “Serum Uric Acid in Relation to Age and Physique in
Health and in Coronary Heart Disease,” Ann. Intern. Med., 34 (1951), 1421-1431.
Glover, E. Psycho-analysis. London: Staples Press, 1949.
Gold, S. “Psycho-Genesis in the ‘Stiff-Man Syndrome’,” Guys Hosp. Rep., 114 (1965), 279-285.
Goldstein Balshan, I. “Role of Muscle Tension in Personality Theory,” Psychol. Bull., 61 (1964),
413-425.
----. “Physiological Responses in Anxious Women Patients,” Arch. Gen. Psychiatry, 10 (1964), 382-
388.
----. “The Relationship of Muscle Tension and Autonomic Activity to Psychiatric Disorders,”
Psychosom. Med., 27 (1965), 39-52.
Goldstein Balshan, I., R. R. Grinker, Sr., H. A. Heath et al. “Study in Psychophysiology of Muscle
Tension: I. Response Specificity,” Arch. Gen. Psychiatry, 11 (1964), 322-330.
Gordon, R. E., R. Lindeman, and K. Gordon. “Some Psychological and Biochemical Correlates of
College Achievement,” J. Am. College Health Assoc., 15 (1967), 326-331.
Gottschalk, L., M. Serota, and K. Roman. “Handwriting in Rheumatoid Arthritics,” Psychosom. Med.,
11 (1949), 354-360.
Gottschalk, L., H. Serota, and L. Shapiro. “Psychologic Conflict and Neuromuscular Tension,”
Psychosom. Med., 12 (1950), 315-319.
Grace, W. J. and D. Graham. “Relationship of Specific Attitudes and Emotions to Certain Bodily
Diseases,” Psychosom. Med., 14 (1952), 243-251.
Graham, D. T., R. M. Lundy, L. S. Benjamin et al. “Specific Attitudes in Initial Interviews with
Patients Having Different ‘Psychosomatic’ Diseases,” Psychosom. Med., 24 (1962),
257-266.
Gregg, D. “The Paucity of Arthritis among Psychotic Cases,” Am. J. Psychiatry, 95 (1939). 853-856.
Grinker, R. R., Sr., S. J. Korchin, Basowitz et al. “A Theoretical and Experimental Approach to
Problems of Anxiety,” Arch Neurol. Psychiatry, 76 (1956), 420-431.
Grinker, R. R., Sr. and J. Spiegel. War Neurosis in North Africa: The Tunisian Campaign. New York:
Josiah Macy Foundation, 1943.
Grokoest, A. W., I. Snyder, and R. Schlaeger. Juvenile Rheumatoid Arthritis. Boston: Little, Brown,
1962.
Grossman, W. I. and H. Weiner. “Some Factors Affecting the Reliability of Surface
Electromyography,” Psychosom. Med., 28 (1966), 78-83.
Guggenheim, P. and L. Cohen. “A Case of Schizophrenia in which Manifestations of Parkinsonism

Appeared during the Course of the Psychosis and Disappeared after Lobotomy,”
Psychosom. Med., 20 (1958), 151-160.
Gutman, A. B., ed. “Proceedings of Conference on Gout and Purine Metabolism,” Arthritis Rheum.,
8 (1965), 589-910.
Halliday, J. L. “Psychological Factors in Rheumatism,” Br. Med. J., 1 (1937), 213-217; 264-269.
----. “The Concept of Psychogenic Rheumatism,” Ann. Intern. Med., 15 (1941), 666-677.
----. “The Psychological Approach to Rheumatism,” Proc. R. Soc. Med., 35 (1941), 455-457.
----. “Concept of a Psychosomatic Affection,” Lancet, 2 (1943), 692-696.
Hays, P., et al. “Psychological Changes following Surgical Treatment of Parkinsonism,” Am. J.
Psychiatry, 123 (1966), 657-663.
Heath, H. A., D. Oken, and W. G. Shipman. “Muscle Tension and Personality,” Arch. Gen. Psychiatry,
16 (1967), 720-726.
Heath, H. A., D. Oken, and W. G. Shipman et al. “Three Factor Analyses of Electromyographic Data
Under Varying Conditions,” Multivariate Behav. Res., 2 (1967), 263-280.
Hellgren, L. “Marital Status in Rheumatoid Arthritis,” Acta Rheumatol. Scand., 15 (1969), 271-276.
Hench, P. S. and E. W. Boland. “The Management of Chronic Arthritis and Other Rheumatic
Diseases among Soldiers of the United States Army,” Ann. Intern. Med., 24 (1946),
808-825.
Hendrie, H. C., F. Paraskevas, and J. D. Adamson. “Stress, Immunoglobulin Levels and Early
Polyarthritis,” J. Psychosom. Res., 15 (1971), 337-342.
----. “Gamma Globulin Levels in Psychiatric Patients,” Can. Psychiatr. Assoc. J., 17 (1972), 93-97.
Hollander, J. L., ed. Arthritis and Allied Conditions: A Textbook of Rheumatology, 6th ed.
Philadelphia: Lea & Febiger, 1960.
Holmes, T. H. and H. Wolff. “Life Situations, Emotions, and Backache,” Psychosom. Med., 14 (1952),
18-33.
Inman, V. T., H. J. Ralston, J. B. de C. M. Saunders et al. “Relation of Human Electromyogram to

Muscular Tension,” Electroencephalogr. Clin. Neurophysiol., 4 (1952), 187-194.
Jackson, J. A., G. B. M. Free, and H. V. Pike. “The Psychic Manifestations in Paralysis Agitans,” Arch.
Jacobson, E. Progressive Relaxation. Chicago: University of Chicago Press, 1938.
Jacobson, E., ed. Tension in Medicine. Springfield, Ill.: Charles C. Thomas, 1967.
James, W. The Principles of Psychology. New York: Holt, 1890.
Jeffrey, M. R. and J. Ball. The Epidemiology of Chronic Rheumatism. Philadelphia: Davis, 1963.
Jelliffe, S. E. “The Mental Pictures in Schizophrenia and in Epidemic Encephalitis,” Am. J.

Psychiatry, 6 (1926), 413-465.
----. “The Parkinsonian Body Posture,” Psychoanal. Rev., 27 (1940), 467.
Jelliffe, S. E. and W. A. White. Diseases of the Nervous System. Philadelphia: Lea & Febiger, 1935.
Jenkins, C. D., S. J. Zyzanski, and R. H. Rosenman. “Progress toward Validation of a Computer-

Scored Test for the Type A Coronary-Prone Behavior Pattern,” Psychosom. Med., 33
(1971), 193-202.
Johnson, A. M., L. Shapiro, and F. Alexander. “Preliminary Report on a Psychosomatic Study of

Rheumatoid Arthritis,” Psychosom. Med., 9 (1947), 295-300.
Kasl, S. V., G. W. Brooks, and Sidney Cobb. “Serum Urate Concentrations in Male High School
Students, a Predictor of College Attendance,” JAMA, 198 (1966), 713-716.
Kasl, S. V., G. W. Brooks, and W. Rodgers. “Serum Uric Acid and Cholesterol in Achievement
Behavior and Motivation: I. The Relationship to Ability, Grades, Test Performance,
and Motivation,” JAMA, 213 (1968), 1158-1164.
----. “Serum Uric Acid and Cholesterol in Achievement Behavior and Motivation: I. The
Relationship to College Attendance, Extracurricular and Social Activities, and
Vocational Aspirations,” JAMA, 213 (1970), 1291-1299.
Kasl, S. V., Sidney Cobb, and G. W. Brooks. “Changes in Serum Uric Acid and Serum Cholesterol in
Men Undergoing Job Loss,” JAMA, 206 (1968), 1500-1507.
Kempe, J. E. “An Experimental Investigation of the Relationship Between Certain Personality

Characteristics and Physiological Responses to Stress in a Normal Population.”
Ph.D. dissertation, Michigan State University, 1956. Unpublished.
Kepecs, J. G. “Some Patterns of Somatic Displacement,” Psychosom. Med., 15 (1953), 425-432.
King, H. E. “Psychomotility: A Dimension of Behavior Disorder,” Proc. Am. Psychopathol. Assoc., 58

(1969), 99-128.
King, S. H. “Psychosocial Factors Associated With Rheumatoid Arthritis,” J. Chronic Dis., 2 (1955),
287-302.
King, S. H. and Sidney Cobb. “Psychosocial Factors in the Epidemiology of Rheumatoid Arthritis,”
J. Chronic Dis., 7 (1958), 466-475.
----. “Psychosocial Studies of Rheumatoid Arthritis: Parental Factors Compared in Cases and
Controls,” Arthritis Rheum., 2 (1959). 322-331.
Lacey, J. I. “Psychophysiological Approaches to the Evaluation of Psychotherapeutic Process and

Outcome,” in E. A. Rubinstein and M. B. Parloff, eds., Research in Psychotherapy, pp.
160-208. Washington, D.C.: American Psychological Association, 1959.
----. “Somatic Response Patterning and Stress: Some Revisions of Activation Theory,” in M. H.
Appley and R. Trumbull, eds., Psychological Stress, pp. 14-37. New York: Appleton-
Lacey, J. I., D. E. Bateman, and R. Vanlehn. “Autonomic Response Specificity,” Psychosom. Med., 15
(1953), 8-21.
Lacey, J. I. and B. Lacey. “The Relationship of Resting Autonomic Activity to Motor Impulsivity,”
Res. Publ. Assoc. Res. Nerv. Ment. Dis., 36 (1956), 144-209.
Lader, M. H. and A. M. Matthews. “Electromyographic Studies of Tension,” J. Psychosom. Res., 15

(1971), 479-486.
Lanese, R. R., G. Gresham, and M. D. Keller. “Behavioral and Physiological Characteristics in

Hyperuricemia,” JAMA, 207 (1969), 1878-1882.
Lewis-Fanning, E. “Report on an Enquiry into the Aetiological Factors Associated with

Rheumatoid Arthritis,” Ann. Rheum. Dis., 9 (1950), Suppl.
Lindsley, D. B. “Emotion,” in S. S. Stevens, ed., Handbook of Experimental Psychology, pp. 473-516.

New York: Wiley, 1951.
Lippold, O. C. J. “The Relation between Integrated Action Potentials in a Human Muscle and Its
Isometric Tension,” J. Physiol., 117 (1952), 492-499.
Lovaas, O. I. “The Relationship of Induced Muscular Tension, Tension Level, and Manifest Anxiety
in Learning,” J. Exp. Psychol., 59 (1960), 145-152.
Lowman, E. W., ed. Arthritis: General Principles, Physical Medicine, Rehabilitation. Boston: Little,
Brown, 1959.
Lowman, E. W., S. Miller, P. Lee et al. “Psycho-Social Factors in Rehabilitation of the Chronic
Rheumatoid Arthritic,” Ann. Rheum. Dis., 13 (1954), 312-316.
Ludwig, A. O. “Emotional Factors in Rheumatoid Arthritis,” Physiother. Rev., 29 (1949), 339-342.
----. “Psychogenic Factors in Rheumatoid Arthritis,” Bull. Rheum. Dis., 2 (1952), 33-34.
----. “Rheumatoid Arthritis,” in E. D. Wittkower and R. A. Cleghorn, eds., Recent Developments in

Psychosomatic Medicine, pp. 232-244. Philadelphia: Lippincott, 1954.
Lundervold, A. “An Electromyographic Investigation of Tense and Relaxed Subjects,” J. Nerv. Ment.
Dis., 115 (1952), 512-525.
Luria, A. The Nature of Human Conflicts. New York: Liveright, 1932.
Luthe, W., ed. Autogenic Training: Psychosomatic Correlations. New York: Grune & Stratton, 1964.
Machover, S. “Rorschach Study on the Nature and Origin of Common Factors in the Personalities
of Parkinsonians,” Psychosom. Med., 19 (1957), 332-338.
MacLean, P. D. “The Limbic (‘Visceral Brain’) in Relation to Central Gray and Reticulum of the
Brain Stem,” Psychosom. Med., 17 (1955), 355-366.
Malmo, R. B. “Symptom Mechanisms in Psychiatric Patients,” Trans. N.Y. Acad. Sci., 18 (1956),
545-549.
----. “Activation: A Neuropsychological Dimension,” Psychol. Rev., 66 (1959), 367-386.
Malmo, R. B., T. J. Boag, and A. A. Smith. “Physiological Study of Personal Interaction,” Psychosom.
Med., 19 (1957), 105-119.
Malmo, R. B. and C. Shagass. “Physiologic Studies of Reaction to Stress in Anxiety and Early
Schizophrenia,” Psychosom. Med., 11 (1949), 9-24.
----. “Physiologic Study of Symptom Mechanisms in Psychiatric Patients under Stress,” Psychosom.
Med., 11 (1949), 25-29.
----. “Studies of Blood Pressure in Psychiatric Patients under Stress,” Psychosom. Med., 14 (1952),
82-93.
Malmo, R. B., C. Shagass, and F. H. Davis. “Symptom Specificity and Bodily Reactions during
Psychiatric Interview,” Psychosom. Med., 12 (1950), 363-376.
Malmo, R. B., C. Shagass, and J. F. Davis. “A Method for the Investigation of Somatic Response
Mechanisms in Psychoneurosis,” Science, 112 (1950), 325-328.
----. “Electromyographic Studies of Muscular Tension in Psychiatric Patients under Stress,” J. Clin.
Exp. Psychopathol., 12 (1951), 45-66.
Malmo, R. B., C. Shagass, and A. Smith. “Responsiveness in Chronic Schizophrenia,” J. Pers., 19

(1951), 359-375.
Malmo, R. B., A. A. Smith, and W. A. Kohlmeyer. “Motor Manifestation of Conflict in Interview: A

Case Study,” J. Abnorm. Soc. Psychol., 52 (1956), 268-271.
Marschall, W. “The Psychopathology and Treatment of the Parkinsonian Syndrome and Other
Post-Encephalitic Sequelae,” J. Nerv. Ment. Dis., 84 (1936), 27-45.
Martin, I. “Levels of Muscle Activity in Psychiatric Patients,” Acta Psychol. (Amst.), 12 (1956), 326-
341.
Martin, I. and H. J. Grosz. “Hypnotically Induced Emotions,” Arch. Gen. Psychiatry, 11 (1964). 203-
213.
Martin, I. and L. Rees. “Reaction Times and Somatic Reactivity in Depressed Patients,” J.
Psychosom. Res., 9 (1966), 375-382.
McFie, J. “Psychological Effects of Stereotaxic Operations for the Relief of Parkinsonian

Symptoms,” J. Ment. Sci., 106 (1960), 1512-1517.
McLaughlin, J. T., R. N. Zabarenko, P. B. Diana et al. “Emotional Reactions of Rheumatoid Arthritics

to ACTH,” Psychosom. Med., 15 (1953), 187-199.
Meltzer, H. Y. and W. Engel. “Histo-chemical Abnormalities of Skeletal Muscle in Acutely Psychotic

Patients,” Arch. Gen. Psychiatry, 23 (1970), 492-502.
Meltzer, H. Y. and R. Moline. “Muscle Abnormalities in Acute Psychoses,” Arch. Gen. Psychiatry, 23
(1970), 481-491.
Mersy, D. J., T. Auyong, and R. Eelkema. “Relationship of Serum Urate Levels to Occupation and
Mental Retardation,” Psychosomatics, 9 (1968), 199-201.
Meyer, D. R. “On the Interaction of Simultaneous Responses,” Psychol. Bull., 50 (1953), 204-220.
Meyer, D. R., H. P. Bahrick, and P. M. Fitts. “Incentive, Anxiety, and the Human Blink Rate,” J. Exp.
Psychol., 45 (1953), 183-187.
Meyerowitz, S. “Editorial: Psychosocial Factors in the Etiology of Somatic Disease,” Ann. Intern.
Med., 72 (1970), 753-754.
----. “The Continuing Investigation of Psychosocial Variables in Rheumatoid Arthritis,” in A. Hill,

ed., Modern Trends in Rheumatology, pp. 92-105. New York: Appleton-Century-
Crofts, 1971.
Meyerowitz, S., R. Jacox, and D. W. Hess. “Monozygotic Twins Discordant for Rheumatoid
Arthritis: A Genetic, Clinical and Psychological Study of 8 Sets,” Arthritis Rheum., 11
(1968), 1-21.
Mikkelsen, W. M., H. Dodge, and H. Valkenburg. “The Distribution of Serum Uric Acid Values in a
Population Unselected as to Gout or Hyperuricemia,” Am. J. Med., 39 (1965), 242-
251.
Mitscherlich, M. “The Psychic State of Patients Suffering from Parkinsonism,” in A. Jores and H.
Freyberger, eds., Advances in Psychosomatic Medicine, pp. 317-324. New York:
Brunner, 1961.
Moldofsky, H. “Occupational Cramp,” J. Psychosom. Res., 15 (1971), 439-444.
Moldofsky, H. and W. J. Chester. “Pain and Mood Patterns in Patients with Rheumatoid Arthritis,”
Psychosom. Med., 32 (1970), 309-318.
Moldofsky, H. and A. I. Rothman. “Personality, Disease Parameters and Medication in Rheumatoid
Montoye, H. J., J. A. Faulkner, H. J. Dodge et al. “Serum Uric Acid Concentration among Business
Executives,” Ann. Intern. Med., 66 (1967), 838-850.
Moos, R. H. “Personality Factors Associated With Rheumatoid Arthritis: A Review,” J. Chronic Dis.,
17 (1964), 41-55.
Moos, R. H. and B. T. Engel. “Psychophysiological Reactions in Hypertensive and Arthritic

Patients,” J. Psychosom. Res., 6 (1962), 227-241.
Moos, R. H., and G. Solomon. “Minnesota Multiphasic Personality Inventory Response Patterns in
Patients with Rheumatoid Arthritis,” J. Psychosom. Res., 8 (1964), 17 28.
arthritic Sisters: I. Personality Test and Interview Rating Data,” Psychosom. Med., 27
(1965), 135-149.
----. “Psychologic Comparisons Between Women with Rheumatoid Arthritis and Their Non-
arthritic Sisters: II. Content Analysis of Interviews,” Psychosom. Med., 27 (1965),
150-164.
----. “Personality Correlates of the Degree of Functional Incapacity of Patients with Physical
Disease,” J. Chronic Dis., 18 (1965), 1019-1038.
Morrison, L. R., C. L. Short, A. O. Ludwig et al. “The Neuromuscular System in Rheumatoid

Arthritis,” Am. J. Med. Sci., 214 (1947), 2-49.
Mueller, A. D. and A. M. Lefkovits. “Personality Structure and Dynamics of Patients with

Rheumatoid Arthritis,” J. Clin. Psychol., 12 (1956), 143-147.
Mueller, A. D., A. M. Lefkovits, J. E. Bryant et al. “Some Psycho-social Factors in Patients with
Rheumatoid Arthritis,” Arthritis Rheum., 4 (1961), 275-282.
Mueller, E. F., S. V. Kasl, G. W. Brooks et al. “Psychosocial Correlates of Serum Urate Levels,”
Psychol. Bull., 73 (1970), 238-257.
Nalven, F. B. and J. O’Brien. “Personality Patterns of Rheumatoid Arthritic Patients,” Arthritis
Rheum., 7 (1964), 18-28.
Nidevar, J. E. A Factor Analytic Study of General Muscle Tension. Ph.D. dissertation, University of
California at Los Angeles, 1959. Unpublished.
Nissen, H. A. “Chronic Arthritis and Its Treatment,” N. Engl. J. Med., 210 (1934), 1109-1115.
Nissen, H. A. and K. A. Spencer. “The Psychogenic Problem (Endocrinal and Metabolic) in Chronic
Arthritis,” N. Engl. J. Med., 214 (1936), 576-581.
Noble, P. J. and M. H. Lader. “An Electromyographic Study of Depressed Patients,” J. Psychosom.

Res., 15 (1971), 233-239.
Oken, D. “An Experimental Study of Suppressed Anger and Blood Pressure,” Arch. Gen. Psychiatry,
2 (1960), 441-456.
----. “The Role of Defense in Psychological Stress,” in R. Roessler and N. S. Greenfield, eds.,
Physiological Correlates of Psychological Disorder, pp. 193-210. Madison: The
Orowan, E. “Origins of Man,” Nature, 175 (1955), 683-684.
Paul, L. “Psychosomatic Aspects of Low Back Pain,” Psychosom. Med., 12 (1950), 116-124.
----. “Mephenesin in Anxiety-tension States,” Psychosom. Med., 14 (1952), 378-382.
Ploski, H., E. Levita, and M. Riklan. “Impairment of Voluntary Movement in Parkinson’s Disease in
Relation to Activation Level, Autonomic Malfunction, and Personality Rigidity,”
Psychosom. Med., 28 (1966), 70-77.
Plutchik, R. “The Role of Muscular Tension in Maladjustment,” J. Gen. Psychol., 50 (1954), 45-62.
Polley, H., W. M. Swenson, and R. M. Steinhilber. “Personality Characteristics of Patients with

Rheumatoid Arthritis,” Psychosomatics, 11 (1970), 45-49.
Popert, A. J. and J. Hewitt. “Gout and Hyperuricaemia in Rural and Urban Populations,” Ann.
Rheum. Dis., 21 (1962), 154-163.
Price, J. P., M. H. Clare, and F. H. Ewerhardt. “Studies in Low Backache with Persistent Muscle
Spasm,” Arch. Phys. Med., 29 (1948), 703-709.
Prick, J. J. G., and K. Van de Loo. The Psychosomatic Approach to Primary Chronic Rheumatoid
Arthritis. Philadelphia: Davis, 1964.
Rahe, R. H. and R. Arthur. “Stressful Underwater Demolition Training. Serum Urate and
Cholesterol Variability,” JAMA, 202 (1967), 1052-1054.
Rahe, R. H. et al. “Serum Uric Acid and Cholesterol Variability,” JAMA, 206 (1968), 2875-2880.
Reich, W. Character-Analysis, 2nd ed. New York: Orgone Institute Press, 1949.
Reis, G. von. “Electromyographical Studies in Writer’s Cramp,” Acta. Med. Scand., 149 (1954), 253-
260.
Riklan, M. and E. Levita. Subcortical Correlates of Human Behavior. Baltimore: Williams & Wilkins,
1969.
Rimón, R. “A Psychosomatic Approach to Rheumatoid Arthritis: A Clinical Study of 100 Female

Patients,” Acta Rheumatol. Scand., (Suppl). 13 (1969), 1-154.
Rimón, R., A. Stenback, and E. Huhmar. “Electromyographic Findings in Depressive Patients,” J.

Psychosom. Res., 10 (1966), 159-170.
Rinehart, R. E. “Physiologic Approach to Rheumatic Disease,” in E. Jacobson, ed., Tension in

Medicine, pp. 55-70. Springfield, Ill.: Charles C. Thomas, 1967.
Robb, J. H. and B. S. Rose. “Rheumatoid Arthritis and Maternal Deprivation: A Case Study in the
Use of a Social Survey,” Br. J. Med. Psychol., 38 (1965), 147-159.
Robinson, C. E. G. “Emotional Factors and Rheumatoid Arthritis,” Can. Med. Assoc. J., 77 (1957).
344-345.
Robinson, H., R. Kirk, and R. Grye. “A Psychological Study of Rheumatoid Arthritis and Selected
Controls,” J. Chronic Dis., 23 (1971). 791-801.
Roessler, R., A. Alexander, and N. Greenfield. “Ego Strength and Physiological Responsivity: I,”
Rossi, A. M. “An Evaluation of the Manifest Anxiety Scale by the Use of Electromyography,” J. Exp.
Psychol., 58 (1959), 64-69.
Ruesch, J. and J. Finesinger. “The Relation between Electromyographic Measurements and

Subjective Reports of Muscular Relaxation,” Psychosom. Med., 5 (1943), 132-138.
Sabshin, M., et al. “Significance of Pre-experimental Studies in the Psychosomatic Laboratory,”

Arch. Neurol. Psychiatry, 78 (1957). 207-219.
Sainsbury, P. “Muscle Responses: Muscle Tension and Expressive Movement,” J. Psychosom. Res., 8
(1964), 179-185.
Sainsbury, P. and W. R. Costain. “The Measurement of Psychomotor Activity: Some Clinical

Applications,” J. Psychosom. Res., 15 (1971), 487-494.
Samra, K., M. Riklan, E. Levita et al. “Language and Speech Correlates of Anatomically Verified
Lesions in Thalamic Surgery for Parkinsonism,” J. Speech Hear. Res., 12 (1969), 510-
540.
Sandler, S. A. “Camptocormia, or the Functional Rent Rack,” Psychosom. Med., 9 (1947), 197-204.
Sands, I. “The Type of Personality Susceptible to Parkinson Disease,” J. Mt. Sinai Hosp. (N.Y.), 9
(1942), 792-794.
Sapirstein, M. R. “The Effect of Anxiety on Human After-Discharges,” Psychosom. Med., 10 (1948),

145-155-
Sarwer-Foner, G. J. “Psychoanalytic Theories of Activity-Passivity Conflicts and the Continuum of
Ego Defenses,” Arch. Neurol. Psychiatry, 78 (1957), 413-418.
Schwab, R. S., H. Fabing, and J. Prichard. “Psychiatric Symptoms and Syndromes in Parkinson’s
Disease,” Am. J. Psychiatry, 107 (1950), 901-907.
Scotch, N. A. and H. Geigeh. “The Epidemiology of Rheumatoid Arthritis,” J. Chronic Dis., 15 (1962),
1037-1067.
Seashore, R. H. “Work and Motor Performance,” in S. Stevens, ed., Handbook of Experimental

Psychology, pp. 1341-1362. New York: Wiley, 1951.
Shagass, C. and R. B. Malmo. “Psychodynamic Themes and Localized Muscular Tension during
Psychotherapy,” Psychosom. Med., 16 (1954), 295-314.
Shaskan, D., H. Yarnell, and K. Alper “Physical, Psychiatric and Psychometric Studies of Post-
Encephalitic Parkinsonism,” J. Nerv. Ment. Dis., 96 (1942), 652-662.
Shipman, W. G., H. Heath, and D. Oken. “Response Specificity Among Muscular and Autonomic
Variables,” Arch. Gen. Psychiatry, 23 (1970), 369-377.
Shipman, W. G., D. Oken, I. Balshan Goldstein et al. “Study in Psychophysiology of Muscle Tension:
II. Personality Factors,” Arch. Gen. Psychiatry, 11 (1964), 330-345.
Shipman, W. G., D. Oken, and H. Heath. “Muscle Tension and Effort at Self-Control during Anxiety,”
Shochet, B. R., E. T. Lisansky, A. F. Schubert et al. “A Medical-Psychiatric Study of Patients with

Rheumatoid Arthritis,” Psychosomatics, 10 (1969), 271-279.
Solomon, G. F. and R. Moos. “Emotions, Immunity and Disease,” Arch. Gen. Psychiatry, 11 (1964),
657-674.
----. “The Relationship of Personality to the Presence of Rheumatoid Factor in Asymptomatic

Relatives of Patients with Rheumatoid Arthritis,” Psychosom. Med., 27 (1965), 350-
360.
Southworth, J. A. “Muscular Tension as a Response to Psychological Stress in Rheumatoid
Arthritis and Peptic Ulcer,” Genet. Psychol. Monogr., 57 (1958), 337-392.
Spielberger, C. D. “Theory and Research on Anxiety,” in C. D. Spielberger, ed., Anxiety and

Behavior, pp. 3-20. New York: Academic, 1966.
Stetten, D. and J. Hearon. “Intellectual Level Measured by Army Classification Battery and Serum
Uric Acid Concentration,” Science, 129 (1959), 1737.
Stonehill, E. and A. H. Crisp. “Problems in the Measurement of Sleep with Particular Reference to
the Development of a Motility Bed,” J. Psychosom. Res., 15 (1970). 495-499.
Swaim, L. J. Arthritis Medicine and the Spiritual Laws. Philadelphia: Chilton, 1962.
Talbott, J. H. Gout, 2nd ed. New York: Grune & Stratton, 1964.
Talland, G. A. “Cognitive Function in Parkinson’s Disease,” J. Nerv. Ment. Dis., 135 (1962), 196-205.
Thomas, G. W. “Psychic Factors in Rheumatoid Arthritis,” Am. J. Psychiatry, 93 (1936), 693-710.
Tyndel, M. “The Other Side of A One-Sided Approach,” Am. J. Psychiatry, 127 (1971), 1101.
Voas, R. B. “Generalization and Consistency of Muscle Tension Levels.” Ph.D. dissertation,

University of California at Los Angeles, 1952. Unpublished.
Weiss, E. “Psychogenic Rheumatism,” Ann. Intern. Med., 26 (1947), 890-900.
Wenger, M. A. “Some Relationships between Muscular Processes and Personality and Their
Factorial Analysis,” Child Dev., 9 (1938), 261-276.
----. “An Attempt to Appraise Individual Differences in Level of Muscular Tension,” J. Exp.
Psychol., 32 (1943), 213-225.
Whatmore, G. B. and R. M. Ellis, Jr. “Some Motor Aspects of Schizophrenia: An EMG Study,” Am. J.
Psychiatry, 114 (1958), 882-889.
----. “Some Neurophysiologic Aspects of Depressed States: An Electromyographic Study,” Arch.
Gen. Psychiatry, 1 (1959), 70-80.
----. “Further Neurophysiologic Aspects of Depressed States,” Arch. Gen. Psychiatry, 6 (1962), 243-
253.
Wiener, D. N. “Personality Characteristics of Selected Disability Groups,” Genet. Psychol. Monogr.,

45 (1952), 175-255.
Williams, J. G. L. “Use of a Resonance Technique to Measure Muscle Activity in Neurotic and

Schizophrenic Patients,” Psychosom. Med., 26 (1964), 20-28.
Williams, R. and A. Krasnoff. “Body Image and Physiological Patterns in Patients with Peptic Ulcer
and Rheumatoid Arthritis,” Psychosom. Med., 26 (1964), 701-709.
Williams, T. A., J. Schachter, and R. Rowe. “Spontaneous Autonomic Activity, Anxiety, and
‘Hyperkinetic Impulsivity’,” Psychosom. Med., 27 (1965), 9-18.
Wolff, B. B. “Experimental Pain Responses as Predictors of Outcome of Surgical Rehabilitation in

Rheumatoid Arthritis,” (Abstract), Arthritis Rheum., 11 (1968), 519-520.
----. “Current Psychosocial Concepts in Rheumatoid Arthritis,” Bull. Rheum. Dis., 22 (1972), 656-
660.
Wolff, B. B. and R. Farr. “Personality Characteristics in Rheumatoid Arthritis,” (Abstract), Arthritis

Rheum., 7 (1964), 354.
Wolpe, J. Psychotherapy by Reciprocal Inhibition. Stanford: Stanford University Press, 1958.
Chapter 31
Obesity
Albert J. Stunkard
Obesity is a condition characterized by excessive accumulations of fat in

the body. By convention, obesity is said to be present when body weight
exceeds by 20 percent the standard weight listed in the usual height-weight
tables. This index of obesity, however, is only an approximate one at lesser
degrees of overweight, since bone and muscle can make a substantial
contribution to overweight. In the future, diagnosis will probably be based

upon newer and more accurate methods of estimating body fat. Skin-fold
calipers are already gaining acceptance because of their convenience and
because much of the excess fat is localized in subcutaneous tissue. But for
most clinical purposes the eyeball test is still the most reasonable: “If a person
looks fat he is fat.”
Epidemiology
Strikingly little information is available about the prevalence of obesity.
Since most good diagnostic methods are too cumbersome for use in large-
scale studies, much of our information is derived from height-and-weight data
of poor quality, averaged over populations, and subjected to the criterion of
20 percent over standard weight. The data we have suggest that prevalence of
obesity reaches a peak at age forty when 35 percent of men and 40 percent of
women can be so designated. Prevalence has been increasing slightly for men,
and decreasing slightly for women, during the past thirty years.
There have been studies of more limited populations utilizing more
reliable data and permitting more valid inferences. Unfortunately these
studies have differed in their criteria of obesity, making their data difficult or
impossible to use for comparisons among studies. These studies show a
striking effect of age, with a monotonic increase in the prevalence of obesity
between childhood and age fifty, and a twofold increase between ages twenty
and fifty. At age fifty, prevalence falls sharply, presumably because of the very
high mortality of the obese from cardiovascular disease in the older age
groups. Since these studies use the height-weight criterion, and since the fat
content of the body increases per unit weight with age, these studies almost
certainly underestimate the prevalence of obesity in older persons. The

increasing use of skin-fold calipers should soon be providing far more
satisfactory data.
All studies that have compared the sexes report a higher prevalence of
obesity among women; this discrepancy is particularly pronounced after age
fifty because of the higher mortality rate among obese men in that age group.
Social factors exert a powerful influence on the prevalence of obesity. In
many countries undernutrition limits the development of obesity. Freed of

this constraint in the affluence of American society, many ethnic groups show
a marked increase in the prevalence of obesity during their first generation in
this country. Thereafter, a variety of social influences combine to radically
reduce the prevalence of obesity. One study reported a fall from 24 to 5
percent between the first and fourth generations in this country.
The most striking antiobesity influence is that of socioeconomic status.

Figure 31-1 shows that obesity is six times as common among women of low
status as among those of high status in New York City. A similar, though
weaker, relationship was found among men. Two findings suggest that a
causal relationship underlies these correlations. First, as Figure 31-1 shows,
social class of origin is almost as closely linked to obesity as is the subject’s
own social class. Although obesity could conceivably influence a person’s own
social class, his obesity can hardly have influenced the social class of his
parents. Furthermore, obesity is far more prevalent among lower-class
children than it is among upper-class children; highly significant differences

are already apparent by age six. Similar analyses have shown that social
mobility, ethnic factors, and generational status in the United States also
influence the prevalence of obesity.
Figure 31-1.
Decreasing prevalence of obesity with increasing socioeconomic status

(S.E.S.) among women in New York City. Socioeconomic status of origin is
almost as strongly linked to obesity as is the person’s own socioeconomic
status. (Reprinted from P. B. Goldblatt, M. E. Moore, and A. J. Stunkard,
“Social Factors in Obesity,” Journal of the American Medical Association, 192
(1965), 1039-1044. Copyright c 1965 by the American Medical Association.)
Genetics
The existence of numerous forms of inherited obesity in animals, and
the ease with which adiposity can be produced by selective breeding, make it
clear that genetic factors can play a determining role in obesity. These factors
must also be presumed to be important in human obesity, although clear-cut
evidence of genetic transmission has been obtained only in such rare
conditions as the Laurence-Moon-Biedl syndrome.
A number of studies have confirmed the layman’s impression that

obesity “runs in families.” In one study obesity was reported in the offspring
of approximately 80 percent of obese-x-obese matings, in 40 percent of
obese-x-nonobese matings, and in no more than 10 percent of nonobese-x-

nonobese matings. In another series, Davenport reported that among fifty-
one children of slender parents none was of more than average weight and
most were slender; among thirty-seven children of obese parents, on the
other hand, none was slender, all were of at least average weight, and a third
were obese. But such figures inevitably confuse genetic and environmental
influences. Although there have been efforts to separate these influences—by
studies of twins and of adopted children—none has elucidated the

mechanism of transmission nor provided more than rough estimates of the
relative contribution of inheritance. Because so many nongenetic factors can
influence body weight, it is generally agreed that overweight per se is an
unsatisfactory phenotype for the study of the genetics of human obesity.
Interest is now shifting to the transmission of somatotypes. Their
relevance is clear from Seltzer and Mayer’s demonstration that obesity occurs
with much greater frequency in some physical types than others. Obese
adolescent girls, for example, show extremely low ratings for ectomorphy; the
presence of even a moderate degree of ectomorphy appeared to protect
against obesity. It has been estimated that two-thirds of women in the general
population may be sufficiently ectomorphic to receive significant protection
against obesity. Preliminary studies by Withers suggest that somatotypes are

heritable, particularly father-daughter transmission of mesomorphy and
mother-son transmission of endomorphy. Further investigations of the
inheritance of body types, and of their relation to obesity are sorely needed.
Obesity in Childhood
The obesity of persons who were obese in childhood—the so-called
“juvenile-onset obese”—differs from that of persons who became obese as
adults. Juvenile-onset obesity tends to be more severe, more resistant to
treatment, and more likely to be associated with emotional disturbances.
Obesity that begins in childhood shows a very strong tendency to

persist. Long-term prospective studies in Hagerstown, Maryland, have
revealed the remarkable degree to which obese children become obese
adults. In the first such study, 86 percent of a group of overweight boys
became overweight men, as compared to only 42 percent of boys of average

weight. Even more striking differences in adult weight status were found
among girls: 80 percent of overweight girls became overweight women, as
compared to only 18 percent of average weight girls. A later study showed
that the few overweight children who reduced successfully had done so by
the end of adolescence. The odds against an overweight child becoming a
normal weight adult, which were 4:1 at age twelve, rose to 28:1 for those who
did not reduce during adolescence. An even more recent study, which used a
longer interval (thirty-five years) and, unfortunately, different (more rigid)
criteria for obesity, found the difference in adult weight status continuing to
grow: 63 percent of obese boys became obese men, as compared to only 10
percent of average weight boys.
A brilliant series of studies of adipose tissue has recently helped to
explain the remarkable persistence of juvenile-onset obesity. Many obese
persons, particularly those with juvenile-onset obesity, show a marked
increase in total number of adipocytes in subcutaneous tissue and in other

depots. Whereas the average nonobese person has a total of 25-30 X 109
adipocytes, obese persons may have five times this number. The average lipid
content of the adipocytes of normal-weight and obese persons varies to a far

smaller degree: 0.7 μg. for the nonobese and 1.0 μg for the obese.
With weight reduction, individual cells shrink greatly, but the total
adipocyte number remains constant. A number of animal studies suggest that

early in life adipose tissue grows both by increasing cell size and increasing
cell number. If feeding patterns are changed during the first three weeks of a
rat’s life, there will be marked changes in cell number. But when the animal is
made obese in adult life, he grows no new adipocytes, the ones he has simply
enlarge.
These studies of cellularity in obesity focus attention on the influence
early feeding patterns have on the later development of obesity. Adipocyte
size and number may be another factor that influences hypothalamic activity
and feeding behavior. Obese persons who have lost weight but whose
increased number of adipocytes persists tend to overeat and thus refill these
extra cells. We have no biochemical data as yet to indicate the nature of the
signal from adipose tissue to the hypothalamus.
Etiology
What causes obesity? In one sense the answer is quite simple—eating
more calories than are expended as energy. In another sense, the answer still
eludes us. For we do not know why some people eat more calories than they
expend. But we are making progress. We no longer, for example, expect to
find the cause of obesity, and we are far more aware than were our
predecessors of the many factors involved in the regulation of body weight.
Our increased awareness of the problem’s complexity has resulted in
the development of an appealing framework for considering the etiology of
obesity. Obesity may profitably be viewed as the end product of a disturbance
in energy balance, or in the regulation of body weight. This view has helped
us organize current information about obesity and has encouraged and
informed the search for new information. I will consider at some length what
is now known about the regulation of body weight, to understand better how
six disparate factors may influence this regulation. I have already discussed
three of these, the genetic, social, and developmental. I will take up the other
three later i.e., physical activity, brain damage, and emotional problems.
The Regulation of Body Weight
An average nonobese man stores fat to the extent of about 15 percent of
his body weight, enough to provide for all of his caloric needs for nearly a
month. This same man consumes approximately one million calories a year.
His body fat stores remain unchanged during this time, because he expends
an equal number of calories. An error of no more than 10 percent in either
intake or output would lead to a thirty-pound change in body weight within
this year.
Rats who are force-fed or deprived of food rapidly return to their
normal body weights when permitted to return to ad libitum feeding. Similar

studies of man are extraordinarily difficult to carry out. Yet in the rare
instances when the body weight of human volunteers has been
experimentally altered, it, too, rapidly returned to normal values. Sims found
that normal-weight volunteers who were fattened by overfeeding and
underactivity returned to their normal body weight soon after returning to
their usual patterns of eating and activity. Keys’ classic study of experimental
semistarvation showed a similar rapid return to normal body weight when

the subjects were permitted free access to food. Clearly body weight is
regulated with the greatest precision in all nonobese animals, including man.
This regulation has been described in detail in two recent scholarly reviews,
as has the powerful glucostatic theory of the regulation of food intake.
As befits such a vital function, the neural control of food intake is widely
distributed throughout the brain. Within the limbic system alone six thousand
different sites have been found to influence eating behavior. Nevertheless,
certain structures seem to play a more important part than others.
The discovery that two different hypothalamic areas control hunger and
satiety—one in the lateral hypothalamus mediating the former, the other in
the ventromedial nucleus mediating the latter—initiated our current

understanding of these clearly separable functions. More recent anatomic
studies have identified extrahypothalamic structures which play a part as
important as that of the hypothalamus in the regulation of food intake.

Feeding, for example, is controlled by a diffuse circuit that links the forebrain
limbic system (and particularly areas in the amygdala) and the globus
pallidus to the midbrain tegumentum via the lateral hypothalamus. The
satiety area in the ventromedial hypothalamus similarly links forebrain
limbic structures and the head of the caudate nucleus to the midbrain. There
are also more direct connections between the feeding and satiety systems, for
example, the inhibitory fibres that run from the ventromedial to the lateral
hypothalamic areas.
Noradrenalin serves as a major neurotransmitter in both the feeding

and satiety systems. Alpha- and beta-adrenergic subsystems have recently
been identified, although their precise functions and locations are still
unclear.
Most of our information about the role of the central nervous system in
food intake regulation has been obtained experimentally, by destroying or
stimulating certain areas electrically or chemically. But what signals normally
activate this complex neural apparatus?
A common-sense view holds that we stop eating at the end of a meal
because we have replenished some nutrient that had been depleted. And we
become hungry again when the nutrient, which had been restored by the
meal, is once again depleted. Specifically it has been proposed that some
metabolic signal, derived from food that has been absorbed, is carried by the
blood to the brain. There this signal activates receptor cells, probably in the
hypothalamus, to produce satiety. Hunger is the consequence of the
decreasing strength of this same metabolic signal, secondary to the depletion
of the critical nutrient.
Four classical theories of hunger and satiety have been based upon this
argument, differing from each other only in the nature of the signal to which
they ascribe primary significance. The thermostatic theory, for example,
proposes that postprandial increases in hypothalamic temperature mediate

satiety; hunger results from a decrease in temperature at this site. Lipostatic,
aminostatic, and glucostatic theories each assign the critical regulatory role to
blood-borne metabolites of fat, protein, and carbohydrate.
Although each of these theories explains some of the many phenomena
involved in the control of food intake, the glucostatic theory has had by far the
greatest predictive power. It starts, as do the others, with the assumption that
the signal to the central nervous system comes from one of the three major
foodstuffs, i.e., fat, carbohydrate, or protein, or from a metabolic product of
one of them. When we consider that the body stores of the key nutrient must
be significantly depleted in the hours between meals, we must rule out the
role of fat and protein. For such a tiny fraction of the total body stores of both
these is used up in those few hours that it is very unlikely that any brain
center could detect the change.
With carbohydrates the situation is quite different. The body as a whole
can store only very small amounts and the liver, which is the principal storage
site of readily available carbohydrate, can actually store no more than half the
body’s daily requirement of calories. In the few hours between meals,
therefore, an enormous percentage of the body’s carbohydrate stores is used
up. Any center sensitive to the depletion of carbohydrate stores should have
no trouble in detecting a depletion of this size, and in letting the brain know
that more carbohydrate is needed.
According to the glucostatic theory, depletion of carbohydrate stores is
signaled by the amount of “available glucose” in the circulating blood; a fall in
the level of available glucose, signaled to hypothalamic glucoreceptors,

becomes the signal for hunger. An increase in available glucose, with
carbohydrate repletion, activates the hypothalamic satiety areas, and
terminates eating. The heuristic value of this theory was demonstrated when
hypothalamic “glucoreceptors” first postulated by Mayer but unknown at the
time that he proposed the theory, were discovered.
The vigor of the glucostatic theory, twenty years after it was first
proposed, is manifested by the many studies it continues to stimulate. Direct
measurements of the electrical activity of the hypothalamus have confirmed
the findings of earlier, indirect studies of the influence of intravenous glucose.

Glucose infusion increases electrical activity in the ventromedial area, and
decreases such activity in the lateral area in accordance with the prediction
that glucose should increase satiety and decrease hunger. Another line of
evidence in support of the glucostatic theory has been derived from studies
using the nonmetabolizable glucose analogue 2-deoxy-D-glucose (2-DG).
Administration of 2-DG to animals produces decreased intracellular

utilization of glucose, particularly in the brain. Such a decrease in available
glucose, a classic example of the signal postulated by the glucostatic theory,
produces a prompt and significant increase in food intake. Recently Russek
has proposed an imaginative variation of the glucostatic theory. He has

amassed considerable evidence in support of the idea that the primary site of
glucoreception is not in the hypothalamus, but in the liver.
Despite the attractiveness of the glucostatic theory, it shares with all
single-factor theories the difficulty of encompassing the many events involved

in the regulation of food intake. Figure 31-2 shows, in schematic outline, the
many variables that must be considered in this regulation.
In addition to this general problem, single factor theories of the control

of food intake encounter also two specific problems. First, how can a
mechanism of short-term, meal-to-meal, control of food intake account for the
remarkable stability of body weight over long periods of time, and in the face
of often marked short-term fluctuations? Second, how can a single-factor
theory, or indeed any physiological theory, account for the function of satiety?
For satiety occurs very soon after the beginning of a meal, when only a small
proportion of the total caloric intake of the meal can have been absorbed. If
satiety were based solely on the limited information about food intake
available at that point, if could contribute little or nothing to the regulation of
food intake.
Figure 31-2.
Scheme of the factors contributing to the regulation of body weight.

(Copyright © 1954 by the Amer. Psychol. Assoc. Reprinted by permission.)
Recent work by LeMagnen has further documented just how imprecise
the mechanism of satiety really is. He has shown that when animals feed ad
libitum, meal size bears little relation to the length of the preceding period of
food deprivation. But meal size does determine, quite precisely, the length of
time until the next meal. The energy needs of the body determine when a
meal is initiated, but not the size of the meal. In other words, what is
regulated is meal-interval, not meal-size. Or, in the regulation of food intake,
hunger is controlled precisely, satiety only approximately.
Man’s ability to alter the interval between meals is sharply limited by
the routines of daily life. As a consequence, he is forced to rely primarily on
changes in meal size to regulate his food intake. Thus the imprecise
mechanism of satiety is burdened even more heavily in man than in animals.
If satiety depended solely on humoral factors such as ingested glucose or
other nutrients, it would be hopelessly inadequate to the task of regulating

food intake.
If humoral factors do not terminate eating, what does? “A full stomach”
may be a better answer than we would have thought even a few years ago.
Certainly common sense and personal experience suggest that the smell and
taste of food, and the feeling of a full stomach, play a part in satiety. Recent
systematic clinical investigations support this view. In man as in animals,

gastric filling, quite irrespective of the nutritive value of the meal, is the major
determinant of satiety in single-meal experiments. The neural mechanism
that mediates this response has also recently been demonstrated: gastric
distention and direct stimulation of the mechanoreceptors of the stomach
wall increase the firing rate of single units within the ventromedial nucleus.
Although the nutritional value of the meal, as we have noted, plays little
or no part in satiety in single-meal experiments, man seems to learn (as do
other animals) to change his food intake and even his meal size, in response
to changes in energy expenditure and in the character of his food. Is this
learning? If so, how does he learn?
Alimentary Learning
An understanding of the mechanism for adjusting food intake, and
particularly changes in meal size and frequency, has long eluded us. Our areas
of ignorance are still vast. But some recent discoveries have made it possible
to entertain a theory which would have been untenable until now. I propose
that the adjustment of meal size and meal frequency is a learned process
involving Pavlovian, or respondent, conditioning. In this theory oral and
gastric factors serve as conditioned stimuli, while humoral factors absorbed
from the gastrointestinal tract serve later as the unconditioned stimuli. This
sequence can account both for the termination of eating early in the process
of food absorption from the intestine and for the long-term adjustment of
meal size to changing caloric needs.
Until recently this theory had an apparently fatal flaw. The interval
between presentation of the postulated conditioned stimuli and presentation
of the unconditioned stimuli may well be an hour long. Pavlov showed early
in this century that classical conditioning cannot occur if the interval exceeds
a few seconds.
The idea that the interval between conditioned and unconditioned
stimuli (the CS-US interval) could not exceed a few seconds went
unchallenged through fifty years of research on conditioning. Then two lines
of investigation produced evidence demolishing this constraint. In a little-
noticed paper in Science, Garcia reported a striking exception to the belief that
the CS-US interval cannot exceed a few seconds in duration. Using saccharine
as the conditioned stimulus, and x-radiation (and the consequent radiation
sickness) as the unconditioned stimulus, he was able to produce in rats a
conditioned aversion to saccharine with CS-US intervals of hours in length.

Further studies showed that, in contrast to the frequent CS-US pairings
necessary to produce most conditioned responses, such aversion can occur

with only one pairing of CS and US. Finally, and again in contrast to the usual
conditioned response, the aversion is remarkably resistant to extinction.
More recently, Rozin has shown that positive reinforcers can produce
food preferences, “specific hungers,” under conditions similar to those in

which aversive reinforcement produces aversions. It has been known for
years that animals deficient in thiamine select diets that contain thiamine
(even if only a trace) out of a wide variety of possible foods. Rozin showed
that this preference results from two factors: (1) a learned aversion, of the
type demonstrated by Garcia, to diets that do not contain thiamine, and (2)
the positively reinforcing effect of the vitamin on the vitamin-deficient
animal. Learning about beneficial consequences over long CS-US intervals is
clearly weaker than learning about the aversive consequences. We do not
know the upper limit of the interval between the conditioned stimulus of
thiamine ingestion and the unconditioned stimulus of well-being, but it can
hardly be shorter than many minutes, and it may be as long as hours.
The food preferences and aversions demonstrated by Rozin and Garcia
seem to represent a special form of Pavlovian conditioning which, for

convenience, we may call “alimentary learning.” The distinctive features of
“alimentary learning” are: (1) the conditioned stimulus must be either taste
or smell; (2) the unconditioned stimulus must be a general body state, either
a dysphoric one such as radiation sickness, fever, nausea or, on the other
hand, a euphoric one such as is presumably produced by thiamine repletion;

(3) the learning can occur with unusual rapidity, after as few as one CS-US
pairing, (4) the CS-US intervals can be as long as ten hours; and (5) these
conditioned responses are unusually resistant to extinction.
The food preferences and aversions which have taught us about
“alimentary learning” are of great importance in their own right.
Furthermore, they have freed us from those constraints of Pavlovian
conditioning which have limited our understanding of control of food intake.
But I believe that they are best understood as special cases of a more general
phenomenon. The primary purpose of “alimentary learning” may be the
mediation of satiety. I see “alimentary learning” as a bridge between the long-
term, physiological regulation of food intake based upon humoral factors, and
the short-term cessation of eating based on gastric filling. If this view is even
approximately correct, then impaired “alimentary learning” may underlie the
eating disorders found in obesity. An impairment of satiety surely plays a
major role in these disorders.
Physical Activity
The only component on the energy-expenditure side of the caloric
ledger that both fluctuates and is under voluntary control is physical activity.
As such, it is a vital factor in the regulation of body weight. Indeed, the
marked decrease in physical activity in affluent societies seems to be the
major factor in the recent rise of obesity as a public health problem. Obesity is
a rarity in most underdeveloped nations, and not solely because of

malnutrition. In some rural areas, a high level of physical activity is at least as
important in preventing obesity. Such levels of physical activity are the
exception in this country. If the trend exemplified by automatic can openers
and mechanized swizzle sticks continues, we may succeed in reducing our
energy expenditure to near basal levels. Among many obese women, the
trend is already far advanced.
Figure 31-3 shows marked reduction of physical activity of a group of

Philadelphia housewives; this reduction is so great as to account almost
entirely for their excess weight. But such low levels of physical activity are
not present among all obese persons. Figure 31-3 shows that the differences
in physical activity among the men were so small that the additional energy
expended by obese subjects in moving their heavier bodies produced a caloric
expenditure equal to that of nonobese men.
Figure 31-3.
Figure 31-3.
Comparison of the physical activity of obese and nonobese men and women.
Each point represents the average distance walked each day by each subject,
as measured by a mechanical pedometer. Most obese women walked shorter
distances than nonobese women. Among men, there is less difference in the
distances walked. (Reprinted by permission from N. Engl. J. Med., 263 (1960),
935-946.)
Until quite recently, physical inactivity was considered to cause obesity
primarily via its restriction of energy expenditure. There is now good
evidence that inactivity may contribute also to an increased food intake.
Although food intake increases with increasing energy expenditure over a
wide range of energy demands, intake does not decrease proportionately

when physical activity falls below a certain minimum level, as shown in
Figure 31-4. In fact, restricting physical activity may actually increase food
intake! Conversely, when sedentary persons increase physical activity, their
food intake may decrease. The mechanism involved in this intriguing control
are still unclear, but its great therapeutic potential makes it worthy of careful
study.
Figure 31-4.
Figure 31-4.
Caloric intake and body weight as functions of duration of exercise in adult

rats. Within the range of normal physical activity, food intake increases with
increasing physical activity and body weight remains stable. In the sedentary
range of activity, however, decreasing physical activity is associated with
increased food intake and an increase in body weight. (Copyright © 1967 by
the Amer. Assoc. Advance. Science. Reprinted by permission.)
Disorders in the Regulation of Body Weight
Our general understanding of the regulation of body weight was greatly
advanced during the late 1940s when it was discovered that destruction of
the satiety areas of the hypothalamus could produce obesity. Many of the
features of the disordered food intake produced by these lesions were

described by Neal Miller in 1950 in a paper with the trenchant title,
“Decreased Hunger and Increased Food Intake in Hypothalamic Obese Rats.”
This remarkably prescient report described for the first time the peculiar
feeding behavior of rats made obese by hypothalamic lesions.
The cardinal feature of the rats’ behavior was that they overate when
food was freely available, but when an impediment was placed in the way of
their eating, they not only decreased their food intake, but actually decreased
it to a far lower level than that of control rats without hypothalamic lesions.
Furthermore, it seemed to make little difference what kind of impediment
was used; motivation to work for food was impaired in every manner of task
that could be devised. These rats seemed to be relatively unresponsive to all
physiological cues about their nutritional state, and they responded
imperfectly to signals both of satiety and of deprivation.
On the other hand, the obese rats seemed hyperresponsive to the taste
of food and to its availability. They increased their overeating when fat and
sweet substances were added to their diet, and radically restricted intake
when the palatability of their food was decreased by the addition of quinine.
Similar eating patterns have been reported in a wide variety of animals when
they became obese for natural reasons, such as in the genetically determined
yellow obese mouse, in the rat when it becomes obese with aging, and even in
the dormouse during the hyperphagia which precedes its hibernation.
The impaired satiety found in different forms of experimental obesity
also characterizes the eating patterns of many obese persons. In the
exceptional instance this disorder results from unequivocal hypothalamic
damage as a result of a strategically placed tumor or vascular lesion; usually
we do not know the cause of this impaired satiety. Such persons
characteristically complain of being unable to stop eating; it is the unusual
obese person who reports being driven by hunger or who eats in ravenous
manner. Instead, obese persons seem inordinately susceptible to food cues in
their environment, to the palatability of foods, and to the inability to stop
eating if food is available.
Bruch has documented these problems of the obese without brain
damage in her vivid descriptions of their misperception of important visceral
events. Some obese persons, who are also neurotic, have difficulty in
identifying hunger and satiety. They frequently seem unable to distinguish

between hunger and other kinds of dysphoria. Bruch has linked this
“conceptual confusion” to severe deficits in identity and to feelings of

personal ineffectiveness. She has convincingly described the need on the part
of these patients for external signals to tell them when to eat and when to
stop eating. Strong support for Bruch’s position has come from a recent study
which shows that neurotic obese persons have a strong response bias that
impairs their perception of gastric motility. Unfortunately, correction of the
bias did not result in weight loss.
Schachter has reported a long series of experiments documenting that

obese persons are unusually susceptible to all kinds of “external” stimuli to
eating, while they remain relatively unresponsive to the usual “internal,” i.e.,
physiological, signals of hunger. In one comparison with normal-weight

controls, obese subjects overate a palatable ice cream and underate an
unpalatable one. Similarly, they overate in an experimental setting when food
was in front of them, while they underate when getting additional food
required no more than opening a refrigerator door. Their eating was even
influenced inordinately by what time of day they thought it was.
These findings suggest the ways in which social factors may influence
the prevalence of obesity. For the ways in which a culture makes food
available (and relatively less available) to its obesity-prone, “externally
controlled” members may well determine the degree to which such
individuals overeat.
Disorders in the Regulation of Body Weight, Emotional Determinants
Many obese persons report that they often overeat and gain weight
when they are emotionally upset. But it has proved singularly difficult to
proceed from this provocative observation to an understanding of the precise
relationship between emotional factors and obesity.
The most clear-cut evidence of how emotional factors influence obesity
has come from two small subgroups of obese persons, each characterized by
an abnormal and stereotyped pattern of food intake. About 10 percent of
obese persons, most commonly women, manifest a “night-eating syndrome”
characterized by morning anorexia, and evening hyperphagia with insomnia.

This syndrome seems to be precipitated by stressful life circumstances and,
once present, tends to recur daily until the stress is alleviated. Attempts at
weight reduction when the syndrome is present have an unusually poor
outcome and may even precipitate a more severe psychological disturbance.
The “binge-eating syndrome,” found in fewer than 5 percent of obese
persons, is one of the rare exceptions to the pattern of impaired satiety. It is
characterized by the sudden, compulsive ingestion of very large amounts of

food in a very short time, usually with great subsequent agitation and self-
condemnation. It too appears to represent a reaction to stress. But in contrast
to the night-eating syndrome, these bouts of overeating are not periodic and
they are far more often linked to specific precipitating circumstances. Binge
eaters can sometimes lose large amounts of weight by adhering to rigid and
unrealistic diets, but such efforts are almost always interrupted by a

resumption of eating binges.
Complications
Troublesome as obesity may be from a cosmetic standpoint, it is the
serious health hazards associated with it that have warranted its description
as the nation’s greatest preventable cause of death. This effect is largely the
result of obesity’s impact on the cardiovascular diseases which now cause
half the deaths in this country.
Effects on Mortality
The evidence is strong that obesity adversely affects morbidity and
mortality rates. The death rate from a variety of diseases is significantly
higher among obese persons, and the rate increases in proportion to the
severity of the obesity and to its duration during adult life. Sudden death is
particularly closely linked to obesity. Furthermore, obese persons who lose
weight and maintain the loss show radically reduced mortality rates. For
women, the rate after weight reduction was as low as if they had never been
obese.
This evidence of the direct effect of obesity on mortality is matched by
evidence of its indirect effect. Two of the most potent risk factors for coronary
artery disease, i.e., adult-onset diabetes and hypertension, are also highly
correlated with obesity. Here again, weight reduction has a powerful effect:
75 percent of adult-onset diabetics may discontinue medication, and the
blood pressure of 60 percent of hypertensives returns to normal levels after
significant weight loss.
In recent years, arguments against the importance of obesity in
coronary disease have been raised on the basis of data from prospective
population studies. These studies report that, if such associated conditions as

hypertension and elevated cholesterol and triglyceride levels are factored out,
obesity is a poor, and often a very poor, predictor of coronary disease. But
since obesity contributes to both hypertension and to disorders of lipid
metabolism, such an analysis may not be justified. Furthermore, many

laboratory studies have demonstrated how obesity may contribute to
coronary disease. Adult-onset obesity predisposes to a response to a
carbohydrate load characterized by hyperglycemia, hyperinsulinism, and

hypertriglyceridemia, all implicated in the pathogenesis of atherosclerosis.
Keys’ seven-country study is worthy of note. Although coronary heart
disease was only weakly correlated with obesity, it was closely correlated
with the saturated fatty acid content of the diet. The very high percentage of
calories from this source in the American diet suggests that treatment of
obesity should include restriction of saturated fatty acids as well as of

calories.
Physical and Laboratory Abnormalities
The most serious physical manifestation of obesity, and the only one
which is (very rarely) life-threatening, is the encircling of the thorax with

fatty tissue together with pressure on the diaphragm from below due to intra-
abdominal accumulations of fat. The result is reduced respiratory excursion,
with dyspnea on even minimal exertion. In very obese persons, this condition
may progress to the so-called “Pickwickian syndrome,” characterized by
hypoventilation with consequent hypercapnia, hypoxia, and, finally,
somnolence.
Severe obesity leads to a variety of orthopedic disturbances, including
low-back pain, aggravation of osteoarthritis, particularly of the knees and

ankles, and often enormous calluses over the feet and heels. Even mild
degrees of obesity are associated with amenorrhea and other menstrual
disturbances. Subcutaneous fat is an excellent heat insulator, and the skin of
obese persons is often warm and sweaty, particularly after meals.

Hyperhidrosis leads to intertrigo in the pendulous folds of tissue, making
itching and skin disorders common. Mild to moderate edema of the feet and
ankles often occurs, probably due to venous obstruction; diuretics are not
indicated. What is most notable about all of these complications is the ease
with which they can be controlled and eliminated by weight reduction, often
of only a moderate degree.
Blood pressure elevations are frequently found in obese persons, often
due to an artifact, i.e., the presence of masses of subcutaneous tissue between
the blood pressure cuff and the brachial artery. This problem can sometimes
be overcome by using a wider blood-pressure cuff. But any serious doubt as
to the existence of hypertension should be resolved by direct intraarterial
measurement, particularly before starting specific antihypertensive therapy.
Hyperuricemia is sometimes found in obesity, and it may reach a
significant degree in persons who fast intermittently. When obesity has
produced respiratory distress, hypercapnia may develop along with a
respiratory acidosis.
A particular problem in the laboratory evaluation of obesity is the

impaired glucose tolerance, and even fasting hyperglycemia, that occurs in
many obese persons without a family history of diabetes. The high insulin
levels in the fasting state and after a glucose load, usually associated with
obesity, are related to the presence of muscle and adipose tissue resistance to
carbohydrate metabolism. The precise relationship between tissue resistance
and insulin levels is not clear. It may be that tissue resistance signals the
pancreas to produce more insulin, or that a high-calorie diet may increase
insulin production, with tissue resistance a secondary phenomenon. However
these questions are finally resolved, the response to weight reduction is

highly gratifying. Most such abnormalities disappear completely unless the
patient is truly diabetic.
Plasma-lipid levels are often moderately elevated in the obese; again

both cholesterol and triglyceride levels decline with weight reduction.
Emotional Disturbances
Numerous reports on psychological disturbances among the obese have
flooded the literature, making it difficult even for the expert to reconcile the
varied and conflicting observations. Many of the problems are the result of
difficulties in establishing suitable control groups. It has generally turned out
that the better the control group the less the evidence for distinctive
psychological features and disabilities. The view that obese persons have a
specific personality pattern is no longer held.
Carefully controlled studies do show that the obese have a higher
degree of psychopathology than do the nonobese. The differences, however,
are relatively small for the obese population as a whole. For certain
subgroups, on the other hand, the differences may be quite significant.
Prominent among these are young women of upper- and middle-
socioeconomic status. The reasons for the special vulnerability of these

groups are of interest.
Since both obesity and emotional disturbance are common among
persons of lower socioeconomic status, any association between the two in
this stratum is quite likely to be coincidental. Higher up on the socioeconomic
ladder, however, obesity is far less prevalent and the sanctions against it far
stronger. There is also far less emotional disturbance at this level. As a result,
when obesity and emotional disturbance coexist in this group, the likelihood
that they are associated is far higher. Among young, upper-class women any
obesity is very often closely linked to neurosis. What is the nature of this
linkage?
Of the various emotional disturbances to which obese persons are
subject, only two are specifically related to their obesity. The first is
overeating, the second, disturbance in body image.
The obese person whose body image is disturbed characteristically feels

that his body is grotesque and loathsome, and that others view it with
hostility and contempt. This feeling is closely associated with self-
consciousness and impaired social functioning. It would seem reasonable to
suppose that all obese persons have derogatory feelings about their bodies.
Such is not the case. Emotionally healthy obese persons have no body-image
disturbances, and, in fact, only a minority of neurotic obese persons have such
disturbances. The disorder is confined to those who have been obese since
childhood; less than half, even among these juvenile-onset obese, suffer from
it. But it is in the group with body image disturbances that neurosis is closely
related to obesity and this group contains a majority of obese persons with
specific eating disorders.
The extent and severity of complications following weight reduction
programs have been the subject of controversy in recent years. It now
appears that as many as half of patients routinely treated for obesity by

family physicians may develop mild anxiety and depression. In addition, a
high incidence of emotional disturbance has been reported among obese
persons undergoing long-term, in-hospital treatment by fasting or severe
caloric restriction. These complications should be balanced against the
likelihood of a decrease in anxiety and depression among those who diet
successfully. Such newer treatments as behavior modification and intestinal

by-pass surgery appear to carry less risk of emotional disturbance.
Obese persons with extensive psychopathology, those with a history of
emotional disturbance during dieting, or those in the midst of a life crisis

should attempt weight reduction, if at all, cautiously and under careful
supervision. For others, the possibility of complications need not preclude
treatment when it is indicated.
Treatment
General Considerations
Weight reduction confers such great benefits upon obese persons, and it
is apparently so simple, that we might expect to find large numbers of

formerly fat people. How can obese people fail to reduce?
The best evidence is that they not only can, but do, fail. Perhaps the
large number of women who try to reduce without medical assistance, on
diets and advice from the women’s magazines, have success. But most obese
persons will not enter outpatient treatment for obesity; of those who do, most
will not lose a significant amount of weight; and of those who do lose weight,
most will regain it. Furthermore, these poor results are due not to failure to
implement any simple therapy of known effectiveness but to the fact that no
simple or generally effective treatment exists. Obesity is a chronic condition,
resistant to treatment, and prone to relapse.
The basis of weight reduction is utterly simple, i.e., establish a caloric
deficit by bringing intake below output. All of the many treatment regimens
have as their goal this simple task. Perhaps its very simplicity helps to
account for an unfortunate aspect of treatment. Unable to understand why his

patients cannot carry out this task, the physician often reacts punitively
towards them. We have recently become aware that intense discrimination is
practiced against obese persons, that it begins in childhood, and that it is
continued throughout life to a degree that approaches that practiced against
other minority groups. Before undertaking treatment of an obese person, the
physician should assure himself that he will not add to this burden. For given
the low probability that sustained weight reduction can be achieved, it may
be wisest to try to dissuade the patient from a treatment that may come to
nothing more than still another experience of failure for him and a source of
frustration for his physician.
The simplest way to reduce caloric intake is by means of a low-calorie
diet. The best longterm effects are achieved with a balanced diet that contains
readily available foods. For most people, the most satisfactory reducing diet
consists of their usual foods, in amounts determined with the aid of tables of
food values available in standard works. Such a diet gives the best chance of
long-term maintenance of the weight lost during dieting. But it is precisely the
most difficult kind of diet to follow during the period of weight reduction.
Many obese persons find it easier to use a novel or even bizarre diet of
which there have been a profusion in recent years. Whatever effectiveness
these diets may have is due in large part to their monotony—almost anyone
will get tired of almost any food if that is all that he gets to eat. As a
consequence, when he stops the diet and returns to his usual fare, the
incentives to overeat are multiplied.
Fasting, which results in rapid weight loss, has had a considerable vogue
as a treatment for obesity in recent years. Many obese persons find it
relatively easy to tolerate. After two or three days without food, hunger
decreases radically and the patient is able to get along well, as long as he
remains in an undemanding environment. For some massively obese persons,
or for the occasional patient in whom rapid weight loss is indicated, it has
some small rationale. However follow-up studies of persons who have

undergone long-term fasts, show that almost all regain at least all of the
weight they lost. Short-term (ten-day) intermittent fasts, by moderately obese
persons, appear to have had somewhat better results, but adequate follow-up
studies are not available. Because of the occasionally serious complications of

fasting, this treatment should be carried out in a hospital.
Effective pharmacological treatment of obesity is largely confined to the
amphetamines. These agents suppress appetite and, when used in

conjunction with diet in a carefully planned treatment program, they may
have limited usefulness. This usefulness is seriously limited, however, by the

fact that the initial dose loses its effectiveness within a few weeks.
Effectiveness can be restored by an increase in dose—a course that has been
so frequently pursued by unscrupulous “diet doctors” and unsupervised

dieters as to cast serious doubt on whether these drugs have any place in the
treatment of obesity. In the face of today’s widespread drug abuse, the mild
and transient value of amphetamines in the treatment of obesity is probably
outweighed by the danger posed by their abuse. This seems to be the view of
the Bureau of Narcotics and Dangerous Drugs which is now taking away from
physicians the option of prescribing amphetamines for obesity.
Thyroid or thyroid analogues are indicated for the occasional obese

person with hypothyroidism, and probably not otherwise. Bulk producers
may have limited value in eliminating the constipation that follows a marked
decrease in food intake, but their effectiveness in weight reduction is
doubtful. Four controlled studies of chorionic gonadotropin have found it to

be ineffective in the recommended dosage.
Increased physical activity is frequently recommended as a part of

weight-reduction regimens, but its usefulness has probably been
underestimated even by many of its proponents. Since caloric expenditure in
most forms of physical activity is directly proportional to body weight, obese
persons expend more calories with the same amount of activity than do those
of normal weight. Furthermore, as mentioned earlier, increased physical
activity may actually cause a decrease in the food intake of sedentary persons.
This combination of increased caloric expenditure and (probably) decreased

food intake makes an increase in physical activity a highly desirable feature of
any weight-reduction program.
Treatment of obesity has generally followed a traditional medical model
in which an authoritarian physician prescribes a diet and appetite-
suppressing medication. The patient loses weight, if at all, largely to please
the doctor and to meet his expectations. When the relationship is terminated
or attenuated, the patient discontinues the diet and regains weight.
Until recently a surgical treatment for obesity would have seemed
highly improbable. Within the past decade, however, a number of surgeons
have attempted to treat obesity by decreasing food absorption via an
intestinal bypass that short-circuits most of the absorptive surface of the
intestine. Early results were discouraging. Although the first jejunocolic
shunts produced large amounts of weight loss, there was a high incidence of
sometimes lethal complications; the reestablishment of intestinal continuity
was followed by rapid weight gain. More recently, experience with a
jejunoileal shunt has been more promising. Complications have been fewer
and less severe. Furthermore, the discovery of a critical length of absorptive
surface that will maintain body weight at approximately normal levels has
made a second operation, to restore intestinal continuity, unnecessary.
Despite these advances, a jejunoileal shunt is fraught with many dangers and
should still be considered an investigative procedure. Until further

information is available, it seems wisest to limit it to carefully selected
patients with massive obesity that has proved uncontrollable by other
methods.
Group therapy extends the number of obese patients the physician can
treat and probably also increases the effectiveness of treatment. One
convincing study showed that patients treated in groups lost more weight
than those treated individually on each of three regimens: anorexigenic

agents, placebo capsules, and no medication. Evidence for the greater
effectiveness of group over individual therapy for obesity is sufficient to
encourage the family physician to attempt this modality, and the psychiatrist
can provide valuable consultative help in encouraging such an undertaking.
Group methods are being applied by two different kinds of nonmedical
groups with promising results. Each may provide useful adjuncts to medical
treatment. TOPS (Take Off Pounds Sensibly), a self-help group with a
membership of over 350,000, has over 15,000 chapters in all parts of the
country and welcomes collaboration with physicians. The TOPS program
suffers from a high rate of drop-outs but those who remain may lose
encouraging amounts of weight. Membership is almost exclusively female,
and predominantly middle-aged and middle-class; such persons would seem
to be good candidates for the program. Weight Watchers, a commercial

organization, has been less carefully studied than TOPS. But the size of its
membership—over two million—must provide a measure of satisfaction with

its results. Both organizations provide powerful vehicles for introducing safe
new measures for the control of obesity.
Specialized Psychotherapeutic Techniques
Information about reducing diets is so widely available that only those

who have already failed to lose weight on their own come to the doctor’s
office. And only the medical-treatment failures reach the psychiatrist. This
process of selection makes it easy to understand why there is no evidence
that psychodynamic psychotherapy is any more effective than other, less

expensive, aids to weight reduction. Less understandable is the widespread
belief in the efficacy of such psychotherapy.
Another unsupported belief is that there is value in uncovering the
unconscious causes of overeating so that the patient no longer resorts to this
form of response to conflict (according to the psychodynamic model

proposed for the resolution of neurotic symptoms). Obese patients may
produce interesting fantasies and memories in response to the therapist’s

interests, but, with one exception discussed below, such production is rarely
useful in producing favorable changes in behavior. Many obese persons seem
particularly vulnerable to the overdependency upon the therapist and
inordinate regression which can occur during the uncovering
psychotherapies. Psychodynamic psychotherapy probably cannot modify the

symptom choice of persons who overeat in response to stress. Years after
successful psychotherapy and successful weight reduction, persons who
overeat under stress continue to do so.
Despite these limitations, psychodynamic psychotherapy has a place in
the management of obesity, and an important place in the treatment of some
carefully selected obese persons. Furthermore, obese persons may seek
psychotherapy for other reasons than their obesity; helping them to cope
with their obesity may help them resolve their other problems. We have
noted that many obese persons overeat under stress. When psychotherapy
can help them to live less stressful and more gratifying lives, they are less apt
to overeat. They may reduce and sometimes stay reduced. These benefits are
not less significant for being nonspecific results of treatment.
Two conditions may constitute specific indications for psychodynamic
psychotherapy: disturbances in body image and the binge-eating syndrome.
Both have been successfully treated, with enduring weight losses. Neither
condition has been influenced by other forms of treatment including,

significantly, weight reduction. Psychotherapy of patients with these
conditions frequently requires years to ensure lasting results. The process
may be facilitated by modifications in traditional technique designed to

minimize intellectualization and regression, to cope with the “conceptual
confusion” described earlier, and to increase the patient’s often seriously

inadequate sense of personal effectiveness. Bruch has provided excellent
descriptions of such measures in her extensive writings.
Behavior modification has recently been applied to the control of

obesity, and it has already proven a major advance in treatment. Within four
years of its introduction in 1967, every one of seven controlled studies
demonstrated that behavior modification was more effective than a wide
variety of alternative treatments. It is particularly important for psychiatrists

to know of these developments, for they have lagged in their appreciation of
the potential of behavior modification. The discipline has been developed
largely by psychologists, educators, and social workers. The extent to which
the medical profession has defaulted is nowhere better illustrated than in
behavioral therapy of the “medical” problem of obesity. Physicians
participated in only one of the first nine applications of behavior modification

to obesity.
Stuart has recently published an extensive description of the application
of behavior modification to the control of obesity. A brief outline of a typical

program consists of the following four elements:
1. Description of the behavior to be controlled. Patients are asked to

keep daily records of the amount, time, and circumstances of their eating. The
immediate results of this time-consuming and inconvenient procedure
frequently are grumbling and complaints. But most patients acknowledge,
often reluctantly, that keeping these records proves very helpful, particularly
in increasing their awareness of how much they eat, the speed with which
they eat, and the large variety of environmental and psychological situations
associated with eating.
2. Modification and control of the discriminative stimuli governing
eating. Most patients report that their eating takes place in a wide variety of
places and at many different times during the day. It has been postulated that
these times and places become so-called discriminative stimuli for eating. In
an effort to decrease the potency of the discriminative stimuli, patients are
encouraged to confine eating, including snacking, to one place. In order not to

disrupt domestic routines of the housewives, who form such a large part of
the patients so far treated in these programs, the kitchen is usually selected as
the site for eating. Further efforts to control discriminative stimuli include
using distinctive table settings, perhaps an unusually colored place mat and
napkin. In addition, patients are encouraged to make eating a pure
experience, unaccompanied by other activities such as reading, watching
television, or arguing with their families.
3. Development of techniques to control the act of eating. Specific
techniques are utilized to help patients decrease the speed of their eating, to
become aware of all the components of the eating process, and to gain control
over these components. Exercises include counting each mouthful of food
eaten during a meal, placing utensils on the plate after every third mouthful
until that mouthful is chewed and swallowed, and introducing a two-minute
interruption of the meal.
4. Prompt reinforcement of behaviors that delay or control eating. A
reinforcement schedule, using a point system, is particularly helpful in the
control of eating behavior. Exercise of the suggested control procedures

during a meal earns the patient a certain number of points. By this means,
rapid reinforcement of the behavior is achieved. The points can then be
converted into various other reinforcers, such as money or gifts from the
spouse.
Conclusion
Obesity, a condition characterized by excessive accumulations of fat, is
profitably viewed as a-result of a disturbance in the regulation of body

weight. This disturbed regulation can result from several different kinds of
causes: genetic and developmental, social and emotional, physical (inactivity)
and neural (impaired brain function). The relative contributions of these
different influences probably varies among different obese persons.
We have strong evidence that obesity adversely affects morbidity and
mortality, particularly in this country and probably because of the high
saturated fatty acid content of the diet by means of which most Americans
become obese. Obesity is also closely associated with many physical
disabilities. The increased morbidity, mortality, and physical disability are all
reversed by successful weight reduction. Because of these evident health
benefits, and for cosmetic reasons, and because weight reduction should be
easy, large numbers of obese persons are always trying to diet. For the most
part they are unsuccessful. The poor results of weight-reduction efforts are
due not to failure to implement any therapy of known effectiveness but to the
fact that no simple or generally effective treatment exists. Obesity is a chronic
condition, resistant to treatment, and prone to relapse.
New therapies, developed within the past decade, have achieved
somewhat better results than the older ones. Most promising among these is
behavior modification, which has proved more effective than a number of

alternative measures. Intestinal by-pass surgery may, for the first time, offer
some hope to massively obese persons who are willing to accept its risks. Lay
groups may provide a useful vehicle for the introduction of new treatments as
they are developed. But the main hope for control of obesity lies in a better
understanding of the factors that regulate body weight. Fortunately research
into this problem is proving increasingly fruitful.
Bibliography
Abraham, S., G. Collins, and M. Nordsieck. “Relationship of Childhood Weight Status to Morbidity
in Adults,” HSM A Health Reports, 86 (1971), 273-284.
Abraham, S. and M. Nordsieck. “Relationship of Excess Weight in Children and Adults,” Publ.
Health Rep., 75 (1960), 263-273.
Anand, B. K. and R. V. Pillai. “Activity of Single Neurons in the Hypothalamic Feeding Centers:
Effect of Gastric Distention,” J. Physiol. (Lond.) 192 (1967), 63-77.
Brobeck, J. “Neural Control of Hunger, Appetite and Satiety,” Yale J. Biol. Med., 29 (1957). 565-574.
Brown, K. A. and R. Melzack. “Effects of Glucose on Multiunit Activity in the Hypothalamus,” Exp.
Neurol., 24 (1969), 363-373.
Brozek, J., ed. “Body Composition” in Annals of the New York Academy of Sciences, Vol. 110, entire
issue. New York: The Academy, 1963.
Bruch, H. “Conceptual Confusion in Eating Disorders,” J. Nerv. Ment. Dis., 133 (1961), 46-54.
----. “The Practical and Psychological Aspects of Weight Change” and “Evaluation of a
Psychotherapeutic Concept,” in H. Bruch, Eating Disorders: Obesity and Anorexia
Nervosa, and the Person Within, pp. 309-333 and 334-376. New York: Basic Books,
1973.
Burwell, S. “Extreme Obesity Associated with Alveolar Hypoventilation—a Pickwickian

Syndrome,” Am. J. Med., 21 (1956), 811-818.
Chiang, B. N., L. V. Perlman, M. Fulton et al. “Predisposing Factors in Sudden Cardiac Death in
Tecumseh, Michigan: A Prospective Study,” Circulation, 41 (1970), 31-37.
Chirico, A. M. and A. J. Stunkard. “Physical Activity and Human Obesity,” N. Engl. J. Med., 263
(1960), 935-946.
Cohn, C. and D. Joseph. “Influence of Body Weight and Body Fat on Appetite of ‘Normal’ Lean and
Obese Rats,” Yale J. Biol. Med., 34 (1962), 598-607.
Davenport, C. B. Body Build and Its Inheritance, Publication no. 329. Washington, D.C.: Carnegie
Institute, 1923.
Dwyer, J. T., J. J. Feldman, and J. Mayer. “The Social Psychology of Dieting,” J. Health Soc. Behav., 11
(1970), 269-287.
Garcia, J., D. J. Kimeldorf, and E. L. Hunt. “Conditioned Aversion to Saccharine Resulting from
Exposure to Gamma Radiation,” Science, 122 (1955), 157-158.
----. “The Use of Ionizing Radiation as a Motivating Stimulus,” Psychol. Rev., 68 (1961), 383-395.
Glucksman, M. L. and J. Hirsch. “The Response of Obese Patients to Weight Reduction: I. A Clinical
Evaluation of Behavior,” Psychosom. Med., 30 (1968), 1-11.
Glucksman, M. L., J. Hirsch, R. S. McCully et al. “The Response of Obese Patients to Weight
Reduction: II. A Quantitative Evaluation of Behavior,” Psychosom. Med., 30 (1968),
359-374.
Goldblatt, P. B., M. E. Moore, and A. J. Stunkard. “Social Factors in Obesity,” JAMA, 192 (1965),
1039-1044.
Hirsch, J. and J. L. Knittle. “Cellularity of Obese and Nonobese Human Adipose Tissue,” Fed. Proc.,
29 (1971), 1516-1521.
Hoebel, B. “Neural Control of Food Intake,” Annu. Rev. Physiol, 33 (1971), 533-568.
Jordan, H. A. “Voluntary Intragastric Feeding: Oral and Gastric Contributions to Food Intake and
Hunger in Man,” J. Comp. Physiol. Psychol., 68 (1969), 498-506.
Kannel, W. B., G. Pearson, and P. M. McNamara. “Obesity as a Force of Morbidity and Mortality in
Adolescence,” in F. P. Heald, ed., Nutrition and Growth, pp. 51—New York:
Kennedy, G. C. “The Role of Depot Fat in the Hypothalamic Control of Food Intake in the Rat,”
Proc. R. Soc. Lond. (Biol.), 140 (1953), 578-592.
Keys, A. “Coronary Heart Disease in Seven Countries,” Circulation, Vol. 41, no. 4 and Vol. 42
Supplements, April (1970).
Keys, A., J. Brozek, A. Henschel et al. The Biology of Human Starvation, 2 vols. Minneapolis:
University of Minnesota Press, 1950.
Knittle, J. L. and J. Hirsch. “Effect of Early Nutrition on the Development of the Rat Epididymal Fat
Pads: Cellularity and Metabolism,” J. Clin. Invest., 47 (1968), 2091-2098.
LeMagnen, J. “Advances in Studies on the Physiological Control and Regulation of Food Intake,”
Prog. Physiol. Psychol., 4 (1971), 203-261.
London, A. M. and E. D. Schreiber. “A Controlled Study of the Effects of Group Discussions and an
Anorexiant in Outpatient Treatment of Obesity with Attention to the Psychological
Aspects of Dieting,” Ann. Intern. Med,., 65 (1966), 80-92.
MacCuish, A. C., J. F. Munro, and L. J. P. Duncan. “Follow-up Study of Refractory Obesity Treated by
Fasting,” Br. Med. J., 1 (1968), 91-92.
Marks, H. H. “Influence of Obesity on Morbidity and Mortality,” Bull. N.Y. Acad. Med., 36 (1960),
296-312.
Mayer, J. “Correlation between Metabolism and Feeding Behavior and Multiple Etiology of
Obesity,” Bull. N.Y. Acad. Med., 22 (1957), 744-761.
----. “Genetic Factors in Obesity,” Ann. N.Y. Acad. Sci., 131 (1965), 412-421.
----. “Some Aspects of the Problem of Regulation of Food Intake and Obesity,” N. Engl. J. Med., 274
(1966), 610-616, 662-673, 722-731.
----. Overweight: Causes, Cost, and Control, pp. 1-218. Englewood Cliffs, N.J.: Prentice-Hall, 1968.
Mayer, J. and D. W. Thomas. “Regulation of Food Intake and Obesity,” Science, 156 (1967). 328-
337.
Mellinkoff, S. M., M. Frankland, D. Boyle et al. “Relationship between Serum Amino Acid
Concentration and Fluctuations in Appetite,” J. Appl. Physiol., 8 (1956), 535-538.
Metropolitan Life Insurance Company. “New Weight Standards for Men and Women,” Statis. Bull.,
40 (1959), 1-4.
Miller, N. E., C. J. Bailey, and J. A. F. Stevenson. “Decreased Hunger and Increased Food Intake in
Hypothalamic Obese Rats,” Science, 112 (1950), 256-259.
Moore, M. E., A. Stunkard, and L. Srole. “Obesity, Social Class and Mental Illness,” JAMA, 181
(1962), 962-966.
National Center for Health Statistics. Weight by Height and Age of Adults-United States 1960-63.
Series 11, no. 14. Washington: Department of Health, Education, and Welfare, 1966.
Payne, J. H. and L. T. DeWind. “Surgical Treatment of Obesity,” Am. J. Surg., 118 (1967), 141-147.
Robinson, B. W. and M. Mishkin. “Alimentary Responses Evoked from Forebrain Structures in

Macaca Mulatta,” Science, 136 (1962), 260-263.
Rozin, P. “Thiamine Specific Hunger,” in W. Heidel, ed., Handbook of Physiology, sect. 6. Physiology
of the Alimentary Canal, pp. 411-431. Washington: American Physiological Society,
1967.
Russek, M. “Hepatic Receptors and the Neurophysiological Mechanisms Controlling Feeding

Behavior,” Neurosci. Res., 4 (1970), 213-282.
Salans, L. B., J. L. Knittle, and J. Hirsch. “The Role of Adipose Cell Size and Adipose Tissue Insulin
Sensitivity in the Carbohydrate Intolerance of Human Obesity,” J. Clin. Invest., 47
(1968), 153-165.
Schachter, S. “Some Extraordinary Facts about Obese Humans,” Am. Psychol., 26 (1968), 129-144.
Seltzer, C. C. and J. Mayer. “Body Build and Obesity—Who Are the Obese?” JAMA, 189 (1964), 677-
684.
----. “A Simple Criterion of Obesity,” Postgrad. Med., 38 (1965), 101-107.
Simborg, E. W. “The Status of Risk Factors and Coronary Heart Disease,” J. Chron. Dis., 22 (1970),
515-552.
Sims, E. A. H. and E. S. Horton. “Endocrine and Metabolic Adaptation to Obesity and Starvation,”
Am. J. Clin. Nutr., 21 (1968), 1455-1470.
Smith, G. P. and A. N. Epstein. “Increased Feeding in Response to Decreased Glucose Utilization in

the Rat and Monkey,” Am. J. Physiol., 217 (1969), 1083-1087.
Stellar, E. “The Physiology of Motivation,” Psychol. Rev., 61 (1954), 5-22.
Stuart, R. B. and B. Davis. Slim Chance in a Fat World: Behavioral Control of Obesity, pp. 1-240.
Champaign, Ill.: Research Press, 1971.
Stunkard, A. J. “Eating Patterns and Obesity,” Psychiatr. Q., 33 (1959), 284-295.
----. “New Therapies for the Eating Disorders: Behavior Modification of Obesity and Anorexia
Nervosa,” Arch. Gen. Psychiatry, 26 (1972), 391-398.
Stunkard, A. J. and V. Burt. “Obesity and the Body Image: II. Age at Onset of Disturbances in the
Body Image,” Am. J. Psychiatry, 123 (1967), 1443-1447.
Stunkard, A. J., E. d’Acquili, S. Fox et al. “The Influence of Social Class on Obesity and Thinness in
Children,” JAMA, 221 (1972), 579-584.
Stunkard, A. J. and S. Fox. “The Relationship of Gastric Motility and Hunger,” Psychosom. Med., 33
(1971), 123-134.
Stunkard, A. J., H. Levine, and S. Fox. “The Management of Obesity: Patient Self-help and Medical
Treatment,” Arch. Intern. Med., 125 (1970), 1067-1072.
Stunkard, A. J. and M. McLaren-Hume. “The Results of Treatment for Obesity: A Review of the
Literature and Report of a Series,” Arch. Intern. Med., 103 (1959), 79-85.
Stunkard, A. J. and M. Mendelson. “Obesity and the Body Image: I. Characteristics of Disturbance
in the Body Image of Some Obese Persons,” Am. J. Psychiatry, 123 (1965), 1296-
1300.
Stunkard, A. J. and A. J. Rush. “Dieting and Depression Re-examined: A Critical Review of Reports
of Untoward Responses to Weight Reduction for Obesity,” Ann. Int. Med., 81 (1974)
526-533.
Withers, R. F. L. “Problems in the Genetics of Human Obesity,” Eugen. Rev., 56 (1964), 81-90.
Chapter 32
Anorexia Nervosa
Hilde Bruch
“Anorexia nervosa” is a misleading name for the condition to which it is

applied. The severe weight loss and emaciation in a typical case are not due to
a true loss of appetite; on the contrary, these patients are frantically
preoccupied with food and eating. Their refusal to eat stands in the service of
a relentless pursuit of thinness which appears to be the driving motive.
Actually, this preoccupation with the body and its size is a late step in an
individual’s struggle to establish a sense of control and identity. Concern with
control and size are the key issues in the classical anorexia nervosa
syndrome, to which I shall refer here as “genuine,” or “primary anorexia

nervosa.”
There are other cases of psychological emaciation where the symbolic
meaning of the eating function itself is interpreted in a distorted way, at times
associated with a true loss of appetite. The weight loss of such patients may
reach the same order of magnitude as in the genuine syndrome, but they are
distinctly different in their behavior and psychological concerns. After the
condition has existed for any length of time, they look deceptively like true
anorexia nervosa, and the different clinical pictures have been continuously
confused. Such patients exhibit an atypical picture of anorexia nervosa. It is
important to make the distinction because the therapeutic needs differ,
according to the underlying problems.
History of Concept
Anorexia nervosa became a modern clinical entity with the reports by
Gull in England, and Lasegue in France, just 100 years ago, and the picture has
remained alive in medical thinking. Occasional references to a condition of
self-inflicted starvation have been discovered in the older literature. Richard

Morton is commonly credited with the earliest medical report, in 1689, of
what he called a “Nervous Consumption.” His crisp description, “a skeleton
only clad with skin,” immediately evokes the most dramatic aspect of the
condition. The medical literature of the eighteenth and nineteenth centuries

contains occasional references to self-inflicted emaciation which have been
mentioned in several recent monographs.
In spite of the rarity of anorexia nervosa and its short history, there
exists an amazingly large literature. I shall refer only to a few authors who
have contributed to the understanding of this enigmatic condition. Since its
discovery a certain atmosphere of controversy attached itself to the
discussion. Lasegue considered some hysterical disturbance in the digestive
tract to be the starting symptom, and named the condition accordingly,

anorexie hysterique. Gull attributed the want of appetite to “a morbid mental
state—I believe, therefore, that its origin is central and not peripheral.” He
described as the outstanding symptom emaciation associated with
amenorrhea, constipation, loss of appetite, slow pulse and respiration, and

absence of somatic pathology. He commented on the restless activity: “It is
curious to note the persistent wish to be on the move, though the emaciation
was so great.”
Considerable contradiction and confusion has been expressed in the

literature during these past 100 years. Some of this may well be related to the
tendency to explain all cases through the same mechanism, and the
unwillingness to concede that the same surface picture, namely emaciation

due to restricted food intake, may be a manifestation of different underlying
factors. The whole issue became even more confused when Simmonds, a
pathologist, reported destructive lesions in the pituitary gland of an
emaciated woman who had died following pregnancy and delivery. Until then,
the assumption that anorexia nervosa was caused by psychological factors
had been unchallenged. Following Simmonds’ publication, in 1914, the whole
approach changed and every case of malnutrition was explained as caused by
some endocrine deficiency, resulting in increasing vagueness in what was
considered to deserve the diagnosis, anorexia nervosa.
It was only during the 1930s that persistent efforts were made to
distinguish a psychological anorexia nervosa syndrome from the so-called

Simmonds disease. Once it had been reestablished that anorexia nervosa was
a disease of psychological origin, publications with this orientation appeared
in a steady stream, without diminishing the confusion. It was assumed that
patients with such a weight loss were “fundamentally alike clinically” and that
they suffered from “concealed conflicts.” The ambition was to explain the
whole complex picture through one specific psychodynamic formulation; this
resulted in imposing stereotyped explanations on a condition that defies such

a simplistic approach.
Some of the “key” publications, illustrating the evolution of the concept,
were collected in a monograph by Kaufman and Heiman; though published in

1964, the most recent paper reviewed was originally published in 1943. I
shall focus here mainly on publications of the 1960s and 1970s. Two main
trends can be recognized: (1) the older approach of dealing with the chief
symptom, i.e., the symbolic significance of the “oral” component; and (2) the
approach concerned with the personality of the patient, disturbances in ego

functions, and interpersonal relations.
Symptomatic Approach
Psychoanalytic studies with focus on the disturbed eating often included
psychogenic vomiting and other forms of neurotic eating disturbances.

Basically, they all rest on Freud’s assumption that impairment in the
nutritional instinct was related to the organism’s failure to master the sexual
excitation. This one-sided emphasis on the “oral” component, with neglect of

other important aspects, has contributed to the confusion with which we are
confronted today. Classical psychoanalysis viewed the whole problem as
symbolically expressing an internalized sexual conflict. The high point of this
approach is a paper published in 1940, by Waller, Kaufman, and Deutsch, that

“psychological factors have a certain specific constellation centering around
the symbolization of pregnancy fantasies involving the gastrointestinal tract.”
The concept that anorexia nervosa was an expression of repudiation of
sexuality, specifically of “oral impregnation” fantasies, has since dominated

clinical thinking. Even today “oral impregnation” is the one psychodynamic
issue most persistently looked for.
Modern psychoanalytic thinking has turned away from this merely

symbolic, and often rather analogistic etiological approach, and focusses more
on the nature of the parent-child relationship from its beginning. Nemiah

considered the excessive dependency, unquestioning obedience, and wilted
kind of passivity in anorexia nervosa to be the expected outcome of a
mother’s overprotective attitude. Meyer and Weinroth pointed to factors that
served to precondition the eating experience in the future anorexic, and felt
that the onset at the time of puberty had given rise to an erroneous evaluation
of the oedipal conflicts in the genesis of anorexia nervosa, and that the
problem needed to be connected with the effects of earlier preoedipal
experiences.
With this increasing emphasis on early development, and on behavior
and attitudes not directly related to food, recent psychoanalytic studies are
approaching the views that have been expressed by authors quoted in the
next section since the early 1930s. There are, of course, still reports in the old
orientation. Thomae’s monograph, published in 1961, is written in the
classical psychoanalytic tradition and gives the impression of belonging to a

bygone era of medical and psychoanalytic thinking, claiming that “obviously it
is a drive disturbance—and that oral ambivalence underlies the whole
symptomatology.”
Personality Problems
A few analysts recognized quite early that the focus on the eating
function failed to deal with the underlying disturbances in the total
personality. Meng compared the regression in anorexia nervosa to what is

observed in psychosis. He focused on the deformation in the ego structure,
that in neurosis the ego is essentially normal though the symptoms are an
expression of inner conflicts. In psychosis, however, the ego is defective in its
primary structure, even though external factors play also a role. Eissler
referred to Meng’s concept of “deformation of the ego” as applicable to his

own observations on a patient who complained that “her mind was in the
mind of other people.” Eissler felt that this weak and stunted ego had evolved
out of the past interactional patterns between mother and child, and that this
attitude was different from the dependency on the mother so frequently

encountered in neurotics. Nicolle differentiated between true anorexia
nervosa and noneating related to hysteria or other neurotic disorders. She
drew attention to the potentially schizophrenic aspects of true anorexia

nervosa, with shallowness of feelings and cooling off in emotional awareness,
as has also been described in the early diagnosis of schizophrenia.
Probably the most detailed account of the inner experiences of an
anorexic patient was given by Binswanger in his report “Der Fall Ellen West.”
This woman had great artistic abilities, wrote poetry, and kept a diary, before
and after she became sick, and Binswanger reconstructed from this her
psychological development. After graduation from high school she took up
horseback riding and attained great skill, doing it in the same overintense
way with which she approached every task. In her nineteenth year, she
noticed the beginning of a new anxiety, namely the fear of becoming fat. She
had developed an enormous appetite and grew so heavy that her friends
would tease her. Immediately thereafter she began to castigate herself,
denying herself sweets and other fattening foods, dropping supper altogether,
and went on long exhausting walks. Though she looked miserable, she was
only worried about getting too fat and continued her endless walks. Parallel to
this fear of becoming fat, her desire for food increased. The persisting conflict
between the dread of fatness and the craving for food overshadowed her
whole life. After many years of illness she wrote: “It is this external tension
between wanting to be thin and not to give up eating that is so exhausting. In
all other aspects I am reasonable, but I know on this point I am crazy. I am
really ruining myself in this endless struggle against my nature. Fate wanted
me to be heavy and strong, but I want to be thin and delicate.”
Recent Contributions
There has been a definite change in the whole approach since about
1960, with convergence of opinion that a true anorexia nervosa syndrome
needs to be differentiated from unspecific types. Reports in the past were
usually based on a few patients only and authors would draw generalized
conclusions from this limited experience. King reported in 1963 from

Australia on twenty-one patients, twelve of whom exhibited great similarities,
a specific syndrome of primary anorexia nervosa which needed to be
differentiated from abstinence from food as a secondary symptom. In 1969
Dally reviewed the course of illness since 1940 of 140 female patients in
whom the diagnosis of anorexia nervosa had been made at a teaching hospital
in England. He reevaluated these patients and subdivided them into

“obsessional” and “hysterical” groups, with seventy-four and thirty patients,
respectively. The refusal to eat, because of fear of possible weight gain or loss
of self-control, was the outstanding feature in the obsessional group. In

addition, there was a group with mixed etiology, thirty-six patients
representing a secondary form of the illness, with loss of appetite, complaint
of abdominal fullness, decreased activity because of lack of energy. Ushakov
reporting on sixty-five patients from Moscow, considers anorexia nervosa a
separate nosological entity, different from unspecific cases of food refusal in
various psychiatric conditions. Leading in the psychopathology is the desire

to be thin which he conceives of as an expression of a supervalent thought.
The manifest picture is usually preceded by behavior changes over a year or

two; after that the need to be thin, the fear of gaining weight, overshadows all
other symptoms. Selvini considers the “combination of conscious and

stubborn determination to emaciate herself, despite the presence of an
intense interest in food” as characteristic for anorexic girls, and that this
constellation distinguishes true anorexia from other forms of psychological
malnutrition. Reports by Russell and Crisp in England, and Theander in
Sweden, give similar definitions of anorexia nervosa, as “a morbid fear of
being fat,” or “a state of weight phobia,” combined with “anorexic behavior.” I
have quoted only a few of the authors who in recent years reexamined the
concept of anorexia nervosa. Independently they arrived at comparable
formulations, with agreement that there is a genuine syndrome, characterized
by “fear of fatness,” which is related to preexisting underlying disturbances.
They are also in good agreement with my own formulation of the essential
aspects of anorexia nervosa.
Primary Anorexia Nervosa
Anorexia nervosa has always been considered a rare disease; there is a
general impression that it is on the increase. In my own experience, based on
seventy-five cases (sixty-five females, ten males) seen between 1942 and
1972, the increase is due mainly to more cases of primary anorexia nervosa.
Among the sixty-five female patients, fifteen were rated as showing the
atypical picture, and fifty the primary syndrome. More than half of the
atypical patients were seen before 1960, whereas the great majority (86
percent) of the primary group developed the syndrome after 1960.
Somatically, there is little difference between the two groups; in both there is
a significant weight loss without organic explanation. The average weight loss
in the primary group was 45 lbs (36.5 percent), and 48 lbs (38 percent) in the
atypical group. The age of onset in the primary group was on the average 15.9
(10-26) years, and 20.3 (13-28) years in the atypical group. There is some
overlap, with the youngest in the atypical group only thirteen years old, and a
few in the primary group over twenty years. In the primary group six girls
were still in prepuberty. The age of menarche was approximately the same in
both groups, 12.6 and 12.4 respectively, with a range from 10 to 16 years.
Amenorrhea was a consistent symptom in the primary group, but occurred
less regularly in the atypical group. The decisive differences are in the
psychological constellation.
The leading dynamic issue in the genuine syndrome is fear of fatness;

the angry refusal to eat stands in the service of maintaining an extreme
degree of thinness. For a dynamic understanding, which is necessary for
pertinent treatment, it is essential to isolate in each individual case the focal

point of the functional disturbances, to recognize the crucial problems with
which a patient struggles, and to identify his tools for dealing with them. Such
an evaluation implies a clear-cut distinction between the dynamic issues of

the developmental impasse which has resulted in anorexia nervosa, and the
secondary, even tertiary problems, symptoms and complications that develop
in its wake. Most patients come to psychiatric attention only after they have
been sick for a considerable period of time, and after various futile treatment
efforts. It is necessary to reconstruct the behavior and problems of a patient,
and the patterns of family interaction and concern, before the illness became
manifest. In genuine or primary anorexia nervosa the main issue is a struggle
for control, for a sense of personal identity, competence, and effectiveness.
Many of these youngsters had tried for years to make themselves over, to be
“perfect” in the eyes of others. Concern with thinness and food refusal are late
steps in this maldevelopment. The underlying personality difficulties had
been camouflaged during childhood by their over-compliant behavior.
The true syndrome is amazingly uniform. Three areas of disordered
psychological functioning can be recognized: (1) a disturbance in body image
and body concept of delusional proportions; (2) inaccurate and confused

perception and cognitive interpretation of stimuli arising in the body, with
failure of recognition of signs of nutritional needs as the most pronounced
deficiency; and (3) a paralyzing sense of ineffectiveness which pervades all

thinking and activities.
Body-Image Disturbances
Of pathognomic significance for true anorexia nervosa is the vigor and

stubborness with which the often gruesome emaciation is defended as
normal and right, as not too thin, and as the only possible security against the
dreaded fear of being fat. Cachexia may occur to the same pitiful degree in
patients with the atypical syndrome, but they will complain about the weight
loss. The true anorexic is identified with her skeletonlike appearance, actively
maintains it, and does not “see” the abnormality.
A woman twenty years old, progressing well in therapy, admitted, “I

really cannot see how thin I am. I look into the mirror and still cannot see it; I
know I am thin because when I feel myself I notice that there is nothing but
bones.” Another girl, age nineteen, also doing well in therapy, showed her
physician two photographs taken on the beach, one when she was fifteen and
of normal weight, and the other when seventeen and quite cachectic,
admitting that she had trouble seeing a difference though she knew there was
one. When she looks at herself in a mirror she sometimes can see that she is
too thin, “but I can’t hold onto it.” She may remember it for an hour and then
begins to feel again that she is much larger; there was an inner mechanism
that kept on “inflating” her self-image. Only through looking in the mirror
could she “let the air out again.”
The misperception of their size is preceded by an exaggerated
interpretation of any curve and increasing weight as excessive and too fat.
One later anorexic girl described this process. She had experienced any bodily
changes during puberty with intense discomfort, and began to deny that she
had breasts or a rounded buttocks, and maintained this denial over the years,
long before her anorexic symptoms began. Like many others she developed a
negative phantom, not seeing and accepting her figure as it matured.
A realistic body image is a precondition for recovery in anorexia
nervosa. Many patients will gain weight for a variety of reasons but no real or
lasting cure is achieved without correction of the body image misperception.
The resolution of this denial was studied through self-image confrontation in
one case by Gottheil and co-workers. After repeated self confrontation this
patient began to see how thin she was, more strikingly on video tape than by
looking into the mirror. Gradually a change in her body image occurred so
that thinness became ugly rather than comforting to her. The same change
occurs in patients during psychotherapy, without such direct confrontation.
Another disturbance is the failure of experiencing the body as being
their own. Not uncommonly, anorexics conceive of the whole illness as
something that “happened to me,” not as themselves having stopped eating.
As they come to recognize this they will make comments like, “I realize now I
was hurting my parents by not eating; the more they worried about me the
more I was hurting them,” without awareness that they themselves
underwent this ordeal of starvation.
A male anorexic who had been sick since age twelve and who had
successfully resisted all treatment efforts, weighing less than 50 lbs at age
eighteen, expressed this even more clearly. Throughout this time he had
struggled and fought against any effort to make him eat. Gradually he
developed a real fear of the scale. “I feel I get evaluated by it and then I am
panicky. If I gain, they are so proud; if I lose, my mother blows her head off. It
is always somebody else’s business.” Talking about his parents he used the
expression, “After all, I am their property.” It was only after considerable
therapeutic progress that he began to conceive of his body and its functions
as his own; only then could he let go of his longstanding symptoms. When he
was transferred to an open ward he expressed his satisfaction as, “I am free, I
own my body—I am not supervised any more by nurses or by mother.” His
attitude towards his weight and what he ate underwent a complete change.
“Now if I lose weight it makes me feel sick, that I am losing something that is
mine.”
Misperception of Bodily Functions
The symptom that arouses most concern, compassion, frustration, and
rage is the anorexic’s refusal to eat. It is this abstinence from food which is
reflected in the name, “anorexia.” However, the underlying disturbance is

more akin to the inability to recognize hunger than to a loss of appetite.
Awareness of hunger and appetite in the ordinary sense seems to be absent,
and a patient’s sullen statement: “I do not need to eat” is probably an accurate
expression of what he feels and experiences most of the time. This deficit in
recognizing signs of nutritional need, and the confusion in hunger awareness,
are part of the essential underlying personality disturbances, which are
closely related to other developmental deficits.
In a study of gastric motility Silverstone and Russell found that anorexic

patients, though their gastric activity was similar to that found in normal
subjects, usually denied sensations of hunger, or feeling anything, though they
could sense the contractions. Coddington and Bruch observed that anorexic
individuals, when measured amounts of food were introduced into the
stomach, were significantly more inaccurate in identifying the amounts than
normal, and also obese subjects. This suggests some abnormality in the
perception and interpretation of enteroceptive stimuli.
Since curtailment of the caloric intake is the outstanding clinical
symptom, there have been unending discussions whether these patients

suffer from a true loss of appetite, stubbornly refuse to eat, repress the
sensation of hunger, or fail to act on its urges. Much more than dietary
restriction is involved. The whole eating pattern, food preferences and tastes,
eating habits and manners, become disorganized, with bizarre and rather
outlandish practices developing as the illness persists.
Characteristic is the paradox of food refusal while frantically

preoccupied with eating. Most develop unusual, even bizarre, highly
individualistic food habits, usually restricting themselves to proteins only.
Invariably they will eat more and more slowly, taking hours to finish a meal,
however small. This dawdling and the continuous preoccupation with food is
commonly observed during starvation. In an experimental study of
semistarvation, carried out during World War II on a group of healthy young
men, they would “toy” with their food and dawdle for almost two hours over a
meal as the starvation progressed, though there was no diminution in the

desire for food which was also the dominant topic of all conversation and
thinking. Much of what has been called “anorexic behavior,” the obsessive
ruminative preoccupation with food, narcissistic self-absorption, infantile

regression, etc., appear identical with what is observed in starvation due to
food shortages, though, of course, the victims will eat whatever they can find,
in contrast to the starving anorexic who lives in the midst of plenty but whose
fear of losing control and other internal inhibitions make him reject food that
is constantly offered, even forced on him. Though without true hunger
awareness the anorexic behaves like a starving organism.
Anorexics will complain of feeling “full” after a few bites of food, or even
a few drops of fluid. One gains the impression that this sense of fullness is a
phantom phenomenon, projection of memories of formerly experienced

sensations. An eighteen-year-old girl, intelligent and articulate, but obsessed
with her size and eating, felt so little differentiated from others that she
would assume the identity of whomever she was with and feel “full” by
watching others eat, “having people eat for me,” without having eaten herself.
She spoke of “keeping my mind eternally occupied with what size I am,
always hoping I will become smaller. If I must eat—that takes so much mental
energy to decide what, how much, and why must I.”
The nutritional disorganization has two phases, absence or denial of
desire for food, and uncontrollable impulses to gorge oneself, usually without
awareness of hunger, and often followed by self-induced vomiting. Patients
identify with the noneating phase, defending it as the realistic expression of
their physiological need. In contrast, they experience the overeating as a
submission to some compulsion to do something they do not want to do, and

they are terrified by the loss of control during such eating binges. They
express it as “I do not dare to eat. If I take just one bite I am afraid that I will
not be able to stop.” In about a quarter of the cases of primary anorexia

nervosa uncontrolled eating binges and vomiting occur as leading symptoms,
but fear of not being able to control their eating seems to be present in all.
In advanced stages of emaciation true loss of appetite may result from

the severe nutritional deficiency, similar to the complete lack of interest in
food in the late stages of starvation during a famine. This indifference to food
must be differentiated from the spirited way with which the anorexic defends
his noneating before the stage of extreme marasmus has been reached.
In their fight against fatness, in an effort to remove unwanted food from
their bodies, many resort to self-induced vomiting and enemas, or the
excessive use of laxatives, and, increasingly often, of diuretics, which may
result in serious disturbances in the electrolyte balance. Although the urgent
need to keep the body weight low is given as the motive, other aspects must
be considered, namely that here too disturbances in the cognitive awareness

of bodily sensations play a role.
Another characteristic manifestation of falsified bodily awareness is
hyperactivity, the denial of fatigue, which impressed the earlier writers but
which has scarcely been mentioned in the recent psychoanalytic literature. It
has often been claimed that the actual amount of exercise may not be large
but only seems remarkable in view of the severe undernutrition. Through
pedometric measurements Stunkard and his co-workers could demonstrate
that anorexia patients were indeed hyperactive, walking an average of 6.8

miles per day, despite their emaciation, while women of normal weight
walked on the average 4.0 miles per day. Patients who continue in school will
spend long hours on their homework, intent on having perfect grades.
Drive for activity continues until the emaciation is far advanced. The
subjective feeling is one of not being tired, of wanting to do things, and this
stands in marked contrast to the lassitude, fatigue, and avoidance of any effort
that is symptomatic for undernutrition in chronic food deprivation, and is
regularly complained of by patients in the atypical group. This paradoxical
sense of alertness must also be considered an expression of conceptual and
perceptual disturbances in body awareness.
One might also consider the failure of sexual functioning and the
absence of sexual feelings as falling within the area of perceptual and
conceptual deficits, though Russell discusses the possibility of primary
gonadal failure contributing to the loss of sexual interest. He observed that

though most of the actions of the anterior pituitary gland are preserved
during the state of starvation, there is a growing body of evidence that the
release of gonadotropin is impaired and does not correct itself spontaneously
after the malnutrition has been corrected.
Other bodily sensations are also not correctly recognized or responded
to, and they appear also deficient in identifying emotional states. One may
consider the limited range with which they describe feelings of anxiety or
other emotional reactions as belonging to this failure in perception or
cognitive interpretation of feeling states. Even severe depressive reactions

may remain masked.
Others will misinterpret their abilities and total functioning. A

seventeen-year-old girl, who had gone on a diet when she learned that her
boyfriend at college was dating other girls, felt for the first time “she was
getting results” when her declining weight aroused concern. She became
convinced that her body had magical qualities. She had started compulsive
walking rituals and would walk whether it was hot or raining, or a
thunderstorm threatened. She would walk for many miles even though she
was increasingly cachectic. “My body could do anything—it could walk
forever and not get tired. I have the will power to walk as far as I want any
time—no matter what the weather is. I felt very powerful on account of my
body. My only weakness was my mind.” She felt the same about her weight:
“This is something I can control. I still don’t know what I look like or what size
I am—but I know my body can take anything.” She was rather contemptuous
of people who expressed concern about her health.
A sixteen-year-old anorexic girl, when at her lowest weight, was afraid
of being “strong.” Her ideal was to be weak and ethereal so that she could
accept everybody’s help without feeling guilty. Her deepest desire was to be
blind; then she would show how noble she was in the face of suffering, and
would be respected by everybody for this nobility. There was no realistic
awareness of what it would be like to be blind, of not being able to see. In
spite of this desire for “weakness” she was extremely active and
perfectionistic, and would not permit herself to go to sleep until she had done
calisthenics to the point of her muscles hurting.
Changes in this distorted self-awareness are necessary milestones on
the road to recovery. To quote from one patient who was doing well, “I took a
walk—not to wear myself out or to prove I could make it’ but just to enjoy the
bright blue sky and the pretty yellow flowers. I seemed to do it without this
‘double track’ thinking.”
Ineffectiveness
The third outstanding feature is a paralyzing sense of ineffectiveness,
which pervades all thinking and activity of anorexic patients. They experience
themselves as acting only in response to demands coming from others, and not
doing anything because they want to. While the two other characteristics are
readily recognized, this deficiency is camouflaged by the enormous
negativism and stubborn defiance of these patients. Its paramount
importance was recognized in the course of extended psychotherapy. Once
defined, this sense of helplessness can be identified readily early in treatment
and be communicated to the patient.
This deep sense of ineffectiveness seems to stand in contrast to the

vigorous behavior and the reports of normal early development which
supposedly had been free of difficulties and problems to an unusual degree.
These girls were described as having been outstandingly good children,
obedient, clean, eager to please, helpful at home, precociously dependable,
and excelling in school work. They were the pride and joy of their parents,
and great things were expected of them. After a childhood of robotlike
obedience, the tasks of adolescence appear insurmountable and reveal them
as deficient in initiative and autonomy. Once this lack has been defined, a
detailed history will reveal many subtle indications earlier in life, though
parents find it difficult to accept that their well-balanced daughter should

have been so troubled and under such strain.
It had always been a puzzle that this serious illness is usually

precipitated by some commonplace event or trivial remark. Most give a fairly
definite time of onset and usually recall the event that had made them feel
“too fat” and not respected. Frequently this occurred when confronted with
new experiences, such as going to camp in the younger group, or entering a
new school or going to college later. In this new situation they feel
embarrassed about being “chubby” and afraid of not being able to make new
friends. An early signal of something wrong with their drastic dieting is that
weight loss does not lead to better social relationships, but to increasing
social withdrawal, often extreme isolation.
Whenever there is a detailed examination of the factors surrounding the
“sudden onset” one will find that the urgent need to lose weight is a cover-up
symptom, expressing an underlying fear of being incompetent, “a nothing,” of

not getting or even deserving respect. In this desperate worry they gain a
sense of accomplishment from manipulating their eating and weight.
Family Transactions
Patterns of disturbed interaction were recognized only through
intensive therapeutic contact with these families. Crisp reviewed the older
literature and found little consistency in the studies which dealt mainly with
the disturbed patterns after onset of the anorexia. There was little agreement
between investigators concerning the nature of the premorbid phenomena

and influences, and the social background. Some authors, Crisp among them,
have been impressed by the high proportion of patients coming from
prosperous and professional homes. Ushakov reports the same from Russia
and speaks of the prosperous and good living conditions and the highly
cultural backgrounds of these adolescents. In my own observation, more than
half of the primary group were of upper-class background, with more than 10
percent belonging to the “super rich.” In the atypical group middle- and
lower-class status was more frequent.
The families are of small size which was more pronounced in the
primary than in the atypical group, but without describable “hard-fact”
characteristics, except that the age of the parents at birth of the anorexic-to-
be was rather high, about thirty years, a fact also commented on by others.
About half of the patients were first-born children, and the position most
frequently observed was that of being the older of two daughters, with a
conspicuous paucity of sons. This too has been observed by others who speak
of the anorexic family as being woman-dominated. The marriages appeared
to be stable, at least in formalistic terms, with only two or three instances of
divorce before or at the time of onset of the illness. Most parents emphasized
the stability, even happiness, of their homes.
Reconstruction of the early development revealed that they had been

well cared-for children to whom many advantages and privileges had been
offered. Yet, on closer contact, it could be recognized that encouragement or
reinforcement of self-expression had been deficient, and thus reliance on
their own inner resources, ideas or autonomous decisions had remained

undeveloped. Pleasing compliance had become their way of life, and they had
functioned with the facade of normalcy, which, however, turned into
indiscriminate negativism when progressive development demanded more

than conforming obedience. No general picture can be given for the
premorbid personalities in the atypical group.
Evidence of disregard of the patient’s needs and emotions could be

readily recognized in joint family sessions. With all the apparent benevolence,
these parents appeared to be impervious to the emotional needs and
reactions of their children. At times there was a shocking discrepancy

between the bland and unobservant attitude of the parents, and the evidence
of the serious physical and emotional illness in the patient.
With widely varying individual features, several common aspects could
be recognized. The parents emphasized the normality of their family life,
sometimes with frantic stress on “happiness,” and they emphasized the
superiority of the now sick child over her siblings. The fathers, despite social
and financial success, which was often considerable, felt in some sense
“second best,” and were enormously preoccupied with outer appearances,
expecting proper behavior and measurable achievement from their children.

The mothers had often been women of achievement, or career women
frustrated in their aspirations, but who had been conscientious in their
concept of motherhood. This description applies probably to many “success-
oriented” upper-middle-class families; these traits are probably more

pronounced in anorexia nervosa, with greater imperviousness to a child’s
authentic need.
In order to visualize how a family, without dramatic signs of discord,

fails to transmit to a child, an adequate sense of self-effectiveness, a simplified
model of personality development was constructed. Behavior, from birth on,

needs to be differentiated into two forms, namely that initiated in the
individual, and that in response to external stimuli. For a normal development
it appears to be essential that there are sufficient appropriate responses to

clues originating in the child, in addition to stimulation from the environment.
If responses to child-initiated clues are continuously inappropriate or
contradictory, a sense of ownership of his own body fails to develop; instead,
such an individual will experience himself as not in control of his body and its
functions, lacking awareness of living his own life. This is the basic psychic
orientation in anorexia nervosa. The gross deficit in initiative and active self-
awareness may not become manifest until puberty makes new demands, and
the impact of new bodily urges provokes a feeling of helplessness, of not
owning his own sensations and his own body.
The early feeding histories which have been reconstructed in great
detail are conspicuous by their blandness. The child never gave any trouble
and ate exactly what was put before him, without fussing about food. Some
mothers would report how they always “anticipated” their child’s needs,
never permitting him to “feel hungry,” that means without opportunity of

developing guideposts for control from within.
Distorting feeding experiences may occur together with distortions in
verbal communication, with direct mislabeling of a child’s feeling states, such

as that he must be hungry (or cold, or tired) regardless of his own sensations.
This mislabeling may also apply to a child’s role in the family, and his feelings
and moods. Thus he comes to mistrust the legitimacy of his own feelings and
experiences; in order to maintain even an unstable equilibrium with the
people on whom he is most dependent, he is obliged to accept these distorted

conceptions about his body, and is thus prevented from developing a clearly
differentiated body scheme and sense of competence.
Sexual Adjustment and Problems
Since puberty is the characteristic time of onset it has been generally

assumed that anorexia nervosa is in some way related to sexual problems.
Crisp observed that the later anorexic girl is heavier at birth than her sisters,
and tends to have an early menarche, and that this premature demand for
sexual adjustment precipitates the illness. In my group, menarche occurred at

a normal age; in two instances of monozygotic twins the later anorexic twin
had been smaller at birth, with menarche at a later age than the healthy twin.
In psychoanalytic teaching the rejection of food has been equated with
the rejection of and disgust with sex, and unconscious fear of impregnation
has been considered the specific conflict situation. This type of sexual anxiety
may play a role in atypical cases of anorexia, but it is rarely encountered in
the primary form. Selvini, too, found impregnation fantasies only rarely; when
they were uncovered they were not related to true sexual fears but rather a
sexual symbol of more primitive experiences.
It is difficult, if not impossible, to evaluate reports about such

unconscious fantasies. When not rigidly negativistic, these patients are
chameleonlike in picking up cues from their therapist. If a therapist is
convinced that feeling “full” after eating is the symbolic expression of an
imagined pregnancy then a patient will reply, sooner or later, that this feels
like having a baby in her stomach. There seems to be a tendency to confront a
patient too early in treatment with specific sexual topics, before they have
developed some sense of identity and self-directed independence. Such

efforts lead to sterile and threatening discussions and account, in my opinion,
for the fact that treatment so often bogs down in a stalemate. One of my
patients married during a remission and, though still amenorrheic, became

pregnant. She experienced the enlargement of her abdomen as something
desirable, as entirely different from the hateful fear of her body being too big
and fat.
My cautionary remarks about “explaining” anorexia nervosa as “caused”
by certain unconscious fantasies do not imply, of course, that the attitude of

the patients toward sex and adulthood is not seriously disturbed. Under the
fragile facade of normality, their whole development has been so distorted
that it would be inconceivable if they functioned normally in this area. The
changes of pubescence, the increase in size, shape, and weight, menstruation

with its bleeding, and new and disturbing sexual sensations, represent a
danger, the threat of losing control. The frantic preoccupation with weight is
an attempt to counteract this fear; rigid dieting is the dimension through

which they try to accomplish control.
Atypical Anorexia Nervosa
Much of the confusion about anorexia nervosa is due to the failure to
differentiate between the genuine syndrome, i.e., the pursuit of thinness, and
other conditions where the eating function is disturbed due to various
symbolic misinterpretations. No general picture can be drawn for this group
except that the loss of weight is incidental to other problems, is often

complained of or valued only secondarily for its coercive effect. Often there is
a desire to stay sick in order to remain in the dependent role, in contrast to
the struggle for an independent identity in the primary group. The
characteristic features of the primary syndrome are absent, namely the

pursuit of thinness, delusional denial of the emaciation, hyperactivity and
striving for perfection, and constant preoccupation with food. In no case of
atypical anorexia nervosa were there episodes of bulemia.
The illness is as serious and treatment problems as difficult as in
primary anorexia nervosa, with poor cooperation, frequent changes of
physician, and impulsive breaking off of treatment. The duration of the illness
appears to be approximately the same, with two patients in each group
having been unsuccessfully in treatment for over ten years, with sixteen years
in a woman with the atypical syndrome as the longest.
Certain subgroups of the atypical cases can be recognized. In eight
patients, neurotic and hysterical symptoms were predominant, and schizoid
features in six; an adolescent depression was observed in a girl of fifteen, with
roots in recurrent traumatic separations during childhood. A few brief
sketches follow to indicate the different flavor of the atypical disorder.
A fourteen-year-old girl felt that her symptoms, i.e., her loss of appetite
and disgust with eating, had some relationship to the birth of a child to a
favorite aunt, an event to which she had reacted with disgust and horror.
More severe symptoms developed when a girl friend was discovered to be
illegitimately pregnant. The thought that her friend had had sexual relations
disgusted her, and she became preoccupied with the idea of sexual
intercourse. She said she hated her parents because they had performed this
act in conceiving her, and she wished she had not been born.
She had many other symptoms, became aphonic, and spoke in a whisper
for over three years. At another time she began to limp and was admitted to
an orthopedic hospital, where there were no organic findings, but she was
discharged on crutches. At another time she complained of severe abdominal

pain and a kidney stone was suspected. What was found was that she had
inserted a pencil into her bladder which was removed through a super-pubic
incision.
Her violent temper and behavior had kept her home in a continuous
state of turmoil and excitement; she refused to eat, had vomiting spells,
remained up all night, and though she had been an excellent student, she had
dropped out of school. After four years of invalidism, she was finally admitted
to a psychiatric service for long-term treatment.
She appeared quite depressed, tense and self-absorbed, with staying
sick her main preoccupation. In her damaged self-image she was an ill,
crippled, and helpless child extorting irritated attention from her parents. The
intrinsic therapeutic difficulty was that throughout her life she had used
illness to maintain her position in the family and thus she “needed to be sick.”
A thirty-two-year-old highly intelligent professional woman had been
nearly continuously in treatment since age sixteen, when she had lost a
considerable amount of weight. Evaluation of her long history revealed as a
major theme of her life the effort to control through weakness. The noneating
was a nearly accidental symptom in a woman with the pervasive hysterical
character structure. She valued her low weight for its coercive effect and had
gradually learned every trick to arouse attention and concern, and to keep her
weight at a dangerously low level.
A nineteen-year-old girl lost 30 lbs. during her first term in college.
When she was fourteen years old her mother had undergone major surgery.
From then on the daughter could not eat, “Unless I could observe the exact
amount mother ate.” As long as she lived at home nobody had noticed this. At
college she lost weight rapidly because “I did not know what mother ate.”
Subsequently many other phobic symptoms became manifest.
Another college student became infatuated with her physician who had
suggested reducing for her when she consulted him about some other
symptom. She received much praise from him for being so cooperative as her
weight dropped from 160 to 110 lbs. When she consulted him again he
reassured her about her weight. She felt he had rejected her, lost her appetite,
and became afraid to eat, and her weight dropped to 85 lbs. Later, in
psychiatric treatment, she repeated the pattern of immediate infatuation,

going to great length to force her attention on her therapist and his family.
She was preoccupied with being “in control,” but not as a step towards
independence; it was an effort to coerce her physician into permitting her

clinging dependent behavior.
A twenty-nine-year-old teacher suffered a severe weight loss after
having witnessed a miscarriage. She was frightened by the amount of blood,

then became obsessed with the smell of blood, first could not eat meat
because it smelled of blood, then all food smelled of it. After losing 20 lbs. she
felt so weak that she took to a wheelchair, and with further loss she
demanded bed care.
In the schizoid group the sense of reality and the misinterpretation of
the whole eating function is more dramatically disturbed, often with
delusional fears of eating, whereas others refuse food for being unworthy.
Characteristically, these patients are often apathetic and indolent, usually
indifferent towards the emaciation; they certainly will not express pride in it.
An eighteen-year-old girl was hospitalized with a severe weight loss and
scruples about sin; she felt paralyzed in doing anything. She had been quite
popular in high school, even had been class president, but she was
continuously preoccupied with the fear of losing her friends. She began to
have peculiar thoughts about food and her digestion; she felt that what she
ate would affect others. Increasingly she became preoccupied with her sins
and fear of punishment. She was quite depressed and suspicious, but when
hospitalized she accepted nourishment, and her weight went up and she
maintained it at around 100 lbs. She suffered another episode of weight loss,
down to 82 lbs., when twenty-five years old, obsessed with delusions about
her digestion and the influence of thoughts on her digestion.
A twenty-one-year-old college student was advised by her professor to

see a psychiatrist, after he had noted changes in her behavior and
peculiarities in her style of writing. Instead she just stayed home, ate less and
less, and finally did not leave her bed. Her mother had died when she was
quite young, and she felt uncomfortable about living with her father. She
complained that he had “not welcomed her properly,” when she came back
from a summer vacation. She looked emaciated and was weak, after having
lost 45 lbs. There was nothing conspicuous in her attitude towards eating and
she gained weight steadily in the hospital, back to the previous level of 125
lbs. She also responded well to psychotherapy and was able to free herself of
her hateful dependence on her father.
These few brief sketches serve to illustrate the great differences in the
precipitating events and in the personality of these patients, who have little in
common except a severe sense of inadequacy and discontent.
Anorexia Nervosa in the Male
Anorexia nervosa in the male requires a separate discussion. It is much
rarer than in females, and the literature on it is even more ambiguous and
contradictory. One finds side-by-side statements that typical anorexia

nervosa does not occur in the male, and that it is not different from that
observed in the female. It has even been doubted whether it was even
justified to make the diagnosis in the male. If amenorrhea is considered a
cardinal symptom then males are ipso facto excluded. Defined in psychiatric
terms the condition does occur in males, and the failure in pubertal
development appears to be the parallel to amenorrhea in females. Both the
genuine syndrome and the atypical form are observed. As in females,
relentless pursuit of thinness is the outstanding motive in primary anorexia
nervosa, representing a frantic effort to establish a sense of control and
identity. In the atypical picture the eating itself is disturbed with various
distortions of its symbolic meaning.
Little attention has been paid to male anorexics in the modern
literature; usually they are briefly mentioned in the form of an appendix or

footnote. Dally surveyed 140 females with anorexia nervosa for whom he
established distinctly different groups. During the same period six male
anorexics were observed, who were described by Dally as more
heterogeneous. He noted that it was difficult to compare the course and
outcome in the two sexes. Selvini stated, in a recent discussion of anorexia
nervosa, that the cases of undereating in males, in her observations, were all
cases of pseudoanorexia, with paranoid delusions and hypochronical ideas
about the digestive system.
In my group of seventy-five patients, observed between 1942 and 1972,

there were ten males (13 percent) who were diagnosed as suffering from
anorexia nervosa at the time of their illness. By focusing on the core dynamic
issues, and by clarifying the whole life pattern, interpersonal experiences,

emotional conflicts, and psychological deficits, it was possible to define the
primary picture in six cases, and to differentiate them from patients with
atypical food refusal (four cases) with various psychiatric disturbances and
the cachexia only an incidental finding.
Atypical Picture
As in the females, the atypical cases were the first to be observed; at the
time of their illness they were considered examples of the classical anorexia
nervosa picture. Two of these atypical anorexics were adults, twenty-four and
twenty-seven years old, respectively, when they became nervous and fearful,
and began to suffer a true loss of appetite, in response to life situations which
they experienced as overdemanding; the birth of the first child in one
instance, and facing independent professional responsibilities in the other.
Both were of good intelligence but had been “underachievers,” performing
below the level of their capacities, throughout their lives. One was frantic
about the weight loss, the other was pathologically indifferent, not having
noticed any changes in his feelings about food, and without awareness of the
weight loss, except for an increasing looseness of his clothes. The older of the
two men, after a seeming recovery, had a relapse six years later and died
rather suddenly, without a definite cause of death being established.
The third patient, a fourteen-year-old adolescent, became preoccupied
with anxieties about the body and its functions, coinciding with pubertal
development. He had been an only child and somewhat obese, always clinging
and extremely dependent on his mother. He complained of headaches,
became depressed and moody, was irritable and became even more
withdrawn than before. He developed fear of swallowing, that the food might
get into his lungs and he would suffocate, and became so phobic about
swallowing that he refused to eat at all. When he became a psychiatric patient

he was frantic with fear about his weight loss (over 40 lbs.), and that he did
not want to be skinny. He was diagnosed as suffering from a psychoneurosis,
conversion type; an effort was made to contact him five years later and it was
learned that he was in a state hospital with the diagnosis of schizophrenia.
In the fourth patient whose illness had begun when he was thirteen
years old, immediately following his bar mitzvah, fasting was one ritual
amongst many others for “atonement of his sins.” This boy was completely
indifferent about his body and his appearance. Like the other boy, he had
stopped going to school when the symptoms developed.
None of these patients had been in psychiatric treatment before the
illness, but there had been many recognized difficulties, complaints about
their poor achievement, disturbances in their eating behavior, and overt
sexual anxieties. The families appeared overtly disturbed.
Many case reports on individual male patients that have been published
are examples of the atypical picture, though they are referred to as
representing the “classical” syndrome. They are usually young adults or even
middle aged, who have nothing in common except the weight loss and certain
degree of “give-up-itis.”
Primary Anorexia Nervosa
In contrast to the divergent atypical picture, the primary group has
many features in common. The psychological issues are similar to those
observed in females. Here, too, relentless pursuit of thinness is the leading
motive. The youngsters are described as having done exceptionally well as

children. Closer studies revealed that these accomplishments were a facade
performance, an expression of compliance, and not of self-initiated and self-
directed goals. In their desperate struggle to become “somebody” and to
establish a sense of differentiated identity, they become overambitious,

hyperactive, and perfectionistic. As in females, manipulation of their own
body through noneating is a late step in this development, but the weight loss
results in a desperate picture that draws attention to their plight and finally
brings them into treatment.
All six boys in this group were still in prepuberty when the illness began
with what looked like a deliberate decision to reduce because they felt “too
fat.” If the planned lower weight had been reached, it proved “not enough,”
because much more than weight loss had been expected. Being and staying
thin became a goal in itself. Their real fear was that of not being truly
respected, of not being in control but of being a helpless product of “them.”
Since no manipulation of the body can possibly provide the experience of self-
confidence, self-respect, and self-directed identity, the pursuit of thinness
becomes more frantic, the amount of food smaller and smaller, and aimless
activity, to “burn off calories,” more hectic.
This acute sense of dissatisfaction had occurred, in all six cases, when
there was a change of the social setting, moving to a new neighborhood,
change of school or going to camp or boarding school. Throughout their lives
these boys had received a great deal of praise for being outstanding from
their families, and also from teachers and peers. The illness became manifest
when the assured status of superior achievement was threatened, when they
feared they could not obtain the same prestige in the new environment. They
had been success and achievement-oriented before they became sick and four
had been outstanding in athletics, greatly encouraged by their fathers. As the
illness progressed, with increasing social isolation, the activities tended to

become aimless, no longer integrated into athletics and group activities.
In none was there a true loss of appetite, in spite of the rigid self-
starvation, which is endured without definite hunger awareness. Periods of

vigorous refusal to eat alternated with eating binges of unbelievable
proportions, which were followed by self-induced vomiting. Bulemia with

vomiting was present to various degrees in five of the six cases. Hyperactivity
and drive for achievement were remarkable, with persisting superior
intellectual achievement. The boys continued to go to school in spite of the
severe emaciation, with some excelling even more than before though one,
observed in 1970, dropped out of school for a while under the influence of
alcohol and drugs.
During psychotherapy it was learned that, in spite of their excellent

performance, they had suffered from severe doubts about their adequacy and
competence. In spite of the stubborn, aggressive and violent negativistic
behavior, they, too, suffered from a conviction of their ineffectiveness, the
dread of not being in touch with or control of their own sensations and
functions. The rigid control over their weight is like a magical touchstone, the
tangible evidence of control over their body. The families appeared to be

stable and well-functioning, but with a transactional pattern of a controlling
mother superimposing her own concepts of his needs and desires upon a
developing child, disregarding the clues originating within him. Since these
mothers were well informed, what they superimposed was quite reasonable,
not contrary to the child’s physiological and developmental needs, and when
young they were healthy children and offered the facade of adequate
functioning. The serious deficits were in the area of autonomy and active self-
awareness which came into the open when life situations arose where
independence, decision making, and self-initiated behavior were expected.
The underlying dynamic picture in male and female anorexics with the
primary syndrome shows great similarity. There is one point of difference,
namely, in the male all cases of primary anorexia nervosa occur in
prepuberty; these boys did not develop sexually until after they had
recovered. This is consistent with the reports by others on young male
patients. Falstein and his co-workers reported on four prepubescent boys
who, they felt, showed the classical picture of anorexia nervosa as the end
result of diverse and multiple contributing factors. All four boys had been
preoccupied with their size. Tolstrup observed four males among fourteen
anorexics with onset before age fourteen; the youngest was only eight years
old. He felt that they showed the typical syndrome. Ushakov found that
admission rates for anorexia nervosa were five times higher for girls than
boys in whom the illness had an early onset between ten to thirteen years of
age.
The fact that anorexia nervosa in males is conspicuously less frequent
than in females may well be related to the fact that it does not occur after
pubescence. In addition, the characteristic slavelike attachment of a child to
the mother is probably more frequent in girls, and efforts to solve
psychological problems through manipulation of the body are also more

common in females. It is probably unusual for a boy to be caught in this
developmental impasse. But even when this type of attachment had
developed, the psychobiological experience of male puberty will flood a boy
with such powerful new sensations, inducing a more aggressive self-
awareness which makes a type of self-assertion possible that he was not
capable of achieving in prepuberty. Once boys are caught in this vicious cycle
of self-starvation and distorted body experience, endocrine treatment
appears ineffective, even disturbing. It becomes of value only after the
underlying psychological problems have been clarified.
Psychiatric Differential Diagnosis
There has been considerable controversy about the proper psychiatric
classification of anorexia nervosa. As long as the focus was on unconscious
conflicts about sexuality or pregnancy, the condition was conceived of as a

neurosis; this was the majority opinion until fairly recently. In a survey of
thirty patients, observed between 1935 and 1959, Rowland noted that the
final diagnosis was a mixture of conversion hysteria, obsessive-compulsive
neurosis, anxiety reactions, schizophrenia, and depressive reaction, with
schizophrenia being diagnosed more often during the 1950s than during the
1930s.
Much of the old confusion was related to the fact that all cases of
psychological malnutrition were lumped together, and that psychiatric
diagnostic categories were conceived of as rather fixed clinical entities.
Modern psychiatric thinking has undergone many changes, and questions
asked today are under what conditions will a patient react in a schizophrenic,
hysterical, depressive, or obsessional fashion, and not whether he has hysteria
or schizophrenia, etc. Following anorexic patients over many years brings the
interrelatedness of various psychiatric syndromes into the open. Not
uncommonly, an early diagnosis of neurosis, in the primary as well as the
atypical group, was changed to schizophrenia as the illness persisted.
Though the concept of schizophrenia has undergone many changes, no
new diagnostic concept has been formulated for clinical conditions
characterized by disturbances in the symbolic processes, with deficits in
personality integration and self-awareness, reality testing and psychosocial
competence. Failure in discriminating awareness of essential bodily

sensations, particularly of hunger, is an outstanding deficiency in anorexia
nervosa, associated with distorted concepts of one’s own body identity. It
may be associated, to various degrees, with disturbances and deficiencies in

the integration of other symbolic processes. Viewed from this angle, primary
anorexia nervosa is more akin to potentially schizophrenic development, or

borderline states, than to a neurosis, though only a few patients with primary
anorexia nervosa were overtly schizophrenic at the onset of their illness, or

progressed to that state of disorganization. In the beginning neurotic
mechanisms, most often obsessive compulsive defenses, stand in the
foreground, efforts to ward off the frightening confrontation with their
complete helplessness, the falsified awareness of their own needs, and their
lack of control over their bodily functions.
Depressive features deserve special evaluation; they may indicate a true
depression as a primary illness, though this is a rare occurrence; more often

they express the underlying despair of a schizophrenic reaction. The earliest
manifestations of something wrong, preceding the actual anorexia nervosa by
months or years, may be moodiness and irritability. After the condition has
existed over a long period a depressive affective state is difficult to

distinguish from apathy, and the corroding effects of isolation.
Recently Selvini suggested subdividing patients suffering from primary

anorexia nervosa according to the differences in their eating behavior and
attitude. By evaluating Rorschach records for communication defects and
deviances, according to the method described by Wynne and Singer, she
observed differences in the style of thinking in patients with different eating

behavior. She found more signs of disorganized thinking in those with eating
binges and vomiting, or frantically preoccupied with fear of losing control;
patients with this fragmented type of thinking had a poorer prognosis than
those who maintained stable control. Using the same scoring technique, I was
unable to establish such differences, either on Rorschach evaluation or

clinically. Two of the three girls who died had been rigid in their food
restriction but never vomited, the type Selvini calls “stable anorexic.” One
died directly of starvation and the other of starvation and circulatory failure.
In the third in whom vomiting had been a conspicuous feature, the fatal
outcome was attributed to irreversible damage due to disturbances in the

electrolyte balance.
Recognition of the underlying potentially schizophrenic core is essential

for effective treatment. I have seen many anorexic patients where increasing
isolation had progressed to apathy and withdrawal into an autistic way of life.
Unfortunately, this may even happen in patients who are in treatment, with
focus on their so-called conflicts, but neglecting to deal with the underlying
essential problems, the ego deficiencies and incompetence in self-awareness
and human relatedness. In a misguided effort, a therapist may “support” an

anorexic’s increasingly bizarre living arrangements, and thus become a
collaborator towards an insidious schizophrenic development.
Prognosis
Anorexia nervosa has always been regarded as a serious condition, with,
at best, a protracted course. Little, if any, relevant information is available on

how to predict the outcome in an individual case. Evaluation of the prognosis
on the basis of the literature is more confusing than enlightening. Often an
inaccurate picture is presented, records at a large medical center are culled
from patients seen over many years and treated by many different physicians
with many different approaches. One such report, supposedly based on the
follow-up histories of 115 patients observed at a university medical center,
actually refers to only twenty-six (21 percent) of the patients who had replied
to a letter of inquiry; even for them evaluation of the long-range outcome is
not based on personal contact. Nothing is known about the fate of the
remaining eighty-nine (79 percent) patients. Nevertheless, the authors speak
of “a significant shift back to health and maintenance of weight.” In a study in

which contact with patients was maintained, even though they had refused
psychiatric treatment, Cremerius found that the later development of fifteen
patients after fifteen to eighteen years, was highly unsatisfactory. Five

showed a chronic anorexic picture, though somewhat ameliorated; five had
achieved a normal, even excessive weight, and some were even menstruating,
but serious maladjustment and personality disturbances persisted. One
patient had died from an intercurrent illness and another was hospitalized as
a chronic schizophrenic. Cremerius concluded that there is no spontaneous
recovery, though five patients would have given this impression on

superficial contact.
Commonly weight gain is interpreted as a sign of improvement,

whereas in reality it may only be a temporary remission. This is most
tragically illustrated by the histories of the five patients in my group with fatal
outcome. Sufficient weight was regained by four, that for a while they were
thought of as recovered; one, a fourteen-year-old boy, died after a few
months, not from inanition but from a severe infection. Death occurred in one
atypical case, a man of twenty-seven, who had become sick and lost his
appetite following the birth of his first child. After several years of seeming
recovery he suffered a relapse and died suddenly at age thirty-three with
vague symptoms of gastric distension. A young woman, anorexic since age

sixteen, had gotten married during what looked like a spontaneous recovery.
Though still amenorrheic, she became pregnant and developed tetany. The
child was stillborn and a relapse of the anorexic picture followed. She came
for psychiatric treatment only after marked physiological changes had taken
place which proved to have caused irreversible damages. She died at age
twenty-two from the effects of general calcinosis (vitamin D poisoning), with

cardiac and renal failure.
The two other girls had become anorexic at age eleven and fourteen,
respectively, and gained satisfactorily while in some form of supportive
psychiatric treatment, which had not dealt with the patient’s inner sense of
incompetence. When a relapse occurred two or three years later, the parents
postponed asking for help. When finally hospitalized, medical intervention

was not active enough, and both girls died of inanition, with weights as low as
45 and 55 lbs. There had been nothing in the early picture of these patients
suggesting that they suffered from a more malignant form of the illness.
In my opinion the long-range outcome runs directly parallel to the

adequacy of the therapeutic intervention. Specifically, there is little
relationship between the diagnostic classification, whether psychoneurosis or
schizophrenia, and the final outcome. Some, in whom the diagnosis of

schizophrenia had been made quite early, did well in the long run, whereas
others, with a consistent psychoneurotic picture, did poorly or even died. This
applies to both the typical and atypical group.
It has been assumed that the prognosis in young prepubertal children is
better than in older patients. These young patients come for treatment earlier
and the therapeutic approach is more comprehensive, with active

involvement of the parents. If the therapeutic intervention with the whole
family is not effective, young patients may be as seriously ill as the older ones.
The onset in three of the patients who died had been below age fourteen.
Probably the case in my group most resistant to treatment was a young man
who had become anorexic at age twelve and whose weight at age eighteen
was below 50 lbs. His case is also an example of the direct relationship of the
prognosis to the pertinence of the therapeutic approach. With therapy

designed to meet his underlying problems, he made a good recovery and was
doing well, actively involved in living, when last heard of ten years after
discharge. There were several others with even longer histories of
unsuccessful treatment, up to eleven years, who responded well to a change
in therapeutic approach. Several reports of effective therapeutic intervention
are to be found in the schizophrenia literature, namely of patients who had
been grossly neglected at the time of their anorexic illness. Without effective
intervention at the crucial point of conflict and maldevelopment, the outlook
is poor, in particular after secondary symptoms have developed and an
anorectic way of life has been adopted.
Selvini has made the same observation, that the statistical evaluation of
long range results, in particular when based on weight information alone, is
not only noninformative but misleading. Recovery is entirely dependent on
the capacity to understand the true conflicts of the anorexic and to help him
find better ways of dealing with them.
Treatment
Treatment involves two distinct tasks, the restitution of normal
nutrition and the resolution of the inner psychological problems so that a
patient no longer needs to abuse the eating function in futile efforts to solve
his problems. For effective long-range results the two aspects should be
integrated; in reality this ideal is rarely fulfilled. All too many patients are
made to gain weight on a medical service, and are then discharged back to the
same environment where the illness had developed. They come for
psychiatric treatment only after years of such futile efforts. In others not
sufficient consideration has been given to the self-perpetuating destructive
effect of the nutritional deficit itself. Psychiatrists may have the unrealistic
expectation that the weight will correct itself after the psychological problems
have been solved; such a wait-and-see attitude where nothing is done to
correct the severe malnutrition, may unnecessarily prolong the illness. A
certain degree of nutritional restitution is a prerequisite for effective
psychotherapy.
Since the first description of anorexia nervosa there has been
continuous debate on how to accomplish the seemingly impossible task of
getting food into patients who are stubbornly determined to starve
themselves. This discussion has extended to what food to offer, how to feed it,
where to do it, and what medication to use. The physiological principles are
very simple: increase the food intake and keep these hyperactive cachectic
youngsters from exhausting themselves. The question is how to persuade,

trick, bribe, cajole, or force a negativistic patient into doing something he or
she is determined not to do.
It is virtually impossible to draw conclusions about the effectiveness of

various regimens from the literature. The case material is extremely
heterogeneous, and the reports refer to patients at various stages of their

illness. One reason for the confusing reports, which is rarely openly stated, is
the fact that frequently the authors themselves have little experience with
such patients. Rowland’s survey is based on the study of the case records of
thirty patients who were observed in different departments of the Columbia
Presbyterian Medical Center in New York, between 1936 and 1959; the
figures suggest that about one patient was observed per year. A variety of
methods were used, such as frequent small feeding of special preparations
with high protein content, or, in contrast, tempting choices from special trays,
or coercion to eat the regular hospital food, or feeding by gastric tube or

threat of it, all with unpredictable results. Similarly discouraging is the survey
by Browning and Miller, who concluded on basis of the records of thirty-six
female anorexics treated at the University Hospital of Cleveland, between

1942 and 1966, that hospitalization did little to improve the course of the
disease. The deaths of three (8 percent) patients while hospitalized is
reported with the implication that vigorous treatment might have hastened
the fatal outcome. This might be interpreted differently, namely, that

hospitalization had been postponed until the patients were in such a
debilitated state that they were beyond help.
In my experience too, a brief admission to a medical service which does
not have special experience in the management of anorexia, creates as many

problems as it attempts to solve. The staff is as helpless and inconsistent in
dealing with the deceitfulness and cunning of these patients as the family, and
is apt to react with anxiety, frustration, and angry coercion. But whether
hospitalization is helpful or not, in reality most patients, long before they are
seen by a psychiatrist, will have been hospitalized at least once. Early in the
disease the focus is on diagnostic procedures, to recognize or exclude possible

organic factors. Later on, hospitalization may be necessary as a life-saving
measure, when there is progressive emaciation, or acute danger to life due to
electrolyte imbalance. This is particularly apt to happen in patients who use

vomiting, laxatives, and diuretics, and which many will continue to use even
after they have become painfully aware of the dire consequences. Under such
conditions rather heroic methods may become necessary for correction of the
electrolyte imbalance. In one of my patients such help came too late; extreme
calcinosis had led to wide-spread irreversible changes, with cardiac and renal
failure as the cause of death.
As to the medical regimen, individualization is essential. A firm attitude
that eating is necessary, combined with the reassurance “We won’t let you
die,” may produce some gain in weight. Some find it useful to prescribe
certain definite amounts of high-protein high-caloric liquid nourishment
which is offered as “medication,” and to leave eating ordinary food to the
patient’s choice. Usually such a program is reinforced by the patient’s

knowledge that the alternative to his eating the prescribed amounts will be
tube feeding. Occasionally a patient will prefer tube feeding. The boy who
fasted “as atonement for his sins” required tube feeding for several years
because it was “harder” and made him feel that he performed one more ritual
of atonement. Other patients, though disliking the procedure, gain a sense of
reassurance that someone cares for them.
The use of various medications reflects changing concepts of the

etiology of anorexia nervosa. As long as it was considered of pituitary origin it
was a matter of course to attempt “replacement” therapy. Prescription of
thyroid was based on the assumption that a “low” basal metabolic rate
indicated deficiency. Insulin was frequently given to stimulate the appetite.

Endocrine products have a legitimate use in the treatment of amenorrhea,
where it is possible now to produce regular bleeding. In males, with delayed
puberty, testosterone may be useful, but only after the underlying condition is
sufficiently corrected that its administration will not stunt the patient’s
growth, or precipitate an untoward psychological reaction.
In recent years the anabolic steroids have been used as adjuncts in the
rehabilitation of long-standing cases, with the achievement of impressive
weight gain and greater sense of well being. However, as far as I know, no
controlled studies have been reported.
The psychiatric problems have also been treated by somatic methods.
Both insulin and electroshock therapy have been used, and also psychotropic
drugs, in my observations with only very temporary results.
Recently a method of behavior therapy has been described, namely,
permitting freely chosen activities as prompt reward for gain in weight. The
immediate results appear to be good and the method is recommended with
much optimism. Yet one patient in the original report, with satisfactory
weight gain, committed suicide after discharge, before the planned

psychotherapy had been instituted. Though this or similar methods have been
in use for a short time only, I have had consultations on patients who had
gained satisfactorily while hospitalized, even maintained the weight for a
brief period after discharge, but then relapsed. Nothing had been changed in
the essential family relationships, or in the patient’s underlying personality
structure. 1
Equally enthusiastic are recent reports on crisis-induced family therapy
in which the family is stimulated to change their habitual patterns of
interaction. These reports deal with young patients, in the beginning of their
illness, before the secondary problems have become entrenched. Thus far
there have been no follow-up reports, whether these dramatic
rearrangements have lasting value. In young patients equally good results can
be achieved by individualized psychotherapy and more conventional work
with the family. The intensity of treatment for each member, the focus and its
length, vary considerably. Some of these young patients can be treated
effectively while living at home; in others hospitalization may be helpful to
effect a gain in weight while the underlying problems are being clarified.
In many instances, when ambulatory methods have failed, when the
family problems were not resolved but have disintegrated, psychiatric
admission for long-term therapy becomes necessary; it is of use only if the
service has a constructive therapeutic philosophy. It has been objected that

psychiatric admission is superfluous, that weight gain could be accomplished
in a medical service and be followed by psychotherapy on an ambulatory
basis. This reflects an outdated concept of the function of a psychiatric
hospital. Great benefits can be derived from the experience of living in the
hospital “milieu” provided this is integrated into the therapeutic experience.
Psychotherapy also needs to be approached in an individualized way.
Since patients with the atypical syndrome vary widely in their personalities,
psychological problems, and the situational and precipitating factors, no
generalized statement can be made about therapy except that it needs to fit
the individual circumstances. The following statements apply to the more
uniform picture of primary anorexia nervosa where many similarities of the
problems have been recognized.
The literature on the value of psychotherapy and psychoanalysis is
hopelessly inconclusive. Psychotherapy has been referred to as useless, or,
conversely, psychoanalysis has been praised as the best method. Authors who
feel that a psychotic core underlies the overt clinical picture have expressed
doubts about verbal forms of treatment resulting in meaningful changes in a
condition that assumedly develops during the preverbal phase. Selvini found
traditional psychoanalysis ineffective and achieved increasingly better results

with a more pertinent understanding of the condition, namely as a concrete
use of the body in the struggle for identity. My own experiences are similar. I
have found traditional psychoanalysis and “insight” giving therapies

ineffective, but that good results could be achieved, even in cases who had
been considered untreatable, with an appropriate change in focus by
modifying psychotherapy to meet the individual need and problems of these
patients.
The intrinsic therapeutic task must aim at effecting a meaningful change

in their selfconcept and sense of incompetence in areas of functioning where
they had been deprived of adequate early learning. There is need to evoke
awareness of impulses, feelings, and needs as originating within themselves.
A patient can become an active participant in the treatment approach, and

thus capable of living his life with competence, even enjoyment, and self-
directed, when the therapist responds with alertness and consistency, to any
selfinitiated behavior and expression.
This formulation is the outgrowth of continuous evaluation, over a
period of thirty years, of the therapeutic process, in particular of the
difficulties and failures encountered with the traditional psychoanalytic
approach. Psychoanalysis has undergone many modifications during that
time, and my emphasis on evoking a better functioning self-concept is in

agreement with now widely accepted modifications, particularly those
developed for treatment of schizophrenia, borderline states, and narcissistic
characters.
The more a therapist conceives of the psychological disorder as
expressing oral dependency, incorporative cannibalism, rejection of
pregnancy, etc., the more likely he will follow a classical psychoanalytic
model. That had been the case in patients who had been unsuccessfully in
treatment for many years, who came for therapy, or whom I saw in
consultation. The concept that the abnormal eating is a late and secondary
step in the whole development, a frantic effort to camouflage underlying
problems, or a defense against complete disintegration, has only recently

been formulated for anorexia nervosa, and is not widely known.
This orientation leads to a therapeutic approach with focus on a
patient’s failure in selfexperience and on his defective tools and concepts for
organizing and expressing his own needs, and his bewilderment in dealing
with others. Instead of interpreting intrapsychic conflicts and the disturbed

eating function, therapy will attempt to help him deal with the underlying
sense of incompetence, encourage correction of the conceptual deficits and
distortions, and thus enable a patient to emerge from his isolation and
dissatisfaction. The patients need help with their lacking sense of autonomy,
their disturbed self-concept and self-awareness. I have been impressed how

often such angry “resisting” patients, if this is communicated to them without
insult to their fragile self-esteem, will become actively interested in therapy,
and even will accept the need for food, instead of fighting against it.
Inability in identifying hunger and other bodily sensations is a specific
deficiency. Other sensations and feeling tones too, are inaccurately perceived
or conceptualized, and this is often associated with a failure in recognizing
the implications of interaction with others. These patients suffer from an
abiding sense of loneliness, and feel that they are not respected by others, or
are insulted and abused, though the real situation may not contain these
elements. The process of exploring and examining such situations and of
alternatives of interpreting and reacting to them, eventually leads to a patient

experiencing himself not as utterly helpless, or the victim of compulsions that
overpower him. Examining their own development in this way becomes an

important stimulus for their acquiring thus far deficient mental tools. The
core problems, their profound sense of ineffectiveness, their lacking self-

awareness of their sensations, not feeling in control, not even owning their
body and its functions, were recognized as related to deficiencies in the
mother-child interaction, which had been without consistent and appropriate
responses to child-initiated clues. The therapeutic situation offers the chance
for new experiences, where what he has to contribute is acknowledged and
reinforced.
This approach involves a reformulation of the therapeutic task, that the

therapist suspend his knowledge and expertise, and permit and encourage a
patient to express what he experiences, without immediately explaining and
labeling it. Some of the current models of psychiatric training emphasize early
formulations of the underlying psychodynamic issues. Such formulations may

tempt a therapist to impose premature interpretations on a patient, and thus
stand in the way of learning the truly relevant facts. The therapeutic goal is to
make it possible for a patient to uncover his own abilities, his resources and
inner capacities for thinking, judging and feeling. Once he has experienced
this capacity of self-recognition, the whole atmosphere surrounding therapy
will undergo a complete change.
Bibliography
Barcai, A. “Family Therapy in the Treatment of Anorexia Nervosa,” Am. J. Psychiatry, 128 (1971),
286-290.
Binswanger, L. “Der Fall Ellen West,” Schweiz. Arch. Neurol. Psychiatr., 53 (1944), 255-277; 54
(1944). 69-117; 55 (1944), 16-40.
Blinder, B. J., D. M. A. Freeman, and A. J. Stunkard. “Behavior Therapy of Anorexia Nervosa:
Effectiveness of Activity as a Reinforcer of Weight Gain,” Am. J. Psychiatry, 126
(1970), 77-82.
Bliss, E. L. and C. H. H. Branch. Anorexia Nervosa—Its History, Psychology and Biology. New York:
Hoeber, 1960.
Browning, C. H. and S. I. Miller. “Anorexia Nervosa—a Study in Prognosis and Management,” Am.
J. Psychiatry, 124 (1968), 1128-1132.
Bruch, H. “Perceptual and Conceptual Disturbances in Anorexa Nervosa,” Psychosom. Med., 24

(1962), 187-194.
----. “Anorexia Nervosa and Its Differential Diagnosis,” J. Nerv. Ment. Dis., 141 (1966), 555-566.
----. “The Insignificant Difference: Discordant Incidence of Anorexia Nervosa in Monozygotic

Twins,” Am. J. Psychiatry, 126 (1969), 123-128.
----. “Death in Anorexia Nervosa,” Psychosom. Med., 33 (1971), 135-144.
----. “Hunger Awareness and Individuation,” in Eating Disorders: Obesity, Anorexia Nervosa and
the Person Within, pp. 44-65. New York: Basic Books, 1973.
----. “Body Image and Self-awareness,” in Eating Disorders: Obesity, Anorexia Nervosa and the
Person Within, pp. 87. New York: Basic Books, 1973.
----. “Primary Anorexia Nervosa,” in Eating Disorders: Obesity, Anorexia Nervosa and the Person
Within, pp. 250-284. New York: Basic Books, 1973.
----. “Evolution of a Psychotherapeutic Approach,” in Eating Disorders: Obesity, Anorexia Nervosa

and the Person Within, PP. 334-377. New York: Basic Books, 1973.
Coddington, R. D. and H. Bruch. “Gastric Perceptivity in Normal, Obese and Schizophrenia

Subjects,” Psychosomatics, 11 (1970), 571-579.
Cremerius, J. “Zur Prognose der Anorexia Nervosa (13 fünfzehn-bis achtzehnjährige Katamnesen
psychotherapeutisch unbehandelter Fälle),” Arch. Psychiatr. Nervenkr., 207 (1965),
378-393-
Crisp, A. H. “Some Aspects of the Evolution, Presentation and Follow-up of Anorexia Nervosa,”
Proc. R. Soc. Med., 58 (1965), 814-820.
----. “Premorbid Factors in Adult Disorders of Weight, with Particular Reference to Primary
Anorexia Nervosa (Weight Phobia)” (A literature review), J. Psychosom. Res., 14
(1970), 1-22.
----. “Reported Birth Weights and Growth Rates in a Group of Patients with Primary Anorexia
Nervosa (Weight Phobia),” J. Psychosom. Res., 14 (1970), 23-50.
Dally, P. Anorexia Nervosa, New York: Grune & Stratton, 1969.
Eissler, K. R. “Some Psychiatric Aspects of Anorexia Nervosa, Demonstrated by a Case Report,”

Psychoanal. Rev., 30 (1943), 121-145.
Falstein, E. I., S. C. Feinstein, and Judas. “Anorexia Nervosa in the Male Child,” Am. J.
Franklin, J. S., B. C. Schiele, J. Brozek et al. “Observations on Human Behavior in Experimental

Semi-Starvation and Rehabilitation,” J. Clin. Psychol., 4 (1948), 28-45.
Gibson, R. W. “The Ego Defect in Schizophrenia,” in G. L. Usdin, ed., Psychoneurosis and

Schizophrenia, pp. 88-97. Philadelphia: Lippincott, 1966.
Gottheil, E., C. E. Backup, and F. S. Cornelison. “Denial and Self-image Confrontation in a Case of
Anorexia Nervosa,” J. Nerv. Ment. Dis., 148 (1969), 238-250.
Gull, W. W. “Anorexia Nervosa (Apepsia Hysterica, Anorexia Hysterica),” Trans. Clin. Soc. Lond., 7
(1874), 22.
----. “Anorexia Nervosa,” Lancet, 1 (1888), 516.
Kaufman, R. M. and M. Heiman, eds. Evolution of Psychosomatic Concepts. Anorexia Nervosa: A
Paradigm. New York: International Universities Press, 1964.
Kay, D. W. K. and D. Leigh. “The Natural History, Treatment and Prognosis of Anorexia Nervosa,
Based on a Study of 38 Patients,” J. Ment. Sci., 100 (1952), 411-431.
King, A. “Primary and Secondary Anorexia Nervosa Syndromes,” Br. J. Psychiatry, 109 (1963),
470-479.
Lasegue, C. “On Hysterical Anorexia,” Med. Times Gaz., 2 (1873), 265-266, 367-369.
Meng, H. Psyche und Hormon. Bern: Huber, 1944.
Meyer, B. C. and L. A. Weinroth. “Observations on Psychological Aspects of Anorexia Nervosa,”

Psychosom. Med., 19 (1957), 389-398-
Morton, R. Phthisiologica—or a Treatise of Consumptions. London: 1694.
Nemiah, J. C. “Anorexia Nervosa—a Clinical Psychiatric Study,” Medicine (Baltimore), 29 (1950),

225-268.
Nicolle, G. “Prepsychotic Anorexia,” Proc. R. Soc. Med., 3 (1938), 1-15.
Rowland, C. V., Jr. “Anorexia Nervosa, A Survey of the Literature and Review of 30 Cases,” Int.
Psychiatry Clin., 7 (1970), 37-137.
Russell, G. F. M. “Anorexia Nervosa: Its Identity as an Illness and Its Treatment,” in J. H. Price, ed.,
Modern Trends in Psychological Medicine, pp. 131-164. London: Butterworth, 1970.
Selvini, M. P. L’Anoressia Mentale. Milan: Feltrinelli, 1963; London: Chaucer Publishing, 1974.
----. “Anorexia Nervosa,” in S. Arieti, ed., The World Biennial of Psychiatry and Psychotherapy, Vol.
1, pp. 197-218. New York: Basic Books, 1971.
Silverstone, J. T. and G. F. M. Russell. “Gastric ‘Hunger’ Contractions in Anorexia Nervosa,” Br. J.
Psychiatry, 113 (1967), 257-263.
Simmonds, M. “Uber embolische Prozesse in der Hypophysis,” Arch. Pathol. Anat., 217 (1914),
226.
Theander, S. “Anorexia Nervosa. A Psychiatric Investigation of 94 Female Patients,” Acta.

Psychiatr. Scand. Suppl., 214 (1970), 1-194.
Thomae, H. Anorexia Nervosa. Bern-Stuttgart: Huber-Klett, 1961; New York: International

Universities Press, 1967.
Tolstrup, K. “Die Charakteristika der jungeren Falle von Anorexia Nervosa,” in J.-E. Meyer and H.
Feldman, eds., Anorexia Nervosa, pp. 51-59. Stuttgart: Georg Thieme, 1965.
Ushakov, G. K. “Anorexia Nervosa,” in J. G. Howells, ed., Modern Perspective in Adolescent

Psychiatry, pp. 274-289. Edinburgh: Oliver & Boyd, 1971.
Waller, J. V., R. Kaufman, and F. Deutsch. “Anorexia Nervosa: A Psychosomatic Entity,” Psychosom.
Med., 2 (1940), 3-16.
Will, O. A., Jr. “Human Relatedness and the Schizophrenic Reaction,” Psychiatry, 22 (1959), 205-
223.
Wynne, L. C. and M. T. Singer. “Thought Disorder and the Family Relations of Schizophrenics: II.
Classification of Forms of Thinking,” Arch. Gen. Psychiatry, g (1963), 199-206.
Ziegler, R. and J. A. Sours. “A Naturalistic Study of Patients with Anorexia Nervosa Admitted to a
University Medical Center,” Compr. Psychiatry, 9 (1968), 644-651.
Notes
1 A series of such therapeutic failures has been reported by H. Bruch, “Perils of Behavior Modification
in Treatment of Anorexia Nervosa,”
Chapter 33
Disturbances of The Body-Image
Lawrence C. Kolb
Since the earlier work of this writer on this subject and publication of
the chapter on “Disturbances of the Body-Image” in the first edition of this
Handbook in 1959, an extraordinary interest has developed in the body-
image as concept, its relation to personality functioning and psychopathology,
the use of psychological tests to ascertain quantitatively its expressions—
particularly in boundary and penetration—the confirmation and expansion of

earlier observations as related to developmental experiences in its evolution,
and finally, the application and elaboration of the preventive and therapeutic
procedures suggested previously as of value in clinical practice.
Body-image disturbances now receive wide recognition, particularly in

psychiatric and neurological practice, and in the consultive services to
medicine and surgery in general hospitals and clinics. The psychiatrist is
frequently called upon to assess the unusual problem of the patient with such
a disturbance and to provide an opinion as to the nature of the clinical
phenomena and the treatment. In the general field of psychiatry, knowledge
of the body-image concept has been applied in furthering understanding of
the bodily preoccupations in the schizophrenias, involutional psychoses,

hypochondriasis, neurasthenias, and the multitude of phenomena that occur
with acute and chronic brain disease, or result from various toxic, metabolic,
and degenerative states. Sound data on the specific developmental factors
which predispose or determine disturbances of the body-image in the major

psychoses and psychoneuroses are sparse.
Body-image phenomena, as observed in the general clinic, may
represent either a healthy psychophysiological reaction, or be evidence of
psychological and emotional maladaptation. The differences between

expected and healthy presentations of body-image phenomena and their
pathological variants are not widely recognized and hence not generally
diagnosed. The distinctions between health, disease, and the rationale of

much of the clinical phenomenology may only be understood in the context of
the developmental process of the personality and by consideration of the

detailed accounts of phantom phenomena.
The material presented in this chapter deals mainly with the general
principles and phenomenology underlying body-image disturbances,

discussion of disturbances which follow dismemberment or disfigurement of
the body or body surface, and considerations for prognosis and treatment.
The concept of the body-image is discussed in the following section.
Historical Perspective
The first written account of body-image disturbance was that of
Ambroise Paré, a sixteenth-century surgeon. Noting the frequent occurrence

of the phantom limb following amputation, Paré advised surgeons that this
disturbance should not prevent their proceeding with additional amputation
if such were indicated. It is most unlikely, however, that Paré’s report was
man’s first awareness of this overt expression of his body-image. Recognition
probably dates back to the earliest days of man, with the phenomenon
providing him with an experience as impressive and of as great psychological
import as his dreams and other reactions to death. Price and Twombly have
translated a Latin dissertation, with commentary, written on the subject by
Lemos in 1798.
Following Paré, Weir Mitchell provided one of the better descriptions of
the phantom, observations which were noted a few years later by Jean-Martin
Charcot. Head was responsible for the description and development of the
first basic concepts of the body schema or body-image, as well as for the
interpretation of its significance for the perception of body functioning in
relation to motility, localization of tactile stimuli, and the phantom
phenomenon. The broader concept of body-image presently utilized in
psychiatry was developed largely by Schilder.
The concept of disturbances in body-image derives from observations of
the affected individual’s failure to perceive his body and its parts, and adapt
to them as they actually exist. The outstanding examples of acute
disturbances occur as a result of traumatic or surgical dismemberment,

where the basic body-image persists, despite the visible or apparent loss of a
body part. The phantom limb is one of the most dramatic and convincing
expressions of the phenomenology. Similar disturbances are seen following
radical excision of tumors or masses of the face, head, and neck;
thoracoplasty; paralysis of extremities following poliomyelitis; sudden
paraplegias or hemiplegias; and distortions of the body resulting from

hyperadrenalism or other endocrine dysfunctioning.
At the present time, body-image disturbances may be classified as
consequent to the following categories of illness: (1) disorders following

neurological diseases and affecting any part of the sensory or motor system
connected with movement and posture, whether involving the peripheral or
the central nervous system; (2) disorders occurring with changes in the body
structure as an expression of acquired or induced toxic or metabolic disorder;
(3) disorders consequent to progressive deformities, occurring either late or

early in life and caused by other somatic diseases; (4) disorders after acute
dismemberment; and (5) disorders of personality development, including the
psychoses, psychoneuroses, and psychopathic states.
Head, the neurologist, visualized the body schema not simply as the
integrated resultant of past sensory experiences, but more as a unity deriving
from past experiences and current sensations organized in the sensory
cortex. These postural schemata, often functioning outside central

consciousness, were considered to be modifying impressions of incoming
sensory impulses for their localization on the body surface. Also, they made
possible the intricate and delicate motor activities through the constant
relationship of the body to other objects. Thus Head conceptualized an area of
sensorimotor functioning, a postural model of the body, which brings about
the possibility of projecting the recognition of posture, movement, and

locality beyond the limits of the body to the ends of instruments held in the
hand, or operated by the body. Anything which participates in movement of
the body was seen as added to the postural model and as becoming a part of
the body schema. The postural model of the body, as described by Head, is of
major importance in understanding many phenomena which occur in the

area of practice shared by the fields of neurology and psychiatry, or the levels
of functioning of the central nervous system.
Schilder, in contrast to Head, extended the body-image concept to

include not only an individual’s personal or psychological investment in his
body and its parts, but also a sociological meaning for both the individual and
society. To Schilder, the image of the human body is that picture or scheme of
our own body which we form in our minds as a tridimensional unity involving
interpersonal, environmental, and temporal factors. He also related the body-

image concept to curiosity, expression of emotions, social relations, duty, and
even ethics. In his considerations, the borderline between body-image and
the psychoanalytic concept of the ego is obscure. He specifically suggests that
one go beyond the purely perceptive side of the body-image development to

that of the expressive. Schilder conceived of the ego as constant and
underlying throughout life, something which takes or views the body as an
object toward which it has percepts, thoughts, and feelings.
Federn, in discussing the individual’s consciousness of himself,

differentiated the ego from the body-image. He writes of the mental and
bodily ego as felt separately; the mental ego is identified alone in the sleeping
state, but it is experienced as inside the bodily ego when awake. According to
Federn, ego is not body-image except when the body-image is invested
completely with ego-feeling. Similarly, the ego, in contrast to the body-image,

is considered to be capable of complete dissolution yet to have a capacity for
preservation of the somatic organization which allows for proper use of the
body and its perceptions. Federn equates ego-feeling with unity, in continuity,
of contiguity and causality of the experiences of the individual: “The body
scheme represents the constant mental knowledge of one’s body; the body
image is the changing presentation of the body in one’s mind. Throughout the
changes, the bodily ego is the continuous awareness of one’s body. Image,
scheme, ego, all three are themselves not somatic but mental phenomena.”
Szasz reviewed the thinking of Schilder and other psychoanalysts

relative to the relation of the body-image and ego. He proposes that the ego
relates not only to other people as objects but also to the body (of the self) as
an object, with mutual interaction between the ego and the body as an object.
His discussion of his position versus that of Schilder is in terms of modern

theories regarding the ego, and his effort to synthesize disparate viewpoints
poses an interrelation between the ego and the developing bodily functions.
This interrelation could be considered theoretically as “a process of

progressive mastery of the ego over the body (as an object), or, to put it more
generally, as the evolution of a progressively more complex ego-body
integration.”
As indicated in this brief historical account, the phantom phenomenon,
as representative of the body-image phenomena, was studied by surgeons
and neurologists. The first theoretical explanations for the changes in

modifications in the limb phantoms were derived from neurology, namely in
the context of Hughlings Jackson’s laws of dissolution and restitution of

function consequent to lesions within the nervous system. These data have
never been contradicted, and the theoretical explanations advanced suffice to
describe the modifications of the body’s postural image organized in the
sensorimotor cerebral center under ordinary conditions.
The second primary source of information on body-image has come
from psychoanalysis. The observations of psychiatrists and psychoanalysts
are based on studies of percepts, thoughts, and feelings toward the body, as
well as personality reactions to disruptions of the body-image. Since these
data represent an organization of information which occurs in the central
nervous system at the highest integrative level, they may be best understood
in terms of the theoretical constructs of modern psychology. Within the later
framework it is possible to predicate current unusual modifications,
perceptions, attitudes, or reactions to the body as consequent to the

individual’s previous life experiences, which determine conflict between the
body-image as perceived and that maintained by the ego as ideal.
A third, and most intriguing new line of study relating to body-image, is

followed extensively by Fisher and Cleveland and their colleagues working in
the field of psychology. Moving away from earlier theoretical concepts of W.
Reich’s armor concept, and Jung’s Mandala formulation, they conceived the
“body boundary” as a protective psychological construct which might be
related to various more or less effective modes of personality functioning,

predictive of different types of personality as correlated to externally or
internally manifested psychosomatic disease. These workers devised
methods of scoring the Rorschach-test responses, so as to give quantitative
“body boundary” and “body penetration” scores which appear to correlate
well with their predictions as to aspects of personality functioning and type of

psychosomatic disease. Their methods and findings are described more fully
below in the section on Special Examinations.
For the purposes of this chapter, the term “body-image” includes both
the postural model of the body as defined by Head, and also the perceptions,
attitudes, emotions, and personality reactions of the individual in relation to
his own body.
The term body-image is too broad. The phenomena largely studied by
the neurologists are best designated as representative of the body-percept, the
accumulated sensory experiencing of the body which establishes the
preconscious body schema and postural model and from which emerge the
body phantoms after loss of parts. The body-concept, on the other hand,
includes those thoughts, feelings, attitudes, and memories which evolve as the
individual (ego) views and experiences his body with others. The body-ego is
the perceiving or viewing aspect of personality as it concerns the body-image.

Each individual projects an idealized image of the body, the body-ideal,
against which he measures the percepts and concepts held of his body. His
ego functions to integrate the disparities within these evaluations which lead
to arousal of either painful or pleasurable affect. The ego defenses alleviate
the painful affect.
The descriptions of the consequences of dismemberment are now
sufficiently extensive to allow discrimination between healthy and
pathological adaptations to modification of the body-image resulting from
trauma, surgical procedures, or disturbances of the central integrating

mechanism. Where the consequence of disturbance of the body-image does
not follow the general expectations of the recognized healthy adaptation, the
influence of neurotic or psychotic personality development or social factors
will be found operative.
The discussions appearing in the succeeding portions of this chapter are
arranged to help the reader gain a clear picture of the factors influencing the
development of the body-image and some of the known consequences of the
expression of the body-image in healthy persons in the face of the acute stress
procedures. From this information, the variations which constitute pathology

and pathological psychodynamics in an individual case may be inferred.
Development of the Body-Image
Over the years, the individual organizes his body-image through the
integration of multiple perceptions, a process beginning with the earliest
stages of development. The embryonic and infantile nervous system is
exposed to proprioceptive sensory impressions from the vestibular apparatus
and the receptors in muscles and joints. (The hand-to-mouth movements
appearing initially in utero are the precursors of the complex and significant
face-hand relationship.)
With the progressive acquisition of motility, the newborn acquires

knowledge of his body from tactile impressions. In the sucking and feeding
process, the mouth is the first area to be stimulated, regardless of whether
hand, breast, or both are presented. Tactile impressions arising from the
regions of the cheeks and oral cavity become closely linked with the
increasingly prominent role of the hand sucking. From approximately the
twelfth week following birth, the structuring of the hand-to-mouth
relationship is accelerated. The child begins to use both hands and arms to
grasp and knead the mother’s breast. From this movement, he then proceeds
to use his hands to explore his own body surface and to contact others.
Concomitantly, he finds that the hand can also substitute for the nipple as a
pleasure part and can thereby relieve tension.
The infant’s exploratory movements of the hands over his own body, the
hands in contact with the mother, and their use in projecting into and
grasping objects in space provide the primary kinesthetic and tactile
sensations underlying the definition of the perceptual/ postural model. These
are the processes upon which the beginnings of self-awareness, of
individuality, and the sense of the ego are founded. Important perceptions
also develop in the early period from exposure to sensations which arouse
varying degrees of pleasure and displeasure; stimulation by self and others,

thermal stimuli, and, occasionally, direct painful contact.
In every instance, however, those sensations subserving optic, olfactory,

auditory, thermal, and pain stimuli are of secondary importance to the
kinesthetic and tactile exploration and perception of the body to form this
model. This is in keeping with our knowledge of the embryological
development of the nervous system in humans. As Langworthy found many
years ago, those sensory paths subserving kinesthetic and tactile activities are
the first to complete myelinization.
Even the influence of visual percepts of the body must be considered as
subsidiary to the kinesthetic and tactile. The fact that the congenitally blind
develop the capacity for adult patterns of response to Bender’s test of double
simultaneous cutaneous stimuli demonstrates the fundamental importance of
the processes of kinesthetic and tactile sensation in structuring the postural
model to subserve location of touch on the body surface. The significance of

early sensory experience for the development of the body-image is further
strengthened by the observations of Pick and Riese and Bruck that infants
and young children who sustain an amputation before the age of five do not
develop a phantom extremity. Similarly, Souques and Poisot and Simmel have
reported that children born without limbs (congenital aplasias) do not
experience a phantom limb. While finding that phantoms were rarely
reported if amputation was performed before the age of four, Simmel did
discover three subjects with phantoms, out of 135 examined, who
experienced the phantom after amputation before the age of two; one was six
months at the time of operation. Weinstein and Sersen, on the other hand,
found phantom representation in five out of thirty children with congenital

limb aplasias. The descriptions of the phantom representation in these cases
were obtained by a play technique with the child where he was required to
determine the length of the limb, while the examiner extended the length by
moving his finger down the existing limb and then beyond the stump. The
reports are not those of a fully developed limb and the children generally
indicated only transitory perceptions. Whether the Weinstein-Sersen account
may be accepted as equivocal to those experiences of phantoms found after

amputations remains for definition and verification by others.
With growth of the individual in size and shape, and with evolving
capacities for intricate motor activities, the body-image is continuously
modified. The progressively developed images of the body and the body parts
remain as memory traces within the nervous system and reappear in states of
neurological dissolution or psychological regression, as clinical observations
have demonstrated. Thus in his therapeutics with hypnosis, Halpern has
focused on the repressed developmental aspect of the body-image. His clinical
reports disclose the reemergence of transactional sequences between parents
and child under hypnosis that establish and modify the body concept, and
which carry the conflict situations between the growing child and parental
figures. Peto, too, has noted the fantasies of bodily fusion of patient and
analyst into an amorphous mass during deeply regressive transference states

in the second or third year of psychoanalytic psychotherapy of patients with
previous acute psychosis. He interprets these experiences as regressions to
the earliest stages of archaic thinking when the individual often experiences
his body as fused with the body of the parent.
In addition to the modifications resulting from developmental and

sensory influences, the character or quality of the body-image is also a
function of the socialization experiences of the individual. The socially
determined qualities commence to appear with the earliest experiences of the

individual in relation to the significant person in his family or home
environment. The child acquires social percepts, attitudes, and affects toward
his body and its various parts, culminating from his interaction with his
parents and members of his family as they represent the molding forces of the
culture. The attitudes of parents impart an indelible impression on the child’s
concept of himself, his body, and its function. Depending on the experience
with the parents, the body and body parts may be conceived as good or bad,
pleasing or repulsive, clean or dirty, loved or disliked.
Among some families as well as some cultures, certain aspects of body
development tend to be prized, while others are derogated. In general, these
attitudes are related to the sex of the individual. Strength and prowess may be
emphasized in boys and men, with a major investment in the development of
strong limbs and muscles. In a similar manner, the parents and the culture
may emphasize the aspects of the body-image which are regarded as qualities
of beauty for girls. Apart from these sexually defined values, there are also
specific body parts which may be deemphasized for both sexes. This de-
emphasis can manifest itself in concealment by clothing; denial through
prohibitions of exposure, touch, or examination; absence of verbal

communication (except in jokes); and outspoken derogation of certain body
features.
Attitudes toward the body also derive from the individual’s perceptions,
comparisons, and identifications with the bodies of other persons. Usually,
children who are accepted by and conform to their family and cultural
expectations, neither over- nor under-evaluate their body. Derogatory

attitudes with over-compensatory mechanisms frequently develop to obscure
either actual or fantasied body defects when the child feels, or is made to feel,
that his body fails to meet the expectations of those about him. Where
families tend to exploit the significance of body functioning and appearance,
overevaluation and reliance upon security through bodily beauty or activity
inevitably follow. Should there be a disruption of the body-image, persons
with such security reliance are less able to adapt and are thus more
susceptible to emotional disturbances.
Insofar as knowledge of the surface of the body and its parts is

concerned, the individual has many sources upon which to draw. Early, and
relatively easily and quickly, he gains a concept of the orifices, including the
mouth, the nose, the ears, anus, and urethra. In contrast, knowledge of the
internal organs is gained from sensations of discomfort. These sensations
may be displaced to the contiguous body surface, referred over related
surface segmental impressions, or transferred to the surface through the

mechanism of segmental pain. The incorporation of internal organs into the
body-image is customarily vague, except when a sense of pain or discomfort
is referred to the surface. Exploration of the body serves as the focus for
establishing language and thought, spatial orientation in differentiation of
laterality (left-right), and enumeration. As has been noted many times,

confusion may ensue in development and reemerge in periods of personality
disturbance in terms of word usage and their symbolic meaning as referrants

to the body. Hirsch has reported on a series of psychotic patients who
equated in their illness those parts of their personality identified as “bad”
with the left side of the body—the “unconscious side” as against the
“accepted” or “good” parts, as reflected in the right. This kind of valued
differentiation of left-right in the body-image has a long cultural heritage. Its
reemergence in psychosis indicates the fluidity of ego organization—a failure

to conceive the body as a whole. The influence of body knowledge and
awareness on language and usage of words referring to the body is shown in
such studies as that of Wright, who analyzed the names of parts of the body
that occur most in literature, and found a correspondence between the ratio
of frequency of body parts as compared with the ratio of distribution of
sensorimotor cortical representation of the same parts. He came to the
conclusion that the linguistic importance of the name of the body part was
related to the extent of sensorimotor experiencing of the part. In Bennett’s
study, groups of sighted, blind, and schizophrenic subjects were requested to

list spontaneously names of parts of the body, as well as other categories of
names as a means of examining their body concept. Both sighted and blind
subjects list the same parts preferentially in the following order: The sighted
list arm, leg, head, fist, hand, finger, eye, neck, ear, nose, toe, and chest. The
blind give the same listing except neck which is replaced in order by mouth
and they add heart and stomach. The schizophrenic responses were very
similar to those of normals excepting that ankle occurred less frequently.
Bennett concludes from his direct approach to body naming by men, in
contrast to Wright’s study of word usage—as derived from a study of word
frequencies as listed in books—that his findings would not substantiate the
Wright correlation with sensorimotor representation. Thus he emphasized
that one might not explain the differences in responding between sighted and
blind regarding the occurrence of nose and eye as the parts first listed by the
blind, while they are less frequently mentioned by the sighted. One may argue
instead that the frequency of linguistic preference represents rather the
result of the social transactional process as it concerns the body in the

interface between the developing child and parents or their substitutes.
Szasz suggested an extension of the concept of the body-image or, as he
calls it, the ego-body integration, to include not only the percepts, affects, and
attitudes experienced historically in the life of the individual but also body
parts which occur in fantasy as wish-fulfillment in defensive operations of the
ego. Thus, Szasz, in broadening the concept of the perceptive ego to the
expressive, would include penis-envy in females, castration in men, fetishism,

and transvestism. In the case of the transvestite, he is seen as creating, with
the aid of garments, a materialization of female phantom parts and an image

of the body to which the ego clings.
In evaluating Szasz’s concept from the standpoint of human experience,
the writer holds that the expression of a phantom part is of a different quality
and order than that expressed in a wished-for and envied missing body part
that has never been experienced in reality. Persons who have not experienced
the existence of a limb do not seem to have the capacity for consciously
experiencing the existence of a phantom, even though they may wish for a
limb. There is a basic physiological substratum imposed upon the cerebral
cortex as the result of perceptual experience which allows development of

quality of experience over and beyond that observed in the case of ego-
adaptive wish-fulfillments. In line with this rationale, the writer is discussing
only those disturbances of the body-image which are derived from actually
perceived body parts in this chapter. Disturbances representative of partial

ego-adaptive mechanisms are discussed by other contributors.
Physiology of the Body-Image
From a neurophysiological standpoint, the postural model of the body is
maintained through integrations of spinal neural activity and those of higher

cerebral levels. That modification of peripheral sensory activity may influence
the subjective appreciation of the body-image is shown by the following
observations. Souques and Poisot found that cocainization of the peripheral
nerves leads to temporary disappearance of a phantom extremity. Schilder

states that Gallinek and
Forster had success in removing a phantom by peripheral changes, and
also that Adler and Hoff noted diminished perception of the phantom with
application of ethlyl chloride to the stump. Head has described the
disappearance of the phantom limb following a cerebral operation. De
Gutierrez-Mahoney and Echols reported abolition of a painful phantom by
surgical excision of the posterior central gyrus. De Gutierrez-Mahoney found,
on follow-up studies, that the original impression of abolition of the pain or

phantom did not hold. In their study, Appenzeller and Bicknell indicate that
spinal-cord lesions may alter phantom sensations and at least temporarily
abolish some. Centralateral parietal-lobe lesions with accompanying sensory
defects may lead to permanent disappearance of the phantom experience.

Yet, their study is incomplete in that neither the extent of the cerebral
impairment is known, nor the length of follow-up of patients claiming
complete disappearance of the phantom. Kolb observed three patients after

removal of the somatosensory cerebral cortex done in an attempt to eradicate
a painful phantom extremity. The phantom was not lost, but it became less
vivid. He also observed that there are no significant modifications in phantom
percepts following explorations of the stump with removal of terminal

neuromata, or with rhizotomies, sympathectomies, cordotomies, injections of
alcohol into neuromata, paravertebral anesthetic blocks of the sympathetic

ganglia, spinal anesthesias, and prefrontal lobotomy.
The body-image is, as Schilder so properly inferred, integrated in the

parietotemporal areas of the cerebral cortex. Pool and Bridges have reported
that unilateral surgical ablation or cortical undercutting of the parietal lobe
does not destroy phantom percepts. From his study of patients with
hemiplegic anosognosia, allachesthesia, and various aphasias, Anastasopoulos
concludes that the right parietal lobe is the major cortical area for corporeal
representation. However, it would, seem that imperception of the body occurs

only in those with bilateral cerebral vascular lesions that have led to
extensive cortical damage. Cook and Druckemiller have suggested that the
body-image is represented in the cortex as the function of a widespread

neural network in the postrolandic area. This network, they postulate, may be
activated by stimuli from the periphery or centrally from other areas of the
brain when the individual turns attention on problems of body functioning or
is actively motile.
Fisher and Cleveland suggested from their studies that, when the
individual ascribes definitive boundaries to his body, this correlates with the
relative reactivity of his body exterior to his body interior. Using the galvanic
skin resistance (GSR) as a measure of reactivity, it was found that when the
individual ascribed greater strength to his right versus his left side—or vice
versa—there exists a variability in the relative GSR. So, too, when the head
area is perceived by the individual as of large magnitude, it is characterized
by a relatively lower skin resistance than the non-head area. When adjudged
to be small it has a higher skin resistance relatively to other parts of the body.
This work remains unconfirmed. Its explanation in terms of integration at
cortical levels of brain functioning remains unknown.
Family and Cultural Attitudes Affecting the Body-Image
Genetic and intrauterine processes and those later accidents of life in
the form of traumatic or surgical experiences determine the bodily structure

adapted to and perceived by the ego. From this ongoing interaction between
perceived body and perceiving ego, consciously and unconsciously, there
arise percepts, attitudes, and affects leading to adaptations of the body-image.
Social psychologists have advanced the hypothesis, supported by
investigations, that when one’s evaluation of a personal trait is unclearly
defined he will depend to a large extent on the opinion given him as to that
trait by “significant others.” In the studies of Kipnis, her subjects perceived
smaller differences between themselves and their friends than between
themselves and a least-liked roommate. When her subjects perceived their

best friends as relatively unlike themselves, they were more inclined to
change their self-evaluations than those who perceive their best friends to be
like themselves. When the subjects perceived their best friends as having
positive personality traits they tended to modify their self-evaluations in a

positive direction. The opposite was true when the best friend was perceived
as possessing negative traits. But when her subjects perceived more negative
traits in their best friend than in themselves they broke off their relationships
more frequently than when the friend was perceived as having more positive
traits.
These findings probably bear upon the attitudinal set which confront
those with obvious body deformity. The deformities bear upon the attitudes
of those who relate to the deformed which, in turn, influence the development
of body concept by the deformed and mutilated. Recent experimental studies

support these contentions. Centers and Centers analyzed the responses to
questionnaire studies of groups of children and report that the presence of
amputation represents a threat to the bodily integrity of the nonamputee.
This reflects in his greater tendency to reject amputee children rather than
nonamputees.
Gilder et al., examined the responses of a group of amputees and
nonamputees when viewing the normal and amputated human figure through
the distortions produced by wearing aniseikonic lenses. Generally, the change
reported was that of less distortion as if the viewer unconsciously wished to

deny the mutilation.
Gross deformities, such as aplasias, lend themselves to the development

of body-image concepts at both the physiological and psychological levels of
integration, which differ from that where there have been less serious
disturbances of the body structure. The body-image of the blind, the deaf, and
persons with other dysplasias has been less well studied than that of
individuals who have acquired deformities as a consequence of illness,
trauma, and surgical procedures.
For the most part, the influence of family attitudes on the development
of disturbed body-images has been neglected in study and practice. In point of
fact, however, the capacity for a satisfactory social adaptation among those
with bodily defects depends more upon the family and cultural attitudes
toward body structures than upon the presence of defect. When the family or
social attitude toward serious body defect is constructive and supportive,
there is greater possibility for successful compensatory development without

personality disorder. In the family with healthy attitudes the defect is
accepted, and personality development is directed by the parents along lines
where other assets can be developed and strengthened. By these means the
afflicted can obtain a kind of satisfaction which, to a degree, compensates for
the effects of the inadequacy of the body-image. MacGregor et al., have
summarized much of the existing knowledge concerning family patterns that
contribute to a healthy and satisfying body-image concept.
The attitude of society toward physical disfigurement is generally that
of disapproval, repulsion, and rejection. The deformed child is rejected on

grounds that his deformities are due to “sins of the fathers,” “punishment for
wrongdoing,” “incestuous parentage,” etc. These myths and conceptions exist
not only among the ignorant or uneducated but also among the well-educated
and highly intelligent. Adoption agencies report that it is difficult to place
children with deformities. For this reason, it is not an uncommon practice for
agencies to offer disfigured children to people who would otherwise not be

considered suitable as adoptive parents. But even under these circumstances,
the agencies report that they have difficulty in finding adoptive parents for
children with physical disfigurement.
The use and misuse of superstitious rationalizations regarding
deformity have a psychological value in that they provide a means for
expressing and projecting an individual’s own conflict and fear about
deformity in his body. In the case of the parents, the acceptance of these
unsound and unrealistic values provides a means or an excuse to project the

blame for the deformity onto another source, to strengthen their existing guilt
feelings, or to support hostile or rejecting attitudes toward those whose
appearance is different.
Despite evidence of social, vocational, and intellectual competency, the
deformed are exposed to a kind of stereotyping which is socially
disadvantageous. Pervasive as these attitudes are, there is a reality basis for

the high concern manifested by patients with physical deformities. As a rule,
the type rather than the severity of the deviation evokes the stereotyped
responses. A receding chin is often associated with weakness or effeminacy. A
large nose may assign its possessor to a minority group. Persons with
protuberant ears, knock-knees, or pigeon toes are frequently ridiculed or
become the butt of jokes and hostile humor. Some facial configurations
precipitate immediate typing as a moron, gangster, drug addict, or sufferer of

some serious disease. On the other hand, certain physical deformities carry a
degree of social prestige, as the broken nose of a prize fighter or the scar
resulting from a war injury.
With the birth of a deformed child, the mother usually responds with
mixed feelings of humiliation, sadness, guilt, or depression. A small group of
mothers consciously fail to see the defect as being as serious as other family
members and the physician do. While this minority of mothers will have
feelings of protectiveness toward their deformed children, they will also feel
jealous toward other mothers with healthy babies. Comments about her
baby’s defect tend to increase the mother’s sensitivity.
MacGregor et al., in their study of persons with facial deformities, point

out that the attitude of the mother varies according to the sex of the child
with the defect. These investigators noted that overemphasis on physical
beauty by mothers led to maladjustment in daughters. The facial defect of the

female child was seen as producing feelings of rejection, hostility, or guilt in
the mothers. As pointed out in this study, boys born with facial deformities
were less likely to suffer from such maternal attitudes. It appears that the
mothers and the culture as a whole did not make a strong connection
between the idea of beauty and the equally desirable idea of “masculinity.”
The attitude of the mother toward the defective body of the child is
strongly influenced by her perception of the attitude of the husband-father.
As a rule, if his response is sympathetic and positive, she finds it easier to
accept the disfigurement. However, in some cases, mothers are less anxious
about the child if the husbands show more distress than they do. In other
cases, the guilt feelings of the mother may become magnified when the father
blames her for the defect and when she has reason to believe that there is a
basis for the accusation.
If the mother has a realistic awareness of the importance of physical
appearance but does not exaggerate this value to the exclusion of all other
assets, it is possible for her to accept the disfigured child. In such instances,
and with the help of teachers and friends, the mother can be instrumental in
helping the child to compensate through good manners, gracefulness, careful

grooming, and attractive clothing. The usefulness of encouraging
compensating personality traits depends, however, on the genuine
acceptance of the child by both parents. Otherwise, parental urgings of

compensatory behavior can aggravate or increase feelings of inadequacy in
the deformed.
In a study of children with excessive body sensitivity but without
particular deformity, Levy found that the specially conducive factors were
parental oversolicitude, histories of significant illnesses and injuries in the
past, exposure to sick persons or frequent discussions of illness, bodily
variations differing significantly from that of peers, and special bodily values
of the group subculture. Parental solicitude leading to excessive bodily
concern in the child was secondary to a variety of conditions in the life of the
parents. For the mother particularly, marital conflict, death of the father,
difficulty with the spouse’s parents or family, absence of neighbors, and
narrow emotional outlets tended to cause her to focus her interest on the
child. To compound this difficulty, the interest carried with it displaced

hostility, and also destructive drives and the reaction-formation of protection.
In sum, parental exploitation of the child to resolve emotional conflicts or
satisfy ambitions, parental ignorance or immaturity linked with vacillatory

overprotection, the death or deformity of siblings, miscarriage and stillbirths,
and other special concerns resulting from personal experience served to
sensitize the protective parent.
Observations of family life indicate that the deformed child does not
receive the same treatment as the other children of the family. The afflicted
child is usually treated either with greater consideration or with less approval
and warmth, and sometimes even with outright hostility. The responses of
the siblings are not necessarily the same as those of the mother to the child. In
families where mothers reject the deformed child, the siblings may
compensate by providing friendship and help to the child with a defective
body. In some other families, the siblings will treat the defective child with
outspoken impatience and resentment. Observations suggest that mothers
and siblings have less pathogenic attitudes toward children who are
accidentally deformed than to children born with a congenital defect; there

also appears to be less likelihood of guilt reaction, resentment, and hostility
on the part of the mothers.
Emulating the rejecting attitudes of their families and society, most
patients with body defects manifest unhealthy attitudes and behavior in
relation to their bodies. The majority of children are unwilling to look into
mirrors, dread making trips away from home, and try to slip into comers and
hide their faces from public view. Contacts at school with other children, who
may jeer or ridicule them, often result in the deformed child’s returning home
in tears or sulking. In small children the ridicule may not at first be
understood, but, once it is within the child’s comprehension, it can lead to his
avoidance of other children. Frequently, a deformed child will persist in
questioning the parents as to why he is different and why he is the only one in
the family who is different. Some children attempt to diminish the importance
of the deformity by joking about it, while still others studiously avoid
mentioning the subject. In every instance, however, these types of behavior
are related to the parents’ behavior and attitudes concerning the deformity.
The parental attitude is a composite of the parental health and
acceptance, and particularly that of the mothers. Some mothers attempt to
protect their deformed children from hardship by insistence on their avoiding

any activity where they might be questioned. The consequence of this
isolation is that both relatives and strangers are kept from contact with the
child. Another type of mother attempts to hide the defect by requiring the
child to wear certain concealing clothing or to assume certain postures. In the

reports of these instances, the mothers failed to recognize that this hiding was
also their effort at withdrawal, although they did mention feelings of anxiety
in the presence of strangers. In studying the children who deny the existence
of the body defect, it has been found that their mothers attempt to deny
anxiety by insistence on exposure of the child to strangers, relatives, and
others. The mothers themselves are reluctant to make personal contacts or to

discuss the disfigurement. When the subject of disfigurement arises in
conversations, parents holding these attitudes tend to minimize their
concern. Still another group of mothers compensate for their belief that the
children are stigmatized by using the mechanism of “undoing.” Here the

deformity is spoken of as “cute,” and a lack of personal concern is stressed. It
is noted in these circumstances that the presence of strangers does not
produce feelings of discomfort, but discussion of the defects does.
Differences between healthy and unhealthy attitudes of mothers have

been comprehensively discussed by MacGregor et al. Healthy mothers do not
consider disfigurement as a stigma or punishment for their own behavior.
They do not hide concern, and they are able to seek advice from professional
persons and their acquaintances. In contrast, mothers whose behavior fits the
child’s pattern of “avoidance” are likely to become angry when the child fails
to follow instructions to conceal the deformity. Such mothers regularly react
by blaming the child when the child complains of discrimination. While the
denying mother may allow the child with a defect a greater degree of
freedom, his complaints of the attitudes of others usually meet with her
rejection. She is inclined to “brush him off” with statements that he should
learn “not to concentrate on the defect.” Those mothers who “undo” the
defect attempt to have the child develop a sense of distinction, which leads to
impairment of reality sense.
The foregoing description of specific interaction between mother and
child in relation to body structure provides the matrix from which the body-
image and consequent ego attitudes and adaptation to the body-image arise.
This knowledge, derived from studies of family instruction with deformed
children, may well apply to children who later show body-image disturbances
in the context of schizophrenic and psychosomatic conditions. Unfortunately,
detailed studies are not available on the family patterning that leads to body-
image disturbance under these conditions, information which is very likely
crucial to understanding the personality character of the schizophrenic,
whose conviction of bodily ugliness is a well-known clinical phenomenon.

This knowledge is essential to formulating rational methods of prevention
and treatment of the body-image disturbance.
Special Examinations for Body-Image Disturbance
Attitudes toward the body and its parts may be elicited, and ego
adaptations to such attitudes may be inferred from the data provided in the
course of the psychiatric anamnesis and examination. While the usual
examinations and techniques underemphasize this aspect of personality,
procedures are now available which may be used to assess the body-ego
integration. These techniques include modifications of the regular diagnostic
examination, new rating scales for measuring and appraising body cathexis,
projective techniques, and specific perceptual tests.
Years ago, Levy suggested a method of integrating physical and
psychiatric examinations for children. The child, at the termination of an

ordinary physical examination and while still undressed, is asked to play the
role of physician and examine his own body. The physician asks him to
comment on what he has noticed about the various parts of his body,
observable differences between himself and others, and preferences as to
how he would like to see his body parts when he is grown. In addition to
these questions, inquiry is made regarding ideas and feelings about the
importance or lack of importance of height, weight, strength, and appearance.

Reporting on his study, Levy noted marked discrepancies between children’s
attitudes toward the various body parts and their actual physical structure.
The visible mouth area produced the most frequent number of responses.
Eyes and hair produced frequent responses from both boys and girls. On the
other hand, mammary and genital responses were more evident in boys than
in girls, a finding related by Levy to the fact that there is no censor of boys in
exposing these parts to nakedness. Children showing a sensitivity to

secondary sexual traits appeared to have many doubts as to their sexual
identity. Individual points of body sensitivity were displaced to other parts of
the body by some children. Jacobson also suggested a method of evaluation.
Secord and Jourard developed a rating scale as a means of appraising

body cathexis. Secord also devised a word-association test utilizing
homonyms as a means of investigating bodily concern. Secord’s test

discriminates three groups of individuals relative to body concern: (1) the
narcissistics who overvalue and overprotect the body because of its intrinsic
personal value; (2) anxious persons who register bodily concern owing to
physical pain, injury, or shame; and (3) overcontrolled individuals who
apparently rid themselves of body concern through denial. The first two
groups in the Secord test gave numerous responses on the word-association
test, in contrast with the few responses by the third group. Using two tests,
the body-cathexis scale and the word association, Secord found that the
narcissistic group scored high for body acceptance and high on the word
association.
The scores of those with high anxiety were low on body acceptance and
high on word association. Overcontrolled persons scored low on both tests.
Hunt and Feldman used both the body cathexis scale of Secord and Jourard,
and the Draw-a-Person test to study the responses of a group of male and
female psychology students. In general, they confirmed earlier findings that
women cathected their bodies more highly than men as they showed greater
variability in both reporting satisfaction and dissatisfaction. The group as a
whole reported more favorable responses to their bodies as perceived in the
present as against earlier in adolescence.
Machover described the Draw-a-Person test, a projective technique
which elicits unconscious attitudes and percepts of the body-image. Using this
test or its modification (the Man-Woman-and-Child test), Noble et al., Kolb,

and Wille found that some limb amputees include amputated extremities in
their drawings. It has not been determined whether the amputated percept
might have existed prior to amputation, nor is it known whether all amputees
provide such mutilated percepts and, if this is not the case, the factors that
differentiate this group from those who fail to do so.
Using the Draw-a-Person test with crippled children, Wysocki and
Whitney found that they express more aggression in their drawings than do
noncrippled children. In expressing their aggression through the medium of
this test the crippled showed a variable intensity of aggression according to

the area of insult.
Centers and Centers, using the same test to study the responses of
amputee children, found that the majority represented themselves
realistically, omitting the missing limb or including a prosthetic device. The
majority then, as might be predicted, do not present in their responses to this
test evidence of greater anxiety or conflict. Yet in this study, the Self-Portrait
Draw-a-Person distinguishes the amputee child from the nonamputee. The
amputee children more often drew self-portraits with absence of one or both
hands. Also, they showed a tendency to incorporate more detail in their self-
portraits than nonamputee children. While the hypothesis of the investigators
is not supported by their studies, it seems evident that the projection of the
body percept in drawing differs in amputee from nonamputee children.
Studies of figure drawings of patients with paralytic poliomyelitis by
Johnson show that this group draws significantly smaller figures than control
groups of nondisabled recovered poliomyelitics. Neither group represented
their defects isomorphically, although both groups drew less distortions in
upper than lower extremities. As in poliomyelitis, there occurs a loss of
muscle function in the absence of loss of sensation in a part of the body;
changes in the body image should offer a contrast to those following cord
transections or amputations. In a study by Wachs and Zaks, paraplegics
tended to draw figures larger than a matched control.
Figure drawings similar to Machover’s have been used by Abel in
studying patients with such facial disfigurements as congenital absence of
ears, harelips, absence of the nose, scarring from burns, oversized nose, or the
sequelae of facial cancers and surgical interventions. Abel has found same-sex
drawings to be especially productive of information supplied by the patient.
Severely disfigured persons seeking corrective (plastic) surgery portrayed

their problem fully in the same-sex drawing. The mildly disfigured were less
likely to do so. The projections of the face in the drawings have been
categorized by Abel into the following four groups: (1) specific portrayal of
the individual’s disfigurement; (2) distortion of the disfigurement (a large

nose for a small nose); (3) omission of all features of the face; and (4) a face
with features but without disfigurement.
While Corah and Corah did not discover overt portrayal of the cleft lip
or palate deformity in their studies of figure drawings of a small group of
children with these deformities, they do report a significant difference in the
scores of these children on an index-discrepancy score, that is the Binet
mental-age. Their study did not support the hypothesis that physical
handicaps will be represented often in figure drawings. The question requires

restatement and restudy.
Fisher and Cleveland have utilized the Rorschach test in relating a single
dimension of body-image concern with the manner in which the individual
sees his body damage.
Thus they correlated personal concept of boundary definiteness with
the responses to the individual’s percepts to the Rorschach inkblot stimuli.
Typical responses considered to equate with expression of definite body-
image boundary were: “cave with rocky walls, man in armor, animal with
striped skin, turtle with shell, mummy wrapped up, woman in fancy costume.”
Such responses, they labeled “barrier responses.” They also defined a second
boundary index termed the “penetration response” and scored by reported

verbal response to the ink blots which were interpreted as emphasizing
weakness, lack of substance, or penetrability of persons and objects. Here
typical verbal responses were “mashed bug, person bleeding, broken body,
torn coat, body seen through a flouroscope.” The method of interpreting
verbally reported percepts and quantitation scoring are given in detail in

their book, Body-image and Personality. The barrier-response score seems not
to change with time in individuals; the penetration response score correlates
more with change.
Patients with rheumatoid arthritis, neurodermatitis, and conversion
symptoms involving muscular functions were found to have barrier scores
higher than those with gastric ulcers or spastic colitis. So, too, those with high
barrier scores seem predictable to adapt more effectively to body

disablement, to maintain ego integration and to communicate well in small
group settings. Roughly, the scores appear to distinguish between several
groups with psychopathology. Schizophrenics have higher barrier and lower
penetration scores while neurotics have lower barrier and increased
penetration scores.
As Fisher mentions, others have questioned his assumptions that these
scores represent measures of body-image and suggest instead that they are
indicative of cognitive or perceptual operations. However, as suggested
earlier, such operations have their beginnings in the developmental processes

connected with exploration of one’s body. To achieve clinical validity and
usefulness, more work must be done to verify and amplify the hypotheses and
findings of Fisher and co-workers. Others have failed to replicate these

correlations. Bard has utilized psychological tests to predict psychogenic
invalidism following radical mastectomy.
Hunt and Weber have devised a Body-image Projective Test in which
varying anterior and lateral silhouettes of the female body are presented in
booklet form to women who are requested to respond to questions as they
view each silhouette in turn: “What looks most like me? What I would least
like to look like? What would I most like to look like?”
Perception, as related to the postural image of the body, has been
studied intensively by Asch and Witkin. In this work, subjects were placed in
a small, tilted room and were instructed to adjust a rod, presented on the
back wall, to the true upright. Judgments were obtained with the body of the
subject upright and with the body tilted. Striking individual differences were
found in the extent to which the perceived upright is affected by the
surrounding tilted field. Individual consistency was considerable. Witkin is
continuing these studies.
Bender’s studies of double simultaneous stimulation of nonsymmetrical
areas of the body provide a special technique of examining perception of the
body-image.
During double simultaneous stimulation of the face and another part of
the body, the facial stimulation is not only invariably reported but is
consistently dominant to all other body parts. The genital region is only
slightly less dominant, with the hand the least, and other body areas falling in
between. Normal persons who make frequent errors in initial trials of
reporting double stimulations tend to correct errors. Persons with brain
disease and schizophrenics appear to modify their responses less readily.
Linn, utilizing Bender’s test in studying patients with organic brain disease,
suggests that the face-hand response is fused and the hand-touch response is
not discriminated verbally. Linn’s patients reported through nonverbal
gestures for the hand-touch test but gave oral responses in the face-touch
experiment. He concludes from these observations that the hand response is

not the result of extinction by more dominant face perceptions of body-image
but rather a nondiscriminated manifestation of fusion of the face-hand
response. Linn’s hypothesis is in keeping with what is known of the early
experiencing of the body by the developing perceptual ego. Pollack and

Goldfarb tested both institutionalized schizophrenic and nonschizophrenic
children with the Bender technique. They found that, by the age of seven, all
normal children perceive both face and hand stimuli within ten trials, while
the pattern of response of the schizophrenic children was significantly
different and more similar to that of younger children and those with mental
changes due to severe brain disease.
Orbach and co-workers devised a new instrument, an adjustable body
distorting mirror, as a means of determining objectively the individual’s

internalized picture of his physical appearance. The observer is requested to
adjust his reflection until it appears undistorted to himself. In their early
experiments using this device they discovered that a wide range of reflections
was acceptable to the various subjects as representing his body. Yet, when
subjects are shown a series of distorted and undistorted photographs of

themselves they accurately select that most approaching the true identity.
Each subject appears to need an external reference point for body
identification. Modifying the test to allow a series of judgments, they

discovered that judgments of one’s head and shoulders are most accurate and
consistent. Next in accuracy are judgments of the vertical halves of the body.
Least accurate are those of the legs and feet. It must be recognized that such
judgments are based on visual stimulation alone whereas the perceptual
image of the body—as mentioned earlier—is derived from kinesthetic and
tactile impairment.
A later study by Cardone and Olson, utilizing this device in examining
the responses of a schizophrenic population, disclosed that such patients

performed less accurately than healthy controls, but the patients seemed to
have, in addition to the defect in body perception, also a more general
perceptual impairment. Hemiplegics, too, have the latter defect but did not
disclose a body perceptual impairment.
Phantom Phenomena
The phantoms of amputated limbs, the first to be recognized, are also
the most frequently encountered, best understood, and best described. To a
lesser degree, phantoms also occur following removal of other body
protuberances such as the nose, eyes, teeth, nipples, penis, and the breasts of
women. Since the phantom is the expected healthy response following
sudden loss of a limb, a detailed account of this phenomenon is presented as a
means of describing the pathological reactions to limb mutilations.
The phantom limb or digit is almost a universal phenomenon following
amputation, having been reported in as many as 98 percent of cases. Ewalt
and his associates, studying 2284 amputees in an American Army hospital
during World War II, developed some significant data on the occurrence of
the painless phantom as compared with the painful phantom. Their report
shows that only eight patients of the total group complained of painful
phantom limb, whereas the remainder had a painless phantom. From 22 to 64

percent of women report breast phantoms following mastectomy, and Jarvis
discusses the variability in the frequency. Figures are not yet available as to
the frequency of observation of the phantom of other lost body appendages.
Riddoch, Henderson and Smyth, and Lhermitte, have provided excellent
descriptions of the characteristics of the phantom delusion. They point out
that the amputee is most aware of the distal portions of the phantom such as
the hand and foot. They also note that following amputation, the individual
initially perceives the phantom as consisting of the whole extremity.
Henderson and Smyth have characterized the sensory phenomena of the
phantom as consisting of three general types. The first is a mild, tingling
sensation, the basic phantom phenomenon, which is dependent upon the

function of the sensorimotor cerebral cortex. The second experience is a
stronger, momentary pins-and-needles sensation such as that felt in the
phantom when the neuromata in the stump are touched. This sensation is
apparently dependent on the functional activity of the lower spinal center.

The third type consists of certain superadded disagreeable or painful
sensations which are described as “twisting,” “burning,” “pulling,” “itching,” or
various other complaints couched in bizarre terms. These epiphenomena are

discussed in the excellent clinical reports of Bailey and Moersch. Frederiks
distinguishes usefully between the perception of the phantom limb per se and
phantom-limb sensations such as tingling, pain, or other sensory phenomena
occurring with the phantom. He emphasizes that phantom sensations do not

exist without the percept of the phantom part.
Most phantoms, regardless of type, are intermittent and more annoying

than agonizing. The introspective and observant amputee may notice
aggravation of the basic tingling sensation by stimulation of the stump. The

aggravation, when a leg has been lost, may also be occasioned by urination, by
changes in the weather, or by emotionally disturbing incidents.
Related to these general types of sensory phenomena, especially the
pins and needles, sensations referred to the phantom are most often elicited
by deep pressure on the amputation stump, less often with algesic skin
stimulation, and least by tactile stimulation. Erickson and his associates, have
demonstrated that similar sensations may be referred to the phantom by
stimulating the appropriate portion of the postcentral gyrus of the cerebral
cortex. Cohen and Jones have described pain of cardiac origin referred to the
phantom left arm. Cronholm has extensively studied the sensations referred
to the phantom by various stimuli applied to the amputation stump and skin
areas contiguous to the stump.
The phantom is experienced as a reality, the absent extremity
occasionally described as feeling swollen, numb, or tight. Following an acute
traumatic dismemberment, the amputee may forget his loss and fall as he
attempts to step on the foot which has been removed. It is not unusual to
obtain accounts of reflex movements in the missing extremity. The amputee
often describes volitional wiggling or movement of his fingers or toes and

flexion of the extremity—wrist or ankle. Weir Mitchell observed that the
conscious awareness of the phantom may be greater than that of the
contralateral intact limb. The patient, preserving an alignment of the phantom

with the stump, is likely to comment upon its capacity to penetrate solid
objects unaccompanied by any sensation of touching. Thus, a patient lying in
bed with a mid-thigh amputation may feel as though his phantom leg is flexed
at the knees and the lower part is penetrating the mattress without
experiencing contact with the mattress.
The phantom extremities existing after denervations of limbs, or
severance of the spinal cord, are similar in many respects to the phantoms
following limb dismemberment. Patients report that they perceive the
phantom extremity in positions other than those actually maintained by the
intact extremity. Occasionally, they speak of a reduplication of the phantom in
which one phantom coincides with the paralyzed limb and another coincides
with the limb in its healthy state. Reduplication is encountered most often in
patients with high cervical transverse lesions of the spinal cord or among
those with lesions in the cerebral hemispheres.
Differing from the phantom produced in the amputee, the phantom of
the paraplegic does not shrink away or telescope, provided the cord
transaction is complete. Also, in the paraplegic, the length and position of the
phantom usually remain unaltered by postural changes of the body or by
vasomotor stimulation. However, paraplegic patients do report volitional
movements of the phantom and occasional homolateral associated

movements. As Bors reports, the most frequently willed movement in the
paraplegic is in the anal sphincter.
The initial perception of the phantom becomes modified through
continuing experiences. With time, the patient comes to feel certain parts less
vividly than others. The faintly perceived parts tend to fade away, while
others persist with undiminished intensity. In the case of the extremities, the
parts which recede first are the upper arm and thighs. Next to disappear are
the lower arm and calf, and these are followed in turn by the joints and parts
of the hands and feet. Among the last to disappear are the toes, instep, and
heel, the lateral margin of the sole of the foot or the fingers, and the palm and
ulnar part of the hand. The great toe, the thumb, and the index and little
fingers are retained longest.
The phantom modification and dissolution take place over varying
periods of time and in some amputees are fully completed. The sequence of
the disappearing parts follows the well-known neurological homunculus as
represented in the sensorimotor cortex. It appears that those body areas

having the most cerebral representation are richly endowed with sensory
fibers that make for high sensory acuity and fine discrimination. On the motor
side, the areas have high innervation ratios and the capacity for discreet and
skilled movements. These highly innervated parts, dominantly perceived
through usage, have not only the longest phantom life but are also subject to
earliest exploration and stimulation.
Telescoping is another characteristic of the reorganization of the
phantom. As the distal portions of the phantom become conspicuous in
relation to the proximal segments, the position of the phantom hand or foot is
at first unchanged. The patient is unaware of empty spaces or gaps between
the stump and the well-perceived distal portions of the extremity. Then the
amputee experiences the emptiness of the inner space, and the persisting
phantom seems to become disconnected. Although it remains in its customary
place and position, it has no sensation of intervening segments. Subsequently,
the distal phantom hand or foot approaches the stump. In some patients the
distal segment of the phantom, once connected to the stump, fades away,
leaving only the toes or fingers, which may also disappear in time. In other
patients the phantom hand or foot may remain intact, but in these cases it is
gradually displaced into the stump, with the toes or fingers protruding.
Occasionally, the stump comes to enclose both the foot or the hand. It is
important to note again that the phantom extremity or portions of the
extremity may diminish in size. This' disconnection of the phantom size,

which is frequently overlooked, is only observed if the patient is requested to
compare the size of the phantom to the healthy foot.
The telescoping phenomenon is never complete. The phantom may be
restored to its former extent when the peripheral stump is stimulated by

pressure, as with the fitting of a prosthesis and during disturbances of
consciousness in the course of severe intercurrent illness. Jackson’s theories
of dissolution and restitution of function within the nervous system, following
either temporary or complete cessation of function of cortical or higher
segmental areas of the brain stem, provide insight into the basis of the
process. According to Jackson, a loss of the most recently acquired and most
highly organized function ensues, with a reemergence of more primitive
functions with later acquisition of new or reappearance of some of the lost
functions. Thus earlier infantile and childhood perceptions or the lost limb
are seen in the telescoping phenomena. As a whole, neurological theories lend
themselves to appropriate and satisfactory explanations of the reorganization
of the phantom parts representative of the postural model of the body.
Neither the psychoanalytic theory of wish-fulfillment nor gestalt psychology
succeeds in explaining the failure to experience the phantom extremities by
those who have an aplasia of the limb from birth or an early amputation.
In the case of an acute illness effecting loss of consciousness, there is a
reduction in the recently acquired modification of the body-image among

those patients in whom the phantom had disappeared. The more primitive,
intact body percept, which includes the phantom, reemerges. It is of interest
that a paraplegic patient with phantom does not experience telescoping
under these circumstances. With these patients the continuing optical image
of the intact extremities prevents reorganization of the body-image.
The life of the phantom has been variously reported to persist from a
period of a few months to as many as twenty or thirty years. While it is
common to hear that the usual phantom disappears within two years after
amputation, no firm evidence is available on the period of survival. It seems
probable that the failure to reorganize the body-image with disappearance of

the phantom extends over a much longer period than is usually thought.
Facial phantoms, following loss of the nose, eyes, teeth, and other
portions of the face, are less frequently reported. It is uncertain whether this
infrequency results from the attending physician’s failure to examine
completely because of psychological denial by the patient, or from
psychophysiological lack of organization of this area of the body. Hoffman
pointed out that the examination for the phantom of the facial organs should
be made in terms of the subjective perception of the function of the organ.

This is in accord with the description of the phantom eye of patients who
have lost an eye. They report scratching or itching sensations in the eyebrow,
expectancy of movements of the eyeball as though the eye were present, and
sometimes blinking of the phantom eye. Among patients having resections on
the nose, there may be a compulsion to touch or palpate the end of the nose.
Some data exist concerning facial phenomena relative to the eye, nose, and
eyebrows following radical maxillectomy with enucleation of the eyeball for

carcinoma of the maxillary sinus. Similar disturbances have been reported
after resection of the mandible for carcinoma.
In the last decade a number of studies have been conducted to ascertain
the frequency and mode of presentation of phantoms of the breast. Jarvis and
Simmel review the literature in this area and report extensively on their own
observations. Often perceived as a percept of the whole breast, or of the
nipple, many patients indicate the presence of the phantom principally in
sensations of itching and scratching, as heaviness, or as “full of milk.” Simmel
discovered that almost all women report a faint breast phantom when
requested to perform a sway test by leaning forward with closed eyes and
slowly swaying backward and forward. Their perception is episodic and less
realistic than that of the limb and is accentuated by menstruation and
changes in the weather. Anal-genital phantoms include those of the testicles,

penis, and rectum. There appears to be no direct correlation between the
occurrence of actual erection and the presence or absence of the flaccid or
erect penis phantom. In the paraplegic patient, Bors has reported that
phantom sensations of the bladder and rectum are more rare than the flaccid
and erect penis.
The infrequency of breast, penis, and testicle phantoms has been
ascribed by Gallinek to the lack of proprioceptive sensibility in immovable
organs. However, the fact that they occur occasionally makes this explanation
inadequate. Bressler’s comment that the breast is not integrated into the
primitive body-image of the female child in the early years of growth and that
full development occurs later seems especially pertinent. Moreover, it is not
unlikely that psychosocial and cultural attitudes toward the genital and pro-
creative organs contribute to the tendency to consciously deny the phantom
phenomena that follow their loss.
Internal organs, per se, are not represented in the body-image,

presumably as there is no sensing and exploration through the kinesthetic
and tactile systems and other sensory during development. When, however,
the individual endures pain in such organs over a prolonged period, as with a
gastric ulcer, or when through surgical or traumatic means a portion of the

organ is brought to the bodily surface, both perceptual and conceptual
experiences take place and come to represent that aspect of the organ in the
body-image. Dorpat reviewed the reports of phantom sensations of internal

organs at length. Druss, O’Connor, and Stern report the interesting series of
body-image changes noted in four women after iliostomy. These women all
wished to be men. Following surgery, the iliostomy was connected with

fantasies of acquiring a phallus in part fulfilling their wish and related to
behavioral changes of exhibitionism, increased aggressivity, and erotisation
of the stoma.
The effects of psychotomimetics, such as mescaline and n-lysergic acid
diethylamide (LSD), as they induce perceptual disturbance and modify the

phantom have not been elucidated. Zador has described changes in the size,
shape, and position of the limb phantoms of two amputees and of a patient
who was paralyzed by poliomyelitis. The latter developed a phantom of a
limb after an Esmarch bandage was applied. The writer and his associates
have conducted a series of experiments on an amputee who continued to

have pain in a phantom arm following resection of the contralateral posterior
central gyrus. In this study, 18 /μg of LSD administered intravenously
produced no change; 86 γ of LSD led to perception of more definite form; with
a larger dose (95 γ), the size of the phantom enlarged. Phantom pain was
unaffected in both trials with LSD.
Adaptation to Disturbance of the Body-Image
A series of emotional, perceptual, and psychosocial reactions are a
natural consequence of disturbance of the body-image. The nature of these

reactions determines whether the individual’s adaptation is healthy or
pathological. The existence of a phantom is the expected healthy response to
amputation of a limb or body part occurring after early childhood. Similarly,
patients who have undergone changes in body configuration as the

consequence of metabolic disorder frequently report bodily perceptions at
variance with those observed by the patient’s medical attendant and his
family. The reports of sudden changes in the body configuration which result
in personality disturbance are in part reactions to disturbance of the body-
image.
Whether a sudden change in the body-image results from a surgical

procedure or from a metabolic disorder, it always arouses anxiety in the
patient. The distortion of the customary body-image is experienced as a
distortion of the self. In instances of dismemberment, mourning for the loss of

the part, similar to that of separation from significant persons, is expected.
Further complications are introduced, with resulting anxiety, as the
disfigured person is threatened by fears of separation from and rejection by
the significant persons upon whom he is dependent. Feelings of hostility may

emerge toward these persons as part of the separation anxiety. The
perceptual life of the patient is disturbed as regards his unreal appreciation of
his own body and also his perceptions of other persons. Some amputees
report unusual sensitivity and discomfort upon seeing other amputees. The
extent of perceptual distortion among patients with body-image disturbance
is not known. The unconscious mental life of the patient is also modified by
the distortion of his body-image. The dream-life may become a wish-fulfilling
type in which the disfigured person sees himself performing activities in
which the lost part plays an active role. Repetitive dreams recapitulating the
incident that led to disfigurement are associated with the affect of anxiety.
A healthy adaptation may be measured by the patient’s willingness to

discuss his disfigurement, dismemberment, functional loss, and the phantom
and by his ability to accept offers of aid. With plastic surgery, eyeglasses,
hearing aids, dentures, and other aids to social and vocational rehabilitation
now widely available, the healthy person reacts by accepting his defect and
cooperating with those who can assist in readaptation. Usually, the limb
amputee is willing to accept the prosthesis. Similar attitudes normally obtain
among those who have lost an eye and require ocular prosthesis.
Psychopathological responses to the disturbance of the body-image are
manifested variously. Denial of disfigurement as a wish-fulfilling mechanism
to maintain the preexisting body-image is occasionally seen, as in the failure
to report the phantom after a limb amputation.
Simmel suggested that denial here represents more the conscious
suppression of the existence of the phantom experience. I would suggest,
however, that unconscious denial does exist as well and is evident in the
behavioral expressions suggesting the continuing wish-fulfillment for the
absent limb. Thus, one of the unconscious manifestations of denial is the

unwillingness to accept devices that aid rehabilitation. Scott has reported the
phenomenon of psychological denial in a manic patient (amputee) after a
suicidal attempt. The question of the frequency of the phantom phenomenon

and its significance as an indication of psychopathology will remain
undetermined until a more systematic study has been made of other than
limb amputees. The failure to report a phantom with absence of a body part
must be distinguished from conditions in which the body-image never
included the absent part, or where slow modification of the image took place
with progressive dismemberment, as in leprosy. The known causes for failure
to report a phantom with absence of a body part are: (1) aplasias of the part
(congenital defect); (2) amputations in infancy and early childhood; (3) loss
of internal organs; (4) slow dismemberments (nonsurgical) as in leprosy; and
(5) psychological denial.
The failure to reorganize the body-image over a period of time
subsequent to its distortion represents a psychopathological adaptation. This
maladaptation is frequent among those individuals in which the integrity of
the body-image, as it existed prior to illness or trauma, is overevaluated for
maintaining selfesteem. Limb amputees, in whom the presence of a limb

symbolized either masculinity or femininity, generally adapt poorly to limb
loss. Renneker and Cutler found that successfully married women with
children adapt easier and faster to the loss of the breast from mastectomy for
cancer than do those who have been unmarried or whose marriages have not
been successful.
Depressive reactions occur frequently as a result of the body

disfigurement. Psychodynamically, these reactions represent not only a
mourning for the loss of the part but have a relation to feelings of
overexpectation of rejection and fear of separation from those upon whom
the patient is dependent. Repression and introjection of hostile impulses
toward the significant persons are part of the reaction complex. Frank
paranoidal reactions are particularly apt to express themselves following
surgical procedures on patients with a selfderogatory body-image. As the

expectation of a satisfying social acceptance cannot possibly be met without
modification of the total personality of the neurotic patient, the hostile
expectation becomes focused upon the surgeon and any others involved in
the corrective procedure and toward whom the patient had built up feelings
of dependent hopefulness.
Complaint of pain in the phantom or in the area of the physical
disturbance may serve as a symbolic expression of the anxiety over the loss
and the threat to the individual’s dependency needs, as well as an expression

of a sadomasochistic identification, a depressive equivalent, and as a
substitute obsessional symptom. The writer has found in his study of
individuals with painful phantom limbs that 70 percent had lived in close
association with an amputee prior to their own loss (see Table 1). This
appears to demonstrate the high frequency of identification as a determinant

for this complaint.
As Kolb pointed out, the characterization of the limb amputee as a
terrifying and threatening individual is well expressed in English literature by

Melville’s Ahab, Stevenson’s Long John Silver, Barrie’s Captain Hook, and
Poe’s General A. B. C. Smith.
Table 33-1. Comparison of Affirmative Answers to Certain Questions as Given to

Amputees with Painful Phantom Limb* and Other Groups
GROUP PERSONS PERCENT RESPONDING “YES” TO QUESTIONS
QUESTIONED
1 2 3
Amputees 22 73 25 13
Healthy 100 20 8 8
Psychoneurotic 100 33 14 9
Psychotic 100 29 9 9
Legend: Each person interviewed was requested to answer “yes” or “no” to the following questions
numbered l, 2, and 3, as indicated in the table:
Question 1. Have you known intimately a person with an amputated limb (friend or member of family)?
Question 2. Was the person with the amputation a member of your own family?
Question 3. Have you lived with a person with an amputated limb?
* Without other physical lesions.
Fantasies of personal mutilation, usually repressed, may become

remobilized by the threat or actuality of trauma of surgical procedure. Many
patients with limb phantoms disclose terrifying and superstitious
rationalizations which they utilize to explain the existence of the phantom
limb. Magical thinking and fantasies concerning the mishandling of the
separated limb or about the nature of the phantom commonly serve a guilt-
allaying function. Patients with limb amputations frequently express a desire
to have the separated part disposed of tenderly and respectfully, as if it were
their whole body or that of a close family member. On some occasions they
may even fantasy arrangement for disposal of the limb. This behavior is less
likely where the illness causing the loss of the limb has been prolonged and
the mourning period has been worked through prior to separation.
Psychotic reactions involving distortions in body-image follow either
acute trauma or prolonged somatic disease. Bender, in particular, described
psychotic reactions in patients suffering Paget’s disease, osteogenesis
imperfecta, and dwarfism. The acromegalic presents a similar symptom
picture. In the slowly developing disease processes which distort the body
structure either directly or through interruption of the growth process,

discrepancy develops between the body-image of the sufferer and the
physical personality. As Bender indicates, the sufferer is made anxious by the

obscurity and mystery of the poorly understood disease process. Moreover,
the patient is thwarted in all his strivings, whether social, sexual, or

vocational, which were predetermined before the illness. In adolescents the
conflict over the idealized image and the fixed image ensues when the
developing body structure fails to conform to the wished-for or ideal image.
For adults suffering any of the somatic disorders described above, the body-
image distortion by illness requires the difficult adaptation from a level of
established satisfaction to one of ill-understood acceptance and
accomplishment. Bychowski and Eickhoff reported specifically upon the
body-image disturbances in adult schizophrenics; Pollack and Goldfarb have

studied the image in the institutionalized schizophrenic child. Kolb contrasts
the body-image of the schizophrenic and of the narcissistic in his discussion
of responses to amputation and emphasizes, too, the often-overlooked

delusions of ugliness represented in the body concept of the schizophrenic.
Harris initiated work on the perceptual responsivity of the same nosological
group to body drawings and word representation of self.
Simmel studied extensively the body-image of the elderly, those with
leprosy and the mental defective. With regard to the leprous, Simmel’s report
is of particular importance as she found that those who lost fingers or toes
through absorption—that is, gradually—never developed phantoms.
However, if that same limb were then amputated for some cosmetic or
prosthetic reason, a full phantom emerged. Bender examined the body-image
disturbance in the brain-damaged, Schontz in those with hemiplegia.
Pazat describes the tinnitus after amputation of the auditory field by

sonic traumatism as an expression of phantom in sensory area. Blank has
written at length on the adaptive problems of those blinded, and a number of

articles have appeared discussing the problems of children and adolescents
with congenital abnormalities and/or amputations (see references 2, 38, 114,
131, and 134).
While not specifically concerned with body-image, the general
responses to disfigurement are considered by Dembo et al.; to plastic surgery
by Updergraff and Menninger; to hare lip and cleft palate by Brophy; to the
face by Baker and Smith, MacGregor et al., and Meerloo; to radical

maxillectomy by Hoffman; to rhinoplasty by Linn and Goldman; to
mastectomy by Renneker and Cutler; and to genitalia by Heusner.
Prognosis
Since body-image disturbances may occur within the context of any

personality structure, only general statements may be made in regard to
prognosis. The outcome of this form of personality disorder is basically
dependent on the meaning of the bodily defect to the individual. The extent
and disabling nature of the defect and the availability of rehabilitative
services have a meaning to the patient which exists, as Kubie emphasizes, on
several levels of psychological functioning, i.e., the reality level, the level of
conscious fantasy, and that of unconscious symbolic fantasy. Depending upon

the individual, the loss may have any meaning, such as a heroic sacrifice or a
deserved punishment, a realization of helplessness and vulnerability, a
conviction of loathsomeness, a despicable mutilation to be hidden or
accepted, or a rejection of the part with defiance toward society and social
customs. The meaning may be determined only through the psychiatric study
of the individual.
A productive and satisfying social existence depends on acceptance of
the changed body structure and the eventual establishment of a new body-
image. The need for psychiatric treatment is evident in order to modify

pathological and unconscious meanings of the change in the body structure
which tend to perpetuate motivations that impede maximum recovery. But
this treatment alone may be ineffective if it is not coupled with the skilled
help of prosthetic experts and evaluation of vocational counselors. For some
patients the attitude of responsible relatives and the local society may finally
decide their success or failure in readapting to productive living. In these

circumstances, educational programs designed to avoid cultural stereotyping
and rejection relative to one or another disability are necessary. Attempts to
predict psychogenic invalidism as a consequence of the disturbance of the

body-image have been made by Bard in relation to mastectomy, MacGregor
and Schaffner in relation to nasal plastic operations, and Fisher and Cleveland
in relation to amputation.
Treatment
Prevention of body-image disturbance includes all those measures
designed to avoid genetic and constitutional defects in bodily development.
Consideration extends also to the role of industry and society generally in
protecting the individual against accidental trauma. The individual’s own
psychological capacity for protecting himself against accidental injuries is

certainly a preventive to the development of the body-image disorders.
However, not only is the current state of knowledge in this area inadequate,
but what is known is ineffectively applied or implemented by our present
social structure.
Various means exist of strengthening the body-image and thereby
enhancing ego functioning and self-esteem. They reside in the use of all those
therapeutic procedures which allow for increased facility in use of the body
musculature as in athletic games, dance, and posture as well as the correction

of bodily defects through surgery, and cosmetic and rehabilitative efforts. It is
important to conceptualize their treatment as ego enhancing—thus placing
their prescriptions to the forefront in the therapeutic management of all

patients suffering personality disorders associated with body-image
disturbance. Goertzel et al. have written specifically on dance therapy in this

context.
In the instance of the individual confronted with an elective surgical
procedure known to produce deformity, the psychiatrist and his medical and
nursing colleagues may aid in the prevention of serious disturbance through
proper use of the knowledge at hand. For those undergoing amputations or
exposure to medications which produce body-image disruption, the
preventive effects of proper preparation include advice as to the variety of
body changes that may occur. In the case of amputation, the patient should be
made aware of the occurrence of the phantom. Considerate inquiry into the
patient’s fears and anxieties is desirable. If a limb is to be amputated, the
patient’s desires as to its disposal and possible burial should be ascertained.
Some initial discussions of the disability, its meaning to the patient, and
compensation for it are advisable.
The family and other persons who are significant to the patient should
be advised as to the expected posttreatment psychological and emotional
phenomena. This is important, so that their aid may be immediately enlisted

in the rehabilitation process and especially in ascertaining the possibility of
the operation’s emotional destructiveness to the patient. Watson and Johnson
have emphasized the significance of the attitude of parents in determining the

management of amputation in children. Despite excellent preoperative
preparation of both the child and parents for amputations for a bone tumor,
the postoperative syndrome was complicated and aggravated by the denying
and rejecting attitudes of the parents. Treatment should be instituted as

quickly as possible when disruption of the body structure leads to personality
disorder. Failure to do so can result in fixation of chronic psychopathic
reactions. In panic reactions with pain after limb amputations, the writer has
utilized a brief psychotherapeutic technique in which the following topics
have been penetrated in successive order from the initial interview: (1) the
concept of the phantom-limb phenomenon and any attendant rationalizations

regarding this; (2) wishes and fears relative to the disposal of the amputated
part; and (3) the significance of present and past attitudes toward the body in
relation to real or fantasied experiences with significant persons. This

procedure has proved effective in alleviating panic and painful complaints in
a number of limb amputees, among those with facial disfigurement following
surgery, and in women with breast deformity consequent to thoracoplasty. It
has also been utilized in initiating psychotherapy on amputees who have
remained chronically disturbed for years following their loss.
In disturbances of the body-image that have led to chronic personality
disorders, whether psychoneurotic or psychotic, the choice of therapy is
dependent on the particular variety of reactions suffered by the individual.

Various forms of psychotherapy including psychoanalysis, hypnosis,
narcosynthesis, electroshock therapy, frontal lobe injection, and treatment
with the phenothiazines and antidepressants have been reported effective.
Indications for and techniques of application of these treatments are

presented elsewhere in this Handbook.
Bibliography
Abel, T. M. “Figure Drawings in Facial Disfigurement,” Am. J. Orthopsychiatry, 23 (1953). 253-264.
Aitken, G. T. “Amputation as a Treatment for Certain Lower Extremity Abnormalities,” J. Bone

Joint Surg., 41-A (1959), 1267-1287.
Anastasopoulos, G. “Le Lobe parietal et l’image de notre corps,” Med. Contemp., 73 (1955), 143-
146.
Appenzeller, O. and J. M. Bicknell. “Effects of Nervous System Lesions on Phantom Experience,”

Neurology, 19 (1969), 141-146.
Arensten, K. “Fantomoplevelsenhos en Amputeret Behandlet med Psykoterapi,” Nord. Med., 39

(1948), 1613.
Asch, S. E. and H. A. Witkin. “Studies in Space Orientation: I. Perception of the Upright with
Displaced Visual Fields,” J. Exp. Psychol, 38 (1948), 325-337.
----. “Studies in Space Orientation: II. Perception of the Upright with Displaced Visual Fields and
with Body Tilted,” J. Exp. Psychol, 38 (1948), 455-477.
Bachet, M. and G. Padovani. “Reflexions sur le traitement psychotherapique des douleurs des
amputes,” Ann. Med. Psychol. (Paris), 1 (1951), 206-211.
Bailey, A. A. and F. P. Moersch. “Phantom Limb,” Can. Med. Assoc. J., 45 (1941), 37-42.
Baker, W. Y. and L. H. Smith. “Facial Disfigurement and Personality,” JAMA, 112 (1939). 301-304.
Bard, M. “The Use of Dependence for Predicting Psychogenic Invalidism following Radical
Mastectomy,” J. Nerv. Ment. Dis., 122 (1955). 152-160.
Bender, L. “Psychoses Associated with Somatic Diseases that Distort the Body Structure,” Arch.
----. “Body Image Problems of the Brain Damaged,” J. Soc. Issues, 4 (1948), 84-89.
Bender, M. B. Disorders in Perception. Springfield, Ill.: Charles C. Thomas, 1952.
Bennett, D. H. “The Body Concept,” J. Ment. Sci., 106 (1960), 56-75.
Blank, R. H. “The Challenge of Rehabilitation,” Israel Med. J., 20 (1961), 127-142.
Blatt, E. F. “Body Image and Psychosomatic Illness,” Am. Psychol. Abstr., 18 (1963), 401-402.
Bors, E. “Phantom Limbs of Patients with Spinal Cord Injury,” Arch. Neurol. Psychiatry, 66 (1951),
610-631.
Bressler, B., S. I. Cohen, and F. Magnussen. “Bilateral Breast Phantom and Breast Phantom Pain,” J.
Nerv. Ment. Dis., (1955), 315-320.
----. “The Problem of Phantom Breast and Phantom Pain,” J. Nerv. Ment. Dis., (1956), 181-187.
Brophy, T. W. “The Deformity of Hare Lip and Cleft Palate,” Dent. Summ. (Toledo), 29 (1909), 465-
471.
Bychowski, G. “Disorders of the Body Image in the Clinical Pictures of the Psychoses,” J. Nerv.
Ment. Dis., 97 (1943), 310-335.
Cardone, S. S. and R. Olson. “Psychophysical Studies of Body-image,” Arch. Gen. Psychiatry, 21

(1969), 464-469.
Cath, S. H., E. Glud, and H. T. Blane. “The Role of the Body Image in Psychotherapy with the
Physically Handicapped,” Psychoanal. Rev., 44 (1957), 34-40.
Cedercreutz, C. "Hypnotic Treatment of Phantom Sensations in 100 Amputees,” Acta. Chir. Scand.,
107 (1954), 158-162.
Centers, L. and R. Centers. “A Comparison of the Body-images of Amputee and Non Amputee
Children as Revealed in Figure Drawing,” J. Proj. Tech., 27 (1963), 158-165.
----. “Peer Group Attitudes toward the Amputee Child,” J. Soc. Psychol, 61 (1963), 127-132.
Cohen, H. and H. W. Jones. “Reference of Cardiac Pain to a Phantom Left Arm,” Br. Heart J., 5
(1943), 67-71.
Cook, A. W. and W. H. Druckemiller. “Phantom Limb in Paraplegic Patients. Report of Two Cases
and Analysis of Its Mechanism,” J. Neurosurg., 9 (1952), 508-516.
Corah, N. L. and P. L. Corah. “A Study of Body-image in Children with Cleft Palate and Cleft Lip,” J.
Genet. Psychol., 103 (1963), 133-137.
Cronholm, B. “Phantom Limbs in Amputees; A Study of Changes in the Integration of Centripetal

Impulses with Special Reference to Referred Sensations,” Acta. Psychiatr. Neurol.
Scand., Suppl., 72 (1951), 310.
De Gutierrez-Mahoney, C. G. “Symposium on Neuro-Surgery: Treatment of Painful Phantom Limb:

Follow-up Study,” Surg. Clin. North Am., 28 (1948), 481-483.
Dembo, T., G. Ladieu-Leviton, and B. A. Wright. “Acceptance of Loss—Amputations,” in I. F.

Garrett, ed., Psychological Aspects of Physical Disability, ser. no. 210. Washington:
Federal Security Agency, Office of Vocational Rehabilitation, 1952.
Dorpat, F. L. “Phantom Sensations of Internal Organs,” Comp. Psychiatry, 12 (1970), 27-35.
Druss, R. G., J. F. O’Connor, and L. O. Stern. “Changes in Body-image following Ileostomy,”

Psychoanal. Q., 41 (1972), 195.
Duke-Elder, P. M. and E. Wittkower. “Psychological Reactions in Soldiers to the Loss of Vision of

One Eye, and Their Treatment,” Br. Med. J., 1 (1946), 155— 158.
Duplay, J. and P. Cossa. “Frontal Lobe Novocaine Injections as a Therapeutic Measure,” Ann. Med.
Psychol. (Paris), 111 (1953), 33-40.
Easson, W. M. “Body-image and Self-image in Children,” Arch. Gen. Psychiatry, 4 (1961), 619-621.
Echols, D. H. and J. A. Colclough. “Abolition, of Painful Phantom Foot by Resection of the Sensory
Cortex,” JAMA, 134 (1947), 1476-1477.
Eickhoff, L. F. W. “The Aetiology of Schizophrenia in Children,” J. Ment. Sci., 98 (1952). 229-234.
Eigenbrode, C. R. and W. G. Shipman. “The Body Image Barrier Concept,” J. Abnorm. Soc. Psychol.,
60 (1960), 450-452.
Erickson, T. C., W. J. Bleckwenn, and N. Woolsey. “Observations on the Postcentral Gyrus in

Relation to Pain,” Trans. Am. Neurol. Assoc., 77 (1952), 57-59.
Ewalt, J. R., G. C. Randall, and H. Morris. “The Phantom Limb,” Psychosom. Med., 9 (1947), 118-123.
Federn, P. Ego Psychology and the Psychoses. New York: Basic Books, 1953.
Fisher, S. “Head-Body Differentiations in Body-image and Skin Resistance Level,” J. Abnorm. Soc.
Psychol., 60 (1960), 283-285.
----. “A Further Appraisal of the Body Boundary Concept,” J. Consult. Psychol., 27 (1963), 62-74.
----. “The Body-image as a Source of Selective Cognitive Sets,” J. Pers., 33 (1965), 536-552.
Fisher, S. and S. E. Cleveland. “An Approach to Psychological Reactivity in Terms of a Body-image

Schema,” Psychol. Rev., 64 (1957), 26-37.
----. Body Image and Personality. Princeton, N.J.: Van Norstrand, 1958.
Frederiks, J. A. M. “Occurrence and Nature of Phantom Limb Phenomena following Amputation of

Body Parts and following Lesions of the Central and Peripheral Nervous Systems,”
Psychiatr. Neurol. Neurochir., 66 (1963), 73-97.
Freud, A. “The Role of Bodily Illness in the Mental Life of Children,” in The Psychoanalytic Study of
the Child, Vol. 7, pp. 69-81. New York: International Universities Press, 1952.
Gallinek, A. “The Phantom Limb: Its Origin and Its Relationship to the Hallucinations of Psychotic
States,” Am. J. Psychiatry, 96 (1939), 413-422.
Gesell, A. and F. L. Ilg. Infant and Child in the Culture of Today. New York: Harper, 1942.
Gilder, R., S. V. Thompson, C. W. Slack et al. “Amputation, Body-image and Perceptual Distortion: a
Preliminary Study,” Res. Rep., Nav. Med. Res. Inst., 12 (1954), 587.
Goertzel, V., P. R. A. May, J. Salken et al. “Body-Ego Technique: An Approach to the Schizophrenic
Patient,” J. Nerv. Ment. Dis., 141 (1965), 53-60.
Guillaume, J. F. and G. Mazars. “Traitement des membres fantomes douloureux par

psychotherapie sous narcose ou hypnose,” Rev. Neurol., 79 (1947), 213-215.
Halpern, S. “Body-image Symbols of Repression,” Int. J. Clin. Exp. Hypn., 13 (1965). 83-91.
Harris, J. E. “Elucidation of Body-Imagery in Chronic Schizophrenia,” Arch. Gen. Psychiatry, 16

(1967), 679-684.
Harvey, F. “Some Social Aspects in the Case of Patients Undergoing Breast Surgery,” Med. Soc.
Work, 4 (1955), 99-110.
Head, H. Studies in Neurology. London: Oxford, 1920.
Henderson, W. R. and G. E. Smyth. “Phantom Limbs,” J. Neurol. Neurosurg. Psychiatry, 11 (1948),

88-112.
Heusner, A. P. “Phantom Genitalia,” Trans. Am. Neurol. Assoc., 75 (1950), 128-131.
Hirsch, S. J. “Left, Right and Identity,” Arch. Gen. Psychiatry, 14 (1966), 84-88.
Hoffer, W. “Mouth, Hand and Ego-Integration,” in The Psychoanalytic Study of the Child, Vol. 3/4,
pp. 49-56. New York: International Universities Press, 1949.
Hoffman, J. “Facial Phantom Phenomenon,” J. Nerv. Ment. Dis., 122 (1955),
----. “Phantom Limb Syndrome. A Critical Review of the Literature,” J. Nerv. Ment. Dis., 119 (1954),
261-270.
Hughes, J. and W. L. White. “Amputee Rehabilitation: Emotional Reactions and Adjustment of
Amputees to Their Injury,” U.S. Nav. Med. Bull. Suppl. (March 1946), 157-163.
Hunt, R. G. and M. J. Feldman. “Body-image and Ratings of Adjustment on Human Figure

Drawings,” J. Clin. Psychol., 16 (1960), 35-38.
Hunt, V. V. and M. E. Weber. “Body-image Projective Test,” J. Proj. Tech., 24 (1960), 3-10.
Jackson, J. H. Neurological Fragments: With Biographical Memoir by James Taylor, and Including
the “Recollections” of the Late Sir Jonathan Hutchinson and the Late Dr. Charles
Mercier. London: Oxford University Press, 1925.
Jacobson, J. R. “A Method of Psychobiologic Evaluation,” Am. J. Psychiatry, 101 (1944), 343-348.
Jarvis, J. H. “Post Mastectomy Breast Phantoms,” J. Nerv. Ment. Dis., 144 (1967), 266-272.
Johnson, F. A. “Figure Drawings in Subjects Recovering from Poliomyelitis,” Psychosom. Med., 34

(1972), 19-29.
Jung, C. G. Psychology of the Unconscious. New York: Dodd-Mead, 1931.
Kinzel, A. F. “Body-Buffer Zone in Violent Prisoners,” Am. J. Psychiatry, 127 (1970), 99-104.
Kipnis, D. M. “Changes in Self Concept in Relation to Perception of Others,” J. Pers., 29 (1961),

449-465.
Kirk, N. T. “The Development of Amputation,” Bull. Med. Libr. Assoc., 32 (1944), 132-163.
Kolb, L. C. “Somatic Sensory Extinction Phenomenon and Body Schema after Unilateral Resection
of the Posterior Central Gyrus,” Trans. Am. Neurol. Assoc., 75 (1950), 138-141.
----. The Painful Phantom. Psychology, Physiology and Treatment. Springfield, Ill: Charles C.
Thomas, 1954.
----. “The Body-image in the Schizophrenic Reaction,” in A. Auerbach, ed., Schizophrenia: An
Integrated Approach, pp. 87-97. New York: Ronald, 1959.
Kolb, L. C., L. M. Frank, and E. J. Watson. “Treatment of the Acute Painful Phantom Limb,” Proc.
Staff Meet. Mayo Clin., 27 (1952), 110-118.
Kubie, L. “Motivation and Rehabilitation,” Psychiatry, 8 (1945), 69-78.
Ladieu, G., E. Hanfmann, and T. Dembo. “Studies in Adjustment to Visible Injuries, Evaluation of
Help by the Injured,” J. Abnorm. Soc. Psychol., 42 (1947), 169-192.
Lambert, C. N. and J. Sciarra. “A Questionnaire Survey of Juvenile to Young Adult Amputees who
had had Prosthesis Supplied Them through the University of Illinois Division of
Services for Crippled Children,” J. Bone Joint. Surg., 41A (1959), 1437-1454.
Langworthy, O. R. “Development of Behavior Patterns and Myelinization of the Nervous System in

the Human Fetus and Infant,” Contrib. Embryol., 443 (1933), 1-57.
Levin, M. “The Concept of Denial and Its Limitations, with Remarks on Phantom Limb
Disorientation and Perseveration,” J. Neuropsychiatry, 2 (1961), 167-174.
Levy, D. M. “Method of Integrating Physical and Psychiatric Examination with Special Studies of
Body Interest, Overt Protection Response to Growth and Sex Difference,” Am. J.
Psychiatry, 9 (1929), 121-194.
----. “Body Interest in Children and Hypochondriasis,” Am. J. Psychiatry, 12 (1932), 295-315.
Lhermitte, J. “L’Image de notre corps,” Nouv. Rev. Crit., (1939), 256 pp. go. Linn, L. “Some
Developmental Aspects of the Body Image,” Int. J. Psycho-Anal., 36 (1955), 36-42.
Linn, L. and I. B. Goldman. “Psychiatric Observations Concerning Rhinoplasty,” Psychosom. Med.,

11 (1949), 307-314.
MacGregor, F. C., T. M. Abel, A. Bryt et al. Facial Deformities, and Plastic Surgery. Springfield, Ill.:
MacGregor, F. C. and B. Schaffner. “Screening Patients for Nasal Plastic Operations,” Psychosom.
Med., 12 (1950), 277-291.
Machover, K. Personality Projection in the Drawing of the Human Figure. Springfield, Ill: Charles C.
Thomas, 1957.
Mednick, S. A. “The Body Barriers Go Rorschach: Review of Body-image and Personality by

Fisher, S. and Seymour, S. E., 1958,” Contemp. Psychol., 4 (1959), 276-277.
Meerloo, J. A. M. “The Fate of One’s Face,” Psychiatric Q., 30 (1956), 31-43.
Miles, J. E. “Psychoses with Phantom Limb Treated by Chlorpromazine,” Am. J. Psychiatry, 112
(1956), 1027-1028.
Mitchell, S. W. “Phantom Limbs,” Lippincott’s Mag. Pop. Lit. Sci., 8 (1871), 563-569.
Noble, D., M. E. Roudebush, and D. Price. “Studies of Korean War Casualties, Part I: Psychiatric
Manifestations in Wounded Men,” Am. J. Psychiatry, 108 (1952), 495-499.
Noble, D., D. B. Price, and R. Gilder. “Psychiatric Disturbances following Amputation,” Am. J.
Psychiatry, 110 (1954), 609-613.
Orbach, J. “Psychophysical Studies of Body-image,” Arch. Gen. Psychiatry, 14 (1966), 41-47.
Paré, A. The Workes of That Famous Chirurgion, Ambrose Parey. Translated out of the Latin and
compared with the French by T. Johnson. London: Cotes, 1649.
Pazat, P. and P. Grateau. “Phantom Hearing (Tinnitus) after Amputation of the Auditory Field by
Sonic Traumatism,” Rev. Otoneuroophtalmol., 42 (1970), 81-90.
Perrin, F. A. C. “Physical Attractiveness and Repulsiveness,” J. Exp. Psychol., 4 (1921), 203-217.
Peto, A. “Body-image and Archaic Thinking,” Int. J. Psychoanal., 40 (1959), 223-231.
Pick, A. “Zur Pathologic des Bewusstseins vom eigenen Korper. Ein Beitrag an Kriegs-medizin,”
Neurol. Zentralbl., 34 (1915), 257-265.
Pick, J. F. “Ten Years of Plastic Surgery in a Penal Institution,” J. Int. Coll. Surgeons, 11 (1948), 315-
319.
Pisetsky, J. E. “Disappearance of Painful Phantom Limbs after Electric Shock Treatment,” Am. J.
Psychiatry, 102 (1946), 599-601.
Pollack, M. and W. Goldfarb. “The Face-Hand Test in Schizophrenic Children,” Arch. Neurol.
Psychiatry, 77 (1957), 635-642.
Pool, J. L. and T. J. Bridges. “Subcortical Parietal Lobotomy for Relief of Phantom Limb Syndrome
in the Upper Extremity,” Bull. N.Y. Acad. Med., 30 (1954), 302-309.
Price, D. B., N. J. Twombly. “A. Lemos: Dedolore Membri Amputati Remanente Explicatio (1798).
The Phantom Limb: An Eighteenth Century Latin Dissertation Text and Translation
with a Medical Historical and Linguistic Commentary,” in Languages and
Linguistics, Working Papers. Washington: Georgetown University Press, 1972.
Radovici, A. and N. Wertheim. “L’Electrochoc comme traitement des douleurs irreductibles.

(Causalgie, Neuralgie Re-belle, Douleurs des morphinomanes. Crises subintrantes
tabetiques),” Presse Med., 54 (1949). 754-755.
Renneker, R. and M. Cutler. “Psychological Problems of Adjustment to Cancer of the Breast,”

JAMA, 148 (1952), 833-838.
Resnik, H. L. P. “Suicide Attempt by a Child after Amputation,” JAMA 212 (1970), 1211-1212.
Riddoch, G. “Phantom Limbs and Body Shape,” Brain, 64 (1941), 197-222.
Riese, W. and G. Bruck. “Le Membre fantomes chez 1’enfant,” Rev. Neurol., 83 (1950), 221-222.
Ross, N. “The Postural Model of the Head and Face in Various Positions (Experiments on
Normals),” J. Gen. Psychol., 7 (1932), 144-162.
Schilder, P. The Image and Appearance of the Human Body. Studies in the Constructive Energies of
the Psyche. London: Kegan Paul, 1935.
Schonfeld, W. A. “Gynecomastia in Adolescence,” Arch. Gen. Psychiatry, 5 (1961), 68-76.
Schontz, F. C. “Body Concept Disturbances of Patients with Hemiplegia,” J. Clin. Psychol., 12

(1956), 293-295.
Scott, W. C. M. “Some Embryological, Neurological, Psychiatric and Psychoanalytic Implications of

the Body Scheme,” Int. J. Psychoanal., 29 (1948), 141-155.
Secord, P. “Objectification of Word-Association Procedures by the Use of Homonyms: A Measure

of Body Cathexis,” J. Pers., 21 (1952-1953), 479-495.
Secord, P. and S. M. Jourard. “The Appraisal of Body Cathexis: Body Cathexis and the Self,” J.
Consult. Psychol, 17 (1953), 343-347.
Selecki, R. B. and J. T. Hebron. “Disturbances of the Verbal Body-image; A Particular Syndrome of

Sensory Aphasia,” J. Nerv. Ment. Dis., 141 (1965), 42-52.
Simmel, M. L. “Phantoms in Patients with Leprosy and in Elderly Digital Amputees,” Am. J. Psychol,
69 (1956), 529-545.
----. “Phantom Experiences in Mental Defective Amputees,” J. Abnorm. Soc. Psychol., 59 (1959),
128-129.
----. “Phantom, Phantom Pain and ‘Denial’,” Am. J. Psychother., 13 (1959), 603-613.
----. “The Absence of Phantoms for Congenitally Missing Limbs,” Am. J. Psychol., 74 (1961), 467-
470.
----. “Phantom Experiences following Amputation in Childhood,” J. Neurol. Neurosurg. Psychiatry,

25 (1962), 69-78.
----. “A Study of Phantoms after Amputation of the Breast,” Neuropsychol., 4 (1966), 337-350.
Simpson, E. B. and H. F. Albronda. “Psychologic Aspects of Amputation of a Lower Limb,” Lancet,
87 (1967), 429-431.
Smythies, J. R. “The Experience and Description of the Human Body,” Brain, 76 (1953), 132-145-
1.33. Souques, A. and Poisot. “Origine peripherique des hallucinations des membres
amputes,” Rev. Neurol., 13 (1905), 1112-1116.
Spring, J. M. and C. H. Epps, Jr. “The Juvenile Amputee. Some Observations and Considerations,”
Clin. Pediatr., (Phila.), 7 (968), 76-79.
Stern, K., A. Lariviere, and G. Founier. “Psychiatric Aspects of Cosmetic Surgery of the Nose,” Can.
Med. Assoc. J., 76 (1957), 469-472.
Strotzka, H. “Psychotherapie des Phantom Schmerz.es,” Klin. Med., 3 (1948), 172.
Szasz, T. S. “Psychiatric Aspects of Vagotomy: IV. Phantom Ulcer Pain,” Arch. Neurol. Psychiatry, 62
(1949), 728-733.
----. Pain and Pleasure, New York: Basic Books, 1957.
Taylor, J., G. Holmes, and F. M. R. Walshe. Selected Writings of John Hughlings Jackson, Vol. 1, On
Epilepsy and Epileptiform Convulsions. New York: Basic Books, 1958.
Thornton, G. R. “The Effect upon Judgements of Personality Traits of Varying a Single Factor in a
Photograph,” J. Soc. Psychol., 18 (1943), 127-148.
Updegraff, H. L. and K. A. Menninger. “Some Psychoanalytic Aspects of Plastic Surgery,” Am. J.

Surg., 25 (1934). 554“ 558.
Wachs, H. and M. Zaks. “Studies of Body-image in Men with Spinal Cord Injury,” J. Nerv. Ment. Dis.,
131 (1960), 121.
Watson, E. J. and A. M. Johnson. “The Emotional Significance of Acquired Physical Disfigurement

in Children,” Am. J. Orthopsychiatry, 28 (1958), 85-97.
Weinstein, S. and E. A. Sersen. “Phantoms in Case of Congenital Absence of Limbs,” Neurol., 11
(1961), 905-911.
White, J. C. and W. H. Sweet. “Effectiveness of Chordotomy in Phantom Pain after Amputation,”

Wille, W. S. “Figure Drawings in Amputees,” Psychiatr. Q., (Suppl.), 28 (1954), 192-198.
Witken, H. Personality Through Perception. New York: Harper, 1954.
Wright, G. H. “The Names of the Parts of the Body. A Linguistic Approach to the Study of the Body
Image,” Brain, 79 (1956), 188-210.
Wysocki, B. A. and E. Whitney. “Body-image of Crippled Children as Seen in Draw-a-Person Test

Behavior,” Percept. Mot. Skills, 21 (1965), 499-504.
Zador, J. “Meskalinwirkung auf das Phantomglied,” Monatsschr. Psychiatr. Neurol., 77 (1930), 71-
99.
Chapter 34
Complex Problems of Pain As Seen In Headache,

Painful Phantom, and Other States
Shervert H. Frazier
To the sociologist, pain and the threat of pain are powerful instruments
of learning and social preservation. To the biologist, pain is a sensory signal
that warns the individual when a harmful stimulus threatens injury. To the
physiologist, pain is a sensation like seeing or hearing, but he tends to ignore
its conscious perceptual aspects, because consciousness has as yet no

physiological equivalents; one might say that he is studying the pain “signal.”
To the psychologist, on the other hand, the important thing about pain is the
brain’s translation of the signal into a sensory experience. He finds pain, like
all perceptions, to be subjective, individual, and modified by degrees of
attention, emotional states, and the conditioning influence of past experience.

To a man with an incurable cancer, pain is a destructive force. His suffering
began too late to serve as an effective warning and it did not stop after the
warning had been given.
To the layman, the sensation of pain, which he has known all his life,
seems a perfectly straightforward, noncontroversial matter. “Hot” and
“sharp” were among the first words he learned; his earliest memories are
associated with the pain of accidental injury and of parental discipline; when
he was hurt, he struggled and cried out. Man has accepted these reactions as
the natural manifestations of physical suffering. Experience has taught him
that pain can be caused by many different kinds of stimuli, even those such as
heat or pressure which are distinctly pleasant in moderate intensities. Almost
all parts of his body are sensitive to pain, and he assumes that other people
are equally sensitive. He knows that pain is caused by physical injury, and
believes that its intensity is proportional to the force of a blow, the heat of an
iron, or the depth of a wound.
While this concept of pain as a physical quantum, measurable in terms
of stimulus intensity or the body’s response to injury, seems a reasonable

everyday interpretation, there are many situations in which it does not apply.
Superficial wounds usually are more painful than deep ones, because the skin
is much more richly supplied with sensory nerve endings than are the deeper
tissues. Bullet wounds are usually painless, partly because the impact of the
missile can temporarily paralyze nerve conduction. Most internal organs can
be cut, crushed, or burned without causing distress. There also are enormous
individual variations in sensitivity to pain. At one extreme are patients with
such conditions as causalgia, facial neuralgia, or postherpetic pain, their skin
so sensitive that the lightest touch or even a breath of air precipitates an
acute exacerbation of pain. At the other extreme are those unfortunate
children who can lean against a hot stove without being distressed, who
constantly injure themselves because they were born without normal
susceptibility to pain, i.e., congenital indifference to pain.
The obvious biological significance of pain leads one to expect that it
must always occur after injury, and to conclude that the intensity of pain felt
is proportional to the amount and extent of the tissue damage. Actually, in

higher species at least, there is much evidence that pain is not simply a
function of the amount of bodily damage alone, but rather that the amount
and quality of pain felt are also determined by previous experiences and how
well memory substantiates them, by an individual’s ability to understand the
cause of the pain and to grasp its consequences, and even by the significance
of pain in one’s own family or group culture.
Considerable evidence shows that persons also attach variable
meanings to pain-producing situations, and that these meanings greatly
influence the degree and quality of pain felt. During World War II, Beecher
observed the behavior of soldiers severely wounded in battle. He found that
when the badly wounded were carried into combat hospitals, only one of
three complained of enough pain to require morphine. Most of the soldiers
either denied having any pain or had so little discomfort as to require no
medication for relief. These patients were not in a state of shock, nor
unusually stoic, nor totally unable to feel pain; for example, vigorous
complaints about inept vein puncture were made. When Beecher returned to
civilian practice as an anesthesiologist, he tested a group of patients, who had
just undergone major surgery with incisions similar to the wounds received
by the soldiers, to determine whether relief of pain was required. In contrast
to the wounded soldiers, four of five were in such severe distress as to

require relief.
Beecher concluded that “. . . the common belief that wounds are
inevitably associated with pain, that the more extensive the wound the worse
the pain, was not supported by observations made as carefully as possible in

the combat zone. . . . There is no simple direct relationship between the
wound per se and the pain experienced. The pain is in very large part
determined by other factors, and of great importance here is the significance

of the wound. . . . In the wounded soldier (the response to injury) was relief,
thankfulness at his escape alive from the battlefield, even euphoria; to the
civilian, major surgery was a depressing, calamitous event.”
The importance of the meaning associated with a pain-producing
situation is made particularly clear in conditioning experiments carried out

by the Russian physiologist, Ivan Pavlov. Dogs normally react violently when
given strong electric shocks to the paw. Pavlov found, however, that if dogs
were consistently presented food after each shock, the animal developed a
new response. Immediately after a shock, the dog would salivate, wag its tail,
and turn toward the food dish. The electric shock now failed to evoke any
responses indicative of pain and became instead a signal indicating that food
was on the way. The dog’s conditioned behavior persisted when Pavlov
increased the intensity of the electric shocks and even when they were
supplemented by burning and wounding the dog’s skin. Masserman carried

the experiment further. After cats had been taught to respond to an electric
shock as a signal for feeding, they were trained to administer the shock
themselves by walking up to a switch and closing it.
The Transmission and Perception of Pain
An excellent survey of medical concepts of pain has been written by
Prococci; Clark and Hunt have updated these theories comprehensively. In
the specific sensory-trans-mission system, epicritic or bright pain is thought
to pass readily from the dorsal root into the spinothalamic tracts to the
thalamus, and thence into the sensory cortex. Pain thresholds are known to
be altered by the state of excitation of the reticular system of the internuncial
pool and by the state of discharge from cortical centers.
The nonspecific sensory system—the reticular activating system—is
known to receive collaterals from the specific fiber pathways to convey
sensations of pain, as well as other sensations. The discovery of this system
and its functions provides one of the links explaining certain clinical
paradoxes. This system has the capacity for the modulation of sensory
attentiveness. Thus, the severely wounded soldier can be nonattentive to pain
when some other state of awareness such as strong feelings, fear of death, or
great joy at being alive, is overriding. It may be speculated that reactions to
pain, or the seeming lack of response observed in the wounded of various

nations, may be modulated by cortical influences directed to the reticular
activating system and then variously fed back to both the cortex and the
periphery. It is known now that, when stimulated in the bulbar and reticular
areas, this system is capable of blocking afferent volleys in the spinal cord.
There is evidence that a physiological system exists that may either intensify
or lessen an incoming sensation and, in fact, may defend the organism against
too intense a stimulation or heighten its capacity to attend threats to the

system.
Of particular interest to the clinician is the fact that transmission of

impulses within the nonspecific activating system may be modified by
pharmacological means. It appears that anesthetics exert their primary effect

in blocking conscious response to noxious stimuli by dampening conduction
through this system. Very likely the phenothiazine derivatives, important in
clinical psychiatry, act upon this system as well. The modern psychological
and pharmacological modes of sensory alarm functioning allow more
comprehensive explanation of many of the variable expressions of pain found
in the clinic.
No longer can complex pain problems be explained solely by relying

upon the older concept of a specific sensation from the periphery to the
cortex. Instead, the concept of a prolonged or intractable painful or anesthetic
state is a perceptual action system designed to signal either distress or,
paradoxically, gratification of pleasure.
Perceptual processes are established by repetitive experience encoded
in the large cortical areas of the brain, where, in turn, the adaptive patterns of
behavior are coded. To the physiological model of the systems subserving
pain must be added the great modifying influences of man’s cerebral cortex
wherein are implanted the long and continuing experiences of suffering, and
the adaptive behavioral patterns for relief that are initiated at birth and
expanded, from experience, throughout life. These learning experiences occur
primarily in the human environment, the surrounding persons, most notably
the family, who inflict and assuage pain.
The experience of pain signifies to the patient that he is suffering
structural or functional damage. When this percept is conveyed to the
clinician as a complaint, the latter commonly interprets it as a consequence of
a “physical” or “organic” lesion. Although the pain percept is an innate
response to injury to the organism, its associated complaint in language may
be modified by learning processes established by the family and the cultural
environment. Through the learning experiences, a patient’s complaint of pain

may communicate not only a signal of bodily damage but also a message of
social importance, that of a need for help or for pleasurable gratification
through a supportive relationship with another person. One may intensify

this conditioning through the secondary gratification obtained by the
avoidance of the painful stimuli. Here is the source of the difficulty in
establishing the meaning of the symptom in chronic pain conditions.
The symbolic meaning of the symptom of pain is established in the
manner in which an individual has learned to complain, or not complain, and

to use the symptom of pain as a means of relating himself to others. The
clinician’s ability to understand this meaning for each individual determines
the ultimate ability to assay the proper meaning, initiate the indicated
intervention, and provide the person with a rational management devoid of

untherapeutic emotionality. Confronted with the complex problem of a
patient complaining of a long-standing painful condition, the clinician must
ascertain not only whether there exists a physical disability causing a painful
percept but also: (1) Will a physical procedure relieve the symptom? (2) Is
the symptom expressive of a psychiatric disability? (3) Will removal of the
symptom unmask a serious personality disorder? (4) Will this, in turn, result
in serious interpersonal issues and even, perhaps, in eventual medico-legal
problems?
What is the investigative evidence to support the contention that the

pain complaint often has meaning determined by other than the activation of
a specific sensory system? Hardy, Wolff, and Goodell attempted to study the
response of various individuals to the measured amount of energy required
to induce a threshold pain. This they did by exposing a small area of the skin
to radiant heat and asking the subject to indicate the feeling of pain. Only by
using trained subjects was it possible to obtain a relatively fixed pain
threshold.
Various other investigators have failed to substantiate any consistency
in the pain threshold, and have discovered that it might be increased as much
as 40 percent by hypnosis and could be altered by analgesics as well as by

suggestion. Furthermore, such studies make it apparent that in addition to
the pain threshold there also is a highly variable threshold for reaction to pain
that is highly individualistic. What has been learned from these careful
studies is that the responses to painful stimuli vary greatly in relation to the
personality makeup and emotional state of the particular individual, and also
that the responses to painful stimuli vary among different individuals.
This point is illustrated by observations on various unsatisfactory
therapeutic efforts. Penman studied 275 patients successfully treated by
alcohol injection of the Gasserian ganglion for trigeminal neuralgia. Only 20-
25 percent were relieved of the pain by this procedure; 22 percent reported
that they were worse off than before treatment. In the latter group there was
either an obsessive preoccupation with the resulting paresthesia or an
eruption of neurotic or psychotic symptoms. In the dissatisfied group were

found dependent, inactive, and elderly persons, all of whom had suffered pain
at least six months before treatment was given. This emphasized once again
the influence of personality organization and the significance of the pain to
the adaptability of the person.
That cultural influences determine the individual’s reaction to pain has
been demonstrated in the report by the sociologist, Zborowski, who examined
the attitudes of Italian, Jewish, and old American patients (those who had
lived three generations in the United States) when confronted by a painful
illness. Some were described by the doctors as being “emotional” in responses

to pain. The underlying attitudes toward pain were different, however, in the
several groups. Some patients seemed concerned mainly with the immediate
fear of the pain experience and were disturbed by the actual pain sensations
experienced in a given situation, while some patients reported concern about
the symptomatic meaning of the pain, the significance of the pain to their
health and to the welfare of their families. It was noticed that once the pain
was relieved, some patients dismissed their suffering and reported
contentment. Other patients were reluctant to accept drug therapy, worried
over the effect of the drug upon health, were concerned that the drug would
not be curative, and sometimes hid the pain-relieving medication. Finally,
even if the pain were relieved, some patients were often depressed and
worried, fearful that the disease was not cured.
These observations are of importance in the management of pain
problems. With pain of immediate importance to the patient, the physician

has to provide early and adequate relief; whereas with pain-threatened
patients, one must relieve the anxiety in regard to the source of the pain, as
well as the pain itself. The members of some groups are not fearful of
expressing their emotions. They complain a great deal, call for help, and
expect sympathy and assistance from their families. Although this behavior is
approved and accepted in their culture, it is not accepted by certain other

patients. The physician, too, may easily be provoked to distrust and dislike
patients because they do not conform to the doctor’s ideas and patterns of
acceptable behavior in facing painful illness. Some more stoic patients tend to
minimize responses to pain and to avoid complaining and provoking pity.

They are anxious to cooperate with those who are expected to take care of
them.
Whenever a patient describes a painful illness, the physician who knows
that some emotional disturbance is associated in time with the onset or
recurrence of his complaint should suspect that psychic processes are
operative in its maintenance. Most frequently such events are the death of or
separation from a parent, spouse, or lover; difficulties in relations with an
employer or some parental figure; or threat of illness. Some patients with an
emotionally motivated, painful complaint have intermittent attacks of pain

that may be induced through discussion of the appropriate anxiety-laden
topics. Others, notably those in whom the-pain represents one of the
symptoms of an obsessive neurosis, a hypochondriacal state, or a depression,
complain of a more or less persistent symptom. In such instances, the psychic

conflict is less easily identified.
Patients complaining of suffering from intractable headache, backache,
atypical facial pains, pain in phantom extremities or other parts, who seem
entirely undisturbed by their symptoms but suddenly grasp at the affected
part when the interview is finally focused on their important personal

conflict, make the difficulty apparent to the skillful examiner who should push
on with further inquiries and not be distracted by the symptom. Also, in
psychotherapy, patients often actively hallucinate pain in localized bodily

areas before revealing the distressing interpersonal events underlying the
painful experience.
Headache
One of the most common pain syndromes which every psychiatrist sees
in patients is headache. The terms “headache” and “head pain” refer to a

variety of symptoms and syndromes of diverse origins, produced by many
mechanisms. An excellent classification has been made by the Ad Hoc
Committee on Classification of Headache.
1. Vascular headache of migraine type
a. classic migraine
b. common migraine
c. cluster headache
d. Hemiplegic and ophthalmoplegic migraine
e. lower-half headache
2. Muscle-contraction headache
3. Combined headache, vascular and muscle contraction
4. Headache of nasal vasomotor reaction
5. Headache of delusional, conversion, or hypochondriacal states
6. Nonmigrainous vascular headaches
7. Traction headaches
8. Headache due to overt cranial inflammation
9.-13. Headache due to disease of ocular, aural, nasal, sinusal, dental,

or other cranial or neck structures
14. Cranial neuritides
15. Cranial neuralgias
Psychiatric or psychogenic aspects of headache are specifically involved
in the vascular, muscle contraction, combined, delusional, conversional, and

hypochondriacal states, and also—to a lesser secondary extent—in the other
types. An excellent review of the literature on psychogenic headache has been
written by Boag. Headache is a symptom, not a disease. Psychological factors

may be precipitating, conversional, or a factor in the selection of the head as
the body part in delusional and hypochondriacal states. In every headache
problem, thorough medical and neurological evaluation should precede or be

conducted concomitantly with the psychological and psychiatric evaluation.
The clinical features, including major and minor criteria, physiological factors,
psychological factors, and treatment will be noted only for the types of
headache most likely to be seen by the psychiatrist.
Vascular Headaches of Migraine or Its Variants
Clinical Features
Sharply defined neurological or visual prodromata usually precede the
onset of a one-sided headache of two to four hours’ duration. The pain is

usually in the anterior part of the head, quite intense, commonly associated
with nausea and vomiting. Early in the headache phase, the pain is throbbing
or pulsatile. Mood disturbances may accompany the prodromal or headache

phase, or both. In some patients the involved cranial artery may be visible,
palpable, and tender. Neurological complications such as ophthalmoplegia,
hemiplegia, and speech disorders may accompany the attack. A family history
of such headaches is found in two-thirds of the patients.
Vascular headache variants are facial cephalgia, weekend headache, and
menstrual headache. These types usually do not have sharply defined
prodromata, may last from two to twenty-four hours, are of variable severity,
and may change from throbbing to a steady ache. Cluster headaches occur in
clusters of short duration, usually without prodromata, are strictly unilateral,
and almost always on the same side in the anterior or orbital distribution. The
pain is severe, accompanied by nasal and ocular congestion, occasionally with
miosis and ptosis, and precipitated by vasodilators such as alcohol.
Physiological Factors
Arterial dilation and surrounding tissue reaction occur concomitantly.
Often one major artery in the carotid system becomes dilated, but
constriction may precede dilation. The cause of the arterial changes is not
known, but evidence suggests a neurogenic factor with subsequent
accumulation of tissue substances which produce small-vessel dilation,
edema, and tenderness. Vasomotor centers and the cerebral cortex play a
major factor in the central origin.
Psychological Factors
Recent studies of a series of vascular-head-ache patients reveal that
while no single personality type predisposes to the vascular headache, many

patients of the obsessional personality type may be liable because they
suppress or repress anger or rage by supercontrol mechanisms.
Substitutionary or compensatory perfectionism, ambition, success-striving,
and excessive environmental demands may produce vulnerability to

autonomic nervous system stress, as well as situational and intrapsychic
conflicts. As a group, the patients are intelligent and demonstrate unusual
adaptational patterns to cope with life stresses.
Difficulties in adapting to major phases of the life cycle, such as
adolescence, menstruation, separation from home and family, starting work,
changing jobs, marriage and parenthood, or in dealing with critical life crises,
such as the death of a spouse or being passed over for promotion, may
precipitate bouts of vascular headache. In many vascular-head-ache patients,
an underlying core of depression may be demonstrated when the usual
defense mechanisms are no longer successful in maintaining repression. The
majority of migraine sufferers who come to psychiatrists (and certainly we
see only a few of them) are from families who take great pride in attainment,
follow rigid forms of behavior, and deny the expression of direct or verbal
aggression. Because such families punish members who defy these standards
by excluding them from the family group, any feelings of resentment or

hostility toward a parent or another close person tend, therefore, to be deeply
rejected or repressed, producing conflict with associated anxiety. The
struggle between inevitable emerging hostility and the need to maintain the
family standards in order to continue the desired relationships shapes the

interpersonal matrix that triggers the headache.
Not infrequently, the anticipation of the headaches becomes a crippling
life pattern, and the patient may show increasing withdrawal from personal
responsibility and socialization. When psychopharmacologieal treatment
accompanied by psychotherapy is successful, many patients find attacks of

vascular headache less frequent, less severe, and life more bearable.
Treatment
Migraine is most successfully treated with ergotamine tartrate with
caffeine. Associated symptoms may be treated with antispasmodics,
antiemetics, or sedatives. Best control is attained when the medication is
taken early in the prodroma stage of the headache. The variants do not
respond so dramatically to ergotamine and caffeine. Cluster headaches are
notorious in their difficulty of treatment; some respond to ergotamine

tartrate, but many do not. Although pain relief is a major goal, narcotics are
dangerous because of the recurrent nature of the illness. Psychotherapy of a
joint-venture type is especially helpful in teaching the patient alternative

adaptational patterns to life stresses. Psychoanalyses have been reported in
detail by Brenner and associates, Fromm-Reichmann, Selinsky, Sperling, and
Robinson. Psychopharmacological treatment of depression with tricyclic
antidepressants is indicated. Because the depressions are unipolar, one must

try the various substances such as imipramine hydrochloride or amitriptyline
hydrochloride in order to find which type of tricyclic drug is effective for a
particular patient. Sufficient dosage must be utilized. Alcohol must be

specifically prohibited to those persons who are sensitive to it. While the
prevention of headaches is not very successful, methysergide maleate has
been useful, but must be carefully monitored because of side effects and
complications in therapy.
Muscle-Contraction Headache
Clinical Features
Autogenic feedback mechanisms have been reported as successful in the
treatment of migraine and muscle-contraction headaches. Recurrent, of
variable severity, and persisting from several hours to days, muscle-
contraction headaches are described as dull, pressing, or aching. The pain is
suboccipital, usually bilateral, and extends to other areas of the head,
including frontal, temporal, and band-around-the-head, and may also involve
the facial musculature. The scalp and neck may be tender on pressure with
the hand. Prodromata are not present, and nausea and vomiting are rare. The
headache may be temporally related in onset to a specific stress. Family
history is usually unimpressive.
Physiological Factors
Ischemia is a possible factor in producing muscle contraction and pain.
It is presumed that tension and emotional stress can cause muscle tightening
with prolonged muscle contraction.
Psychological Factors
Persons of every personality type have been demonstrated to be subject
to muscle-contraction headaches. States of prolonged chronic anxiety are

most common. Irritability, depression, insomnia, fits of weeping, and
overconcern about the opinions of others are usual accompaniments in
patients with this type of headache. In the worst cases, there is severe
regression with constant headache and the patient is bedridden day and
night, requiring total nursing care. Invariably the family is involved, and the
frequency of interpersonal conflict is high. Uncovering psychotherapy leads to
denied and repressed hostile, aggressive feelings, and unacceptable sexual
impulses and ideas. In the early stages, attempts to hide the weakness
associated with headaches are accompanied by holding the head high or
craning the neck in defiance of the urge to give up and give in. This type of
psychological body language most commonly demonstrates anxiety neurosis.

Characterological disorders, neuroses, body-image disorders, posttraumatic
neuroses, depressions, and psychoses have frequently been identified initially
as muscle-contraction headaches.
Treatment
Although psychiatric treatment is necessary, the first consideration is
providing some respite from the pain. Antianxiety psychopharmacological
substances, such as chlordiazepoxide hydrochloride, diazepam, and
meprobamate in adequate dosage give much relief. Muscle relaxants such as

carisoprodol may also be helpful. Heat and massage are usually beneficial if
used concomitantly. These pharmacological substances and physical
therapies are sustaining while the psychiatric problem is in process of

definition.
The taking of a detailed history, exploring the patient’s complaints with
great care and precision, requires much time. The psychiatrist should
evaluate the pain and explore the social, family, work, and pleasure attitudes
and environment, as well as the patient’s responses to stress, personality
traits, long-range life goals, and habitual patterns of coping with tension in
order to build, in his own mind, a model of the patient’s life. Once this has
been attained, the problem areas can be specifically defined. Such an

evaluation may reveal a characterological disorder, a neurosis, a body-image
disorder, a posttraumatic neurosis, a depression, or even a psychosis.
Depending on the psychodynamic formulation of the meaning of the
symptoms to a particular patient, a psychiatric treatment program can be

planned and a treatment goal established. Whether the route lies with
supportive psychotherapy, uncovering psychotherapy, guidance and
educative approaches, or psychoanalytic investigation must be decided. One

would usually strive for resolution of the patient’s conflict and some
modification of personality structure.
Combined Headache
Combined headache is a combination of the vascular and muscle-
contraction types. A clear definition of the factors which fall into each
category assists the psychiatrist to understand the physiological and
psychological components, and plan a treatment program to encompass the
various identifiable parts of the combination. Experience teaches that, in
many instances, successful treatment of the combined-headache patient
requires close collaboration between internist, neurologist, and psychiatrist,

with each physician understanding the nature of the expertise and treatment
plans of the others, and willing to interact in this way. When cooperation is
not present, the patient collects conflicting statements, involves the

physicians in divisive maneuvers, and can easily sabotage the therapeutic
efforts of everyone involved.
Delusional States and Conversion
Friedman and Frazier showed in 1971 in a selected series of 250
headache patients—all of whom had had previous treatments, multiple

physicians, and were treatment failures by their own declarations—that 25
percent had organic brain disorders not previously diagnosed, and 28 percent
had psychoses not previously diagnosed. This highly selective sample of long-
term headache sufferers clearly indicated that headache can mask very
severe illnesses, and that such masks are utilized defensively, for long periods
of time, to avoid knowing the true cause and treatment of the symptoms.
Monosymptomatic delusions of headache and body delusions occur
frequently in schizophrenia, as well as in manic-depressive psychosis
(bipolar), involutional melancholia, and unipolar illness.
Conversion reaction may present symptomatically as headache. The

symbolic meaning of the head and its special importance have been
recognized throughout history. From earliest childhood, developmental
experiences involve the head-placed organs of special sense, i.e., eating and
learning. Considering the head as locus of the intelligence and so many critical
senses imprints the necessity of protecting it, and also defines it as the source
of many conflicts.
Every psychiatrist has seen a delusional patient who concretely defines
a perception in terms of the organ of perception. Similarly, our society,
regarding the head as symbolic of organizer, controller, or director of the

entire organism, uses the terms “headman,” “headmaster,” “headquarters,”
and “headwaiter;” or, very simply, calls the person in charge “the head.” This
metaphor, with some variations, is constant in everyday speech, even in
regard to inanimate things and natural phenomena. The “head” is the upper
end of beds, valleys, stairs, and pages; the useful section of hammers, golf
clubs, and many other objects; the culminating point of cabbages, flowers, and
pimples; the source of a stream; and the leading end of a ship, train, or
parade. The head of the table, even when the ends are identical, is, of course,
the place of prestige.
Some authors have considered headache in broad adaptational and
psychogenic context. It has, for instance, been suggested that the vascular
mechanisms in many headaches are related to normal circulatory changes
that accompany intense and prolonged mental activity, especially in a setting
of relative frustration, with the circulatory process extending beyond normal
range when the activity is not brought to a resolution or conclusion. Grinker
and Robbins related it to the evolutionary migration of complex and

integrated functions toward the head end of the organism and the complex
sensory, postural, and symbolic activities integrated there. Interest in the
expression of psychological and emotional tension in this part of the body has
led, in turn, to consideration of postural reflexes and muscle tension. This

points up a general tendency, identified in headache sufferers, both to locate
the ego and psychic functions generally in the head, and to elaborate further
symbolic transformations of such beliefs. Wolff wrote: “Since the human

animal prides himself on ‘using his head’ it is perhaps not without meaning
that his head should be the source of so much discomfort ... or that the vast
majority of discomforts and pains of the head . . . are accompaniments of

resentments and dissatisfactions.” Kolb, observing that personal attitudes
toward the head are derived from early learning and appreciation of body
functioning and image, sees the expression of concerns related to intellect,
brain function, or emotional capacities in terms of head-referred complaints,

particularly headache. Rangell and Rosenbaum discuss the more complex
symbolism of the headache symptom as a compromise formation
representing the impulse and the defense against it. Both authors describe
cases illustrating different complex patterns of interrelated defense
mechanisms. Rangell notes that conversion symptoms of this type are not
confined to hysterical patients but may also occur with either obsessive-
compulsive neuroses or depressions.
Posttraumatic Headaches
This type of headache is reminiscent of the war neurosis and so-called
“combat fatigue.” Patients so afflicted often have vivid and terrifying
nightmares as well as “startle” reactions, that symbolize the threat to survival

experienced at the time of trauma.
Often, very careful intravenous administration of sodium pentothal or
sodium amytal provides the patient with just enough sedation to release his
mental controls, allowing him to talk freely of the events surrounding the
traumatic accident and to abreact the terror he experienced. When this is
done, several persons should be present because these patients often abreact
with considerable physical and motor excitement.
One of my posttraumatic headache patients, a twenty-one-year-old
Canadian farm boy, had suffered a leg fracture and toe amputation from
catching his foot in a hay baler. Because of the loud noise of the machinery,
his father did not hear the son’s cries until the baler turned at the end of a
fence row. When he saw the boy writhing in pain and in a state of shock, he
shouted, “Oh, my God, he’s dead!” Under amytal sedation the young man
fought furiously, as if trying to free himself from the machine. Reliving the
situation with great clarity, he then fainted. In the weeks after this session,
the material he abreacted during the amytal interview was slowly brought to
his awareness and he was relieved of his headache. The syndrome such
patients suffer has a quality resembling a psychoneurotic conversion type of
symptom, with the symptom as the symbolic mental representation of an
unacceptable conflictual impulse.
In some cases of posttraumatic headache, the most significant
component in perpetuating the symptoms is the compensation received by

the patient. The most usual compensation is, quite simply, relief from disliked
duties, responsibilities, or employment. The patient utilizes the accident as a
means of flight from an unpleasant job or some other situation about which
he has had long-harbored fantasies of escape. A second factor, desire for

financial remuneration and security, is demonstrated by the fact that these
patients often are employees of big corporations, the government, or other
institutions which provide benefits for injured workers.
Still a third component sometimes interwoven into the continuation of
symptoms is the attention, support, and solicitude these patients may long
have desired, and now gain from family members or an “understanding”
physician. They are, therefore, understandably reluctant to surrender a
symptom that provides such remarkable profits. Such individuals tend to

project, assigning their feelings and attitudes to those around them. They
sense and react to the wariness and suspicion that they arouse in the
physician, and in other ways also demonstrate great insecurity.
One of my posttraumatic headache patients was a forty-one-year-old
chemical-industry worker who injured his knee on a cracking tower, became
faint, and fell against an outside steel ladder. His faintness was associated
with fear of a fatal fall off the ladder onto the ground seven or eight stories
below, or into a mass of pipes, boilers, and other equipment. Immediately

following his feeling of faintness, the patient developed a headache. Results of
a neurological examination were negative, but after recovering from the
minor knee injury, he still complained of severe head pain associated with
dizziness. He found the condition so disabling that he could not leave the
ground to climb into the towers as his work required.
During an amytal interview, the patient associated his fear of death

from a fall with the memory of a friend’s fatal plunge at the same plant six
years before. He then voluntarily described a childhood experience in which

he fell from a bicycle, striking his head on the pavement. He recalled his
parents’ oversolicitous attitude toward the minor head pains he suffered.
After the interview, the patient connected the multiple accident history
with his expectation that his company would continue the compensation
which he had been receiving for nine months. After short-term
psychotherapy, with direct interpretation of his desire to be cared for, the
patient came to understand the nature of the psychological connections he

had made about the accident and returned to work with a gradually abating
headache pattern.
Hypochondriasis
Hypochondriasis, i.e., persistent pathological concern about the health

of the body, is expressed in marked diffuse preoccupation about
malfunctioning organs or parts. This concern tends to usurp all other
interests. Although at one time the term “hypochondriacal” was used only for
those patients who had no organic pathology, it is now used sometimes for
those with excessive preoccupation about actual organic illness. Symptoms of
the hypochondriacal state include complaints of pressure in the head,
inadequate memory, inability to concentrate, irritability, poor sleep patterns,

with any of these accompanied by multiple aches and pains, and all of them
dwelt on and described compulsively and repeatedly.
Many of the patients have basic character defects, or a serious internal
or visceral body-image problem. Although typically classified as a neurotic
disorder, hypochondriasis may actually incorporate beliefs about the body
which are delusional, hence psychotic.
Hypochondriasis is a compensation for serious defects in self-esteem or

for unaccomplished ideals in life. Many of the patients are bored, self-
centered, and lead dull, uninteresting lives. Many are victims of a series of
embittering misfortunes. Their symptomatology is the somatic expression of
the resentment and concern they are otherwise unable to express, and serves
to maintain their balance between rationality and irrationality.
The patients usually present the physician with a list of bodily

complaints in addition to headaches. Although the psychiatric approach
should aim toward reeducation, it is unrealistic to expect total relief of the

symptoms. In general, the prognosis is poor. It is difficult to discuss their
symptomatology with them or to treat the headaches directly. After the
therapist gives a long explanation of the nature of body symptoms and of how
the condition might have come about, the hypochondriacal patient will say,
“Well, of course, that doesn’t apply to me. Now what about my headaches?”
The lesson that body symptoms can be expressions of psychological

problems must be subtly taught. For the patient to acquire a new view of
frustration, tension, and anxiety, the physician must maintain an objective,
unemotional approach and be careful not to promise, even by implication or
attitude, that the patient’s physical symptoms will disappear; nor must he
permit the patient to think that just visiting the physician will make the
symptoms magically go away.
The physician should assume a joint-venture approach: “Yes, you have

symptoms, and yes, I have some knowledge. Perhaps, working together, we
may be able to understand the nature of your headaches and other
symptoms.” This attitude eventually reassures the patient and enlists his
cooperation. He gradually understands that the doctor will make no

pronouncements, and that it is the verbal explorations between the doctor
and himself which, by leading to a more lucid comprehension of his life
situation and bodily complaints, may in some measure ameliorate his

condition.
Causalgia and Painful Phantom
Causalgia is a posttraumatic syndrome characterized by persistent,
diffuse, burning pain, which is aggravated by stimuli that may be trivial or
purely emotional. The frequency of causalgic pain following, nerve injury is

approximately 2-5 percent in case reports, being much more common in the
upper than in the lower extremities. The patient is usually debilitated by it
and sometimes completely dominated by its timelessness.
Phantom pain can occur after the healing phase of an amputation or an

extensive avulsion. It is described as a burning, twisting, cramping, sharp,
shooting, cyclic pain perceived in the vicinity of the absent body part, usually
an extremity. While the nonpainful phantom is considered to be a normal
condition following amputation, the painful phantom is a pathological

circumstance reported in as few as 8 (0.36 percent) of 2200 patients by
Ewalt, Randall, and Morris.
There are three main theories attempting to explain the phantom
phenomenon and the painful phantom:
The Peripheral Theory
The peripheral theory states that persisting sensations from the nerve
endings in the stump are assigned to those parts originally innervated by the
severed nerves and result in these phenomena. According to this theory, a

neuroma develops, scar tissue is formed, and the circulation is decreased.
These factors, plus other mechanical defects and irritants, result in a constant
bombardment of impulses to the conscious mind giving rise to the phantom

and the pain.
The Central Theory
The central theory proposes that phantoms are due to conscious
processes that are more or less independent of sensory impulses from the
periphery. A question in this theory is whether awareness of the body is
learned or innate. In the structural or nativistic version, the phantoms reflect
the constant features of central representation of the sensory and motor

systems.
The body image is built up in the early years of life from multiple
postural, tactile, and visual-sensory impressions. The body image usually has
the same extension as the body surface, so that with loss of a body part there
is a reactivation of former perceptive patterns. The organization of these

sensory impressions probably takes place in the parietotemporal cortex. With
the passage of time, the phantom part shrinks as the body image is
reorganized through new sensory impressions. The evidence given for this
theory is the following:
1. No phantoms are found with congenital absence of limbs or early

childhood amputations, evidently because the body image is
not fully developed before the age of six. Also, no phantoms
are seen in adults if there is long anesthesia of the limb prior
to amputation.
2. The phantom is kept natural and more vivid if the patient exercises
it.
3. There is increased sensitivity in the stump with a telescoped

phantom than in the contralateral homologous limb. This is
interpreted as reflecting central reorganization, since there
are no changes in the stump to account for this heightened
sensitivity.
4. Incorporation into the phantom of extra factors such as rings is

observed.
5. Phantoms fade and telescope according to cortical representation.

The fingers and toes are more in contact with the
environment and have more nerves and cortical
representation than many other body parts. Therefore, they
are of greater importance in the body image, and their
phantoms will persist longer.
6. Fading is considered to be due to the gradual increase of central

suppression of afferent impulses as the body image is
reorganized.
7. Involuntary movements of the phantom are likened to Jacksonian

seizures, a central process.
8. The patient has the ability to call up the phantom at will and to
move it voluntarily.
9. Phantoms may be temporarily lost after certain brain injuries or

surgery only to reappear later because of central
reorganization.
The Mixed Theory
The mixed theory combines the peripheral and central theories and
proposes that the state of the internuncial pool is responsible for the
phantom sensations. According to this theory, peripheral irritation stimulates
internuncial neurons so that reverberatory, self-perpetuating circuits are set

up. Impulses go peripherally and centrally from these neurons, resulting in
perception of the phantom and pain. As impulses are overcome by conscious
inhibition, the phantom approaches the stump. If sensations are too painful
and enduring, the conscious inhibition is ineffective, and the phantom and
pain persist. This accounts for the success of peripheral methods of treatment
in the early stages of development of the painful phantom, and for failure
later when cord and brain surgery may not work. However, the phantom pain
is often unrelieved by surgical procedures. Thus, there has been more inquiry
into the dynamics and motivation in phantom limbs.
One psychiatric theory proposes that the phantom is a wish-fulfilling
hallucination resulting from the denial of a lost part, and that pain results
from denial of the affect associated with the loss. Some psychoanalysts stress
the decreased positive aspects of self-concepts, i.e., that the amputee feels
castrated and deprived, and that he lacks an intact personality.
The rule of denial is also stressed, although it is held by many that
denial has a limited place in the phenomenon. Kolb feels that denial does not
cause the phantom, which is a healthy psychological response. Rather, those
patients who do not experience a phantom are in fact denying their loss. He
attributes the lower incidence of phantom breast, penis, and so forth, to the
mechanism of denial. The phantoms are repressed because the patients
cannot accept the loss.
Weiss and English maintain that the phantom results from the
amputee’s narcissistic demand to retain the limb, and that the pain has the
functional value of convincing him on an unconscious level that the limb is
present. He manages this denial through activity.
Simmel believes that the phantom is genuinely experienced and may
become a focus for denial instead of being motivated by denial. Also, the
emotions and anxiety associated with the body loss are not denied but rather
the patient is overwhelmed by the effect.
It has been proposed that the phantom is a product of the unconscious
and subject to its law. Phantoms, like dreams and hallucinations, undergo
condensation, displacement, and secondary elaboration, and can pass through
solid objects. Simmel explains that phantoms are lacking in early childhood
amputations because there are not enough wishes about body organs at that
time. Pain results from provocation of the unconscious by peripheral
stimulation or by psychic conflicts between the opposed desires, regaining
the loss versus adjusting to reality.
The importance of the patient’s personality in his reaction to
amputation or afferent denervation should not be underemphasized. In a
study of combat casualties, psychiatric disturbances were related to the

patient’s personality and not to the nature of the injury. It is felt that the
patient’s emotions give force to the perceptive patterns activated by body
loss, and that the variety of responses to mutilation results from the varying
personalities.
The patient’s attitude about his body and the emotional significance of
his body parts are determined by family and cultural attitudes toward the
body and its parts. His body image is reinforced by these emotions and
attitudes. Therefore, on loss of certain body parts, varying emotions and
reactions to the event will come into play depending on the personality
makeup. The obsessional patient, for example, has considerable difficulty in

adapting to any bodily change, whether it’s a small dental bridge or an
extremity prosthesis.
It is only natural that a patient shows some anxiety concerning an
amputation. It is normal that an amputee mourns for the lost body part and is
anxious about its disposal. It was found in a study of war casualties that 64
percent of the patients showed anxiety or other psychiatric symptoms, which
were unobserved by ward personnel. It is abnormal, however, when an
amputee has persistent pain unrelieved by narcotics and not characteristic of
physical disease. Of those with a painful phantom, less than 20 percent had
signs of physical disease in the stump.
Kolb claims that states of fear, perception, and associated ideas
influence the internuncial pool in such a way that pain results, i.e., psychic
pain is projected via the internuncial pathways into the phantom, resulting in
the painful phantom. In the war studies, patients with this kind of pain
showed a marked psychopathology that was thought to reflect a premorbid
personality disorder. They gave evidence, for instance, of reckless behavior
and exhibitionism. Such patients are often hostile, demanding, and

uncooperative, and complain about neglect within and outside the hospital.
There seems to be a parallel between these patients and paranoids.
Kolb finds no consistent personality structure or defect, but feels that

these patients are generally maladjusted to their environment and to a
prosthesis. A chronic painful phantom represents an emotional response to
the loss of an important body part that is significant in the patient’s

relationship with others. Hostile feelings with resultant guilt feelings develop
toward those with whom the patient identifies as mutilating or mutilated, and
also toward those on whom he is dependent and whose rejection he fears. It
was noted that hostility was the forbidden impulse in these amputees. The
pain may symbolize punishment for these hostile and guilty emotions. Of
twenty-one patients with painful phantoms, fourteen had previously had a

close emotional attachment to another amputee.
Kolb thinks that amputations arouse fantasies of personal mutilation

which are overcome by repression. These fantasies may come to the fore after
amputation, resulting in such hostility and guilt feelings that even reference
to an amputee can elicit phantom pain. Pain can also be caused by mentioning
a person on whom the patient depends. Besides the hostility factor, pain has
the functional role of binding this person to the patient. An interesting finding
is that there seems to be a correlation between loss of function and phantom

pain. Patients with functioning prostheses tend to have normal phantoms,
whereas those with no prostheses or only cosmetic ones show an increased
incidence of pain.
An interesting psychological phenomenon found in amputees is the
projection of their own defects into the environment. For example, an
amputee often thinks normal people have amputations, while on closer

inspection he finds this is not so. On figure drawing tests, a patient may fail to
draw in the part that he lacks, or he may distort the figure in other ways. In
Rorschach tests, figures are cut off. Amputees may have wish-fulfilling dreams
in which the limb is present and functioning normally, or anxiety laden,
repetitive dreams reexperiencing the injury leading to amputation. All these
illustrations may be considered manifestations of a disturbance of body
image. Haber, in a study of postoperative reactions following amputation,

found that some amputees try to overcompensate to make up for their loss,
but others may become depressed and mournful.
Treatment
What then are some of the treatments for causalgia and the painful
phantom? Initially, rapid interruption of sensory impulses could be assured
by the use of local block in the area of injury, or by such modalities as
rhizotomy, cordotomy, tractotomy, thalamotomy, or leucotomy. The use of
ultrasound physiotherapy with the stump, psychopharmacologic agents, and
psychotherapy when indicated may be helpful. Relief by the use of
chlorpromazine, reserpine, and electroshock alone has been reported.

Imipramine and amitriptyline have been helpful as analgesics.
The psychotherapist should investigate the overall circumstances of the
patient, exploring his attitudes about the injury or amputation, preferably
before an elective amputation, with a view toward understanding the
patient’s feelings about his body image, his associations to his body parts, and
the relative value placed on body parts by himself and by his family. In
addition, the patient should be given the opportunity to discuss his fantasies
about the appearance of his injured extremity or about the disposal of the
amputated part. Considerable time should be spent exploring the patient’s
attitudes towards amputees and mutilated people, and previous associations

with individuals who have undergone amputation or mutilating injuries. His
attitudes, as gleaned from literature, about Captain Ahab in Moby Dick,
Captain Hook, or others, should also be investigated in an effort to assess his
overall feeling about bodily parts in terms of his own relative overevaluation
of them.
The patient should be reassured by the surgeon or physician as to the
mode of disposal of the amputated part. The damaged remaining body parts,
that is, the stump or the causalgic area, should be shown to be accepted by the
physician by his viewing and examining the area frequently, and thus
communicating to the patient its acceptability. More important, prior to an
elective amputation, the patient should be counselled that he can expect to

have phantom sensations and that this is a normal phenomenon. If this is
done, he may be spared much of the considerable anxiety that will occur
when he awakes from the anesthetic still feeling the absent extremity.
After a satisfactory sympathectomy, causalgia patients often make a
much more satisfactory social adjustment when placed on a schedule of

regular supportive contact with their physicians. This medical dependent
relationship offers opportunity for discussions of personal problems under
the symbolic presentation of mild sedative-analgesic combinations.
Conclusion
In summary, when evaluating and treating patients with a complicated
pain problem, one cannot understand the meaning of persistent, painful

complaining unless one considers the meaning of the symptom and its origin
in prolonged learned experiences in the patients’ family, culture, and daily
life. One should investigate their personality structures and those emotional
stresses to which they are abnormally reactive.
Bibliography
American Medical Association. Ad Hoc Committee on Classification of Headache. “Special Report,”

JAMA, 179 (1962), 717-718.
Beecher, H. K. “Pain in Man Wounded in Battle,” Ami. Surg., 123 (1946), 96-105.
Boag, T. J. “Psychogenic Headaches,” in P. J. Vinken and G. W. Bruyn, eds., Handbook of Clinical

Neurology, Vol. 5, pp. 247-257. New York: American Elsevier, 1969.
Brenner, C., A. P. Friedman, and S. Carter. “Psychological Factors in the Etiology and Treatment of
Chronic Headache,” Psychosom. Med., 11 (1949), 53-56.
Clark, W. C. and H. F. Hunt. “Pain,” in J. A. Downey and R. C. Darling, eds., Physiological Basis of
Rehabilitation Medicine, pp. 373-401. Philadelphia: Saunders, 1971.
Ewalt, J. R., G. C. Randall, and H. Morris. “The Phantom Limb,” Psychosom. Med., 9 (1947), 118-123.
Forrer, G. R. “Hallucinated Headache,” Psychosomatics, 3 (1962), 120-128.
Frazier, S. H. “The Psychotherapeutic Approach to Patients with Headache,” Mod. Treat., 1 (1964),
1412-1424.
----. “Psychotherapy of Headache,” Res. Clin. Stud. Headache, 2 (1969), 195-220.
Frazier, S. H. and A. C. Carr. Introduction to Psychopathology. New York: Macmillan, 1964.
Frazier, S. H. and L. C. Kolb. “Psychiatric Aspects of Pain and the Phantom Limb,” Orthop. Clin.
North Am., 1 (1970), 481-495.
Friedman, A. P. “Migraine and Tension Headaches,” Conn. State Med. J., 20 (1956). 440-444-
----. “The Mechanism and Treatment of Migraine and Tension Headaches,” Miss. Valley Med., 80
(1958), 141-146.
----. “Headache,” in A. M. Freedman, H. I. Kaplan, and H. S. Kaplan, eds., Comprehensive Textbook of

Psychiatry, pp. 1110-1113. Baltimore: Williams & Wilkins, 1967.
----. “The Headache in History, Literature, and Legend,” Bull. N.Y. Acad. Med. 2nd Ser., 48 (1972),
661-681.
----. “Current Concepts in the Diagnosis and Treatment of Chronic Recurring Headache,” Med. Clin.
North Am., 56 (1970), 1257-1271.
Friedman, A. P. and C. Brenner. “Psychological Mechanism in Chronic Headache,” Assoc. Res. Nerv.
Dis. Proc., 29 (1950), 605-608.
Friedman, A. P. and S. H. Frazier. “Critique of the Psychiatric Treatment of Chronic Headache

Patients,” Proc. 5th World Congr. Psychiatry, Mexico City, 1971. New York:
American Elsevier, 1973.
----. Personal communications, 1973.
Friedman, A. P., S. H. Frazier, and Schultz. The Headache Book. New York: Dodd-Mead, 1973.
Friedman, A. P. and H. H. Merritt. Headache: Diagnosis and Treatment. Philadelphia: Davis, 1959.
Fromm-Reichman, F. “Contribution to the Psychogenesis of Migraine,” Psychoanal. Rev., 24

(1937), 26-33.
Gittleson, N. L. “Psychogenic Headache and the Localization of the Ego,” J. Ment. Sci., 108 (1962),
47-52.
Graham, J. R. Treatment of Muscle Contraction Headache. New York: Harper & Row, 1964.
Grinker, R. R. and L. Gottschalk. “Head aches and Muscular Pain,” Psychosom. Med., 11 (1949), 45-
52.
Grinker, R. R. and F. P. Robbins. Psychosomatic Case Book. New York: Blakiston, 1954.
Haber, W. B. “Reactions to the Loss of Limb: Physiological and Psychological Aspects,” Ann. N.Y.
Acad. Sci., 74 (1958), 14-24.
Hardy, J. D., H. G. Wolff, and H. Goodell. “Studies on Pain Sensation. I. Measurement of Pain
Threshold with Thermal Radiation” (Abstract), Am. J. Physiol., 125 (1939), 523-524.
Kolb, L. C. “Pain as a Psychiatric Problem,” Lancet, 72 (1952), 50-54.
----.The Painful Phantom, Psychology, Physiology and Treatment. Springfield, Ill: Charles C.
Thomas, 1954.
----. “Psychiatric Aspects of the Treatment of Headache,” Neurology, 13 (1963), 34-37.
----. Modern Clinical Psychiatry, 8th ed. Philadelphia: Saunders, 1973.
Martin, M. J., H. P. Rome, and W. M. Swenson. “Muscle-Contraction Headache, A Psychiatric
Review,” Res. Clin. Stud. Headache, 1 (1967), 184-204.
Masserman, J. H. “The Neurotic Cat,” Psychol. Today, 1 (1967), 36-39.
Melville, H. Moby Dick. New York: Franklin Watts, 1967.
Pavlov, I. Experimental Psychology and Other Essays. New York: Philosophical Library, 1957.
Penman, J. “Trigeminal Sensoz Root Injection,” Opert. Surg., 16 (1958), 45-51.
Procacci, P. “A Survey of Modern Concepts of Pain,” in P. J. Vinken and G. W. Bruyn, eds.,

Handbook of Clinical Neurology, Vol. 1, pp. 114-146. New York: American Elsevier,
1969.
Rangell, L. “Psychiatric Aspects of Pain,” Psychosom. Med., 15 (1953), 22-37.
Robinson, D. B. “Psychological Aspects of Migraine,” Clin. Res. Rev., in press.
Rosenbaum, M. “Symposium; Psychogenic Headache,” Cincinn. J. Med., 28 (1947), 7-16.
Sacks, O. W. “Migraine: Intelligence, Social Class, and Family Prevalence,” Br. Med. J., 2 (1971), 77-
81.
Sargent, J. D., E. E. Green, and E. D. Walters. “Preliminary Report on the Use of Autogenic
Feedback Techniques in the Treatment of Migraine and Tension Headaches,”
Psychosom. Med. (in press).
Selinsky, H. “Psychologic Study of the Migrainous Syndrome,” Bull. N.Y. Acad. Med., 15 (1939),
757-763.
Simmel, M. L. “A Study of Phantoms after Amputation of the Breast,” Neuropsychologia, 4 (1966),

331-350.
Sloane, R. B. “Psychological Aspects of Headache,” Can. Med. Assoc. J., 91 (1963), 908-911.
Sperling, M. “A Psychoanalytical Study of Migraine and Psychogenic Headache,” Psychoanal. Rev.,
39 (1952), 152-163.
----. “A Further Contribution to the Psycho-Analytical Study of Migraine and Psychogenic

Headaches,” Int. J. Psychoanal., 45 (1964), 549-557.
Sternbach, R. A. Pain: A Psychophysiological Analysis. New York: Academic, 1968.
Touraine, G. A. and G. Draper. “The Migrainous Patient; A Constitutional Study,” J. Nerv. Ment. Dis.,
80 (1934), 1-23,182-204.
Weiss, F. and O. S. English. Psychosomatic Medicine. Philadelphia: Saunders, 1957.
Wolberg, L. R. “Psychosomatic Correlations in Migraine,” Psychiatr. Q., 19 (1945), 60-70.
Wolff, H. G. “Personality Features and Reactions of Subjects with Migraine,” Arch. Neurol.
Psychiatry, 37 (1937), 895-921.
Wolff, H. G., ed. Headache and Other Head Pain, 2nd ed. London: Oxford University Press, 1963.
Wood, E. H., A. P. Friedman, A. J. Rowan et al. “Observations on Vascular Headache of the Migraine
Type.” Paper presented before the 5th Symposium of the Migraine Trust, London,
September 1972.
Zborowski, M. People in Pain. San Francisco: Jossey-Bass, 1969.
Chapter 35
Sleep Disorders and Disordered Sleep
Robert L. Williams and Ismet Karacan
Introduction
Observers who enjoy speculating about such statistics have offered
various estimates as to how many times the stream of EEG paper generated in
sleep research would reach around the world. The fact that a recording for a
single night for one subject is often a quarter-mile in length stimulates a
variety of metaphors to describe this almost endless flow made possible by

the technological “breakthroughs” of the old dams which limited the size and
scope of sleep studies. Hopefully, the thousands of miles of EEG wiggles and
squiggles have produced information which can be useful to the clinician for
the solution of problems he encounters in the everyday practice of medicine.
In this chapter, we will concentrate on the findings which are pertinent
to sleep disorders. Under this category we will consider the so-called primary
sleep disorders. These are conditions in which various abnormalities of sleep
represent the cardinal and often only sign or symptom from which the patient
suffers. We will discuss secondary sleep disorders in which chronic clinical
problems are accompanied by specific or nonspecific sleep disturbances.

Parasomnias, in which an activity normally associated with waking behavior
appears during sleep, will be discussed. Sleep-modified disorders, in which
the basic disorder worsens or occurs primarily in sleep, will be mentioned
briefly, and additional references will be suggested for the interested reader.
The clinical information and research data about sleep disorders and
disordered sleep have been organized under the categories mentioned above
for convenience. In most instances, the etiology and the pathophysiological
mechanisms of these conditions are unknown or only suspected. This fact

makes it impossible at this time to classify them by etiology or mechanisms as
is typically done for diseases which are better understood. A group of
investigators in the Association for the Psychophysiological Study of Sleep has

been meeting periodically during the period of preparation of this chapter in
an effort to develop a standardized classification of sleep disorders and

disordered sleep which would provide a common point of reference for
clinicians and researchers in the field. Hopefully, a standard will be developed

with which the classification used in this chapter will be compatible.
The reader unfamiliar with the terminology employed by EEG sleep
researchers should consult Chapter 8 in Volume 6 of this Handbook. Briefly,
the classification of EEG sleep stages proposed by Dement and Kleitman, and
used by most workers, consists of four sleep stages and the waking state: (1)
wakefulness, or stage o, which is predominantly alpha activity; (2) stage 1, a

mixed-voltage fast pattern without sleep spindles; (3) stage 2, K-complex or
12-16 cycles per second (cps) spindle activity against a low-voltage
background; (4) stage 3, high-voltage, 1-2 cps activity (delta waves) during no
more than half of each scoring epoch; and (5) stage 4, delta activity during at
least half of the scoring epoch. Conjugate, rapid eye movements (REMs), as
monitored by the electrooculogram (EOG), and depressed electromyogram
(EMG) activity, periodically accompany stage-1 sleep. This special form of

stage-1 sleep is designated stage l-REM. Stage 1-REM, which has also been
called paradoxical sleep, typically occurs four to six times per night in healthy
adults, and subjects awakened from REM sleep usually report dreams much
more frequently than when awakened from non-REM (NREM) sleep. Stages-3
and -4 sleep (slow-wave sleep) are commonly considered to be the deepest
stages of sleep.
Primary Sleep Disorders
Under this category, as defined above, we have included insomnia,

narcolepsy, chronic hypersomnia, the Kleine-Levin and Pickwickian
syndromes, sleep paralysis, and frightening dreams.
Insomnia
This is probably one of the most common problems encountered by the

physician in his day-to-day practice. Until recently, the term “insomnia” was
often used loosely to describe any or all of the disorders discussed in this
chapter. As research has progressed, it has become possible to distinguish a

number of specific entities which were once lumped together under this
general term. Many authors in the past have listed physical or organic factors
as primary causes of some types of insomnia. We have been able to refine our
classification so that many conditions can now be considered as sleep-

modified disorders, or, as in the case of insomnia accompanying depression
or schizophrenia, they can be listed as secondary sleep disturbances.
We view the disorders which we shall include under this heading as a
very specific type of primary sleep disorder. Primary insomniacs suffer from a
persistent inability to obtain adequate sleep but they exhibit no gross

physical or psychological pathology. This restricted definition of insomnia is
relatively new, and as a consequence there are limited data from polygraphic
studies of this condition where the more circumscribed definition has been
utilized.
The incidence of insomnia has been assessed by both indirect and direct
methods. There are many reports which provide indirect evidence about the
prevalence of the disorder. The United States Department of Health,
Education, and Welfare reported a 535 percent increase in retail sales of
sedatives and tranquilizers between 1952 and 1963. In 1971, the consumer
newsletter Moneysworth stated that $170 million is spent annually in the
United States on sleeping pills.
More direct evidence is provided by Weiss et al., who obtained reports
of sleep disturbances in 72 percent of 108 male veterans who were
psychiatric outpatients, in 22 percent of 101 veterans being treated for
medical complaints, and in 15 percent of 110 active Air Force personnel with
no known medical or mental disturbance. They also found that sleep
disturbances increased with increasing age. One should pay special attention
to their finding of complaints in 15 percent of a supposedly healthy

population.
In the past, the most commonly accepted etiology for most cases of
insomnia was emotional disturbance. Such a conclusion was reached by a

study of the case history and an examination of the psychodynamics. The
hypotheses developed by these approaches had implicated almost every type
of psychopathological mechanism and led to a wide range of diagnostic

formulations. Insomnia has been described as a habit and a psychoneurosis, a
typical psychosomatic syndrome, or a type of reaction formation. Anxiety and
fear, including fear of unconscious repressed desires, fear of homicidal or
suicidal wishes, and fear of death, have all been implicated as primary causes.
Systematic studies of groups of insomniacs support the hypothesis that
some are more disturbed psychologically than are noninsomniacs. Monroe
examined the psychological, physiological, and sleep EEG characteristics of a

number of poor and good sleepers. In a questionnaire, his subjects were
asked about the length of time required to fall asleep, the number of nightly
awakenings, and the degree of subjective difficulty in falling asleep. Although
the poor sleepers self-categorized by the questionnaire were not suffering
from severe sleep disturbances and did not consider themselves insomniacs,
they were found to differ significantly from good sleepers because of greater
pathology on nine of the thirteen clinical scales of the MMPI (Minnesota
Multiphasic Personality Inventory). They also reported significantly more
somatic and emotional symptoms on the Cornell Medical Index. In a similar

study, Rechtschaffen was unable to detect any significant differences between
good and poor sleepers on MMPI scores, although the poor sleepers had
scores indicative of greater pathology on each of the scales. He suggested that
a smaller sample size and smaller initial sleep differences between his good
and poor sleepers may have prevented the detection of statistically significant
differences in the MMPI scores. Other workers have reported results similar
to those of Monroe.
Monroe found that poor sleepers showed greater amounts of

physiological activation than good sleepers. They exhibited greater numbers
of body movements and peripheral vascular constrictions, and higher basal
temperatures during sleep than the good sleepers. The poor sleepers also
tended to have higher heart rates and pulse volumes. The poor sleepers
appeared to be more activated—as reflected by levels of heart rate,
peripheral vasoconstriction, and rectal temperature— than good sleepers,
even before they retired. Rechtschaffen and Monroe concluded that the
persistence of physiological activation during the sleep of poor sleepers may
represent a failure of the rest-inducing mechanisms of sleep rather than a
continuation of the presleep level.
Insomniacs have usually been classified according to the time during the
sleep period when wakefulness is more troublesome. Some patients complain
mainly of difficulty in falling asleep. Some complain of frequent and/or long

awakenings after falling asleep. And others complain of early morning
awakenings. Many clinicians are aware of patients who have of a combination
of these complaints. However, if polygraphic data reported from the sleep

EEG’s of insomniacs can be considered more objective descriptors of the
qualitative and quantitative disturbances in the sleep of insomniacs, then it

becomes clear that the classification mentioned above is too simplistic. Data
from the limited number of polygraphic studies which have been performed
indicate that there are many different types of insomnia and various
combinations of disturbances. These studies have been reviewed elsewhere.
As an example, we will briefly describe two studies performed in our

laboratories. The first was a study of “hardcore” insomniacs. We found on the
second and third laboratory recording nights that eight male and two female
insomniacs between the ages of thirty and fifty-five exhibited significantly
longer sleep latencies and longer latencies of arising (time from morning
awakening to arising) than did the age- and sex-matched controls. Insomniacs
also obtained less total sleep than controls, but the large variability in the
insomniacs’ total sleep times prevented this difference from attaining

statistical significance. There was no difference between groups in the
number of awakenings, primarily because some of the controls awoke quite
frequently during the night. However, the ratio of total sleep time to time in
bed, which summarized the relative sleep efficiency, was significantly smaller
in the insomniacs. Many insomniacs and controls failed to obtain stage-4
sleep. Most of the subjects did obtain some stage 3, and the latency to the first
appearance of this stage from sleep onset was significantly longer in the
insomniacs. In the insomniacs, once stage l-REM sleep appeared it occurred at

a faster pace than in the controls, with the average time between stage l-REM
intervals being consistently shorter. During the first four hours of sleep the
cumulative minutes of stage l-REM was higher for the insomniacs. After the
first four hours, however, the insomniacs began to wake up and no
comparison was possible for the later hours of sleep. It is nevertheless clear
that insomniacs establish and maintain a higher absolute amount of stage l-
REM than controls as the night progresses.
In the second study, we examined the EEG sleep patterns of eleven male
insomniacs, ages thirty-four to fifty-six, and their age- and sex-matched
controls. Each subject’s sleep was recorded for eight consecutive nights. We
found that differences among subjects in the insomniac group were
significantly greater than the differences among control subjects in the
percentage of stage o and of stage 4. This suggested that our insomniac group
may have contained several different subtypes of insomniacs. Furthermore,
the insomniacs varied more from night-to-night than controls in total time in
bed; total sleep time; ratio of total sleep time to time in bed; sleep latency;
number of stage shifts; number of awakenings; percentages of stages l-REM,

2, and 4; latency to stage 4 from sleep onset; and the ratio of minutes of REM
sleep to minutes of stage 4 sleep. These results led us to speculate that part of
the insomniac’s problem may be that he can never predict whether or not he
will obtain a satisfactory night of sleep.
From our studies of insomniacs, we have noted several additional
factors which may contribute to the difficulties of adequately describing

them. Some patients who complain of not sleeping at all have apparently
normal sleep patterns in terms of the percentages of each sleep stage, but
exhibit alpha activity superimposed on the delta waves. These patients are
often quite resistant to pharmacological treatment. Other patients seem to
exhibit greater amounts of theta and beta activity. Since these qualitative
characteristics are not usually measured in the present sleep-stage scoring
system they may have been overlooked in other studies.
In conclusion, insomnia has been redefined to refer to a persistent
inability to obtain adequate sleep in individuals exhibiting no gross physical
or psychological pathology. Judging from sales of hypnotic medications,
insomnia is quite prevalent in the general population. Many early
explanations of insomnia attributed it primarily to emotional disturbance,
and more recent systematic studies support the conclusion that psychological
factors may play a role. However, there is also evidence of a physiological
basis for these patients’ complaints. Their sleep is considerably disturbed,
according to EEG criteria, both in terms of the kinds and amounts of sleep
they obtain, the night-to-night variability of their sleep patterns, and the
qualitative aspects of their EEG activity. From such studies it appears that
there may be several subtypes of insomniacs. Although the study of insomnia,
as we have defined it, has only just begun, it is obvious that these and future
findings may have major implications for the identification of more rational
therapeutic procedures for this sleep disturbance.
Narcolepsy
Although the symptom complex had been described earlier, Gelineau
was the originator of the term “narcolepsy” to refer to a condition consisting

of recurring, uncontrollable episodes of brief sleep. This syndrome has been
described with increasing refinement, and the criteria presented by Yoss and
Daly form the basis for present diagnoses.
In narcolepsy the primary symptom of sleep attacks is often
accompanied by one or more of three associated symptoms, i.e., cataplexy,

sleep paralysis, and hypnogogic hallucinations. Yoss and Daly referred to this
symptom complex as the “narcoleptic tetrad” and reported that 11 percent of
approximately 300 narcoleptics examined at the Mayo Clinic presented the

full set of symptoms.
Cataplexy, which occurred in 68 percent of Yoss and Daly’s patients, was

first described by Loewenfeld in 1902.253 It is characterized by brief
episodes of isolated or generalized muscular weakness, and the degree of
disability may range from a subjective feeling of weakness, through loss of
use of one or more extremities, to almost total paralysis. Emotion-provoking

events and other strong stimulations are common precipitators of these
attacks, and many patients develop peculiar stratagems for avoiding or
alleviating the effects of these situations.
Sleep paralysis is similar to cataplexy in that it involves loss of muscle
tone. However, it is usually experienced as a full-blown paralysis of the entire
body, and occurs solely during the transition between sleep and wakefulness,
or vice versa. Yoss and Daly reported that 24 percent of their patients
experienced this symptom. As will be discussed in a later section of this
chapter, this symptom has been increasingly described as an isolated
symptom in otherwise normal individuals. In either case, the individual

usually remains quite conscious during the attack, which may last from
several seconds to several minutes. A touch will usually terminate the attack,
if it has not ended spontaneously.
Visual and auditory hypnogogic hallucinations often occur during sleep
paralysis attacks in these patients. Yoss and Daly reported that 30 percent of
the Mayo Clinic narcoleptics exhibited this symptom, while Roth and Bruhova
observed an incidence of 19 percent in their sample of narcoleptics. The

experience is often a frightening one, but many patients appear to be aware of
the hallucinatory nature of it, which has prompted Roth and Bruhova to
describe it as a pseudohallucination. In any case, these hallucinations are
characteristically quite bizarre and kaleidoscopic in nature. Oswald has fully
discussed the psychological and neurophysiological aspects of these events.
It has become common practice to differentiate between idiopathic

narcolepsy and symptomatic narcolepsy. In the former the etiology of the
disorder remains unknown, while in the latter there is a history of, or an
association with, some organic disorder such as trauma, encephalitis,
epilepsy, etc. As will be discussed below, data from polygraphic studies of
narcoleptics suggest that there may be two forms of idiopathic narcolepsy-—

independent narcolepsy, in which sleep attacks are the only symptom, and
narcolepsy accompanied by one or more of the other symptoms in the
narcoleptic tetrad.
Although no systematic studies have been made of the incidence of
narcolepsy, Roth has estimated the incidence to be between 0.2 and 0.3
percent. At the Mayo Clinic, 241 cases were seen from 1950 through 1954,
and in 1960 Yoss and Daly reported that approximately 100 new cases are
seen there each year. The disorder appears to be equally distributed between
the two sexes, and the typical age of onset is during the second or third
decade. There is some evidence of a genetic basis for narcolepsy in the high
incidence in certain families.
Diplopia is a common and early symptom of narcolepsy in many cases,
and McCrary and Smith have described two narcoleptics with altered color
vision. Gunne and Lidvall found narcoleptics to excrete greater amounts of

noradrenaline in the urine than controls. These patients also exhibited
smaller daily fluctuations of noradrenaline levels. There were no

abnormalities in urine levels of dopamine, adrenaline, or vanillyl-mandelic
acid or in cerebrospinal fluid content of 5-hydroxyindolacetic acid.
Administration of 100 mg. of L-dopa or 200 mg. of DL-dopa had no alerting
effects on either patients or controls. These results should be somewhat
cautiously interpreted, however, for the patients had been withdrawn from
various medications, including amphetamine, just twenty-four hours prior to
the beginning of the study. Sjaastad et al. reported increased estriol secretion
in male narcoleptics, although some complicating factors did not allow them
definitely to attribute this increase to the narcolepsy per se. And finally,
Goodwin et al. have described a narcoleptic with an extremely high sensitivity
to alcohol.
The nature of the narcoleptic’s symptoms may often lead to the
misdiagnoses of hypothyroidism, hypoglycemia, and epilepsy, and each of

these disorders has at one time or another been assigned an etiological role in
narcolepsy. However several lines of evidence suggest that these factors are
not characteristic or critical in the etiology of the disorder. Yoss and Daly
have commented that lower basal metabolism rates in these patients may
seem to confirm the patient’s complaint of being always tired. However, if

care is taken to determine basal metabolism rates during times of relaxed
alertness, normal values are usually obtained. Furthermore, administration of

thyroid extract has not proved effective in increasing these patients’
alertness. Hypoglycemia may be diagnosed on the basis of the persistent
drowsiness and periods of impaired consciousness. However, sleep attacks
are often most common after meals, which would rule out hypoglycemia as a
precipitator. Furthermore, some narcoleptics are actually hyperglycemic,
while others exhibit no differences from controls in blood glucose values

during various phases of nocturnal sleep.
The evidence concerning the relationship of narcolepsy to epilepsy is
contradictory. Some investigators (see references 35, 72, 360, 395, and 414)
have detected abnormal or epileptiform waveforms in the waking EEG’s of
narcoleptics. Others have found most patients to have essentially normal

EEG’s. In Dynes and Finley’s study all but one of the seventeen patients with
normal EEG’s also suffered from cataplexy, while none of the five patients
exhibiting EEG abnormalities suffered from this symptom. As a result, the

authors proposed that patients with normal EEG’s be considered idiopathic
narcoleptics, and those showing EEG abnormalities as symptomatic. Daly and
Yoss found only two grossly abnormal EEG’s in a study of 100 patients during
a true alert state. On the other hand, they noted that although true sleep was
rare during the recordings, a majority of the patients exhibited patterns of
drowsiness at some time during the recording, often from the very onset of
the recording and for long periods. Daly and Yoss suggested that this
persistent drowsiness may lead to the impression that the EEG shows
generalized slowing. Furthermore, the EEG artifact produced by head
nodding during drowsiness may be misinterpreted as evidence of an akinetic
seizure. Dement and Rechtschaffen and their associates have suggested that
the periods of drowsiness (stage-i sleep) observed by Yoss and Daly may in
fact have been REM sleep which was undetected because' eye movements
were not monitored during the clinical EEG. However, Berti Ceroni et al. have
confirmed that prolonged periods of stage-1 sleep without eye movements
may characterize the daytime EEG’s of these patients.
Psychological factors have quite naturally been assigned a role in the
etiology of narcolepsy because of the apparent escapism involved in the

symptoms and because of the apparent psychotic nature of the hypnogogic
hallucinations. Sours has reviewed these propositions and particularly that
concerning the relationship between narcolepsy and schizophrenia. More

recently Mitchell et al. reported that all of twenty-two patients had undergone
prolonged periods of sleep deprivation and disturbance, in association with
major life transitions, prior to the recognition of their narcolepsy.

Nevertheless, both Roth and Yoss and Daly, who have studied large numbers
of these patients, have failed to detect any consistent evidence of
psychopathology. As Yoss and Daly noted, the social and economic disruption
in the narcoleptic’s life due to his symptoms may well lead to emotional
disturbance, but it remains to be shown that this disturbance is the basis of
the disorder.
Although modern sleep-research techniques have been extensively
applied to the study of narcolepsy since the early 1960s, their use has not yet
supplied any clear-cut evidence concerning the etiology of this disorder. Use
of them has, however, considerably refined the description of the various
narcoleptic phenomena, and in this way will undoubtedly contribute to the
ultimate explication of the etiology.
It is now rather commonly agreed that narcoleptics who experience
sleep attacks and one or more of the auxiliary symptoms of the narcoleptic
tetrad can be recognized on the basis of the sleep EEG. Whereas the normal
individual, even when napping during the day, proceeds through various
phases of NREM sleep before the first REM period occurs, narcoleptics with
cataplexy and/or the other symptoms exhibit a very strong tendency to enter
REM sleep directly from wakefulness during both daytime sleep attacks and
nocturnal sleep (see references 30, 31, 89, 187, 312, 315-317, 355, 356, and
399). Although this sleep-onset REM period has not characterized every
recording taken from every patient, it has occurred with sufficient frequency
to suggest strongly that in this type of narcolepsy there is some
neurophysiological or biochemical disturbance of the REM sleep system.
Furthermore, both direct and indirect evidence indicates that cataplexy,
sleep paralysis, and hypnogogic hallucinations represent dissociated forms of

REM sleep. It is well known that one of the unique and reliable characteristics
of normal REM sleep is the inhibition of muscle tone in some muscle groups,
and of tibial nerve-calf muscle and tibial-plantar electrically induced reflexes.
The relevance of this inhibition to cataplexy and sleep paralysis is obvious, as
is the dreaming of REM sleep to hypnogogic hallucinations. In fact, it has been

shown that, as in normal REM sleep, tonic EMG activity and H-reflexes are
depressed during the narcoleptic’s sleep-onset REM period, and that motor
inhibition is more pronounced during the sleep-onset REM period than
during these patients’ later REM periods or during the REM sleep of normals.
Polygraphic recordings (see references 31, 61, 88, 89, 184, 187, 189, 312, 313,
316, 317, 341, 355, 356, 399, and 402) during sleep-paralysis attacks and
accompanying hypnogogic hallucinations have consistently revealed patterns

of REM sleep. Although the early part of a cataplectic attack may be
accompanied by waking EEG patterns, REM sleep may develop if the attack
lasts long enough. Most patients who exhibit sleep attacks and other
symptoms of the narcoleptic tetrad have nocturnal sleep which is

characterized by numerous and long awakenings, decreased sleep time, and
frequent body movements, and even though these patients typically exhibit
sleep-onset REM periods, they obtain essentially normal amounts of REM
sleep and normal numbers of REM periods. However, there have been
occasional reports of increased REM time and numbers of REM periods. On
the other hand, with only one exception, deep slow-wave sleep has been
found to be rare or nonexistent in these patients.
Recordings of twenty-four-hour periods of patients with sleep attacks
and auxiliary symptoms have revealed increased REM time, as compared to
normals sleeping approximately eight hours, in many, but not all, patients.
Passouant and his colleagues reported that the REM sleep attacks occur
approximately every two hours during the day, suggesting a continuation
during the daytime of the REM cycle of normal nocturnal sleep. These
investigators also noted that the frequent daytime sleep attacks and
interrupted night sleep of these patients produce a polyphasic twenty-four-
hour sleep pattern, which contrasts with the monophasic pattern of normal
adults but resembles the typical sleep pattern of infants.
In contrast to narcoleptics with auxiliary symptoms, narcoleptics who
experience only sleep attacks very rarely exhibit sleep-onset REM periods
(see references 30, 89, 187, 315, 316, 355, and 356). Instead, their attacks
resemble normal NREM sleep periods. Furthermore, the nocturnal sleep of

these patients appears to be essentially normal both quantitatively and
qualitatively.
These observations originally suggested that only patients exhibiting

auxiliary symptoms should be classified as narcoleptics, since the NREM sleep
attacks of independent narcoleptics could not be distinguished from the
NREM sleep periods of normals. However, it has been consistently observed

that narcoleptics with auxiliary symptoms may at least occasionally exhibit
NREM sleep attacks and nocturnal sleep onset, that some of these patients
never exhibit sleep-onset REM periods, and that NREM sleep frequently
follows the sleep-onset REM period in an attack. Furthermore, imipramine,
which is effective in alleviating the auxiliary symptoms of narcolepsy, but

ineffective in relieving the sleep attacks, has been shown to suppress REM
sleep in narcoleptics. On the other hand, amphetamine, phenmetrazine and
methylphenidate, which are effective against sleep attacks but not against the
auxiliary symptoms, have less drastic effects on REM sleep and also appear to
decrease NREM sleep to a certain degree. These observations have led to
more recent suggestions that there is a NREM sleep disturbance in many, if
not all, narcoleptics, but that REM sleep disturbances are also important in
narcoleptics with auxiliary symptoms.
Although the narcoleptic who exhibits sleep-onset REM periods displays
an abnormal propensity to enter REM sleep, it has generally been argued that
this does not reflect an excessive need to spend large amounts of time in REM
sleep. This conclusion is based on observations that various degrees of REM-
sleep deprivation in normal subjects, with the resulting, presumed build-up of

a “need” for REM sleep, only rarely produce sleep-onset REM periods during
the recovery period. Furthermore, the narcoleptic’s typically normal amount

of nocturnal REM sleep contrasts with the rebound of REM sleep during
recovery from REM deprivation in normals.
As an alternative to this explanation, Rechtschaffen and Dement
proposed that the REM disturbance reflects a failure of wakefulness and
NREM sleep to inhibit the appearance of REM sleep. Passouant and his
colleagues have made a similar suggestion. However, as Rechtschaffen and
Dement have commented more recently, the admission of an important
NREM-sleep disturbance would necessitate the postulation of a failure of
wakefulness to inhibit NREM as well as REM sleep.
To summarize, narcolepsy and the narcoleptic tetrad of symptoms
probably affect less than 1 percent of the population, but the bothersome and
sometimes dangerous nature of the attacks makes them serious public-health
problems. It is generally agreed that hypothyroidism, hypoglycemia, and
epilepsy are not significant etiological factors. Although the narcoleptic may
develop emotional disturbance as a result of the problems caused by the
disorder, there is little empirical evidence that psychological factors play a

major role in the etiology of this disorder. On the other hand, disturbances of
both REM and NREM sleep would seem, in some as yet unknown fashion, to
be basic to the disorder. There is substantial evidence suggesting that
narcoleptics who experience only sleep attacks suffer primarily from a NREM
sleep disturbance. In patients who also experience the other symptoms of the
narcoleptic tetrad, both the REM and NREM systems appear to be disturbed,
and cataplexy, sleep paralysis, and hypnogogic hallucinations probably
represent dissociated forms of REM sleep. It has been suggested that the
narcoleptic’s attacks reflect a failure of wakefulness to suppress REM and/or
NREM sleep.
Chronic Hypersomnia
As its name implies, hypersomnia is characterized by excessive sleep.
Although this disturbance may also characterize narcoleptics and patients

suffering from the Pickwickian syndrome, and is a periodic manifestation in
the Kleine-Levin syndrome, in chronic hypersomnia the excessive sleep is the
primary chronic symptom. According to Roth there are two categories of
chronic hypersomnia. In the first, there is good evidence that the excessive
sleep or sleepiness is associated with or precipitated by some central-
nervous-system (CNS) disorder such as skull trauma, brain tumor,

encephalitis, or cerebrovascular accident, and for this reason Roth called it
“symptomatic hypersomnia.” Functional hypersomnia has no demonstrable

organic basis. In patients with either disorder there is a notable increase in
daily sleep time, and this increase may result from an excessively long
nocturnal sleep period and/or frequent or long daytime sleep periods.
Rechtshaffen and Roth noted that these patients rarely complain of disturbed
nocturnal sleep, in contrast to narcoleptics. However, they often experience
extreme difficulty in awakening and postdormital confusion, or “sleep
drunkenness,” once they do awaken. Daytime sleep attacks lack the
compelling and irresistible nature of the narcoleptic’s sleep attacks and may
last for several hours or days. In their latest report, Roth et al. concluded that
there is a complete form of hypersomnia, consisting of postdormital

confusion, very deep and prolonged sleep, diurnal hypersomnia, and rapid
onset of nocturnal sleep. There is also an incomplete form, which consists
only of postdormital confusion and deep and prolonged sleep.
Data on the incidence of this disorder are virtually nonexistent, both
because of an as yet unclear distinction between natural long sleepers and

hypersomniacs, and because of the relatively recent recognition of chronic
hypersomnia as a distinct clinical entity. Roth et al. reported that 161 cases of
hypersomnia, with and without sleep drunkenness, were seen in their clinic
in Prague over the last twenty years, with 71 percent being classified as
idiopathic cases. These investigators noted that incidence figures cannot be
reliably based on numbers of self-selected clinic patients. They believe that

many patients with hypersomnia do not seek medical help for their problem,
and that the ratio of idiopathic to symptomatic cases may be higher in the
general population since symptomatic cases are more likely to be seen in a
clinic because of additional symptoms and more sudden changes in sleep

patterns.
From the meager evidence concerning this disorder it appears that in
idiopathic cases the age of onset may range from childhood through the third
or fourth decade. In symptomatic cases, the age of onset would of course
depend on the age at which the CNS disorder occurred, but in one study of
hypersomniacs with sleep drunkenness age of onset was generally later than
in idiopathic cases. In both types the disorder usually continued throughout
life, with only minor periodic increases or decreases in symptomatology.
From the samples of patients studied there is a suggestion that hypersomnia
occurs about equally in the two sexes. In idiopathic cases there is frequently a
family history of the disorder.
In their study of these patients Rechtschaffen and Roth described the
polygraphic nocturnal sleep patterns of a rather heterogeneous group of
hypersomniacs. Ages ranged from twenty to fifty-three years, and some

patients were essentially normal psychologically while others showed greater
or lesser degrees of psychopathology; various constellations of the
hypersomnia symptom complex were present. Although there was a relative

decrease in symptoms during the laboratory sleep nights, Rechtschaffen and
Roth felt confident in concluding that there were no deviations from normal
patterning or percentages of sleep stages in these patients. None of the
patients exhibited the sleep-onset REM periods characteristic of narcoleptics.

Sleep averaged 8.8 hours in length, excluding one subject who typically slept
over twenty hours in the laboratory. The sleep period beyond the normal
seven or eight hours was a continuation of the typical alternation of sleep
stages. Although the patients often complained of difficulty in awakening,
there was no evidence of abnormal amounts of slow-wave sleep, in which
auditory awakening thresholds are elevated in normals. In two instances of

postdormital confusion the EEG showed an alternation of wakefulness and
stage-1 sleep.
In a second report Roth et al. described the daytime sleep patterns of
hypersomniacs who experienced postdormital confusion and daytime
hypersomnia. Sleep consisted primarily of alternations between stages-1 and

-2 sleep, and was interrupted by frequent awakenings. Stages-3 and -4 sleep
were rare, although this may have been due to the fact that most of the
recordings were made in the early afternoon, when these stages are less
prevalent in normals. REM sleep was also absent, but the authors noted that
this may have resulted from the brevity of the recording period.
Among the most suggestive results in this series of studies was the fact
that hypersomniacs exhibited faster heart and respiratory rates than “good
sleepers,” “poor sleepers,” and “deep sleepers,” both before and during
nocturnal sleep. There was some evidence that severity of hypersomnia might
be related to the degree of elevation of these rates.
Although Rechtschaffen and Roth cautioned against speculating
extensively on the basis of these findings until and unless they are replicated,
these investigators have suggested that the heightened activation manifested
by hypersomniacs may reflect activation of neural mechanisms controlling
heart and respiratory function as well as sleep, or release from centers which
inhibit these functions. It may also be that the activation reflected by heart
and respiratory rates produces an increased need for sleep in the
hypersomniac. These are intriguing possibilities, but there remain many
questions which must be answered before this disorder is fully understood.

For example, Roth et al. have drawn attention to the fact that there seems to
be more than a chance relationship between narcolepsy and the
hypersomniac symptom of sleep drunkenness, even though hypersomnia and
narcolepsy are typically clearly distinguishable from each other. On the other
hand, the difference between the hypersomniac and the normal “long sleeper”
described by Webb and Agnew is unclear, especially since postdormital
confusion can occur in normals following excessive sleep.
Thus we have seen that there is a distinct clinical entity of chronic
hypersomnia which may be symptomatic or functional. Rapid sleep onset,

deep and prolonged nocturnal sleep, postdormital confusion, and diurnal
hypersomnia characterize the complete form of this disorder, while deep and
prolonged sleep and postdormital confusion characterize the incomplete

form. The few studies exploring this disorder have failed to reveal any
abnormalities in the sleep patterns of hypersomniacs, although these patients
appear to exhibit higher heart and respiratory rates than normals and certain
other types of individuals. Neither the mechanism of this disorder nor the
manner in which hypersomniacs differ from natural long sleepers and other
patients who exhibit sleep attacks or excessive sleep has yet been elucidated.
The Kleine-Levin Syndrome
In 1942 Critchley and Hoffman called attention to the syndrome
described by Kleine and Levin and characterized by periodic hypersomnia
and morbid hunger. Critchley and Hoffman proposed that this syndrome be
called the Kleine-Levin syndrome and described two additional cases. In 1962
Critchley reviewed the thirty-one cases reported up to that time, and
emphasized several characteristics of the symptom picture. Among these

were a preponderant or unique occurrence in males, a typical onset in
adolescence, a spontaneous disappearance, compulsive eating rather than

excessive appetite, and behavioral abnormalities. Critchley concluded that
only twenty-six of the reported cases, including eleven described by him,
could be considered genuine examples of this syndrome. Sours confirmed the
rare incidence of the disorder. He reviewed the histories of 115 patients seen
at Columbia Presbyterian Medical Center in New York for various complaints
of excessive sleepiness from 1932 to 1961, and did not find a single case of
Kleine-Levin syndrome. Since Critchley’s review in 1962 a number of new
cases have been described (see references 24, 29, 39, 98, 100, 105, 142, 150,
157, 190, 265, and 407), but in the process Critchley’s original diagnostic
criteria have been somewhat broadened and modified. For example, several
female cases have been described. The case presented by Thacore et al. began
displaying symptoms at age eight and did not exhibit excessive eating, while
Berti Ceroni’s case evolved into narcolepsy. Such differences, as well as others
to be discussed below, led Oswald and Thacore et al. to conclude that the
existence of a distinct nosological entity characterized by periodic
hypersomnia and excessive eating has yet to be proven, and that placement of
a case in this category is largely a matter of preference. Pai had earlier
concluded that the Kleine-Levin syndrome is not a definite clinical entity.
With this controversy in mind, we will nevertheless review some of the
major findings from the reported cases. One of the two primary
characteristics of Kleine-Levin patients is what has been termed periodic

hypersomnolence. Oswald has noted, however, that it has yet to be
established that these patients in fact sleep excessively. For this to be done
would require systematic monitoring of various physiological parameters,
including brain waves, during the periods of so-called sleep. Although

numerous investigators have reported EEG findings, the lack of precise
descriptions of the patient’s status (during or between exacerbations, asleep
or awake) or of the examination situation (patient sitting or lying down, day
or night recording, length of recording) makes it very difficult to derive a
clear picture of the EEG characteristics of these patients. Furthermore, even
the results which are clearly interpretable are contradictory. For example,
Rosenkotter and Wende reported that sleep EEG activity during sleep attacks
corresponded to that of natural sleep. Barontini and Zappoli found afternoon
sleep during an attack to be light and unstable, but concluded that there was
“no evidence of significant abnormality of the cortical biorhythms . . .”
Barontini and Zappoli’s patient was a twenty-nine-year-old male and the
recorded sleep period lasted from 4:30 to 8:00 p.m. We have reported that
normal males between the ages of twenty-one and twenty-eight obtained 14
percent stage-4 sleep and 19 percent REM sleep during naps between 4 and 6
p.m. Barontini and Zappoli’s patient obtained no stage-4 or REM sleep and
only moderate amounts of stage-3 sleep. Thus, there did appear to be a
significant lightening of this patient’s sleep pattern during this

hypersomnolent episode. On the other hand, other investigators failed to
detect any spindles during “sleep” attacks. Since the presence of spindles is a
criterion for the existence of EEG sleep, these data indicate that true sleep
may not appropriately characterize the daytime state of the Kleine-Levin

patient. Garland et al. reached a similar conclusion when they described their
patient as withdrawn rather than somnolent during the exacerbation.
One recording made of the night sleep of a Kleine-Levin patient revealed
that sleep was generally light and unstable, although stage-3 sleep was
moderately present. Stage-4 sleep occurred several times but never for long
intervals. Only two very short REM periods occurred during the seven-hour
recording period. A similar recording made following the exacerbation
revealed more normal amounts of deep sleep, but REM periods were still
quite short. Markman confirmed this last result.
If these sleep-EEG data prove to be accurate when more subjects have
been studied, it may well be argued that both the night and daytime sleep of
Kleine-Levin patients is disturbed, especially in comparison to age-matched
normals. From the sparse data available it would appear that these patients
obtain significantly less REM and deep-stage-4 sleep at night. Their daytime
sleep is either unusually light or not really sleep at all. Furthermore, even
between attacks these patients seem to obtain abnormally low amounts of

REM sleep at night. This last fact might indicate that this disorder is not truly
periodic, as has been claimed, but that these patients suffer from persistent
sleep abnormalities which are periodically exaggerated.
The second primary characteristic of this disorder is excessive eating.
Although Critchley considered it to be a necessary component of the clinical
syndrome, subsequent cases have not always exhibited this behavior.

Critchley suggested that this characteristic consisted of compulsive eating
rather than bulimia, but Gilbert has contested this view. Garland et al. have
criticized Critchley’s use of various terms for overeating and Pai noted that
often there have been no quantitative data to support reports of overeating.
Among the other characteristics reported more or less frequently
during excerbations in Kleine-Levin patients are sexual excitement or
disinhibition; particular preference for sweets; irritability, especially when

aroused from sleep; full or partial amnesia either during or following the
attack; and depression and insomnia following the attack. Weight gains
during the attacks and euphoria following them have also been reported for
some patients. There have been no consistent abnormalities discovered by
radiological or laboratory studies.
Critchley found a psychiatric explanation of this disorder to be
unsatisfactory, particularly since most of his patients appeared to be normal
before the onset of symptoms. However Oswald noted that many of
Critchley’s cases showed apparent schizophreniform abnormalities during

attacks. Pai concluded that the hypersomnolence and excessive eating
characteristic of this disorder occur together coincidentally, and that both are
hysterical in nature.
Levin proposed the first organic theory of the etiology of the syndrome
bearing his name. He suggested that the symptoms result from excessive
inhibition or exhaustion of frontal-lobe centers controlling these behaviors.
Gallinek subsequently suggested that the frontal lobes and/or the
hypothalamus are implicated on the basis of studies of lesions or tumors in
these areas. Most authors (see references 24, 74, 98, 105, 140, 142, 157, 190,
311, and 351) have agreed that dysfunction of hypothalamic or diencephalic

areas is involved, in view of the disturbances in sleeping, alimentary, and
sometimes sexual behavior. Several investigators have proposed that this
disorder is related to narcolepsy or to convulsive disorders.
Interactions between psychological and organic factors have received
attention from some investigators. Thus Gilbert proposed that

psychodynamically the Kleine-Levin exacerbation might represent an escape
from a threatening environment by an individual who can sense its demands
but who is unable to cope with them. According to Gilbert these psychological
factors would determine the temporal occurrence of the syndrome, but an
underlying diencephlic dysfunction would determine the specific
manifestations of the syndrome. Earle suggested that this condition is a
psychosomatic disorder which emerges when individuals with

psychopathology in the oral sphere also experience some pathology on the
organic level, and possibly at the level of the hypothalamus. Bonkalo has also
proposed an interactive interpretation of the etiology of the Kleine-Levin

syndrome and of other hypersomnia syndromes.
As we have seen, there is considerable debate about the exact nature of
the characteristics defining the Kleine-Levin syndrome. There is suggestive
evidence that patients suffering from this disorder may not in fact be truly
asleep during their periodic attacks of daytime hypersomnolence; their
nocturnal sleep patterns are abnormally light. In addition, two patients have
shown persistent REM-sleep abnormalities following clinical improvement.
Excessive eating has not been an entirely consistent finding in these patients,
and there have been few quantitative descriptions of this symptom. A variety
of abnormal behaviors, including sexual disinhibition, irritability, and
depression, have been reported to occur during or following the attacks. Most
authors agree that some dysfunction at the diencephalic or hypothalamic

level is the basis for this syndrome, although several have proposed
exclusively psychological or combined psychological and organic
explanations. At this point, the paucity of data concerning this disorder allows
only speculation as to the etiology or localization of the dysfunction. The
debate about the reality of the Kleine-Levin syndrome as a distinct clinical
entity may contribute to the difficulty in more fully illuminating this rather
interesting set of symptoms.
The Pickwickian Syndrome
Readers of Charles Dickens’s The Posthumous Papers of the Pickwick
Club will remember the description of the rotund lad, Joe, who could not
manage to stay awake. Recalling this description in 1956, Burwell and his
associates coined the apt term “Pickwickian syndrome” to refer to a condition
characterized by marked obesity, somnolence, twitching, cyanosis, periodic

respiration, secondary polycythemia, right ventricular failure, hypoxia, and
hypercapnea. The syndrome had previously been described under less
spectacular names. Subsequent study of this condition has often failed to reveal
all of the symptoms listed by Burwell et al., and obesity, hypersomnia and
periodic respiration are now considered to be primary diagnostic criteria.
Escande et al. have proposed that there are two subcategories of this syndrome,
a “Burwell type,” which is the most advanced form and is characterized by
obesity, hypersomnolence, and alveolar hypoventilation and its concomitants,
and a “Joe type,” which consists only of obesity and hypersomnia.
Polygraphic studies have begun to provide some interesting
information on the relationships between two of the primary symptoms of

this disorder, hypersomnolence and periodic respiration. Drachman and
Gumnit were the first to describe the cyclical changes in EEG and respiration
patterns during the sleep of these patients, and their observations have been
confirmed and elaborated by others. Very shortly after the Pickwickian

patient enters sleep, apneic intervals lasting from five to sixty seconds begin
to appear. During the periods of apnea typical sleep patterns occur, and the
length of these intervals depends on the depth of sleep during which they
occur, with deeper stages being characterized by longer, and possibly less
frequent, periods of apnea. Just prior to the return of respiration there is an
EEG arousal response consisting of alpha activity or a K-complex. The EEG

may not necessarily show waking patterns, but only lightening of sleep.
Concurrently the patient takes several deep breaths, and then the whole cycle
begins again. During successive cycles the sleep stage during the apneic
periods may progressively deepen. At the end of several cycles, the arousal
terminating the apnea may be particularly intense and accompanied by a
body movement. Eventually one of these more intense arousals becomes a
more complete awakening, after which begins a new series of deepening
sleep episodes terminated by arousal.
This pattern of EEG and respiratory changes has been observed during
both diurnal and nocturnal sleep in Pickwickian patients. As a result, it is not
surprising that a cardinal feature of their sleep, whatever the time of day, is
its discontinuity. Although these patients have been reported to obtain over
ten hours of sleep per twenty-four hours, this represents the sum of many
short sleep periods rather than one extended sleep period. The discontinuity
is accompanied by further sleep abnormalities. In many cases REM and deep

slow-wave sleep are absent or rare (see references 69, 147, 185, 211, 330,
and 406). In other patients, REM-sleep periods may still be present but are
somewhat shorter than normal. Some investigators have reported a lessening
of the apneic disturbances during REM sleep, while others have found the
disturbance to persist and interact with the respiratory irregularities
normally characteristic of REM sleep.
Since the systematic study of Pickwickian patients is relatively new,

there are, understandably, insufficient data to allow full agreement on the
mechanisms and etiology of this disorder. As Escande and his colleagues have
suggested, the parallel but virtually independent work performed by
internists and electroencephalographers has also contributed to some of the

debates about these matters. One widely discussed topic is the pulmonary
function status of Pickwickian patients. Some investigators believe that
chronic hypercapnea and hypoxia, secondary to chronic alveolar

hypoventilation, characterize the Pickwickian, possibly as a result of the
increased work required to breathe in the extremely obese. Others maintain
that in the “pure” Pickwickian waking pulmonary function is normal enough

to allow adequate blood-gas exchange to occur. As noted earlier, Escande et
al. have proposed that there may be two forms of the Pickwickian syndrome,
one characterized by primary alveolar hypoventilation and the other not.
A second area of controversy is the nature of the apneic mechanism in
these patients. Gastaut et al. found that 80 percent of one patient’s apneic
episodes were peripheral or obstructive in nature, while 15 percent were of
central origin and 5 percent were of mixed type. Coccagna et al. also observed
both central and obstructive types of apnea, but concluded that central
mechanisms control the apnea, with the obstructive phenomena sometimes
occurring as a result of hypotonia and thus prolonging the existent central

apnea. Hishikawa et al. found that apnea was obstructive in nature in their
two patients, but suggested that centrally determined apnea may eventually
appear as a result of the development of a permanent hyposensitivity of the
respiratory centers to C02 retention. This would occur following the rather
chronic nocturnal hypercapnea accompanying the initial obstructive apnea.
Several authors have stressed the fact that the periodic respiration of
Pickwickian patients is an exaggeration of respiratory changes occurring
during normal sleep. In normal individuals, the onset of sleep is characterized

by decreased ventilation, increased C02 tension, and decreased arterial
oxygen saturation, and the conclusion has been that respiratory centers are
less sensitive to C02 during sleep. Bülow has reported that C02 sensitivity is
lower during the deeper stages of sleep than during the lighter stages.
Furthermore, some normal individuals may exhibit short apneic episodes

during sleep. These observations have led to the suggestion that the nocturnal
respiratory disturbances of the Pickwickian are a function of a coordinated

disturbance of respiratory rhythm and sleep-waking regulation in the brain
stem. However, the fact that disturbed nocturnal respiration may persist even
after improvement of other clinical symptoms (hypersomnolence, pulmonary
ventilation) following loss of weight, suggests that these patients retain a

tendency to C02 hyposensitivity.
The postulation of an intimate relationship between disturbances in
respiration and sleep-waking mechanisms naturally introduces the question

of the etiology of the hypersomnolence in these patients. Jung and Kuhlo, as
well as others, have suggested that chronic C02 hyposensitivity, with the
resulting hypoventilation and hypercapnea, disposes the Pickwickian to
diurnal sleep attacks in the absence of arousing stimuli. Another view is that
diurnal sleepiness and sleep are the result of poor and disturbed nocturnal
sleep. Still another view is that a primary disturbance of the sleep-waking
mechanism, analogous to that of narcoleptics, produces the daytime sleep

attacks. It should be noted, however, that most investigators have clearly
distinguished Pickwickians from narcoleptics, primarily on the basis of the
facts that Pickwickians do not exhibit cataplexy, sleep paralysis, hypnogogic

hallucinations, or the sleep-onset REM periods characteristic of many
narcoleptic sleep attacks, while narcoleptics do not exhibit marked periodic
respiration during sleep.
From this discussion it is clear that the Pickwickian syndrome, although
relatively rare, has engendered lively interest on the part of sleep

researchers. It has been confirmed that Pickwickians suffer from distinct
disturbances in the maintenance and quality of sleep. These disturbances
appear to be intimately related to these patients’ respiratory disturbances,
but the exact nature of this relationship, as well as the relationship of the
sleep and respiratory disturbances to other clinical symptoms such as

obesity, has yet to be fully determined.
Sleep Paralysis
Sleep paralysis, as described in the recent literature, occurs during the

transition between the waking and sleeping states. The individual is aware of
his surroundings but is unable to move voluntarily. Respiration is not usually
impaired to a significant degree. In most cases the sufferer is unable to talk,
although he may manage to moan and thus attract the attention of others.
Anxiety and hypnogogic hallucinations are frequent concomitants of the
paralysis. In some cases the anxiety subsides as the individual becomes
accustomed to the benign nature of the attacks, but in others the attacks are
always accompanied by anxiety. The individual experiencing hypnogogic
hallucinations is generally aware of the unreal nature of his perceptions. Most
sleep paralysis attacks last a maximum of several minutes, but often the time
sense of the sufferer is quite distorted. The frequency of attacks is highly

variable both between and within individuals. In most instances any external
stimulus, and particularly a touch, will terminate the attack, although in some
cases a stronger stimulus is required. If the attack is not terminated by
external means, it eventually ends spontaneously. In some cases the
individual must get up and move around in order to prevent a series of
attacks.
This disturbance has been most frequently described as one of the

constituents of the narcolepsy syndrome. Thus 34.4 percent and 28 percent of
two samples of narcoleptic patients displayed this symptom. There are also
occasional reports of sleep paralysis accompanying psychosis. However, sleep
paralysis as an isolated symptom has been described more and more

frequently (see references 40, 67, 154, 247, 250, 363, 369-373, and 412).
Although Rushton and Schneck had expressed the belief that isolated sleep
paralysis is much more common than case reports would indicate, it

remained for Goode to support this belief with a systematic incidence study.
He found that fifteen of 231 medical students, none of fifty-three nursing
students, and two of seventy-five hospital inpatients reported isolated sleep

paralysis. Subsequently Everett reported that 15.4 percent of fifty-two
medical students claimed to have experienced sleep-paralysis attacks and
none had experienced either narcoleptic sleep attacks or cataplexy. In
Goode’s study the age of onset of sleep-paralysis attacks ranged from eight to
fifty years, and among Everett’s medical students the onset age ranged from
childhood to the college years in those individuals who responded to this
question. Of Goode’s subjects, three experienced both pre- and postdormital
attacks, two experienced predormital attacks only, and twelve experienced
postdormital attacks only. Several of Everett’s subjects reported a greater
likelihood of having attacks during naps than at night. Histories of

parasomnias, such as sleep hallucinations, sleepwalking and sleep talking,
were also reported by some of Goode’s subjects.
There are contradictory data on the sex distribution of sleep paralysis.
Approximately 80 percent of Goode’s subjects who reported sleep paralysis
were males. However, in his survey sample over two-thirds of the

respondents were males, and this may have contributed to the unequal sex
distribution among the sleep-paralysis sufferers. In a study of two families
with isolated sleep paralysis Roth et al. found a conspicuous predominance of

women with the disturbance. This study indicated that sleep paralysis is a
genetically determined disturbance which is invariably transmitted by the
mother. Roth et al. concluded that dominant heredity bound to the X-

chromosome is the method of transmission. Other authors have described
cases with family histories of sleep paralysis.
Sleep paralysis is particularly difficult to study, both because of its

variable frequency of occurrence, and because the stimulation involved in
examining the patient during an attack usually terminates the paralysis. In

addition, aside from the reports that individuals suffering from isolated sleep-
paralysis attacks exhibit essentially normal waking EEGs, there are no
systematic descriptions of the clinical characteristics of these individuals.
As is the case with many of the sleep disorders, etiological theories of
sleep paralysis tend to stress either psychological or organic factors.
Langworthy and Betz offered a psychological interpretation in which sleep
paralysis is viewed as a neurotic defense against primary anxieties associated

with realistic adjustments in interpersonal relationships. Others have
suggested that the disorder is related to a state of confusion as to emotion
and intention, fear of destructive impulses, or anxiety reflecting the
individual’s own specific conflicts. Schneck, who has written extensively on
the topic, has modified his earlier assertion that sleep paralysis is an
expression of homosexual conflict, and suggested more recently that general

conflicts between passive and aggressive personality trends are involved.
The notion of dissociation or asynchrony between various aspects of the
sleep mechanism has been invoked by some as a more organic explanation of

this disorder. Other authors have considered sleep paralysis to be a variant of
cataplexy. However, Chodoff and Goode have enumerated several differences
between these two phenomena, suggesting that they are not identical
disorders. Still others have proposed that sleep paralysis is a form of epilepsy.
As Goode notes, however, EEG recordings made during sleep-paralysis

episodes offer little support for this hypothecs
In 1953 Aird et al. advanced the hypothesis that either blockage of the
reticular facilitatory system and the resultant predominance of the reticular
inhibitory system, or primary stimulation of the inhibitory system, may be
sufficient to produce sleep paralysis. Although it has not yet been determined
whether isolated sleep-paralysis attacks are identical to narcoleptic sleep-
paralysis attacks, recent polygraphic studies of narcoleptics have led to a
revival of the dissociation hypothesis, in a more specific form, as the

explanation of narcolepsy and of its concomitant symptoms. It has been
amply demonstrated (see references 89, 187, 188, 341, and 355) that
narcoleptics who exhibit sleep attacks and one or more of the other
narcolepsy symptoms frequently experience REM periods at or soon after

sleep onset. This contrasts with the normal pattern, in which the first REM
period typically occurs approximately ninety minutes after sleep onset.
Although earlier descriptions of EEG activity during sleep-paralysis attacks in

narcoleptics mentioned only patterns of drowsiness during the episode, more
recent studies in which eye movements were monitored have indicated that
the attacks are accompanied by REM sleep. Moreover, there is a loss of spinal
reflexes during REM sleep in both normal subjects and narcoleptics, and early
parts of the narcoleptic’s sleep-onset REM period seem to be composed of
lighter sleep than either the drowsy state, the later part of the sleep-onset
REM period, or later REM periods. These data suggest that the mechanism of
sleep paralysis in narcoleptics involves a dissociation of REM sleep. This
dissociation refers to the occurrence of certain REM phenomena, such as
muscular inhibition and dreamlike state, against a background of relative
awareness. Roth et al. believe that independent sleep paralysis is also due to
such a disturbance in the REM system. Whether or not this is the case must be
explored in future work, along with a determination of whether there is an
analogous explanation for postdormital sleep-paralysis attacks.
Frightening Dreams
Polygraphic investigations have provided evidence that there are two
types of unpleasant nocturnal “dream” attacks, i.e., night terrors and dream
anxiety attacks. The former, also called “pavor noctumus” in children and
“incubus attacks” in adults, are characterized by a sudden scream and arousal.
Intense anxiety, hypermotility, increased heart and respiration rates,
confusion, unresponsiveness, hallucinations, choking sensations, and feelings

of impending doom accompany the arousal. The sufferer is usually unable to
remember the attack the next morning. The dream anxiety attack is generally
less intense than, and lacks the quality of panic associated with the night
terror. It may, however, precipitate an arousal, and dream reports are
typically more complete than after arousal from night terrors. Although these
two types of nightmares are usually easily differentiated on the basis of sleep
EEG data, Mack has pointed out that this may not be the case when only
clinical reports are available.
These sleep attacks have been described in people of all ages and
cultures, and are not confined to the mentally ill. The incidence of night
terrors appears to be much lower than that of dream anxiety attacks. Fisher
et al. cite a report by Kurth et al. according to which night terrors were
described by 2.9 percent of 991 children between the ages of one and
fourteen years. Hersen studied 352 inpatients who were primarily diagnosed
as having psychotic disorders and found that 32 percent reported having
frightening dreams leading to awakening at least once a month. Among

college undergraduates the analogous figure was 5 percent. Whether the
respondents in these two studies were reporting night terrors or anxiety
attacks, or both, is not clear. After reviewing the literature on the incidence of
unpleasant dreams in children, Mack concluded that such dreams
predominate in preschool children and that the incidence decreases after six
years of age.
Sleep EEG studies of the two types of dreams have shown that the night
terror is a NREM, slow-wave sleep phenomenon, while the anxiety dream
occurs during REM sleep. Most NREM sleep dreams occur during the first half
of the night. During the first or second NREM period a K-complex or a burst of
delta waves presages the onset of the attack. Alpha activity and investigative
eye movements quickly follow, and are accompanied by sharp increases in
heart and respiration rates, and by body movement and muscle contractions.
With the end of the attack all measures gradually return to normal. Although
Broughton reported that relative tachycardia characterized the slow-wave
sleep of night-terror sufferers, Fisher et al. found heart and respiration rates
to be normal, or even reduced, in the interval prior to the abrupt onset of the
attack. They also noted that the length of the stage-4 interval preceding the
attack and the quantity of delta activity during the interval were positively
related to the intensity of the attack. Gastaut and Broughton were able to
elicit only minimal dream content from subjects following arousal from
NREM attacks, but several of Fisher’s subjects provided lengthy reports. The
content was of two types. The first consisted of a single vivid scene which
appeared to occur at the same time as or just before the arousal scream. The
second type was more elaborate and seemed to be related to the autonomic
activity following the scream.
Autonomic activation may or may not occur before and during the
arousal terminating a REM-sleep dream-anxiety attack. Fisher et al. studied
twenty such attacks in eleven subjects. They found that in twelve attacks
which were characterized as producing mild to marked anxiety, there was no
change from control levels of heart and respiratory rates. In five other attacks,
less than maximal degrees of activation were present, and in the remaining
three there were clear-cut increases in the heart and respiratory rates.
Content elicited after REM attacks is much more elaborate than that elicited
after NREM attacks, and one individual appears not to suffer from both types
of attacks.
There are, of course, numerous psychological interpretations of these
sleep attacks, but there have been relatively few systematic studies of the
variables involved. One exception is the series of studies carried out by
Hersen. In the first there was a significant relationship between conscious
concern with death and frequency of nightmares in a college-student sample.
In the second study similar results were obtained with psychotic inpatients.
In addition, the degree of manifest anxiety and the number of other sleep
disturbances were positively related to frequency of bad dreams, while ego
strength was negatively related.
Among sleep researchers there is agreement that these attacks are most
probably psychological in origin. Broughton suggested that NREM night
terrors are disorders of arousal, similar to enuresis and somnambulism, and

that the sufferers are physiologically predisposed, possibly as exhibited by
their relative tachycardia during slow-wave sleep and their hyperactive heart
rate during the arousal response, to experience night terrors during

otherwise normal slow-wave sleep arousals. The exact precipitator of the
attacks on any particular night may be the expression of repressed conflicts

by mental activity released when protective barriers are lowered during the
deepest stages of sleep. Or it may be that the attacks arise out of a
“psychological void” and that the subjective experience of terror on arousal
derives mainly from the perception of the accompanying physiological
changes. In another formulation, Broughton elaborated on the first

explanation and proposed that unresolved conflicts alter the arousal
mechanism of the night-terror sufferer, producing a psychosomatic arousal
disorder.
Fisher et al. believe that more immediate psychological factors
precipitate both REM and NREM attacks. Specifically, increasing ego
regression accompanying the progressive deepening of stage-4 sleep is
suggested as the precipitator of NREM terrors, although the fact that attacks
can be produced by sounding a buzzer during stage-4 deep suggests that

external stimulation may also play a precipitating role. On the other hand, the
REM dream is hypothesized to have a modulating influence on anxiety, and by
reducing or eliminating the physiological concomitants of anxiety it serves to

guard REM sleep. This would explain the desomatization of the anxiety
accompanying a majority of the REM attacks these investigators have

described. When the desomatization mechanism breaks down, however,
autonomic activation is seen to accompany the anxiety dream. It is the view of

Fisher and his colleagues that the stage-4 nightmare represents a failure of
the ego to control anxiety, and, rather than being a dream, it is a relatively
rare pathological formation of NREM sleep. By contrast, the REM anxiety
dream is a normal phenomenon throughout life and deals with controlled
anxiety.
Secondary Sleep Disorders
Schizophrenia
Throughout the history of modern medicine, clinicians and researchers
have been intrigued by the possibility of a relationship between sleep
disturbances and psychopathology. The apparent similarity between dreams
and hallucinations has led a number of authorities to speculate upon the

etiological role of disturbances in the dreaming process in the development of
schizophrenia.
The discovery of REM sleep and initial reports that REM deprivation in
normal subjects resulted in various psychological disturbances seemed to
provide tentative support for this speculation. Although later studies have
raised questions about the consistency and severity of these psychological
effects, the earlier studies and the theories accompanying them served as
compelling stimuli for polygraphic examination of the sleep of schizophrenics.
One hypothesis which attracted investigators was that the
hallucinations and delusions of the schizophrenic represent eruptions of REM
“pressure” into the waking state. As Vogel discusses, this notion, which is
essentially hydraulic in nature, implies that some condition such as chronic
REM deprivation exists in schizophrenics prior to the psychotic episode. In
addition Vogel and Traub pointed out that it has never been clear whether the
intrusion of REM sleep into wakefulness represents a continuation of the
build-up of REM pressure or a discharge of that pressure, and thus
predictions of how REM should behave during the course of the disease are
often confusing and contradictory.
In any case, persistent efforts to find evidence of REM phenomena

during wakefulness and of REM abnormalities during sleep in schizophrenics
have produced far from conclusive results. In examining five actively ill
patients, newly admitted to the hospital, Rechtschaffen et al. were unable to

detect any consistent patterns of EEG, EOG, and EMG activity which indicated
the presence of REM sleep during wakefulness. Chronic adult schizophrenics
and children exhibiting schizophrenia or autism have shown no severe
abnormalities of REM sleep, although adults at or near remission have been

found to exhibit increased amounts of REM, decreased latencies to REM onset,
and incomplete EMG suppression during REM sleep. “Actively ill” or acute
patients have not shown significant changes in REM time, although changes in
REM latencies have been observed in some. Feinberg et al. did observe lower
REM times in short-term as compared to long-term patients. In addition,
hallucinating patients have exhibited greater eye-movement densities than
nonhallucinating patients. Feinberg and his colleagues have consistently
failed to find any REM abnormalities in several remitted patients.
The general conclusion would seem to be that schizophrenics do not

exhibit striking changes in REM sleep or evidence of REM phenomena during
wakefulness. The occasional changes observed, however, may to some extent
reflect drug effects, for in these studies varying degrees of control have been
exercised over the drug status or length of time since drug withdrawal. In
addition, the exact type and point of evolution of the patient’s disease may be
a significant factor. For example, Struve and Becka found that “B-mitten” EEG
discharges occur in a significantly greater proportion of reactive

schizophrenics than process schizophrenics. Furthermore, Snyder and Kupfer
et al. observed several patients longitudinally through the course of an acute
psychotic episode and described distinct changes in various sleep

parameters, including those of REM sleep, associated with both the waxing
and waning phases of the episode.
Although the evidence of changes in the conventional measures of REM

sleep of schizophrenics is at best inconclusive, there is suggestive evidence
that the schizophrenic’s response to experimental manipulation of REM sleep

depends on the phase of the disease, and this may indicate that the
underlying neurophysiological and biochemical mechanisms of the REM state
operate differently in these patients. For example, actively ill patients exhibit
little or no compensatory increase in REM sleep following several nights of
REM deprivation, but remitted patients exhibit normal or even exaggerated

REM rebounds following such procedures. Zarcone and Dement have updated
the REM-intrusion hypothesis of schizophrenic symptoms by suggesting that
it is the behavior of pontine-geniculate-occipital (PGO) spikes which accounts
for these differential effects of REM deprivation, and possibly for the
psychotic symptoms. In animals, these PGO spikes are normally confined to
REM-sleep periods, and it is suspected that deprivation and rebound of these
spikes, rather than of other aspects of REM sleep, produce the REM rebounds
following REM-sleep deprivation. When animals are administered p-
chlorophenylalanine, an inhibitor of serotonin synthesis, the PGO spikes can
be dissociated from REM sleep and may be discharged during the waking
state. With this waking discharge of PGO spikes the animals may exhibit what
appear to be hallucinations accompanying the PGO spike bursts, restlessness,
insomnia, and decreases in REM time. Zarcone and Dement have noted that
the last three symptoms are very similar to those described by Snyder and
Kupfer et al. for patients at the onset of an acute psychotic episode.

Furthermore, REM deprivation in animals exhibiting PGO spikes during the
waking state does not result in a compensatory rebound of REM. Zarcone and
Dement have speculated that REM deprivation is ineffective because the PGO
spikes are no longer confined to the REM periods. Since extended REM
deprivation is not sufficient to produce a dissociation of the PGO spikes and
other REM phenomena, they suggested that some abnormality of the
neurochemical regulators of PGO spikes, which appear to include serotonin,
must account for this dissociation of PGO spikes. Zarcone and Dement believe
that such an abnormality of PGO function could determine many of the
symptoms of the schizophrenic psychosis. It must be understood, however,

that the existence of PGO spikes, or functionally equivalent events, in humans
has yet to be demonstrated.
The early emphasis on the REM-sleep characteristics of schizophrenics
resulted in a comparative neglect of the other aspects of EEG sleep. However,
deficits in the stage-4 sleep of schizophrenics are well-documented, and
appear to be much more prevalent than abnormalities of REM sleep. Although
some authors have hesitated to attribute any specific importance to these

deficits since similar types of disturbance are observed in various other
disease or natural conditions, Feinberg noted that the same could be said of
the sporadically observed REM-sleep abnormalities. Furthermore, since sleep
deprivation is ineffective in producing increased levels of stage-4 sleep in
schizophrenics, there is evidence equivalent to that for REM sleep that basic
disturbances of the sleep mechanisms themselves are important
characteristics of schizophrenia.
In conclusion, although sleep researchers have found a REM-intrusion
hypothesis to be particularly attractive as an explanation of the
schizophrenic’s psychotic symptoms, there is little consistent evidence that
the more traditional measures of REM sleep are significantly changed in many
schizophrenics. However, more attention to the specific types of
schizophrenics, to the changes occurring during the evolutionary course of
the disease, and to the phasic events of REM sleep, may reveal specific
disturbances in the basic mechanism of REM sleep. This is particularly
suggested by the failure of acute schizophrenics to exhibit a compensatory
REM rebound following REM-sleep deprivation. On the other hand,
schizophrenics also appear to suffer from important disturbances of slow-

wave sleep. It seems certain that these sleep disturbances will be found to be
intimately linked to biochemical abnormalities associated with schizophrenia.
Depression
Sleep disturbance is one of the more common and important features of
the depressive illnesses, and it has long been thought that certain types of
sleep disturbance discriminate reliably among the various subtypes of
depression. Thus, delayed sleep onset has been thought to characterize
reactive depression, while early awakening supposedly occurs more in
endogenous depression.
The objective description of the polygraphic sleep patterns of depressed
patients was initiated by Diaz-Guerrero et al. in 1946, before the discovery of
REM sleep. These pioneers observed that in comparison to normals, manic-
depressive patients in the depressive phase of their illness exhibited difficulty
falling asleep, early and frequent awakenings, greater proportions of light
sleep, and greater numbers of shifts from one sleep stage to another.
Since this early study, much information has accumulated on the EEG
sleep patterns of depressed patients, and many more refined descriptions
have appeared. Although certain characteristics of EEG sleep have been
consistently noted in these studies, other characteristics are still disputed. It
has generally been observed (see references 93, 158, 160, 179-181, 254, 272,
273, 308, 385, 386, and 446) that depressed patients take longer to fall
asleep, obtain less sleep, awaken more often, and awaken earlier than
normals. In a vast majority of cases slow-wave or stage-4 sleep is moderately

to markedly suppressed. Increased frequencies of stage shifts have also been
noted occasionally.
These consistent observations can be contrasted with the results

pertaining to REM sleep (see references 158, 160, 174, 175, 177-181, 254,
272, 273, 308, and 385-387). Many investigators have reported decreases in
REM-sleep time in depressed patients, but several have also commented upon
the high variability among patients with respect to REM time. Others have
described normal or elevated REM times. Latency to REM onset has generally
been found to be shorter than average, and sleep-onset REM periods have
been observed in some cases. Measures of the density of eye movements
during REM, when made, have usually been high.
Clinical improvement, whether occurring spontaneously or with the aid
of pharmacological or electroconvulsive therapy, is generally accompanied by

a normalization of the disturbed sleep parameters. However, slow-wave sleep
may not return to normal levels even with clinical improvement (see
references 158, 160, 180, 181, 272, and 274).
Vogel et al. found that experimental REM deprivation in these patients
has varying effects. Some patients show evidence of REM “pressure”
(decreased latency to REM onset, increased number of awakenings required
to effect the deprivation) during deprivation and exhibit REM rebounds
following the deprivation period. The REM sleep of others seems to be
unaffected by the procedure. When deprivation is accompanied by the

buildup of REM pressure there is a concomitant improvement in the clinical
picture. A similar improvement accompanies the REM deprivation associated
with administration of monoamine oxidase inhibitors.
One of the most striking characteristics of the patients in these studies,
and probably one of the determinants of the inconsistent results with respect
to REM sleep, is the high degree of variability among patients, even within the
same study. Hawkins and Mendels have repeatedly emphasized this point,
and have suggested that differences in severity of illness may determine
much of this variability. Although these investigators were unable to detect
any statistically significant differences between patients rated as severely

depressed and those rated mildly to moderately depressed, there was a
tendency for the severely depressed patients to exhibit greater sleep
disturbance. Furthermore, patients over fifty years of age tended to have

more disturbed sleep than younger patients.
It appears that an even more important contributor to the variability in

the EEG sleep patterns of depressed patients are differences in the diagnostic
subtypes of the patients. Although there has been no consistent evidence that
endogenous depressives are characterized by early awakening while reactive

depressives have difficulty falling asleep, Mendels and Hawkins found that
psychotic depressives show significantly greater sleep disturbance than
neurotic depressives. In addition, Hartmann found that manic depressives
exhibit sleep abnormalities somewhat different from those reported for

groups of mixed psychotic depressives. He also observed that sleep
disturbances during the depressed phase are different from those in the
manic phase. However, Mendels and Hawkins have reported that the sleep
patterns of one hypomanic patient were generally similar to those of patients
with psychotic depressive illness. Finally, Detre et al. have recently described
distinct differences in reported sleep patterns between bipolar and unipolar
depressives, as well as evidence of hypersomnia in many patients, and
particularly in bipolar depressives.
As with interpretations of the sleep disturbances characteristic of

schizophrenia, some researchers have sought to relate the depressive’s
clinical symptoms to abnormalities in REM sleep. On the basis of his data
Snyder concluded that psychotic depression is accompanied and perhaps
exacerbated, by the effects of REM deprivation (REM pressure). The

fragmented and short sleep of these patients would gradually produce this
deprivation, and therefore the degree of REM pressure should reflect the
duration of earlier unrelieved sleep disturbance. Hartmann also believes that

REM pressure is an important aspect of depression, but he suggests that it
may be intrinsic to depression rather than the result of earlier deprivation.
Furthermore, according to Hartmann this REM pressure is associated with

low levels of available functional norepinephrine. On the other hand, in
discussing their study of experimental REM deprivation in depressives Vogel
et al. suggested that REM pressure produces an accumulation of
catecholamines which alleviates depression.
Other researchers have taken a more global view of the depressive’s

sleep disturbances. Mendels and Hawkins have interpreted the short, light
and fragmented sleep patterns and the reductions in REM and stage-4 sleep
as indicating increased activity of CNS arousal mechanisms. Presumably the
heightened arousal characteristic of depression would tend to prevent these
two sleep stages from occurring. More recently Whybrow and Mendels
reviewed neurophysiological, electromyographical, waking and sleep EEG,
and chemotherapeutic evidence suggesting that in depression, and possibly
mania, there is a state of CNS hyperexcitability.
Iskander and Kaelbling concluded that changes in delta or stage-4 sleep
are probably of greater significance in the etiology of depression than
changes in REM sleep. In their opinion, the deficits in REM sleep are
secondary to the deficits in slow-wave sleep since REM sleep typically occurs
only after a “primer” period of delta sleep. Therefore if slow-wave sleep failed
to occur, or occurred only minimally, there would be less likelihood that REM
sleep would occur. Iskander and Kaelbling also suggested that the residual
disturbance of delta-sleep patterns exhibited by clinically improved

depressives lends further support to their conclusion.
In summary, arousal disturbances of EEG sleep (short sleep time, long
sleep latency, high number of awakenings, etc.) have consistently been found
to characterize depressed patients. The reduction or absence of delta sleep is
also a reliable characteristic. Many patients obtain less REM sleep, but this
has been less consistently observed than the above disturbances. Depressed
patients appear to be rather variable in their EEG sleep patterns. Differences
in severity of illness, age, and diagnostic subtype may contribute to this
variability. Attempts have been made to implicate both REM- and NREM-sleep
disturbances in the etiology and maintenance of depression, but, as with

many clinical disorders, there is as yet no completely satisfactory explanation
of this relationship.
Alcohol and Chronic Alcoholism
The effect of alcohol on human sleep patterns has received attention
from researchers for several reasons. First, alcohol, caffeine and nicotine are
probably the most widely used drugs in the general population, and, for this
reason, all are potential contaminators of polygraphic sleep studies. Second, it
is suspected that alcohol may play some role in either the precipitation or the
maintenance of some types of sleep disturbance. Finally, sleep disturbance
has long been observed to be one of the symptoms of various phases of the
chronic alcoholic’s disease process.
Administration of one g./kg. of body weight of 95 percent ethonol to
normal subjects on one night resulted in a significant decrease in REM sleep.
Continued administration of identical amounts of alcohol either immediately
before retiring, or four hours before retiring, for several consecutive nights,
had a similar effect on REM sleep during the first one or two nights. However
on subsequent nights of alcohol administration, REM returned to normal
levels or above. On early recovery nights, REM remained at high levels or
even increased more, but it returned to control levels by the third or fourth
recovery night. When alcohol was given immediately before retiring stage-2
sleep varied inversely with REM sleep, while stages 3 and 4 tended to
fluctuate around control levels. There were no consistent changes in the time
awake, the number of stage shifts, body movements, or latency of the first
REM period. When alcohol was consumed four hours before retiring the
changes in REM and NREM sleep were less consistent. In a longterm study of
one normal subject drinking somewhat lower doses of alcohol, there was
evidence of a dose-response effect in the suppression of REM, as well as an

indication that increasing the dose during subsequent nights resulted in a
continued suppression of REM below control levels.
From these studies of normal individuals it would appear that alcohol
has an initial suppressing effect on REM sleep, that this effect decreases with
continued constant doses of alcohol, that increasing doses of alcohol may
sustain the effect, and that following several consecutive nightly doses of
alcohol there may be a rebound of REM sleep on nonalcohol nights. Although
the data are still meager, it appears that NREM sleep and certain variables
reflecting wakefulness are unchanged by acute alcohol consumption.
There are no data specifically related to the use of alcohol by
insomniacs. Nevertheless, it is well known by clinicians that some insomniacs
use alcohol at bedtime as a hypnotic. The fact that alcohol has a stimulating
effect at low doses, and must be taken in large amounts for depressant effects
to appear undoubtedly results in the insomniac’s having to ingest rather large

quantities to obtain the desired effect. Moreover, the demonstrated sleep-
disturbing effects of alcohol may well prompt the patient to discontinue his
self-treatment. Withdrawal effects on sleep patterns may then lead him to
resume his use of alcohol, or perhaps some other hypnotic. In this manner he
may become trapped in a vicious circle of alcohol consumption and
withdrawal, both of which are accompanied by the sleep disturbance he is
trying to prevent.
The nature of the sleep disturbances in the alcoholic psychoses is

somewhat clearer. It appears that both delta sleep and REM sleep are
disturbed throughout the various stages of this disorder. During inebriation
in chronic alcoholics REM sleep is moderately to severely suppressed, at least

initially. Continued suppression of REM may depend on increasing dosages of
alcohol. However, there are nights on which “REM escape” or abnormally high
amounts of REM may occur. There is some disagreement about the exact
nature of the delta-sleep disturbance during this phase. In two patients

undergoing chronic alcoholization, Gross and Goodenough observed an initial
increase in delta sleep, followed by a decrease to normal or subnormal levels.
On the other hand, Johnson et al. found thirteen of fourteen patients
undergoing acute alcoholization to be completely without stage-4 sleep and
eight were without stage-3 sleep. They also noted that, compared to
withdrawal nights, there were a greater number of stage shifts and

awakenings, greater amounts of wakefulness, and fewer K-complexes during
this phase. Although Gross and Goodenough described disturbances in
spindle activity during acute intoxication, Johnson et al. failed to find such
changes in their patients. In a non-EEG study Mello and Mendelson observed
that chronic inebriation resulted in an increased amount of daily sleep,
although sleep became more fragmented.
During the chronic alcoholic’s withdrawal from alcohol ingestion, there
are consistent reports of increased REM sleep on initial recovery nights, with
a gradual return to normal levels on later recovery nights. Johnson et al. have
also described decreased REM-onset times and increased numbers of REM
periods in these patients. They found that the increased REM time reflected
shorter intervals between REM periods rather than longer REM periods. In
addition, the patients appeared to have difficulty maintaining REM sleep, as
evidenced by the noticeable fragmentation of this sleep stage. There appears
to be a strong relationship between this increased REM sleep during alcohol

withdrawal and both the delirium and the hallucinations which are frequent
signs of withdrawal. Greenberg and Pearlman found that patients who
exhibited delirium had more nights with increased REM sleep and showed
greater increases in REM than patients who did not exhibit this symptom.
Gross and Goodenough observed that one patient began experiencing
hallucinations on the first day of withdrawal and following a night without

REM or stage-4 sleep. Another withdrawing patient with 100 percent REM
sleep also exhibited hallucinations, while a third with 44 percent REM sleep
did not. These authors interpreted this as evidence that the rebound of REM
above a certain threshold following alcohol-induced REM suppression is the
basis for the hallucinations. Gross and Goodenough believe that REM rebound
is also related to seizures during withdrawal.
It has also been reported that stage 4 is absent during the withdrawal
phase. Gross and Goodenough have suggested that the complaints of sleep
disturbance in these patients are related to this decrease in stage 4, and that
“sudden and massive” return of stage 4 is signaled by the terminal sleep often
observed in the recovering patient. Rut Johnson et al. have suggested that lack
of stage 4 is a characteristic of chronic alcoholics in general, and that the
return of stage 4 is not a necessary condition for clinical improvement.
Insomnia is commonly accepted as one of the clinical symptoms of

withdrawal. Many of the patients described by Gross and Goodenough were
sleepless on some nights during recovery, and these authors suggested that
complete insomnia is related to a more advanced state of withdrawal.
Johnson et al. reported a significant improvement in various measures of
restless and disturbed sleep during the withdrawal phase, as compared to the
alcoholization period, but noted that their patients still appeared disturbed by
normal standards. Mello and Mendelson found that fragmented sleep was a
frequent, but not invariable, concomitant of withdrawal. In addition, abrupt
withdrawal was not necessarily accompanied by insomnia.
In summary, alcoholization in chronic alcoholics is accompanied by
significant changes in REM sleep and delta sleep, as well as by fragmented or
disturbed sleep. Total sleep time per day may increase, however. During
withdrawal there is a rebound of REM sleep, which may be related to the
appearance of both hallucinations and seizures. Delta sleep remains
depressed in many cases, although a rebound of this type of sleep may

accompany the terminal sleep observed in some patients. Insomnia or other
complaints of sleep disturbance may occur, but they are not invariable
symptoms of withdrawal. Although there is an improvement in the quality of

sleep during withdrawal, these patients continue to exhibit noticeable sleep
disturbances as compared to normals.
Chronic Renal Insufficiency, Hemodialysis, and Renal Transplantation
Clinical reports have indicated that the uremic syndrome, in addition to

its characteristics of lethargy, depression, restlessness, and muscular
twitching, is frequently characterized by a paradoxical state of daytime
drowsiness and nighttime insomnia. This disturbance has been reported to
persist when the patients are maintained on hemodialysis, although Shea et
al. noted that the dialysis procedure may have some immediately beneficial
effects on sleep. One report indicated that dialyzed patients suffer
predominantly from difficulty in falling asleep, and several investigators
found these patients to be particularly refractory to pharmacological
treatment of the sleep disturbances.
Only two polygraphic studies of uremic patients have been reported. In
1970 Passouant et al. described the sleep patterns of eighteen patients, some
of whom were undergoing regular dialysis and some of whom were treated
principally by dietary means. They studied five patients both before and after
dialysis. Although this report is rather unclear as to the observations
contributing to the data presented, the authors concluded that in the uremic
syndrome sleep is characterized by decreased sleep time; increased awake

time, primarily in the middle of the night; decreased slow-wave sleep;
irregularity of sleep cycles; and frequent body movements. The sleep of

patients regularly maintained on dialysis was not significantly disturbed,
although there were some differences in sleep patterns before and after
dialysis. Before dialysis, the alternations between NREM and REM were
normal, but there were frequent awakenings and reductions in slow-wave
and REM sleep. After dialysis, the number of awakenings decreased and slow-
wave and REM sleep increased. In the patients who were dialyzed only when
other means of management were temporarily ineffective, sleep problems
were constant during periods of stabilization, i.e., there were frequent

awakenings and decreases in slow-wave and REM sleep. The number of sleep
cycles was normal and the lengths of the cycles were regular. During
exacerbations the existing sleep problems were magnified, sleep cycling

became very irregular, and the number of body movements increased.
Dialyzing these patients, either peritoneally or by artificial kidney, resulted in
increases in slow-wave and REM sleep and stabilization of REM sleep. The
number of body movements remained high until several dialyses had been
performed. In three patients who underwent peritoneal dialysis REM sleep
appeared within ten minutes after sleep onset. Correlations among sleep and
other physiological variables indicated that an increase in blood urea
nitrogen was significantly correlated with decreases in slow-wave and REM

sleep and increases in the number of awakenings.
In a recent study, we have systematically examined the EEG sleep
patterns of ten uremic patients on the night immediately preceding and the
night following regular hemodialysis sessions, and have compared these

patterns to those of age- and sex-matched healthy controls. In comparison to
the controls, before dialysis the patients exhibited significantly shorter total
sleep times, increased numbers and lengths of awakenings and percentages of
awake time, decreased time from sleep onset to the first awakening,
decreased ratios of total sleep time to time in bed (sleep efficiency),
decreased percentages of REM and stage-2 sleep, and increased percentages

of stage-3 sleep. In comparison to controls, patients after dialysis exhibited
significantly lower sleep efficiency, greater percentages of awake time, longer
awakenings, and lower percentages of stage-2 sleep. Direct comparisons of

the patients before and after dialysis revealed no significant differences in the
quantitative measures of sleep, although the fewer number of significant
differences from control values in the patients after dialysis suggested that
some improvement in sleep patterns had occurred as a result of the dialysis.
This was further evidenced when we examined the sequence in which the
various sleep stages first appeared during the first cycle. In the controls, this
sequence (stage 1, 2, 3, 4, REM, o) was identical to that usually observed in
healthy subjects. Before dialysis, the sequence (1, 2, 3, 0, 4, REM) was

interrupted by the early appearance of the first awakening. After dialysis, the
sequence (1, 2, 4, 3, REM, o) approached that of the controls, indicating that

dialysis resulted in a more normal sleep organization during the first sleep
cycle.
In a second study we examined the sleep patterns of nine uremic
patients who had received kidney transplants from three months to four
years before the study. Compared to age- and sex-matched controls, these
patients exhibited significantly greater percentages of awake time and
lengths of awakenings, greater numbers of REM periods, shorter latencies to
REM sleep, and lower percentages of stage-4 sleep. The sequence of stages
during the first sleep cycle was perfectly normal.
In addition to these findings, we noted that both dialysis and transplant
patients showed certain qualitative changes in their sleep EEGs. Some
patients exhibited an intermingling of alpha activity with delta activity.
Decreased numbers, durations, and quality of spindles were common. The K-

complexes were poorly formed and had unusually low voltages. Some
patients showed an increase in theta activity. Abnormally low-voltage delta
activity was characteristic of many patients, both young and old. Dialysis and
kidney transplantation appeared to have no significant effect on these EEG
changes.
Although both dialysis and renal transplantation appear to produce

some improvement in uremic patients’ sleep patterns, there is never a
complete normalization of sleep following these procedures. This fact
suggests that chronic renal insufficiency may produce irreversible,

fundamental changes in the CNS. These changes are undeniably seen at the
functional level, and may even exist at the cellular level.
Pregnancy and Postpartum Emotional Disturbance
Disturbances in the sleep system have long been considered important
symptoms of postpartum emotional disturbances (see references 78, 137,

171, 201, 202, 206, 258, 367, and 432). Although there have been no
systematic polygraphic studies of these concomitant sleep disturbances,
indirect evidence from studies of other psychiatric disorders, such as

depression and schizophrenia, and from studies of certain hormonal
disorders would suggest that disturbed EEG sleep patterns might be an
important concomitant of the postpartum emotional disturbances. More
recent studies of sleep patterns during normal pregnancy and the postpartum
period have provided further evidence of this. During the early stage of
normal pregnancy there is a noticeable increase in time spent asleep. Sleep
time normalizes during the second trimester, decreases to below normal
during the third, and remains low for some time following delivery. During
the second trimester several additional changes begin to appear, i.e.,
awakenings become more frequent and the number of REM periods may
temporarily increase. Of even greater significance, however, is the fact that

stage-4 sleep begins to decline during this period. Although decreased levels
of stage 4 are the most striking characteristic of groups of pregnant women in
their last trimester of pregnancy, individual women may exhibit various
degrees of variability in this pattern. In some women REM sleep may decline
slightly during the second trimester, only to increase sharply during the third
and begin to decrease as delivery approaches. In others, the decline in REM
sleep may persist through the last trimester. During the last trimester there
are also increased sleep latencies, increased amounts of awake time and
numbers of awakenings, and increased percentages of stage-2 sleep.
Petre-Quadens et al. observed that sleep patterns during the two weeks
following delivery were similar to those of late pregnancy in their subjects
(high REM, decreased or absent stage 4), and that by the third postpartum
week REM and stage-4 sleep had begun to move toward normal levels. In our
studies we looked closely at the two or three nights immediately following
delivery. On the first night there was a sharp increase in awake time and a
sharp decrease in REM sleep. Stage-4 sleep was slightly increased above late
prepartum levels. During the second and third postdelivery nights these
parameters showed gradual movement toward normal levels. Nevertheless,

the immediate postpartum period as a whole was still significantly disturbed
in several respects. Compared to nonpregnant control subjects the new

mothers exhibited longer sleep latencies, greater amounts of awake time and
numbers of awakenings, decreased REM time, and decreased stage-2 sleep.
Even with the return of the menses, sleep patterns had still not completely
normalized in the new mothers. Although sleep latency had become more
normal, there were still significantly high amounts of wakefulness and
numbers of awakenings. REM sleep had essentially reached normal levels, but
stage-2 sleep was somewhat depressed. The amount of stage-4 sleep was
often greater than in nonpregnant controls.
These data from normal women would seem to indicate that rather
profound alterations in sleep patterns are natural concomitants of the

pregnancy and postpartum periods. Although sleep patterns generally
normalize during the first several postpartum weeks, at the onset of the first
menses following delivery there is still sufficient disturbance to suggest that
this event does not represent the full attainment of the prepregnant state. The
striking changes in total sleep time, and particularly in stage-4 sleep, during
late pregnancy seem to be especially important since significant decreases in
stage-4 sleep are concomitants of various types of psychopathology (see

references 62, 93, 160, 179, 386, and 446). We may speculate that a mother’s
failure to recover this type of sleep following delivery is a prodromal sign of,
or perhaps even an etiological factor in, postpartum emotional disturbance.

This must remain a speculation, however, until more direct studies of
postpartum emotional disturbances can be undertaken.
Perusal of any medical textbook and clinical experience will uncover

numerous other conditions which produce or are accompanied by disordered
sleep. Various CNS disorders, including infections and other toxic states, and
certain nutritional and endocrine disorders, are known to be accompanied by
changes in EEG sleep patterns. Many more remain to be examined by sleep
researchers. From this review it should be clear that although the information
produced by sleep research has raised more questions than it has answered,
the sleep EEG provides a unique tool for the exploration of the
neurophysiological bases of many medical and psychiatric conditions.
Parasomnias
Sleepwalking
In sleepwalking, the individual sits up in bed, arises, and begins to move
around in an uncoordinated manner. His eyes are open but his appearance is
rather blank and dazed. Most often his movements are stereotyped and
purposeless, but occasionally more complex behaviors, such as dressing or
going to the bathroom, may be exhibited. The sleepwalker may mumble or
emit other sounds, but rarely does he converse if spoken to. Eventually he
returns to bed or is easily led there. It is very difficult to awaken the
sleepwalker during his wanderings, and if he is awakened he is quite
confused and disoriented. He is usually amnesic for the episode when either
awakened during it or questioned about it the next morning.
The reported incidence of sleepwalking varies with the age and clinical
condition of the groups sampled, and with their past or current history. From
1-33 percent of various groups have reported current histories of
sleepwalking (see references 11, 138, 309, 362, and 380), while from 3-34
percent of groups sampled have described a past history of this disturbance
(see references 79, 138, 299, 319, and 404). It is commonly stated that
sleepwalking occurs more often in males. However, several studies failed to
reveal any significant male predominance, and one case was remarkable for
the number of female relatives of the patient who were also sleepwalkers. As
with this patient, many sleepwalkers show a positive family history for the
disturbance (see references 10, 21, 79, 219, 321, and 365).
Sleepwalking typically first appears in childhood or adolescence (see
references 11, 138, 219, 325, and 391), and in many cases disappears by the
third decade. However, if the disturbance persists into adulthood it often first
appeared at puberty. Among the various concomitants of sleepwalking in
many patients are EEG evidence of epilepsy and other EEG abnormalities, CNS
infection or trauma, genitourinary complaints, and more or less severe forms

of psychopathology (see references 5, 10, 11, 115, 192, 196, 198, 212, 219,
252, 299, 309, 319-321, 365, 391, 400, 405, and 421).
Several other types of sleep disturbance are frequently observed in

sleepwalkers. Pierce and Lipcon found that three times as many enuretic
naval recruits reported a past history of sleepwalking as did nonenuretic

recruits. In a second study these authors found that 47 percent of
sleepwalkers reported concurrent nocturnal enuresis, whereas controls did
not. Others also noted the parallel occurrence of these two phenomena.
Sleeptalking occurs in some sleepwalkers, as do nightmares and night terrors
(see references 101, 198, 212, 217, 219, and 320).
Sleep-EEG studies of sleepwalking have revealed that the episodes
occur during slow-wave sleep (see references 53, 144, 198, 200, 216, and
217), although Gastaut and Broughton have reported one episode which
occurred during the transition from stage-2 to REM sleep.
Gastaut and Broughton described episodes whose onset consisted of
intense awakening EEG reactions concomitant with or shortly preceding signs
of movement. Flattening of the EEG records and then continuous ample
nonreactive alpha activity followed, with the latter giving way to stage-2 or
occasionally REM sleep at the end of the episode.
Jacobson et al. described the episode as starting with the sudden
appearance of increased EMG discharge and 1-3 cps high-voltage EEG activity.
After ten to thirty seconds of this EEG pattern, lower-amplitude delta waves
appeared, producing a pattern resembling slow-wave sleep. If the incidents

were brief (twenty to forty seconds) this EEG pattern characterized the entire
incident. If the incidents were longer, theta, alpha, and beta frequencies
against a low-voltage background were characteristic. Most incidents were
followed by periods of mixed spindles and slow waves, but approximately
one-fourth of the incidents were followed by waking EEG activity.
Visual investigation of the environment, stereotyped movements,

nonreactivity, amnesia for the event, and lack of dream recall characterized
the sleepwalkers in both studies. Further investigations showed that
sleepwalkers up to sixteen years of age exhibited many more episodes of

sudden rhythmical bursts of high-voltage delta activity in slow-wave sleep
than did normals. These events occurred both with sleepwalking incidents
and at other times, principally with some body movement. Sleepwalking has
been induced in sleepwalkers and sometimes in normals by standing the

subject up during slow-wave sleep. Sleepwalkers may exhibit more complex
gestural movements than normals during slow-wave sleep, and appear to be
more confused following forced awakenings from slow-wave sleep.
The etiology postulated for sleepwalking has often depended upon the
theoretical persuasion of the writer or on his particular research orientation.
Thus the psychologically inclined (see references 5, 212, 252, 295, 299, 309,
320, 325, 365, 380, 391, and 405) have considered sleepwalking to be a
neurotic symptom, an immature habit pattern, a form of personality
dissociation, or the acting out of a dream. In one case, sleepwalking was a

prelude to an acute schizophrenic episode.
On another level, several investigators (see references 10, 115, 192,
319, and 320) have suggested that sleepwalking is a manifestation of
epilepsy. There is evidence of a genetic predisposition for the disturbance.
Broughton suggested that sleepwalkers are physiologically predisposed to
sleepwalk during slow-wave sleep arousals, whereas some other individuals
are predisposed to exhibit nocturnal enuresis or night terrors. However, the
nature of the specific precipitator of the sleepwalking episode remains

unclear. Jacobson and Kales suggested that both psychological and organic
factors are involved in the disturbance. In their view the abnormal high-
voltage delta-activity bursts observed in sleepwalking children may represent
an organic immaturity factor, and psychological factors may be necessary to

precipitate incidents in predisposed individuals.
Sleeptalking
Sleeptalking has long been of interest to physicians and laymen alike
because of its supposed reflection of mental activity during sleep. The
nocturnal utterances may be simple, mumbled monosyllables, or close

approximations of waking, conversational speech, and there are many reports
of sleep-talkers responding to a waking individual’s questions, commands, or
comments.
The incidence of sleep talking has been little studied. One difficulty in
deriving realistic figures is that the sleep talker is frequently unaware of this
nocturnal behavior. In an early study, Child found that 40 percent of a college
sample between the ages of twenty and thirty years reported ever having
talked in their sleep. In Gahagan’s later study of 559 university students, 61.5
percent reported a past history of sleep talking and 51.2 percent reported
that sleep talking still persisted. Goode found 53.1 percent of one group of
medical students, 58.5 percent of a second group, 72.2 percent of student
nurses, and 69.2 percent of hospital inpatients reporting histories of the

phenomenon. Among fifty-five enuretic marine recruits, twenty-six had
talked in their sleep during the past three months, while only fourteen of 135
nonenuretic recruits reported having done so. Since these incidence figures
are, in all likelihood, conservative, it would appear that at least a majority of
the population has experienced sleep talking at one time or another.
In an extensive review of the literature, Arkin noted that sleepwalking
may occur in the absence of any noticeable disorder, or in conjunction with

various types of physical or psychological pathology (see references 28, 163,
309, 322, 391, 405, and 418). Based on his clinical experience and research,
however, Arkin concluded that sleep talking “is usually benign but may reflect
deeper disturbance.”
The discovery of REM sleep and of its relationship to dreaming

engendered new interest in the psychophysiological aspects of sleep talking.
Kamiya was among the first to perform a polygraphic investigation of sleep-
talking. He reported that 88 percent of ninety-eight sleep talking episodes
occurred during NREM sleep, and that 71 percent of the episodes were
accompanied by body movements. Subsequent investigations usually

confirmed the predominance of sleep talking during NREM sleep, although
Arkin et al. and Tani et al. described subjects who talked predominantly or
exclusively during REM sleep. Several reports indicate that NREM-sleep
speeches are more likely to be accompanied by muscle-tension artifact than

are REM-sleep speeches, making it difficult to determine the quality of the
EEG activity during the episode. Nevertheless, Rechtschaffen et al. reported
that in NREM-sleep speeches a period of stage-2, -3, or -4 sleep would

suddenly be interrupted by muscle-tension artifact accompanied by sleep
speech. Occasionally a burst of high-voltage slow waves or K-complexes
preceded the muscle tension by several seconds. When EEG activity was
discernible through the artifact, it was usually in the 7-10 cps range and
appeared to be alpha activity. The muscle-tension artifact persisted for ten to
twenty seconds beyond the end of the sleep speech. The typical postepisode
EEG pattern was that of stage-2 sleep. Cohen et al. described one case of
stage-4 sleep speech in which there was no muscle artifact. Analysis of the
EEG during the speech suggested that the subject passed briefly into stage 1
during the episode. Schwartz described an episode which occurred during a
period of EEG wakefulness which interrupted stage-4 sleep. The subject did
not recall the event when questioned about it later.
The nature of the relationship between sleep talking and mentation
during sleep has been of interest both for theoretical and for practical
reasons. If it could be shown that sleep talking is reliably related to sleep
mentation, then content of sleep speeches might prove to be more “pure” than
content elicited after involuntary awakenings, and might thus provide a
better method of monitoring sleep mentation. After studying a small sample
of sleep speeches, Rechtschaffen et al. tentatively concluded that REM-sleep
speeches are characterized by affect in the voice and little relationship to the
experimental situation. Ry contrast, NREM speeches are usually flat and
unemotional, tend to concern the experimental situation, and are only
infrequently followed by reports of mental content with involuntary
awakening. In a more elaborate study of the degree of concordance between
the content of sleep speeches and recalled mentation, Arkin et al. found that
79.2 percent of REM speeches showed some degree of concordance with
mentation, while 45.8 percent of stage-2 speeches, 21.1 percent of stage-3

and -4 speeches and 80 percent of stage-i-NREM speeches exhibited some
degree of concordance. Whether the differences in degree of concordance in
REM and NREM speeches reflect differences in recall of sleep mentation, in

the mechanism of sleep speech, in types of concordance (manifest vs. latent
content), or real differences in the amount of sleep mentation in the two types
of sleep, remains to be determined.
Nocturnal Enuresis
Nocturnal enuresis refers to bed-wetting in individuals old enough to

have acquired voluntary control of micturition. Although most writers
consider a child to be enuretic if he wets his bed after three years of age,
several studies have shown wide individual differences, as well as possible

sex differences, in the age of acquisition of urinary control, suggesting that the
child who acquires control somewhat later than three years should not
necessarily be considered enuretic.
The incidence of enuresis has been reported to range from 4 percent for
six-year-old Child-Welfare-Clinic patients to 87 percent of idiots. Other
incidence figures between these extremes have been reported (see references
8, 38, 55, 91, 167, 207, 234, 244, 280, 281, and 409) for groups of various ages
and clinical conditions. Many authors have noted at least a slight
predominance of the disorder in males (see references 38, 91, 132, 169, 281,
and 392), although Frary found no evidence that enuresis is a sex-linked
character. There are numerous observations of a high family history for the
disturbance. Frary concluded that it is determined by a single recessive gene
substitution, while Hallgren suggested that in “genetic cases” the mode of

inheritance may be either by a dominant major gene or by the interaction of
polygenes and the environment.
A wide variety of physical anomalies has been observed in enuretics,

and quite frequently these anomalies have been assigned etiological roles in
the disturbance. Various neuromuscular and anatomical abnormalities of the
urogenital system have been described (see references 47, 51, 53, 70, 128,
130, 269, 327, and 394). Of particular interest are the observations that the
enuretic’s bladder capacity may be lower than normal, that some enuretics
may have less concentrated urine at night, and that enuretics excrete a larger
amount of urine at night than normals. However, Vulliamy found no
differences in nocturnal urine output among enuretics when diet and fluid
intake were strictly controlled. Numerous other more or less relevant
afflictions have received attention in the literature, including epilepsy.

Although high incidences of EEG epileptiform features, and frequent personal
and family histories of epilepsy have been reported for enuretics, Poussaint et
al. failed to find any clinical evidence of seizure activity in what they
considered to be a more representative sample of enuretics.
The psychological characteristics of enuretics have received equal
attention (see references 8, 26, 91, 149, 167, 169, 182, 248, 280, 319, 392, and
445). These individuals exhibit a variety of associated behavioral problems,
including nail biting, stealing, and truancy, criminal and especially aggressive
offenses, thumb sucking, speech impediments, temper tantrums, and
sleepwalking. They have been characterized as being temperamental, timid,
and sensitive, disturbed in the sexual realm, of loose personality organization,
fearful of the opposite sex, lacking inhibitory control, emotionally immature,
and passive. In one study it was found that five traits—enuresis, thumb
sucking, nail biting, speech impediments, and temper tantrums—occurred
more often in combination than in isolation in a sample of children. On the
other hand, Lapouse and Monk found no statistically significant relationship
between a number of fears and worries and enuresis in a large random

sample of children. Werry and Cohrssen concluded that enuretic children
seen by physicians tend to exhibit more psychiatric symptoms than
nonenuretics, but they emphasized that more than half of their enuretic
subjects were emotionally healthy. This is especially meaningful since they
also suggested that children with several behavioral and somatic symptoms
are more likely to be brought to a physician and thus load nonrandom
samples with disturbed subjects.
Clinical EEG studies of enuretics have generally revealed a high
percentage of abnormal or immature EEGs (see references 165, 282, 322,

377, and 411). In addition, Gunnarson and Melin found more EEG
abnormalities in enuretics who had never been dry than in those who had
experienced a dry period. Contradictory evidence was presented by Ditman
and Blinn, who noted no clinical abnormalities in their patients. In a sample of
sixty-eight subjects five to sixteen years old, only 10 percent of the EEGs were
read as abnormal. Some of these discrepancies may arise from differences in
characterizing normal records for a given age.
Deep sleep has been reported as a characteristic of and/or an etiological
factor in enuresis (see references 9, 44, 47, 169, 350, and 396), principally on
the basis of parents’ reports and observations on the difficulty in arousing
enuretics after micturition. Sleep EEG studies have revealed that enuresis can
occur in all stages of sleep and during periods of nocturnal wakefulness (see
references 27, 94, 122, 144, 324, 346, 368, and 424).
Pierce et al. observed an increase in restlessness and a gradual
reduction of heart rate to a stable low level during the thirty minutes
preceding micturition. Light sleep or waking patterns accompanied the
restlessness until a final body movement signaled a change to deep-sleep
patterns. Enuresis followed the body movement and slow-wave EEG activity
continued throughout micturition.
Gastaut and Broughton’s patients typically exhibited a gradual increase
in primary spontaneous bladder contractions as they passed from

wakefulness to deep sleep during the early part of the night. The “enuretic
episode” began with a series of bladder contractions during slow-wave sleep.
There followed a series of K-complexes or a burst of rhythmic delta activity in
the EEG, and then a body movement. Sleep patterns began to lighten and
micturition occurred at some point following the body movement. Micturition
could occur at any point along a continuum of increasing vigilance from deep
to light sleep or wakefulness. Broughton suggested that this finding may help
reconcile some of the earlier, apparently discrepant, observations that

micturition can occur in all stages of sleep and wakefulness, although
differences in apparatus for signaling the onset of micturition probably
contributed to some of the variability in the observations.
There is little evidence that nocturnal enuresis is related in any special
way to REM sleep. Only occasional episodes have been observed during this
sleep stage, and, if awakened following micturition, most patients fail to recall
dreams. On the other hand, awakenings from REM periods following
micturition are more likely to yield reports of dreams of micturition if the

bedclothes have been left unchanged, suggesting that dreams of micturition
result from incorporation of external stimuli.
Etiological theories of nocturnal enuresis are varied and plentiful (see

references 9, 20, 26, 42, 43, 47, 70, 91, 94, 113, 122, 132, 144, 149, 165, 167,
169, 170, 248, 249, 279, 280, 288, 289, 322, 324, 327, 350, 368, 377, 392, 394,
396, 409, 419, 427, and 445), and the classification scheme used by Werry
and Cohrssen is helpful in considering them. Genetic theories are based on
the high familial incidence of the disorder. Maturational theories derive from
observations of physical or psychological immaturity in enuretics. Data
concerning physical or psychological abnormalities in enuretics give rise to
the pathological theories, while the numerous and varied observations of
psychological disturbances in enuretics have produced psychogenic theories.

Poor habit training has been ascribed an etiological role by some authors. As
Werry and Cohrssen noted, these categories are not mutually exclusive and
several writers (see references 51, 149, 169, 346, and 394). have emphasized
the multiple etiologies of nocturnal enuresis.
Sleep EEG studies have given rise to several explanations of this
disorder. Ditman and Blinn and Bental stressed the discrepancy between
behavioral reactivity and EEG sleep before and during the enuretic event.
Ditman and Blinn suggested that enuretics are in a dissociative state, while
Bental hypothesized that the enuretic child develops a “will” to remain awake
in order to avoid wetting the bed. This will is reflected in the waking EEG
activity accompanying behavioral sleep. Pierce et al. and Schiff considered the
enuretic event to be a dream equivalent or variant. On the basis of their data,
Ritvo et al. concluded that there are three types of enuretic events: (1) awake
enuresis occurs during EEG wakefulness; (2) nonarousal enuresis occurs
during stages 2, 3, or 4 and is not preceded by arousal phenomena; and (3)

arousal enuresis occurs during stages 2, 3, and 4 and is preceded by arousal
phenomena. According to Ritvo et al., all patients appear to have a
pathophysiological substrate for enuresis, but psychological factors are
probably very important in the maintenance of enuresis in patients exhibiting
predominantly awake and arousal enuresis.
Broughton suggested that enuresis is a slow-wave-sleep arousal
phenomenon, similar to sleepwalking night terrors. In Broughton’s opinion,

slow-wave-sleep arousals occur in all individuals but enuretics are
physiologically predisposed to enuretic attacks during the arousals. Finley
has also viewed enuresis as an arousal defect within the CNS.
Bruxism
Bruxism, or teeth grinding, is of interest to the physician primarily
because of the damage it may cause to the teeth and related structures, but it
causes an unknown amount of annoyance to the sufferer’s close associates.

Although most writers consider diurnal and nocturnal bruxism to be a single
entity, Reding et al. suggested that they are separate phenomena. Nocturnal
bruxism is typically characterized by rhythmic patterns of masseter EMG

activity which is frequently accompanied by sounds of teeth grinding, while
diurnal bruxism is idiosyncratic and silent, except in individuals with organic
brain lesions. Reding et al. noted that the two phenomena occur during
different states of consciousness, and that if nocturnal bruxists are awakened

they appear to have no awareness of their teeth grinding. In one sample of
forty-five nocturnal bruxists, none gave evidence of diurnal bruxism.
Among periodontal patients 78 percent have been described as bruxists.

In studies of somewhat more representative samples, Reding and his
associates have reported the following incidence figures: 5.1 percent of 2290
undergraduate and graduate students between the ages of sixteen and thirty-
six years reported current bruxism; 5.5 percent of 1157 laboratory school
students ages three to seventeen years reported to be current bruxists by
parents, and 15.1 percent reported to have either current or past histories;
and 8 percent of 2168 undergraduate and graduate students reported current
or past histories. Bruxism appears to affect people of all ages, but seems to
decline in incidence with increasing age. There is some evidence that bruxism
is a familial disorder.
A primary difficulty in studying bruxism has been the reliable and
artifact free monitoring of teeth grinding. In early work it was concluded that
bruxism is temporally related to REM sleep. This conclusion has been revised
with the use of stricter criteria for the detection of bruxism episodes. The
latest evidence indicates that bruxism occurs predominantly during stage-2
sleep. There is no change in the nature of sleep or in the relative proportions

of sleep stages when bruxists are compared to controls. The bruxism episode,
which lasts an average of nine seconds, is often preceded by a K-complex or a

K-complex wave without a spindle. During the episode, trains of alpha or a
temporary change toward lower-voltage, fast, random activity, without K-
waves or spindles, may occur. Heart rate may increase just before or during
the episode, and subcutaneous blood vessels are constricted. Pulse rate and
respiration may also change. Forearm and palm electrodermal potentials

have been observed during a number of episodes. Sound stimuli during the
various stages of sleep have provoked teeth grinding in some subjects. There
is evidence that teeth grinding is not associated with any specific manifest
content during stage-2 sleep.
Diurnal and nocturnal bruxism have been attributed to a variety of
causes, including genetically determined behavior patterns, local or intraoral
factors, lesions of the CNS, and psychological factors (see references 131, 136,
173, 290, 378, 397, 408, 413, and 420). Several authors have suggested that
psychological disturbance is a necessary condition for the disorder and that
dental problems are precipitating factors.
The oral expression of aggression has been one of the most common
psychological interpretations of bruxism. However, in a study of bruxists,
presumably of both the diurnal and the nocturnal type, Frisch et al. failed to
find a significant relationship between degree of dental evidence of bruxism

and mode of expressing aggression as determined by the Rosenzweig Picture-
Frustration Study, an instrument designed to measure responses to

frustration. Reding et al. concluded that nocturnal bruxists and their controls
do not show any statistically significant personality differences as measured
by the MMPI and the Cornell Medical Index.
On the basis of their sleep EEG and psychological studies of nocturnal
bruxists, Reding and his associates concluded that none of the factors listed
above plays the primary etiological role in bruxism. They proposed instead
that nocturnal bruxism is a partial arousal phenomenon similar to the slow-

wave-sleep arousal phenomena (sleepwalking, enuresis, and night terrors)
described by Broughton. Satoh and Harada extended this explanation by
proposing that bruxism often occurs if the dopaminergic nigrostriatal system
excessively drives the areas controlling jaw movements during the transition
from sleep to wakefulness. This hypothesis is indirectly supported by a report
that administration of dihydroxyphenylalanine, the precursor of dopamine, to

an individual suffering from Parkinson’s disease provoked bruxism.
Jactatio Capitis Nocturna
Jactatio capitis nocturna, or sleep rocking, is a motor-behavior pattern

consisting of rhythmical movements of the head or body prior to or during
sleep. Evans, who extensively reviewed the literature concerning this rather
rare disorder, concluded that the movements may be regular or intermittent
bursts of activity and that they may appear to be voluntary, even though the
individual is usually unable to recall the episode the next morning. Mental
retardation and daytime tics, and rocking movements may characterize some
sufferers, but more commonly they exhibit symptoms of behavioral disorders.
Most patients have rocked from the second six months of life, and the
disturbance may persist into adulthood.
Only a few cases of sleep rocking have been studied in the sleep
laboratory. Gastaut and Broughton found that the onset of rocking associated
with going to sleep is typically signaled by several slow nystagmoid eye
movements. The episodes usually appear during stage-1 sleep and produce
no significant EEG, cardiac, or respiratory changes. Baldy-Moulinier et al.
observed one case where rocking movements seemed to facilitate the return
to sleep after periods of wakefulness.
Rocking movements during sleep have been observed in all phases of
sleep. Slow-wave sleep episodes begin rather abruptly, and seem not to
produce noticeable changes in heart rate or respiration. Although Gastaut and
Broughton observed no important modifications in the EEG during the

episodes, Oswald found that periods of slow waves and spindles were
interspersed with periods of low-voltage activity as the episode ran its
course.
Episodes of REM-sleep rocking also occur. In one of his cases, Oswald
found that rocking episodes were most frequent and violent during this stage.
As with episodes occurring during other stages, there were no significant EEG
or heart-rate changes during these REM-sleep episodes.
Evans noted that both organic and psychological etiologies have been
proposed for this disturbance. Evans himself suggested that the rocking
movements relieve anxiety associated with sleep, and produce sleep through
autohypnosis, much as the rhythmic stimulation employed by Oswald

produced sleep in an experimental situation. Oswald also considers sleep
rocking to be motivated, and suggested that it may reflect the use of a
previously learned mechanism to relieve unhappy thoughts during sleep.
Gastaut and Broughton have categorized the disorder as an unconscious,

semipurposeful automatism which is liberated with the depression of cortical
and subcortical systems during falling asleep and during sleep.
Sleep-Modified Disorders
In sleep there are many physiological changes which might account for
modifications of various medical complaints. The changes may or may not be

sleep dependent, i.e., they may be circadian. During REM sleep, pulse rate,
respiration rate, and blood pressure increase and show greater variability,
penile erections occur, and there are increases in plasma and urinary levels of
17-hydroxycorticosteroids, brain temperature, oxygen consumption, unit
neuronal discharge rates, antidiuretic hormone activity, and urinary 3-
methoxy-4-hydroxymandelic acid. Many other physiological changes occur
during sleep, but this list should make the point sufficiently clear.
Several cardiovascular and respiratory disorders are exacerbated
during sleep. There is great variability in the EEG sleep patterns of angina
patients, and nocturnal angina attacks, evidenced by ST-segment depression
on the electrocardiogram, appear to occur predominantly during REM sleep.

Clinically it has been noted that myocardial infarctions occur with a high
frequency during sleep. In our laboratory preliminary evidence suggests that
myocardial infarct patients maintained on an intensive-care ward are sleep-
deprived, either because of discomfort or because of disturbances produced
when therapeutic procedures are carried out. We have also noted that these
patients often show increases in premature ventricular contractions during

REM sleep.
Paroxysmal nocturnal hemoglobinuria is a rare disease affecting both
sexes. It is most common between the ages of twenty and fifty and is usually
fatal. Hemolysis is increased during the sleep of victims.
Left ventricular failure is commonly associated with pulmonary edema

at night and results in episodes of paroxysmal nocturnal dyspnea. The
mechanism appears to involve an increase in plasma volume and a shift of
blood from the lower extremities to the pulmonary circulation on assumption
of the supine position. The resultant increase in pulmonary blood promotes
pulmonary congestion and produces pulmonary edema.
Paroxysmal nocturnal headaches are also called cluster headaches

because they tend to occur in series. The patient usually awakens during the
night with a severe, throbbing, unilateral headache, which may be
accompanied by vomiting, watering and redness of the eyes, and stuffiness of

the nose. The disorder appears to result from a periodic dilatation of the
extracranial vessels in the territory of the external carotid artery.
Emphysema patients, who exhibit increased alveolar C02 tension and

decreased arterial oxygen saturation during the waking state, suffer their
most difficult periods soon after awakening. The fact that these patients show
abnormal increases in alveolar CCL tension and decreases in arterial oxygen
saturation while asleep may explain these postawakening exacerbations.
Sleep EEG studies of asthmatic children have shown that these patients
have decreased stage-4 sleep, frequent awakenings, and decreased total sleep
time. Asthmatic episodes are confined to the last two-thirds of the night. In
asthmatic adults episodes occur throughout the night, with no relation to any
specific sleep stage. The patients have shorter total sleep times and less stage
4 than controls. Johns et al. found that patients experiencing dyspnea as a
result of bronchial asthma reported frequent night awakenings without
significant loss of sleep, and more daytime sleep than average.
Snoring is the nocturnal emission of various grunts, snorts, wheezes,
buzzes, and gurgles. The immediate cause of these noises is vibration of the
soft structures in the nose and throat accompanying mouth breathing during
sleep. It has been estimated that one in eight persons snores most of the
night. In 1961 over 300 antisnore devices were recorded in the U.S. Patent
Office. Diverse etiologies have been suggested, including structural
abnormalities of the upper respiratory tract, sleeping position, allergies,
overheated or overventilated rooms, and psychological factors. There are no
known polygraphic studies of snoring. Since the etiology of this extremely

common disorder is apparently mixed, such a study might help to
differentiate the various types of snorers, as well as determine whether or not
snoring is confined to any particular sleep stage.
Various neuromuscular conditions are exacerbated during sleep. In
acroparasthesia, or carpal tunnel syndrome, the patient awakens in the later
part of the night with pain, tingling, and numbness in the first three or four
digits of one or both hands. Attacks last for thirty minutes or more and are
more frequent in women than men. This disorder appears to result from
compression of the median nerves in the carpal tunnel at the wrist.
Night cramps, usually of the calf, occur increasingly with age, and also
during pregnancy. They are thought to result from a serum calcium deficiency
in pregnant women, but the etiology in the elderly is unclear.
Tired-arm syndrome affects middle-aged women, who awaken with

pain in the forearm and may detect a weakness in the hand. Excessive
muscular exertion has been attributed a causative role.
The elderly are primary sufferers of nocturnal pseudohemiplegia. This
disorder is characterized by numbness and immobility of one arm or one side
of the body upon awakening at night or in the morning. It is of short duration
and is possibly some form of pressure palsy.
Familial periodic paralysis is characterized by episodes of muscular

weakness and eventual flaccid paralysis. Onset is usually at night, and the
attacks can last as long as several days. The apparent cause of the paralysis is
an exaggeration of the normal loss of plasma potassium to the muscles, and

the resulting decrease in muscle membrane excitability.
The restless-legs syndrome was first described by Wittmaack as

anxietas tibiarum, which is defined in Dorland’s Illustrated Medical Dictionary
as “a painful condition of unrest leading to a continual change of position of
limbs, and due to an increase of the muscular sense.” This disorder has been
briefly described by several authors, but Ekbom has presented the most
detailed discussion. He coined the term “restless legs” for this syndrome and
differentiated two clinical forms, asthenia crurum parasthetica and asthenia

crurum dolorosa. The disorder is frequently familial in nature and sleep
disturbance is an almost constant concomitant. Our recent study of a patient
confirmed the findings of Lugaresi et al. that the motor disturbances occur
every twenty to thirty seconds. We also noted that the EEG burst activity
signaling the limb movements became progressively stronger over a period of
five to ten minutes until the patient awoke. During REM sleep the myoclonic
jerks subsided, but movements of the toes continued to occur periodically. It

has been proposed that restless legs is a somatic form of anxiety or a
manifestation of disturbed lower-limb circulation. Several authors have
attributed the disorder to disturbances in the reticular formation.
Several additional medical conditions have been shown to occur or be

exacerbated during sleep. Microfilaria of Wuchereria bancrofti can be found
in the blood most frequently between midnight and 2 a.m. Patients suffering
from diabetes mellitus show a fairly wide variation in blood-sugar
concentrations during sleep, whereas in normal individuals there are only

small variations in blood-sugar levels.
A sleep EEG study of patients with duodenal ulcers revealed that the
high nocturnal secretion rate of gastric acid by ulcer patients is particularly

exaggerated during REM sleep. The authors suggested that content of dreams
may determine the magnitude of the secretion rate.
Hypnalgia, or psychogenic pain during sleep in children, is attributed to

underlying emotional disturbance.
Painful nocturnal penile erections may awaken men at night and induce
a special type of sleep disturbance. They appear to be REM-related

phenomena.
Nocturnal proctalgia, or proctalgia fugax, is an early morning pain
seeming to arise from the rectum. It is more common in men than in women,
is reported most frequently by people twenty to fifty years old, and is often a
familial disorder. It has been attributed to segmental cramp of the
puboccocygeus muscle.
From this very brief review of some sleep-modified disorders it is clear
that many sleep-related phenomena have yet to be studied by sleep

researchers. With further study it may become necessary to reclassify some of
these disorders as secondary sleep disorders. In any case, there can be no

doubt that sleep research has contributed in many ways to a better
understanding of numerous clinical conditions, and there is every reason to

expect a similar contribution in the area of the sleep-modified disorders.
Bibliography
Abe, K. and M. Shimakawa. “Genetic and Developmental Aspects of Sleeptalking and Teeth-
Grinding,” Acta Paedopsychiatr. (Basel), 33 (1966), 339-344.
Adie, W. J. “Idiopathic Narcolepsy: A Disease ‘Sui Generis’; with Remarks on the Mechanism of
Sleep,” Brain, 49 (1926), 257-306.
Aird, R. B., N. S. Gordon, and H. C. Gregg. “Use of Phenacemide (Phenurone) in Treatment of

Narcolepsy and Cataplexy. A Preliminary Report,” Arch. Neurol. Psychiatry, 70
(1953), 510-515.
Aitken, R. S., E. N. Allott, L. I. M. Castleden et al. “Observations on a Case of Familial Periodic

Paralysis,” Clin. Sci., 3 (1937). 47-57.
Allen, I. M. “Somnambulism and Dissociation of Personality,” Br. J. Med. Psychol., 11 (1931), 319-
331.
Allison, F. G. “Obscure Pains in Chest, Back or Limbs,” Can. Med. Assoc. J., 48 (1943), 36-38.
Altshuler, K. Z. “Snoring: Unavoidable Nuisance or Psychological Symptom,” Psychoanal. Q., 33

(1964), 552-560.
Anderson, F. N. “The Psychiatric Aspects of Enuresis,” Am. J. Dis. Child., 40 (1930), 591-618.
----. “The Psychiatric Aspects of Enuresis,” Am. J. Dis. Child., 40 (1930), 818-850.
André-Balisaux, G. and R. Gonsette. “L’Electroencéphalographie dans le somnambulisme et sa

valeur pour l’établissement d’un diagnostic étiologique,” Acta Neurol. Psychiatr.
Belgica, 56 (1956), 270-281.
Anthony, J. “An Experimental Approach to the Psychopathology of Childhood: Sleep

Disturbances,” Br. J. Med. Psychol., 32 (1959). 19-37.
Arduini, A., G. Berlucchi, and P. Strata. “Pyramidal Activity during Sleep and Wakefulness,” Arch.
Ital. Biol., 101 (1963). 530-544.
Arkin, A. M. “Sleep-Talking: A Review,” J. Nerv. Ment. Dis., 143 (1966), 101-122.
Arkin, A. M., J. M. Hastey, and M. F. Reiser. “Dialogue between Sleep-Talkers and the
Experimenter.” Paper presented at the Ann. Meet, of the Assoc, for the
Psychophysiological Study of Sleep, Gainesville, Florida, March, 1966.
Arkin, A. M., M. F. Toth, J. Baker et al. “The Frequency of Sleep Talking in the Laboratory among
Chronic Sleep Talkers and Good Dream Recallers,” J. Nerv. Ment. Dis., 151 (1970),
369-374.
----. “The Degree of Concordance between the Content of Sleep Talking and Mentation Recalled in
Wakefulness,” J. Nerv. Ment. Dis., 151 (1970), 375-393.
Armstrong, R. H., D. Burnap, A. Jacobson et al. “Dreams and Gastric Secretions in Duodenal Ulcer
Patients,” New Physician, 14 (1965), 241-243.
Aserinsky, E. and N. Kleitman. “Regularly Occurring Periods of Eye Motility, and Concomitant
Phenomena, during Sleep,” Science, 118 (1953), 273-274.
Auchincloss, J. H., E. Cook, and A. D. Renzetti. “Clinical and Physiological Aspects of a Case of
Obesity, Polycythemia and Alveolar Hypoventilation,” J. Clin. Invest., 34 (1955),
1537-1545.
Bakwin, H. “Enuresis in Children,” J. Pediatr., 58 (1961), 806-819.
----. “Sleep-Walking in Twins,” Lancet, 2 (1970), 446-447-
Baldy-Moulinier, M., M. Levy, and P. Passouant. “A Study of Jactatio Capitis during Night Sleep,”
Electroencephalogr. Clin. Neurophysiol., 28 (1970), 87.
Balla, J. I. and J. N. Walton. “Periodic Migrainous Neuralgia,” Br. Med. J., 1 (1963), 219-221.
Barontini, F. and R. Zappoli. “A Case of Kleine-Levin Syndrome. Clinical and Polygraphic Study,” in
H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The Abnormalities of Sleep in Man.
Proc. 15th Europ. Meet. Electroencephalogr., Bologna, 1967, pp. 239-245. Bologna:
Aulo Gaggi, 1968.
Behrman, S. “Disturbed Relaxation of Limbs,” Br. Med. J., 1 (1958), 1454-1457.
Benowitz, H. H. “The Enuretic Soldier in an AAF Basic Training Center. (A Study of 172 Cases),” J.
Nerv. Ment. Dis., 104 (1946), 66-79.
Bental, E. “Dissociation of Behavioural and Electroencephalographic Sleep in Two Brothers with

Enuresis Nocturna,” J. Psychosom. Res., 5 (1961), 116-119.
Berdie, R. F. and R. Wallen. “Some Psychological Aspects of Enuresis in Adult Males,” Am. J.
Berti Ceroni, G. “An Episode of Hypersomnia and Megaphagia and Its Evolution to a Narcoleptic
Syndrome,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The Abnormalities
of Sleep in Man. Proc. 15th Europ. Meet. Electroencephalogr., Bologna, 1967, pp.
247-249. Bologna: Aulo Gaggi, 1968.
Berti Ceroni, G., G. Coccagna, D. Gambi et al. “Considerazioni Clinico-Poligrafiche sulla Narcolessia
Essenziale ‘A Sonno Lento’,” Sist. Nerv., 19 (1967), 81-89.
Berti Ceroni, G., G. Coccagna, and E. Lugaresi. “Twenty-Four Hour Polygraphic Recordings in
Narcoleptics,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The
Abnormalities of Sleep in Man. Proc. 15th Europ. Meet. Electroencephalogr.,
Bologna, 1967, pp. 235-238. Bologna: Aulo Gaggi, 1968.
Bing, R. Lehrbuch der Nervenkrankheiten, p. 522. Berlin: Karger, 1913.
Birchfield, R. I., H. O. Sieker, and A. Heyman. “Alterations in Blood Gases during Natural Sleep and
Narcolepsy. A Correlation with the Electroencephalographic Stages of Sleep,”
Neurology (Minneap.), 8 (1958), 107-112.
----. “Alterations in Respiratory Function during Natural Sleep,” J. Lab. Clin. Med., 54 (1959), 216-
222.
Bjerk, E. M. and J. J. Hornisher. “Narcolepsy: A Case Report and a Rebuttal,” Electroencephalogr.
Blake, H., R. W. Gerard, and N. Kleitman. “Factors Influencing Brain Potentials during Sleep,” J.
Neurophysiol., 2 (1939), 48-60.
Bleuler, E. (1908) Dementia Praecox or the Group of Schizophrenias, pp. 439-441. Translated by Z.
Zinkin. New York: International Universities Press, 1950.
Blomfield, J. M. and J. W. B. Douglas. “Bedwetting, Prevalence among Children Aged 4-7 Years,”
Lancet, 1 (1956), 850-852.
Bonkalo, A. “Hypersomnia. A Discussion of Psychiatric Implications Based on Three Cases,” Br. J.

Psychiatry, 114 (1968), 69-75.
Bonstedt, T. “Emotional Aspects of the Narcolepsies. (With Report of a Case of Sleep Paralysis),”
Dis. Nerv. Syst., 15 (1954), 291-297.
Bornstein, B. “Restless Legs,” Psychiatr. Neurol., 141 (1961), 165-201.
Bostock, J. “Exterior Gestation, Primitive Sleep, Enuresis and Asthma: A Study in Aetiology. Part
1,” Med. J. Aust., 2 (1958), 149-153.
----. “Exterior Gestation, Primitive Sleep, Enuresis and Asthma: A Study in Aetiology. Part 2,” Med.
J. Aust., 2 (1958), 185-188.
----. “The Deep Sleep-Enuresis Syndrome,” Med. J. Aust., 1 (1962), 240-243.
Boulware, M. H. “Coping with Snoring Problems of Children,” Rehabilit. Lit., 27 (1966), 141-142.
Boyens, P. J. “Value of Autosuggestion in the Therapy of ‘Bruxism’ and other Biting Habits,” J. Am.
Dent. Assoc., 27 (1940), 1773-1777.
Braithwaite, J. V. “Enuresis in Childhood,” Practitioner, 165 (1950), 273-281.
Branchey, M. and O. Petre-Quadens. “A Comparative Study of Sleep Parameters during
Pregnancy,” Acta Neurol. Belg., 68 (1968), 453-459.
Brebbia, D. R. and K. Z. Altshuler. “Oxygen Consumption Rate and Electroencephalographic Stage

of Sleep,” Science, 150 (1965), 1621-1623.
Brock, S. and B. Wiesel. “The Narcoleptic-Cataplectic Syndrome—an Excessive and Dissociated

Reaction of the Sleep Mechanism—and Its Accompanying Mental States,” J. Nerv.
Ment. Dis., 94 (1941), 700-712.
Brodny, M. L. and S. A. Robins. “Enuresis. The Use of Cystourethrography in Diagnosis,” JAMA, 126
(1944), 1000-1006.
Brooks, D. C. and E. Bizzi. “Brain Stem Electrical Activity during Deep Sleep,” Arch. Ital. Biol., 101
(1963), 648-665.
Broughton, R. J. “Sleep Disorders: Disorders of Arousal?” Science, 159 (1968), 1070-1078.
----. “The Incubus Attack,” Int. Psychiatry Clin., 7 (1970), 188-192.
Browne, R. C. and A. Ford-Smith. “Enuresis in Adolescents,” Br. Med. J., 2 (1941), 803-805.
Bruhova, S., O. Nevsimal, and A. Ourednik. “Polygraphic Study in the So Called Pickwickian
Syndrome,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The Abnormalities
Bülow, K. “Respiration and Wakefulness in Man,” Acta Physiol. Scand. (Suppl.), 209 (1963), 1-110.
Bülow, K. and D. H. Ingvar. “Respiration and State of Wakefulness in Normals, Studied by

Spirography, Capnography and EEG. A Preliminary Report,” Acta Physiol. Scand., 51
(1961), 230-238.
----. “Respiration and Electroencephalography in Narcolepsy,” Neurology (Minneap.), 13 (1963),

321-326.
Burwell, C. S., E. D. Robin, R. D. Whaley et al. “Extreme Obesity Associated with Alveolar
Hypoventilation—a Pickwickian Syndrome,” Am. J. Med., 21 (1956), 811-818.
Cadilhac, J., M. Baldy-Moulinier, M. Delange et al. “Diurnal and Nocturnal Sleep in Narcolepsy,”
Caldwell, D. F. and E. F. Domino. “Electroencephalographic and Eye Movement Patterns during

Sleep in Chronic Schizophrenic Patients,” Electroencephalogr. Clin. Neurophysiol., 22
(1967), 414-420.
Cameron, W. B. “Some Observations and a Hypothesis Concerning Sleep-Talking,” Psychiatry, 15

(1952), 95-96.
Carroll, J. D. “Migraine: Its Variants, Differential Diagnosis and Treatment,” Res. Clin. Stud.
Headache, 1 (1967), 46-61.
Chee, P. H. Y. “Ocular Manifestations of Narcolepsy,” Br. J. Ophthalmol., 52 (1968), 54-56.
Child, C. M. “Statistics of ‘Unconscious Cerebration’,” Am. J. Psychol., 5 (1892), 453-463.
Chodoff, P. “Sleep Paralysis. With Report of Two Cases,” J. Nerv. Ment. Dis., 100 (1943), 278-281.
Coccagna, G. and E. Lugaresi. “Insomnia in the Restless Legs Syndrome,” in Gastaut, E. Lugaresi, G.
Berti Ceroni et al., eds., The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet.
Electroencephalogr., Bologna, 1967, pp. 139-144. Bologna: Aulo Gaggi, 1968.
Coccagna, G., A. Petrella, G. Berti Ceroni et al. “Polygraphic Contribution to Hypersomnia and
Respiratory Troubles in the Pickwickian Syndrome,” in H. Gastaut, E. Lugaresi, G.
Berti Ceroni et ah, eds., The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet.
Cohen, D. L. “Nocturnal Enuresis in the Adult Male: A Urological Study,” J. Urol., 57 (1947). 331-
337.
Cohen, H. D., A. Shapiro, D. R. Goodenough et al. “The EEG during Stage 4 Sleep-Talking,” Paper
presented at the Ann. Meet, of the Assoc, for the Psychophysiological Study of
Sleep, Washington, March, 1965.
Cohn, R. and B. A. Cruvant. “Relation of Narcolepsy to the Epilepsies,” Arch. Neurol. Psychiatry, 51
(1944), 163-170.
Critchley, M. “Periodic Hypersomnia and Megaphagia in Adolescent Males,” Brain, 85 (1962),

627-657.
Critchley, M. and H. L. Hoffman. “The Syndrome of Periodic Somnolence and Morbid Hunger
(Kleine-Levin Syndrome),” Br. Med. J., 1 (1942), 137-139.
Dacie, J. V. The Haemolytic Anaemias, Congenital and Acquired, Part 4, 2nd ed., pp. 1128-1260.
New York: Grune & Stratton, 1967.
Daly, D. D. and R. E. Yoss. “Electroencephalogram in Narcolepsy,” Electroencephalogr. Clin.

Neurophysiol., 9 (1957), 109-120.
Daniels, L. E. “Narcolepsy,” Medicine (Baltimore), 13 (1934), 1-122.
Davidson, G. M. “Concerning Schizophrenia and Manic-Depressive Psychosis Associated with

Pregnancy and Childbirth,” Am. J. Psychiatry, 92 (1936), 1331-1346.
Davis, E., M. Hayes, and B. H. Kerman. “Somnambulism,” Lancet, 1 (1942), 186.
Delorme, F., J. L. Froment, and M. Jouvet. “Suppression du sommeil par la p.

chloromethamphetamine et la p. chloraphenylalanine,” Compt. Rend. Soc. Biol.
Filial., 160 (1966), 2347-2351.
Dement, W. C. “Dream Recall and Eye Movements during Sleep in Schizophrenics and Normals,” J.
Nerv. Ment. Dis., 122 (1955), 263-269.
----. “The Effect of Dream Deprivation,” Science, 131 (1960), 1705-1707.
----. “Experimental Dream Studies,” in J. H. Masserman, ed., Science and Psychoanalysis. Vol. 7,
Development and Research, pp. 129-184. Academy of Psychoanalysis. New York:
Grune & Stratton, 1964.
----. “Psychophysiology of Sleep and Dreams,” in S. Arieti, ed., American Handbook of Psychiatry,
1st ed., Vol. 3, pp. 290-332. New York: Basic Books, 1966.
----. “The Biological Role of REM Sleep (Circa 1968),” in A. Kales, ed., Sleep. Physiology and
Pathology. A Symposium, pp. 245-265. Philadelphia: Lippincott, 1969.
Dement, W. C. and C. Fisher. “Experimental Interference with the Sleep Cycle,” Can. Psychiatr.
Assoc. J., 8 (1963), 400-405.
Dement, W. C. and N. Kleitman. “The Relation of Eye Movements during Sleep to Dream Activity:
An Objective Method for the Study of Dreaming,” J. Exp. Psychol., 53 (1957), 339-
346.
Dement, W. C. and A. Rechtschaffen. “Narcolepsy: Polygraphic Aspects, Experimental and

Theoretical Considerations,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds.,
The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet. Electroencephalogr.,
Bologna, 1967, pp. 147—Bologna: Aulo Gaggi, 1968.
Dement, W. C., A. Rechtschaffen, and Gulevich. “The Nature of the Narcoleptic Sleep Attack,”
Neurology (Min-neap.), 16 (1966), 18-33.
Department of Health, Education and Welfare. A Report to the President on Medical Care Prices.
Washington: U.S. Govt. Print. Off., 1967.
Despeht, J. L. “Urinary Control and Enuresis,” Psychosom. Med., 6 (1944), 294-307.
Detre, T., J. Himmelhoch, M. Swartzburg et al. “Hypersomnia and Manic-Depressive Disease,” Am.
J. Psychiatry, 128 (1972), 1303-1305.
Diaz-Guerrero, R., J. S. Gottlieb, and J. R. Knott. “The Sleep of Patients with Manic-Depressive
Psychosis, Depressive Type. An Electroencephalographic Study,” Psychosom. Med.,
8 (1946), 399-404.
Ditman, K. S. and K. A. Blinn. “Sleep Levels in Enuresis,” Am. J. Psychiatry, 111 (1954). 913-920.
Dorland’s Illustrated Medical Dictionary, 24th ed., p. 113. Philadelphia: Saunders, 1965.
Douthwaite, A. H. “Proctalgia Fugax,” Br. Med. J., 2 (1962), 164-165.
Drachman, D. B. and R. J. Gumnit. “Periodic Alteration of Consciousness in the ‘Pickwickian’

Syndrome,” Arch. Neurol., 6 (1962), 471-477.
Duffy, J. P. and K. Davison. “A Female Case of the Kleine-Levin Syndrome,” Br. J. Psychiatry, 114
(1968), 77-84.
Dynes, J. B. and K. H. Finley. “The Electroencephalograph as an Aid in the Study of Narcolepsy,”

Earle, B. V. “Periodic Hypersomnia and Megaphagia (The Kleine-Levin Syndrome),” Psychiatr. Q.,
39 (1965), 79-83.
Edmonds, C. “Severe Somnambulism: A Case Study,” J. Clin. Psychol., 23 (1967), 237-239.
Ekbom, K. A. “Restless Legs,” Acta Med. Scand., (Suppl.), 158 (1945), 1-123.
----. “Restless Legs Syndrome,” Neurology (Minneap.), 10 (1960), 868-873.
Elenewski, J. J. “A Study of Insomnia: The Relationship of Psychopathology to Sleep Disturbance,”

Ph.D. dissertation, University of Miami, 1971.
Elian, M. and B. Bornstein. “The Kleine-Levin Syndrome with Intermittent Abnormality in the
EEG,” Electroencephalogr. Clin. Neurophysiol., 27 (1969), 601-604.
Escande, J. P., B. A. Schwartz, M. Gentilini et al. “Le Syndrome Pickwickien,” Presse Med., 75
(1967), 1607-1610.
Ethelberg, S. “Sleep-Paralysis or Postdormitial Chalastic Fits in Cortical Lesion of the Frontal

Pole,” Acta Psychiatr. Neurol. Scand., (Suppl.), 108 (1956), 121-130.
Evans, J. “Rocking at Night,” J. Child Psychol. Psychiatry, 2 (1961), 71-85.
Evarts, E. V. “Activity of Neurons in Visual Cortex of the Cat during Sleep with Low Voltage Fast
EEG Activity,” J. Neurophysiol., 25 (1962), 812-816.
Everett, H. C. “Sleep Paralysis in Medical Students,” J. Nerv. Ment. Dis., 136 (1963), 283-287.
Every, R. G. “The Significance of Extreme Mandibular Movements,” Lancet, 2 (1960), 37-39.
----. “The Teeth as Weapons. Their Influence on Behaviour,” Lancet, 1 (1965), 685-688.
Eysenck, H. J. “Learning Theory and Behaviour Therapy,” J. Ment. Sci., 105 (1959), 61-75.
Fabricant, N. D. “Snoring,” Practitioner, 187 (1961), 378-380.
Faure, J., C. Martin, J. D’Aulnay et al. “Enuresie et somnambulisme, formes lar-vees de la

comitialite chez l’enfant,” Arch. Fr. Pedia.tr., 8 (1951), 678-679.
Feinberg, I. “Commentary on Sleep and Schizophrenia,” Schizophr. Bull., 4 (1971), 70-71.
Feinberg, I., M. Braun, R. L. Koresko et al. “Stage 4 Sleep in Schizophrenia,” Arch. Gen. Psychiatry,
21 (1969), 262-266.
Feinberg, I., R. L. Koresko, and F. Gottlieb. “Further Observations on Electro-physiological Sleep

Patterns in Schizophrenia,” Compr. Psychiatry, 6 (1965), 21-24.
Feinberg, I., R. L. Koresko, F. Gottlieb et al. “Sleep Electroencephalographic and Eye-Movement

Patterns in Schizophrenic Patients,” Compr. Psychiatry, 5 (1964), 44-53.
Feldman, M. J. and M. Hersen. “Attitudes towards Death in Nightmare Subjects,” J. Abnorm.

Psychol., 72 (1967), 421.425.
Ferguson, J., S. Henriksen, K. McGarr et al. “Phasic Event Deprivation in the Cat,” Psychophysiology,
5 (1968), 238-239.
Finley, W. W. “An EEG Study of the Sleep of Enuretics at Three Age Levels,” Clin.
Electroencephalogr., 2 (1971), 35-39.
Fisher, C. “Psychoanalytic Implications of Recent Research on Sleep and Dreaming. Part I:
Empirical Findings,” J. Am. Psychoanal. Assoc., 13 (1965), 197-270.
Fisher, C., J. Byrne, A. Edwards et al. “A Psychophysiological Study of Nightmares,” J. Am.

Psychoanal. Assoc., 18 (1970), 747-782.
----. “REM and NREM Nightmares,” Int. Psychiatry Clin., 7 (1970), 183-187.
Fisher, C., J. Gross, and J. Zuch. “Cycle of Penile Erection Synchronous with Dreaming (REM) Sleep.
Preliminary Report,” Arch. Gen. Psychiatry, 12 (1965), 29-45.
Fisher, C., E. Kahn, A. Edwards et al. “Total Suppression of REM Sleep with the MAO Inhibitor
Nardil in a Subject with Painful Nocturnal REMP Erection,” Psychophysiology, 9
(1972), 91.
Fisher, O. D. and W. I. Forsythe. “Micturating Cysto-Urethrography in the Investigation of

Enuresis,” Arch. Dis. Child., 29 (1954), 460-471.
Ford, F. R. “The Tired Arm Syndrome,” Johns Hopkins Med. J., 98 (1956), 464-466.
Forsythe, W. E. and S. C. Karlan. “Enuresis in Young Male Adults,” J. Urology, 54 (1945), 22-38.
Franks, A. S. T. “Masticatory Muscle Hyperactivity and Temporomandibular Joint Dysfunction,” J.

Prosthet. Dent., 15 (1965), 1122-1131.
Frary, L. G. “Enuresis. A Genetic Study,” Am. J. Dis. Child., 49 (1935). 557-578.
Freud, S. (1932-33) New Introductory Lectures on Psycho-analysis, in J. Strachey, ed., Standard

Edition, Vol. 22, pp. 15-16, 221, 244-245. London: Hogarth, 1964.
Friedell, A. “A Reversal of the Normal Concentration of the Urine in Children Having Enuresis,”
Am. J. Dis. Child., 33 (1927). 717-721.
Frisch, J., L. Katz, and A. J.. Ferreira. “A Study on the Relationship between Bruxism and
Aggression,” J. Periodontol., 31 (1960), 409-412.
Frohman, B. S. “Occlusal Neuroses. The Application of Psychotherapy to Dental Problems,”
Psychoanal. Rev., 19 (1932), 297-309.
Fürstner, C. “Ueber Schwangerschafts und Puerperalpsychosen,” Arch. Psychiatr. Nervenkr., 5

(1875), 505-543.
Gahagan, L. “Sex Differences in Recall of Stereotyped Dreamt, Sleep-Talking, and Sleep-Walking,”

J. Genet. Psychol., 48 (1936), 227-236.
Gallinek, A. “Syndrome of Episodes of Hypersomnia, Bulimia, and Abnormal Mental States,” JAMA,
154 (1954), 1081-1083.
----. “The Kleine-Levin Syndrome: Hypersomnia, Bulimia, and Abnormal Mental States,” World
Neurol., 3 (1962), 235-241.
Garland, H., J. P. P. Bradshaw, and J. M. P. Clark. “Compression of Median Nerve in Carpal Tunnel
and Its Relation to Acroparaesthesiae,” Br. Med. J., 1 (1957), 730-734.
Garland, H., D. Sumner, and P. Fourman. “The Kleine-Levin Syndrome. Some Further
Observations,” Neurology, 15 (1965), 1161-1167.
Gastaut, H. and R. Broughton. “Paroxysmal Psychological Events and Certain Phases of Sleep,”
Percept. Mot. Skills, 17 (1963), 362.
----. “A Clinical and Polygraphic Study of Episodic Phenomena during Sleep,” Recent Adv. Biol.
Psychiatry, 7 (1964), 197-221.
Gastaut, H., B. Duron, J.-J. Papy et al. “Etude polygraphique comparative du cycle nycthemerique
chez les narcoleptiques, les Pickwickiens, les obeses et les insuffisants
respiratoires,” Rev. Neurol. (Paris), 115 (1966), 456-462.
Gastaut, H. and B. Roth. “A propos des Manifestations electroencephalographiques de 150 cas de

narcolepsie avec ou sans cataplexie,” Rev. Neurol. (Paris), 97 (1957). 388-393.
Gastaut, H., C. A. Tassinari, and Duron. “Polygraphic Study of the Episodic Diurnal and Nocturnal
(Hypnic and Respiratory) Manifestations of the Pickwick Syndrome,” Brain Res., 2
(1966), 167-186.
Gelineau, J. B. “De la Narcolepsie,” Gaz. Hopit., 53 (1880), 626-628, 635-637.
Gerard, M. W. “Enuresis. A Study in Etiology,” Am. J. Orthopsychiatry, 9 (1939), 48-58.
Gilbert, G. J. “Periodic Hypersomnia and Bulimia. The Kleine-Levin Syndrome,” Neurology

(Minneap.), 14 (1964), 844-850.
Glicklich, L. B. “An Historical Account of Enuresis,” Pediatrics, 8 (1951), 859-876.
Globus, G. G. “A Syndrome Associated with Sleeping Late,” Psychosom. Med., 31 (1968), 528-535.
Gonzalez, F. M., R. C. Pabico, H. W. Brown et al. “Further Experience with the Use of Routine
Intermittent Hemodialysis in Chronic Renal Failure,” Trans. Am. Soc. Artif. Intern.
Organs, 9 (1963), 11-17.
Goode, G. B. “Sleep Paralysis,” Arch. Neurol., 6 (1962), 228-234.
Goodwin, D. W., F. Freemon, B. M. Ianzito et al. “Alcohol and Narcolepsy,” Br. J. Psychiatry, 117
(1970), 705-706.
Grabfield, G. P. “The Treatment of Insomnia,” Med. Clin. North Am., 19 (1936), 1597-1601.
Green, L. N. and R. Q. Cracco. “Kleine-Levin Syndrome. A Case with EEG Evidence of Periodic Brain
Dysfunction,” Arch. Neurol., 22 (1970), 166—175.
Green, W. J. and P. P. Stajduhar. “The Effect of ECT on the Sleep-Dream Cycle in a Psychotic
Depression,” J. Nerv. Ment. Dis., 143 (1966), 123-134.
Greenberg, R. and C. Pearlman. “Delirium Tremens and Dreaming,” Am. J. Psychiatry, 124 (1967),
133-142.
Gresham, S. C., H. W. Agnew, Jr., and R. L. Williams. “The Sleep of Depressed Patients. An EEG and
Eye Movement Study,” Arch. Gen. Psychiatry, 13 (1965), 503-507.
Gresham, S. C., W. B. Webb, and R. L. Williams. “Alcohol and Caffeine: Effect on Inferred Visual
Dreaming,” Science, 140 (1963), 1226-1227.
Gross, M. M. and D. R. Goodenough. “Sleep Disturbances in the Acute Alcoholic Psychoses,”

Psychiatr. Res. Rep. Am. Psychiatr. Assoc., 24 (1968), 132-147.
Gross, M. M., D. R. Goodenough, M. Tobin et al. “Sleep Disturbances and Hallucinations in the
Acute Alcoholic Psychoses,” J. Nerv. Ment. Dis., 142 (1966), 493-514.
Gulevich, G. D., W. C. Dement, and V. P. Zarcone. “All-Night Sleep Recordings of Chronic

Schizophrenics in Remission,” Compr. Psychiatry, 8 (1967), 141-149.
Gunnarson, S. and K.-A. Melin. “The Electroencephalogram in Enuresis,” Acta Paediatr. Scand., 40
(1951), 496-501.
Gunne, L. M. and H. F. Lidvall. “The Urinary Output of Catecholamines in Narcolepsy under

Resting Conditions and following Administration of Dopamine, DOPA, and DOPS,”
Scand. J. Clin. Lab. Invest., 18 (1966), 425-430.
Hader, M. “Persistent Enuresis,” Arch. Gen. Psychiatry, 13 (1965), 296-298.
Hadfield, J. A. Dreams and Nightmares. London: Penguin Books, 1954.
Hallgren, B. “Enuresis. A Clinical and Genetic Study,” Acta Psychiatr. Neurol. Scand., (Suppl.), 114
(1957), 1-159.
Hallman, N. “On the Ability of Enuretic Children to Hold Urine,” Acta Paediatr. Scand., 39 (1950),
87-93.
Hamilton, J. A. Postpartum Psychiatric Problems. St. Louis: Mosby, 1962.
Hanretta, A. G. “Sleep in Signs, Symptoms, and Syndromes,” Dis. Nerv. Syst., 24 (1963), 81-94.
Hart, H. H. “Practical Psychiatric Problems in Dentistry,” J. Dent. Med., 3 (1948), 83-94.
Hartmann, E. “Longitudinal Studies of Sleep and Dream Patterns in Manic-Depressive Patients,”
----. “Mania, Depression, and Sleep,” in A. Kales, ed., Sleep. Physiology and Pathology. A Symposium,
pp. 183-191. Philadelphia: Lippincott, 1969.
----. “A Note on the Nightmare,” Int. Psychiatry Clin., 7 (1970), 192-197.
Hartmann, E., P. Verdone, and F. Snyder. “Longitudinal Studies of Sleep and Dreaming Patterns in
Psychiatric Patients,” J. Nerv. Ment. Dis., 142 (1966), 117-126.
Hauhi, P. and D. R. Hawkins. “Phasic REM, Depression, and the Relationship between Sleeping and
Waking,” Arch. Gen. Psychiatry, 25 (1971), 56-63.
Hawkins, D. R. and J. Mendels. “Sleep Disturbance in Depressive Syndromes,” Am. J. Psychiatry,

123 (1966), 682-690.
----. “The Psychophysiologic Investigation of Sleep in Patients with Depression,” Excerpta Medica
Int. Congr. Ser., 150 (1960), 1893-1897.
Hawkins, D. R., J. Mendels, J. Scott et al. “The Psychophysiology of Sleep in Psychotic Depression:
A Longitudinal Study,” Psychosom. Med., 29 (1967), 329-344.
Herrman, C. “The Treatment of Enuresis by Re-education,” Arch. Pediatr., 27 (1910), 600-601.
Hersen, M. “Personality Characteristics of Nightmare Sufferers,” J. Nerv. Ment. Dis., 153 (1971).
27-31.
Hishikawa, Y. “Neurophysiological Nature of Narcoleptic Symptoms,” in H. Gastaut, E. Lugaresi, G.

Berti Ceroni et al., eds., The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet.
Hishikawa, Y., E. Furuya, and H. Wakamatsu. “Hypersomnia and Periodic Respiration—

Presentation of Two Cases and Comment on the Physiopathogenesis of the
Pickwickian Syndrome,” Folia Psychiatr. Neurol. Jap., 24 (1970), 163-173.
Hishikawa, Y., H. Ida, K. Nakai et al. “Treatment of Narcolepsy with Imipramine (Tofranil) and
Desmethylimipramine (Pertofran),” J. Neurol. Sci., 3 (1966), 453-461.
Hishikawa, Y. and Z. Kaneko. “Electroencephalographic Study on Narcolepsy,”
Hishikawa, Y., H. Nan’no, M. Tachibana et al. “The Nature of Sleep Attack and Other Symptoms of
Narcolepsy,” Electroencephalogr. Clin. Neurophysiol., 24 (1968), 1-10.
Hishikawa, Y., N. Sumitsuji, K. Matsumoto et al. “H-Reflex and EMG of the Mental and Hyoid
Muscles during Sleep, with Special Reference to Narcolepsy,” Electroencephalogr.
Hnayal, A. and F. Regli. “Contribution a l’etude clinique des anomalies du sommeil. Trois cas de
‘somnolence periodique’ (Kleine-Levin),” Encephale, 56 (1967), 33-44.
Hodes, R. and W. C. Dement. “Depression of Electrically Induced Reflexes (‘H-Reflexes’) in Man

during Low Voltage EEG ‘Sleep’,” Electroencephalogr. Clin. Neurophysiol., 17 (1964),
617-629.
Huber, Z. “EEG Investigation in 200 Somnambulic Patients,” Electroencephalogr. Clin.

Neurophysiol., 14 (1962), 577.
Huttenlocher, P. R. “Evoked and Spontaneous Activity in Single Units of Medial Brain Stem during
Natural Sleep and Waking,” J. Neurophysiol., 24 (1961), 451-468.
Imlah, N. “Narcolepsy in Identical Twins,” J. Neurol. Neurosurg. Psychiatry, 24 (1961), 158-160.
Iskander, T. N. and R. Kaelbling. “Catecholamines, a Dream Sleep Model, and Depression,” Am. J.
Psychiatry, 127 (1970), 43-50.
Jackson, D. D. “An Episode of Sleep walking,” J. Am. Psychoanal. Assoc., 2 (1954), 503-508.
Jackson, J. H. “The Factors of Insanities,” in J. Taylor, G. Holmes, and F. Walshe, eds., Selected
Writings of John Hughlings Jackson, Vol. 2, pp. 411-421. New York: Basic Books,
1958.
Jacobson, A. and A. Kales. “Somnambulism: All-Night EEG and Related Studies,” Res. Publ. Assoc.
Res. Nerv. Ment. Dis., 45 (1967), 424-448.
Jacobson, A., A. Kales, D. Lehmann et al. “Muscle Tonus in Human Subjects during Sleep and
Dreaming,” Exp. Neurol., 10 (1963), 418-424.
Jacobson, A., A. Kales, D. Lehmann et al. “Somnambulism: All-Night Electroencephalographic

Studies,” Science, 148 (1965), 975-977.
Jansson, B. “Psychic Insufficiencies Associated with Childbearing,” Acta Psychiatr. Scand. (Suppl.),
172 (1963), 1-168.
Jelly, A. C. “Puerperal Insanity,” Boston Med. Surg. J., 144 (1901), 271-275.
Johns, M. W., P. Egan, T. J. A. Gay et al. “Sleep Habits and Symptoms in Male Medical and Surgical
Patients,” Br. Med. J., 2 (1970), 509-512.
Johnson, L. C., J. A. Burdick, and J. Smith. “Sleep during Alcohol Intake and Withdrawal in the
Chronic Alcoholic,” Arch. Gen. Psychiatry, 22 (1970), 406-418.
Jones, E. On the Nightmare. London: Hogarth, 1949.
Jones, R. “Puerperal Insanity,” Br. Med. J., 1 (1902), 579-585.
Journal of the American Medical Association. Editorial. “Nocturnal Enuresis,” 154 (1954), 509.
Jouvet, M. “Telencephalic and Rhombencephalic Sleep in the Cat,” in G. E. W. Wolstenholme and

M. O’Connor, eds., Ciba Foundation Symposium on the Nature of Sleep, pp. 188-208.
Boston: Little, Brown, 1960.
----. “Biogenic Amines and the States of Sleep,” Science, 163 (1969), 32-41.
Jung, C. G. “The Practical Use of Dream-Analysis,” in R. F. C. Hull, transl., The Practice of
Psychotherapy, Vol. 16, pp. 139-143. New York: Pantheon Books, 1954.
Jung, R. and W. Kuhlo. “Neurophysiological Studies of Abnormal Night Sleep and the Pickwickian
Syndrome,” Prog. Brain Res., 18 (1965), 140-159.
Kahn, B. I. and R. L. Jordan. “Paternal Domination as a Cause of Somnambulism,” Calif. Med., 80

(1954), 23-25.
Kales, A., G. N. Beall, G. F. Bajor et al. “Sleep Studies in Asthmatic Adults: Relationship of Attacks to
Sleep Stage and Time of Night,” J. Allergy, 41 (1968), 164-173.
Kales, A. and G. Cary. “Treating Insomnia,” in E. Robins, ed., Psychiatry, 1971, pp. 55-56. New
York: Medical World News, 1971.
Kales, A., F. S. Hoedemaker, A. Jacobson et al. “Dream Deprivation: An Experimental Reappraisal,”

Nature, 204 (1964), 1337-1338.
Kales, A., A. Jacobson, T. Kun et al. “Somnambulism: Further All-Night EEG Studies,”
Kales, A., A. Jacobson, M. J. Paulson et al. “Somnambulism: Psychophysiological Correlates. I. All-

Night EEG Studies,” Arch. Gen. Psychiatry, 14 (1966), 586-594.
Kales, A., J. D. Kales, R. M. Sly et al. “Sleep Patterns of Asthmatic Children: All-Night
Electroencephalographic Studies,” J. Allergy, 46 (1970), 300-308.
Kales, A., M. J. Paulson, A. Jacobson et al. “Somnambulism: Psychophysiological Correlates. II.

Psychiatric Interviews, Psychological Testing, and Discussion,” Arch. Gen.
Psychiatry, 14 (1966), 595-604.
Kamiya, J. “Behavioral, Subjective, and Physiological Aspects of Drowsiness and Sleep,” in D. W.

Fiske and S. R. Maddi, eds., Functions of Varied Experience, pp. 145-174. Homewood,
111.: Dorsey, 1961.
Karacan, I. “Insomnia: All Nights Are Not the Same,” Paper presented at the Fifth World Congress
of Psychiatry, Mexico City, November, 1971.
----. “Painful Nocturnal Penile Erections,” JAMA, 215 (1971), 1831.
Karacan, I., J. Bose, R. L. Williams et al. “Insomnia in Hemodialytic Patients,” Paper presented at
the First International Congress of the Association for the Psychophysiological
Study of Sleep, Bruges, Belgium, June, 1971.
Karacan, I., W. W. Finley, R. L. Williams et al. “Changes in Stage l-REM and Stage 4 Sleep during
Naps,” Biol. Psychiatry, 2 (1970), 261-265.
Karacan, I., D. R. Goodenough, A. Shapiro et al. “Erection Cycle during Sleep in Relation to Dream
Anxiety,” Arch. Gen. Psychiatry, 15 (1966), 183-189.
Karacan, I., W. Heine, H. W. Agnew, Jr. et al. “Characteristics of Sleep Patterns during Late
Pregnancy and the Postpartum Periods,” Am. J. Obstet. Gynecol., 101 (1967), 579-
586.
Karacan, I. and R. L. Williams. “Insomnia: Old Wine in a New Bottle,” Psychiatr. Q., 45 (1971), 1-15.
Karacan, I., R. L. Williams, C. J. Hursch et al. “Some Implications of the Sleep Patterns of Pregnancy
for Postpartum Emotional Disturbances,” Br. J. Psychiatry, 115 (1969), 929-935.
Karacan, I., R. L. Williams, P. J. Salis et al. “New Approaches to the Evaluation and Treatment of
Insomnia (Preliminary Results),” Psychosomatics, 12 (1971), 81-88.
Karacan, I., R. L. Williams, and W. J. Taylor. “Sleep Characteristics of Patients with Angina
Pectoris,” Psychosomatics, 10 (1967), 280-284.
Kawamura, H. and C. H. Sawyer. “Elevation in Brain Temperature during Paradoxical Sleep,”

Science, 150 (1965), 912-913.
Keefe, W. P., R. E. Yoss, T. G. Martens et al. “Ocular Manifestations of Narcolepsy,” Am. J.

Ophthalmology, 49 (1960), 953-958.
Kerr, W. J., and J. B. Lagen. “The Postural Syndrome Related to Obesity Leading to Postural
Emphysema and Cardiorespiratory Failure,” Ann. Intern. Med., 10 (1936), 569-595.
Klackenberg, G. “Primary Enuresis. When Is a Child Dry at Night?” Acta Paediatr. Scand., 44
(1955), 513-518.
Kleine, W. “Periodische Schlafsucht,” Monatsschr. Psychiatr. Neurol., 57 (1925), 285-320.
Kleitman, N. Sleep and Wakefulness, pp. 37-39. Chicago: University of Chicago Press, 1963.
Knowles, J. B., S. G. Laverty, and H. A. Kuechler. “Effects of Alcohol on REM Sleep,” Q. J. Stud.
Alcohol, 29 (1968), 342-349.
Koresko, R. L., F. Snyder, and I. Feinberg. “ ‘Dream Time’ in Hallucinating and Non-hallucinating
Schizophrenic Patients,” Nature, 199 (1963), 1118-1119.
Krabbe, E. and G. Magnussen. “On Narcolepsy. I. Familial Narcolepsy,” Acta Psychiatr. Neurol., 17
(1942), 149-173.
Kuhlo, W. “Sleep Attacks with Apnea,” in Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The
Abnormalities of Sleep in Man. Proc. 15th Europ. Meet. Electroencephalogr.,
Bologna, 1967, pp. 205-207. Bologna: Aulo Gaggi, 1968.
Kupfer, D. J., R. J. Wyatt, J. Scott et al. “Sleep Disturbance in Acute Schizophrenic Patients,” Am. ].
Psychiatry, 126 (1970), 1213-1223.
Kurth, V. E., I. Gohler, and H. H. Knaape. “Untersuchungen liber den Pavor Nocturnus bei Kindem,”
Psychiatr. Neurol. Med. Psychol. (Leipz.), 17 (1968), 1-7.
Langworthy, O. R. and B. J. Betz. “Narcolepsy as a Type of Response to Emotional Conflicts,”

Psychosom. Med., 6 (1944), 211-226.
Lapouse, R. and M. A. Monk. “Fears and Worries in a Representative Sample of Children,” Am. J.
Levin, M. “Narcolepsy (Gelineau’s Syndrome) and other Varieties of Morbid Somnolence,” Arch.
----. “Periodic Somnolence and Morbid Hunger: A New Syndrome,” Brain, 59 (1936), 494-504.
----. “Premature Waking and Postdormitial Paralysis,” J. Nerv. Ment. Dis., 125 (1957), 140-141.
Levine, A. “Enuresis in the Navy,” Am. J. Psychiatry, 100 (1943), 320-325.
Levy, D. “Discussion of Michaels and Goodman,” Am. J. Orthopsychiatry, 4 (1934), 103-106.
Lichtenstein, B. W. and A. H. Rosenblum. “Sleep Paralysis,” J. Nerv. Ment. Dis., 95 (1941), 153-155.
Liddon, S. C. “Sleep Paralysis, Psychosis, and Death,” Am. J. Psychiatry, 126 (1970), 1027-1031.
Lindner, R. M. “Hypnoanalysis in a Case of Hysterical Somnambulism,” Psychoanal. Rev., 32

(1945), 325-339.
Loewenfeld, L. “Ueber Narkolepsie,” Munch. Med. Wochenschr., 49 (1902), 1041-1045.
Lowy, F. H., J. M. Cleghorn, and D. J. McClure. “Sleep Patterns in Depression,” J. Nerv. Ment. Dis.,
153 (1971), 10-26.
Luby, E. D. and D. F. Caldwell. “Sleep Deprivation and EEG Slow Wave Activity in Chronic
Schizophrenia,” Arch. Gen. Psychiatry, 17 (1967), 361-364.
Lugaresi, E., G. Coccagna, G. Berti Ceroni et al. “Restless Legs Syndrome and Nocturnal
Myoclonus,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al., eds., The Abnormalities
Lugaresi, E., C. A. Tassinari, G. Coccagna et al. “Particularites cliniques et polygraphiques du

syndrome d’impatience des membres inferieurs,” Rev. Neurol. (Paris), 113 (1965),
545-555-
Macdonald, J. “Puerperal Insanity,” Am. J. Insanity, 4 (1847), 113-163.
Mack, J. E. Nightmares and Human Conflict. Boston: Little, Brown, 1970.
Magee, K. R. “Bruxism Related to Levodopa Therapy,” JAMA, 214 (1970), 147.
Mandell, A. J., P. L. Brill, M. P. Mandell. et al “Urinary Excretion of 3-Methoxy-4-Hydroxymandelic

Acid during Dreaming Sleep in Man,” Life Sci. I, 5 (1966), 169-173.
Mandell, A. J., B. Chaffey, P. Brill et al. “Dreaming Sleep in Man: Changes in Urine Volume and
Osmolality,” Science, 151 (1966), 1558-1560.
Mandell, M. P., A. J. Mandell, R. T. Rubin et al. “Activation of the Pituitary-Adrenal Axis during
Rapid Eye Movement Sleep in Man,” Life Sci. I, 5 (1966), 583-587.
Marie, P. and Pietkiewicz. “La Bruxomanie,” Rev. Stomatol., 14 (1907), 107-116.
Markman, R. A. “Kleine-Levin Syndrome: Report of a Case,” Am. J. Psychiatry, 123 1967), 1025-
1026.
Marks, J. “The Marchiafava Micheli Syndrome (Paroxysmal Nocturnal Haemo-globinuria),” Q. J.

Med., 18 (1949), 105-121.
Maron, L., A. Rechtschaffen, and E. A. Wolpert. “The Sleep Cycle during Napping,” Arch. Gen.
Psychiatry, 11 (1964), 503-508.
McCrary, J. A. and J. L. Smith. “Cortical Dyschromatopsia in Narcolepsy,” Am. J. Ophthalmol., 64

(1967), 153-155.
McFadden, G. D. F. “Enuresis,” Br. Med. J., 1 (1964), 632.
Mello, N. K. “Some Aspects of the Behavioral Pharmacology of Alcohol,” in D. Efron, ed.,

Psychopharmacology. A Review of Progress, 1957-1967. Proc. 6th Annu. Meet. Am.
Coll. Neuropsychopharmacol., San Juan, Puerto Rico, December, pp. 787-809. PHS
publication no. 1836. Washington: U.S. Govt. Print. Off., 1968.
Mello, N. K. and J. H. Mendelson. “Behavioral Studies of Sleep Patterns in Alcoholics during
Intoxication and Withdrawal,” J. Pharmcol. Exp. Thera., 175 (1967), 94-112.
Mendels, J. and D. R. Hawkins. “The Psychophysiology of Sleep in Depression,” Ment. Hyg., 51

(1967), 501-511.
----. “Sleep and Depression. A Controlled EEG Study,” Arch. Gen. Psychiatry, 16 (1967), 334-354.
----. “Sleep and Depression. A Follow-up Study,” Arch. Gen. Psychiatry, 16 (1966), 536-542.
----. “Sleep and Depression—Further Considerations,” Arch. Gen. Psychiatry, 19 (1968), 445-452.
----. “Longitudinal Sleep Study in Hypomania,” Arch. Gen. Psychiatry, 25 (1971), 274-277.
Mendelson, J. “Biochemical Pharmacology of Alcohol,” in D. H. Efron, ed., Psychopharmacology. A

Review of Progress, 1957-1967. Proc. 6th Annu. Meet. Am. Coll.
Neuropsychopharmacol., San Juan, Puerto Rico, December, 1967, pp. 769-785. PHS
publication no. 1836. Washington: U.S. Govt. Print. Off., 1968.
Menzies, I. C. and W. K. Stewart. “Psychiatric Observations on Patients Receiving Regular Dialysis

Treatment,” Br. Med. J., 1 (1968), 544-547.
Michaels, J. J. “Enuresis in Murderous Aggressive Children and Adolescents,” Arch. Gen. Psychiatry,
5 (1961), 94-97.
Michaels, J. J. and S. E. Goodman. “Incidence and Intercorrelations of Enuresis and Other

Neuropathic Traits in So-called Normal Children,” Am. J. Orthopsychiatry, 4 (1934),
79-102.
----. “The Incidence of Enuresis and Age of Cessation in One Thousand Neuropsychiatric Patients:
With a Discussion of the Relationship between Enuresis and Delinquency,” Am. J.
Michaels, J. J. and L. Secunda. “The Relationship of Neurotic Traits to the Electroencephalogram in

Children with Behavior Disorders,” Am. J. Psychiatry, 101 (1944), 407-409.
Michel, F., M. Jeannerod, J. Mouret et al. “Sur les Mecanismes de l’activite de pointes au niveau du
systeme visuel au cours de la phase paradoxale du sommeil,” Compt. Rend. Soc. Biol.
Filial., 158 (1964), 103-106.
Mitchell, S. A., W. C. Dement, and G. D. Gulevich. “The So-called ‘Idiopathic’ Narcolepsy Syndrome.”
Paper presented at the Ann. Meet, of the Assoc, for the Psychophysiological Study
of Sleep, Gainesville, Florida, March, 1966.
Moll, A. (1889) The Study of Hypnosis, pp. 127, 200—201. New York: Julian Press, 1958.
Moneysworth. “Dollars and Sense,” 1, no. 13, April 5, (1971), 1.
Monroe, L. J. “Psychological and Physiological Differences between Good and Poor Sleepers,” J.
Abnorm. Psychol., 72 (1967), 255-264.
Mowrer, O. H. and W. M. Mowrer. “Enuresis—A Method for Its Study and Treatment,” Am. J.
Muellner, S. R. “Development of Urinary Control in Children. Some Aspects of the Cause and
Treatment of Primary Enuresis,” JAMA, 172 (1960), 1256-1261.
Nadler, S. C. “Bruxism, a Classification: Critical Review,” J. Am. Dent. Assoc., 54 (1956), 615-622.
----. “The Effects of Bruxism,” J. Periodontol., 37 (1966), 311-319.
Nan’no, H., Y. Hishikawa, H. Koida et al. “A Neurophysiological Study of Sleep Paralysis in

Narcoleptic Patients,” Electroencephalogr. Clin. Neurophysiol., 28 (1969), 382-390.
Notkin, J. and S. E. Jelliffe. “The Narcolepsies. Cryptogenic and Symptomatic Types,” Arch. Neurol.
Psychiatry, 31 (1934), 615-634.
Nowlin, J. B., W. G. Troyer, Jr., W. S. Collins et al. “The Association of Nocturnal Angina Pectoris
with Dreaming,” Ann. Intern. Med., 63 (1965), 1040-1046.
Noyes, A. P. and L. C. Kolb. Modern Clinical Psychiatry, 5th ed., pp. 62-63. Philadelphia: Saunders,
1958.
Olsen, S. “The Brain in Uremia,” Acta Psychiatr. Neurol. Scand. (Suppl.), 156 (1961), 11-20, 119-
122.
Onheiber, P., P. T. White, M. K. De Myer et al. “Sleep and Dream Patterns of Child Schizophrenics,”
Oppenheim, H. Lehrbuch der Nervenkrankheiten, 7th ed., p. 1774. Berlin: Karger, 1923.
Orme, J. E. “The Incidence of Sleepwalking in Various Groups,” Acta Psychiatr. Scand., 43 (1967),
279-281.
Ornitz, E. M., E. R. Ritvo, and R. D. Walter. “Dreaming Sleep in Autistic and Schizophrenic
Children,” Am. J. Psychiatry, 122 (1965), 419-424.
----. “Dreaming Sleep in Autistic Twins,” Arch. Gen. Psychiatry, 12 (1965), 77-79.
Oswald, I. “Experimental Studies of Rhythm, Anxiety and Cerebral Vigilance,” J. Ment. Sci., 105
(1959), 269-294.
----. “Falling Asleep Open-eyed during Intense Rhythmic Stimulation,” Br. Med. J., 1 (1960), 1450-
1455.
----. Sleeping and Waking. Physiology and Psychology, pp. 110, 196-200. Amsterdam: Elsevier,
1962.
---. “Rocking at Night,” Electroencephalogr. Clin. Neurophysiol., 16 (1964), 312-313.
----. “Some Psychophysiological Features of Human Sleep,” Prog. Brain Res., 18 (1963), 160-168.
----. “Sleep and Its Disorders,” in P. J. Vinken and G. W. Bruyn, eds., Handbook of Clinical Neurology,
Vol. 3, pp. 80-111. Amsterdam: North-Holland Publishing, 1969.
Oswald, I., R. J. Berger, R. A. Jaramillo et al. “Melancholia and Barbiturates: A Controlled EEG, Body
and Eye Movement Study of Sleep,” Br. J. Psychiatry, 109 (1963), 66-78.
Pai, M. N. “Sleep-Walking and Sleep Activities,” J. Ment. Sci., 92 (1946), 756-765.
----. “Hypersomnia Syndromes,” Br. Med. J., 1 (1950), 522-524.
Palmer, H. “The Klein[e]-Levin Syndrome, Narcolepsy and Akinetic Epilepsy as Related Disorders
of the Hypothalamus,” N. Z. Med. J., 49 (1950), 28-37.
Passouant, P. “Problemes physiopathologiques de la narcolepsie et periodicite du ‘sommeil

rapide’ au cours du nycthemere,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et al.,
eds., The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet.
Passouant, P., J. Cadilhac, and M. Baldy-Moulinier. “Physiopathologie des hyper-somnies,” Rev.

Neurol. (Paris), 116 (1967), 585-629.
Passouant, P., J. Cadilhac, M. Baldy-Moulinier et al. “Etude du sommeil nocturne chez des
uremiques chroniques soumis a une epuration extrarenale,” Electroencephalogr.
Passouant, P., F. Halberg, R. Genicot et al. “La Periodicite des acces narcoleptiques et le rythme
ultradien du sommeil rapide,” Rev. Neurol. (Paris), 121 (1969), 155-164.
Passouant, P., L. Popoviciu, G. Velok et al. “Etude polygraphique des narcolepsies au cours du
nycthemere,” Rev. Neurol. (Paris), 118 (1968), 431-441.
Passouant, P., R.-S. Schwab, J. Cadilhac et al. “Narcolepsie-Cataplexie. Etude du sommeil de nuit et
du sommeil de jour. Traitement par une amphetamine levo-gyre,” Rev. Neurol.
(Paris), 111 (1964), 415-426.
Petre-Quadens, O., A. M. De Barsy, J. Devos et al. “Sleep in Pregnancy: Evidence of Foetal-Sleep

Characteristics,” J. Neurol. Sci., 4 (1967), 600-605.
Pierce, C. M., and H. H. Lipcon. “Clinical Relationship of Enuresis to Sleepwalking and Epilepsy,”
----. “Somnambulism: Psychiatric Interview Studies,” U.S. Armed Forces Med. J., 7 (1956), 1143-
1153.
----. “Somnambulism. Electroencephalographic Studies and Related Findings,” U.S. Armed Forces
Med. J., 7 (1956), 1419-1426.
Pierce, C. M., H. H. Lipcon, J. H. McLary et al. “Enuresis: Clinical, Laboratory, and

Electroencephalographic Studies,” U.S. Armed Forces Med. J., 7 (1956), 208-219.
Pierce, C. M., J. L. Mathis, and J. T. Jabbour. “Dream Patterns in Narcoleptic and Hydranencephalic
Patients,” Am. J. Psychiatry, 122 (1965), 402-404.
Pierce, C. M., R. M. Whitman, J. W. Maas et al., “Enuresis and Dreaming. Experimental Studies,”
Podolsky, E. “Somnambulistic Homicide,” Dis. Nerv. Syst., 20 (1959), 534-536.
Pond, D. A. “Narcolepsy: A Brief Critical Review and Study of Eight Cases,” J. Ment. Sci., 98 (1952),
595-604.
Poulton, E. M. and E. Hinden. “The Classification of Enuresis,” Arch. Dis. Child., 28 (1953), 392-397.
Poussaint, A. F., R. R. Koegler, and J.-L. R. Riehl. “Enuresis, Epilepsy, and the
Electroencephalogram,” Am. J. Psychiatry, 123 (1967), 1294-1295.
Powell, R. N. “Tooth Contact during Sleep: Association with Other Events,” J. Dent. Res., 44 (1965),
959-967.
Radonic, M., D. Dimov-Butkovic, and F. Hajnsek. “The Pickwickian Syndrome,” Lijec. Vjesn., 92
(1970), 465-474.
Ramfjord, S. P. “Bruxism, a Clinical and Electromyographic Study,” J. Am. Dent. Assoc., 62 (1961),
21-44.
Rechtschaffen, A. “Polygraphic Aspects of Insomnia,” in H. Gastaut, E. Lugaresi, G. Berti Ceroni et
al., eds., The Abnormalities of Sleep in Man. Proc. 15th Europ. Meet.
Rechtschaffen, A., P. Cornwall, W. Zimmerman et al. “Brain Temperature Variations with

Paradoxical Sleep: Implications for Relationships among EEG, Cerebral Metabolism,
Sleep and Consciousness,” Paper presented at the Symposium on Sleep and
Consciousness, Lyon, France, 1965.
Rechtschaffen, A. and W. C. Dement. “Studies on the Relation of Narcolepsy, Cataplexy and Sleep
with Low Voltage Random EEG Activity,” Res. Publ. Assoc. Res. Nerv. Ment. Dis., 45
(1967), 488-498.
----. “Narcolepsy and Hypersomnia,” in A. Kales, ed., Sleep. Physiology and Pathology. A Symposium,
pp. ng-130. Philadelphia: Lippincott, 1969.
Rechtschaffen, A., D. R. Goodenough, and A. Shapiro. “Patterns of Sleep Talking,” Arch. Gen.
Psychiatry, 7 (1962), 418-426.
Rechtschaffen, A., P. Hauri, and M. Zeitlin. “Auditory Awakening Thresholds in REM and NREM
Sleep Stages,” Percept. Mot. Skills, 22 (1966), 927-942.
Rechtschaffen, A. and L. J. Monroe. “Laboratory Studies of Insomnia,” in A. Kales, ed., Sleep.

Physiology and Pathology. A Symposium, pp. 158-169. Philadelphia: Lippincott,
1969.
Rechtschaffen, A. and B. Roth. “Nocturnal Sleep of Hypersomniacs,” Activ. Nerv. Superior, 11

(1969), 229-233.
Rechtschaffen, A., F. Schulsinger, and S. A. Mednick. “Schizophrenia and Physiological Indices of

Dreaming,” Arch. Gen. Psychiatry, 10 (1964), 89-93.
Rechtschaffen, A., E. A. Wolpert, W. C. Dement et al. “Nocturnal Sleep of Narcoleptics,”

Reding, G. R., W. C. Rubright, A. Rechtschaffen et al. “Sleep Pattern of Tooth-Grinding: Its

Relationship to Dreaming,” Science, 145 (1964), 725-726.
Reding, G. R., W. C. Rubright, and S. O. Zimmerman. “Incidence of Bruxism,” J. Dent. Res., 45
(1966), 1198-1204.
Reding, G. R., H. Zepelin, and L. J. Monroe. “Personality Study of Nocturnal Teeth-Grinders,”

Percept. Mot. Skills, 26 (1966), 523-531.
Reding, G. R., H. Zepelin, J. E. Robinson, Jr. et al. “Nocturnal Teeth-Grinding: All-night

Psychophysiologic Studies,” J. Dent. Res., 47 (1968), 786-797.
Ritvo, E. R., E. M. Ornitz, F. Gottlieb et al. “Arousal and Nonarousal Enuretic Events,” Am. J.
Psychiatry, 126 (1969), 77-84.
Roberts, H. J. “Obesity due to the Syndrome of Narcolepsy and Diabetogenic Hyperinsulinism:

Clinical and Therapeutic Observations on 252 Patients,” J. Am. Geriatr. Soc., 15
(1967), 721-743.
Robin, E. D. “Some Interrelations between Sleep and Disease,” Arch. Int. Med., 102 (1957), 669-
675.
Robin, E. D., R. D. Whaley, C. H. Crump et al. “The Nature of the Respiratory Acidosis of Sleep and
of the Respiratory Alkalosis of Hepatic Coma,” J. Clin. Invest., 36 (1957), 924.
Roland, S. I. “Essential Nocturnal Enuresis Treated with D-Amphetamine Sulphate,” J. Urol., 71

(1954), 216-218.
Rosenkotter, L. and S. Wende. “EEG-Befunde beim Kleine-Levin-Syndrom,” Monatsschr. Psychiatr.

Neurol., 130 (1955), 107-122.
Roth, B. Narkolepsie und Hypersomnie. Berlin: Verlag Volk und Gesundheit, 1962.
Roth, B. and S. Bruhova. “Dreams in Narcolepsy, Hypersomnia and Dissociated Sleep Disorders,”
Exp. Med. Surg., 27 (1966), 187-209.
Roth, B., S. Bruhova, and L. Berkova. “Familial Sleep Paralysis,” Arch. Suiss. Neurol. Neurochir.
Psychiatr., 102 (1968), 321-330.
Roth, B., S. Bruhova, and M. Lehovsky. “On the Problem of Pathophysiological Mechanisms of
Narcolepsy, Hypersomnia and Dissociated Sleep Disturbances,” in G. Gastaut, E.
Lugaresi, G. Berti Ceroni et al., eds., The Abnormalities of Sleep in Man. Proc. 15th
Europ. Meet. Electroencephalogr., Bologna, 1967, pp. 191-203. Bologna: Aulo Gaggi,
1968.
----. “REM Sleep and NREM Sleep in Narcolepsy and Hypersomnia,” Electroencephalogr. Clin.
Neurophysiol., 26 (1969), 176-182.
Roth, B., J. Faber, S. Nevsimalova et al. “The Influence of Imipramine, Dexphen-metrazine and
Amphetaminsulphate upon the Clinical and Polygraphic Picture of Narcolepsy-
Cataplexy,” Arch. Suiss. Neurol. Neurochir. Psychiatr., 108 (1971), 251-260.
Roth, B., S. Figar, and O. Simonova. “Respiration in Narcolepsy and Hypersomnia,”

Roth, B., S. Nevsimalova, and A. Rechtschaffen. “Hypersomnia with ‘Sleep Drunkenness’,” Arch.
Gen. Psychiatry, 26 (1972), 456-462.
Roth, N. “Some Problems in Narcolepsy: With a Case Report,” Bull. Menninger Clin., 10 (1946),
160-170.
Rothenberg, S. “Psychoanalytic Insight into Insomnia,” Psychoanal. Rev., 34 (1947), 141-168.
Rottersman, W. “The Selectee and His Complaints,” Am. J. Psychiatry, 103 (1946), 79-86.
Rushton, J. G. “Sleep Paralysis: Report of Two Cases,” Proc. Staff Meet. Mayo Clin., 19 (1944), 51-
54.
Sampson, H. “Psychological Effects of Deprivation of Dreaming Sleep,” J. Nerv. Ment. Dis., 143
(1966), 305-317.
Sandler, S. A. “Somnambulism in the Armed Forces,” Ment. Hyg., 29 (1945), 236-247.
Satoh, T. and Y. Harada. “Tooth-Grinding during Sleep as an Arousal Reaction,” Experientia, 27

(1971), 785-786.
Savage, G. H. “Prevention and Treatment of Insanity of Pregnancy and the Puerperal Period,”
Lancet, 1 (1896), 164-165.
Schiff, S. K. “The EEG, Eye Movements and Dreaming in Adult Enuresis,” J. Nerv. Ment. Dis., 140
(1965), 397-404.
Schneck, J. M. “Sleep Paralysis: Psychodynamics,” Psychiatr. Q., 22 (1948), 462-469.
----. “Sleep Paralysis,” Am. J. Psychiatry, 108 (1952), 921-923.
----. “Sleep Paralysis, a New Evaluation,” Dis. Nerv. Syst., 18 (1957), 144-146.
----. “Sleep Paralysis without Narcolepsy or Cataplexy. Report of a Case,” JAMA, 173 (1960), 1129-
1130.
----. “Personality Components in Patients with Sleep Paralysis,” Psychiatr. Q., 43 (1969), 343-348.
Schreiner, G. E. “Mental and Personality Changes in the Uremic Syndrome,” Med. Ann. D.C., 28
(1959). 316-323, 362.
Schwartz, B. A. “Discussion of N. Kleitman’s Paper, ‘The Nature of Dreaming’,” in G. E. W.

Wolstenholme and M. O’Connor, eds., Ciba Foundation Symposium on the Nature of
Sleep, p. 366. Boston: Little, Brown, 1960.
Schwartz, B. A., M. Seguy, and J.-P. Escande. “Correlations E.E.G., respiratoires, oculaires et
myographiques dans le ‘syndrome Pickwickien’ et autres affections paraissant
apparentees: proposition d’une hypothese,” Rev. Neurol. (Paris), 117 (1966), 145-
152.
Secunda, L. and K. H. Finley. “Electroencephalographic Studies in Children Presenting Behavior

Disorders,” N. Engl. J. Med., 226 (1942), 850-854.
Shapiro, S. and J. Shanon. “Bruxism as an Emotional Reactive Disturbance,” Psychosomatics, 6

(1965), 427-430.
Shea, E. J., D. F. Bogdan, R. B. Freeman et al. “Hemodialysis for Chronic Renal Failure. IV.
Psychological Considerations,” Ann. Intern. Med., 62 (1965), 558-563.
Shirley, H. F. and J. P. Kahn. “Sleep Disturbances in Children,” Pediatr. Clin. North Am., 5 (1958),
629-643.
Sieker, H. O., E. H. Estes, Jr., G. A. Kelser et al. “A Cardiopulmonary Syndrome Associated with
Extreme Obesity,” J. Clin. Invest., 34 (1955), 916.
Simpson, R. G. “Nocturnal Disorders of Medical Interest,” Practitioner, 202 (1969), 259-268.
Sjaastad, O., E. Hultin, and N. Norman. “Narcolepsy: Increased Urinary Excretion of Estriol. A
Preliminary Report,” Acta Neurol. Scand., 46 (1970), 111-118.
Sjostrand, T. “Volume and Distribution of Blood and Their Significance in Regulating the
Circulation,” Physiol. Rev., 33 (1953), 202-228.
Snyder, F. “Electrographic Studies of Sleep in Depression,” in N. S. Kline and E. Laska, eds.,

Computers and Electronic Devices in Psychiatry, pp. 272-303. New York: Grune &
Stratton, 1968.
----. “Sleep Disturbance in Relation to Acute Psychosis,” in A. Kales, ed., Sleep. Physiology and
Pathology. A Symposium, pp. 170-182. Philadelphia: Lippincott, 1969.
Snyder, F., D. Anderson, W. Bunney, Jr. et al. “Longitudinal Variation in the Sleep of Severely
Depressed and Acutely Schizophrenic Patients with Changing Clinical Status,”
Psychophysiology, 5 (1968), 235.
Snyder, F., J. A. Hobson, and F. Goldfrank. “Blood Pressure Changes during Human Sleep,” Science,
142 (1963), 1313-1314.
Snyder, F., J. A. Hobson, D. F. Morrison et al. “Changes in Respiration, Heart Rate, and Systolic
Blood Pressure in Human Sleep,” J. Appl. Physiol., 19 (1964), 417-422.
Sours, J. A. “Narcolepsy and other Disturbances in the Sleep-Waking Rhythm: A Study of 115
Cases with a Review of the Literature,” J. Nerv. Ment. Dis., 137 (1963), 525-542.
Sours, J. A., P. Frumkin, and R. R. Indermill. “Somnambulism. Its Clinical Significance and Dynamic
Meaning in Late Adolescence and Adulthood,” Arch. Gen. Psychiatry, 9 (1963), 400-
413.
Stalker, H. and D. Band. “Persistent Enuresis: A Psychosomatic Study,” J. Ment. Sci., 92 (1946),
324-342.
Stern, M., D. H. Fram, R. Wyatt et al. “All-Night Sleep Studies of Acute Schizophrenics,” Arch. Gen.
Psychiatry, 20 (1969), 470-477.
Stockwell, L. and C. K. Smith. “Enuresis. A Study of Causes, Types and Therapeutic Results,” Am. J.
Dis. Child., 59 (1940), 1013-1033.
Stoupel, M. N. “Etude electroencephalographique de sept cas de narcolepsie-cataplexie,” Rev.

Neurol. (Paris), 83 (1950), 563-570.
Strom-Olsen, R. “Enuresis in Adults and Abnormality of Sleep,” Lancet, 2 (1950), 133-135.
Strother, E. W. and G. E. Mitchell. “Bruxism: A Review and a Case Report,” J. Dent. Med., 9 (1954),
189-201.
Struve, F. A. and D. R. Becka. “The Relative Incidence of the B-Mitten EEG Pattern in Process and
Reactive Schizophrenia,” Electroencephalogr. Clin. Neurophysiol., 24 (1968), 80-82.
Suzuki, J. “Narcoleptic Syndrome and Paradoxical Sleep,” Folia Psychiatr. Neurol. Jap., 20 (1966),
123-149.
Szabo, L., O. Corfariu, and C. Csiky. “Electro-Clinical Aspects of Nocturnal Ambulatory Automatism
(Somnambulism),” Electroencephalogr. Clin. Neurophysiol., 21 (1966), 98.
Takahama, Y. “Bruxism,” J. Dent. Res., 40 (1961), 227.
Takahashi, Y. and M. Jimbo. “Polygraphic Study of Narcoleptic Syndrome, with Special Reference
to Hypnagogic Hallucination and Cataplexy,” Folia Psychiatr. Neurol. Jap. (Suppl), 7
(1964), 343-347.
Tani, K., N. Yoshii, I. Yoshino et al. “Electroencephalographic Study of Parasomnia: Sleep-Talking,
Enuresis and Bruxism,” Physiol. Behav., 1 (1966), 241-243.
Tapia, F., J. Werboff, and G. Winokur. “Recall of Some Phenomena of Sleep. A Comparative Study
of Dreams, Somnambulism, Orgasm and Enuresis in a Control and Neurotic
Population,” J. Nerv. Ment. Dis., 127 (1958), 119-123.
Teplitz, Z. “The Ego and Motility in Sleep walking,” J. Am. Psychoanal. Assoc., 6 (1958), 95-110.
Terzian, H. “Syndrome de Pickwick et narcolepsie,” Rev. Neurol. (Paris), 115 (1966), 184-188.
Thacore, V. R., M. Ahmed, and I. Oswald. “The EEG in a Case of Periodic Hypersomnia,”
Thaller, J. L., G. Rosen, and S. Saltzman. “Study of the Relationship of Frustration and Anxiety to
Bruxism,” J. Periodontol., 38 (1967), 193-197.
Thorne, F. C. “The Incidence of Nocturnal Enuresis after Age Five,” Am. J. Psychiatry, 100 (1944),
686-689.
Trask, C. H. and E. M. Cree. “Oximeter Studies on Patients with Chronic Obstructive Emphysema,
Awake and during Sleep,” N. Engl. J. Med., 266 (1962), 639-642.
Turton, E. C. and A. B. Spear. “E.E.G. Findings in 100 Cases of Severe Enuresis,” Arch. Dis. Child., 28
(1953), 316-320.
Van der Heide, C. and J. Weinberg. “Sleep Paralysis and Combat Fatigue,” Psychosom. Med., 7
(1945), 330-334.
Vernallis, F. F. “Teeth-Grinding: Some Relationships to Anxiety, Hostility, and Hyperactivity,” J.

Clin. Psychol., 11 (1955), 389-391.
Vizioli, R. and A. Giancotti. “EEG Findings in a Case of Narcolepsy,” Electroencephalogr. Clin.

Neurophysiol., 6 (1954), 307-309.
Vogel, G. W. “REM Deprivation. III. Dreaming and Psychosis,” Arch. Gen. Psychiatry, 18 (1968),
312-329.
Vogel, G. W. and A. C. Traub. “REM Deprivation. I. The Effect on Schizophrenic Patients,” Arch. Gen.
Psychiatry, 18 (1968), 287-300.
Vogel, G. W., A. C. Traub, P. Ben-Horin et al. “REM Deprivation. II. The Effects on Depressed
Patients,” Arch. Gen. Psychiatry, 18 (1968), 301-311.
Vogl, M. “Sleep Disturbances of Neurotic Children,” Int. Ser. Monogr. Child Psychiatry, 2 (1964),
123-134.
Vulliamy, D. “The Day and Night Output of Urine in Enuresis,” Arch. Dis. Child., 31 (1956), 439-
443.
Walsh, J. P. “The Psychogenesis of Bruxism,” J. Periodontol., 36 (1965), 417-420.
Walton, D. “The Application of Learning Theory to the Treatment of a Case of Somnambulism,” J.

Clin. Psychol., 17 (1961), 96-99.
Waterfield, R. L. “The Effects of Posture on the Circulating Blood Volume,” J. Physiology, 72 (1931),
110-120.
Webb, W. B. and H. W. Agnew, Jr. “Sleep Stage Characteristics of Long and Short Sleepers,”
Science, 168 (1970), 146-147.
Weinmann, H. M. “Telemetric Recording of Sleep Rhythms in Enuretic Children,” Electroence

phalogr. Clin. Neurophysiol., 24 (1968), 391.
Weiss, H. R., B. H. Kasinoff, and M. A. Bailey. “An Exploration of Reported Sleep Disturbance,” J.
Nerv. Ment. Dis., 134 (1961), 528-534.
Weitzman, E. D., H. Schaumburg, and W. Fishbein. “Plasma 17-Hydroxycorticosteroid Levels

during Sleep in Man,” J. Clin. Endocrinol. Metab., 26 (1966), 121-127.
Werry, J. S. and J. Cohrssen. “Enuresis—an Etiologic and Therapeutic Study,” J. Pediatr., 67 (1965),
423-431.
Westphal, C. “Eigenthümliche mit Einschläfen verbundene Anfalle,” Arch. Psychiatr., 7 (1877),

631-635.
Wexberg, L. E. “Insomnia as Related to Anxiety and Ambition,” J. Clin. Psychopathol, 10 (1949),

373-375-
Whybrow, P. C. and J. Mendels. “Toward a Biology of Depression: Some Suggestions from

Neurophysiology,” Am. J. Psychiatry, 125 (1969). 1491-1500.
Wittmaack, T. Pathologie und Therapie der Sensibilität-Neurosen, pp. 458-460. Leipzig: Ernst
Schafer, 1861.
Wolff, H. G. and D. Curran. “Nature of Delirium and Allied States. The Dysergastic Reaction,” Arch.
Neurol. Psychiatry, 33 (1935), 1175-1215-433
Wyatt, R. J., D. H. Fram, D. J. Kupfer et al. “Total Prolonged Drug-Induced REM Sleep Suppression
in Anxious-Depressed Patients,” Arch. Gen. Psychiatry, 24 (1971), 145-155
Wyatt, R. J., B. A. Termini, and J. Davis. “Biochemical and Sleep Studies of Schizophrenia: A Review
of the Literature, 1960.
Part I. Biochemical Studies,” Schizophr. Bull., 4 (1971), 10-44.
----. “Biochemical and Sleep Studies of Schizophrenia: A Review of the Literature, 1960-1970. Part
II. Sleep Studies,” Schizophr. Bull., 4 (1971), 45-66.
Yoss, R. E. and D. D. Daly. “Criteria for Diagnosis of the Narcoleptic Syndrome,” Proc. Staff Meet.
Mayo Clin., 32 (1957), 320-328.
----. “Hereditary Aspects of Narcolepsy,” Trans. Am. Neurol. Assoc., 85 (1960), 239-240.
----. “Narcolepsy,” Arch. Intern. Med., 106 (1960), 168-171.
----. “Narcolepsy,” Med. Clin. North Am., 44 (1960), 953-968.
Yules, R. B., D. X. Freedman, and K. A. Chandler. “The Effect of Ethyl Alcohol on Man’s
Electroencephalographic Sleep Cycle,” Electroencephalogr. Clin. Neurophysiol., 20
(1966), 109-111.
Yules, R. B., M. E. Lippman, and D. X. Freedman. “Alcohol Administration Prior to Sleep,” Arch. Gen.
Psychiatry, 16 (1967), 94-97.
Zarcone, V. and W. C. Dement. “Sleep Disturbances in Schizophrenia,” in A. Kales, ed., Sleep.

Physiology and Pathology. A Symposium, pp. 192-199. Philadelphia: Lippincott,
1969.
Zarcone, V., G. Gulevich, T. Pivik, and W. C. Dement. “Partial REM Phase Deprivation and
Schizophrenia,” Arch. Gen. Psychiatry, 18 (1968), 194-202.
Zierler, K. L. “Diseases of Muscle,” in R. H. S. Thomson and E. J. King, eds., Biochemical Disorders in

Human Disease, PP 598-656. New York: Academic, 1964.
Zufall, R. B. “Adult Male Enuresis: A Study of 200 Cases,” J. Urol., 70 (1953), 894-897.
Zung, W. W. K., W. P. Wilson, and W. E. Dodson. “Effect of Depressive Disorders on Sleep EEG
Responses,” Arch. Gen. Psychiatry, 10 (1964), 439-445.
Chapter 36
The Teaching Of Psychosomatic Medicine

Consultation-Liaison Psychiatry
F. Patrick McKegney
In this volume of the Handbook, the content of the field of
“psychosomatic medicine” is impressively portrayed. It should be apparent
that the brain and all other biological components of the human organism
influence, and can be influenced by the psychological phenomena
encompassed by the terms “mind,” “personality,” “interpersonal

relationships,” etc. It should also be apparent that the psychosomatic field can
be discussed in terms of specific clinical disorders, normal basic mechanisms
of psychosocial-physiological interactions, or specific known precipitating or

causal factors. Amidst all of these approaches, one may lose sight of the fact
that psychosomatic medicine also implies a broad statement of a

philosophical position which directly relates to the practice of medicine.
Meyer cited the principle of the American Psychosomatic Society formulated
more than thirty years ago:
. . . psychosomatic medicine is a way of approaching problems of health
and disease. It is an approach which attempts to apply the best and most
modern psychodynamic understanding of human personality function in
all phases of medical practice, diagnosis, therapy and research ... It is
emphasized that psychosomatic medicine is not a specialty in medicine but
rather an elaboration of medical theory and practice which takes into
account the role of psychological processes in the form and functions of
the body in health and disease.
As we learn more about the “role of psychological processes in . . . health

and disease,” we must also concern ourselves with the application of this
knowledge to the improvement of health-care delivery to the sick and to the
maintenance of health. Therefore, this chapter is intended as a transitional
one, from the “What?” of psychosomatic medicine to the “Now What?” How
can we ensure that the accumulating body of knowledge about psychosomatic
medicine will be available to those who care for the disabled? How can the
principles of psychosomatic medicine be finally expressed in the skills and
attitudes of the “helping professions?”
Thus, this chapter will emphasize the pedagogy of psychosomatic

medicine, particularly through the activity which has, somewhat
ambiguously, become known as “consultation-liaison psychiatry.” After

presenting the need for such education, the aims and the objects of the effort
will be discussed. Traditional teaching methods, their opportunities and
apparent obstacles, will be contrasted with alternative educational
approaches. The issues of evaluation of educational effectiveness, a frequently
neglected subject, will be presented in a tentative fashion. In fact, many of the
proposals in this chapter are tentative and speculative— reflecting the
general neglect by psychosomatic medicine and the rest of education, to
assess and improve its educational impact.
The Educational Need
From the time of Hippocrates, there has been little controversy about
the need for a physician to recognize the intimate relationship between the
mind and body. Even the surgeon, John Hunter (1728-1793) remarked, “He
who chooses to anger me holds my life in his hands.” Neurologists such as
John Hughlings Jackson and Sigmund Freud pursued the “concomitant
phenomena” of “brain” and “mind” and emphasized the need to take both into
account in clinical practice. More recently, a wide range of laboratory and

clinical researchers have identified a myriad of interactions between the
biological and psychological aspects of the human organism and some of the
clinical ramifications of such interactions.
Problem Incidence
Estimates of the prevalence of psychiatric illness in general or “medical
populations” range from 15 to 85 percent. In a beautifully designed study by
Zabarenko and co-workers, psychiatrists observed physicians in their actual
office practices. They found that only 6 percent of these general-practice
patients had a primary diagnosis of “mental disorder,” if very strictly defined
according to the International Classification of Diseases. However, they found
that there was a need for intervention in psychological problems in more than
60 percent of these patients. In another study by Cross and Bjorn of their
problem-oriented general practice in Maine, the five most common problems
of the patient population served were: (1) depression; (2) conversion
reaction; (3) obesity; (4) acute bronchitis; and (5) anxiety. These problems
were more frequent than infectious diseases, arteriosclerotic cardiovascular
disease, diabetes mellitus, or any other physical or social problem.
In response to the educational needs highlighted by such incidence
studies, there has been a revolution in the recognition of the role of

psychiatry in medicine. Medical schools rarely had departments of psychiatry
before 1945. All now have full-time departments with a major segment of the
students’ curriculum time being devoted to psychiatry. Courses in behavioral

sciences and psychopathology are now offered in almost all medical schools,
and considerable time is devoted to clinical clerkships on psychiatric services.

Psychiatric units in general hospitals, postgraduate education courses in
psychiatry for physicians, and the availability of special funding for residency
training in consultation-liaison psychiatry have all become much more
common since the early 1950s. It must be added that the teaching of the
psychiatric aspects of medical illness has increased slightly but significantly
in psychiatry departments. Werner Mendel has been quoted, referring to the
teaching of psychiatric consultation in medical care: “It is like motherhood—
everyone is for it.”
Clinical Competence
With all of this increased emphasis on psychiatry in general and also in

the psychiatric teaching about our general health-care problems, is there still
a need for improvement of education? The study of Zabarenko et al., cited
above, found that the general physician detected and responded to only a
small fraction of the 60 percent of patients needing attention for

psychological problems. Peterson’s study demonstrated that few physicians
in general practice were able to do something about the psychiatric problems

of their patients, even when recognized. Mendel, who cited the general
acceptance of psychiatric consultation in medical care, went on to say that

“very little is being done” about the actual teaching of the psychiatric aspects
of medical patients. In 1966, his nationwide survey found that only 25
percent of psychiatric training programs conducted formal lectures or
seminars on the consultation process. The experience of consultation-liaison

psychiatrists around the country would indicate that its acceptance or
efficacy, as it has been traditionally pursued, still leaves much to be desired in
terms of educational impact and influence on the change of medical care
practice. Consultation and liaison psychiatry remains only a small component
of general psychiatric training programs and represents a minor involvement
in the actual practice of psychiatrists and other mental-health personnel in

general. For example, the community mental-health-center movement was
designed separately from general-health-care systems and is only now
belatedly being considered in relationship to the growing movement toward

centralized and coordinated health-care programs.
New Technology
New developments in medical care have been accompanied by new

psychological problems, creating a greater need for psychiatric consultation
and teaching input into medical care. Some of these problems arise from the
increased survival of chronically ill patients with major disabilities and
complex rehabilitative needs. Other needs result from the newly developed
treatment approaches themselves, such as intensive coronary care units,
chronic dialysis, and organ transplantation. In the latter two situations, the
needs of the family, as well as of the patient, and the complexities of the
socioeconomic aspects demand new collaborative approaches between

psychiatrists and the health team. Unfortunately, the new technology also
hampers the effectiveness of the psychiatrist’s teaching of psychosomatic
issues. By demanding careful attention to mechanical or biological details, the
new medical machines and techniques tend to distract the medical team, and
even the psychiatrist, from attending to the patient and his world.
Therefore, the indications for the need for more education concerning
psychological and psychosocial problems of general medical populations

would seem obvious, based upon both the high incidence of such problems,
the continuing low involvement of psychiatry in general-health-care systems
and the low level of expertise of health-care professionals in those fields. But
what should be the specific educational objectives of consultation-liaison

psychiatry?
Educational Objectives
The teaching of psychosomatic medicine can be considered in terms of
the three traditional pedagogical objectives: transmitting factual knowledge,

developing skills, and influencing attitudes.
Consultation-liaison psychiatry, as a clinically based activity, concerns

itself primarily with the last two objectives. However, many psychosomatic
psychiatrists find themselves increasingly involved in teaching “content-
oriented” behavioral science or psychopathology courses to first- and second-
year medical students under the pressure to increase the “clinical relevance”
of preclinical medical education. Thus, this chapter must touch upon the role
of the consultation and liaison psychiatrist in all phases of medical- and
health-care professional education.
Psychosomatic Knowledge
In terms of factual knowledge, the theory of psychosomatic medicine
and its mechanismic base can be conveyed by assigned readings in the
growing literature, lectures, and seminars. Yet, greater interest in and

acquisition of such knowledge seems to accrue from a combination of clinical
involvement of students and the transmittal of related facts. Such an approach
can be used with students not involved in clinical responsibilities but it poses
problems of finding appropriate patients, scheduling them and, finally, not

diverting the students from the psychobiological knowledge they are being
asked to acquire.
Psychosomatic Skills
Because of these difficulties, most of the teaching of psychosomatic
medicine has been traditionally based in the clinical phases of medical
education, and combined with the objectives of developing psychosomatic
skills. The usual mode of achieving these objectives is through exercises in
medical interviewing or history-taking and the clinical practice of psychiatric
consultation and liaison with nonpsychiatric patients. In this context the
objectives can be simply stated but much more difficultly achieved or
measured. They are:
1. The student should be able to gather, reliably, thoroughly and

efficiently, the observational and historical data base about
the patient sufficient to understand the patient and his
problems and to plan, with a “sound analytical sense,” the
treatment approaches appropriate to these problems.
2. The student should be able to develop a relationship with the

patient which will enhance objective and provide the basis for
a collaboration between the physician and the patient in the
ongoing treatment program.
3. The student should demonstrate the abilities to synthesize the

clinical data which he gathers, independent of current
theories; to critically examine the syntheses of others; and to
hypothesize original explanations for the data which he
observes. These skills obviously have much interrelationship
with student attitudes toward patients, disease, and their
own roles.
Psychosomatic Attitudes
When one attempts to explicitly teach attitudes, the effect is frequently
as if the action word were preach. Therefore, attitudes are usually conveyed
implicitly by creating an example in the clinical situation. It is important,
however, for a teacher to recognize that he has two roles in which modelling
takes place: vis-a-vis the patient and vis-a-vis the student. The latter has been
characterized as the “learning alliance” by Lazerson. In both roles, the teacher
can influence the students’ attitudes toward the following objectives:
1. The student (and teacher) should demonstrate an appreciation and

respect for the patient (and student) as a person and for the
relevance of the principles of psychosomatic medicine.
2. The student (and teacher) should demonstrate a dedication to

completeness, which implies that a description, if not
diagnosis, of a patient’s personality and adaptational
capacity is necessary in every case.
3. The student (and teacher) should demonstrate a capacity for

empathy, by which the student can communicate
emotionally with the patient and convey the presence of this
capacity to the patient. This objective critically interdigitates
with the following one.
4. The student (and teacher) should demonstrate an ability to

develop, and act according to professional standards, to
achieve a “detached concern” or an “optimal distance,” to act
in accordance with the needs of the patient and not in
response to one’s own personal needs.
Though cast in operational terms, these objectives need subdefinitions
in terms of actual behaviors which are ideally quantifiable. When this difficult
and so far unaccomplished task is approached, the teacher must recognize
there are different groups of potential learners of psychosomatic medicine,
each with a distinctive background, professional role, and task-specific needs.
Types of Learners and Learning Problems
Student Physicians
Traditionally, the primary focus of educational efforts in psychosomatic

medicine has been upon the medical students, interns, and residents in
University teaching hospitals, usually on the nonpsychiatric services. These
consumers of the psychosomatic educational product are a very heterogenous

lot, yet are rather strikingly uniformly negative in their regard of psychiatry,
the specialty with which psychosomatic medicine is usually associated. Data
by Funkenstein indicate that the most recent freshmen medical student

groups are changing rapidly in the direction of showing greater social
concern. However, whether this will be accompanied by a greater receptivity
to the learning of psychosomatic medicine remains to be seen.
Given these predisposed student attitudes, the consultation-liaison
psychiatrist working in the nonpsychiatric setting meets another obstacle in
the nonpsychiatric teaching staff— either the full-time faculty or practicing
physicians.
Full-time Faculty Staff
The full-time clinical faculty of medical schools are usually chosen for an
in-depth research competence in the biological mechanisms of disease. Often,
they see no patients. At most, and reluctantly, they may see a few outpatients
and serve as “ward attending” six or eight weeks a year. The presence of a
liaison psychiatrist or even the act of a psychiatric consultation complicates

their teaching role, by asking them to look beyond the narrow field of their
scholarly expertise in their role as physician in charge. Resistance to such
involvement with the patient is reflected in the very small amounts of time
Payson et al., found were spent discussing the “psychosomatic” aspects of
patient care on teaching rounds, or in patient contact. This preselected or
preconditioned characteristic of academic clinicians is a powerful obstacle to
their and their students’ learning, since these full-time faculty members are
usually more powerful models for their students than their colleagues, the
practicing physicians.
Practicing Physicians
Privately practicing physicians (or local medical doctors, LMD’s) on the

attending staffs of teaching hospitals spend much less time with the student
physicians than do the full-time academic physicians. Furthermore, what
exposure occurs is frequently in the context of the LMD’s brief morning or
evening visits with his patients, which conflict with the teaching schedule of
the ward and prevent the students from participating in his visit. The student
physician rarely has a meaningful involvement in the physician’s daily
practice of office visits, house calls, and phone contacts with his patients.
Finally, most University hospital staff members are specialists or even
superspecialists, and hence tend to have a narrower perspective than the

psychosomatic concept implies.
The practicing physician also presents problems as a learner of
psychosomatic medicine. His small involvement within the University
hospital reduces his potential contact with the psychosomatic psychiatrist.

Only rarely, and then usually for research purposes, do psychiatrists spend
significant time in physicians’ practices. This has been one factor in the
experience that continuing-education programs in psychiatry are not

particularly successful. Other factors relate to economics, psychiatric
capability, and the availability of manpower (see below), and the probably
limited flexibility of practitioners with ten to thirty years of their own style of
doing things.
Nurses and Other Health Professionals
Increasing attention to the health team in a variety of medical-care
situations has led to increased involvement by the psychosomatic teacher
with nurses, physical therapists, social workers, and others delivering patient
care. Since they usually spend much more time with hospital patients than do
physicians or student physicians, these health professionals have many
immediate and pressing problems which relate to the psychosomatic sphere.
When able to ask a psychiatrist for help, they pose many pertinent and
important questions about their particular role and activity in caring for and
relating to the patient. Yet, this interest creates many problems for the
psychosomatic teacher.
In order to convey accurate and useful opinions, the psychiatrist needs a
modicum of data about the patient. The medical record is usually inadequate,
and the data from the individual nurse, for example, are narrow in
perspective. If not requested to do so by the patient’s physician, the

psychiatrist cannot easily gather that data himself from the patient.
Furthermore, the concern about a given patient may come independently

from several sources, since the usual hospital administrative structure
separates nursing, social service, physical therapy, etc., and the physician
staff. The psychiatrist frequently finds himself repeating his opinions four or
five times, to different professional groups, about one patient situation.
Finally, any recommendation, and the learning which might accrue to the
health professionals, depends in effectiveness upon the degree to which the
health professionals are a team which must involve the patient’s physician.
The subculture of patient care, which operates independently of the physician,
may have short-term value but has little long-range, postdischarge impact on
patient and staff learning. Working solely with this subculture may be a waste
of psychiatrists’ teaching efforts. This nonteam aspect of health care is a
major frustration for the psychiatrist or psychiatric resident in the

consultation-liaison field.
The Psychiatric Resident
The psychiatrist in training is, on occasion, both a consumer of

education in psychosomatic medicine and a teacher of such. Perhaps most
significant is the fact that the future career teachers and practitioners of
consultation-liaison psychiatry will come from the pool of psychiatric
residents. Although nurses and social workers can develop many

psychosomatic teaching skills and functions, the psychosomatically oriented
physician should still be the main resource for the diagnostic and therapeutic
planning, and management functions.
The traditional role of the psychiatric resident in consultation-liaison
psychiatry and its many learning opportunities will be discussed in a later

section. Even after more than thirty years’ experience, consultation-liaison
psychiatry is not well represented in most residency training programs.
Mendel’s nationwide survey in 1966 showed that only 25 percent of
programs offer even formal lectures or seminars on the subject. Training
residents to teach psychosomatic medicine above and beyond psychiatric

consultations, is even less common. Some liaison services do not regularly
involve psychiatric residents but rather train residents with primarily
internal medicine backgrounds. This low emphasis is, at least in part, related
to the characteristics of psychiatric residents. Kardener et al., for example,

found that nonpsychiatric patients seen for psychiatric consultation are very
low in psychiatric residents’ preferences.
What are the learner characteristics which limit participation in
furthering psychosomatic education? Many residents are attracted to

psychiatry as a specialty for reasons which have little to do with the practice
of medicine. These may include (1) a history of personal or family emotional
problems; (2) a major interest in people which may not be satisfied in other
medical specialties; (3) strong social concerns which seem to be best served
in psychiatry; (4) a reaction-formation to anxiety about physical disease; and

(5) a wish to avoid the apparent competitiveness, pace, or responsibilities of
other types of medical practice. Any of these reasons may make it more
difficult for a psychiatric resident to function in the medical setting, to work
with dirty, smelly, or seriously sick persons, or to identify with nonpsychiatric
physicians.
As elective programs comprise a larger segment of medical school

curricula, a student disposed toward psychiatry for such reasons can more
and more avoid “medical experience.” The elimination, by the National Board
of Psychiatry and Neurology, of the requirements of an internship can result

in a loss of valuable training for the future consultation and liaison resident.
Finally, the psychiatric resident in his training is increasingly exposed to the
continuing departure from the medical model in psychiatry, which may divert
him from the psychosomatic context, despite some exposure to consultation

and liaison training.
Traditional Educational Techniques of Consultation-Liaison Psychiatry
The most common current model of consultation-liaison teaching dates
back at least forty years to the goals of Franklin Ebaugh’s Colorado program,
described by Billings:
1. To sensitize the physicians and students to the opportunities

offered them by every patient, no matter what complaint or
ailment was present, for the utilization of a common sense
psychiatric approach for the betterment of the patient’s
condition, and for making that patient better fitted to handle
his problems, somatic or personality-determined or both.
2. To establish psychobiology as an integral working part of the
professional thinking of physicians and students of all
branches of medicine.
3. To instill in the minds of physicians and students the need the

patient-public has for tangible and practical conceptions of
personality and sociological functioning.
The general strategies of a hospital consultation-liaison service fall into
three categories. The following is an adaptation of Kaufman and Margolin’s
outline written in 1948. While these authors emphasize the primary
professional needs of the institution, the goals are equally applicable to any
healthcare setting:
1. Psychiatric services, i.e., the diagnosis and treatment of the hospital

population (consultation).
2. Teaching involving the training of the psychiatric staff and the

indoctrination and teaching of every member of the hospital
staff in the principles of psychosomatic medicine (liaison).
3. Research in the field of psychosomatic medicine and in the process

of both the consultation and liaison functions.
Margolin and Kaufman went on to add the important guiding concept
that, “these three functions should be regarded as separate, chronological
phases in the development of a psychiatric service in a general hospital”
(emphasis added).
In terms of specific educational tactics, a staff consultation-liaison
psychiatrist is given a major assignment to one or more specific
nonpsychiatric services. He usually attends the work and teaching rounds of
that service and may hold special psychosomatic conferences. He sees
patients upon request, and may generate the referral himself on the basis of
the patient’s history or his own observation of the patient on rounds. Every
consultation is followed by often extensive communication with those caring
for the patient in which he includes relevant concepts of psychosomatic
medicine. In certain cases, the psychiatrist may assume major responsibility

for the direction of patient management and aftercare, but usually he
collaborates with the other health professionals, who retain their primary
roles in the continuing care of the patient.
Traditional Psychiatric Resident Role
Of course, almost all training programs in psychiatry have residents
assigned to see patients in the general hospital who are referred for
psychiatric consultation, usually on an emergency basis. In a minority of
psychiatric training programs, a few residents have consultation-liaison

duties, with the additional tasks of establishing collaborative relationships,
teaching, and research, as defined by Kaufman and Margolin. Not all residents
in a given program may have this rotation, it being either completely elective,
or required for only a certain number of residents. As in the original Colorado
program, the psychiatric resident usually becomes involved at first as an
assistant to the liaison staff psychiatrist, on a part-time basis and for brief
rotations of three to six months. This resident may participate in the
nonpsychiatric service’s work rounds, may generate consultations, and
initially evaluate all patients for whom consultation is requested. The
psychiatric resident may also lead, or participate in, conferences about

comprehensive patient care which are, incidentally, frequently called “social
service rounds”—implying nonmedical and dispositional, as well as
comprehensive-care purposes. The psychiatric resident may also hold regular

or ad hoc conferences for nurses about patient care.
Certain psychiatric residents may elect longer and more advanced levels
of training in consultation-liaison work. This seems to be an only occasionally
exercised option; exact figures are not available. An advanced resident usually
functions in a semisupervisory role, performing many of the tasks of the staff
psychiatrist. He may organize and coordinate the seminars or lectures in

psychosomatic medicine offered in some programs, and may also have the
opportunity to pursue research activities.
Appropriately, residents with either a minor or major time commitment

to consultation-liaison work usually reserve a certain amount of time for
seeing outpatients. This arrangement serves two functions: it ensures the
resident’s being able to continue seeing psychotherapy patients for an
extensive period of time throughout his residency, and it also allows him the
flexibility of being able to follow certain patients initially seen in consultation.

However rational, this follow-up capability frequently causes difficulty, in
terms of discontinuity and/or contradiction in the resident’s supervision.
Should this patient be considered an “outpatient” or a “consultation patient,”
for administrative and supervisory purposes? Most departments have

separate organizational divisions for these outpatient populations. Some
programs, such as that at Johns Hopkins in the 1960s, avoided this area of
potential conflict by establishing a separate outpatient service under the aegis

of the psychosomatic service. Others, such as that at the University of
Rochester from 1959 to 1962, considered outpatient care as crossing all
departmental divisional lines and the resident continued to be supervised by
the liaison staff for those outpatients originally seen in consultation.

However, this scheme does add to the supervisory time per resident.
In such psychiatric residency training experiences, there are many

unique learning opportunities. By being required to communicate with
nonpsychiatric personnel, the resident can sharpen his psychological

concepts and recognize their limitations, as he goes through the necessary
process of adapting his psychiatric observations and opinions to everyday
English from the jargon used so loosely among psychiatrists. However, the
resident can become aware of the fact that a clear transmittal of his ideas, in
and of itself, does not constitute their validation. For example, our scientific
forebearers used deductive logic to precisely and irrefutably describe a large

number of nonexistent creatures, such as the unicorn.
Another opportunity for the psychiatric resident may present itself
when he may be obliged to utilize Adolf Meyer’s “life chart” concept, taking
into account the biological, social, economic, and situational influences on
behavior, as well as the interpersonal and intrapsychic factors emphasized in

traditional psychiatric training. He may be called upon to deal with the
interface between the behavioral and the somatic, and—quoting Meyerowitz
— “to approach problems as a physician, but a physician who is

simultaneously a behavioral expert.” Meyerowitz goes on to point out another
learning task for the resident. “The resident as consultant frequently
experiences an uncomfortable sense of time pressure, crisis and distance

from his own familiar setting. He has to make practical decisions based upon
relatively inadequate data and without indulgence in careful longitudinal
observation. The increasing capacity to act effectively under these
circumstances is a measure of his further development as a psychiatric

physician.”
In consultation-liaison work, the resident has an opportunity to see a
much larger number of patients with neurological syndromes than he would
in traditional psychiatric settings. Kligerman and McKegney found in a four-
year survey of 2835 inpatients seen in consultation, 14.2 percent had an acute
brain syndrome, 16.8 percent a chronic brain syndrome, and 10.8 percent
other neurological diseases. By examining a large number of physically ill
patients, the resident becomes atuned to the subtle manifestations of
biological disease which, in his future patients, may initially present as a
psychiatric syndrome.
Another important benefit of a consultation-liaison experience for a
psychiatric resident is the opportunity of developing a sense of humility. As a
consultant, the resident is considered an “expert” and is expected to
contribute something of value to the medical staff and, usually, to also solve
the clinical problem to everyone’s satisfaction. However, frequently the
psychiatric resident neither can add anything of significance, nor can he
substantially affect the problem. In these situations, any consultant is liable to

the temptation of trying to live up to the “expert” label, by theorizing or
focusing on the minutiae of the clinical problems, usually at considerable

length. As a result, the consultant bores and aggravates his busy consultees,
making it less likely he will be called upon again, and may actually interfere
with optimal patient care.
The psychiatric resident must learn to say in situations, in which
pressing questions about complex problems are beyond his own or anyone
else’s expertise, “I don’t know, but I will try to find out,” or “I agree with what
you have done and can add nothing.” He must do this regardless of criticism
from others and without a sense of inadequacy. As McKegney stated: “The

real world of the sick does not afford completely satisfactory solutions. For
example, a major problem in consultation-liaison work involves the dying
patient and the reactions of the medical staff. This situation highlights the
relative helplessness of the psychiatrist and that of the medical staff in many
other medical situations. The psychiatrist must learn, and convey the attitude
to the others, that possible goals may fall far short of the optimal ones, and
that all of our medical interventions may have limited efficacy.”
Finally, the consultation-liaison psychiatric resident has an opportunity

to learn about the ethos and social systems of a foreign “turf.” This experience
can clearly aid him in many other areas of psychiatric involvement, such as
community, forensic, and military psychiatry. In contact with such conflicting

value systems, the psychiatrist can learn a great deal about
“countertransference” problems, complementing the learning about them in

individual psychotherapy.
Although this training in psychosomatic medicine has been effective for
the few psychiatric residents so exposed, it hardly effects the vast potential
learner population of student physicians and other health professionals.
Toward this end, another major teaching effort of consultation and liaison
psychiatry has been in the curricular time devoted to interviewing or history
taking.
Teaching Medical Interviewing
As Kimball has stated, “interviewing may be considered the basic
science of clinical medicine. It is the vehicle through which all data and
evaluations regarding the patient’s condition are obtained, whether these be

for the purpose of research or therapy.” This classical position of the
psychosomatic physician has never been refuted, but is rarely recognized or
implemented in medical school curricula or medical practice. Consultation-
liaison psychiatrists are usually highly involved in teaching medical
interviewing to medical students. Yet, their small numbers, the small amount
of curriculum time so assigned, and the large classes of 100-200 medical
students seem to preclude any significant impact of such interview teaching.

Interns and residents are rarely, if ever, supervised by anyone in their contact
with patients, and thus have little further opportunity for corrective feedback
about their interviewing.
In a school which puts a large emphasis on teaching interviewing and
clinical observation, Engel, at the University of Rochester, found that 88

percent of its graduates felt better prepared than their colleagues in the “. . .
overall clinical approach to the patient: .... This included the ability to make
accurate observations and to elicit information; greater comfort in dealing
with difficult patients; the capability to consider the patient as a whole and to
identify, define, and respond to the patient’s problems; more understanding

of the implications of the psychological and social dimensions of the illness;
greater skill in working with the family; and better appreciation of the
vicissitudes of the doctor-patient relationship.” These data indicate that such
educational goals can be approached, but only by a very strong commitment

to both the preclinical teaching of interviewing-observation, coupled with the
clinical teaching of psychosomatic medicine via a medicine-psychiatry liaison
service. Yet, very few medical schools currently make such a strong
commitment to preclinical teaching. Furthermore, the shortening of the
undergraduate medical curriculum may well truncate the time spent toward
achieving these goals. In that case, more attention may need to be directed to
the student physicians, particularly those medical students and house officers
in training on nonpsychiatric clinical services.
Student Physician Education
The teaching of psychosomatic medicine to student physicians in

nonpsychiatric settings seems to have several strategic advantages toward
achieving the goals cited by Billings and Engel. These advantages are
proposed as hypotheses, without documentation as being educationally valid.
Medical education has met the tasks of goal setting and evaluation no better
than other educational fields, though it has recently begun to change.
The advantages of teaching psychosomatic medicine to student
physicians in nonpsychiatric settings derive from at least four factors:
1. The student’s role on the nonpsychiatric service is different from

his position on a psychiatric service. On the latter, residents,
clinical directors, nursing personnel, in fact everyone is
concentrating on the psychological factors and
understanding them more completely than the student
because of an early level of sophistication and training. As a
result of his “bottom-rung” role on a psychiatric service, the
student often retreats from competition with the others, and
neglects observing and understanding the psychological
factors operating in his patients. On a nonpsychiatric service,
however, and with medical or surgical patients, the student
often finds he can assume an unique role among the clinical
staff and achieve recognition, by emphasizing the same
psychological factors he ignored or deprecated in the patient
in the psychiatric setting. This “backing into” dealing with
such psychological factors and concepts seems nonetheless
to be an effective learning approach to these problems for
the student 011 the nonpsychiatric service.
2. A major determinant in the student’s reluctance to recognize,

accept, or understand psychological factors in his patient is,
of course, his own anxiety about himself. Experience
suggests that such anxiety is less prominent and more
readily dealt with on the nonpsychiatric service than on a
psychiatric service. On the nonpsychiatric service, the
primary focus of attention is on the anatomic-physiological
aspects of the patients’ illnesses. These aspects are less
threatening and anxiety-provoking than the psychological
ones and permit the student to recognize some of his own
neurotic involvements, acting-out or “blind spots,” without
becoming overwhelmed by the additive effects of both
sources of anxiety. If such recognition is a major element in
the physician’s educative process, both to increase his
personal efficiency and to enable him to recognize and deal
with similar psychological factors in his patients, such
learning may be enhanced on a nonpsychiatric service.
3. The student has an opportunity to see, in a nonpsychiatric setting,

patients in whom the organic factors have been “ruled out,”
in whom there is no conceivable physiological explanation
for symptoms, or in whom the symptoms contrast clearly
with those he finds in other patients due to organic disease.
Because of this contrast, the impact on the student of the
presence and importance of these psychological factors is
greater than it may be in a psychiatric setting, where
psychopathology is more common and, therefore, less
outstanding by contrast. The surprise value of this contrast
lends another advantage to the teaching of certain principles
of psychological medicine in a medical setting rather than a
psychiatric one.
4. The relevance of the nonpsychiatric setting and patient population
to the future career goals of the student physician heighten
his acceptance and learning of psychosomatic medicine.
Most student physicians will not be psychiatrists. Students
constantly contrast their learning experiences with their
sophisticated or unsophisticated expectations of their future
challenges as medical specialists or generalists. Therefore,
on a nonpsychiatric service, most student physicians rightly
feel these are the patient problems he will face as a surgeon,
obstetrician, pediatrician, etc. As we broaden the clinical
settings of medical student education to other than acute
hospitals, the relevance of psychosomatic factors in medical
care should become even more apparent, as the students
recognize the psychosomatic nature of all patient problems
and the knowledge and skills demanded for their care.
However, the teaching of these student physicians on
nonpsychiatric services implies a commitment of
educational resources not very common in psychiatric
education.
Though perhaps not because of these advantages, many of the new
schools of medicine are shifting their basic teaching of psychiatry to
nonpsychiatric services. For example, McMaster University’s basic medical

curriculum does not include the free-standing clerkship on a psychiatric
service. The core of clinical teaching of psychiatry is done in a three-month
combined family practice-psychiatry clerkship using the students’ experience

with nonpsychiatric patients as a means of teaching psychiatry.
Such a shift can have serious implications for the traditional education
of psychiatrists. If students do not work with psychiatrists and psychiatric
patients in psychiatric settings, they will have a limited opportunity to gain
experience with psychiatry as a specialty. As a result, their career choices may
be made in comparative ignorance about psychiatry. The specialty field might
then attract fewer and less qualified students than in the past, with a
consequent detrimental impact on the large number of clearly psychiatric

patients who need specialized care. This is only one of the problems related to
consultation-liaison psychiatric teaching.
Obstacles to Psychosomatic Teaching
Among the obstacles to consultation-liaison teaching, the career
motivation factors of psychiatric residents and psychiatrists have already
been cited. Psychiatry has for some time been “riding madly in all directions,”
resulting in a major diffusion of psychiatry into areas outside of medicine or

even of health-care systems. Indeed, “psychiatric consultation” today can
refer to a psychiatrist’s meeting with a group of teachers, police, or industrial
managers. This departure from the “medical model” of psychiatry imposes
serious limitations upon student physicians’ and psychiatric residents’

receptiveness to traditional consultation-liaison practice.
Economic factors also limit the practice of consultation-liaison
psychiatry. Since the bulk of the liaison-staff psychiatrist’s activity is spent in
teaching, it is not compensated by patient-care fees on an hourly basis, as in
office psychotherapy. The amount of time necessary for a staff psychiatrist to
perform an adequate teaching role on one nonpsychiatric inpatient unit

seems to approximate ten hours per week. At the current average hourly rate
for psychotherapy, $50, this primary educational service could cost at least
$15,000-$20,000 per year per inpatient unit, if it were not for either the
academic pressures forcing the voluntary contribution of clinical faculty time,

or the lower salaries paid full-time faculty. Federal funding, however
munificent in the past, has never approached this figure in supporting
consultation-liaison psychiatry, nor can most medical institutions underwrite

such expensive teaching programs. Governmental funding of psychosomatic
education of nonpsychiatrists is, paradoxically, being phased out in the face of
the data increasingly substantiating the psychological needs of the general
medical patient population.
Even most national legislation concerning national health-insurance
plans or health-maintenance organizations (HMO) specifically excludes

payment for treatment of psychological or psychosomatic disorders. Thus,
any efforts of academic institutions to maintain or expand the teaching of

psychosomatic medicine will meet the obstacles of combined learner-
consumer resistance, patient nonacceptance, scarcity of teachers, and
economic constraints. These defined obstacles would seem to indicate a need
for new and different approaches to the strategies and tactics of teaching
psychosomatic medicine. The areas for potential modification will be
discussed in terms of curricular change and administrative-organizational

change.
Educational Approaches—Curricular Change
The Definition of Minimum Objectives
The emphasis on defining objectives of educational programs has some
very practical implications for the future teaching of psychosomatic medicine.

Traditional approaches have involved spending approximately the same
amount of teaching time with every student, attempting to teach the broad
range of psychosomatic medicine, without consideration of essential core

material/abilities or differing individual student capabilities. Faculty time and
curriculum hours are very precious commodities. If the minimum
psychosomatic knowledge, skills, and attitudes needed for all physicians
could be defined, and found acceptable even within one medical school,
substantial savings could accrue in both faculty effort and student-exposure
time.
Once the bare essentials for all physicians are defined, knowledge, skills,
and attitudinal goals would be more narrowly defined for all students than
heretofore. For example, not all medical students might need to hear a lecture
or read (or more operationally, to know specific facts) about the possible
psychophysiological mechanisms involving the hypothalamic-pituitary axis,

however important such material may be for our future understanding of the
human organism. In essence, we would not spend the faculty’s and students’
precious time in attempting to teach a bit about everything in psychosomatic
medicine.
The second type of saving from goal setting would accrue from
measuring individual student abilities for comparison with the criteria for
minimum objectives for all students. It has long been recognized that students
vary tremendously in their abilities and motivations to learn different things

and in different amounts of time. Once minimum objectives are set, certain
students may be able to achieve these in a very short time, if they have not
already done so. These students would then be freed to pursue other sets of
core objectives or to select more advanced objectives in any field. These fast
learners would not be required to spend their time, nor would they continue
to take up faculty effort, once they had achieved the minimum psychosomatic
educational goals.
The Definition of Differential Objectives
As there is clear evidence that students vary in their abilities to learn,
there is evidence that different tasks in medicine require different
professional aptitudes. In the case of the physician, most of the technical skills
required of the cardiac surgeon are qualitatively different from those of the
family physician, who may assume overall medical responsibility for a three-
generation family over forty years. Given the fact of increasing specialization
within medicine, the teachers of psychosomatic medicine must attempt to

differentiate the educational goals in their field for the wide range of health
professional roles. This setting of different objectives obviously must consider
the different role-models and practice of all types of health professionals,
most of which have not well defined themselves, especially vis a vis other
types.
In this process of defining professional roles, many hard questions are
raised, some of which confront the mythologies gradually developed through

the history of medicine. For example, are all physicians expected to
completely observe, define, and plan for the complete range of patient
problems? Clearly, medical practice has been specialized to the point where
the answer to this question is unequivocally negative. Dermatologists,
anesthesiologists, surgeons, psychiatrists, neurologists, or obstetricians

rarely gather a complete data base or assume primary medical managerial
responsibility for the patient and his life situation. However, to explicitly
remove this expertise from the responsibility of the physician-specialist is to
painfully confront the mystique of the physician modeled upon Hippocrates
and Osier.
Nonetheless, the teachers of psychosomatic medicine must, for efficacy
and therefore maximal effectiveness, work with other medical-curriculum

planners in determining the role requirements for psychosomatic education
in each type of health-care practice. For example, the diagnostic role of the
primary physician may require a great deal more teaching emphasis on basic
psychological-physiological mechanisms than does the role of the cardiac

surgeon or family psychotherapist. The emergency-room nurse needs
knowledge, attitudes, and skills quite different from the rehabilitation-unit
nurse since their patient-responsibility roles are so different. The teacher of

psychosomatic medicine must be able to define and to teach, according to the
different task requirements of the different health professionals. In fact, the
psychosomatic psychiatrist may be a most appropriate source of educational

expertise for the different health professionals in their distinguishing their
own roles and educational needs.
The Problem-Oriented Approach to Care
Alvan Feinstein’s conceptual approach to clinical problems and

Lawrence Weed’s problem-oriented approach to medical records and the
management of patient care are among the most innovative and radical
contributions to medical care in this century. Each complements the other in
demanding precise definitions of diagnoses, treatments, and follow-up. The
concepts of Weed and Feinstein have vast implications for all medical
teaching, including psychosomatic medicine. Global diagnoses such as
rheumatic fever or depression are no longer acceptable. The patient’s
problems must be defined according to the specific clinical phenomena of the
patient, the laboratory data, and his environment. The treatment plan must
include the specific approaches to the patient’s behaviors, including patient
education. Each element of the patient’s situation must be isolated and
defined, together with its appropriate treatment.
If these approaches to medical care are valid, then psychosomatic

teaching must work in accord with such principles. Grant has begun adapting
the problem-oriented approach to psychiatric services, but the actual
psychosomatic input to the problem-oriented approach needs to be further

developed. This input is needed in the screening process, the data analysis,
the patient-management decision-making process—especially in the

involvement of the patient and his family at each stage of care—and the
evaluation of the outcome of treatment.
If such a patient-problem oriented approach is in operation in medical

centers, the teacher of psychosomatic medicine has a clear responsibility. He
must assist the staff to be efficient, reliable, thorough, and soundly analytical
in the (1) collection of the data base; (2) construction of an appropriate
problem list; (3) decision about a relevant treatment plan; and (4)
implementation of an appropriate follow-through treatment and evaluation

program. In the problem-oriented system, the teacher of psychosomatic
medicine can help the staff to develop a clear set of objectives. He can assist in
the assignment of appropriate patient care and learning responsibilities to
the various members of the health-care team. This teaching function can be
extended to students, irrespective of a specific health-care discipline, to the
degree that the student is actually involved in the useful work of patient care.
The mechanisms of such psychosomatic teaching could be varied. The
most efficient would seem to be in the audit of the problem-oriented patient-

care medical record. The thorough, reliable, efficient, and analytical problem
solving of the student, house officer, or attending physician can be maintained
by peer review, according to consensually developed criteria, with the input of

the psychosomatic teacher. This educational role necessarily involves the
psychosomatic teacher in the actual patient-care situation, as a participant

auditor and source of feedback, especially regarding the data base, rather
than as a theoretical critic or second-hand reviewer. This teaching role of the

psychosomaticist requires that he be a responsible member of the patient-
care team, a patient advocate, and a self-critical commentator about the
treatment process. This complex, triple-agent role has been described by
McKegney in the hemodialysis unit and is not substantively different from
many traditional consultation-liaison roles. The problem-oriented approach,
however, does change the context of the psychiatrist’s participation and

makes new demands on him, as well as upon all other members of the health-
care team.
Specific Learning Techniques
Several recently developed educational techniques can well be used by
the teacher of psychosomatic medicine. The patient-management-problem
approach developed by McGuire et al., has shown considerable promise in

teaching clinical care and in the evaluation of its learning. Methodological
problems have arisen because clinicians frequently do not agree on criteria

for optimal result of care, or even for appropriate sequences of diagnostic and
therapeutic procedures. Other problems derive from the mechanics of the

patient-management-problem learning-evaluation process. An random
access-and-retrieval computer program is needed for best results which is
frequently not readily available.
Another rather similar learning technique concerns critical incidents. In
this approach, specific decision-making points of clinical care are presented.

The student is asked to choose from among alternative courses of action and
his decisions are compared to the criteria established by a panel of expert
clinicians. This approach suffers from the same consensus difficulty as does
the patient-management-problem technique. In addition, many clinical
problems, especially those involving the psychosocial sphere, are not readily
presented in either the critical-incident or patient-management-problem
format. Some of these difficulties arise from the admitted complexities of
human behavior but others may eventually yield an improved definition of
patients’ problems by the psychiatrist.
Administrative-Organizational Approaches
Overall Curriculum Planning
The psychiatrist should be considered as a behavioral scientist resource
to general curriculum planning, although other health professionals may also
be able to have such a function. A psychiatrist may be important in general

curriculum planning because he is more aware of behaviorally defined
characteristics of different students and health practitioners. In addition, he
may be able to help curriculum planners to recognize the interpersonal

phenomena which distract, or at least distort, their pursuit of well-defined
objectives. This role of the psychiatrist in admissions committees has already
been recognized. A national NIMH-sponsored conference was held in October,
1972, to examine this role. The eventual impact of this conference, entitled
“The Psychiatrist as a Teacher,” is still to be realized but its thrust emphasized
the potential central role of the behavioral clinician in medical education.
Planning for New Patterns of Health-Care Delivery
Health is coming to be recognized as a “right,” rather than a privilege, of
every citizen. As a result, those responsible for health care are under
increasing pressure to improve the effectiveness of the prevention and

treatment of illness in every geographic and economic segment of the
population. At the same time, the expense of medical care as currently
practiced is giving rise to demands for improved efficiency in health-care
delivery. Most approaches to these problems generally suggest greater

coordination among the traditionally independent professional disciplines, as
teams or groups. Furthermore, these approaches imply a more comprehensive

approach to the patient and his problems than heretofore present in medical
practice.
The psychosomatic concept and the thrust of consultation-liaison

psychiatry have long advocated these goals of comprehensive and
coordinated care, now being mandated by economic, social, and political
forces. Psychosomatic psychiatrists may possess a unique expertise by having
an overview of medical practice and an interest in the broadest definition of

patient problems. They have usually become more familiar with the ranges of
health-care settings, types of patient problems, medical-care practices, and
abilities of different health-care professionals than any other group of
physicians. As a result, psychosomatic clinicians may be able to make a
unique contribution to the current demands for a revolution of medical care

and health education.
Despite this historical emphasis and long clinical experience, however,

psychosomatic medicine should not pretend to have answers to these
complex problems. Yet, it may be able to lead in their elucidation. For
example, one particular patient need, long recognized and taught in
psychosomatic medicine, is that of a therapeutic relationship between the
patient and physician. The traditional focus of consultation-liaison teaching
about relationships has been on the student or practicing physician, since

medical tradition has placed the primary patient care upon the physician.
Yet, general medical care in the future is almost surely to be delivered
by a multiprofessional team, each member of which will assume

responsibility for certain components of the patient-care plan. For efficiency,
not all team members will do the same thing or their “own thing.” The
responsibility for the primary, ongoing, and general therapeutic relationship

will usually be given to one member of the team. Will this person be the
physician member? Present time-cost considerations would indicate not.

While cost-effectiveness must also be considered, effectiveness should be a
function of goal-directed education. The intensively trained general physician,
with his broad biological knowledge, and expertise in the diagnosis of
pathology and disease, may well come to function primarily as the initial
diagnostician and long-term patient-care-plan manager. As such, he will need

to know a great deal about psychophysiological and psychological
manifestations of disease in the general population, a clear educational role
for consultation-liaison psychiatry. If this role of the physician emerges, the
task of developing the primary relationship with the patient may become the
responsibility of the nurse or social worker, or the physician assistant on the
team. In this case, the teaching efforts concerning the development and use of
psychotherapeutic relationships in a general health-care program should be

directed at nurses, social workers, or physician assistants, both as students
and practitioners.
If these health professionals, other than physicians, assume major
responsibilities for tasks in the health-care plan currently assumed, rightly or

wrongly, to be the physicians,’ who will prepare them for these tasks? Health-
profession schools have regrettably ignored other professions in many ways.

Faculty composition and student teaching are almost always homogeneous to
the profession. Specifically, the importance of the psychotherapeutic aspects

of patient care is neglected in the curricula of most professional schools, such
as nursing, social work, psychology, physical therapy, etc., as it is in medicine.
In the future, the same efficiency considerations forcing changes in health-
care-delivery patterns should also break down these traditional educational
walls. The consultation-liaison psychiatrist should be asked, or perhaps invite
himself, to participate centrally in the education of other health professionals,

who need to learn the knowledge, skills, and attitudes of psychosomatic
medicine. Similarly, medical education should be forced to assign certain
educational roles to nonphysicians. For example, many coronary-care nurses

are better able to administer emergency cardiac measures than most
physicians. They should teach these skills to those health-care students who
need those skills—irrespective of “profession of designation.” The extent to
which we are in a “crisis of health care delivery,” we are also in a crisis of
health-care education, in which the broad concepts and concerns of
psychosomatic medicine should be essential.
Determining Medical School Priorities
The changes in the political, economic, and social climate are
challenging the traditional priorities of all education. A specific question is
raised for psychiatry departments vis-a-vis medical school priorities. Should
all schools continue to try to teach all things in medicine? If not, some schools
might concentrate, for example, on developing research in basic biological
mechanisms. Psychiatry departments in those schools would, consistently,
need to set their highest priorities on gathering faculty with complementary
expertise' in basic psychobiological relationships.
Other schools may decide to put their highest priorities on teaching the
physicians to be involved in the general practice of health care and not many
narrow and highly trained specialist physicians, such as surgeons or

psychiatrists. In such schools, the departments of psychiatry might attempt to
assume a departmental task of consultation-liaison, in which all members
make a significant contribution by participating as teacher-clinicians in
nonpsychiatric health-care settings. These departments could assume a

primary role of collectively learning and teaching those attitudes, skills, and
facts which will enable all health professionals to observe, understand, and
respond appropriately to the behavior of the human beings for whom they
have professional responsibility.
These reorganizations of medical schools and departments of
psychiatry will take place, if at all, over many years. In the near future,
changes can be made in the organization of academic departments of
psychiatry in such a way as to reduce the subspecialization connotations of
consultation and liaison psychiatry. The traditional designation of a separate

psychosomatically oriented “service” or “division” gave teaching
responsibilities to a few select members. This designation often diminishes

the departmental effectiveness in psychosomatic teaching by isolating the
task from the rest of the psychiatry department. Traditionally, consultation-
liaison services seem to float somewhere between departments of psychiatry
and, for instance, departments of medicine, leading to a diffusion of roles only
heightened by joint appointments, which are usually only titular ties between
departments in two different worlds.
Many departments of psychiatry could move to broadening the teaching

of psychosomatic medicine to medical students, house officers, and other
health professions by increasing the commitment of most, if not all, faculty
members to that educational task. New faculty members would be recruited
on the basis of their interest, among other interests, in consultation-liaison
work. Departmental composition would have to remain sufficiently diverse in
interests and skills to provide a solid-core psychiatric-residency program.

Senior psychiatric residents would go elsewhere for subspecialty areas of
psychiatry not represented in depth by the particular department’s faculty.
Others who wished to gain more experience in the consultation-liaison field

could, of course, remain. This definition of narrowed focus at advanced levels
of training would presumably have a preselection effect on resident

applicants and might actually reduce the identity crises found in most
psychiatric residency programs.
Some very large medical school psychiatry departments may feel they
are able to accept greater responsibilities for psychosomatic education of all
health professionals and maintain an in-depth expertise in the many fields
within psychiatry. However, with increasing limitations on growth, all
departments will have to reexamine their priorities and cut back some
programs to allow for expansion in others. The teaching of psychosomatic

medicine has not been a high priority of psychiatry in the past. As a group of
leading psychiatric educators emphasized, it must be in the future.
Bibliography
Adsett, A. “Psychiatric Education in New Medical Schools—Undergraduate Programs.” Paper

presented at Conference on Psychiatric Education in New Medical Schools, Airlee
House, Warrenton, Virginia, February 21-23, 1972.
Billings, E. G. “The Psychiatric Liaison Department of the University of Colorado Medical Schools
and Hospitals,” Am. J. Psychiatry, 122 (1966), 28-33.
Branch, C. H. “Psychiatric Education of Physicians: What Are Our Goals?” Am. J. Psychiatry, 125
(1968), 237-241.
Bjorn, J. and H. Cross. The Problem Oriented Private Practice of Medicine. Chicago: Modem Hospital
Press, 1970.
Bruhn, J. G. and O. A. Parsons. “Attitudes toward Medical Specialties: Two Follow-up Studies,” J.
Med. Educ., 40 (1965), 273-280.
Dohbs, H. I. and D. L. Carek. “The Conceptualization and Teaching of Medical Interviewing,” J. Med.
Educ., 47 (1972), 272-276.
Enelow, A. J. and V. H. Myers. “Post graduate Psychiatric Education: The Ethnography of a

Failure,” Am. J. Psychiatry, 125 (1968), 627-631.
Engel, G. L. “The Education of the Physician for Clinical Observation, the Role of the
Psychosomatic (Liaison) Teacher,” J. Nerv. Ment. Dis., 154 (1972), 159-164.
Feinstein, A. R. Clinical Judgement. Baltimore: Williams & Wilkins, 1967.
Funkenstein, D. H. “Medical Students, Medical Schools, and Society during Three Eras,” in R. H.
Coombs and C. E. Vincent, eds., Psychosocial Aspects of Medical Training, pp. 229—
281. Springfield: Charles C. Thomas, 1971.
Graham, J. R. “Measuring Psychiatric Competence and Curriculum in Undergraduate Medical

Education,” Am. J. Psychiatry, 125 (1969), 213-219.
Grant, R. and B. M. Maletzky. “Application of the Weed System to Psychiatric Records,” Psychiatry
Med., 3 (1972), 119-129.
Hamburg, D. A., ed. Psychiatry as a Behavioral Science. Engelwood Cliffs, N.J.: Prentice-Hall, 1970.
Hoffman, F. H. “The Psychiatrist on the Medical School Admissions Committee,” Paper presented
at 123rd Meeting Am. Psychiatr. Assoc., Detroit, May 8-12, 1967.
Jason, H. “Defining Objectives and Setting Priorities For Instruction in Psychiatry,” Paper
presented at Conference on Psychiatric Education in New Medical Schools, Airlee
House, Warrenton, Virginia, February 21-23, 1972.
Kardener, S. H., M. Fuller, I. Mensh et al. “The Trainees’ Viewpoint of Psychiatric Residency,” Am. J.
Psychiatry, 126 (1970), 1132-1143.
Kaufman, M. R. and S. G. Margolin. “Theory and Practice of Psychosomatic Medicine in a General

Hospital,” Med. Clin. North Am., 32 (1948), 611-616.
Kimball, C. P. “Techniques of Interviewing: Interviewing and the Meaning of the Symptom,” Ann.
Intern. Med., 71 (1969), 147-153’
Kligerman, M. J. and F. P. McKegney. “Patterns of Psychiatric Consultation in Two General

Hospitals,” Psychiatry Med., 2 (1971), 126-132.
Lazerson, A. M. “The Learning Alliance and Its Relation to Psychiatric Teaching,” Psychiatry Med.,
3 (1972), 81-91.
McGuire, C. H. and D. Babbott. “Simulation Technique in the Measurement of Problem Solving

Skills,” J. Educ., Measur., 4 (1967), 1-10.
McKegney, F. P. “Emotional and Interpersonal Aspects of Rehabilitation,” in S. Licht, ed.,

Rehabilitation and Medicine, pp. 229-251. New Haven: Elizabeth Licht, 1968.
----. “Consultation-Liaison Teaching of Psychosomatic Medicine: Opportunities and Obstacles,” J.

Nerv. Ment. Dis., 154 (1972), 198-205.
McKegney, F. P. and P. F. Lange. “The Decision To No Longer Live on Hemodialysis,” Am. J.

Psychiatry, 128 (1971), 267-274.
Mager, R. F. Preparing Instructional Objectives. Palo Alto: Fearon, 1962.
Mandell, A. J. “Western Humanism, Liberal Politics and Psychiatric Training: Relatives, Friends or
Enemies?” Paper presented 128th Annu. Meet. Am. Psychiatr. Assoc., Dallas, May 1-
5, 1972.
Mendel, W. M. “Psychiatric Consultation Education—1966.” Am. J. Psychiatry, 123 (1966), 150-

155.
----. “A Prescription for Improving the Psychiatric Consultation,” Roche Rep., 4 (1966), 1-11.
Mendelson, M. and E. Meyer. “Countertransference Problems of the Liaison Psychiatrist,”

Psychosom. Med., 23 (1961), 115-122.
Meyer, E. M. “The Psychosomatic Concept, Use and Abuse,” J. Chronic Dis., 9 (1959), 298-314.
Meyerowitz, S. “Consultation,” Paper presented at Conference on Psychiatric Education,

Rochester, New York, March 31, 1971.
Mowbray, R. M. and B. Davies. “Personality Factors in Choice of Medical Specialty,” Br. J. Med.
Educ., 5 (1971), 110-117.
Osmond, H. “The Medical Model in Psychiatry,” Hosp. Community Psychiatry, 21(1970), 275-281.
Payson, H. E. and J. D. Barchas. “A Time Study of Medical Teaching Rounds,” N. Engl. J. Med., 273
(1965), 1468-1471.
Payson, H. E., E. C. Gaenslen, and F. L. Stargardter. “Time Study of Internship on University

Medical Service,” N. Engl. J. Med., 264 (1961), 439-443.
Pellegrino, E. D. “Research in Medical Education: The Views of a Friendly Philistine,” J. Med. Educ.,
46 (1971), 750-756.
Peterson, O. L., L. P. Andrews, R. Spain et al. “An Analytical Study of North Carolina General
Practice, 1953-54,” J. Med. Educ., 31 (1956), 1-165.
Reiser, M. F. “Psychiatry in the Undergraduate Medical Curriculum,” Paper presented 128th

Annu. Meet. Am. Psychiatr. Assoc., Dallas, May 1-5, 1972.
Romano, J. “The Teaching of Psychiatry to Medical Students: Past, Present, and Future,” Am. J.
Psychiatry, 126 (1970), 1115-1126.
----. “The Elimination of the Internship—An Act of Regression,” Am. J. Psychiatry, 126 (1970),
1565-1576.
Schumacher, C. F. “Interest and Personality Factors as Related to Choice of Medical Career,” J.

Med. Educ., 38 (1963), 932-942.
Sedlacek, W. E. and L. W. Natress. “A Technique for Determining the Validity of Patient

Management Problems,” J. Med. Educ., 47 (1972), 263-266.
Stratas, N. E. “Training of Non-Psychiatric Physicians,” Am. J. Psychiatry, 125 (1969), 1110-1111.
Webster, T. “The Behavioral Sciences in Medical Education and Practice,” in R. Coombs and C. E.
Vincent, eds., Psychosocial Aspects of Medical Training, pp. 285-348. Springfield:
Weed, L. Medical Records, Medical Education, and Patient Care. Cleveland: Press of Case Western
Reserve University, 1970.
West, L. J. “The Future of Psychiatric Education,” Am. J. Psychiatry, 130 (1973), 521-528.
White, T. H. The Bestiary. New York: Capricorn Books, 1954.
Zabarenko, L., R. A. Pittenger, and R. N. Zabarenko. Primary Medical Practice, A Psychiatric

Evaluation. St. Louis: Warren Green, 1968.
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American

Silvano Arieti, Editor-in-Chief

Organic Disorders and Psychosomatic Medicine

Morton F. Reiser, Editor

Copyright © 1975 by Basic Books

All Rights Reserved

Created in the United States of America

1. Physical Illness, The Patient And His Environment: Psychosocial

2. Delirium And Related Problems Stanley S. Heller and Donald S. Kornfeld

3. Aging and Psychiatric Diseases of Late Life Ewald W. Busse

4. The Neuropathology Associated With The Psychoses Of Aging Armando

5. Neurosyphilitic Conditions: General Paralysis, General Paresis,

6. Postencephalitic States Or Conditions Henry Brill

7. Head Injury Kenneth Tuerk, Irving Fish, and Joseph Ransohoff

8. Functional Disturbances In Brain Damage Kurt Goldstein

9. Psychiatric Conditions Associated With Focal Lesions Of The Central

10. The Neural Organization Of Language: Aphasia And Neuropsychiatry

11. Aphasia: Behavioral Aspects J.P. Mohr and Murray Sidman

13. Epilepsy: Neuropsychological Aspects Gilbert H. Glaser

15. Alcoholism: A Biobehavioral Disorder Nancy K. Mello and Jack H.

16. Psychosis Associated With Hereditary Disorders I. Herbert Scheinberg

17. Mental Disorders with Huntington's Chorea

B. Neuropathology Leon Roizin and Mavis A. Kaufman

18. MENTAL RETARDATION I. Nature and Manifestations Sterling D.

19. MENTAL RETARDATION II. Care and Management Sterling D. Garrard

20. Biomedical Types Of Mental Deficiency George A. Jervis

21. Changing Theoretical Concepts In Psychosomatic Medicine Morton F.

22. Autonomic Psychophysiology: Peripheral Autonomic Mechanisms And

24. CLINICAL PSYCHOPHYSIOLOGY Psychoendocrine Mechanisms John W.

25. Psychosocial And Epidemiological Concepts In Medicine John J.

26. Psychological Aspects Of Cardiovascular DiseaseChase Paterson

27. Psychological Aspects Of Gastrointestinal Disorders George L. Engel

28. Psychosomatic Aspects Of Bronchial Asthma Peter H. Knapp

29. Disorders Of Immune Mechanisms Raul C. Shiavi and Marvin Stein

31. Obesity Albert J. Stunkard

32. Anorexia Nervosa Hilde Bruch

33. Disturbances of The Body-Image Lawrence C. Kolb

34. Complex Problems of Pain As Seen In Headache, Painful Phantom, and

36. The Teaching Of Psychosomatic Medicine Consultation-Liaison

Frank Benson, M.D.

Malcolm B. Bowers, Jr., M.D.

Henry Brill, M.D.

Jason W. Brown, M.D.

Hilde Bruch, M.D.

Walter L. Bruetsch, M.D.

Ewald W. Busse, M.D.

Armando Ferraro, M.D.

Irving Fish, M.D.

Shervert H. Frazier, M.D.

Daniel X. Freedman, M.D.

Sterling D. Garrard, M.D.

Norman Geschwind, M.D.

Gilbert H. Glaser, M.D.

Kurt Goldstein, M.D.

Stanley S. Heller, M.D.

Myron A. Hofer, M.D.

George A. Jervis, M.D.

Ismet Karacan, M.D., Med.D.Sc.

Mavis A. Kaufman, M.D.

Chase Patterson Kimball, M.D.