SCHIZOPHRENIA

Definition:
Schizophrenia is a psychotic disorder characterized by deterioration of personal social occupational functioning as a result of strange perceptions, disturbed thought processes, unusual emotions and motor abnormalities. (Abnormal Psychology, R. J. Comer, 5th Edition).

History:
Schizophrenia has been with us throughout history, it is one of the conditions commonly described as madness (Cutting, 1985). In 1865 a Belgian psychiatrist, Benedict Morel applied the label dmence prcoce, meaning early dementia. In 1899, Emil Kraeplin used the Latin version of Morels term, dementia praecox. In 1911, a Swiss psychologist Eugen Bleuler coined a new term schizophrenia, combining the Greek works that mean split mind. Bleuler meant the name to imply (1) a fragmentation of thought process, (2) a split between thoughts and emotions, and (3) a withdrawal from reality. It is noteworthy however, that, the earlier description of James Matthew Tillys psychosis by John Haslam (17641844) in his Illustrations of Madness (Haslam 1810) accords well with the present conception of paranoid schizophrenia.

Epidemiology:
In the United States, the lifetime prevalence of schizophrenia is about 1 percent, which means that about 1 person in 100 will develop schizophrenia during their lifetime. The Epidemiologic Catchment Area study sponsored by the National Institute of Mental Health reported a lifetime prevalence of 0.6 to 1.9 percent. According to DSM-IV-TR, the annual incidence of schizophrenia ranges from 0.5 to 5.0 per 10,000, with some geographic variation (e.g., the incidence is higher for persons born in urban areas of industrialized nations). Schizophrenia is found in all societies and geographical areas, and incidence and prevalence rates are roughly equal worldwide. In the United States, about 0.05 percent of the total population is treated for schizophrenia in any single year, and only about half of all patients with schizophrenia obtain treatment, despite the severity of the disorder.

Prognostic Factors:
Factors which are responsible for a good prognostic outcome of schizophrenia are:

Age of the patient The older the patient, the more favorable the prognosis The duration of illness The shorter the duration prior to treatment, the better the outcome. The rapidity of development of the symptoms Surprisingly, it has been found that the more speedily the symptoms develop, the faster do they respond to treatment; a very slow, insidious, and gradual onset of illness suggests a final poor outcome.

A patient who had close friendships and multiple relationships prior to illness has a brighter chance of recovering than a patient with few or no such relationships. Life stress prior to onset An episode brought on by a major identifiable life stress will respond more quickly than an episode without any obvious cause. Marital history A patient with a stable and helpful marital partner has a favorable prognosis as compared to an unmarried patient. Educational history The higher the level of education, the more are the chance of a patient coming rapidly to terms with the illness and handling the post illness sequence. Occupational history A patient with a good stable occupation or business prior to onset of illness will respond better than a patient who is jobless and economically unsound. Family history An absence of schizophrenia in the family points to a better prognosis. Family's attitude towards the returning patient hostile behavior by family members or vice versa, excessive care and attention by them can undermine the patients sense of confidence and hamper recovery. Social support systems A patient with a joint family and a staunch circle of friends who are ready lend a helping hand, is much better off than a lone man afflicted with the illness, whose relatives are in some far off land, and who has no one to turn to. Organic brain damage Presence of concurrent obvious brain damage (mental retardation, epilepsy, head injury etc.) hinders the final adequate recovery from schizophrenia.

Symptoms and Clinical Manifestations:

Acc to Schneider, there are two categories of symptoms --First rank symptoms, which include, a. b. c. d. e. f. g. h. Audible thoughts Voices arguing or discussing or both Voices commenting Somatic passivity experiences Thought withdrawal and other experiences of influenced thought Thought broadcasting Delusional perceptions All other experiences involving volition made affects, and made impulses

Second rank symptoms, which include, a. b. c. d. e. Other disorders of perception Sudden delusional ideas Perplexity Depressive and euphoric mood changes Feelings of emotional impoverishment

Acc to DSM IV, the essential features are a mixture of characteristic signs and symptoms of both positive and negative symptoms. The Positive Symptoms are the psychological excess, those in which something has been added to normal repertoire of behavior and experience, such as thought alienation, delusions (false beliefs), hallucinations (false perceptions), inappropriate affect, disorganized thought and speech, which seems to repeat a pathological pattern. THOUGHT ALIENATION comprises of thought broadcasting, thought insertion and thought withdrawal. Thought Broadcasting refers to the feature where the person with schizophrenia feels that his thoughts are being broadcasted in the media and other people can hear them. Thought insertion refers to the feature where the person feels that thoughts, that are actually not his are being inserted in his mind by external agencies. Thought withdrawal refers to the feature where the person feels that his thoughts are being 'taken out' of his mind. It often accompanies thought blocking. He may experience a break in the flow of his thoughts believing that the missing thoughts have been withdrawn from his mind by some outside agency. DELUSIONS are strange, firm yet false beliefs that have no base in the reality. There are several types of delusions found in schizophrenia. The deluded person may consider the ideas enlightening or may feel confused by them. Some people hold a single delusion that dominates their lives and behavior, whereas others have many delusions. Delusions of persecution are the most common in schizophrenia (APA, 2000). People with such delusions believe they are being plotted or discriminated against, spied on, slandered, threatened, attacked, or deliberately victimized. People with schizophrenia may also experience delusions of reference: they attach special and personal meaning to the actions of others or to various objects or events. People who experience delusions of grandeur believe themselves to be great inventors, religious saviors, or other specially empowered persons. And those with delusions of control believe their feelings, thoughts, and actions are being controlled by other people. Somatic delusions are also found wherein the person believes that he is a passive, unwilling recipient of bodily senses imposed by an external agency. HALLUCINATIONS are the experiencing of sights, sounds, or other perceptions in the exception of external stimuli. Similarly, the perceptions and attention of some people with schizophrenia seem to intensify. The persons may feel that their senses are being flooded by all the sights and sounds that surround them. The various perception and attention problems found in schizophrenia may develop years before the onset of the actual disorder (Cornblatt & Keilp, 1994). It is also possible that such problems further contribute to the memory impairments that are experienced by many individuals with the disorder (Savla et al., 2008; Hartman et al., 2003). People who have auditory hallucinations, by far the most common kind in schizophrenia, hear sounds and voices that seem to come from outside their heads (Waters, Badcock, & Maybery, 2007; Folsom et al., 2006). Auditory hallucinations are hardly unique to schizophrenia. Many normal people hear sounds or voices just as they are about to drift off to sleep. Among people with schizophrenia, the auditory hallucinations may talk directly to the hallucinator, perhaps giving commands or warning of dangers, or they may be experienced as overheard. Hallucinations can also involve any of the other senses. Tactile hallucinations may take the form of tingling, burning, or electricshock sensations. Somatic hallucinations feel as if something is happening inside the body, such as a snake crawling inside one's stomach. Visual hallucinations may

produce vague perceptions of colors or clouds or distinct visions of people or objects. People with gustatory hallucinations regularly find that their food or drink tastes strange, and people with olfactory hallucinations smell odors that no one else does, such as the smell of poison or smoke. Hallucinations and delusional ideas often occur together (Bach, 2007). A woman who hears voices issuing commands, for example, may have the delusion that the commands are being placed in her head by someone else. INAPPROPRIATE AFFECT are a common symptom of schizophrenia, displaying emotions that are unsuited to the present situation. They may smile when making a somber statement or upon being told terrible news, or they may become upset in situations that should make them happy. They may also undergo inappropriate shifts in mood. During a tender conversation with his wife, for example, a man with schizophrenia suddenly started yelling obscenities at her and complaining about her inadequacies. In at least some cases, these emotions may be merely a response to other features of the disorder. Consider a woman with schizophrenia who smiles when told of her husband's serious illness. She may not actually be happy about the news; in fact, she may not be understanding or even hearing it. She could, for example, be responding instead to another of the many stimuli flooding her senses, perhaps a joke coming from an auditory hallucination. DISORGANIZED THINKING AND SPEECH are found in people with schizophrenia who may not be able to think logically and may speak in peculiar ways. These FORMAL THOUGHT DISORDERS can cause the sufferer great confusion and make communication extremely difficult. Often they take the form of positive symptoms (pathological excesses), as in loose associations, neologisms, perseveration, and clang. People who have loose associations, or derailment, the most common formal thought disorder, rapidly shift from one topic to another, believing that their incoherent statements make sense. A single, perhaps unimportant word in one sentence becomes the focus of the next. Some people with schizophrenia use neologisms, made-up words that typically have meaning only to the person using them. Others may display the formal thought disorder of perseveration, in which they repeat their words and statements again and again. Finally, some use clang, or rhyme, to think or express themselves. In contrast, the negative symptoms refer to a psychological deficit or absence of behaviors that are normally present in a persons repertoire, such as alogia (poverty of speech), avolition (loss of desire), social withdrawal, and flat or blunted affect. People with schizophrenia often display ALOGIA, or POVERTY OF SPEECH, a reduction in speech or speech content. Some people with this negative kind of formal thought disorder think and say very little. Others say quite a bit but still manage to convey little meaning. These speech problems do not necessarily carryover to the realm of writing (Salome et aI., 2002). Many people with schizophrenia have A BLUNTED AFFECT-they show less anger, sadness, joy, and other feelings than most people. And some show almost no emotions at all, a condition known as FLAT AFFECT. Their faces are still, their eye contact is poor, and their voices are monotonous. In some cases, people with these

problems may have anhedonia, a general lack of pleasure or enjoyment. In other cases, however, blunted or flat affect may reflect an inability to express emotions as others do. Many people with schizophrenia experience AVOLITION, OR APATHY, FEELING DRAINED OF ENERGY AND OF INTEREST in normal goals and unable to start or follow through on a course of action (Lysaker & Bell, 1995). This problem is particularly common in people who have had schizophrenia for many years, as if they have been worn down by it. Similarly, individuals with the disorder may display ambivalence, or conflicting feelings, about most things. People with schizophrenia may WITHDRAW FROM THEIR SOCIAL ENVIRONMENT and attend only to their own ideas and fantasies. Because their ideas are illogical and confused, the withdrawal has the effect of distancing them still further from reality. In fact, studies have found that participants with this disorder are typically less knowledgeable about everyday social issues than are other people (Venneri et al., 2002; Cutting & Murphy, 1990, 1988). The social withdrawal seems also to lead to a breakdown of social skills, including the ability to recognize other people's needs and emotions accurately (Tenhula & Bellack, 2008; Moore & Walkup, 2007). People with schizophrenia often experience PSYCHOMOTOR SYMPTOMS, for example awkward movements or repeated grimaces and odd gestures. These symptoms can collectively be called CATATONIA (Manschreck, 2003). People in a catatonic stupor stop responding to their environment, remaining motionless and silent for long stretches of time. People who display catatonic rigidity maintain a rigid, upright posture for hours and resist efforts to be moved. Others exhibit catatonic posturing, assuming awkward, bizarre positions for long periods of time. They may spend hours holding their arms out at a 90-degree angle or balancing in a squatting position. They may also display "waxy flexibility," indefinitely maintaining postures into which they have been placed by someone else. If a nurse raises a patient's arm or tilts the patient's head, for example, the individual will remain in that position until moved again. Finally, people who display catatonic excitement, a different form of catatonia, move excitedly, sometimes with wild waving of arms and legs.

Course of the Disorder:

Schizophrenia usually first appears between the person's late teens and mid-30s (APA, 2000). Although its course varies widely from case to case, many sufferers seem to go through three phases ---- prodromal, active, and residual (Hafner & an der Heiden, 2008; Andreasen, 2001). During the prodromal phase, symptoms are not yet obvious, but the individuals are beginning to deteriorate. They may withdraw socially, speak in vague or odd ways, develop strange ideas, or express little emotion. During the active phase, symptoms become apparent. Sometimes this phase is triggered by stress in the person's life. Finally, many people with schizophrenia eventually enter a residual phase, in which they return to a prodromal-like level of functioning. The striking symptoms of the active phase lessen, but some negative symptoms, such as blunted emotions, may remain. Although one quarter or more of patients recover completely from schizophrenia, the majority continue to have at least some residual problems for the rest of their lives (Fischer & Carpenter, 2008; Roe & Davidson, 2008). Each of these phases may last for days or for years. A fuller

recovery from schizophrenia is more likely in persons who functioned quite well before the disorder (had good premorbid functioning) or whose disorder was initially triggered by stress, came on abruptly, or developed during middle age (Conus et al., 2007; Mamounas et al., 2001). Relapses are apparently more likely during times of life stress (Bebbington & Kuipers, 2008).

Subtypes of Schizophrenia:
Schizophrenia can be categorized in several ways. Andreasen classified schizophrenia into Type I and Type II symptoms, the Type I symptoms are mostly comprised of the positive symptoms while the Type II symptoms are mostly comprised of the negative symptoms. The commonest form of classification of schizophrenia is given by the DSM IV, which categorizes schizophrenia into: Paranoid type A type of schizophrenia in which the following criteria are met: A. Preoccupation with one or more delusions or frequent auditory hallucinations. B. None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect. Disorganized type A type of schizophrenia in which the following criteria are met: A. All of the following are prominent: 1. disorganized speech 2. disorganized behavior 3. flat or inappropriate affect B. The criteria are not met for catatonic type. Catatonic type A type of schizophrenia in which the clinical picture is dominated by at least two of the following: 1. motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor 2. excessive motor activity (that is apparently purposeless and not influenced by external stimuli) 3. extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism 4. peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing 5. echolalia or echopraxia Undifferentiated type A type of schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the paranoid, disorganized, or catatonic type.

Residual type A type of schizophrenia in which the following criteria are met: A. Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior. B. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for schizophrenia, present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences). The ICD 10 classifies schizophrenia as: F20 Schizophrenia F20.0 Paranoid schizophrenia F20.1 Hebephrenic schizophrenia F20.2 Catatonic schizophrenia F20.3 Undifferentiated schizophrenia F20.4 Post-schizophrenic depression F20.5 Residual schizophrenia F20.6 Simple schizophrenia F20.8 Other schizophrenia F20.9 Schizophrenia, unspecified The Hebephrenic schizophrenia classified by ICD 10 coincides with the Disorganized schizophrenia of DSM IV. A type of schizophrenia classified only by ICD 10 is Simple Schizophrenia and Post Schizophrenic Depression. Post-schizophrenic depression A depressive episode, which may be prolonged, arising in the aftermath of a schizophrenic illness. Some schizophrenic symptoms must still be present but no longer dominate the clinical picture. These persisting schizophrenic symptoms may be "positive" or "negative", though the latter are more common. It is uncertain, and immaterial to the diagnosis, to what extent the depressive symptoms have merely been uncovered by the resolution of earlier psychotic symptoms (rather than being a new development) or are an intrinsic part of schizophrenia rather than a psychological reaction to it. They are rarely sufficiently severe or extensive to meet criteria for a severe depressive episode (F32.2 and F32.3), and it is often difficult to decide which of the patient's symptoms are due to depression and which to neuroleptic medication or to the impaired volition and affective flattening of schizophrenia itself. This depressive disorder is associated with an increased risk of suicide. Simple schizophrenia An uncommon disorder in which there is an insidious but progressive development of oddities of conduct, inability to meet the demands of society, and decline in total performance. Delusions and hallucinations are not evident, and the disorder is less obviously psychotic than the hebephrenic, paranoid, and catatonic subtypes of schizophrenia. The characteristic "negative" features of residual schizophrenia (e.g. blunting of affect, loss of volition) develop without being preceded by any overt

psychotic symptoms. With increasing social impoverishment, vagrancy may ensue and the individual may then become self-absorbed, idle, and aimless.

Etiology of the disorder: BIOLOGICAL CAUSES ---- Genetic Factors: There is a genetic contribution to
some, perhaps all, forms of schizophrenia, and a high proportion of the variance in liability to schizophrenia is due to additive genetic effects. For example, schizophrenia and schizophrenia-related disorders (e.g., schizotypal, schizoid, and paranoid personality disorders) occur at an increased rate among the biological relatives of patients with schizophrenia. In the case of monozygotic twins who have identical genetic endowment, there is an approximately 50 percent concordance rate for schizophrenia. This rate is four to five times the concordance rate in dizygotic twins or the rate of occurrence found in other first-degree relatives (i.e., siblings, parents, or offspring). The role of genetic factors is further reflected in the drop-off in the occurrence of schizophrenia among secondand third-degree relatives, in whom one would hypothesize a decreased genetic loading. The finding of a higher rate of schizophrenia among the biological relatives of an adopted-away person who develops schizophrenia, as compared to the adoptive, nonbiological relatives who rear the patient, provides further support to the genetic contribution in the etiology of schizophrenia. Nevertheless, the monozygotic twin data clearly demonstrate the fact that individuals who are genetically vulnerable to schizophrenia do not inevitably develop schizophrenia; other factors (e.g., environment) must be involved in determining a schizophrenia outcome. If a vulnerability-liability model of schizophrenia is correct in its postulation of an environmental influence, then other biological or psychosocial environment factors may prevent or cause schizophrenia in the genetically vulnerable individual. There is robust data indicating that the age of the father has a direct correlation with the development of schizophrenia. In studies of schizophrenic patients with no history of illness in either the maternal or paternal line, it was found that those born from fathers older than the age of 60 were vulnerable to developing the disorder. Presumably, spermatogenesis in older men is subject to greater epigenetic damage than in younger men. The modes of genetic transmission in schizophrenia are unknown, but several genes appear to make a contribution to schizophrenia vulnerability. Linkage and association genetic studies have provided strong evidence for nine linkage sites: 1q, 5q, 6p, 6q, 8p, 10p, 13q, 15q, and 22q. Prevalence of Schizophrenia in Specific Populations Prevalence Population (%) General population 1 Non-twin sibling of a 8 schizophrenia patient Child with one parent with 12 schizophrenia Dizygotic twin of a schizophrenia 12 patient

Child of two parents with schizophrenia Monozygotic twin of a schizophrenia patient Biochemical Factors:

40 47

Dopamine Hypothesis: The simplest formulation of the dopamine hypothesis of schizophrenia posits that schizophrenia results from too much dopaminergic activity. The theory evolved from two observations. First, the efficacy and the potency of many antipsychotic drugs (i.e., the dopamine receptor antagonists [DRAs]) are correlated with their ability to act as antagonists of the dopamine type 2 (D2) receptor. Second, drugs that increase dopaminergic activity, notably cocaine and amphetamine, are psychotomimetic. The basic theory does not elaborate on whether the dopaminergic hyperactivity is due to too much release of dopamine, too many dopamine receptors, hypersensitivity of the dopamine receptors to dopamine, or a combination of these mechanisms. Which dopamine tracts in the brain are involved is also not specified in the theory, although the mesocortical and mesolimbic tracts are most often implicated. The dopaminergic neurons in these tracts project from their cell bodies in the midbrain to dopaminoceptive neurons in the limbic system and the cerebral cortex. Excessive dopamine release in patients with schizophrenia has been linked to the severity of positive psychotic symptoms. Position emission tomography studies of dopamine receptors document an increase in D2 receptors in the caudate nucleus of drug-free patients with schizophrenia. There have also been reports of increased dopamine concentration in the amygdala, decreased density of the dopamine transporter, and increased numbers of dopamine type 4 receptors in the entorhinal cortex. However, the dopamine hypothesis has certain limitations. The recent discovery of a new group of antipsychotic drugs, referred to as atypical antipsychotics, have thrown light to another aspect of the neurotransmitter approach. These drugs bind not only to D-2 receptors, like the traditional or conventional antipsychotic drugs but also to many D-1 receptors and receptors for other neurotransmitters, such as serotonin. It may be therefore said, that schiz is related to abnormal activity or interactions of both dopamine and serotonin and perhaps other neurotransmitters, say glutamate as well, rather than to abnormal dopamine activity alone (Grilly, 2002; Meltzer, 2002; Andreasen, 2001). Challenging the dopamine hypothesis some theorists claim that excessive dopamine activities contributes only to Type I schiz (Ragin et al., 1989; Crow, 1980). It turns out that Type I cases respond particularly well to the conventional antipsychotic drugs, which bind strongly to D-2 receptors, whereas Type II cases respond better to atypical antipsychotic drugs, which bind less strongly to the D-2 receptors. Thus it is assumed that the dopamine hypothesis is relevant only to Type I schiz. Serotonin: Current hypotheses posit serotonin excess as a cause of both positive and negative symptoms in schizophrenia. The robust serotonin antagonist activity of clozapine and other second-generation antipsychotics, coupled with the effectiveness

of clozapine to decrease positive symptoms in chronic patients has contributed to the validity of this proposition. Norepinephrine: Anhedonia, the impaired capacity for emotional gratification and the decreased ability to experience pleasure has long been noted to be a prominent feature of schizophrenia. A selective neuronal degeneration within the norepinephrine reward neural system could account for this aspect of schizophrenic symptomatology. However, biochemical and pharmacological data bearing on this proposal are inconclusive. GABA: The inhibitory amino acid neurotransmitter -aminobutyric acid (GABA) has been implicated in the pathophysiology of schizophrenia based on the finding that some patients with schizophrenia have a loss of GABAergic neurons in the hippocampus. GABA has a regulatory effect on dopamine activity, and the loss of inhibitory GABAergic neurons could lead to the hyperactivity of dopaminergic neurons. Neuropeptides: Neuropeptides, such as substance P and neurotensin, are localized with the catecholamine and indolamine neurotransmitters and influence the action of these neurotransmitters. Alteration in neuropeptide mechanisms could facilitate, inhibit, or otherwise alter the pattern of firing these neuronal systems. Glutamate: Glutamate has been implicated because ingestion of phencyclidine, a glutamate antagonist, produces an acute syndrome similar to schizophrenia. The hypotheses proposed about glutamate include those of hyperactivity, hypoactivity, and glutamate-induced neuro- toxicity. Acetylcholine and Nicotine: Postmortem studies in schizophrenia have demonstrated decreased muscarinic and nicotinic receptors in the caudate-putamen, hippocampus, and selected regions of the prefrontal cortex. These receptors play a role in the regulation of neurotransmitter systems involved in cognition, which is impaired in schizophrenia. Brain Imaging Studies: Functional brain imaging methods have been applied to the study of schizophrenia aiming at elucidating the neurobiology of this complex and heterogeneous disorder. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography (PET) for assessing metabolism, CBF and neuroreceptor functioning; single photon emission computerized tomography (SPECT) for studying CBF and neuroreceptors; and, more recently, functional magnetic resonance imaging (fMRI) for measuring changes attributable to cerebral blood flow. This chapter will review the application of this technology in schizophrenia research. Studies of cerebral metabolism and blood flow (CBF) can be divided into those measuring the physiologic parameters at a resting state and those introducing a perturbation, or challenge, in the form of a neurobehavioral probe or pharmacologic intervention. Initially, investigators assessed whether resting CBF and glucose metabolism differed between patients with schizophrenia and healthy controls. The topography of physiologic activity was examined along the dimensions stated above. This research is summarized in special reviews.

The frontal lobes were implicated in early physiologic studies of CBF in schizophrenia. Patients did not show the normal pattern of increased anterior relative to posterior CBF. This "hypofrontal" disturbance in the anterior-posterior gradient has been supported by some, but not all studies of resting CBF(133Xenon and SPECT) and glucose metabolism (PET). The relationship between this pattern of metabolic activity and clinical variables has also been examined. Decreased frontal metabolic activity has been associated with duration of illness; a longer duration was associated with negative symptoms and a lower anteroposterior gradient. Liddle et al. found that patients with poor performance on the Stroop test, which measures attention, had abnormal CBF in anterior cingulate cortex. Mozley et al. noted that patients with poorer memory displayed greater mid-temporal glucose metabolism. Differences in resting values between patients and controls were also found in laterality indices, suggesting relatively higher left hemispheric values in severely disturbed patients. Furthermore, improvement in clinical status correlated with a shift toward lower left hemispheric relative to right hemispheric metabolism. This supports hypotheses derived from behavioral data concerning lateralized abnormalities in schizophrenia, as well as perhaps the more specific form of the hypothesis which proposes that schizophrenia is associated both with left hemispheric dysfunction and overactivation of the dysfunctional left hemisphere. Subsequent to assessing global, anterior/posterior and laterality dimensions, investigators have begun the study of functional changes in brain systems linked to other impaired behavior. Dysfunction in temporo-limbic structures, including the hippocampus as well as temporal cortex, is supported by neuroanatomic and neuropsychological studies. Lateralized abnormalities in these regions, with greater left than right hemispheric dysfunction, are implicated by characteristic clinical features of schizophrenia, such as thought disorder, auditory hallucinations, and language disturbances. PET studies of temporal lobe metabolism showed both increased and decreased glucose utilization. Decreased metabolism was also noted in hippocampus and anterior cingulate cortex. Metabolism and flow patterns in temporo-limbic regions have also been related to symptoms. Liddle et al. used 15O-labeled water with PET and described abnormal CBF in the parahippocampal gyrus that was associated with positive symptoms. Musalek et al. found hallucinations to be associated with SPECT flow changes in hippocampus, parahippocampus and amygdala. There are conflicting reports of superior temporal gyrus functional changes in schizophrenia during active auditory hallucinations. Cleghorn et al. suggested that patients with hallucinations have significantly lower relative metabolism in Wernicke's region. Anderson et al. showed asymmetric temporal lobe perfusion (lower in the left than the right) in schizophrenic patients with auditory hallucinations. Delisi et al. found greater metabolic activity in the left anterior temporal lobe, which was related to the severity of symptoms. Further research is indicated to elucidate the nature and extent of temporal lobe changes in schizophrenia. Given that this region is linked to memory functions, an appropriate neurobehavioral probe would be aimed at memory.

As can be seen, resting CBF values and topography were normal, but abnormalities in activation-induced changes were observed. These abnormalities were both in degree of activation and in lateralized changes as a function of whether the memory task required processing of words or faces. In healthy controls, the mid-temporal region was the only cortical area showing hemispherically appropriate changes (left > right for words; right > left for faces). By contrast, patients did not show a significantly lateralized response in this region and instead showed such responses in other regions. Functional changes in the basal ganglia have been examined with PET and SPECT. Several PET studies implicated basal ganglia dysfunction in schizophrenia. The withdrawal-retardation factor (emotional withdrawal, blunted affect, and motor retardation) of the Brief Psychiatric Rating Scale, has been negatively correlated with PET basal ganglia metabolic activity. Neuroleptic-naive schizophrenic patients were reported to have relatively increased blood flow in left globus pallidus. Some PET studies reported decreased basal ganglia metabolism in schizophrenia, while others found increased basal ganglia metabolic rates following administration of neuroleptic medication. The introduction of functional MRI (fMRI) is an exciting development in functional imaging research. The method is radiation-free and more amenable to repeated measures. The application of this technology to the study of schizophrenia is still in the early stages. Renshaw et al. measured the relative magnitude of the change in image signal intensity caused by photic stimulation in eight patients and nine controls. The mean signal intensity change in the primary visual cortex was significantly greater in patients than in controls. Sensorimotor cortex and supplementary motor area (SMA) activation were examined in right-handed patients and controls during finger-to-thumb opposition. All subjects showed significant activation of the SMA and both ipsilateral and contralateral sensorimotor cortices. Compared with controls, patients showed a decreased activation of both sensorimotor cortices and SMA, as well as a reversed lateralization effect. Yurgelun-Todd et al. examined 12 schizophrenic patients and 11 controls during performance of a word fluency task. Patients showed less left frontal activation and greater left temporal activation than controls. With increased understanding of the technology and elucidation of neural systems processing tasks in healthy people, our ability to apply the methodology to schizophrenia will also be enhanced.

THE PSYCHODYNAMIC EXPLANATION

Freud (1924, 1915, 1914) believed that schizophrenia develops from two psychological processes: (1) regression to a pre-ego stage and (2) efforts to reestablish ego control. He proposed that when their world is extremely harsh or withholding-for example, when parents are cold or unnurturing-people who develop schizophrenia regress to the earliest point in their development, to the pre ego state of primary narcissism, in which they recognize and meet only their own needs. Their near-total regression leads to self-centered symptoms such as neologisms, loose associations, and delusions of grandeur. Once people regress to such an infantile state, Freud continued, they then try to reestablish ego control and contact with reality. Their efforts give rise to yet other schizophrenic symptoms. Auditory

hallucinations, for example, may be an individual's attempt to substitute for a lost sense of reality. Years later, noted psychodynamic clinician Frieda Fromm-Reichmann (1948) elaborated on Freud's notion that cold or unnurturing parents may set schizophrenia in motion. She described the mothers of people who develop this disorder as cold, domineering, and uninterested in their children's needs. According to FrommReichmann, these mothers may appear to be self-sacrificing but are actually using their children to meet their own needs. At once overprotective and rejecting, they confuse their children and set the stage for schizophrenic functioning. She called them schizophrenogenic (schizophrenia-causing) mothers. Fromm Reichmann's theory, like Freud's, has received little research support (Willick, 2001). The majority of people with schizophrenia do not appear to have mothers who fit the schizophrenogenic description. In fact, some studies have suggested that quite a different personality style may prevail among their mothers. In one study the mothers of individuals with this disorder were found to be shy, withdrawn, and anxious, among other qualities, while the mothers of nonschizophrenic persons seemed more likely to display what Fromm-Reichmann would have called a schizophrenogenic maternal style (Waring & Ricks, 1965). Regardless of the theoretical model, all psychodynamic approaches are founded on the premise that psychotic symptoms have meaning in schizophrenia. Patients, for example, may become grandiose after an injury to their self-esteem. Similarly, all theories recognize that human relatedness may be terrifying for persons with schizophrenia. Although research on the efficacy of psychotherapy with schizophrenia shows mixed results, concerned persons who offer compassion and a sanctuary in the confusing world of the schizophrenic must be a cornerstone of any overall treatment plan. Long-term follow-up studies show that some patients who bury psychotic episodes probably do not benefit from exploratory psychotherapy, but those who are able to integrate the psychotic experience into their lives may benefit from some insight-oriented approaches. There is renewed interest in the use of long-term individual psychotherapy in the treatment of schizophrenia, especially when combined with medication.

THE BEHAVIORAL VIEW

Behaviorists usually cite operant conditioning and principles of reinforcement as the cause of schizophrenia. They propose that most people become quite proficient at reading and responding to social cues-that is, other people's smiles, frowns, and comments. People who respond to such cues in a socially acceptable way are better able to satisfY their own emotional needs and achieve their goals (Bach, 2007; Liberman, 1982; Ullmann & Krasner, 1975). Some people, however, are not reinforced for their attention to social cues, either because of unusual circumstances or because important figures in their lives are socially inadequate. As a result, they stop attending to such cues and focus instead on irrelevant cues-the brightness of light in a room, a bird flying above, or the sound of a word rather than its meaning. As they attend more and more to irrelevant cues, their responses become increasingly bizarre. Because the bizarre responses are rewarded with attention or other types of

reinforcement, they are likely to be repeated again and again. Support for the behavioral position has been circumstantial. Researchers have found that patients with schizophrenia are capable of learning at least some appropriate verbal and social behaviors if hospital personnel consistently ignore their bizarre responses and reinforce normal responses with cigarettes, food, attention, or other rewards (Kopelowicz, Liberman, & Zarate, 2007). If bizarre verbal and social responses can be eliminated by appropriate reinforcements, perhaps they were acquired through improper learning in the first place. Of course, an effective treatment does not necessarily indicate the cause of a disorder. Today the behavioral view is usually considered at best a partial explanation for schizophrenia. Although it may help explain why a given person displays more schizophrenic behavior in some situations than in others, it is too limited, in the opinion of many, to account for schizophrenia's origins and its many symptoms.

THE COGNITIVE VIEW

A leading cogmtlve explanation of schizophrenia agrees with the biological view that during hallucinations and related perceptual difficulties the brains of people with schizophrenia are actually producing strange and unreal sensations-sensations triggered by biological factors. According to the cognitive explanation, however, further features of the disorder emerge when the individuals attempt to understand their unusual experiences (Tarrier, 2008; Waters et al., 2007). When first confronted by voices or other troubling sensations, these people turn to friends and relatives. Naturally, the friends and relatives deny the reality of the sensations, and eventually the sufferers conclude that the others are trying to hide the truth. They begin to reject all feedback, and some develop beliefs (delusions) that they are being persecuted, especially if the voices are perceived as negative or malicious (Perez-Alvarez et aI., 2008; Bach, 2007). In short, according to this theory, people with schizophrenia take a "rational path to madness" (Zimbardo, 1976). Researchers have established that people with schizophrenia do indeed experience sensory and perceptual problems. As you saw earlier, many of them have hallucinations, for example, and most have trouble keeping their attention focused. But researchers have yet to provide clear, direct support for the cognitive notion that misinterpretations of such sensory problems actually produce a syndrome of schizophrenia.

FAMILY DYNAMICS
In a study of British 4-year-old children, those who had a poor motherchild relationship had a sixfold increase in the risk of developing schizophrenia, and offspring from schizophrenic mothers who were adopted away at birth were more likely to develop the illness if they were reared in adverse circumstances compared to those raised in loving homes by stable adoptive parents. Nevertheless, no wellcontrolled evidence indicates that a specific family pattern plays a causative role in the development of schizophrenia. Some patients with schizophrenia do come from dysfunctional families, just as do many nonpsychiatrically ill persons. It is important, however, not to overlook pathological family behavior that can significantly increase the emotional stress with which a vulnerable patient with schizophrenia must cope. Double Bind: The double-bind concept was formulated by Gregory Bateson and Donald Jackson to describe a hypothetical family in which children receive

conflicting parental messages about their behavior, attitudes, and feelings. In Bateson's hypothesis, children withdraw into a psychotic state to escape the unsolvable confusion of the double bind. Unfortunately, the family studies that were conducted to validate the theory were seriously flawed methodologically. The theory has value only as a descriptive pattern, not as a causal explanation of schizophrenia. An example of a double bind is the parent who tells the child to provide cookies for his or her friends and then chastises the child for giving away too many cookies to playmates. Schisms and Skewed Families: Theodore Lidz described two abnormal patterns of family behavior. In one family type, with a prominent schism between the parents, one parent is overly close to a child of the opposite gender. In the other family type, a skewed relationship between a child and one parent involves a power struggle between the parents and the resulting dominance of one parent. These dynamics stress the tenuous adaptive capacity of the schizophrenic person. Pseudomutual and Pseudohostile Families: As described by Lyman Wynne, some families suppress emotional expression by consistently using pseudomutual or pseudohostile verbal communication. In such families, a unique verbal communication develops, and when a child leaves home and must relate to other persons, problems may arise. The child's verbal communication may be incomprehensible to outsiders. Expressed Emotion: This concept formulated by George W. Brown says that parents or other caregivers may behave with overt criticism, hostility, and overinvolvement toward a person with schizophrenia. Many studies have indicated that in families with high levels of expressed emotion, the relapse rate for schizophrenia is high. The assessment of expressed emotion involves analyzing both what is said and the manner in which it is said. R. D. Laing's View According to Laing's existential principles, human beings must be in touch with their true selves in order to give meaning to their lives. Unfortunately, said Laing, this is difficult to do in present-day society. Other people's expectations, demands, and standards require us to develop a false self rather than a true one. Some people-those who develop schizophrenia-have especially difficult obstacles to deal with, according to Laing. They experience a lifetime of confusing communications and demands from their families and community. Out of desperation they eventually undertake an inner search for strength and purpose. They withdraw from others and attend increasingly to their own inner cues in order to recover their wholeness as human beings. Laing argued that these people would emerge stronger and less confused if they were allowed to continue this inner search. Instead, as he saw it, society and its clinicians tell the individuals that they are sick, manipulate them into the role of patient, and subject them to treatments that actually serve to produce further psychotic symptoms. In attempting to cure these people, he said, society dooms them to suspension in an inner world. However, most of today's theorists reject Laing's controversial notion that schizophrenia is constructive. For the most part, research simply has not addressed the issue. Laing's ideas do not lend themselves to empirical research, and the existentialists who embrace his view typically have little confidence in traditional research approaches (Burston, 2000; Howells & Guirguis, 1985). It is also

worth noting that many persons with schizophrenia have themselves rejected the theory.

DIATHESIS STRESS MODEL:

The premise underlying the diathesis-stress model is that a person is more likely to suffer an illness if he or she has a particular diathesis (i.e., vulnerability or susceptibility) and is under a high level of stress. Diathesis factors that have been studied include family history of substance abuse or mental illness; individual psychological characteristics such as hostility or impulsivity; biological characteristics (e.g., cardiovascular reactivity, hypothalamic-pituitary-adrenal responsivity); and environmental characteristics such as childhood maltreatment or low socioeconomic status. Diathesis factors are generally assumed to be relatively stable but not necessarily permanent. The term stress refers to events and experiences that may cause psychological distress. Stress can influence mechanisms that help to maintain the stability of an individuals cognition, physiology, and emotion. Although the notion that stress can influence the development of illness has been held since the mid-nineteenth century, it was not until theories of schizophrenia proposed during the 1960s that the concepts of stress and diathesis were combined. In studies of depression that found empirical support for the model, stress has most commonly been operationalized as having experienced major negative events within the past year. An implication of the diathesis-stress model is that the greater the vulnerability an individual has, the less stress is required for that individual to become ill. It is necessary to consider both the presence of a diathesis and a persons level of stress in order to determine the degree of risk for the onset or reoccurrence of an illness. The common psychological disorder to which the diathesis-stress model has been widely applied is schizophrenia. Studies have investigated a broad range of both environmental and psychological vulnerabilities, as well as biological vulnerabilities, some of which involve genetic expression. Interest in the role of genetics in disease onset has also led to studies on gene-environment interaction, which suggest that elevation of disease risk by an environmental factor occurs primarily for individuals with a susceptible genotype. Empirical support for the applicability of the diathesis-stress model is robust and has warranted preventive interventions targeting those at highest risk of developing negative health outcomes. For example, psychological interventions address the way a person with high vulnerability appraises and responds to stressful life events. Researchers seek to refine measures of vulnerability, provide suggestions for preventive strategies, and gather empirical evidence for the effectiveness of preventive interventions. Overall, the diathesis-stress model has provided researchers and clinicians with a framework in which knowledge about biological, environmental, and psychological processes can be used to decrease the likelihood that an illness will develop or reoccur. As with most other psychological disorders, clinical theorists now believe that schizophrenia, in any of its forms, is probably caused by a combination of factors. At the same time, researchers have been far more successful in identifying the biological

influences than the psychological and socio-cultural ones. While biological investigations have closed in on specific genes, abnormalities in brain biochemistry and structure, and even viral infections, most of the psychological and socio-cultural research has been able to cite only general factors, such as the roles of family conflict and diagnostic labeling. Clearly, researchers must identify psychological and sociocultural factors with greater precision if we are to gain a full understanding of the disorder. The exciting, at times spectacular, progress now being made in the biological study of schizophrenia is indeed impressive, but it must not blind us to the significant gaps, uncertainties, and confusions that continue to obscure our view . Reference: Abnormal Psychology, R. J. Comer, 7th Edition Essentials of Abnormal Psychology, Vincent Mark Durand, David H. Barlow, V. Mark Durand Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition http://www.encyclopedia.com/doc/1G2-3045300590.html http://www.aarogya.com/index.php? option=com_content&view=article&id=4665:prognostic-factors-inschizophrenia&catid=113:schizophrenia&Itemid=3510