Papers by Shigenobu Kanba
American Journal of Psychiatry, 2013
The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When... more The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.
Psychiatry and clinical neurosciences, Jan 9, 2015
Japan's prototype of depression had traditionally been a melancholic depression based on the ... more Japan's prototype of depression had traditionally been a melancholic depression based on the premorbid personality "shūchaku-kishitsu" proposed by Mitsuzo Shimoda in the 1930s. However since around 2000, a novel form of depression has emerged among youth. Called 'modern type depression (MTD)' by mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives (Kato TA et al. J Affect Dis 2011) that begin to suggest that MTD is a phenomenon that MTD may exist not only in Japan but also in ...
The Journal of biological chemistry, Jan 27, 2014
Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxid... more Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocy...
PloS one, 2015
Maladaptive social interaction and its related psychopathology have been highlighted in psychiatr... more Maladaptive social interaction and its related psychopathology have been highlighted in psychiatry especially among younger generations. In Japan, novel expressive forms of psychiatric phenomena such as "modern-type depression" and "hikikomori" (a syndrome of severe social withdrawal lasting for at least six months) have been reported especially among young people. Economic games such as the trust game have been utilized to evaluate real-world interpersonal relationships as a novel candidate for psychiatric evaluations. To investigate the relationship between trusting behaviors and various psychometric scales, we conducted a trust game experiment with eighty-one Japanese university students as a pilot study. Participants made a risky financial decision about whether to trust each of 40 photographed partners. Participants then answered a set of questionnaires with seven scales including the Lubben Social Network Scale (LSNS)-6 and the Patient Health Questionnaire ...
Psychiatry and clinical neurosciences, Jan 31, 2014
Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abn... more Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype. Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale. We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to...
Psychiatry research, Jan 30, 2010
Previous studies have demonstrated both functional and structural abnormalities in the frontal-st... more Previous studies have demonstrated both functional and structural abnormalities in the frontal-striatal-thalamic circuits in obsessive-compulsive disorder (OCD). The purpose of this study was to assess volume abnormalities not only of gray matter (GM), but also of white matter (WM) in patients with OCD using voxel-based morphometry (VBM). Subjects consisted of 23 patients with OCD and 26 normal control subjects. All patients were drug-free for at least 2 weeks before the study. Three-dimensional T1-weighed MR images were obtained in all subjects. Optimized voxel-based morphometry was performed to detect structural difference between the two groups. The patients with OCD demonstrated a significant reduction of GM volume in the bilateral medial prefrontal cortex, right premotor area, right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex, and bilateral temporal and occipital regions. The OCD patients also showed a significant WM volume increase in the right anterior li...
Psychiatry research, Jan 30, 2008
The ability of the brain to suppress incoming irrelevant sensory input is termed 'sensory gat... more The ability of the brain to suppress incoming irrelevant sensory input is termed 'sensory gating,' and auditory sensory gating is often indexed by the auditory evoked response. We recorded the auditory evoked magnetic fields to the human voice, using the conditioning-testing paradigm, to investigate whether or not healthy subjects show less activation to the second voice stimulus. Seventeen healthy adults (mean age 27.9+/-4.8 years, 9 males and 8 females) participated in the experiment. The auditory stimuli were presented monaurally as a series of 120 paired voices, with 500-ms interstimulus intervals and 6-s interpaired stimulus intervals. The P50m and the N100m responses were investigated, and dipole source localization was performed. Root mean squares of both P50m and N100m were significantly suppressed to the second stimulus bilaterally, and the suppression was more significant in N100m. The N100m was located significantly more laterally than the P50m for both hemisphere...
Neurochemistry international, 2006
The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in... more The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained el...
Molecular psychiatry, 2002
In order to evaluate the hypothesis that one set of genetic risk factors may be common to disorde... more In order to evaluate the hypothesis that one set of genetic risk factors may be common to disorders and dimensions of temperament, whereas environmental risk factors are disorder specific, we have conducted a genetic analysis of dimensions of temperament and symptoms of depression in about 201 pairs of monozygotic and dizygotic twins. Dimensions of temperament associated with novelty seeking, harm avoidance, reward dependence, and persistence were measured by using the Temperament and Character Instruments developed by Cloninger, and depressive symptoms were measured using the Hospital Anxiety and Depression Scale. Differences among individuals on these measures can be explained by differences in their genes and in their environmental experiences. There are no differences between the sexes in gene action affecting temperament. Each dimension of temperament is genetically dependent, and genetic variations in symptoms of depression are largely dependent on the same factors that affect...
Scientific reports, 2014
Microglia have been implicated in various neurological and psychiatric disorders in rodent and hu... more Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique prom...
JAMA psychiatry, Jan 14, 2015
A major goal of translational neuroscience is to identify neural circuit abnormalities in neurops... more A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ. To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ. We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 3...
Schizophrenia Research, 2007
Microglia has recently been regarded to be a mediator of neuroinflammation via the release of pro... more Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.
Journal of affective disorders, Jan 15, 2014
These analyses compared efficacy of olanzapine in patients with bipolar mania with or without mix... more These analyses compared efficacy of olanzapine in patients with bipolar mania with or without mixed features, as defined in the DSM-5. Pooled data from 3 placebo-controlled olanzapine studies in patients having bipolar I disorder with manic/mixed episode were analyzed (N=228 olanzapine; N=219 placebo). Patients were categorized for mixed features by number of concurrent depressive symptoms at baseline (0, 1, and 2 [category A; without mixed features], and ≥3 [category B; with mixed features]), as determined by HAM-D17 item score ≥1. Depressive symptoms corresponded to 6 HAM-D17 items in the DSM-5 definition of manic episode with mixed features. Primary efficacy was evaluated by changes in the baseline-to-3-week YMRS total score. Patients were categorized into A (N=322; 72.0%) or B (N=125; 28.0%). Mean baseline YMRS total scores were 28.1 in category A and 27.8 in category B. Least-squares mean change of YMRS total scores in categories A and B (olanzapine versus placebo) were -11.78 ...
The International Journal of Neuropsychopharmacology, 2007
Neuroscience Letters, 2002
Recently identified hypothalamic peptides called orexins (or hypocretins) have been implicated in... more Recently identified hypothalamic peptides called orexins (or hypocretins) have been implicated in the sleep–wake cycle and in sleep disorder narcolepsy. Neuropathological studies have shown that in patients with narcolepsy, global reduction in the expression of orexins occurs due to the loss of orexin neurons in the hypothalamus. Cerebrospinal fluid analysis has confirmed a reduced or undetectable level of orexin-A in
General Hospital Psychiatry - GEN HOSP PSYCHIAT, 2009
ObjectiveTo assess the reliability and validity of the Japanese version of the Peritraumatic Dist... more ObjectiveTo assess the reliability and validity of the Japanese version of the Peritraumatic Distress Inventory (PDI).
Journal of Neuroscience, 2008
Synapse, 2003
The human serotonin transporter (5-HTT) gene has a polymorphism in the 5&... more The human serotonin transporter (5-HTT) gene has a polymorphism in the 5'-flanking promoter region that is called the serotonin transporter gene-linked polymorphic region (5-HTTLPR). In lymphoblast cell lines, the promoter activity of the 5-HTT gene is dependent on 5-HTTLPR allelic variants. The transcriptional activity of the l allele was more than twice as high as that of the s allele. The s allele is considered to be associated with mood disorders and anxiety-related personality traits. To evaluate the functional differences of 5-HTTLPR in the brain in vivo, we examined the allelic variations of 5-HTTLPR and measured 5-HTT binding in the living human brain using positron emission tomography (PET) with C(11)-labeled trans-1, 2, 4, 5, 6, 10-beta-hexahydro-6-[4-(methylthio) phenyl]pyrrolo[2,1-a]isoquinoline (McN5652) as a ligand. Twenty-seven healthy male subjects participated in this study. Although the human lymphoblast cells with the l/l genotype was reported to produce higher concentrations of both mRNA and protein of 5-HTT than those with the l/s or s/s genotype in a human lymphoblast in vitro study, 5-HTT binding in vivo was not significantly different among subjects with the three genotypes (l/l: 0.842 +/- 0.184, l/s: 0.708 +/- 0.118, s/s: 0.825 +/- 0.209). In conclusion, this study does not support the assumption that the genotype-dependent differences of 5-HTTLPR directly contributes to the regulation of the 5-HTT binding site in the living human brain.
Social Psychiatry and Psychiatric Epidemiology, 2012
To explore whether the &a... more To explore whether the 'hikikomori' syndrome (social withdrawal) described in Japan exists in other countries, and if so, how patients with the syndrome are diagnosed and treated. Two hikikomori case vignettes were sent to psychiatrists in Australia, Bangladesh, India, Iran, Japan, Korea, Taiwan, Thailand and the USA. Participants rated the syndrome's prevalence in their country, etiology, diagnosis, suicide risk, and treatment. Out of 247 responses to the questionnaire (123 from Japan and 124 from other countries), 239 were enrolled in the analysis. Respondents' felt the hikikomori syndrome is seen in all countries examined and especially in urban areas. Biopsychosocial, cultural, and environmental factors were all listed as probable causes of hikikomori, and differences among countries were not significant. Japanese psychiatrists suggested treatment in outpatient wards and some did not think that psychiatric treatment is necessary. Psychiatrists in other countries opted for more active treatment such as hospitalization. Patients with the hikikomori syndrome are perceived as occurring across a variety of cultures by psychiatrists in multiple countries. Our results provide a rational basis for study of the existence and epidemiology of hikikomori in clinical or community populations in international settings.
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Papers by Shigenobu Kanba