Missense variants of the alanine:glyoxylate aminotransferase 2 gene are not associated with Japanese schizophrenia patients.

Alanine:glyoxylate aminotransferase 2 (AGXT2) is the only enzyme that degrades D-3-aminoisobutyrate (D-AIB), which is an intermediate product of thymine, and 30-40% of Japanese lack AGXT2 activity genetically and excrete high amounts of D-AIB in their urine. Recently, AGXT2 is reported to metabolize asymmetric dimethyl arginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Since AGXT2 is expressed in the central nervous system, the loss of AGXT2 activity will be related to the vulnerability for neuropsychiatric disorders related to the NO system. In this study, we recruited 85 Japanese subjects to discover loss variants of the AGXT2 gene with the amount of D-AIB excretion in their urine. From the statistical relevance between them, we found three missense polymorphisms (rs37370, rs37369, and rs180749) independently related to AGXT2 activity (P<0.0001). Then, we performed a case-control association analysis of its missense polymorphisms with 1136 schizophrenia and 1908 control subjects because the NO system may be involved in the vulnerability of schizophrenia processes. We could not find any associations of three functional SNPs with schizophrenia pathogenesis in the analyses of either genotypic or allelic models. We concluded that the AGXT2 gene is not associated with schizophrenia in Japanese subjects.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions.

DNA methylation, which is the transference of a methyl group to the 5'-carbon position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of epigenetic modifications. A number of studies have demonstrated altered DNA methylation of peripheral blood cells in schizophrenia (SCZ) in previous studies. However, most of these studies have been limited to the analysis of the CpG sites in CpG islands in gene promoter regions, and cell-type proportions of peripheral leukocytes, which may be one of the potential confounding factors for DNA methylation, have not been adjusted in these studies. In this study, we performed a genome-wide DNA methylation profiling of the peripheral leukocytes from patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42 control subjects) using a quantitative high-resolution DNA methylation microarray which covered across the whole gene region (485,764 CpG dinucleotides). In the DNA methylation data analysis, we first estimated the cell-type proportions of each sample with a published algorithm. Next, we performed a surrogate variable analysis to identify potential confounding factors in our microarray data. Finally, we conducted a multiple linear regression analysis in consideration of these factors, including estimated cell-type proportions, and identified aberrant DNA methylation in SCZ at 2,552 CpG loci at a 5 % false discovery rate correction. Our results suggest that altered DNA methylation may be involved in the pathophysiology of SCZ, and cell heterogeneity adjustments may be necessary for DNA methylation analysis.


Successful Treatment of Anorexia Nervosa in a 10-year-old Boy with Risperidone Long-acting Injection.

Although the effectiveness of medication in the treatment of anorexia nervosa is uncertain, atypical antipsychotics such as olanzapine and risperidone have been used empirically for decades. we describe the case of a 10-year-old boy with anorexia nervosa in whom remarkable improvement was seen following the administration of risperidone or risperidone long-acting injection and deterioration when these agents were ceased. Because this is, to the best of our knowledge, the first report describing the usefulness of risperidone long-acting injection for adolescent anorexia nervosa.

Clinical Psychopharmacology and Neuroscience


Psychiatric symptoms in a patient with isolated adrenocorticotropin deficiency: case report and literature review.

We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency.


Microarray analysis of global gene expression in leukocytes following lithium treatment.

To elucidate the molecular effects of lithium, we studied global gene expression changes induced by lithium in leukocytes from healthy subjects. Eight healthy male subjects participated in this study. Lithium was prescribed for weeks to reach a therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 and 2 weeks of medication and at 2 weeks after stopping medication. Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays (The Agilent Technologies, Santa Clara, CA, USA). Expression of some candidate genes was also assessed by real-time polymerase chain reaction (PCR). Gene ontology analysis revealed that the cellular and immune responses to stimulus and stress indeed played a major role in the cellular response to lithium treatment. Pathway analysis revealed that the interleukin 6 pathway, the inhibitor of differentiation pathway, and the methane metabolism pathway were regulated by lithium. Using real-time PCR, we also confirmed that five candidate genes in these pathways were significantly changed, including suppressor of cytokine signaling 3 and myeloperoxidase. Our investigation suggests that the molecular action of lithium is mediated in part by its effects on the cellular and immune response to stimulus and stress followed by the interleukin 6, inhibitor of differentiation, and methane metabolism pathways.


An evaluation of association between a novel hippocampal biology related SNP (rs7294919) and schizophrenia.

Recent genetic analyses have implicated several candidate susceptibility variants for schizophrenia. The single nucleotide polymorphism (SNP) rs7294919 is likely a schizophrenia-susceptibility variant according to its significant association with hippocampal volume, hippocampus function, and cognitive performance as well as the nominal association with schizophrenia. However, all previous analyses were conducted only in Europeans, and whether rs7294919 is associated with schizophrenia in other populations are yet to be tested. Here, we conducted a case-control analysis of rs7294919 with schizophrenia in six independent Chinese (N = 3) and Japanese (N = 3) samples, including a total of 7,352 cases and 10,824 controls. The results of our association analysis were not able to confirm the association of rs7294919 with schizophrenia (p = 0.51 in total samples, odds ratio = 1.02 for allele[C]). The absence of rs7294919's association in Chinese and Japanese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating associations of schizophrenia across different ethnic populations.


Japan useful medication program for schizophrenia (JUMPs)-long-term study on discontinuation rate, resolution and remission, and improvement in social functioning rate associated with atypical antipsychotic medications in patients with schizophrenia.

It is desirable to establish evidence for the selection of antipsychotics from the viewpoint of recovery of social activity in individual patient with schizophrenia receiving medication. From this perspective, awareness of the importance of studies about drug effectiveness on treatment discontinuation rate, remission rate, and improvement in QOL has grown recently. In Western countries, numerous reports are available in effectiveness studies, which are related to olanzapine and risperidone primarily, whereas evidence for other second-generation antipsychotics (SGAs) is poor. In Japan, no effectiveness study has been reported: thus, it is desirable to collect data that will serve as evidence for selection of the 3 SGAs approved after olanzapine. The present study was a long-term effectiveness study under healthcare setting in Japan. It was designed as an open-label, multicenter, randomized, comparative study involving 104-week oral treatment with 1 of the 3 drugs (aripiprazole, blonanserin, and paliperidone) in patients with schizophrenia aged 20 years or over who required antipsychotic medication or switching of the current medication to others for reasons such as lack of efficacy and intolerability. The primary endpoint is treatment discontinuation rate for any causes. The secondary endpoints include remission rate, improvement of social activity, alleviation, aggravation or recurrence of psychiatric symptoms, and safety. The target number of subjects was set at 300. Because this study is expected to yield evidence regarding the selection of antipsychotics for facilitating the recovery of social activity in patients with schizophrenia, it is considered highly valuable to perform this effectiveness study under ordinary healthcare setting in Japan. UMIN Clinical Trials Registry 000007942.


A case of steroid psychosis in outpatient cancer chemotherapy

外来での抗がん剤治療中にステロイド精神病を発症した1症例


Aripiprazole augmentation to antidepressant therapy in Japanese patients with major depressive disorder: a randomized, double-blind, placebo-controlled study (ADMIRE study).

This randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3mg/day) and flexible dose (3-15 mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT). During an 8-week prospective treatment phase, patients experiencing a major depressive episode received clinicians' choice of ADT. Subjects with inadequate response to ADT were randomized to receive adjunctive treatment with placebo (n=195), fixed dose aripiprazole (n=197) or flexible dose aripiprazole (n=194) for 6 weeks. The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of prospective treatment (baseline) to the end of randomized treatment. More than 90% of patients in all treatment groups completed the 6-week double-blind treatment phase. Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole (-10.5 and -9.6, respectively) than with placebo (-7.4). Aripiprazole was well tolerated. The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6(*)10 allele in Asian populations. Six weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole. Exclusion of patients with established medical comorbidities does not reflect real-world practice. Aripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT.


A Case of Recurrent Depressive Patient with SIADH Induced by Three Different Class of Antidepressants

異なる機序の抗うつ薬3剤でSIADHを呈した反復性うつ病性障害の1例


Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia.

Schizophrenia (SCZ) is a devastating psychiatric disorder with a median lifetime prevalence rate of 0.7-0.8%. Elevated plasma total homocysteine has been suggested as a risk factor for SCZ, and various biological effects of hyperhomocysteinemia have been proposed to be relevant to the pathophysiology of SCZ. As increased attention is paid to aberrant DNA methylation in SCZ, homocysteine is attracting additional interest as a potential key substance. Homocysteine is formed in the methionine cycle, which is involved in one-carbon methyl group-transfer metabolism, and it acts as a methyl donor when it is converted to S-adenosyl-methionine. To date, no studies have examined the relationship between homocysteine and genome-wide DNA methylation in SCZ. We examined the relationship between plasma total homocysteine and DNA methylation patterns in the peripheral leukocytes of patients with SCZ (n = 42) using a quantitative high-resolution DNA methylation array (485,764 CpG sites). Significant homocysteine-related changes in DNA methylation were observed at 1,338 CpG sites that were located across whole gene regions, including promoters, gene bodies and 3'-untranslated regions. Of the 1,338 sites, 758 sites (56.6%) were located in the CpG islands (CGIs) and in the regions flanking CGIs (CGI: 15.8%; CGI shore: 28.2%; CGI shelf: 12.6%), and positive correlations between plasma total homocysteine and DNA methylation were observed predominantly at CpG sites in the CGIs. Our results suggest that homocysteine might play a role in the pathogenesis of SCZ via a molecular mechanism that involves alterations to DNA methylation.


Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: validation of the Japanese version.

This preliminary study was performed to test the reliability and validity of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), developed by the National Institute of Mental Health MATRICS initiative, as an assessment tool in a Japanese-language version (MCCB-J). The subjects for the present study were 37 patients with schizophrenia. Each subject gave written informed consent to participate in the research. In order to examine the validity of the MCCB-J, the correlation between the MCCB-J and the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) was determined. Cronbach's alpha for the MCCB-J was 0.72. The MCCB-J composite score was significantly correlated with all subtests of the MCCB-J. There was a significant correlation between the MCCB-J and the BACS composite score. This preliminary study indicates that the MCCB-J has good psychometric properties and validity.


Evaluation of Cognitive Functions in a Normal Population in Japan using the Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J)

統合失調症認知機能簡易評価尺度日本語版(BACS-J)標準化の試み


[Multi-channel near-infrared spectroscopy shows reduced activation in the prefrontal cortex during facial expression processing in pervasive developmental disorder]


[Pharmacotherapy for schizophrenia: are newer drugs truly superior?]


薬物療法が無効でECTが著効した精神病性うつ病の1例

薬物療法が無効でECTが著効した精神病性うつ病の1例


多チャンネル近赤外線スペクトロコピーが示す広汎性発達障害の表情処理過程における前頭前野の賦活反応性の低下


ジェイゾロフト錠の使用実態下における安全性と有効性 第二報 -2つの特定使用成績調査の52週目までの解析結果-


DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.


Association Study of Fat-mass and Obesity-associated Gene and Body Mass Index in Japanese Patients with Schizophrenia and Healthy Subjects.

Fat-mass and obesity-associated (FTO) gene is known to be involved in the pathophysiology of obesity and a single-nucleotide polymorphism (SNP) rs9939609 of FTO gene is repeatedly confirmed to be associated with body mass index (BMI) and obesity. The aim of this study is to elucidate effects of FTO gene polymorphism on BMI in Japanese patients with schizophrenia and healthy subjects. Three hundred fifty one patients with schizophrenia and 342 age- and sex-matched healthy subjects participated in the study. Information on BMI and antipsychotic medication was also collected from patients and healthy subjects. Genotype of the FTO SNP rs9939609 was determined by TaqMan SNP Genotyping Assays. There was no significant difference in BMI between patients and healthy subjects. No significant difference in BMI was observed among any medications. We observed no significant difference in rs9939609 allele frequencies between patients and healthy subjects. There was a significant difference in BMI between healthy subjects with risk (AA or TA) genotypes and those with TT genotype. We also observed a significant positive correlation between the number of risk allele (A allele) and BMI in healthy subjects. Our study suggested that FTO rs9939609 polymorphism might have some impacts on the BMI in healthy subjects, but might not have same impacts on the BMI of patients with schizophrenia.

Clinical Psychopharmacology and Neuroscience


Clinical correlates associated with cognitive dysfunction in people with schizophrenia.


Meta-analysis of association studies between DISC1 missense variants and schizophrenia in the Japanese population.


One-year outcomes in schizophrenia after switching from typical antipsychotics to olanzapine in Japan: an observational study

The purpose of this study was to assess the 1-year clinical, functional, and safety-related outcomes following a switch to olanzapine of at least one typical antipsychotic drug in the previous regimen in the treatment of patients of schizophrenia in Japan. Using data from a large 1-year prospective, multicenter, naturalistic study of olanzapine for the treatment of schizophrenia in Japan, patients who were switched from any oral typical antipsychotic to olanzapine were identified. Mixed models for repeated measures, controlling for baseline demographics, were utilized to assess outcomes for clinical and functional measures. Of the 262 patients who switched from typical antipsychotics to olanzapine, 41% were outpatients and 59% were inpatients. Most of these patients were switched due to poor medication efficacy (71.0%) or medication intolerability (25.6%). Most patients (71.4%) completed the 1-year study. Clinically and statistically significant (P < 0.01) improvements were observed in patient illness severity and health-related quality of life, including improvements in global symptom severity and in positive, negative, depressive, and cognitive symptoms. Over half of the patients (58.3%) demonstrated a treatment response to olanzapine and 47.4% achieved symptom remission. Mean weight gain from baseline to endpoint was 2.31 ± 4.72 kg, with 30.4% of patients experiencing clinically significant weight gain (at least 7% of baseline weight). During this 1-year naturalistic treatment of schizophrenia patients in Japan, switching from typical antipsychotics to olanzapine resulted in significant improvements in patients' clinical and functional outcomes. Approximately one-third of patients had clinically significant weight gain. These findings highlight the favorable benefit to risk profile of switching to olanzapine following failure on typical antipsychotics.


Improved outcomes following a switch to olanzapine treatment from risperidone treatment in a 1-year naturalistic study of schizophrenia patients in Japan

This study assessed clinical and functional outcomes following a switch from risperidone to olanzapine in a 1-year naturalistic study of schizophrenia patients in Japan. We used data from a large 1-year prospective, multicenter, observational non-interventional study of individuals who were initiated on olanzapine for the treatment of schizophrenia in Japan. Current analyses focused on patients who were switched at study entry from risperidone to olanzapine (n = 258). Repeated measures analysis was employed to assess outcomes on validated measures. At study entry, 45% were inpatients and 55% outpatients. Participants were in their early 40s with mean illness duration of 14 years. Approximately half were male. Most were switched from risperidone to olanzapine due to poor medication efficacy (67.8%) rather than medication intolerability (29.1%). Most patients (67.8%) completed the 1-year study. Patients experienced clinically and statistically significant (P < 0.05) improvements in global symptom severity, positive, negative, depressive, and cognitive symptoms, health-related quality of life, and paid work rates. Most patients (59.2%) demonstrated treatment response to olanzapine and 43.4% experienced symptom remission. Mean weight gain was 2.19 kg, with one-third of patients (33.3%) experiencing clinically significant weight gain (≥7%). In this 1-year naturalistic study, inpatients and outpatients who were switched from risperidone to olanzapine experienced clinically and statistically significant improvements in their clinical and functional outcomes. One-third of all patients experienced clinically significant weight gain. Current findings highlight the favorable benefit-to-risk profile of switching to olanzapine therapy following treatment failure on risperidone among patients with schizophrenia in Japan.


Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population.


Functional genetic variation at the NRGN gene and schizophrenia: evidence from a gene-based case-control study and gene expression analysis.

Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P = 0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR = 1.14, P = 0.0019) and lower (OR = 0.85, P = 0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR = 1.10, P = 0.057) and rs2075713 (OR = 1.10, P = 0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z = 2.69, P = 0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z = 3.09, P = 0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics


Psychological care for anticipatory grief and mourning work to a family with a child with malignant glioma

悪性脳腫瘍患者家族の予期悲嘆への対応とグリーフケアを経験した事例


Multi-channel near-infrared spectroscopy reveals reduced activation in the prefrontal cortex during the facial expression processing in patients with pervasive developmental disorders

The purpose of the present study was to investigate whether individuals with pervasive developmental disorders (PDD) show differential activation during an emotional activation task compared with age- and sex-matched controls, by measuring changes in the concentration of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin, using near-infrared spectroscopy (NIRS). Fourteen patients with PDD and 14 age- and sex-matched healthy controls participated in the study. The relative changes of concentrations of oxyHb and deoxyHb were measured on NIRS during an implicit processing task of fearful expression using Japanese standard faces. PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. PFC dysfunction may exist in PDD.


両側視床下核深部脳刺激術を施行され左側電極Onによってうつ状態から躁状態に転じたパーキンソン病の一例


興奮性アミノ酸仮説に基づく統合失調症の薬物療法の試み NMDA受容体フルアゴニスト(グリシン，D-セリン，D-アラニン)の臨床エビデンス


子どもの悪性脳腫瘍再発に情緒不安定になった母親への心理的支援の事例

子どもの悪性脳腫瘍再発に情緒不安定になった母親への心理的支援の事例


ジェイゾロフト錠の使用実態下における安全性と有効性第一報 -使用成績調査およびパニック障害に関する特定使用成績調査の結果より-


統合失調症治療における認知機能とQOLの重要性

統合失調症治療における認知機能とQOLの重要性


精神症状を伴ったChurg-Strauss症候群の1症例

精神症状を伴ったChurg-Strauss症候群の1症例


Lithium decreases VEGF mRNA expression in leukocytes of healthy subjects and patients with bipolar disorder.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to be involved in the pathophysiology of mood disorders and the target of antidepressants. The aim of this study was to elucidate molecular effects of lithium on VEGF expression by using leukocytes of healthy subjects and patients with bipolar disorder. METHODS: Eight healthy male subjects participated in the first study. Lithium was prescribed for 2 weeks, enough to reach therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline, at 1- and 2-week medication, and at 2 weeks after stopping medication. VEGF mRNA levels were also examined in nine lithium-treated bipolar patients and healthy controls in the second study. RESULTS: In the first study, leukocyte counts were significantly increased at 2 weeks compared with those at baseline and were normalized after 2 weeks. VEGF mRNA levels were significantly decreased at 2 weeks and after 2 weeks compared with those at baseline. Consistent with the first study, VEGF mRNA levels were significantly decreased in the lithium-treated bipolar patients compared with healthy controls. CONCLUSIONS: Our investigation suggests that VEGF mRNA expression may be useful as a peripheral marker of the effects of lithium. Copyright © 2011 John Wiley & Sons, Ltd.


No association between the PCM1 gene and schizophrenia: A multi-center case-control study and a meta-analysis.

Alterations in centrosomal function have been suggested in the pathology of schizophrenia. The molecule pericentriolar material 1 (PCM1) is involved in maintaining centrosome integrity and in the regulation of the microtubule cytoskeleton. PCM1 forms a complex at the centrosome with the disrupted-in-schizophrenia 1 (DISC1) protein, which is a major susceptibility factor for schizophrenia. The association between genetic variants in the PCM1 gene and schizophrenia has been reported by several case-control studies, linkage studies and a meta-analysis. The aims of this study are to replicate the association between four single-nucleotide polymorphisms (SNPs) in the PCM1 gene and schizophrenia in a Japanese population (1496 cases and 1845 controls) and to perform a meta-analysis of the combined sample groups (3289 cases and 3567 controls). We failed to find a significant association between SNPs or haplotypes of the PCM1 gene and schizophrenia in the Japanese population (P>0.28). The meta-analysis did not reveal an association between the four examined SNPs and schizophrenia. Our data did not support genetic variants in the PCM1 gene as a susceptibility locus for schizophrenia.


Criterion and Construct Validity of the Cogstate Schizophrenia Battery in Japanese Patients with Schizophrenia

The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia. Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors. This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia.


Gene expression and association analysis of the epithelial membrane protein 1 gene in major depressive disorder in the Japanese population.

The epithelial membrane protein 1 (EMP1) plays a role in neuronal differentiation and neurite outgrowth, which are involved in the pathogenesis of major depressive disorder (MDD). We sought to determine whether the EMP1 gene is implicated in MDD. We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n=27 each). Next, we performed case-control association analyses (MDD, n=182; controls, n=350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P<0.001). The association analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls and male patients for marker rs7315725 (permutation P=0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population.


Quality of life and cognitive dysfunction in people with schizophrenia

The main purpose of the present study was to examine the relationship between quality of life (QOL) and cognitive dysfunction in schizophrenia. Subjects were 61 stabilized outpatients. Quality of life and cognitive function were assessed using the Quality of Life Scale (QLS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The BACS composite score and the BACS Verbal memory score were positively correlated with the QLS total score and two subscales. The BACS Attention and speed of information processing score had positive correlation with the QLS total and all the subscales scores. The PANSS Positive and Negative syndrome scores also had significant correlations with the QLS total score and all of the subscales. In addition, the CDSS score was negatively correlated with the QLS total score and some of the subscales. Stepwise regression analysis showed that the BACS Attention and speed of information processing score was an independent predictor of the QLS total score but it was less associated with the QLS than the PANSS Negative syndrome score and the CDSS score. The results suggest that negative and depressive symptoms are important factors on patients' QOL and also support the view that cognitive performance provides a determinant of QOL in patients with schizophrenia.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


統合失調症の最新薬物治療ガイドライン

統合失調症の最新薬物治療ガイドライン


Psychological features of pregnant women predisposing to depressive state during the perinatal period

周産期の抑うつに影響を与える心理特性に関する検討


The schizophrenia cognition rating scale Japanese version (SCoRS-J)

統合失調症認知評価尺度日本語版(SCoRS-J)


GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study.

Gamma-amino butyric acid (GABA) is thought to play a role in the pathophysiology of schizophrenia. High magnetic field proton magnetic resonance spectroscopy ((1)H-MRS) provides a reliable measurement of GABA in specific regions of the brain. This study measured GABA concentration in the anterior cingulate cortex (ACC) and in the left basal ganglia (ltBG) in 38 patients with chronic schizophrenia and 29 healthy control subjects. There was no significant difference in GABA concentration between the schizophrenia patients and the healthy controls in either the ACC (1.36+/-0.45 mmol/l in schizophrenia patients and 1.52+/-0.54 mmol/l in control subjects) or the ltBG (1.13+/-0.26 mmol/l in schizophrenia patients and 1.18+/-0.20 mmol/l in control subjects). Among the right handed schizophrenia patients, the GABA concentration in the ltBG was significantly higher in patients taking typical antipsychotics (1.25+/-0.24 mmol/l) than in those taking atypical antipsychotics (1.03+/-0.24 mmol/l, p=0.026). In the ACC, the GABA concentration was negatively correlated with the dose of the antipsychotics (rs=-0.347, p=0.035). In the ltBG, the GABA concentration was positively correlated with the dose of the anticholinergics (rs=0.403, p=0.015). To the best of our knowledge, this is the first study to have directly measured GABA concentrations in schizophrenia patients using (1)H-MRS. Our results suggest that there are no differences in GABA concentrations in the ACC or the ltBG of schizophrenia patients compared to healthy controls. Antipsychotic medication may cause changes in GABA concentration, and atypical and typical antipsychotics may have differing effects. It is possible that medication effects conceal inherent differences in GABA concentrations between schizophrenia patients and healthy controls.


The chitinase 3-like 1 gene and schizophrenia: evidence from a multi-center case-control study and meta-analysis.

The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in response to several environmental and psychosocial stresses. The expression level of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of patients with schizophrenia. Genetic variants of the CHI3L1 gene have been significantly associated with schizophrenia in two distinct ethnic groups, the Chinese and Irish populations. The aims of this study are to confirm the association between the CHI3L1 gene and schizophrenia in a Japanese population using the largest sample size to date (1463 cases and 1795 controls) and perform a meta-analysis of the combined samples (3005 cases, 3825 controls and 601 trios). We found significant associations between single nucleotide polymorphism (SNP) 4/rs4950928 (p=0.009), which is located in the promoter region of the CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most significant global p<0.001). As the meta-analysis of the combined samples showed significant heterogeneity among studies of SNP3/rs10399805 (p=0.026) and SNP4 (p<0.001), we performed meta-analyses separately in the Japanese (2033 cases and 2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios), the major groups analyzed in association studies of the CHI3L1 gene. The meta-analysis in Japanese populations showed stronger evidence for the association of schizophrenia with SNP4 (p=0.003), while the meta-analysis in Chinese populations showed an association with a different variant (SNP3) (p=0.003). We conclude that the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a susceptibility to schizophrenia in Asian populations.


緊張病状態を繰り返す高齢女性患者に対する維持修正電気けいれん療法の実施経験

緊張病状態を繰り返す高齢女性患者に対する維持修正電気けいれん療法の実施経験


Association Study Between the Pericentrin (PCNT) Gene and Schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia (SZ) and major depressive disorder (MDD), interacts with several proteins and some of them are reported to be genetically associated with SZ. Pericentrin (PCNT) also interacts with DISC1 and recently single-nucleotide polymorphisms (SNPs) within the PCNT gene have been found to show significant associations with SZ and MDD. In this study, case-controlled association analysis was performed to determine if the PCNT gene is implicated in SZ. Nine SNPs were analyzed in 1,477 individuals (726 patients with SZ and 751 healthy controls). No significant difference was observed between the controls and the patients in allelic frequencies or genotypic distributions of eight SNPs. Although allelic distribution of rs11702684 was different between the two groups (P = 0.042), the difference did not reach statistical significance after permutation correction for multiple comparisons. In the haplotypic analysis, we could not find any significant association in our subjects, either. This gene may not play a major role independently in the etiology of SZ in the Japanese population.


No association between Rho-associated coiled-coil forming protein serine/threonine kinase1 gene and schizophrenia in the Japanese population.


Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population.

The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics


Positive association of the pericentrin (PCNT) gene with major depressive disorder in the Japanese population.

BACKGROUND: Pericentrin (PCNT) interacts with disruption-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). We sought to determine whether the PCNT gene is implicated in MDD. METHODS: We performed case-control association analyses in the Japanese population. We analyzed 9 single nucleotide polymorphisms (SNPs) in 173 patients with MDD and 348 healthy controls. RESULTS: We found a significant allelic association between 3 SNPs (rs3788265, rs2073376 and rs2073380) of the PCNT gene and MDD (p = 0.006, 0.005 and 0.021, respectively). After correction for multiple testing, 2 SNPs (rs3788265 and rs2073376) retained significant allelic associations with MDD. In addition, we found a significant association between the 2 marker haplotypes (r3788265 and rs2073376) and MDD (permutation p = 0.011). LIMITATIONS: Our sample was small and comprised only Japanese participants. In addition, owing to the late onset of MDD, it is possible that the disorder will develop in at least some participants in our control group. Finally, we did not show how SNPs of the PCNT gene alter its function. CONCLUSION: Our results suggest that genetic variations in the PCNT gene may play a significant role in the etiology of MDD in the Japanese population.


Association study of the G72 gene with schizophrenia in a Japanese population: a multicenter study.

G72 is one of the most widely tested genes for association with schizophrenia. As G72 activates the D-amino acid oxidase (DAO), G72 is termed D-amino acid oxidase activator (DAOA). The aim of this study is to investigate the association between G72 and schizophrenia in a Japanese population, using the largest sample size to date (1774 patients with schizophrenia and 2092 healthy controls). We examined eight single nucleotide polymorphisms (SNPs), which had been associated with schizophrenia in previous studies. We found nominal evidence for association of alleles, M22/rs778293, M23/rs3918342 and M24/rs1421292, and the genotype of M22/rs778293 with schizophrenia, although there was no association of allele or genotype in the other five SNPs. We also found nominal haplotypic association, including M15/rs2391191 and M19/rs778294 with schizophrenia. However, these associations were no longer positive after correction for multiple testing. We conclude that G72 might not play a major role in the risk for schizophrenia in the Japanese population.


Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine.

OBJECTIVE: The aim of the present study was to compare the effects on serum cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor, and kamishoyosan, a Japanese traditional medicine, in midlife women with psychological symptoms. METHODS: Seventy-six women with psychological symptoms such as anxiety and mild depression as menopausal symptoms were enrolled in this study. Thirty-eight women received oral administration of 10mg paroxetine every day, and 38 women received oral administration of kamshoyosan every day for 6 months. Overall climacteric symptoms were assessed using Greene's climacteric scale. Serum levels of cytokines were measured using a multiplexed human cytokine assay. RESULTS: Greene's total scores in both women treated with paroxetine and in women treated with kamishoyosan decreased significantly. Percentage decreases in Greene's total, psychological and vasomotor scores during the 6-month period in the paroxetine group were significantly greater than those in the kamishoyosan group. Serum IL-6 concentration in women treated with paroxetine decreased significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory protein (MIP)-1beta and monocyte chemoattractant protein-1 in women treated with paroxetine decreased significantly. On the other hand, serum IL-6 concentration in women treated with kamishoyosan decreased significantly, but other serum concentrations did not change significantly. CONCLUSION: Decrease in IL-6 concentration may be involved in the mechanism of the actions of both paroxetine and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be useful as a marker of treatment. The action of paroxetine may also be associated with decreases in IL-8, IL-10, MIP-1beta.


Metabolite changes and gender differences in schizophrenia using 3-Tesla proton magnetic resonance spectroscopy (1H-MRS).

A change in the glutamatergic system is thought to play an important role in the pathophysiology of schizophrenia. The aim of this study was to investigate the changes in metabolites, including glutamate (Glu), in the anterior cingulate cortex (ACC) and the left basal ganglia (ltBG) of patients with chronic schizophrenia using proton magnetic resonance spectroscopy ((1)H-MRS). In addition, since gender differences in this illness were known, we examined the effects of gender on these metabolites. The (1)H-MRS was performed on the ACC and ltBG of 30 patients with schizophrenia and 25 healthy individuals who acted as the control group. The levels of Glu, glutamine (Gln), creatine plus phosphocreatine (Cre), myo-inositol (mI), N-acetylaspartate (NAA), and choline-containing compounds (Cho) were measured. Two-way analysis of variance revealed that the illness significantly affected the levels of Glu and mI in the ACC; both metabolites were lower in the patients with schizophrenia as compared to the control subjects. The results also revealed that gender significantly affected the level of Gln in the ACC and the levels of Cre and NAA in the ltBG; the level of Gln in the ACC were higher in male subjects versus female subjects, whereas Cre and NAA levels in the ltBG were lower in male subjects as compared to female subjects. These results confirmed a change in the glutamatergic system and suggested an involvement of mI in the pathophysiology of schizophrenia.


Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects

Genetic variants of the transcription factor 7-like 2 (TCF7L2) gene affect the risk of type 2 diabetes in populations with multiple ethnic groups. However, a comprehensive survey of this gene has not been done for a Japanese population. Thus, we conducted this gene-based association study, in which the common genetic variants were analyzed. Using 24 Japanese type 2 diabetic subjects, we first screened a 9.5 kb region, which included the entire coding sequence, to assess potential functional variants of TCF7L2. Sequencing revealed a common coding variant (Pro477Thr) in exon 14 of TCF7L2 that was not enrolled in the public SNP database. Nineteen SNPs and the microsatellite DG10S478 were genotyped across the gene in 2,877 unrelated Japanese subjects. This independent screen identified the previously reported rs7903146 with a strongest association (allele P = 0.0001, odds ratio = 1.59 [95% confidence interval 1.25-2.01]), but there was no significant association between Pro477Thr and type 2 diabetes (allele P = 0.64). Expression of the Pro477Thr variant did not alter TCF7L2 expression in 30 lymphoblast cells. Although a genotypic effect of Pro477Thr on expression of TCF7L2 was not apparent, Pro477Thr was identified as a common variant of TCF7L2 in 2,877 Japanese subjects. Further functional studies are required to determine the possible effect of this coding variant on type 2 diabetes.


The brief assessment of cognition in schizophrenia Japanese version (BACS-J)

統合失調症認知機能簡易評価尺度日本語版(BACS-J)


Construction and reliability of the Japanese version of the Adolescent Egocentrism-Sociocentrism(AES) scale and its preliminary application in the Japanese university students

In recent years, the problem of interpersonal relationships has been reported to be associated with various adolescent psychiatric problems. Egocentrism is one factor related to the problem of interpersonal relationships. The Adolescent Egocentrism-Sociocentrism (AES) scale is used to assess egocentrism in Western countries, but no such scale has been developed in Japan. The purpose of our current study was to develop the Japanese version of the AES scale and investigate the relationship between the egocentrism assessed by the AES scale and the self-consciousness assessed by the Japanese version of the self-consciousness scale. The original version of the AES scale was first translated into Japanese using the forward-backward method and examined for factorial reliability and validity. The results demonstrated that the Japanese version of the AES scale shows adequate factorial reliability and validity, but different from the original version the "egocentrism personal fable" subscale which measures the feeling that oneself is special and unique was not extracted in the Japanese version. We found a moderate correlation between the non-social focuses of the AES scale and the public self-consciousness subscale of the self-consciousness scale. This correlation suggests that a strong attention of others' view on oneself results in the avoidance of others. The Japanese version of the AES scale can examine egocentrism adequately together with sociocentrism and non-social focuses. As this scale is self-reporting and easy to complete, it may have practical utility in a clinical setting.

The Journal of Medical Investigation : JMI


Predictors of subjective and objective quality of life in outpatients with schizophrenia.

AIM: In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease-specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL. METHODS: Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively. RESULTS: Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL. CONCLUSION: Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL.


TGFBR2 gene expression and genetic association with schizophrenia

TGFBR2 gene is a tumor suppressor gene located at chromosome 3p22, and the locus is reported to be linked with schizophrenia susceptibility. According to the previous studies, a reduced incidence of cancer is observed in schizophrenic patients compared with the general population and tumor suppressor genes may be associated with schizophrenia. We measured the mRNA expression of TGFBR2 gene in the peripheral leukocytes from 19 medication-free schizophrenics and 25 medication-free major depressive patients compared with age- and sex-matched control subjects using a quantitative real-time PCR method. We also followed up the TGFBR2 mRNA expression levels from 13 schizophrenics after several weeks - antipsychotic treatments. The TGFBR2 mRNA levels of medication free schizophrenics were significantly higher than those of control subjects and decreased to almost the same level as controls after antipsychotic treatment. On the other hand, the TGFBR2 mRNA levels of medication-free major depressive patients were not significantly different from controls. In genetic studies, we failed to find any association between the TGFBR2 gene and schizophrenia with 10 SNPs of TGFBR2 gene in Japanese subjects (279 subjects each) and there was no significant difference with haplotype analysis, either. Our results suggest that the TGFBR2 gene itself does not link to schizophrenia but that the TGFBR2 mRNA levels in the peripheral leukocytes may be a potential state marker for schizophrenia.


Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population.

The phosphodiesterase 4B (PDE4B) gene is located at 1p31, a susceptibility region for schizophrenia (SZ). Moreover, PDE4B interacts with DISC1, which is a known genetic risk factor for SZ. Recently, it was reported that the PDE4B gene is associated with SZ in Caucasian and African American populations. In this study, case-controlled association analyses were performed in the Japanese population to determine if the PDE4B gene is implicated in SZ. Thirteen single nucleotide polymorphisms (SNPs) were analyzed in 444 schizophrenic patients and 452 control subjects. Three SNPs (rs2180335, rs910694 and rs472952) were significantly associated with SZ after applying multiple test correction (p=0.039, 0.004 and 0.028). In addition, a significant association was found between specific haplotypes (rs2180335 and rs910694) and SZ (permutation p=0.001). Our result suggests that variations at the PDE4B locus may play a significant role in the etiology of SZ in the Japanese population.


No association between the NDE1 gene and schizophrenia in the Japanese population.


FKBP5, SERT and COMT mRNA expressions in the peripheral leukocytes during menstruation cycle in healthy reproductive females.

There have been several evidences that the mRNA expressions in the peripheral leukocytes may indicate not only physical but also psychological states. The purpose of this study is whether the mRNA expressional changes in the leukocytes are related to the mental states across the menstrual cycle in reproductive healthy female subjects. Thirty-eight female subjects (22.4+/-1.4 year-old) were participated in this study at three menstruation cycle periods (menstrual, follicular and luteal phase). The FKBP5 (FK506-binding protein gene), SERT (serotonin transporter gene) and COMT (catechol-o-methyltransferase gene) mRNA expressions in the leukocytes were determined with hormonal data. The psychological changes were assessed with self-rating hospital anxiety and depression scale (HADS). Only one thirds of subjects (n=12) had regular menstrual cycles during the experiment. So we analyzed the data from these 12 subjects. The anxiety score of each subject was changed across the menstrual cycle (Friedman test: P<0.05). The FKBP5 mRNA expression was significantly lower in the follicular phase than in the other phases but no changes were seen in either SERT or COMT mRNA expressions among the phases. In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA.


The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with psychotic feature and suicidal behavior in Japanese major depressive patients

Recent researches have suggested that brain-derived neurotrophic factor (BDNF) may be implicated in the pathophysiology of mood disorder. This study examined the association between the BDNF Val66Met polymorphism and major depressive disorder (MDD) in a Japanese population. We genotyped the BDNF Val66Met polymorphism in 154 major depressive patients and 154 age- and sex-matched control subjects. The genotypic distributions and allele frequencies were similar among the patients and control subjects. When the relationships of the polymorphism with several clinical variables (i.e., age, sex, age of onset, number of episode, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of Met allele had significant effects on psychotic feature and suicidal behavior and family history. These results suggest that the BDNF Val66Met polymorphism is not related to the development of MDD but related to clinical features of MDD in a Japanese population.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics


Brief assessment of cognition in schizophrenia: validation of the Japanese version.

This preliminary study was performed to test the reliability and validity of the Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a Japanese-language version (BACS-J). The subjects for the present study were 30 outpatients with chronic schizophrenia. Each subject gave written informed consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77. The BACS-J composite score was significantly correlated with all primary measures of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention, and executive function). All BACS-J primary measures and the composite score were significantly correlated between two assessments. The mean score of the Digit Sequencing Task and composite score on the second assessment were significantly larger than those on the first assessment. All BACS-J primary measures except the Symbol Coding Task were significantly correlated with relevant standard neurocognitive tests. Also, the BACS-J composite score was significantly correlated with all standard neurocognitive tests except the Continuous Performance Test. A principal components analysis with varimax rotation resulted in a three-factor solution (executive function and memory; motor speed and general cognitive functions; and working memory). This preliminary study indicates that the BACS-J is a reliable and practical scale to evaluate cognitive function.


Association between PNPO and schizophrenia in the Japanese population

Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically-active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population.


Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder

Vascular endothelial growth factor (VEGF) has been implicated in neuronal survival, neuroprotection, regeneration, growth, differentiation, and axonal outgrowth, which are known to be involved in the pathophysiology of major depressive disorder (MDD). Recently, the VEGF mRNA expression in the peripheral leukocytes from Alzheimer's disease or cardiovascular disease was reported to be changed. We hypothesized that the expression of the VEGF mRNA in the peripheral leukocytes may be a good candidate for the biological marker for MDD. Thirty two patients with MDD and age- and sex-matched control subjects were included in this expression study. The VEGF mRNA levels in the peripheral leukocytes from drug-naive MDD patients were significantly higher than those from the control subjects and the magnitude of the decrease of VEGF mRNA after 8-week treatment significantly correlated with clinical improvement. Then, we genotyped two single nucleotide polymorphic markers of VEGF gene, which were reported to be associated with amyotrophic lateral sclerosis and Alzheimer's disease, in patients with MDD and control subjects (n=154, each). We did not find any significant association between these markers and MDD or its clinical subtypes. Our investigation indicates that the higher expression levels of VEGF mRNA in the peripheral leukocytes are associated with the depressive state and their recovery after treatment may be associated with the clinical improvement.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression

Gene expressions of the peripheral leukocytes in depressive patients might reflect the systemic dysfunction of major depression. We determined mRNA expression levels of Histone deacetylase 5 (HDAC5) gene and cyclic AMP response element-binding protein 1 (CREB) gene in the leukocyte of depressive patients. HDAC5 and CREB are reported to be important targets of antidepressants, the latter being located in the downstream of the former in lymphocyte calcium signaling. 25 patients with major depression and 25 age- and sex-matched healthy controls were included in this study. Twenty patients were able to be followed up until the 8 week-treatment. The mRNA levels were determined by a quantitative RT-PCR method. Levels of HDAC5 and CREB mRNA were significantly higher in drug-free depressive patients than those of controls and the higher mRNA levels decreased to control levels after 8-week paroxetine treatment. There were positive correlation between levels of HDAC5 and CREB. Our results suggest the alteration of HDAC5 and CREB gene expression in the systemic pathophysiology of major depression.


Association of serum cytokine concentrations with psychological symptoms in midlife women.

The purpose of the present study was to clarify the association of serum cytokine concentrations, determined using a multiplexed cytokine assay, with psychological symptoms in midlife women. Fifty-three peri- and post-menopausal women with and without psychological symptoms in Greene's climacteric scale were enrolled in this study. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Serum interleukin (IL)-6 concentration in women with psychological symptoms (2.71+/-047 pg/ml) was significantly (p=0.009) higher than that in women without psychological symptoms (0.98+/-0.18 pg/ml). Serum IL-8 concentration in women with psychological symptoms (33.4+/-8.17 pg/ml) was also significantly (p=0.022) higher than that in women without psychological symptoms (7.87+/-1.64 pg/ml). In addition, serum IL-10 concentration in women with psychological symptoms (0.74+/-0.26 pg/ml) was significantly (p=0.048) higher than that in women without psychological symptoms (0.07+/-0.04 pg/ml). Tumor necrosis factor (TNF)-alpha in serum was detected only in women with psychological symptoms. Serum IL-2 concentration in women with psychological symptoms tended (p=0.066) to be higher than that in women without psychological symptoms. No significant differences were found between levels of other cytokines in women with and without psychological symptoms. Psychological stress manifested as climacteric symptoms in midlife women may be associated with increases in serum concentrations of IL-6, IL-8, IL-10, and TNF-alpha.


Gene expression in the peripheral leukocytes and association analysis of PDLIM5 gene in schizophrenia

PDLIM5 modulates neuronal calcium signaling, co-localizes with synaptic vesicles of neurotransmitters and positive association between its gene and schizophrenia was reported but its relation is still ambiguous. The differential expression of the PDLIM5 gene both in the brain and in the lymphoblasts has been found in schizophrenia compared to control subjects. In this study, we measured the expression level of the PDLIM5 gene transcripts in the peripheral leukocytes from 19 medication-free and 21 chronically medicated schizophrenic patients as well as age- and sex-matched control subjects using a quantitative real-time PCR method. The mRNA levels of the PDLIM5 gene in the leukocytes of medication-free schizophrenic patients were significantly higher than those of control subjects. On the other hand, our group has previously shown that its mRNA expression in the leukocytes of medication-free major depressive patients was significantly lower compared with controls. There was no difference in the PDLIM5 mRNA levels between chronic schizophrenic patients with antipsychotic medication and their controls. Further, we failed to find any genetic association between the PDLIM5 gene and schizophrenia with six single nucleotide polymorphics (SNPs) of the PDLIM5 gene in Japanese subjects (279 subjects each) and there was no significant relation between PDLIM5 gene and schizophrenia with the haplotype analysis (P=0.48), either. We suggest that the higher expression levels of the PDLIM5 mRNA in the peripheral leukocytes may be a candidate marker for medication-free schizophrenic patients.


The Influence of Obsessive Compulsive Symptoms on Quality of Life among the Female Nursing Staffs

女性看護職の強迫傾向が主観的QOLに及ぼす影響

Background: The influence of obsessive compulsive symptoms on subjective Quality of Life (QOL) among the woman nursing staff has been scarcely studied. Subject and methods: We examined the correlations of the scores on the Toronto Alexithiymia Scale (TAS-20) with the scores on the Maudsley Obsessive Compulsive Inventory (MOCI). We also assessed the influence of obsessive compulsive symptoms measured by the MOCI or depressive symptoms by the Zung Self-rating Depression Scale (SDS) on subjective QOL by the Brief Version of World Health Organization Quality of Life Assessment (WHO-QOL26) in the staff of 221 female nursing at a general hospital. The correlations of the MOCI or the SDS scores with the WHO-QOL26 total (t-QOL) and the domain scores ("physical", "psychological", "social", and "environmental" domains) were assessed by Spearman rank-correlations. Results: The TAS-20 total scores and the subfactor scores of "Difficulty identifying feelings", and "Difficulty describing feelings" positively correlated with the MOCI scores. Spearman rank-correlations showed negative correlations of the t-QOL with the MOCI and the SDS scores. The MOCI scores revealed significant negative correlations with "physical" and "psychological" but no correlation with "social" and "environmental", though the SDS scores showed significant negative correlations with each domain. The MOCI scores revealed significant negativecorrelations with the t-QOL only in the group in their twenties but the SDS scores showed significant negative correlations with the t-QOL in the group ranging from twenties to fifties. Only in over-fifties-group the MOCI scores revealed positive correlations with "social" domain. Conclusions: Among Japanese female nursing staff in the present study, alexithiymia by the TAS-20 affects on obsessive compulsive symptoms by the MOCI. Both obsessive compulsive symptoms and depressive symptoms had negative effects on their subjective QOL. While depressive symptoms showed negative correlations withsubjective QOL in each age bracket and on each domain, obsessive compulsive symptoms had negative correlations on the subjective QOL only in the younger age group and just on subjective "physical" and "psychological" well-beings. Obsessive compulsive symptoms would improve subjective "social" functioning in the mature age group.

看護職は高い専門性や自律性を求められると同時に,確認や清潔などの徹底も要求される.職場適応障害や燃え尽き症候群など心身医学的治療を要する症状を訴える者も多い.女性看護職に対する質問紙調査では強迫傾向が指摘される.われわれは,心身医学的見地より女性看護職の強迫傾向を検討し,強迫傾向と抑うつ度がQuality of Life (QOL)に与える影響の違いを比較した.自己記入式質問紙MOCI邦訳版(Maudsley Obsessional Compulsive Inventory)による強迫傾向群は16.3%と多かった.心身症患者の心理的特徴とされるアレキシサイミア(失感情症:alexithiymia)傾向は,強迫傾向に有意な相関を示した.アレキシサイミアの中でも「感情の同定困難因子」が,強迫傾向の「確認」「優柔不断」「疑惑」の高さと関係していた.抑うつ度は年齢層やQOL構成項目に限定されず,主観的QOLの低さと相関した.しかし強迫傾向は,若年女性看護職では「身体的領域」「心理的領域」の主観的QOLの低さと相関し,熟年看護職においては「社会的関係」の主観的QOLの高さと相関し,年齢や主観的QOLの領域により異なる影響をもたらす可能性が示唆された.若年看護職は強迫傾向と同時にアレキシサイミア傾向も高く,アレキシサイミアの中でも感情の同定困難と主観的QOLの低さとが関係していた.今後,このような若年看護職に対する心理的サポートをどのようなかたちで,どのような方法で行っていくのかが問われ,心身医学的検討が待たれるところである.

Japanese Journal of Psychosomatic Medicine


Clinical Features of Patients with Obsessive-compulsive Disorder showing Different Pharmacological Responses

強迫性障害の薬物応答性と臨床特徴について


Subjective and objective measures of quality of life have different predictors for people with schizophrenia.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.


Gene expression and association analysis of LIM (PDLIM5) in major depression.

LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n=130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant.


Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.


Activation of the prefrontal cortex during the Wisconsin Card Sorting Test as measured by multichannel near-infrared spectroscopy.

The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system. A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.


Correlation between the plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia

The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.


Serotonin transporter mRNA expression in peripheral leukocytes of patients with major depression before and after treatment with paroxetine.

Serotonin transporter (5HTT) is thought to be involved in the pathophysiology of major depression and the target of antidepressants. We hypothesized that 5HTT mRNA levels in peripheral leukocytes may be associated with depressive states and the therapeutic response to antidepressant treatments. Fifteen patients with major depression and age-, sex-matched control subjects were studied. 5HTT mRNA levels were determined with quantitative real-time PCR method. 5HTT mRNA levels in leukocytes were significantly higher in depressive patients at baseline (before medication) than in control subjects. 5HTT mRNA levels were decreased significantly after 8 weeks of paroxetine medication compared with those at baseline. Our investigation suggested that the increased expression of 5HTT mRNA in peripheral leukocytes may be related with the pathophysiology of depression and its reduction after treatment may reflect the adaptive change induced by the antidepressant.


Hemodynamic changes in the prefrontal cortex during mental works as measured by multi channel near-infrared spectroscopy (NIRS)

To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals.

The Journal of Medical Investigation : JMI


Central pontine myelinolysis associated with a hypoglycemic coma in anorexia nervosa


Expression analysis of psychological stress-associated genes in peripheral blood leukocytes

In this study, we have developed a microarray including 1467 cDNAs that were selected to specifically measure stress response in peripheral blood leukocytes. Venous blood was collected from 10 graduate students 2 h before and 2 or 24 h after an open presentation for their Ph.D. The mRNA levels in leukocytes were compared with those prepared 4 weeks before the presentation. Hierarchical cluster showed that distinct groups of genes uniformly changed their expression values in response to the stress. Bayesian t test identified significantly up-regulated 49 genes and down-regulated 21 genes. Most of them are categorized into cytokines, cytokine receptors, growth- or apoptosis-related molecules, and heat shock proteins, suggesting that stressful life events trigger acute responses in leukocytes. Our results suggest that gene expression profile in peripheral blood leukocytes may be a potentially useful method for the assessment of complex stress responses.


The effect of milnacipran (serotonin noradrenaline reuptake inhibitor) on memory in Korsakoff's syndrome after encephalitis


Relation between estradiol and negative symptoms in men with schizophrenia

The authors tested the hypothesis that estradiol would be associated with negative symptoms in 30 male schizophrenia inpatients. Medications were switched from typical to atypical antipsychotics. Estradiol concentrations were inversely correlated with negative symptoms significantly before the switch and at a trend level of significance after the switch. Changes in negative symptoms were positively correlated with those in estradiol concentrations at a trend level of significance. Estradiol could be a biological marker for negative symptoms even in male schizophrenia patients.

The Journal of Neuropsychiatry and Clinical Neurosciences


Fluvoxamine induced complex partial seizure in the treatment of bulimia nervosa


The Elgin Behaviooral Rating Scale日本語版(JEBRS)


Left atrial thrombosis associated with antipsychotic drugs

The authors report a case of a 36-year-old shizophrenic patient with left atrial thrombosis. There have been small number of case reports of antipsychotic drugs-associated thromboembolic events. All of them are venous ones. This paper describes the first case of atrial thrombosis associated with antipsychotic drugs.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


低Na血症を認めなかったにもかかわらず中心性橋髄鞘崩壊症を合併した摂食障害の1例


作業療法およびデイケア導入により頻発した対人トラブルや衝動行為の改善を認めた慢性疼痛の1例


Acute abdominal distension secondary to urinary retention in a patient after alcohol withdrawal.

Several cases of alcohol-induced bladder dysfunction have been reported previously, but the mechanism of its development is varied and unclear. We report a case of symptomatic abdominal distension due to urinary retention after alcohol withdrawal. The timing of the onset suggests that it was induced by alcohol withdrawal.


Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

The Journal of Medical Investigation : JMI


The Schizophrenia Quality of Life Scale 日本語版(JSQLS)


精神科臨床における下肢深部静脈血栓症

精神科臨床における下肢深部静脈血栓症


A case of social phobia with obsessive-compulsive symptoms improved by paroxetine in combination with risperidone


Impact of a switch from typical to atypical antipsychotic drugs on quality of life and gonadal hormones in male patients with schizophrenia

We investigated the effects of a switch from typical to atypical antipsychotic drugs (olanzapine, n=8; perospirone, n=9; or quetiapine, n=13) on quality of life and hypothalamo-pituitary-gonadal axis hormones. The subjects were 30 male chronic schizophrenia inpatients. The assessment was done before and after the switch. After the switch, (i) scores of the Brief Psychiatric Rating Scale total and three factors (anxiety-depression, anergia, and thought disturbance) decreased, (ii) the overall severity score of the Drug Induced Extra-Pyramidal Symptoms Scale tended to decrease, (iii) prolactin decreased but gonadal hormones remained unchanged, and (iv) scores on all three subscales (psychosocial, motivation/energy, and symptoms/side effects) in the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS) decreased. However, there were no significant group effects, or time-by-group interactions. In addition, score changes from baseline in psychosocial and motivation/energy subscales in the JSQLS were correlated with those in psychotic symptoms, particularly in the anxiety-depression factor. Moreover, responders had been taking lower doses of typical antipsychotic drugs, and had higher serum estradiol concentrations than non-responders before the switch. The study indicated that the switch to atypical antipsychotic drugs was effective in reducing elevated prolactin without affecting the gonadal hormones and in improving quality of life patients who had been treated with typical antipsychotic drugs.


バルプロ酸が用量依存的に病相予防効果を発揮した双極性感情障害の1症例

バルプロ酸が用量依存的に病相予防効果を発揮した双極性感情障害の1症例


高用量のFluvoxamineが奏効した強迫買いを含む衝動制御障害の1症例

高用量のFluvoxamineが奏効した強迫買いを含む衝動制御障害の1症例


定型抗精神病薬から非定型抗精神病薬へのスイッチングが統合失調症患者のQOLおよび性腺機能に及ぼす影響


長期にわたる摂食障害が躁状態発症とともに消失した一症例

長期にわたる摂食障害が躁状態発症とともに消失した一症例


Lithium投与中の甲状腺中毒症(無痛性甲状腺炎)

Lithium投与中の甲状腺中毒症(無痛性甲状腺炎)


Impact of risperidone medication on quality of life and gonadal axis hormones in schizophrenia male patients with acute exacerbation

We investigated the effects of risperidone on quality of life (QoL) and hypothalamo-pituitary-gonadal (HPG) axis hormones. In this prospective, open-label study, the subjects were 10 male schizophrenia patients with acute exacerbation. After a mean period of 44.6 d treatment, patients were taking a mean dose of 7.0 mg risperidone daily. After treatment, we found that (i) the total BPRS score decreased, (ii) the scores on psychosocial and motivation/energy subscales in the Japanese version of the Schizophrenia Quality of Life Scale decreased, but the scores on symptoms/side-effects subscale did not, (iii) prolactin increased, but the HPG axis hormones did not change, and (iv) the mean plasma homovanillic acid concentration decreased. Eight patients needed anticholinergic medications, one patient reported impotence, and one patient reported ejaculatory dysfunction during treatment. Our findings suggested that risperidone might improve psychosocial and motivation/energy QoL subscales, and increase prolactin without affecting the HPG axis hormones.

The International Journal of Neuropsychopharmacology


Effects of quetiapine on gonadal axis hormones in male patients with schizophrenia: a preliminary, open study

The authors investigated the effects of a novel antipsychotic agent, quetiapine administration on hypothalamo-pituitary-gonadal (HPG) axis hormones in patients with chronic schizophrenia. In this prospective, open-label study, the subjects were nine male inpatients. We tried to switch the patients from typical antipsychotics to quetiapine. The patients took a mean dose of 636.1 mg quetiapine daily for a mean period of 104.7 days. (i) Although the total Brief Psychiatric Rating Scale score did not show significant changes, no patients needed anticholinergic medications after the switch. (ii) Before the switch, only the prolactin concentration showed a significant difference between the patients and normal subjects. After the switch, neither prolactin nor HPG axis hormone concentrations showed significant differences between the groups. Our preliminary results indicated that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenia patients with normal levels of HPG axis hormones.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


Temperament,character,and eating attitudes in japanese college women

精神分裂病と本態性パーキンソン病は，前者が脳内ドパミンの過剰仮説により説明されることが多く，後者がドパミン欠乏により生ずることにより，互いに相反する疾患として一般的には理解され，合併することはないと考えられている．しかし，筆者らはその治療経過から，全く相反する疾患として捉える根拠がないことを，その発症機制についての検討を加えて報告した．


Repetitive behaviors in chronic schizophrenia: using the Japanese version of the Elgin Behavior Rating Scale (JEBRS)

The main aim of this study was to test the reliability and value of the Japanese Elgin Behavior Rating Scale (JEBRS) with 92 schizophrenia patients. Cronbach's alpha for the JEBRS was 0.61. All inter-rater reliability coefficients were in the satisfactory range. The JEBRS had a high stability over time. Almost all of the correlations among the nine item scores and total score in the JEBRS were significant. The total score for nine repetitive behaviors in the JEBRS was positively correlated with positive and negative symptoms. This study showed that the JEBRS is a useful and reliable scale.


Levodopa improved rapid eye movement sleep behavior disorder with diffuse Lewy body disease


発作後もうろう状態時に多飲水し水中毒の症状を呈したてんかん患者の1症例

発作後もうろう状態時に多飲水し水中毒の症状を呈したてんかん患者の1症例


Olanzapineにより知覚変容発作を来した統合失調症の1症例

Olanzapineにより知覚変容発作を来した統合失調症の1症例


Schizophrenia Quality of Life Scale: validation of the Japanese version

This study was performed to test the validity and value of the Schizophrenia Quality of Life Scale as an assessment tool in a Japanese-language version (JSQLS). The subjects for the present study were 55 inpatients with a diagnosis of schizophrenia as defined by DSM-IV. The JSQLS was administered together with two other self-report measures, the Medical Outcomes Study 36-item short-form health survey questionnaire (SF-36) and the WHO QOL-26, to assess validity. Psychotic symptoms and extrapyramidal symptoms were assessed using the BPRS and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), respectively. All the scales (psychosocial, motivation/energy and symptoms/side effects) showed good internal consistency reliability (Cronbach's alpha=0.93, 0.73 and 0.80, respectively). The correlations of items with their scale total revealed that almost all items were significantly correlated with their own scale score. There were associations with relevant SF-36, WHO QOL-26, and DIEPSS scores. From the results of the testing of the reliability and validity of the JSQLS, it is concluded that the JSQLS is a simple and reliable scale.


Paroxetineが著効した幼児期発症の社会恐怖の一症例

Paroxetineが著効した幼児期発症の社会恐怖の一症例


Silent thyroiditis associated with short-term lithium therapy


Personality profiles in patients with eating disorders

The present review focused on the personality profiles of patients with eating disorders. Studies using the Structured Clinical Interview for DSM-III-R Personality Disorder showed high rates of diagnostic co-occurrence between eating disorders and personality disorders. The most commonly observed were histrionic, obsessive-compulsive, avoidant, dependent and borderline personality disorders. Studies using the Cloninger's personality theory suggested that high Harm Avoidance might be relevant to the pathology of anorexia nervosa and high Novelty Seeking and Harm Avoidance to bulimia nervosa. Moreover, high Self-Directedness was suggested to be associated with favorable outcome in bulimia nervosa. The assessment of personality in a cross-sectional study, however, might be influenced by the various states of the illness. Therefore, a sophisticated longitudinal study will be required to advance this area of research.

The Journal of Medical Investigation : JMI


Radiofrequency catheter ablation enabled antipsychotic treatment in a schizophrenic patient with idiopathic ventricular tachycardia


The hypothalamic-pituitary-adrenal axis in chronic schizophrenic patients long-term treated with neuroleptics

The authors investigated the hypothalamic-pituitary-adrenal (HPA) axis of regularly medicated schizophrenic patients. The subjects were 53 patients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) criteria for schizophrenia. Each patients gave informed consent for the research. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Based on the dosages of neuroleptics (NLPs), the subjects were classified into two groups: those with lower dosages (LD) and those with higher dosages (HD). (a) The medicated schizophrenic patients had significantly higher plasma corticotropin (ACTH) levels than the normals. (b) There was no significant difference in plasma cortisol levels between the schizophrenic patients and normals. (c) There was a significant difference in plasma ACTH levels between the HD and normal groups, but not between the LD and normal groups. (d) There was no significant difference in administration periods of NLPs, positive (POS) or negative symptoms (NES) between the HD and LD groups. (e) There was a positive correlation between the plasma ACTH and plasma cortisol levels in patients. Our results showed that, in chronic schizophrenic patients long-term treated with NLPs, ACTH secretion was elevated.


薬原性錐体外路症状を有する症例におけるquetiapineへの切り替え効果

薬原性錐体外路症状を有する症例におけるquetiapineへの切り替え効果


強迫性障害におけるproton MRSによる評価 --- 特にグルタミン酸とグルタミン代謝に対して

Japanese Journal of Magnetic Resonance in Medicine


長期にわたる過食と嘔吐がfluvoxamineにより消失した中年男性の一症例

長期にわたる過食と嘔吐がfluvoxamineにより消失した中年男性の一症例


Evaluation of quazepam treatment of anxiety with insomnia


The serotonin syndrome: investigation using the Japanese version of the Serotonin Syndrome Scale

This preliminary study was performed to investigate the prevalence of the serotonin syndrome in a group of Japanese patients in a clinical setting and to test the reliability and value of the Serotonin Syndrome Scale (SSS) as an assessment tool in a Japanese-language version (JSSS). Twenty-three patients, all being treated with serotonin agonists, gave informed consent to participate. Only one patient fulfilled strict diagnostic criteria of the serotonin syndrome and none of the JSSS scores reached the cutoff point of the SSS. Cronbach's alpha coefficient for the JSSS was 0.56. All inter-rater reliability coefficients were in the excellent range, and the JSSS had a high stability over time. The mean dose of fluvoxamine in the subgroup with high scores on the JSSS was significantly larger than that in the subgroup with low scores and there was a positive but non-significant correlation between total JSSS scores and doses of fluvoxamine. This preliminary study indicates that (1) a full serotonin syndrome was a rare phenomenon in a group of Japanese patients in a clinical setting and (2) the JSSS is a simple and reliable scale for evaluating the serotonin syndrome.


A case of Korsakoff's syndrome improved by high doses of donepezil.

We present a case of Korsakoff's syndrome that was successfully treated with high doses of donepezil, an inhibitor of acetylcholine esterase, known to retard the progress of symptoms in Alzheimer's disease. The patient was a 46-year-old married Japanese woman who began to drink alcohol after she married. After several years of drinking she developed typical symptoms of the Korsakoff syndrome. Donepezil was started after treatment with thiamine or thiamine plus fluvoxamine had failed. Her amnestic symptoms as well as her quality of life improved markedly during donepezil treatment. Inhibition of acetylcholine esterase may be an effective treatment for Korsakoff's syndrome.


Fluvoxamineとrisperidoneの併用が効果的であった分裂病性人格障害を伴うOCDの一症例

Japanese Journal of Psychiatric Treatment


This preliminary study was performed to investigate the prevalence and severity of the serotonin-related symptoms for a group of patients in a clinical setting during fluvoxamine (FLU) using the Japanese version of the Serotonin Syndrome Scale (JSSS). The subjects for the present study were 37 patients (20 and 17 patients with mood and anxiety disorders, respectively), meeting a diagnosis of DSM-IV. Each subject gave informed consent for the research involved in this study. Presence and severity of the serotonin-related symptoms were determined by Sternbach's criteria and the JSSS, respectively. (1) At the time of assessment, none of the patients fulfilled the diagnostic criteria of SS proposed by Sternbach, or none of the total JSSS scores of the patients was sufficient to reach the cutoff point of 7. (2) Sixteen of the 37 patients (43.2%) showed at least one symptom in the JSSS. (3) Spearman's rank correlations showed that there was a positive but nonsignificant correlation between the total JSSS scores and dosages of FLU. This preliminary study suggested that milder forms of the serotonin syndrome may exist for a group of patients in a clinical setting during FLU therapy.


Stereotyped behaviors in chronic schizophrenia in a Japanese mental hospital


幼児期の心的外傷体験がなく発症した解離性同一性障害の1症例

幼児期の心的外傷体験がなく発症した解離性同一性障害の1症例


行為障害 --- 症例と考察

行為障害 --- 症例と考察


Context determines the type of sensitized behaviour:a brief review and a hypothesis on the role of environment in behavioural sensitization.


Psychometric properties of the Japanese version of the Calgary Depression Scale for Schizophrenics

The Journal of Nervous and Mental Disease


Psychotic relapse and maintenance therapy in paranoid schizophrenia:a 15 year follow up

European Archives of Psychiatry and Clinical Neuroscience


Depression in X-linked dystonia-parkinsonism:A case-control study


ステロイド補充により精神症状が改善したACTH単独欠損症の1例

ステロイド補充により精神症状が改善したACTH単独欠損症の1例


MATRICSコンセンサス認知機能評価バッテリー日本語版の計量心理学的特性

MATRICSコンセンサス認知機能評価バッテリー日本語版の計量心理学的特性


Restless legs syndrome with chest and back restlessness as the initial symptom


高齢女性の遅発緊張病患者に対する維持修正電気けいれん療法の実施経験

高齢女性の遅発緊張病患者に対する維持修正電気けいれん療法の実施経験

精神神経学雑誌 2010特別

精神神経学雑誌 2010特別


Quetiapine Impact on Quality of Life in Patients with Schizophrenia


Serotonin syndrome - 'potential' role of the CYP2D6 genetic polymorphism in Asians

The International Journal of Neuropsychopharmacology


Possible mild serotonin syndrome related to co-prescription of tandospirone and trazodone