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Tomoya Takeda,1 Masahito Nakataki,2 Masashi Ohta,2 Sayo Hamatani,3 Kanae Matsuura,2 Reona Yoshida,2 Naomi Kameoka,2 Takeo Tominaga,4 Hidehiro Umehara,2 Makoto Kinoshita,2 Shinya Watanabe,4 Shusuke Numata,4 Satsuki Sumitani,5 Tetsuro Ohmori4 1Graduate School of Medical Science, Tokushima University, Tokushima, Japan; 2Department of Psychiatry, Tokushima University Hospital, Tokushima, Japan; 3Research Center for Child Mental Development, Chiba University, Chiba, Japan; 4Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 5Academic Support Office for Students with Special Needs, Tokushima University, Tokushima, Japan Purpose: Recently, cognitive variables such as negative and positive self-belief and thoughts have attracted much attention because they are associated with functional outcomes and quality of life (QOL). However, it is unclear how cognitive variables affect subjective and objective QOL. This study aimed to investigate the relationship of negative and positive self-belief and thoughts with subjective and objective QOL.Participants and methods: Thirty-six people with schizophrenia participated in this study. Subjective and objective QOL were assessed with the Schizophrenia Quality of Life Scale (SQLS) and Quality of Life Scale (QLS), respectively. Neurocognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Clinical symptoms were assessed with the Positive and Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia. Side effects were assessed with the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). Negative and positive self-belief and thoughts were assessed with the Defeatist Performance Belief Scale and Automatic Thoughts Questionnaire-Revised. A generalized linear model was tested, with subjective and objective QOL as the response variable and symptoms, neurocognitive function, and cognitive variables that were significantly correlated with subjective and objective QOL as explanatory variables.Results: In the schizophrenia group, the common objects score on the QLS was predicted by the composite BACS score, and the total QLS score was predicted by the DIEPSS score. Motivation and Energy, Psychosocial, and Symptoms and Side effects scores on the SQLS were predicted by depression and by negative automatic thought (NAT) and positive automatic thought (PAT).Conclusion: Our results indicated that key targets for improving objective and subjective QOL in people with schizophrenia are side effects, neurocognitive function, depression, and NAT and PAT. Keywords: defeatist performance belief, negative and positive automatic thoughts, subjective quality of life, objective quality of life, schizophrenia

Masatoshi Inoshita,1 Hidehiro Umehara,1 Shin-ya Watanabe,1 Masahito Nakataki,1 Makoto Kinoshita,1 Yukiko Tomioka,1 Atsushi Tajima,2 Shusuke Numata,1 Tetsuro Ohmori1 1Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 2Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Ishikawa, Japan Purpose: There is growing evidence that glutamatergic signaling may be involved in major depressive disorder (MDD). In regard to peripheral blood glutamate changes in MDD, inconsistent findings have been reported. The purpose of the present study was to evaluate whether blood glutamate levels differed between MDD patients and control participants. Materials and methods: We conducted a systematic review and meta-analysis of 12 association studies between blood glutamate levels and MDD in a total of 529 MDD patients and 590 controls. Subsequently, we conducted subgroup analyses and a meta-regression analysis to examine the sources of potential heterogeneity. Results: A random effects model showed that blood glutamate levels were significantly higher in MDD patients than in controls (standardized mean difference=0.54, 95% CI=0.27–0.82, p=8.5×10-5) with high heterogeneity (I2=75.0%, p

Shin-ya Watanabe,1 Shusuke Numata,1 Jun-ichi Iga,2 Makoto Kinoshita,1 Hidehiro Umehara,1 Kazuo Ishii,3 Tetsuro Ohmori1 1Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 2Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, 3Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan Purpose: Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder.Patients and methods: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD.Results: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively.Conclusion: Further research to identify MDD-specific markers is needed to improve the performance of this biological test. Keywords: depressive disorder, biomarker, gene expression, schizophrenia, bipolar disorder

Hidehiro Umehara,1 Shusuke Numata,1 Makoto Kinoshita,1 Shinya Watanabe,1 Shutaro Nakaaki,2 Satsuki Sumitani,1,3 Tetsuro Ohmori1 1Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 2Laboratory of Aging, Behavior and Cognition, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 3Academic Support Office for Students with Special Needs, Tokushima University, Tokushima, Japan Aim: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population.Methods: We first performed a case–control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD.Results: We found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05).Conclusion: Our results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population. Keywords: obsessive-compulsive disorder, BDNF, treatment response, association study, SSRI, atypical antipsychotic

Aim: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population., Methods: We first performed a case-control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD., Results: We found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05)., Conclusion: Our results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population.