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Kiyohiro Yamazaki,1 Yuta Yoshino,1 Kentaro Kawabe,1 Tomomasa Ibuki,1 Shinichiro Ochi,1 Yoko Mori,1 Yuki Ozaki,1 Shusuke Numata,2 Jun-ichi Iga,1 Tetsuro Ohmori,2 Shu-ichi Ueno1 1Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; 2Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima 770-8503, JapanCorrespondence: Jun-ichi IgaDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, JapanTel +81-89-960-5315Fax +81-89-960-5317Email iga.junichi.it@ehime-u.ac.jpIntroduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimer’s disease, the relationship between ABCA7 and schizophrenia has been unknown.Methods: Schizophrenia patients (n = 50; 24 males, 62.1 ± 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area.Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner.Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia.Keywords: schizophrenia, ATP-binding cassette sub-family A member 7 gene, single nucleotide polymorphism, rs3764650, mRNA expression

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

Chikako Kane,1 Masahito Tomotake,2 Sayo Hamatani,3 Shinichi Chiba,2 Naomi Kameoka,4 Shinya Watanabe,4 Masahito Nakataki,4 Shusuke Numata,4 Tetsuro Ohmori4 1Department of Nursing, Tokushima University Hospital, Tokushima-shi, Tokushima, Japan; 2Department of Mental Health, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-shi, Tokushima, Japan; 3Research Center for Child Mental Development Chiba University, Chuouku, Chiba, Japan; 4Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima-shi, Tokushima, Japan Purpose: This study was to elucidate clinical factors influencing resilience in anorexia nervosa (AN) patients. Patients and methods: Twenty female patients with AN (median age =30.0 years, quartile deviation =6.8) and 40 female healthy controls (HCs) (median age =30.0 years, quartile deviation =8.6) participated in the present study. Resilience was assessed with the Connor–Davidson resilience scale (CD-RISC). Clinical symptoms were evaluated with the structured interview guide for the Hamilton depression rating scale (SIGH-D) and the eating disorder inventory-2 (EDI-2). Results: Scores of the CD-RISC in the AN group were lower than those in the HC group, and the SIGH-D score in the AN group was higher than that in the HC group. Scores of interoceptive confusion, interpersonal difficulty and negative self-image subscales of the EDI-2 negatively correlated with the CD-RISC score. Moreover, stepwise regression analysis showed that negative self-image score was an independent predictor of the CD-RISC score. Conclusion: These results suggest that among these clinical factors including psychopathologies, self-dissatisfaction and feeling of being rejected by others are the most important influencing factors on an AN patients’ resilience. Keywords: anorexia nervosa, resilience, influencing factor, negative self-image

Takeo Tominaga,1 Masahito Tomotake,2 Tomoya Takeda,1 Yoshinori Ueoka,3 Tsunehiko Tanaka,4 Shin-ya Watanabe,1 Naomi Kameoka,5 Masahito Nakataki,5 Shusuke Numata,1 Yumiko Izaki,6 Satsuki Sumitani,7 Hiroko Kubo,8 Yasuhiro Kaneda,9 Tetsuro Ohmori1 1Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 2Department of Mental Health, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 3Field of Psychology, Department of Human Sciences, Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Japan; 4Faculty of Education, Specialized Courses Educational Psychology, Niigata University, Niigata, Japan; 5Department of Psychiatry, Tokushima University Hospital, Tokushima, Japan; 6Health Service and Counseling Center, Tokushima University, Tokushima, Japan; 7Academic Support Office for Students with Special Needs, Tokushima University, Tokushima, Japan; 8Department of Psychiatry, Aizato Hospital, Itano-gun, Tokushima, Japan; 9Department of Psychiatry, Iwaki Clinic, Anan, Tokushima, Japan Purpose: The purpose of the present study was to examine clinical factors related to social function in people with schizophrenia. Patients and methods: The participants were 55 stabilized outpatients with schizophrenia. Their mean age was 39.36 (SD =10.65) years. Social function was assessed using the Quality of Life Scale (QLS). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. Results: Neither the MCCB cognitive domain score nor composite score was correlated with the QLS scores. However, of the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively correlated with the QLS scores. Among clinical variables, especially the PANSS negative syndrome scale score had a strong negative correlation with the QLS scores. Stepwise regression analyses showed that the PANSS negative syndrome scale score was an independent predictor of the QLS scores, and although the BACS-SC score predicted the QLS common objects and activities subscale score, the association was not so strong compared to the PANSS negative syndrome scale score. Conclusion: These results indicate that speed of processing evaluated by BACS-SC could predict some aspect of social function but negative symptoms have a much stronger impact on global social function in people with schizophrenia. Keywords: schizophrenia, social function, negative symptom, cognitive function, speed of processing

Masashi Ohta,1 Masahito Nakataki,1 Tomoya Takeda,1 Shusuke Numata,1 Takeo Tominaga,1 Naomi Kameoka,2 Hiroko Kubo,1 Makoto Kinoshita,1 Kanae Matsuura,2 Maki Otomo,3 Naoya Takeichi,4 Masafumi Harada,3 Tetsuro Ohmori1 1Department of Psychiatry, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 2Department of Psychiatry, Tokushima University Hospital, Tokushima, Japan; 3Department of Radiology and Radiation Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; 4Department of Radiology, Tokushima University Hospital, Tokushima, Japan Purpose: Quality of life (QOL) is an important clinical outcome for patients with schizophrenia, and recent studies have focused on subjective QOL. We evaluated the causal relationship between psychosocial aspect of subjective QOL, symptoms, cognitive functions, and salience network (SN) dysfunction in schizophrenia using structural equation modeling (SEM). Patients and methods: We performed a cross-sectional study of 21 patients with symptomatically stabilized schizophrenia and 21 age-, sex-, and education level-matched healthy controls who underwent resting-state functional magnetic resonance imaging. We evaluated SN dysfunction in schizophrenia using independent component analysis (ICA). We rated participant psychopathology using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), and the Calgary Depression Scale for Schizophrenia (CDSS). We rated psychosocial aspect of subjective QOL using the Schizophrenia Quality of Life Scale (SQLS) psychosocial subscale. We applied SEM to examine the relationships between SN dysfunction, PANSS positive and negative scores, CDSS total scores, BACS composite scores, and SQLS psychosocial subscale scores. Results: In second-level analysis after group ICA, patient group had significant lower right pallidum functional connectivity (FC) within the SN than the controls did (Montreal Neurological Institute [MNI] [x y z] = [22 -2 -6]) (p = 0.027, family-wise error [FWE] corrected). In SEM, we obtained a good fit for an SEM model in which SN dysfunction causes depressed mood, which in turn determines psychosocial aspect of subjective QOL (chi-squared p = 0.9, root mean square error of approximation (RMSEA) < 0.001, comparative fit index [CFI] = 1.00, and standardized root mean square residual [SRMR]= 0.020). Conclusion: We found a continuous process by which SN dysfunction causes depressed moods that determine psychosocial aspect of subjective QOL in schizophrenia. This is the first report that offers a unified explanation of functional neuroimaging, symptoms, and outcomes. Future studies combining neuroimaging techniques and clinical assessments would elucidate schizophrenia’s pathogenesis. Keywords: depressed mood, salience network, schizophrenia, structural equation modeling, subjective quality of life, resting-state fMRI

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

Tomoya Takeda,1 Satsuki Sumitani,2 Sayo Hamatani,1 Yosuke Yokose,3 Megumi Shikata,4 Tetsuro Ohmori5 1Department of Psychiatry, Tokushima University Hospital, 2Department of Support for Students with Special Needs, Institute of Biomedical Sciences, Tokushima University Graduate School, 3Taoka Higashi Hospital, Tokushima, 4Department of Psychiatry, Ibogawa Hospital, Tatsuno, 5Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan Objective: We investigated oxyhemoglobin change in the prefrontal cortex (PFC) of patients with obsessive–compulsive disorder (OCD) who showed different responses to pharmacotherapy during neuropsychological tasks with near-infrared spectroscopy. Subjects and methods: A total of 42 patients with OCD (mean age: 35.6±9.6 years, 14 men, 28 women) and healthy control subjects (mean age: 35.4±9.7 years, 13 men, 29 women) were selected. Patients with OCD were divided into three groups (responders to selective serotonin-reuptake inhibitors (SSRIs), responders to SSRIs with antipsychotics, and nonresponders to SSRIs and SSRIs with antipsychotics) based on pharmacological response. We investigated oxyhemoglobin change in the PFC of subjects during Stroop tasks and a verbal fluency test with near-infrared spectroscopy. Results: Responders to SSRIs showed smaller activation compared to control subjects during the Stroop incongruent task and verbal fluency test, but not during the Stroop congruent task. In contrast, responders to SSRIs with antipsychotics showed smaller activation compared to control subjects during all three tasks. Conclusion: Our results suggest that activation of the PFC during Stroop tasks might predict responses to pharmacotherapy of patients with OCD. Keywords: obsessive–compulsive disorder, pharmacotherapy, near-infrared spectroscopy, Stroop task, verbal fluency test

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