176 research outputs found

    Gene expression-based biological test for major depressive disorder: an advanced study

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    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 disorde

    Clinical factors influencing resilience in patients with anorexia nervosa

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    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-imag

    Elevated peripheral blood glutamate levels in major depressive disorder

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    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<0.05). Subgroup analyses showed elevated glutamate levels in MDD patients compared with controls in plasma, but not serum studies, and in studies using high-performance liquid chromatography but not with mass spectrometry for glutamate assay. A meta-regression analysis showed no effects of age, gender, medication use, sample size, and published year on blood glutamate levels. Conclusion: Our findings suggest that altered glutamate levels may be implicated in MDD, which provides further evidence of glutamatergic dysfunction in MDD. Keywords: glutamate, major depressive disorder, blood, association study, meta-analysi

    Relationship between social and cognitive functions in people with schizophrenia

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    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 processin

    Analytical regularization of hypersingular integral for Helmholtz equation in boundary element method

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    This paper presents a gradient field representation using an analytical regularization of a hypersingular boundary integral equation for a 2-dimensional time harmonic wave equation called the Helmholtz equation. The regularization is based on cancelation of the hyper-singularity by considering properties of hypersingular elements that are adjacent to a singular node. Advantages to this regularization include applicability to evaluate cornet nodes, no limitation for element size, and reduced computational cost compared to other methods. To demonstrate capability and accuracy, regularization is estimated for a problem about plane wave propagation. As a result, it is found that even at a corner node the most significant error in the proposed method is due to truncation error of non-singular elements in discretization, and error from hypersingular elements is negligibly small

    Structural equation modeling approach between salience network dysfunction, depressed mood, and subjective quality of life in schizophrenia: an ICA resting-state fMRI study

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    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 fMR

    Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

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    Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis
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