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Shogo Hashimoto,1,* Masahiko Ichiki,2,* Yoshitaka Ishii,2,3 Chihiro Morishita,2 Akiyoshi Shimura,2 Ichiro Kusumi,1 Takeshi Inoue,2 Jiro Masuya2 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, 160-0023, Japan; 3Fuji Psychosomatic Rehabilitation Institute Hospital, Fujinomiya, Shizuoka, 418-0035, Japan*These authors contributed equally to this workCorrespondence: Takeshi Inoue, Tel +81 3 3342 6111, Fax +81 3 3340 4499, Email tinoue@Tokyo-med.ac.jpBackground: Victimization in childhood profoundly influences the mental health of individuals in adulthood, causing depression, anxiety disorder, suicidality, and self-harm, which leads to productivity loss in the workplace, ie, presenteeism. However, the specific effects of victimization on presenteeism remain unclear. We hypothesized that victimization affects the presenteeism of workers through neuroticism and perceived job stressors and analyzed the association among these factors by path analysis.Methods: A questionnaire survey, including demographic and clinical data, Japanese versions of victimization scale in childhood, Brief Job Stress Questionnaire, and Work Limitations Questionnaire (WLQ), was administered to 443 adult volunteers between April 2017 and April 2018 in Tokyo, Japan. Multiple variables were analyzed by multiple regression analysis and path analysis. The Institutional Review Board of Tokyo Medical University approved this study.Results: Path analysis demonstrated that neuroticism and perceived job stressors had direct effects on presenteeism in the WLQ. Victimization indirectly increased presenteeism via neuroticism and its subsequent effects on perceived job stressors. This model accounted for 18% of the variability of presenteeism (R2 = 0.180).Limitations: There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the causal associations among variables should be validated in a prospective study.Conclusion: The present study indicates that the experience of victimization in childhood is a risk factor of adulthood presenteeism, and this effect is mediated by neuroticism and adverse effects on job stressors. These results suggest that multiple factors, including childhood victimization, neuroticism, and job stressors, should be considered when assessing and preventing presenteeism.Keywords: victimization, neuroticism, job stressor, presenteeism, childhood

Hiroshi Nakazawa,1 Jiro Masuya,1 Hajime Tanabe,2 Ichiro Kusumi,3 Takeshi Inoue,1 Masahiko Ichiki1 1Department of Psychiatry, Tokyo Medical University, Shinjuku-ku, Tokyo, 160-0023, Japan; 2Faculty of Humanities and Social Sciences, Shizuoka University, Suruga-ku, Shizuoka, 422-8529, Japan; 3Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, 060-8638, JapanCorrespondence: Takeshi InoueDepartment of Psychiatry, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, JapanTel +81 3 3342 6111Fax +81 3 3340 4499Email tinoue@tokyo-med.ac.jpBackground: Childhood maltreatment has long-lasting psychological effects, which often manifest in adulthood. Previous studies have suggested that the effects of childhood maltreatment are not only direct but also indirect, being mediated by other factors. In this study, we hypothesized that the effects of childhood maltreatment on state anxiety in adulthood are mediated by interpersonal sensitivity and the evaluation of life events, and investigated this possibility by covariance structure analysis.Subjects and Methods: Self-administered questionnaires (Child Abuse and Trauma Scale, State-Trait Anxiety Inventory Form Y, Life Experiences Survey, and Interpersonal Sensitivity Measure) were distributed to adult community volunteers in Japan, and 404 eligible responses were collected. A structural equation model was constructed to analyze the direct and indirect effects of childhood maltreatment on state anxiety, with interpersonal sensitivity and the evaluation of life events as potential mediators.Results: Our model showed that childhood maltreatment increases state anxiety in adulthood both directly and indirectly via interpersonal sensitivity. In addition, interpersonal sensitivity mediated the effects of childhood maltreatment on the negative evaluation of life events, and the negative evaluation of life events mediated the effects of interpersonal sensitivity on anxiety symptoms.Limitations: There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the results should be validated by a prospective study.Conclusion: The effects of childhood maltreatment on the state anxiety of adult volunteers are not only direct but are also mediated by interpersonal sensitivity. Our results suggest that assessing interpersonal sensitivity may help to determine optimal treatments for patients with anxiety who experienced maltreatment in childhood.Keywords: covariance structure analysis, child abuse and trauma scale, state-trait anxiety inventory form Y, interpersonal sensitivity measure, life experiences survey

Kuniyoshi Toyoshima,1,* Masahiko Ichiki,2,* Takeshi Inoue,2 Jiro Masuya,2 Yota Fujimura,2,3 Shinji Higashi,3,4 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, 160-0023, Japan; 3Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Tokyo, 193-0998, Japan; 4Department of Psychiatry, Ibaraki Medical Center, Tokyo Medical University, Ibaraki, 300-0395, Japan*These authors contributed equally to this workCorrespondence: Kuniyoshi ToyoshimaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Sapporo, 060-8638, JapanTel +81 011 716 1161Fax +81 011 706 5081Email toyoshima@med.hokudai.ac.jpPurpose: Trait anxiety, depressive symptoms, and cognitive complaints affect mental health. The mediating role of cognitive complaints has been reported recently. However, the mediating effects of cognitive complaints in the relationships between trait anxiety, depressive symptoms, and subjective well-being (SWB) and ill-being (SIB) remain unknown. Therefore, we used path analyses to investigate these mediating effects.Materials and Methods: A total of 554 adult community volunteers in Japan were studied using the State-Trait Anxiety Inventory (Form Y), Patient Health Questionnaire-9, Cognitive Complaints in Bipolar Disorder Rating Assessment, and Subjective Well-Being Inventory. These assessment tools evaluated trait anxiety, depressive symptoms, cognitive complaints, SWB, and SIB. Path analyses were performed in this study.Results: Path analyses revealed that there were significant indirect effects, via cognitive complaints, of trait anxiety and depressive symptoms on SIB. However, there were no significant indirect effects of trait anxiety and depressive symptoms on SWB. There were significant indirect effects, via depressive symptoms, of trait anxiety on cognitive complaints, SWB, and SIB.Conclusion: The role of cognitive complaints may be different between SWB and SIB associated with trait anxiety and depressive symptoms. Evaluating the mediating effect of cognitive complaints may be more useful on SIB than SWB associated with trait anxiety and depressive symptoms. These findings may be useful when considering intervention targets in mental health.Keywords: trait anxiety, depressive symptoms, cognitive complaints, well-being, ill-being, mediator

Kuniyoshi Toyoshima,1 Takeshi Inoue,2 Jiro Masuya,2 Yota Fujimura,2 Shinji Higashi,2,3 Ichiro Kusumi1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, Japan; 3Department of Psychiatry, Ibaraki Medical Center, Tokyo Medical University, Ibaraki, JapanCorrespondence: Kuniyoshi ToyoshimaDepartment of Psychiatry, Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Sapporo 060-8638, JapanTel +81 11 716 1161Fax +81 11 706 5081Email toyoshima@med.hokudai.ac.jpPurpose: Functional disability is affected by subjective cognitive function, depressive symptoms, and affective temperaments in adults. However, the role of subjective cognitive function as a mediator of affective temperaments in functional disability remains unknown. Therefore, we aimed to determine how subjective cognitive function mediates the effect of affective temperaments on functional disability in adults.Materials and Methods: A total of 544 participants completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Auto questionnaire version (TEMPS-A), the Patient Health Questionnaire-9 (PHQ-9), the cognitive complaints in bipolar disorder rating assessment (COBRA), and the Sheehan Disability Scale (SDS). The association among these instruments was evaluated by multiple regression and covariance structure analyses.Results: The structural equation model showed that the COBRA scores could be predicted directly by the four affective temperaments of the TEMPS-A (cyclothymic, depressive, irritable, and anxious) and indirectly by the PHQ-9. Moreover, the SDS score was predicted directly by these four affective temperaments and indirectly by the COBRA and PHQ-9.Conclusion: Subjective cognitive function mediates the effect of affective temperaments on functional disability in Japanese adults. However, the cross-sectional design may limit the identification of causal associations between the parameters. In the present study, the participants were from a specific community population; therefore, the results may not be generalizable to other communities.Keywords: cognition, depression, adult, Sheehan Disability Scale, TEMPS-A, subjective cognitive dysfunction

Yumi Wakatsuki,1 Takeshi Inoue,2 Naoki Hashimoto,1 Yota Fujimura,2 Jiro Masuya,2 Masahiko Ichiki,2 Hajime Tanabe,3 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo 160-0023, Japan; 3Department of Clinical Human Sciences, Graduate School of Humanities and Social Sciences, Shizuoka University, Shizuoka 422-8529, JapanCorrespondence: Takeshi InoueDepartment of Psychiatry, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanTel +81-3-3342-6111Fax +81-3-3340-4499Email tinoue@tokyo-med.ac.jpBackground: Previous studies have shown that childhood maltreatment is associated with premenstrual dysphoric disorder (PMDD). In this study we analyzed how multiple factors, such as childhood maltreatment, affective temperaments, and adult life events influence the severity of premenstrual mental (PMM) symptoms in nonclinical adult volunteers from the community.Methods: A total of 204 participants were recruited and administered the following self-administered questionnaire surveys: PMDD scale, visual analogue scale, Patient Health Questionnaire-9, Life Experience Survey, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire version, and the Child Abuse and Trauma scale. In addition to single and multiple regression analyses, structural equation modeling was used for the statistical analyses.Results: A history of neglect indirectly predicted PMM symptoms through affective temperaments in nonclinical adult volunteers. Three affective temperaments (irritable, cyclothymic, and anxious) directly predicted PMM symptoms.Conclusion: This study is the first to report that childhood maltreatment, particularly neglect, indirectly predicted PMM symptoms through affective temperaments. The results of our study suggest that affective temperament is a mediator of the influence of childhood maltreatment on PMM symptoms.Keywords: premenstrual mental symptoms, neglect, childhood maltreatment, affective temperament, TEMPS-A, structural equation modeling

Naoki Hashimoto,1 Atsuhito Toyomaki,1 Matsuhiko Oka,1 Keisuke Takanobu,1 Ryo Okubo,2 Hisashi Narita,1 Kan Kitagawa,1 Niki Udo,1 Tamaki Maeda,1 Shinya Watanabe,1 Yuka Oyanagi,1 Akane Miyazaki,1 Koki Ito,1 Ichiro Kusumi1 1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; 2Department of Clinical Epidemiology, Translational Medical Center, National Center for Neurology and Psychiatry, Tokyo 187-8551, JapanCorrespondence: Naoki HashimotoDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, 060-8638 North 15, West 7, Sapporo, JapanTel +81-11-706-5160Fax +81-11-706-5081Email hashinao@med.hokudai.ac.jpPurpose: The brief negative symptoms scale (BNSS) is a concise instrument used to assess negative symptoms of subjects with schizophrenia covering five domains of negative symptoms and is suitable for use in clinical, experimental, and epidemiological settings. The original and translated version of BNSS has thus far been shown to have adequate psychometric properties. This study aimed to examine internal consistency, inter-rater and test-retest reliability, discriminant and convergent validity, and factor structure of the Japanese version of BNSS.Patients and methods: The assessment was performed by 11 raters using interview videos of nine subjects. Reliability was calculated with Cronbach’s alpha for internal consistency and intra class correlation coefficient (ICC) for inter-rater reliability. Pearson’s correlation coefficients were calculated to estimate the test-retest reliability. In addition to BNSS, Scale for assessment of negative symptoms (SANS) and scale for assessment of positive symptoms (SAPS) was obtained to assess the convergent and discriminant validity. Factor structure was assessed using principle factor analysis.Results: The Japanese BNSS showed excellent internal consistency (Cronbach’s alpha=0.95), inter-rater reliability (intra class correlation coefficient=0.97), and test-retest reliability (r=0.94, p

Kuniyoshi Toyoshima,1 Takeshi Inoue,2 Jiro Masuya,2 Masahiko Ichiki,2 Yota Fujimura,2 Ichiro Kusumi1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, JapanCorrespondence: Kuniyoshi ToyoshimaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Sapporo 060-8638, JapanTel +81-11-716-1161Fax +81-11-706-5081Email toyoshima@med.hokudai.ac.jpPurpose: To examine the relationship between depressive symptoms, subjective cognitive function, and quality of life in Japanese adults using the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA).Patients and methods: We evaluated 585 adult community volunteers using the Patient Health Questionnaire-9 (PHQ-9) for evaluation of depressive symptoms and the COBRA for evaluation of subjective cognitive function. We additionally used the 8-item Short-Form Health Survey and the Sheehan Disability Scale to evaluate the quality of life (QoL).Results: Measures of subjective cognitive function were significantly correlated with depressive symptoms and QoL. Structural equation modeling demonstrated that depressive symptoms directly and indirectly decreased QoL via their effects on subjective cognitive dysfunction. Measures of depressive symptoms were more closely related to QoL than were measures of subjective cognitive function.Limitations: Study participants were general adult population community volunteers and included healthy people; thus, these results may not be generalizable to patients with depression or bipolar disorder. In addition, the cross-sectional design of this study prevented the identification of causal relationships among the parameters.Conclusion: Changes in subjective cognitive function may affect QoL via depressive symptoms. Evaluations of subjective cognitive function may help identify factors that reduce QoL.Keywords: 8-item Short-Form Health Survey, Sheehan Disability Scale, Patient Health Questionnaire-9, QoL, subjective cognitive dysfunction

Motoki Higashiyama,1 Taito Hayashida,1 Keisuke Sakuta,1 Yota Fujimura,2 Jiro Masuya,3 Masahiko Ichiki,1 Hajime Tanabe,4 Ichiro Kusumi,5 Takeshi Inoue11Department of Psychiatry, Tokyo Medical University, Tokyo 160-0023, Japan; 2Department of Psychiatry, Tokyo Medical University Hachioji Medical Center, Tokyo 193-0998, Japan; 3Department of Psychiatry, Tokyo Medical University Ibaraki Medical Center, Ibaraki 300-0395, Japan; 4Department of Clinical Human Sciences, Graduate School of Humanities and Social Sciences, Shizuoka University, Shizuoka 422-8529, Japan; 5Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, JapanCorrespondence: Takeshi InoueDepartment of Psychiatry, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanTel +81 33 342 6111Fax +81 33 340 4499Email tinoue@tokyo-med.ac.jpBackground: How subjective social status is associated with childhood abuse and affective temperament in the mechanism of depressive symptom exacerbation remains unknown. In this study, we investigated how the complex effects of subjective social status, childhood abuse, and affective temperament influence depressive symptoms in adulthood.Methods: Self-report questionnaires were distributed to 853 adult volunteers between January and August 2014. Of them, 404 people gave full consent and returned complete anonymous responses. The following five questionnaires were analyzed: demographic information, Patient Health Questionnaire-9, subjective social status, Child Abuse and Trauma Scale, and Temperament Evaluation of Memphis, Pisa, Paris and San Diego autoquestionnaire. The associations between the scores were analyzed by structural equation modeling. This study was conducted with approval from the ethics committees of Tokyo Medical University and Hokkaido University Hospital.Results: Covariance structure analysis demonstrated that childhood abuse and subjective social status did not have a direct effect on adulthood depressive symptoms. Childhood abuse had direct effects on subjective social status and affective temperament and childhood abuse indirectly affected adulthood depressive symptoms through subjective social status and affective temperament. Subjective social status also affected depressive symptoms through an effect on affective temperament. This model explained 43% of the variability in depressive symptoms and the fitness of this model was good.Conclusion: Regarding childhood abuse and adulthood depressive symptoms, subjective social status as well as affective temperament may be mediators. The results of this study are expected to contribute to the elucidation of the mechanism of depression.Keywords: childhood abuse, subjective social status, affective temperament, depression, covariance structure analysis

Yoshihiro Uchida,1–3 Toshinao Takahashi,1,3 Shigemasa Katayama,1,3 Jiro Masuya,1,2 Masahiko Ichiki,1 Hajime Tanabe,4 Ichiro Kusumi,5 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan; 2Department of Psychiatry, Ibaraki Medical Center, Tokyo Medical University, Ami-machi, Inashiki-gun, Ibaraki 300-0395, Japan; 3Department of Psychiatry, Seijin Hopital, Adachi-ku, Tokyo 121-0815, Japan; 4Department of Clinical Human Sciences, Graduate School of Humanities and Social Sciences, Shizuoka University, Suruga-ku, Shizuoka 422-8529, Japan; 5Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan Background: Various personality traits mediate the association between childhood stress and depressive symptoms in adulthood. The aim of this study was to clarify the indirect effects of the experience of child maltreatment on depressive symptoms and appraisal of life events in adulthood through trait anxiety. Subjects and methods: A total of 404 participants who were volunteer subjects from the community were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9, which measures depressive symptoms; State-Trait Anxiety Inventory Form Y, which measures trait anxiety; the Child Abuse and Trauma Scale, which measures child maltreatment; and Life Experiences Survey, which measures negative and positive appraisal of adulthood life events. Results: Structural equation modeling demonstrated that the experience of child maltreatment increased depressive symptoms in adulthood as well as the negative appraisal of life events in adulthood through an increase in trait anxiety. Furthermore, trait anxiety affected depressive symptoms in adulthood through its influence on the negative appraisal of adulthood life events. The following indirect effect was also significant: the experience of child maltreatment increased the negative appraisal of adulthood life events via trait anxiety and subsequently influenced adult depressive symptoms. Limitations: The subjects of this study are volunteer subjects from the community including healthy people, and hence the results may not be generalizable to major depressive patients. Recall bias should be considered when interpreting the results. Because this study is a cross-sectional study, the causality between the experience of child maltreatment and depression is not clear. Conclusion: This study suggests that trait anxiety may play a mediating role in the influence of the experience of child maltreatment on depressive symptoms in adulthood and negative appraisal of adulthood life events. Keywords: child maltreatment, covariance structure analysis, depression, STAI-Y, trait anxiety, life events

Ayano Otsuka,1 Yoshikazu Takaesu,1 Mitsuhiko Sato,1 Jiro Masuya,1 Masahiko Ichiki,1 Ichiro Kusumi,2 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Tokyo, 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Recent studies have suggested that multiple factors interact with the onset and prognosis of major depressive disorders. In this study, we investigated how child abuse, affective temperaments, and interpersonal sensitivity are interrelated, and how they affect depressive symptoms in the general adult population. Subjects and methods: A total of 415 volunteers from the general adult population completed the Patient Health Questionnaire-9, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version, the Child Abuse and Trauma Scale, and the Interpersonal Sensitivity Measure, which are all self-administered questionnaires. Data were subjected to structural equation modeling (Mplus), and single and multiple regression analyses. Results: The effect of child abuse on depressive symptoms was mediated by interpersonal sensitivity and 4 affective temperaments, including depressive, cyclothymic, anxious, and irritable temperaments. In addition, the effect of these temperaments on depressive symptoms was mediated by interpersonal sensitivity, indicating the indirect enhancement of depressive symptoms. In contrast to these 4 temperaments, the hyperthymic temperament did not mediate the effect of child abuse on depressive symptoms; its effect was not mediated by interpersonal sensitivity. However, a greater hyperthymic temperament predicted decreased depressive symptoms and interpersonal sensitivity, independent of any mediation effect. Limitations: Because this is a cross-sectional study, long-term prospective studies are necessary to confirm its findings. Therefore, recall bias should be considered when interpreting the results. As the subjects were adults from the general population, the results may not be generalizable towards all patients with major depression. Conclusion: This study suggests that child abuse and affective temperaments affect depressive symptoms partly through interpersonal sensitivity. Interpersonal sensitivity may have a major role in forming the link between abuse, affective temperament, and depression. Keywords: child abuse, affective temperament, TEMPS-A, interpersonal sensitivity, depression, structural equation modeling

Kotaro Ono,1 Yoshikazu Takaesu,1 Yukiei Nakai,2 Akiyoshi Shimura,1 Yasuyuki Ono,1 Akiko Murakoshi,1 Yasunori Matsumoto,1 Hajime Tanabe,3 Ichiro Kusumi,2 Takeshi Inoue1 1Department of Psychiatry, Tokyo Medical University, Tokyo, 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Hokkaido, 3Department of Clinical Human Sciences, Graduate school of Humanities and Social Sciences, Shizuoka University, Shizuoka, Japan Background: Recent studies have suggested that the interactions among several factors affect the onset, progression, and prognosis of major depressive disorder. This study investigated how childhood abuse, neuroticism, and adult stressful life events interact with one another and affect depressive symptoms in the general adult population. Subjects and methods: A total of 413 participants from the nonclinical general adult population completed the Patient Health Questionnaire-9, the Child Abuse and Trauma Scale, the neuroticism subscale of the shortened Eysenck Personality Questionnaire – Revised, and the Life Experiences Survey, which are self-report scales. Structural equation modeling (Mplus version 7.3) and single and multiple regressions were used to analyze the data. Results: Childhood abuse, neuroticism, and negative evaluation of life events increased the severity of the depressive symptoms directly. Childhood abuse also indirectly increased the negative appraisal of life events and the severity of the depressive symptoms through enhanced neuroticism in the structural equation modeling. Limitations: There was recall bias in this study. The causal relationship was not clear because this study was conducted using a cross-sectional design. Conclusion: This study suggested that neuroticism is the mediating factor for the two effects of childhood abuse on adulthood depressive symptoms and negative evaluation of life events. Childhood abuse directly and indirectly predicted the severity of depressive symptoms. Keywords: childhood abuse, depression, neuroticism, stressful life events, structural equation modeling

Hiroyuki Toda,1 Takeshi Inoue,2,3 Tomoya Tsunoda,1 Yukiei Nakai,2 Masaaki Tanichi,1 Teppei Tanaka,1 Naoki Hashimoto,2 Yasuya Nakato,2 Shin Nakagawa,2 Yuji Kitaichi,2 Nobuyuki Mitsui,2 Shuken Boku,4 Hajime Tanabe,5 Masashi Nibuya,1 Aihide Yoshino,1 Ichiro Kusumi2 1Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan; 2Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan; 3Department of Psychiatry, Tokyo Medical University, Tokyo, Japan; 4Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan; 5Department of Clinical Human Sciences, Graduate School of Humanities and Social Sciences, Shizuoka University, Shizuoka, Japan Background: Previous studies have shown the interaction between heredity and childhood stress or life events on the pathogenesis of a major depressive disorder (MDD). In this study, we tested our hypothesis that childhood abuse, affective temperaments, and adult stressful life events interact and influence the diagnosis of MDD. Patients and methods: A total of 170 healthy controls and 98 MDD patients were studied using the following self-administered questionnaire surveys: the Patient Health Questionnaire-9 (PHQ-9), the Life Experiences Survey, the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire, and the Child Abuse and Trauma Scale (CATS). The data were analyzed with univariate analysis, multivariable analysis, and structural equation modeling. Results: The neglect scores of the CATS indirectly predicted the diagnosis of MDD through cyclothymic and anxious temperament scores of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire in the structural equation modeling. Two temperaments – cyclothymic and anxious – directly predicted the diagnosis of MDD. The validity of this result was supported by the results of the stepwise multivariate logistic regression analysis as follows: three factors – neglect, cyclothymic, and anxious temperaments – were significant predictors of MDD. Neglect and the total CATS scores were also predictors of remission vs treatment-resistance in MDD patients independently of depressive symptoms. Limitations: The sample size was small for the comparison between the remission and treatment-resistant groups in MDD patients in multivariable analysis. Conclusion: This study suggests that childhood abuse, especially neglect, indirectly predicted the diagnosis of MDD through increased affective temperaments. The important role as a mediator of affective temperaments in the effect of childhood abuse on MDD was suggested. Keywords: neglect, major depressive disorder, affective temperament, mediator

Naoki Hashimoto,1,2 Atsuhito Toyomaki,1 Masahiro Hirai,3 Tamaki Miyamoto,1 Hisashi Narita,1 Ryo Okubo,1 Ichiro Kusumi1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Child and Adolescent Psychiatry, Department of Psychiatry, University of California, San Francisco, CA, USA; 3Center for Development of Advanced Medical Technology, Jichi Medical University, Yakushiji, Shimotsuke, Tochigi, Japan Background: Patients with schizophrenia show disturbances in both visual perception and social cognition. Perception of biological motion (BM) is a higher-level visual process, and is known to be associated with social cognition. BM induces activation in the “social brain network”, including the superior temporal sulcus (STS). Although deficits in the detection of BM and atypical activation in the STS have been reported in patients with schizophrenia, it remains unclear whether other nodes of the “social brain network” are also atypical in patients with schizophrenia.Purpose: We aimed to explore whether brain regions other than STS were involved during BM perception in patients with schizophrenia, using functional magnetic resonance imaging (fMRI).Methods and patients: Seventeen patients with schizophrenia, and 17 age- and sex- matched healthy controls, underwent fMRI scanning during a one-back visual task, containing three experimental conditions: (1) BM, (2) scrambled motion (SM), and (3) static condition. We used one-sample t-tests to examine neural responses selective to BM versus SM within each group, and two-sample t-tests to directly compare neural patterns to BM versus SM in schizophrenics versus controls.Results: We found significant activation in the STS region when BM was contrasted with SM in both groups, with no significant difference between groups. On the contrary, significant activation in the medial prefrontal cortex (MPFC) and bilateral temporoparietal junction (TPJ) was found only in the control group. When we directly compared the two groups, the healthy controls showed significant greater activation in left MPFC and TPJ to BM versus SM than patients with schizophrenia. Conclusion: Our findings suggest that patients with schizophrenia show normal activation to biologically and socially relevant motion stimuli in the STS, but atypical activation in other regions of the social brain network, specifically MPFC and TPJ. Moreover, these results were not due to atypical processing of motion, suggesting that patients with schizophrenia lack in the recruitment of neural circuits needed for the visual perception of social cognition. Keywords: cognitive processing, social cognition, social brain network, mentalizing, theory of mind

Yuki Kako, Koki Ito, Naoki Hashimoto, Kuniyoshi Toyoshima, Yusuke Shimizu, Nobuyuki Mitsui, Yutaka Fujii, Teruaki Tanaka, Ichiro Kusumi Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan Objectives: To examine the relationship between level of insight and various subjective experiences for patients with schizophrenia.Materials and methods: Seventy-four patients with schizophrenia who were discharged from our hospital were evaluated. The level of insight into their illness and various subjective experiences were evaluated at discharge. We used the Scale to Assess Unawareness of Mental Disorder (SUMD) for evaluation of insight. In addition, five different rating scales were used to evaluate subjective experiences: Subjective Experience of Deficits in Schizophrenia (SEDS), Subjective Well-being under Neuroleptic drug treatment Short form (SWNS), Schizophrenia Quality of Life Scale (SQLS), Beck Depression Inventory (BDI), and the Drug Attitude Inventory (DAI)-30.Results: The SWNS and the scores for awareness of mental disorder and awareness of the social consequences of mental disorder on SUMD showed a weak positive correlation. The DAI-30 showed a significant negative correlation with most general items on SUMD and a negative correlation between the subscale scores for the awareness and attribution of past symptoms. SEDS, SWNS, SQLS, and the BDI significantly correlated with the subscale scores for awareness of current symptoms on SUMD, and weakly correlated with the subscale scores for attribution of current negative symptoms.Conclusion: Awareness of subjective distress was related to awareness of having a mental disorder. Feeling subjective distress was related to awareness of current symptoms, as well as to the ability to attribute current negative symptoms to a mental disorder. Positive attitudes toward medication correlated with better general insight into the illness. Keywords: schizophrenia, insight, subjective experiences, subjective deficit, subjective well-being, subjective quality of life

Yuji Kitaichi,1 Takeshi Inoue,1 Nobuyuki Mitsui,1 Shin Nakagawa,1 Rie Kameyama,1 Yoshiyuki Hayashishita,1 Tohru Shiga,2 Ichiro Kusumi,1 Tsukasa Koyama1 1Department of Psychiatry, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Abstract: We report a case in which selegiline, an irreversible monoamine oxidase B (MAO-B) inhibitor, greatly improved depressive symptoms in an adult with stage 5 treatment-resistant major depressive disorder. Four antidepressants and four augmentation therapies had previously been ineffective or intolerable, and electroconvulsive therapy had only a temporary effect. After 20 weeks of treatment with selegiline (10 mg/day), the patient's score on the 17-item Hamilton Depression Rating Scale (HDRS) had decreased from 19 to 4 points. [18F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased glucose metabolism in the bilateral basal ganglia after initiating selegiline treatment; blood dopamine levels were also increased after selegiline treatment. These results raise the possibility that selegiline enhances dopaminergic neural transmission in treatment-resistant depression, thus leading to an improvement in depressive symptoms. Keywords: treatment-resistant depression, FDG-PET, glucose metabolism, basal ganglia

Hiromi Kimura, Akemi Osaki, Rui Kawashima, Takeshi Inoue, Shin Nakagawa, Katsuji Suzuki, Satoshi Asakura, Teruaki Tanaka, Yuji Kitaichi, Takuya Masui, Nobuki Kitagawa, Yuki Kako, Tomohiro Abekawa, Ichiro Kusumi, Hiroyoshi Yamanaka, Kenzo Denda, Tsukasa KoyamaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, JapanBackground: The bipolar-unipolar distinction in patients with a major depressive episode is the most important issue related to the diagnosis and treatment of mood disorders, but remains unresolved. This study was undertaken to compare bipolar and unipolar depression on Rorschach testing using the Comprehensive System with reference to healthy Japanese controls.Methods: Patients with bipolar or unipolar depression who had undergone the Rorschach test for routine clinical purposes were followed up naturalistically for a long period. Based on diagnostic confirmation after long-term follow-up, scores on this test for patients with bipolar and unipolar depression were compared with those published elsewhere for healthy Japanese controls.Results: The bipolar depression group showed significantly higher scores or positive findings in five variables of the Rorschach test, ie, WSum6, DR2 > 0, (CF + C) > FC + 2, PureC > 1, and Populars > 7, as assessed using the Comprehensive System, than did the unipolar depression group and healthy controls. These scores did not differ between the unipolar depression and control groups.Conclusion: The results of this study show thought disorder or cognitive slippage and marked laxness in modulating emotion in bipolar depression, indicating the psychopathological characteristics of bipolar disorder.Keywords: bipolar depression, bipolar disorder, Rorschach test, thought disorder, unipolar depression

Yuji Kitaichi, Takeshi Inoue, Shin Nakagawa, Shuken Boku, Akiko Kato, Ichiro Kusumi, Tsukasa KoyamaDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, JapanBackground: Up to 30% of depressed patients are partially or totally resistant to antidepressant therapy. The administration of triiodothyronine (T3) to antidepressant nonresponders can be an effective augmentation strategy, although the mechanism is not fully understood.Methods: In vivo microdialysis was used to examine the effect of T3 augmentation of the antidepressant, milnacipran. Basal extracellular serotonin, norepinephrine, and dopamine levels were measured before and after acute milnacipran administration in the medial prefrontal cortex and amygdala of rats which had received subchronic (7 days) T3 treatment or control saline.Results: Subchronic administration of T3 at 0.1 mg/kg significantly increased basal extracellular levels of serotonin in the medial prefrontal cortex, but not in the amygdala. In contrast, subchronic administration of T3 at 0.2 mg/kg did not alter basal extracellular serotonin levels in the medial prefrontal cortex. Basal extracellular levels of norepinephrine and dopamine were not modified by either dose of T3 in either region. Acute administration of milnacipran, a serotonin-norepinephrine reuptake inhibitor, to control animals resulted in a significant increase of extracellular levels of serotonin, norepinephrine, and dopamine. When administered to animals treated subchronically with T3 at 0.1 mg/kg, milnacipran produced an additional increase in extracellular serotonin levels but not in levels of norepinephrine or dopamine in the medial prefrontal cortex of rats.Conclusion: These results suggest that the mechanism of the augmentation effect of milnacipran by T3 administration occurs via enhancement of serotonergic neurotransmission, but not through noradrenergic or dopaminergic neurotransmission.Keywords: depression, in vivo microdialysis, milnacipran, monoamines, triiodothyronine

Nakato Y, Inoue T, Nakagawa S, Kitaichi Y, Kameyama R, Wakatsuki Y, Kitagawa K, Omiya Y, Kusumi I.Neuropsychiatr Dis Treat. 2016;12: 2173–2179. On pages 2175 and 2177, Figures 1 and 2 were transposed.The correct version of Figure 1 is shown. Read the original article