特集 精神疾患患者の就労･復職を支援する 統合失調症患者の就労･復職を支援する
15 Mar. 2025

Increased structural covariance of cortical measures in individuals with an at-risk mental state.
Daiki Sasabayashi; Sakiko Tsugawa; Shinichiro Nakajima; Tsutomu Takahashi; Yoichiro Takayanagi; Shinsuke Koike; Naoyuki Katagiri; Masahiro Katsura; Atsushi Furuichi; Yuko Mizukami; Shimako Nishiyama; Haruko Kobayashi; Yusuke Yuasa; Naohisa Tsujino; Atsushi Sakuma; Noriyuki Ohmuro; Yutaro Sato; Kazuho Tomimoto; Naohiro Okada; Mariko Tada; Motomu Suga; Norihide Maikusa; Eric Plitman; Cassandra M J Wannan; Andrew Zalesky; Mallar Chakravarty; Kyo Noguchi; Hidenori Yamasue; Kazunori Matsumoto; Takahiro Nemoto; Hiroaki Tomita; Masafumi Mizuno; Kiyoto Kasai; Michio Suzuki
Progress in neuro-psychopharmacology & biological psychiatry, 22 Nov. 2024
An anomalous pattern of structural covariance has been reported in schizophrenia, which has been suggested to represent connectome changes during brain maturation and neuroprogressive processes. It remains unclear whether similar differences exist in a clinical high-risk state for psychosis, and if they are associated with a prodromal phenotype and/or later psychosis onset. This multicenter magnetic resonance imaging study cross-sectionally examined structural covariance in a large at-risk mental state (ARMS) sample with different outcomes. The whole-brain structural covariance of four cortical measures (thickness, area, volume, and gyrification) was assessed in 155 individuals with ARMS, who were subclassified into 26 (16.8 %) with a later psychosis onset (ARMS-P), 44 with persistent subthreshold psychotic symptoms, and 53 with the remission of psychotic symptoms (ARMS-R) during the clinical follow-up, and 191 healthy controls. The relationships of changes in structural covariance with clinical symptoms and cognitive impairments were also investigated in the ARMS subsample. Structural covariance was significantly higher in widespread cortical regions in the ARMS group than in the controls, with each cortical measure having a different pattern in affected cortical regions. The higher structural covariance of the cortical area was partly related to severe suspiciousness-persecutory ideation. Structural covariance was significantly higher, mainly in fronto-parietal gyrification, in the ARMS-P group than in the ARMS-R group. The present results suggest that changes in structural covariance result in psychosis vulnerability and the excessive structural covariance of brain gyrification in ARMS subjects may contribute to their later clinical course.

Characteristic association of symbol coding test score with occupational function in Japanese patients with schizophrenia
Yukako Watanabe; Sho Kanata; Motomu Suga; Akiko Inagaki; Sayaka Sato; Naoki Hayashi; Hiroshi Kunugi; Emi Ikebuchi
Neuropsychopharmacology Reports, 08 Feb. 2023
Abstract

Aim

Studies showed that cognitive function affects occupational function in patients with schizophrenia. This study aimed to determine the effects of cognitive function on occupational function in Japanese patients with schizophrenia using the Brief Assessment of Cognition in Schizophrenia (BACS).

Methods

Participants were 198 outpatients with schizophrenia or schizoaffective disorder (66 females; mean age 34.5 ± 6.8 years). Occupational function was assessed using the work subscale of the Life Assessment Scale for Mental Ill (LASMI‐w). Multiple regression analysis was performed using the BACS as the independent variable and LASMI‐w as the dependent variable. Furthermore, we divided the LASMI‐w score into three groups, <11, 11–20, and >21, and performed a multinomial logistic regression analysis.

Results

Multiple regression analysis revealed that LASMI‐w score was negatively associated with BACS composite score (β = −0.20, p < 0.01). Among the sub‐items of the BACS, only the symbol‐coding score showed a significant negative association (β = −0.19, p < 0.05). Multinomial logistic analysis showed that the better the composite and symbol coding scores, the smaller the impairment of the occupational function (composite score: β = 2.39 between mild and moderate occupational impairments, p < 0.05; symbol coding score: β = 2.44 between mild and severe impairments, p < 0.05).

Conclusion

The occupational function of patients with schizophrenia was associated with overall cognitive function (composite score). In particular, the symbol coding score of the BACS was suggested to be related to work ability. These results might be useful in the assessment and training of cognitive rehabilitation aimed at employment support.

Betaine supplementation improves positive symptoms in schizophrenia.
Kenji Kirihara; Mao Fujioka; Motomu Suga; Shinsuke Kondo; Kayo Ichihashi; Daisuke Koshiyama; Kentaro Morita; Tempei Ikegame; Mariko Tada; Tsuyoshi Araki; Seiichiro Jinde; Kazuki Taniguchi; Taiga Hosokawa; Kazuyuki Sugishita; Shinjiro Dogan; Kohei Marumo; Masanari Itokawa; Kiyoto Kasai
Schizophrenia research, 16 Nov. 2022

精神科デイケアを利用した統合失調症患者のリカバリーに関する縦断的観察研究　　　　　　　　　　　　　　　
Apr. 2022

統合失調症の対人機能・労働機能に寄与する要因 認知機能や精神症状との関連　　　　　　　　　　　　　　　
Apr. 2022

The association between clinical symptoms and later subjective quality of life in individuals with ultra-high risk for psychosis and recent-onset psychotic disorder: A longitudinal investigation.
Kaori Usui; Kenji Kirihara; Mariko Tada; Mao Fujioka; Daisuke Koshiyama; Motoko Tani; Maiko Tsuchiya; Susumu Morita; Shintaro Kawakami; Akiko Kanehara; Kentaro Morita; Yoshihiro Satomura; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Psychiatry and clinical neurosciences, 29 Mar. 2022
AIM: Subjective quality of life is a clinically relevant outcome that is strongly associated with the severity of clinical symptoms in individuals with ultra-high risk for psychosis and patients with recent-onset psychotic disorder. Our objective was to examine whether longitudinal changes in clinical symptoms are associated with quality of life in ultra-high risk individuals and patients with recent-onset psychotic disorder. METHODS: Individuals with ultra-high risk and patients with recent-onset psychosis disorder were recruited in the same clinical settings at baseline and were followed up with more than 6 months and less than 5 years later. We assessed five factors of clinical symptoms using the positive and negative syndrome scale, and quality of life using the World Health Organization quality of life questionnaire-short form. We used multiple regression to examine the relationships between clinical symptoms and quality of life while controlling for diagnosis, follow-up period, age, and sex. RESULTS: Data were collected from 22 individuals with ultra-high risk and 27 patients with recent-onset psychosis disorder. The multiple regression analysis results indicated that the more severe anxiety/depression was at baseline, the poorer the quality of life at follow-up. Further, improvement of anxiety/depression and disorganized thoughts were associated with improvement in quality of life. The difference in diagnosis did not affect the association between clinical symptoms and quality of life. CONCLUSION: These findings suggest that the improvement of anxiety/depression and disorganized thoughts is important in the early stages of psychosis before it becomes severe, affecting the quality of life.

Improvements in obsessive-compulsive disorder and schizophrenia after left putaminal hemorrhage.
Kohei Echizen; Eisuke Sakakibara; Motomu Suga; Kiyoto Kasai
Psychiatry and clinical neurosciences, 13 Aug. 2021, [Reviewed]

Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes.
Daiki Sasabayashi; Yoichiro Takayanagi; Tsutomu Takahashi; Shimako Nishiyama; Yuko Mizukami; Naoyuki Katagiri; Naohisa Tsujino; Takahiro Nemoto; Atsushi Sakuma; Masahiro Katsura; Noriyuki Ohmuro; Naohiro Okada; Mariko Tada; Motomu Suga; Norihide Maikusa; Shinsuke Koike; Atsushi Furuichi; Mikio Kido; Kyo Noguchi; Hidenori Yamasue; Kazunori Matsumoto; Masafumi Mizuno; Kiyoto Kasai; Michio Suzuki
Translational psychiatry, 14 Jul. 2021, [Reviewed]
Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.

Neurocognitive Deficits Mediate the Relationship Between Structural Abnormalities and Clinical Outcomes in Individuals With Ultrahigh Risk for Psychosis: A Multimodal Neuroimaging and Longitudinal Neurocognitive Study
Shinsuke Koike; Mao Fujioka; Yosuke Takano; Norichika Iwashiro; Yoshihiro Satomura; Tatsuya Nagai; Daisuke Koshiyama; Mariko Tada; Tatsunobu Natsubori; Naohiro Okada; Osamu Abe; Kenji Kirihara; Hidenori Yamasue; Motomu Suga; Kiyoto Kasai
Schizophrenia Bulletin Open, 01 Jan. 2021
Abstract

Background

Cognitive deficits and improvements have been observed in individuals with ultrahigh risk for psychosis (UHR) over their clinical course, but the relationship between brain structural and functional characteristics, neurocognitive deficits and improvements, and clinical prognosis remains unclear.

Methods

A total of 50 UHR individuals were assessed using 129 neurocognitive assessments to explore cognitive deficits and improvements over 3 years. Neurocognitive deficits (intercept) and improvements (slope) were investigated using a general linear mixed model, and their relationship with symptom severity was assessed using the Positive and Negative Syndrome Scale five factor scores. In addition, psychobiological measurements including brain structure, brain activity during a verbal fluency task, and mismatch negativity were also tested. Possible models including the paths from brain structure, brain function, neurocognitive function, and symptom severity outcomes were compared.

Results

The intercept of verbal fluency was negatively associated with negative symptoms at baseline (corrected P = .0001) and at the 4-month follow-up (corrected P = .0016).A model including these relationships exhibited significant paths from the cortical surface area in the right banks of the superior temporal sulcus to verbal fluency (P &lt; .001) and from verbal fluency to 4-month negative symptoms (P &lt; .001), but not from brain activity to negative symptoms (P = .072).

Conclusion

Structural and functional characteristics of the brain may not be directly associated with short-term symptom severity, and these relationships may be partly mediated by neurocognitive function.

Is Utena's Brief Objective Measures (UBOM) useful in real-world behavioral assessment of functioning? Validity and utility testing in patients with schizophrenia.
Kingo Sawada; Eisuke Sakakibara; Akiko Kanehara; Haruna Koike; Motomu Suga; Yumiko Fujieda; Yuki Miyamoto; Masato Fukuda; Kiyoto Kasai
Psychiatry and clinical neurosciences, Jan. 2020, [Reviewed]
AIM: Utena's Brief Objective Measures (UBOM) was developed to assess psychophysiological functions proximal to real-world functioning in individuals with psychiatric disorders, including schizophrenia (SCZ), to facilitate shared decision-making. However, the validity of UBOM has not been fully examined. METHODS: We conducted a cross-sectional observational study to evaluate the validity of each of the three tests in UBOM: UBOM-Pulse, UBOM-Ruler, and UBOM-Random. We investigated associations: (i) between UBOM and existing cognitive- and autonomic-function tests; and (ii) between UBOM and daily social functioning. The participants included SCZ individuals and healthy controls. We evaluated the cognitive and autonomic function using UBOM, the heart rate variability test, the simple reaction time test, and the Brief Assessment of Cognition in Schizophrenia, Japanese version. We also assessed the daily social functioning using the WHO Disability Assessment Schedule 2.0 and the modified Global Assessment of Functioning, Japanese version. RESULTS: Thirty-one SCZ individuals and 35 healthy control individuals participated in this study. In the SCZ group, UBOM-Ruler was significantly associated with the Cognition and Getting Along domains of WHO Disability Assessment Schedule 2.0. UBOM-Random was significantly associated with the Brief Assessment of Cognition in Schizophrenia's Working Memory, Verbal Fluency and Attention domains, and the modified Global Assessment of Functioning in the SCZ group. CONCLUSION: The validity of the current version of UBOM is imperfect and further improvements will be necessary to attain the originally intended goal of developing a brief assessment tool for real-world functioning in SCZ.

Mismatch Negativity Predicts Remission and Neurocognitive Function in Individuals at Ultra-High Risk for Psychosis.
Mao Fujioka; Kenji Kirihara; Daisuke Koshiyama; Mariko Tada; Tatsuya Nagai; Kaori Usui; Susumu Morita; Shintaro Kawakami; Kentaro Morita; Yoshihiro Satomura; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Frontiers in psychiatry, 2020, [Reviewed]
Background: In the early intervention in psychosis, ultra-high risk (UHR) criteria have been used to identify individuals who are prone to develop psychosis. Although the transition rate to psychosis in individuals at UHR is 10% to 30% within several years, some individuals at UHR present with poor prognoses even without transition occurring. Therefore, it is important to identify biomarkers for predicting the prognosis of individuals at UHR, regardless of transition. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR. Materials and Methods: Individuals at UHR (n = 24) and healthy controls (HC; n = 18) participated in this study. In an auditory oddball paradigm, both dMMN and fMMN were measured at baseline. Remission and neurocognitive function after > 180 days were examined in the UHR group. Remission from UHR was defined as functional and symptomatic improvement using the Global Assessment of Functioning (GAF) score and Scale of Prodromal Symptoms (SOPS) positive subscales. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia (BACS). We examined differences in MMN amplitude at baseline between those who achieved remission (remitters) and those who did not (non-remitters). Multiple regression analyses were performed to identify predictors for functioning, positive symptoms, and neurocognitive function. Results: Compared with the HC group, the UHR group had a significantly attenuated dMMN amplitude (p = 0.003). In the UHR group, GAF scores significantly improved during the follow-up period (mean value 47.1 to 55.5, p = 0.004). The dMMN amplitude at baseline was significantly larger in the remitter (n = 6) than in the non-remitter group (n = 18) (p = 0.039). The total SOPS positive subscale scores and fMMN amplitude at baseline could predict BACS attention subscore at the follow-up point (SOPS positive subscales, p = 0.030; fMMN, p = 0.041). Conclusion: Our findings indicate that dMMN and fMMN predicted remission and neurocognitive function, respectively, in individuals at UHR, which suggests that there are both promising biomarker candidates for predicting prognosis in individuals at UHR.

Why some depressive patients perform suicidal acts and others do not
Tatsuo Akechi; Tadashi Kato; Noboru Fujise; Naohiro Yonemoto; Aran Tajika; Toshi A. Furukawa; Tatsuo Akechi; Shinji Shimodera; Mitsuhiko Yamada; Masatoshi Inagaki; Norio Watanabe; Naohiro Yonemoto; Kazuhira Miki; Yusuke Ogawa; Nozomi Takeshima; Aran Tajika; Teruhiko Higuchi; Yoshio Hirayasu; Akiko Kada; Tsukasa Koyama; Ichiro Kusumi; Takeshi Inoue; Yuki Kako; Kiyoto Kasai; Motomu Suga; Masafumi Mizuno; Naohisa Tsujino; Tatsuo Akechi; Masaki Kondo; Shigeto Yamawaki; Yasumasa Okamoto; Shinpei Inoue; Shigeru Morinobu; Shinji Shimodera; Naohisa Uchimura; Shingo Yasumoto; Keiichiro Mori; Manabu Ikeda; Noboru Fujise; Kahori Itoh; Kunihiko Kawamura; Takeshi Inoue; Masahito Tsukamoto; Miki Noda; Ikuko Nitta; Shin Nakagawa; Koichi Ito; Teruaki Tanaka; Yukie Usukubo; Tomoko Fujie; Yuki Kako; Ihoko Suzuki; Kazuyuki Sugishita; Naohiro Okada; Masaru Kinou; Kohei Marumo; Makoto Motoyama; Eisuke Sakakibara; Kazuki Taniguchi; Fumichika Nishimura; Mariko Tada; Shinjiro Dogan; Shuntaro Ando; Norichika Iwashiro; Bun Chino; Kazuhira Miki; Naohisa Tsujino; Yuki Kato; Sayaka Aikawa; Michiko Nakamura; Hiroko Hasuya; Tadashi Kato; Yoshio Ikeda; Yoshihiro Shinagawa; Masaki Kondo; Yoshiyuki Itakura; Ushio Isobe; Taku Sugiura; Toshiyuki Watanabe; Mino Kayukawa; Norio Watanabe; Tatsuo Akechi; Yumi Nakano; Akio Mantani; Ken'ichi Kurata; Ichiro Yanai; Kyoka Ozaki; Hiroaki Izumi; Yasuyuki Iwamoto; Yukitaka Morita; Ken Wada; Hajime Kubouchi; Hirotoshi Sato; Shinji Shimodera; Hirokazu Fujita; Takashi Itoh; Ryosuke Fujito; Sawako Kanno; Hiroshi Hashizume; Ippei Morokuma
Psychiatry and Clinical Neurosciences, 01 Oct. 2019, [Reviewed]

Gamma-band auditory steady-state response is associated with plasma levels of d-serine in schizophrenia: An exploratory study.
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Mao Fujioka; Kaori Usui; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kenji Hashimoto; Kiyoto Kasai
Schizophrenia research, Jun. 2019, [Reviewed]

Predictors of hypomanic and/or manic switch among patients initially diagnosed with unipolar major depression during acute-phase antidepressants treatment
Tatsuo Akechi; Tadashi Kato; Norio Watanabe; Shiro Tanaka; Toshi A. Furukawa; Toshi A. Furukawa; Tatsuo Akechi; Shinji Shimodera; Mitsuhiko Yamada; Masatoshi Inagaki; Norio Watanabe; Naohiro Yonemoto; Kazuhira Miki; Yusuke Ogawa; Nozomi Takeshima; Aran Tajika; Teruhiko Higuchi; Yoshio Hirayasu; Akiko Kada; Tsukasa Koyama; Ichiro Kusumi; Takeshi Inoue; Yuki Kako; Kiyoto Kasai; Motomu Suga; Masafumi Mizuno; Naohisa Tsujino; Tatsuo Akechi; Masaki Kondo; Shigeto Yamawaki; Yasumasa Okamoto; Shinpei Inoue; Shigeru Morinobu; Shinji Shimodera; Naohisa Uchimura; Shingo Yasumoto; Keiichiro Mori; Manabu Ikeda; Noboru Fujise
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Feb. 2019, [Reviewed]

Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: A longitudinal investigation.
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Mao Fujioka; Eriko Ichikawa; Kazusa Ohta; Motoko Tani; Maiko Tsuchiya; Akiko Kanehara; Kentaro Morita; Kingo Sawada; Jun Matsuoka; Yoshihiro Satomura; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, Nov. 2018, [Reviewed]
OBJECTIVES: The gamma-band auditory steady-state response (ASSR) is thought to reflect the function of parvalbumin-positive γ-aminobutyric acid (GABA)-ergic interneurons and may be a candidate biomarker in early psychosis. Although previous cross-sectional studies have shown that gamma-band ASSR is reduced in early psychosis, whether reduced gamma-band ASSR could be a predictor of the long-term prognosis remains unknown. METHODS: In this longitudinal study, we investigated the association between gamma-band ASSR reduction and future global symptomatic or functional outcome in early psychosis. We measured 40-Hz ASSR in 34 patients with recent-onset schizophrenia (ROSZ), 28 ultra-high risk (UHR) individuals, and 30 healthy controls (HCs) at baseline. After 1-2 years, we evaluated the global assessment of functioning (GAF) in the ROSZ (N = 20) and UHR (N = 20) groups. RESULTS: The 40-Hz ASSR was significantly reduced in the ROSZ and UHR groups. The attenuated 40-Hz ASSR was correlated with the future global symptomatic outcome in the ROSZ, but not in the UHR groups. CONCLUSIONS: A reduction in the gamma-band ASSR after the onset of psychosis may predict symptomatic outcomes in early psychosis. SIGNIFICANCE: Gamma-band ASSR may be a potentially useful biomarker of the long-term prognosis in patients with recent-onset schizophrenia.

Electrophysiological evidence for abnormal glutamate-GABA association following psychosis onset.
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Mao Fujioka; Eriko Ichikawa; Kazusa Ohta; Motoko Tani; Maiko Tsuchiya; Akiko Kanehara; Kentaro Morita; Kingo Sawada; Jun Matsuoka; Yoshihiro Satomura; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Translational psychiatry, 08 Oct. 2018, [Reviewed]
Previous studies have shown glutamatergic dysfunction and γ-aminobutyric acid (GABA)-ergic dysfunction in schizophrenia. Animal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dysfunction and GABA-ergic dysfunction interact with each other and lead to alterations in excitatory/inhibitory balance. The NMDAR and GABAergic-interneuron functions may be indexed by mismatch negativity (MMN) and auditory steady-state gamma-band response (ASSR), respectively. However, no previous studies have tested the hypothesis of an abnormal association between MMN and gamma-band ASSR in the same patients to identify the in vivo evidence of NMDAR-GABA association during the early stages of psychosis. Participants were individuals with recent-onset schizophrenia (ROSZ; N = 21), ultra-high risk (UHR; N = 27), and healthy controls (HCs; N = 24). The MMN amplitude was significantly impaired in ROSZ (p = 0.001, d = 1.20) and UHR (p = 0.003, d = 1.01) compared with HCs. The intertrial phase coherence (ITC) index of gamma-band ASSR was significantly reduced in ROSZ compared with HCs (p < 0.001, d = -1.27) and UHR (p = 0.032, d = -0.75). The event-related spectral perturbation (ERSP) index of gamma-band ASSR was significantly smaller in ROSZ compared with HCs (p < 0.001, d = -1.21). The MMN amplitude was significantly correlated with the ITC in ROSZ (r = -0.69, p < 0.001). These findings provide the first in vivo evidence that an abnormal association of the electrophysiological indices of NMDAR and GABA dysfunctions may be present in recent-onset schizophrenia.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.
Tadashi Kato; Toshi A Furukawa; Akio Mantani; Ken'ichi Kurata; Hajime Kubouchi; Susumu Hirota; Hirotoshi Sato; Kazuyuki Sugishita; Bun Chino; Kahori Itoh; Yoshio Ikeda; Yoshihiro Shinagawa; Masaki Kondo; Yasumasa Okamoto; Hirokazu Fujita; Motomu Suga; Shingo Yasumoto; Naohisa Tsujino; Takeshi Inoue; Noboru Fujise; Tatsuo Akechi; Mitsuhiko Yamada; Shinji Shimodera; Norio Watanabe; Masatoshi Inagaki; Kazuhira Miki; Yusuke Ogawa; Nozomi Takeshima; Yu Hayasaka; Aran Tajika; Kiyomi Shinohara; Naohiro Yonemoto; Shiro Tanaka; Qi Zhou; Gordon H Guyatt
BMC medicine, 11 Jul. 2018, [Reviewed]
BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Lack of correlation between phonetic magnetic mismatch field and plasma D-serine levels in humans
Motomu Suga; Yuki Kawakubo; Yukika Nishimura; Kenji Hashimoto; Masato Yumoto; Kiyoto Kasai
CLINICAL NEUROPHYSIOLOGY, Jul. 2018, [Reviewed]

Association between mismatch negativity and global functioning is specific to duration deviance in early stages of psychosis.
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Mao Fujioka; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Schizophrenia research, May 2018, [Reviewed]
BACKGROUND: Mismatch negativity (MMN) is a candidate biomarker for early stages of psychosis. Although an association among duration MMN (dMMN), cognitive deficits, and functional outcome in chronic schizophrenia has been shown by a large-scale study, the effects of deviant type and clinical stages have not been investigated. METHODS: We investigated the relationships among dMMN, frequency MMN (fMMN), global functioning, and cognitive function in early stages of psychosis. The participants included 26 individuals with recent-onset schizophrenia (ROSZ), 30 individuals with ultra-high risk (UHR), and 20 healthy controls. RESULTS: The correlational analyses revealed that dMMN amplitude, which was impaired in the ROSZ group compared to the healthy controls, correlated with global functioning (Global Assessment of Functioning-Functioning scale) in the ROSZ (r=-0.45) and UHR (r=-0.37) groups. The amplitude of fMMN, which did not differ among the groups, correlated with working memory (r=-0.57) only in the ROSZ group. The path analyses indicated that dMMN had a direct effect on global functioning in the ROSZ and UHR groups while fMMN had a direct effect on working memory only in the ROSZ group. CONCLUSIONS: Our findings suggested that the association between MMN and global functioning was specific to the duration deviant and was already present in early stages of psychosis. These findings confirm the usefulness of dMMN as a biological marker of early psychosis to guide treatment interventions.

Duration and frequency mismatch negativity shows no progressive reduction in early stages of psychosis.
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
Schizophrenia research, Dec. 2017, [Reviewed]

Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis.
Tatsuya Nagai; Kenji Kirihara; Mariko Tada; Daisuke Koshiyama; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kenji Hashimoto; Kiyoto Kasai
Scientific reports, 23 May 2017, [Reviewed]

Identifying neurocognitive markers for outcome prediction of global functioning in individuals with first-episode and ultra-high-risk for psychosis.
Kingo Sawada; Akiko Kanehara; Eisuke Sakakibara; Satoshi Eguchi; Mariko Tada; Yoshihiro Satomura; Motomu Suga; Shinsuke Koike; Kiyoto Kasai
Psychiatry and clinical neurosciences, May 2017, [Reviewed]
AIM: There is an increasing need for identifying neurocognitive predictors of global functional outcome in early psychosis toward optimizing an early intervention strategy. METHODS: We conducted a longitudinal observational study to investigate an association between neurocognitive assessments at baseline and global functional outcome at an average of 1-year follow up. Participants included ultra-high-risk for psychosis (UHR) individuals who had not converted to psychosis during the follow-up period (UHR-NP) and those with first-episode psychosis (FEP). We evaluated neurocognition at baseline using the Brief Assessment of Cognition in Schizophrenia Japanese version, including Verbal Memory, Working Memory, Motor Speed, Verbal Fluency, Attention/Processing Speed, and Executive Function. We also assessed global functional outcome using the modified Global Assessment of Functioning (mGAF) scale both at baseline and after the follow-up period. RESULTS: Thirty-four UHR-NP individuals (34/47, 72%) and 29 FEP individuals (29/36, 81%) completed assessment of neurocognitive function at baseline and functional outcome at follow up. In the UHR-NP group, Attention/Processing Speed was significantly associated with the mGAF score at follow up. In the FEP group, Executive Function was significantly associated with the average mGAF score during follow up. CONCLUSION: Attention/Processing Speed and Executive Function at baseline may predict global functional outcome of early psychosis. These neurocognitive tests are easy to incorporate in clinical settings and, if replicated in independent samples, may be included in routine clinical assessments for prediction of functional outcome in early psychosis.

Associations between daily living skills, cognition, and real-world functioning across stages of schizophrenia; a study with the Schizophrenia Cognition Rating Scale Japanese version.
Yuko Higuchi; Tomiki Sumiyoshi; Tomonori Seo; Motomu Suga; Tsutomu Takahashi; Shimako Nishiyama; Yuko Komori; Kiyoto Kasai; Michio Suzuki
Schizophrenia research. Cognition, Mar. 2017, [Reviewed]

Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins.
Yukika Nishimura; Yuki Kawakubo; Motomu Suga; Kenji Hashimoto; Yuichi Takei; Kunio Takei; Hideyuki Inoue; Masato Yumoto; Ryu Takizawa; Kiyoto Kasai
Molecular neuropsychiatry, Oct. 2016, [Reviewed]
Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

Letter to the editor; A corrigendum with respect to our research article entitled "Association between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study".
Norichika Iwashiro; Shinsuke Koike; Yoshihiro Satomura; Motomu Suga; Tatsuya Nagai; Tatsunobu Natsubori; Mariko Tada; Wataru Gonoi; Ryu Takizawa; Akira Kunimatsu; Hidenori Yamasue; Kiyoto Kasai
Schizophrenia research, Oct. 2016, [Reviewed]

Magnetoencephalographic recording of auditory mismatch negativity in response to duration and frequency deviants in a single session in patients with schizophrenia
Motomu Suga; Yukika Nishimura; Yuki Kawakubo; Masato Yumoto; Kiyoto Kasai
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Jul. 2016, [Reviewed]

Association between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study.
Norichika Iwashiro; Shinsuke Koike; Yoshihiro Satomura; Motomu Suga; Tatsuya Nagai; Tatsunobu Natsubori; Mariko Tada; Wataru Gonoi; Ryu Takizawa; Akira Kunimatsu; Hidenori Yamasue; Kiyoto Kasai
Schizophrenia research, Apr. 2016, [Reviewed]
Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia.

Differential Alterations of Auditory Gamma Oscillatory Responses Between Pre-Onset High-Risk Individuals and First-Episode Schizophrenia
Mariko Tada; Tatsuya Nagai; Kenji Kirihara; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Tetsuo Kobayashi; Kiyoto Kasai
CEREBRAL CORTEX, Mar. 2016, [Reviewed]

Role of Departments of Psychiatry in University Hospitals as a Developer, Provider, and Educator of Innovative Clinical Psychiatry
Kiyoto Kasai; Akiko Kanehara; Yoshihiro Satomura; Motomu Suga; Go Taniguchi; Kayo Ichihashi; Yukiko Kano; Shinsuke Kondo
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 2016, [Reviewed]
The roles of university hospital psychiatric departments are: 1) the development and pro- vision of advanced psychiatric treatments unique to university hospitals, 2) the provision of psychiatric intervention models for patients with physical diseases, and 3)the provision of real- world environments for young psychiatrists to learn the principles and experience the practice of such innovative care. As for 1), our facility offers a hospitalization for examination program, which uses near-infrared spectroscopy as a biomarker useful for the auxiliary diagnosis of psy- chiatric disease and selection of the treatment method. University psychiatric departments also play a major role in neuropsychiatry, such as through the use of Epilepsy Monitoring Units (EMU) to differentiate between epilepsy and psychogenic non-epileptic seizures (PNES). Additionally, hospitalizations for examination programs are being implemented for psychosocial and employment support for psychiatric patients, and the diagnosis and evaluation of develop- mental disorders. With regard to 2), our facility has a psychiatric liaison-consultation team. In addition to providing consultation for all departments on delirium, anxiety, and depression, they are actively committed to various transplant treatments. There is also a strong cooperative relationship between the critical care center and psychiatric department. Of the patients hospi- talized for physical conditions and emergencies, over ten percent require psychiatric support, and without the psychiatric department, many patients with severe physical diseases cannot be treated. As such, the medical fees for psychiatric departments in universities and general hospitals should be evaluated appropriately. We would like to propose an "Advanced Psychiat- ric Treatment Development Management Center" (tentative name) to manage the following cycle : a) every university psychiatric department will develop and offer model projects utiliz- ing their respective expertise and specialties ; b) after collecting information on best practices, they will establish evidence through multicenter research, Diagnosis Procedure Combination (DPC) data, and others ; c) they will progress to advanced medical treatments and insurance coverage ; and d) they will continue to improve quality. Finally, I emphasize the role of univer- sity psychiatric departments as the center of education where young psychiatrists learn the principles and experience the practice of such an advanced care model, which will innovate and reform future mental health care.

Psychological symptom and social functioning subscales of the modified Global Assessment of Functioning scale: reliability and validity of the Japanese version.
Satoshi Eguchi; Shinsuke Koike; Motomu Suga; Ryu Takizawa; Kiyoto Kasai
Psychiatry and clinical neurosciences, Feb. 2015, [Reviewed]

Oxytocin improves behavioural and neural deficits in inferring others' social emotions in autism.
Yuta Aoki; Noriaki Yahata; Takamitsu Watanabe; Yosuke Takano; Yuki Kawakubo; Hitoshi Kuwabara; Norichika Iwashiro; Tatsunobu Natsubori; Hideyuki Inoue; Motomu Suga; Hidemasa Takao; Hiroki Sasaki; Wataru Gonoi; Akira Kunimatsu; Kiyoto Kasai; Hidenori Yamasue
Brain : a journal of neurology, Nov. 2014, [Reviewed]

Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene.
Yuki Saito; Motomu Suga; Mamoru Tochigi; Osamu Abe; Noriaki Yahata; Yuki Kawakubo; Xiaoxi Liu; Yoshiya Kawamura; Tsukasa Sasaki; Kiyoto Kasai; Hidenori Yamasue
Social cognitive and affective neuroscience, Oct. 2014, [Reviewed]

SUNoD 大うつ病に対する新規抗うつ剤の最適使用戦略を確立するための大規模無作為割り付け比較試験
古川 壽亮; 下寺 信次; 明智 龍男; 山田 光彦; 渡辺 範雄; 稲垣 正俊; 三木 和平; 米本 直裕; 小川 雄右; 田近 亜蘭; 竹島 望; 篠原 清美; 藤瀬 昇; 相澤 明憲; 池田 学; 安元 眞吾; 広田 進; 内村 直尚; 岡本 泰昌; 高石 佳幸; 萬谷 昭夫; 倉田 健一; 山脇 成人; 藤田 博一; 窪内 肇; 森信 繁; 近藤 真前; 加藤 正; 辻野 尚久; 茅野 分; 水野 雅文; 管 心; 杉下 和行; 笠井 清登; 井上 猛; 伊東 かほり; 久住 一郎; SUN-D臨床試験グループ
精神医学, Jun. 2014, [Reviewed]

A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study
Koike S; Bundo M; Iwamoto K; Suga M; Kuwabara H; Ohashi Y; Shinoda K; Takano Y; Iwashiro N; Satomura Y; Nagai T; Natsubori T; Tada M; Yamasue H; Kasai K
TRANSLATIONAL PSYCHIATRY, Apr. 2014, [Reviewed]

Genetic influences on prefrontal activation during a verbal fluency task in adults: a twin study based on multichannel near-infrared spectroscopy.
Eisuke Sakakibara; Ryu Takizawa; Yukika Nishimura; Shingo Kawasaki; Yoshihiro Satomura; Akihide Kinoshita; Shinsuke Koike; Kohei Marumo; Masaru Kinou; Mamoru Tochigi; Nao Nishida; Katsushi Tokunaga; Satoshi Eguchi; Syudo Yamasaki; Tatsunobu Natsubori; Norichika Iwashiro; Hideyuki Inoue; Yosuke Takano; Kunio Takei; Motomu Suga; Hidenori Yamasue; Junko Matsubayashi; Kenji Kohata; Chie Shimojo; Shiho Okuhata; Toshiaki Kono; Hitoshi Kuwabara; Ayaka Ishii-Takahashi; Yuki Kawakubo; Kiyoto Kasai
NeuroImage, 15 Jan. 2014, [Reviewed]

Development of brief versions of the Wechsler Intelligence Scale for schizophrenia: Considerations of the structure and predictability of intelligence
Chika Sumiyoshi; Miki Uetsuki; Motomu Suga; Kiyoto Kasai; Tomiki Sumiyoshi
PSYCHIATRY RESEARCH, 30 Dec. 2013, [Reviewed]

双極性障害II型に線維筋痛症を合併し、mECTに抵抗性を示した1例　　　　　　　　　　　　　　　
Aug. 2013

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
兼田 康宏; 住吉 太幹; 中込 和幸; 池澤 聰; 大森 哲郎; 古郡 規雄; 功刀 浩; 松尾 淳子; 宮本 聖也; 中村 純; 久住 一郎; 岡久 祐子; 小林 正義; 岡村 愛子; 鈴木 雄太郎; 管 心; 尾崎 紀夫; 吉田 泰介; 長田 泉美; 加藤 淳一; 浦田 暁菜; 佐久間 寛之; 永嶌 朋久; 石郷岡 純; 船橋 英樹; 羽下 路子; 赤澤 将文; 芳賀 大輔; 羽鳥 乃路; 原田 俊樹; 中谷 真樹; 児嶋 亮; 上原 優子; 松本 香子
精神医学, Feb. 2013

A multimodal approach to investigate biomarkers for psychosis in a clinical setting: the integrative neuroimaging studies in schizophrenia targeting for early intervention and prevention (IN-STEP) project.
Shinsuke Koike; Yosuke Takano; Norichika Iwashiro; Yoshihiro Satomura; Motomu Suga; Tatsuya Nagai; Tatsunobu Natsubori; Mariko Tada; Yukika Nishimura; Syudo Yamasaki; Ryu Takizawa; Noriaki Yahata; Tsuyoshi Araki; Hidenori Yamasue; Kiyoto Kasai
Schizophrenia research, Jan. 2013, [Reviewed]
Longitudinal clinical investigations and biological measurements have determined not only progressive brain volumetric and functional changes especially around the onset of psychosis but also the abnormality of developmental pathways based on gene-environment interaction model. However, these studies have contributed little to clinical decisions on their diagnosis and therapeutic choices because of subtle differences between patients and healthy controls. A multi-modal approach may resolve this limitation and is favorable to explore the pathophysiology of psychosis. The integrative neuroimaging studies for schizophrenia targeting early intervention and prevention (IN-STEP) is a research project aimed at exploring the pathophysiological features of the onset of psychosis and investigating possible predictive biomarkers for the clinical treatment of psychosis. Since 2008, we have adopted blood sampling, neurocognitive batteries, neurophysiological assessment, structural imaging, and functional imaging longitudinally for help-seeking ultra-high-risk (UHR) individuals and patients with first-episode psychosis (FEP). Here, we intend to introduce the IN-STEP research study protocol and present preliminary clinical findings. Thirty-seven UHR individuals and 30 patients with FEP participated in this study. Six months later, there was no difference in objective and subjective scores between the groups, which suggests that young people having symptoms and functional deficits should be cared for regardless of their history of psychosis according to their clinical stages. The rate of transition to psychosis was 7.1%, 8.0%, and 35.3% (at 6, 12, and 24months, respectively). Through this research project, we expect to clarify the pathophysiological features around the onset of psychosis and improve the prognosis of psychosis through clinical application.

Activations in the prefrontal cortex predict functional outcome in ultra-high risk and first-episode psychosis
Koike Shinsuke; Kawasaki Shingo; Satomura Yoshihiro; Nishimura Yukika; Takano Yosuke; Iwashiro Norichika; Suga Motomu; Takizawa Ryu; Araki Tsuyoshi; Kasai Kiyoto
EARLY INTERVENTION IN PSYCHIATRY, Oct. 2012, [Reviewed]

Localized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia.
Norichika Iwashiro; Motomu Suga; Yosuke Takano; Hideyuki Inoue; Tatsunobu Natsubori; Yoshihiro Satomura; Shinsuke Koike; Noriaki Yahata; Mizuho Murakami; Masaki Katsura; Wataru Gonoi; Hiroki Sasaki; Hidemasa Takao; Osamu Abe; Kiyoto Kasai; Hidenori Yamasue
Schizophrenia research, May 2012, [Reviewed]
Recent studies have suggested an important role for Broca's region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Broca's region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3 Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.

Phonological fluency is uniquely impaired in Japanese-speaking schizophrenia patients: confirmation study.
Motomu Suga; Miki Uetsuki; Ryu Takizawa; Tsuyoshi Araki; Kiyoto Kasai
Psychiatry and clinical neurosciences, Dec. 2011, [Reviewed]
In alphabet-based language-speaking patients with schizophrenia, category fluency is disproportionately disturbed as compared with phonological fluency. Deficits in category and phonological fluency observed in Japanese patients, however, were similar. The aim of the present study was to replicate these findings by modifying the task to minimize the influence of lack of motivation and concentration in the patients. Similar deficits were found in both types of fluency in Japanese patients. Patients who speak Japanese have deficits in phonological fluency, compared with patients who speak alphabet-based languages, suggesting that the pattern of impairment in verbal fluency in schizophrenia is dependent on the specific language system.

Reply to: Neurogenetic Effects of OXTR rs2254298 in the Extended Limbic System of Healthy Caucasian Adults
Hidenori Yamasue; Motomu Suga; Noriaki Yahata; Hideyuki Inoue; Mamoru Tochigi; Osamu Abe; Xiaoxi Liu; Yoshiya Kawamura; Mark A. Rogers; Kunio Takei; Haruyasu Yamada; Shigeki Aoki; Tsukasa Sasaki; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, Nov. 2011, [Reviewed]

Criterion and Construct Validity of the CogState Schizophrenia Battery in Japanese Patients with Schizophrenia
Taisuke Yoshida; Motomu Suga; Kunimasa Arima; Yasuko Muranaka; Tsunehiko Tanaka; Satoshi Eguchi; Crystal Lin; Sumiko Yoshida; Masanori Ishikawa; Yuko Higuchi; Tomonori Seo; Yoshinori Ueoka; Masahito Tomotake; Yasuhiro Kaneda; David Darby; Paul Maruff; Masaomi Iyo; Kiyoto Kasai; Teruhiko Higuchi; Tomiki Sumiyoshi; Tetsuro Ohmori; Kiyohisa Takahashi; Kenji Hashimoto
PLOS ONE, May 2011, [Reviewed]

Impaired ability to organize information in individuals with autism spectrum disorders and their siblings
Chika Sumiyoshi; Yuki Kawakubo; Motomu Suga; Tomiki Sumiyoshi; Kiyoto Kasai
NEUROSCIENCE RESEARCH, Mar. 2011, [Reviewed]

Gray matter volume changes of subregions in inferior frontal gyrus around the onset of schizophrenia
Iwashiro Norichika; Yamasue Hidenori; Suga Motomu; Natsubori Tatsunobu; Takano Yousuke; Inoue Hideyuki; Satomura Yoshihiro; Koike Shinsuke; Yahata Noriaki; Murakami Mizuho; Katsura Masaki; Gonoi Wataru; Sasaki Hiroki; Takao Hidemasa; Abe Osamu; Kasai Kiyoto
NEUROSCIENCE RESEARCH, 2011, [Reviewed]

Effects of metabotropic glutamate receptor 3 genotype on phonetic mismatch negativity.
Yuki Kawakubo; Motomu Suga; Mamoru Tochigi; Masato Yumoto; Kenji Itoh; Tsukasa Sasaki; Yukiko Kano; Kiyoto Kasai
PloS one, 2011, [Reviewed]
BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia.

Reduced Gray Matter Volume of Pars Opercularis Is Associated with Impaired Social Communication in High-Functioning Autism Spectrum Disorders
Syudo Yamasaki; Hidenori Yamasue; Osamu Abe; Motomu Suga; Haruyasu Yamada; Hideyuki Inoue; Hitoshi Kuwabara; Yuki Kawakubo; Noriaki Yahata; Shigeki Aoki; Yukiko Kano; Nobumasa Kato; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, 15 Dec. 2010, [Reviewed]

Association between the oxytocin receptor gene and amygdalar volume in healthy adults.
Hideyuki Inoue; Hidenori Yamasue; Mamoru Tochigi; Osamu Abe; Xiaoxi Liu; Yoshiya Kawamura; Kunio Takei; Motomu Suga; Haruyasu Yamada; Mark A Rogers; Shigeki Aoki; Tsukasa Sasaki; Kiyoto Kasai
Biological psychiatry, 01 Dec. 2010, [Reviewed]

A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation.
Yosuke Eriguchi; Hidenori Yamasue; Nagafumi Doi; Takuji Nishida; Osamu Abe; Haruyasu Yamada; Shigeki Aoki; Motomu Suga; Hideyuki Inoue; Hiroi Nonaka; Takayuki Obata; Hiroo Ikehira; Keiko Kobayashi; Kiyoto Kasai
Epilepsia, Dec. 2010, [Reviewed]

【大脳機能局在はここまで分かった】その他 脳梁の解剖と機能　　　　　　　　　　　　　　　
Oct. 2010

Reduced gray matter volume of Brodmann's Area 45 is associated with severe psychotic symptoms in patients with schizophrenia.
Motomu Suga; Hidenori Yamasue; Osamu Abe; Syudo Yamasaki; Haruyasu Yamada; Hideyuki Inoue; Kunio Takei; Shigeki Aoki; Kiyoto Kasai
European archives of psychiatry and clinical neuroscience, Sep. 2010, [Reviewed]
Previous literature has suggested an important role of inferior frontal gyrus, which mainly consists of Brodmann's Area (BA) 44 and 45, in the pathophysiology of schizophrenia. While recent neuroimaging techniques have revealed differential functional correlates of BA 44 and 45 in healthy individuals, previous studies have not yet separately evaluated the gray matter volume reduction of BA 44 and 45 and their relationships to psychotic symptoms in patients with schizophrenia. In the present study, magnetic resonance images were obtained from 29 right-handed male patients with schizophrenia and from 29 age- and handedness-matched healthy male controls. The reliable manual tracing methodology was employed to measure the gray matter volume of BA 44 and BA 45. The severities of psychotic symptoms were evaluated using the five-factor model of positive and negative syndrome scale in the patient group. A significant gray matter volume reduction of both the BA 44 and BA 45 was found bilaterally in the patients with schizophrenia compared with the healthy controls. Among these inferior frontal sub-regions, reduced volume of right BA 45 revealed the largest effect size. In addition, the reduced volume of BA 45 in left hemisphere showed a significant association with the increased severity of delusional behavior, while the severity of disorganized and positive symptoms were correlated with the bilateral BA 45 volumes in the patient group. The findings support an important role of inferior frontal gyrus in the pathophysiology of schizophrenia. The present study further demonstrated that BA 45 might especially contribute to the production of psychotic symptoms in the patients with schizophrenia.

Sex dimorphism in gray/white matter volume and diffusion tensor during normal aging.
Osamu Abe; Hidenori Yamasue; Haruyasu Yamada; Yoshitaka Masutani; Hiroyuki Kabasawa; Hiroki Sasaki; Kunio Takei; Motomu Suga; Kiyoto Kasai; Shigeki Aoki; Kuni Ohtomo
NMR in biomedicine, Jun. 2010, [Reviewed]

Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes.
Hideyuki Inoue; Hidenori Yamasue; Mamoru Tochigi; Kunio Takei; Motomu Suga; Osamu Abe; Haruyasu Yamada; Mark A Rogers; Shigeki Aoki; Tsukasa Sasaki; Kiyoto Kasai
Brain research, 17 May 2010, [Reviewed]

Functional (GT)n polymorphisms in promoter region of N-methyl-d-aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumes.
H Inoue; H Yamasue; M Tochigi; M Suga; Y Iwayama; O Abe; H Yamada; M A Rogers; S Aoki; T Kato; T Sasaki; T Yoshikawa; K Kasai
Genes, brain, and behavior, Apr. 2010
The glutamate system including N-methyl-d-aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene (GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers (n = 89) than in those with homozygous long alleles (n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development.

Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression.
Osamu Abe; Hidenori Yamasue; Kiyoto Kasai; Haruyasu Yamada; Shigeki Aoki; Hideyuki Inoue; Kunio Takei; Motomu Suga; Koji Matsuo; Tadafumi Kato; Yoshitaka Masutani; Kuni Ohtomo
Psychiatry research, 30 Jan. 2010, [Reviewed]

Association between the oxytocin receptor gene (OXTR) and amygdalar volume in healthy adults
Hideyuki Inoue; Hidenori Yamasue; Mamoru Tochigi; Osamu Abe; Kunio Takei; Motomu Suga; Haruyasu Yamada; Mark A. Rogers; Shigeki Aoki; Xiaoxi Liu; Yoshiya Kawamura; Tsukasa Sasaki; Kiyoto Kasai
NEUROSCIENCE RESEARCH, 2010, [Reviewed]

Structural disruption of the dorsal cingulum bundle is associated with impaired Stroop performance in patients with schizophrenia
Kunio Takei; Hidenori Yamasue; Osamu Abe; Haruyasu Yamada; Hideyuki Inoue; Motomu Suga; Miya Muroi; Hiroki Sasaki; Shigeki Aoki; Kiyoto Kasai
SCHIZOPHRENIA RESEARCH, Oct. 2009, [Reviewed]

Structural and diffusional brain abnormality related to relatively low level alcohol consumption.
Hiroki Sasaki; Osamu Abe; Hidenori Yamasue; Rin Fukuda; Haruyasu Yamada; Kunio Takei; Motomu Suga; Hidemasa Takao; Kiyoto Kasai; Shigeki Aoki; Kuni Ohtomo
NeuroImage, Jun. 2009, [Reviewed]
Chronic excessive alcohol intake results in alcohol-related brain damage. Many previous reports have documented alcohol-related global or local brain shrinkage or diffusional abnormalities among alcoholics and heavy to moderate drinkers; however, the influence of relatively low levels of alcohol consumption on brain structural or diffusional abnormality is unclear. We investigated structural or diffusional abnormalities related to lifetime alcohol consumption (LAC) using voxel-based morphometry (VBM) among Japanese non-alcohol-dependent individuals (114 males, 97 females). High-resolution three-dimensional magnetic resonance images and diffusion tensor imaging were acquired in all subjects. The collected images were normalized, segmented, and smoothed using SPM 5. Gray matter volume (GMV) and white matter volume (WMV) were normalized for each total intracranial volume (TIV), and partial correlation coefficients were estimated between normalized GMV or WMV and lifetime alcohol consumption (LAC) adjusted for age. To investigate regional GMV or WMV abnormalities related to LAC, multiple regression analyses were performed among regional GMV or WMV and LAC, age, and TIV. To investigate subtle regional abnormalities, multiple regression analyses were performed among fractional anisotropy (FA) or mean diffusivity (MD), and LAC and age. No LAC-related global or regional GMV or WMV abnormality or LAC-related regional FA abnormality was found among male or female subjects. Significant LAC-related MD increase was found in the right amygdala among female subjects only. The current results suggest female brain vulnerability to alcohol, and a relation between subtle abnormality in the right amygdala and alcohol misuse.

非定型抗精神病薬治療群における統合失調症症状と認知機能障害の特徴、およびその個体差の脳形態基盤同定　　　　　　　　　　　　　　　
Mar. 2009

The influence of gender and personality traits on individual difference in auditory mismatch: a magnetoencephalographic (MMNm) study.
Junko Matsubayashi; Yuki Kawakubo; Motomu Suga; Yuichi Takei; Sumie Kumano; Masato Fukuda; Kenji Itoh; Masato Yumoto; Kiyoto Kasai
Brain research, 21 Oct. 2008, [Reviewed]
The mismatch negativity (MMN; and its magnetic counterpart, MMNm) is widely used to assess early-stage auditory cortical function in humans and its impairment in various neuropsychiatric disorders. To establish MMN as a useful clinical tool for objective monitoring of auditory cortical function in an individual, we investigated the effect of gender and personality traits on individual difference in MMNm in healthy subjects. Participants were 88 healthy adults (31 women and 57 men). The MMNm in response to the duration or frequency change of tones and those in response to across-phoneme change between vowels /a/ and /o/ were recorded using 204-channel whole-head magnetoencephalography. The temperament and character inventory (TCI) was used to assess individual personality traits. Women were associated with significantly delayed peak latency of phonetic MMNm for the right hemisphere compared with men. Men had greater strength of tonal duration MMNm for the left hemisphere than women. Additionally, the persistence score predicted the strength of phonetic MMNm for the left hemisphere in the combined sample and the tonal duration MMNm for the left hemisphere in men; reward dependence predicted the latency of the tonal duration MMNm for the left hemisphere in men; and cooperativeness predicted the strength of the tonal frequency MMNm for the right hemisphere in women. These results suggest that gender and personality traits have an effect on individual variability of the MMNm. Our observation may provide useful information to establish MMN/MMNm as a clinical tool for monitoring auditory cortical function on an individual basis.

Sex-linked neuroanatomical basis of human altruistic cooperativeness
Hidenori Yamasue; Osamu Abe; Motomu Suga; Haruyasu Yamada; Mark A. Rogers; Shigeki Aoki; Nobumasa Kato; Kiyoto Kasai
CEREBRAL CORTEX, Oct. 2008, [Reviewed]

Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdala.
H Yamasue; C Kakiuchi; M Tochigi; H Inoue; M Suga; O Abe; H Yamada; T Sasaki; M A Rogers; S Aoki; T Kato; K Kasai
Genes, brain, and behavior, Aug. 2008
Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders.

Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia
Kunio Takei; Hidenori Yamasue; Osamu Abe; Haruyasu Yamada; Hideyuki Inoue; Motomu Suga; Kayoko Sekita; Hiroki Sasaki; Mark Rogers; Shigeki Aoki; Kiyoto Kasai
SCHIZOPHRENIA RESEARCH, Aug. 2008, [Reviewed]

The association between the val158met polymorphism of the catecol-O-methyl transferase gene and morphological abnormalities of the brain in patients with schizophrenia
Suga M; Yamasue H; Tochigi M; Inoue H; Iwayama Y; Abe O; Yamada H; Aoki S; Kato T; Sasaki T; Yoshikawa T; Kasai K
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Feb. 2008, [Reviewed]

Schizophrenia susceptibility genes and the volume of hippocampus
Inoue H; Yamasue H; Tochigi M; Suga M; Abe O; Yamada H; Aoki S; Sasaki T; Kasai K
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Feb. 2008, [Reviewed]

Gender-common and -specific neuroanatomical basis of human anxiety-related personality traits
Hidenori Yamasue; Osamu Abe; Motomu Suga; Haruyasu Yamada; Hideyuki Inoue; Mamoru Tochigi; Mark Rogers; Shigeki Aoki; Nobumasa Kato; Kiyoto Kasai
CEREBRAL CORTEX, Jan. 2008, [Reviewed]

Aging in the CNS: comparison of gray/white matter volume and diffusion tensor data.
Osamu Abe; Hidenori Yamasue; Shigeki Aoki; Motomu Suga; Haruyasu Yamada; Kiyoto Kasai; Yoshitaka Masutani; Nobuyuki Kato; Nobumasa Kato; Kuni Ohtomo
Neurobiology of aging, Jan. 2008, [Reviewed]

統合失調症のMMN研究 統合失調症における純音・音素刺激ミスマッチ磁場の異常と臨床応用の可能性
Oct. 2007

肝移植後もてんかん発作が出現している成人発症2型高シトルリン血症の1例 画像統計解析と脳内グルタミン酸濃度測定の臨床応用　　　　　　　　　　　　　　　
Jul. 2007

[Investigating endophenotype of endogeneous psychotic disorders].
Hidenori Yamasue; Motomu Suga; Kiyoto Kasai
Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, Jun. 2007, [Reviewed]
Accumulated evidence from a number of previous structural MRI studies have revealed 1) the existence of abnormalities even at the brain structural level in subjects at an early stage of endogeneous psychotic illness, including schizophrenia and bipolar disorder, and 2) the existence of similar brain structural abnormalities to the patients even in individuals at high-risk of endogeneous psychotic illness. Recently, an increasing number of studies have investigated the associations between the functional polymorphism of candidate genes for susceptibility to schizophrenia and regional brain volume, a highly heritable trait marker, to uncover the linkage between the candidate genes and endophenotype of schizophrenia. Firstly, this review article overviewed recent literature examining the relationship between the candidate genes for susceptibility to schizophrenia and indices obtained from neuroimaging modalities. In contrast, a relatively limited number of previous studies examined associations between candidate genes for susceptibility to bipolar disorder and regional brain volume, although the high heritability of bipolar disorder has been reported as comparable to that of schizophrenia. Then, we discussed the possibility of endophenotyping of bipolar disorder and introduced our preliminary study. Finally, methodological considerations and future directions of endophenotyping of endogeneous psychosis were suggested.

Functional (GT)N polymorphisms in the promoter region of N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene affects hippocampal and amygdala volume in humans
Inoue Hideyuki; Yamasue Hidenori; Tochigi Mamoru; Suga Motomu; Iwayama Yoshimi; Abe Osamu; Yamada Haruyasu; Mark Rogers; Aoki Shigeki; Kato Nobumasa; Kato Tadafumi; Sasaki Tsukasa; Kasai Kiyoto; Yoshikawa Takeo
BIOLOGICAL PSYCHIATRY, 15 Apr. 2007, [Reviewed]

Effect of COMT (val/met) genotype on prefrontal function in schizophrenia; A multi-channel NIRS study
Ryu Takizawa; Mamoru Tochigi; Kohei Marumo; Yuki Kawakubo; Motomu Suga; Hidenori Yamasue; Tsukasa Sasaki; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, 15 Apr. 2007, [Reviewed]

Effect of catechol-O-methyltranseferese (Val/Met) genotype on prefrontal function in schizophrenia: a multi-channel near-infrared spectroscopy study
R. Takizawa; K. Kasai; M. Tochigi; K. Marumo; Y. Kawakubo; M. Suga; H. Yamasue; M. Fukuda; N. Kato; T. Sasaki
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Apr. 2007, [Reviewed]

Neurotrophic factor genotypes and regional brain volume measured with manually-traced volumetry as well as voxel-based morphometry
H. Yamasue; M. Tochigi; C. Kakiuchi; M. Suga; H. Inoue; K. Kasai; T. Kato; T. Sasaki
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Apr. 2007, [Reviewed]

The brain-derived neurotrophic factor val66met polymorphism and amygdala and hippcampal volumes
Inoue H; Yamasue H; Tochigi M; Suga M; Minato T; Abe O; Yamada H; Aoki S; Kato N; Kasai K; Sasaki T
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Apr. 2007, [Reviewed]

Neuroanatomical correlates of schizophrenia in Broca's area: Parcellation of inferior frontal gyrus
Suga M; Yamasue H; Abe O; Yamada H; Araki T; Kudo N; Uetuki M; Maeda K; Iwanami A; Aoki S; Kato N; Kasai K
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Apr. 2007, [Reviewed]

Disturbance of the integrity of the fornix correlates with the verbal and learning dysfunctions in schizophrenia - A diffusion tensor imaging study
Kunio Takei; Hidenori Yamasue; Osamu Abe; Haruyasu Yamada; Hideyuki Inoue; Motomu Suga; Kayoko Sekita; Hiroki Sasaki; Miki Uetsuki; Keiko Maeda; Nobumasa Kato; Shigeki Aoki; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, Apr. 2007, [Reviewed]

Gender-common and -specific neuroanatomical basis of human anxiety-related personality traits
Hidenori Yamasue; Osamu Abe; Motomu Suga; Haruyasu Yamade; Hideyuki Inoue; Mamoru Tochigi; Mark Rogers; Shigeki Aoki; Nobumasa Kato; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, Apr. 2007, [Reviewed]

Neuroanatomical correlates of schizophrenia in Brodmann area 44 and 45: A parcellation study of inferior frontal gyrus subregions
Motomu Suga; Hidenori Yamasue; Osamu Abe; Haruyasu Yamada; Shigeki Aoki; Nobumasa Kato; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, Apr. 2007, [Reviewed]

The function of selective attention to non-emotional and emotional information in patients with schizophrenia
MUROI Miya; KASAI Kiyoto; UETSUKI Miki; SUGA Motomu
The Japanese Journal of Cognitive Psychology, 2007, [Reviewed]
The function of selective attention for emotional and non-emotional information in schizophrenic patients is examined with the Stroop task and an emotional Stroop task. In the Stroop task, no significant differences in response times were observed between the incongruent and neutral conditions with schizophrenic patients, although the difference in error rates for the incongruent and neutral conditions was larger for schizophrenic patients than for the control group. These results suggest that for schizophrenic patients the suppression function for irrelevant information is lower and that it is difficult to maintain task demands.
In the emotional Stroop task, response times and error rates did not differ across word conditions. This suggests that the cognitive functional difficulties of schizophrenic patients for emotional information is due to reduced processing for emotional information rather than an attentional bias for emotional information.

Human brain structural change related to acute single exposure to sarin
Hidenori Yamasue; Osamu Abe; Kiyoto Kasai; Motomu Suga; Akira Iwanami; Haruyasu Yamada; Mamoru Tochigi; Toshlyuki Ohtani; Mark A. Rogers; Tsukasa Sasaki; Shigeki Aoki; Tadafumi Kato; Nobumasa Kato
ANNALS OF NEUROLOGY, Jan. 2007, [Reviewed]

統合失調症患者の発病前知能推定に関する日本語版National Adult Reading Test（JART）短縮版妥当性の検討　　　　　　　　　　　　　　　
植月美希; 松岡恵子; 笠井清登; 荒木剛; 管心; 山末英典; 前田恵子; 山崎修道; 古川俊一; 岩波明; 加藤進昌; 金吉晴
精神医学, 2007, [Reviewed]

No association between the metabotropic glutamate receptor type 3 gene (GRM3) and schizophrenia in a Japanese population
Mamoru Tochigi; Motomu Suga; Jun Ohashi; Takeshi Otowa; Hidenori Yamasue; Kiyoto Kasai; Tadafumi Kato; Yuji Okazaki; Nobumasa Kato; Tsukasa Sasaki
SCHIZOPHRENIA RESEARCH, Dec. 2006, [Reviewed]

No association between the metabotropic glutamate receptor type 3 gene (GRM3) and schizophrenia in a Japanese population
Mamoru Tochigi; Motomu Suga; Jun Ohashi; Takeshi Otowa; Hidenori Yamasue; Kiyoto Kasai; Tadafumi Kato; Yuji Okazaki; Nobumasa Kato; Tsukasa Sasaki
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, Oct. 2006, [Reviewed]

No evidence for an association between the BDNF Val66Met polymorphism and schizophrenia or personality traits
Mamoru Tochigi; Takeshi Otowa; Motomu Suga; Mark Rogers; Takanobu Minato; Hidenori Yamasue; Kiyoto Kasai; Nobumasa Kato; Tsukasa Sasaki
SCHIZOPHRENIA RESEARCH, Oct. 2006, [Reviewed]

BDNF Val66Met多型が扁桃体,海馬の体積に及ぼす影響　　　　　　　　　　　　　　　
Aug. 2006

Regionally localized abnormality of cerebral lateralization in patients with schizophrenia: An optimized voxel-based morphometry study
Yamasue H; Abe O; Yamada H; Suga M; Yamasaki S; Aoki S; Kato N; Kasai K
BIOLOGICAL PSYCHIATRY, 15 Apr. 2006, [Reviewed]

神経画像を中間表現型として用いた遺伝子多型との関連解析 BDNF Val66Met多型と扁桃体・海馬の体積は日本人において関連しない　　　　　　　　　　　　　　　
Mar. 2006

日本語版National Adult Reading Test(JART)を用いた統合失調症患者の発病前知能推定の検討
植月美希; 松岡恵子; 金吉晴; 荒木剛; 管心; 山末英典; 前田恵子; 山崎修道; 古川俊一; 岩波明; 加藤進昌; 笠井清登
精神医学, 15 Jan. 2006, [Reviewed]

統合失調症における思考障害の脳基盤下前頭回構造異常の検討.　　　　　　　　　　　　　　　
管心; 山末英典; 阿部修; 山田晴耕; 山崎修道; 荒木剛; 工藤紀子; 植月美希; 前田恵子; 岩波明; 青木茂樹; 加藤進昌; 笠井清登
神経化学, 2006, [Reviewed]

Neuroanatomy in monozygotic twins with Asperger disorder discordant for comorbid depression.
H Yamasue; M Ishijima; O Abe; T Sasaki; H Yamada; M Suga; M Rogers; I Minowa; R Someya; H Kurita; S Aoki; N Kato; K Kasai
Neurology, 09 Aug. 2005

統合失調症患者を対象としたメタ認知トレーニング効果の予備的検討
Dec. 2023

統合失調症認知機能簡易評価尺度日本語版(BACS-J)における当事者の疲労感・達成感に関する面接調査
2021

Provide patients with schizophrenia with total support from preparations for job search to job retention
Nov. 2019

統合失調症認知機能簡易評価尺度日本語版(BACS-J)短縮版の提案(中間報告)　　　　　　　　　　　　　　　
稲垣 晃子; 渡邊 由香子; 金田 渉; 佐藤 研一; 管 心; 藤枝 由美子; 佐藤 さやか; 伊藤 順一郎; 安西 信雄; 池淵 恵美
日本社会精神医学会雑誌, Aug. 2019
(一社)日本社会精神医学会

統合失調症認知機能簡易評価尺度日本語版(BACS-J)短縮版の提案(中間報告)
稲垣 晃子; 渡邊 由香子; 金田 渉; 佐藤 研一; 管 心; 藤枝 由美子; 佐藤 さやか; 伊藤 順一郎; 安西 信雄; 池淵 恵美
日本社会精神医学会雑誌, Aug. 2019
(一社)日本社会精神医学会

わが国のベストプラクティスを展望する 若年精神疾患当事者の治療とリカバリーを目指すデイケアの実践　　　　　　　　　　　　　　　
管 心
精神障害とリハビリテーション, Jun. 2019
日本精神障害者リハビリテーション学会

統合失調症のデイケア利用者を対象としたリカバリー実態調査　　　　　　　　　　　　　　　
佐藤 研一; 金田 渉; 稲垣 晃子; 藤枝 由美子; 渡邊 由香子; 管 心; 安西 信雄; 池淵 恵美
精神神経学雑誌, Apr. 2019
(公社)日本精神神経学会

【CBT for psychosis-幻覚・妄想に対処する】外来(デイケア)における実践のヒント
江口 聡; 管 心
臨床心理学, Mar. 2019
(株)金剛出版

ミスマッチ陰性電位は精神病ハイリスク者の寛解および認知機能を予測する
藤岡 真生; 切原 賢治; 越山 太輔; 多田 真理子; 永井 達哉; 臼井 香; 小池 進介; 管 心; 荒木 剛; 笠井 清登
臨床神経生理学, Oct. 2018
(一社)日本臨床神経生理学会

若年統合失調症を対象とした通過型デイケアでの集団認知行動療法の実践　　　　　　　　　　　　　　　
藤枝 由美子; 江口 聡; 石橋 綾; 清水 希実子; 株元 麻美; 小澤 藍; 飯田 美恵; 佐藤 信子; 管 心
日本認知療法・認知行動療法学会プログラム・抄録集, Oct. 2018
日本認知療法・認知行動療法学会

ペアレントトレーニングの手法を青年期発達障害者の家族支援に用いる際の工夫　　　　　　　　　　　　　　　
石橋 綾; 藤枝 由美子; 柴田 貴美子; 濱田 純子; 管 心
日本作業療法学会抄録集, Sep. 2018
(一社)日本作業療法士協会

簡易でSDMに役立つ精神機能指標を求めて-UBOMを例として 統合失調症患者に対する臺式簡易客観的精神指標(UBOM)の有用性についての検討　　　　　　　　　　　　　　　
澤田 欣吾; 榊原 英輔; 金原 明子; 小池 春菜; 藤枝 由美子; 管 心; 宮本 有紀; 福田 正人; 笠井 清登
精神神経学雑誌, Jun. 2018
(公社)日本精神神経学会

帝京大学デイケア利用者を対象としたリカバリー実態調査(トリプルR研究)における,リカバリー関連諸要因の予備的解析
佐藤研一; 金田渉; 稲垣晃子; 藤枝由美子; 渡邊由香子; 管心; 安西信雄; 池淵恵美
統合失調症研究, 01 Mar. 2018

【元気になるデイケアI:魅力的なプログラムをどう作るか】(第1章)デイケア総論 デイケアにおける集団活動(縦糸)と個人受け持ちスタッフとの関わり(横糸)を通じて個人が成長する　　　　　　　　　　　　　　　
管 心; 藤枝 由美子
精神科臨床サービス, Jan. 2018
(株)星和書店

統合失調症の早期段階におけるミスマッチ陰性電位と認知機能・全般的社会適応レベルとの相関解析　　　　　　　　　　　　　　　
越山 太輔; 切原 賢治; 多田 真理子; 永井 達哉; 藤岡 真生; 小池 進介; 管 心; 荒木 剛; 笠井 清登
日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, Sep. 2017
日本生物学的精神医学会・日本神経精神薬理学会

Employment support for patients with schizophrenia
03 Jun. 2017

Mismatch Negativity in Patients with Early Stages of Psychosis and in Nonhuman Primate
Kenji Kirihara; Tatsuya Nagai; Yuki Suda; Mariko Tada; Daisuke Koshiyama; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kenji Hashimoto; Takanori Uka; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, May 2017

Associations between Mismatch Negativity and Neurocognition and Global Functioning in Ultra-High Risk for Psychosis and First-Episode Psychosis
Daisuke Koshiyama; Kenji Kirihara; Mariko Tada; Tatsuya Nagai; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kiyoto Kasai
BIOLOGICAL PSYCHIATRY, May 2017

統合失調症患者を対象に脳磁計を用いた単一課題中のduration/frequency MMNの測定
2017

精神医学のフロンティア 統合失調症患者を対象に脳磁計を用いた時間性変化と周波数変化MMNの測定と臨床応用の可能性について
管 心; 笠井 清登
精神神経学雑誌, 2017
(公社)日本精神神経学会

Past and present rehabilitation for patients with mental disorders, Day Hospital in Tokyo University Hospital
Nov. 2016

早期精神病に対する機能的アウトカムの予測における神経心理検査の有用性の検討
01 Mar. 2016

Mismatch negativity is associated with plasma levels of D-serine in patients with first-episode psychosis
Daisuke Koshiyama; Tatsuya Nagai; Mariko Tada; Kenji Kirihara; Shinsuke Koike; Motomu Suga; Tsuyoshi Araki; Kenji Hashimoto; Kiyoto Kasai
EARLY INTERVENTION IN PSYCHIATRY, Nov. 2014

Quality assurance in SUN(^_^)D, The third largest trial in major depression in the world.　　　　　　　　　　　　　　　
Yamada, M; Inoue T; Suga M; Tsujino N; Kondo M; Ogawa Y; Okamoto Y; Shimodera S; Yasumoto S; Fujise N; Watanabe, N
7th Biennial Congress of International Society of Affective Disorders, Berlin, Germany, Apr. 2014

アットリスク精神状態を対象とした臨床心理士による精神療法の効果を検討し、治療のあり方と教育・普及法の開発を検討する研究
小池 進介; 山崎 修道; 市川 絵梨子; 菊次 彩; 管 心; 夏堀 龍暢; 笠井 清登
メンタルヘルス岡本記念財団研究助成報告集, 31 Mar. 2014
(公財)メンタルヘルス岡本記念財団

広い視点を身につけた精神科リハビリテーションの人材育成について : 東京大学医学部附属病院精神科デイホスピタルにおける「精神保健･臨床心理デイケア研修プログラム」の紹介 (特集 精神科デイケアと評価)
2014

統合失調症の前駆期研究の最前線 At-Risk Mental State(ARMS)の縦断的経過 ARMSの生物学的指標は臨床場面に応用できるのか　　　　　　　　　　　　　　　
小池 進介; 岩白 訓周; 里村 嘉弘; 多田 真理子; 夏堀 龍暢; 永井 達哉; 西村 幸香; 高野 洋輔; 滝沢 龍; 管 心; 笠井 清登
精神神経学雑誌, May 2013
(公社)日本精神神経学会

初回エピソード統合失調症における末梢血血漿成分のメタボロミクス解析
KOIKE SHINSUKE; IWAMOTO KAZUYA; BUNDO MIKI; TAKANO YOSUKE; IWASHIRO NORICHIKA; SATOMURA YOSHIHIRO; NAGAI TATSUYA; TADA MARIKO; NATSUHORI TATSUNOBU; SUGA MOTOMU; KASAI KIYOTO
統合失調症研究, Apr. 2013

統合失調症の早期段階における脳波ガンマ帯域反応と臨床症状,認知機能障害との関連
TADA MARIKO; NAGAI TATSUYA; KIRIHARA KENJI; ARAKI TSUYOSHI; KOIKE SHINSUKE; SUGA MOTOMU; KASAI KIYOTO
統合失調症研究, Apr. 2013

精神病性障害の早期段階におけるミスマッチ陰性電位と血中D‐serine濃度の関連:予備的検討
NAGAI TATSUYA; TADA MARIKO; KIRIHARA KENJI; KOIKE SHINSUKE; SUGA MOTOMU; ARAKI TSUYOSHI; HASHIMOTO RYUICHIRO; YAHATA NORIAKI; HASHIMOTO KENJI; KASAI KIYOTO
統合失調症研究, Apr. 2013

双極性障害II型に線維筋痛症を合併し,mECTに抵抗性を示した1例
2013

ARMSの生物学的指標は臨床場面に応用できるのか
2013

統合失調症の発症におけるブローカ野の皮質体積減少と神経活動低下との関連
2013

統合失調症早期段階における脳波ガンマ帯域反応と認知機能障害の関連
TADA MARIKO; NAGAI TATSUYA; KIRIHARA KENJI; ARAKI TSUYOSHI; KOIKE SHINSUKE; SUGA MOTOMU; KASAI KIYOTO
日本精神保健・予防学会学術集会プログラム・抄録集, 2013

精神病性障害の早期段階におけるミスマッチ陰性電位とNMDA受容体機能の関連:予備的検討
Sep. 2012

東京大学医学部附属病院「こころのリスク外来」における支援・治療・人材育成の取り組み 特集 リハビリテーションからみた早期介入支援
小池進介; 山崎修道; 夏堀龍暢; 岩白訓周; 市川絵梨子; 高野洋輔; 里村嘉弘; 管心; 荒木剛; 古川俊一; 笠井清登
精神障害とリハビリテーション, 30 Jun. 2012

LONGITUDINAL HEMODYNAMIC CHANGES AND PREDICTION OF FUNCTIONAL OUTCOME IN AT-RISK MENTAL STATE AND FIRST-EPISODE PSYCHOSIS
Shinsuke Koike; Yoshihiro Satomura; Yukika Nishimura; Yosuke Takano; Norichika Iwashiro; Motomu Suga; Ryu Takizawa; Tsuyoshi Araki; Kiyoto Kasai
SCHIZOPHRENIA RESEARCH, Apr. 2012

初回エピソード統合失調症における語流暢性課題を用いた近赤外線スペクトロスコピィによる血流変化の縦断的変化と社会機能の予測
Mar. 2012

統合失調症認知評価尺度を用いた精神病発症前後における予後予測因子の検討
Mar. 2012

初発統合失調症群と精神病状態の高リスク群に共通して認められる下前頭回における三角部に限局した灰白質体積減少とその陽性症状発現との関連
岩白訓周; 管心; 高野洋輔; 井上秀之; 夏堀龍暢; 里村嘉弘; 小池進介; 八幡憲明; 村上瑞穂; 五ノ井渉; 佐々木弘喜; 高尾英正; 阿部修; 笠井清登; 山末英典
統合失調症研究, Mar. 2012, [Invited]

Inappropriate hemodynamic response in the individuals with at-risk mental state
Koike Shinsuke; Takizawa Ryu; Nishimura Yukika; Takano Yousuke; Iwashiro Norichika; Satomura Yoshihiro; Suga Motomu; Araki Tsuyoshi; Kasai Kiyoto
Japanese Journal of Biological Psychiatry, 2012
Japanese Society of Biological Psychiatry

Metabolomics of blood plasma in patients with first-episode psychosis
Shinsuke Koike; Kazuya Iwamoto; Yosuke Takano; Miki Bundo; Motomu Suga; Norichika Iwashiro; Yoshihiro Satomura; Tsuyoshi Araki; Kiyoto Kasai
NEUROSCIENCE RESEARCH, 2011

ARMS(at risk mental state)群と初発統合失調症群における下前頭回の灰白質体積減少
IWASHIRO NORICHIKA; YAMASUE HIDENORI; SUGA MOTOMU; NATSUBORI RYUCHO; TAKANO YOSUKE; INOUE HIDEYUKI; SATOMURA YOSHIHIRO; KOIKE SHINSUKE; YAHATA NORIAKI; MURAKAMI MIZUHO; KATSURA MASAKI; GONOI WATARU; SASAKI HIROKI; TAKAO HIDEMASA; ABE OSAMU; KASAI KIYOTO
日本生物学的精神医学会誌, Oct. 2010

オキシトシン受容体遺伝子多型(OXTR)が扁桃体体積に与える影響(Association between the oxytocin receptor gene (OXTR) and amygdalar volume in healthy adults)　　　　　　　　　　　　　　　
井上 秀之; 山末 英典; 栃木 衛; 阿部 修; 武井 邦夫; 管 心; 山田 晴耕; Rogers Mark A; 青木 茂樹; 劉 暁渓; 河村 代志也; 佐々木 司; 笠井 清登
神経化学, Aug. 2010
日本神経化学会

成人の発達障害 特集：スペシャリストの知識と技術で腕をあげる 第3章 地域の現場で活きるスペシャリストの知恵と技
山崎修道; 石橋綾; 清水希実子; 森山亜希子; 五十嵐美紀; 浅井久栄; 藤枝由美子; 永井真理子; 白澤知恵; 管心; 切原賢治; 古川俊一
精神科臨床サービス, 25 Oct. 2009

大学病院精神科デイケアを中心とした精神障害者のリハビリテーションと社会復帰支援活動
山崎 修道; 浅井 久栄; 石橋 綾; 清水 希実子; 永井 真理子; 白澤 知恵; 藤枝 由美子; 管 心; 切原 賢治; 古川 俊一
精神障害とリハビリテーション, Jun. 2009
日本精神障害者リハビリテーション学会

統合失調症における作業記憶課題遂行時の前頭葉機能の検討―多チャンネルNIRS研究―
KOIKE SHINSUKE; TAKIZAWA RYU; KINO KEN; MARUSHIGE KOHEI; NISHIMURA YUKIKA; SUGA MOTOMU; KASAI KIYOTO
日本生物学的精神医学会プログラム・講演抄録, 2009

統合失調症の生物学的研究 統合失調症の発症・進行とMRI脳画像
KOIKE SHINSUKE; SUGA MOTOMU; KASAI KIYOTO
月刊メディカル・サイエンス・ダイジェスト, 30 Nov. 2008
(株)ニュー・サイエンス社

統合失調症の病態解明から病因解明へ (第12回認知神経科学会) -- (シンポジウム 統合失調症の病態生理--脳機能・脳画像による解析)
Apr. 2008

Effect of polymorphism of susceptibility genes on prefrontal function in schizophrenia; a NIRS study
R. Takizawa; M. Tochigi; K. Marumo; M. Kinou; Y. Kawakubo; M. Suga; T. Sasaki; K. Kasai
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Feb. 2008

Investigating Endophenotype of Endogeneous Psychotic Disorders
YAMASUE Hidenori; SUGA Motomu; KASAI Kiyoto
25 Jun. 2007

Differential effect of GRM3 and BDNF genotypes on auditory cortical response to phoneme change
Y. Kawakubo; M. Tochigi; M. Suga; M. Kato; M. Yumoto; K. Itoh; T. Sasaki; N. Kato; K. Kasai
PSYCHIATRY AND CLINICAL NEUROSCIENCES, Apr. 2007

Perospirone in the treatment of schizophrenia: effect on verbal memory organization.
Tsuyoshi Araki; Hidenori Yamasue; Tomiki Sumiyoshi; Hitoshi Kuwabara; Motomu Suga; Akira Iwanami; Nobumasa Kato; Kiyoto Kasai
Progress in neuro-psychopharmacology & biological psychiatry, Mar. 2006

統合失調症における非情動的・情動的情報に関する選択的注意機能の検討
2006

統合失調症における精神生理学的および神経画像にもとづいたエンドフェノタイプ (特集 精神疾患のエンドフェノタイプ)
Apr. 2005

健常成人における純音・音素刺激によって誘発されたMMFと気質の関連　　　　　　　　　　　　　　　
加藤 正人; 神尾 聡; 工藤 紀子; 川久保 友紀; 山末 英典; 清野 絵; 管 心; 山田 晴耕; 阿部 修; 湯本 真人; 伊藤 憲治; 加藤 進昌; 笠井 清登
臨床神経生理学, Oct. 2004
(一社)日本臨床神経生理学会