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HISHIMOTO Akitoyo
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Researcher basic information

■ Research Keyword
  • Epigenetics
  • メタボローム解析
  • バイオマーカー
  • 性差
  • 死後脳
  • 統合失調症
  • 自殺
  • 臨床精神分子遺伝学
■ Research Areas
  • Life sciences / Neuroscience - general
  • Life sciences / Psychiatry

Research activity information

■ Award
  • Jan. 2011 ドパミンパーシャルアゴニスト研究会, 第7回 ドパミンパーシャルアゴニスト研究会優秀賞, 難治性強迫性障害に対するアリピプラゾールの増強療法
    Hishimoto Akitoyo
    Japan society

  • 2008 2nd WFSBP Asia Pacific Congress and 30th Annual Meeting of Japanese Society of Biological Psychiatry, Young Scientist Award, Neurexin 1: novel mRNA transcripts, differential expression in and association with Alzheimer disease
    Hishimoto Akitoyo

■ Paper
  • Nobuhiko Noguchi, Toshiyuki Shirai, Akira Suda, Saki Hattori, Masatoshi Miyauchi, Satoshi Okazaki, Junichi Fujita, Takeshi Asami, Ikuo Otsuka, Akitoyo Hishimoto
    AIM: Social anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging-related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm-based predictive values of aging-related proteins (GrimAge components and GrimAge2 components), including leptin level. METHODS: We used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50 years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates. RESULTS: None of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm-based predictive values of aging-related proteins, leptin level in GrimAge components (q = 0.0123) and GrimAge2 components (q = 0.0123) were significantly lower in patients with SAD than in controls. CONCLUSIONS: The results of this study suggested that leptin may be involved in SAD pathogenesis as an aging-related protein. Therefore, further studies with different designs are required.
    Dec. 2024, Neuropsychopharmacology reports, 44(4) (4), 774 - 783, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshiyuki Shirai, Satoshi Okazaki, Takaki Tanifuji, Shusuke Numata, Tomohiko Nakayama, Tomohiro Yoshida, Kentaro Mouri, Ikuo Otsuka, Noboru Hiroi, Akitoyo Hishimoto
    Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is ≥10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.
    Nov. 2024, Schizophrenia (Heidelberg, Germany), 10(1) (1), 108 - 108, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Mai Hatano, Waki Nakajima, Hideaki Tani, Hiroyuki Uchida, Tomoyuki Miyazaki, Tetsu Arisawa, Yuuki Takada, Sakiko Tsugawa, Akane Sano, Kotaro Nakano, Tsuyoshi Eiro, Hiroki Abe, Akira Suda, Takeshi Asami, Akitoyo Hishimoto, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Shunya Kurokawa, Yohei Ohtani, Kie Takahashi, Yuhei Kikuchi, Taisuke Yatomi, Shiori Honda, Masahiro Jinzaki, Yoji Hirano, Ryo Mitoma, Shunsuke Tamura, Shingo Baba, Osamu Togao, Hirotaka Kosaka, Hidehiko Okazawa, Yuichi Kimura, Masaru Mimura, Takuya Takahashi
    Abstract Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.
    Springer Science and Business Media LLC, Oct. 2024, Molecular Psychiatry, English, International magazine
    [Refereed]
    Scientific journal

  • Toshiyuki Shirai, Takaki Tanifuji, Ikuo Otsuka, Satoshi Okazaki, Tadasu Horai, Naruhisa Yamaki, Haruka Minami, Masao Miyachi, Shohei Okada, Akitoyo Hishimoto
    Anorexia nervosa (AN) is life-threatening because of many physical complications, hence a quantitative indicator for early therapeutic intervention through hospitalization is needed. Here, we compared the demographics of 21 patients with AN who required intensive treatment in the internal medicine ward and those of 61 patients with AN who directly admitted to the psychiatric ward. We developed a risk score for severe physical complications in patients with AN, by using six items with significant differences between two groups; body mass index, blood urea nitrogen, corrected calcium, albumin, aspartate transaminase, and C-reactive protein (area under the curve = 0.824).
    Sep. 2024, Psychiatry research, 342, 116151 - 116151, English, International magazine
    Scientific journal

  • Ryo Sasaki, Takeshi Asami, Masao Takaishi, Ryota Nakamura, Tomohide Roppongi, Asuka Yoshimi, Akitoyo Hishimoto
    In panic disorder (PD), functional disturbance of the hypothalamus-pituitary-adrenal (HPA) axis has been considered. However, in neuroimaging studies of PD, the hypothalamus and pituitary gland are poorly studied.We investigated the volume of PD patients' hypothalamus and pituitary gland, enrolling 38 PD patients and 38 healthy controls. Severity of PD was mild to moderate according to the Panic Disorder Severity Scale, and the illness duration was relatively short (median = 2.8 years). The hypothalamus' gray matter was automatically extracted and segmented, whereas the pituitary gland was manually traced. Regarding the hypothalamus, the paraventricular nucleus (PVH), which produces the corticotropin-releasing hormone, was of interest.The volumes of the pituitary and the bilateral anterior-superior hypothalamic subunits, where the PVH would be located, were compared by the multiple regression analyses controlling for age and intracranial content volume. To compensate for limitation in the abovementioned segmentation and analyses, the voxel-based morphometry with small volume correction (VBM-SVC) targeting the whole hypothalamus was also performed.The multiple regression analyses did not find significant effect of PD diagnosis on the volumes. However, in the VBM-SVC analysis, volume reduction of the PVH was suggested in PD even when patients who experienced PD for ≥ 3 years were excluded [peak coordinate (x, y, z = -2, 3, -8), FWE-corrected P = .022 (cluster-level) and 0.003 (peak-level), voxel size = 63]. Our results suggested structural alteration of the PVH in PD patients for the first time, indicating importance of the HPA-axis in PD pathology.
    Aug. 2024, Brain imaging and behavior, 18(4) (4), 701 - 709, English, International magazine
    Scientific journal

  • Haruka Minami, Toshiyuki Shirai, Shohei Okada, Masao Miyachi, Takaki Tanifuji, Satoshi Okazaki, Tadasu Horai, Kentaro Mouri, Ikuo Otsuka, Akitoyo Hishimoto
    AIM: Internet gaming disorder (IGD) is receiving increasing attention. In particular, violent gameplay or in-game spending affects the psychiatric conditions and economic difficulties of patients. We conducted regression analysis and path analysis to investigate the associations between a comprehensive list of factors in patients with IGD, including the degree of internet or gaming dependence, developmental problems, family background, severity of depression, sleeping habits, in-game spending, and first-person shooter (FPS) and third-person shooter (TPS) game playing. METHODS: The participants were 47 Japanese individuals (39 males and 8 females) aged ≤20 years diagnosed with IGD with complete data from the internet addiction test, autism spectrum quotient, Quick Inventory of Depressive Symptomatology, and Pittsburgh Sleep Quality Index. All participants were asked whether their parents have divorce history, whether they have siblings, whether they play FPS or TPS games, and whether they engage in in-game spending. Firstly, we compared these factors between males and females; secondly, we conducted regression analysis and path analysis in male patients. RESULTS: As for simple comparison between sex, female patients showed greater severity of IGD and depressive score. In regression analysis of male patients, significant associations were found between FPS or TPS game playing and in-game spending. We also created path diagrams. CONCLUSION: The results of the comprehensive analyses suggest the possibility that bidirectional synergistic effects could be achieved by gradually reducing both violent game playing and in-game spending. The concept of internet dependence has a wide range of meanings, and for each subtype, it is important to consider the background that led to the dependence to make individualized environmental adjustments and provide psychotherapy.
    Jul. 2024, Neuropsychopharmacology reports, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 生活習慣病を有する高齢者の認知症進展予防を目指した多因子介入ランダム化比較試験 J-MINT Prime神奈川
    井出 恵子, 小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 田栗 正隆, 鈴木 翔子, 千葉 悠平, 阿部 紀絵, 吉見 明香, 菱本 明豊, 山中 太郎, 荒井 秀典
    (公社)日本精神神経学会, Jun. 2024, 精神神経学雑誌, (2024特別号) (2024特別号), S561 - S561, Japanese

  • Yuhei Chiba, Asaki Kumamoto, Nobuhiko Noguchi, Asuka Yoshimi, Akira Suda, Akitoyo Hishimoto, Akihiko Kase
    Falls, wheelchair dependence, and bedridden status are the results of reduced mobility in the mid-late course of dementia. Kinematic gait analysis for patients with dementia is lacking because practically setting sensors on their bodies is particularly difficult. We analyzed the parameters of kinematic gait analysis that are related to the risks of wheelchair dependence in patients with dementia using wearable accelerometers and gyroscopes for detecting 3-dimensional physical movements. We collected data from 34 patients with dementia regarding demographics, cognitive function, CT scan findings, medications, and gait analysis parameters. The patients were followed up for 6 months. We compared data between dementia patients with and without wheelchair dependence by t-test or Fisher's exact test, multiple comparison, and simple logistic regression analysis for wheelchair dependence by gait analysis parameters. Eleven patients became wheelchair-dependent during the 6 months. The score on the clinical dementia rating scale was significantly higher and the hip extensor angle in walking was significantly lower in patients with dementia with wheelchair dependence than in those without. The severity of dementia and the lower angle of the hip extensor during walking may indicate the necessity of a wheelchair for patients with this disease.
    May 2024, Assistive technology : the official journal of RESNA, 1 - 7, English, International magazine
    Scientific journal

  • 精神疾患のエピジェネティクス研究 自殺のエピジェネティクス
    岡崎 賢志, 大塚 郁夫, 谷藤 貴紀, 白井 寿行, 毛利 健太朗, 菱本 明豊
    日本臨床精神神経薬理学会・日本神経精神薬理学会, May 2024, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 34回・54回, JSY1 - 3, Japanese

  • Toshiyuki Shirai, Satoshi Okazaki, Ikuo Otsuka, Masao Miyachi, Takaki Tanifuji, Ryota Shindo, Shohei Okada, Haruka Minami, Tadasu Horai, Kentaro Mouri, Akitoyo Hishimoto
    Alcohol dependence poses a global health threat associated with aging and reduced life expectancy. Recently, aging research through deoxyribonucleic acid (DNA) methylation has gained attention. New epigenetic clocks have been developed; however, no study has investigated GrimAge components, GrimAge2 components and DunedinPACE in patients with alcohol dependence. In this study, we aimed to perform epigenetic clock analysis to evaluate epigenetic age acceleration and DNA methylation-based age-predictive components in patients with alcohol dependence and controls. We utilized publicly available DNA methylation data (GSE98876) for our analysis. Additionally, we compared the values of the same items before and after the patients underwent a treatment program. The dataset comprised 23 controls and 24 patients. We observed that DunedinPACE accelerated more in patients with alcohol dependence. AgeAccelGrim and AgeAccelGrim2 decelerated more after the treatment program than before, and beta-2-microglobulin and Cystatin C decreased after the treatment program than before. These findings are crucial as they affect the cranial nerve area, potentially contributing to cognitive dysfunction and psychiatric symptoms in patients with alcohol dependence.
    May 2024, Journal of psychiatric research, 173, 175 - 182, English, International magazine
    Scientific journal

  • Toshiyuki Shirai, Satoshi Okazaki, Takaki Tanifuji, Ikuo Otsuka, Masao Miyachi, Shohei Okada, Ryota Shindo, Tadasu Horai, Kentaro Mouri, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Akitoyo Hishimoto
    BACKGROUND: More than 800 000 people die by suicide annually. The heritability of suicide is 30%-50%. We focused on the hypoxia response element (HRE), which promotes the expression of macrophage migration inhibitory factor (MIF) via the hypoxia-inducible factor (HIF) pathway, important in neurogenesis and neuroprotection. We examined a genetic polymorphism of rs17004038, a single-nucleotide polymorphism (SNP), in suicide completers and controls. METHODS: The study population included 1336 suicide completers and 814 unrelated healthy controls. All participants were Japanese. We obtained peripheral blood, extracted DNA, and genotyped the patients for SNP rs17004038 (C > A). RESULTS: No significant differences were observed between the two groups in either the allele or genotype analyses. Subgroup analyses by sex, age (<40 or ≥40), and suicide method (violent or nonviolent suicide) were performed with similar results. CONCLUSION: No association was observed between SNP rs17004038 and suicide completion. Although it is challenging to collect a large number of samples from suicide completers, further MIF-related genetic studies, including those of rs17004038, are necessary with larger sample sizes.
    Mar. 2024, Neuropsychopharmacology reports, 44(1) (1), 262 - 266, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshiyuki Shirai, Satoshi Okazaki, Takaki Tanifuji, Ikuo Otsuka, Tadasu Horai, Kentaro Mouri, Yukihiro Takemura, Katsuro Aso, Noriya Yamamoto, Akitoyo Hishimoto
    Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.
    Mar. 2024, Addiction biology, 29(3) (3), e13383, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • インターネットゲーム障害における認知機能障害について MCCB日本語版による検討
    南 陽香, 谷藤 貴紀, 白井 寿行, 大塚 郁夫, 毛利 健太朗, 岩本 直子, 倉永 雅子, 菱本 明豊
    (公社)日本精神神経学会, Feb. 2024, 精神神経学雑誌, 126(2) (2), 150 - 150, Japanese

  • Yamagata H, Fujii Y, Ochi S, Seki T, Hasegawa N, Yamada H, Hori H, Ichihashi K, Iga J, Ogasawara K, Hashimoto N, Iida H, Ohi K, Tsuboi T, Numata S, Hishimoto A, Usami M, Katsumoto E, Muraoka H, Takaesu Y, Nagasawa T, Komatsu H, Miura K, Matsumoto J, Inada K, Nakagawqa S, Hashimoto R
    Feb. 2024, Psychiatry Research Communications, 4, 100158, English
    [Refereed]
    Scientific journal

  • Taishiro Kishimoto, Shotaro Kinoshita, Momoko Kitazawa, Akitoyo Hishimoto, Takeshi Asami, Akira Suda, Shogyoku Bun, Toshiaki Kikuchi, Mitsuhiro Sado, Akihiro Takamiya, Masaru Mimura, Yasunori Sato, Ryo Takemura, Kengo Nagashima, Takashi Nakamae, Yoshinari Abe, Tetsufumi Kanazawa, Yasuo Kawabata, Hiroaki Tomita, Koichi Abe, Seiji Hongo, Hiroshi Kimura, Aiko Sato, Hisashi Kida, Kei Sakuma, Michitaka Funayama, Naoya Sugiyama, Kousuke Hino, Toru Amagai, Maki Takamiya, Hideyuki Kodama, Kenichi Goto, Shuichiro Fujiwara, Hisanobu Kaiya, Kiichiro Nagao
    AIM: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. METHODS: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. RESULTS: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. CONCLUSION: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.
    Dec. 2023, Psychiatry and clinical neurosciences, English, International magazine
    Scientific journal

  • Toshinori Chiba, Kentarou Ide, Misa Murakami, Nao Kobayashi, Taiki Oka, Fumiya Nakai, Rumi Yorizawa, Yuka Miyake, Toshitaka Hamamura, Masaru Honjo, Hiroyuki Toda, Tetsufumi Kanazawa, Shuken Boku, Takatomi Kubo, Akitoyo Hishimoto, Mitsuo Kawato, Aurelio Cortese
    Springer Science and Business Media LLC, Dec. 2023, Nature Mental Health, 1(12) (12), 1013 - 1022
    Scientific journal

  • Shotaro Kinoshita, Momoko Kitazawa, Yoshinari Abe, Akira Suda, Takashi Nakamae, Tetsufumi Kanazawa, Hiroaki Tomita, Akitoyo Hishimoto, Taishiro Kishimoto
    Springer Science and Business Media LLC, Dec. 2023, Journal of Technology in Behavioral Science
    Scientific journal

  • 井出 恵子, 小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 田栗 正隆, 千葉 悠平, 阿部 紀絵, 吉見 明香, 菱本 明豊, 山中 太郎, 荒井 秀典
    (株)ワールドプランニング, Oct. 2023, 老年精神医学雑誌, 34(増刊II) (増刊II), 194 - 194, Japanese

  • 生活習慣病を有する高齢者の認知症進展予防を目指した多因子介入ランダム化比較試験
    井出 恵子, 小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 田栗 正隆, 鈴木 翔子, 千葉 悠平, 阿部 紀絵, 吉見 明香, 菱本 明豊, 山中 太郎, 荒井 秀典
    (一社)日本認知症学会, Oct. 2023, Dementia Japan, 37(4) (4), 670 - 670, Japanese

  • Naomi Hasegawa, Yuka Yasuda, Norio Yasui-Furukori, Hisashi Yamada, Hikaru Hori, Kayo Ichihashi, Yoshikazu Takaesu, Hitoshi Iida, Hiroyuki Muraoka, Fumitoshi Kodaka, Jun-Ichi Iga, Naoki Hashimoto, Kazuyoshi Ogasawara, Kazutaka Ohi, Kentaro Fukumoto, Shusuke Numata, Takashi Tsuboi, Masahide Usami, Akitoyo Hishimoto, Ryuji Furihata, Taishiro Kishimoto, Toshinori Nakamura, Eiichi Katsumoto, Shinichiro Ochi, Tatsuya Nagasawa, Kiyokazu Atake, Chika Kubota, Hiroshi Komatsu, Hirotaka Yamagata, Kenta Ide, Masahiro Takeshima, Mikio Kido, Saya Kikuchi, Tsuyoshi Okada, Junya Matsumoto, Kenichiro Miura, Taichi Shimazu, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.
    Oct. 2023, Psychiatry and clinical neurosciences, 77(10) (10), 559 - 568, English, International magazine
    Scientific journal

  • Anna R Docherty, Niamh Mullins, Allison E Ashley-Koch, Xuejun Qin, Jonathan R I Coleman, Andrey Shabalin, JooEun Kang, Balasz Murnyak, Frank Wendt, Mark Adams, Adrian I Campos, Emily DiBlasi, Janice M Fullerton, Henry R Kranzler, Amanda V Bakian, Eric T Monson, Miguel E Rentería, Consuelo Walss-Bass, Ole A Andreassen, Chittaranjan Behera, Cynthia M Bulik, Howard J Edenberg, Ronald C Kessler, J John Mann, John I Nurnberger Jr, Giorgio Pistis, Fabian Streit, Robert J Ursano, Renato Polimanti, Michelle Dennis, Melanie Garrett, Lauren Hair, Philip Harvey, Elizabeth R Hauser, Michael A Hauser, Jennifer Huffman, Daniel Jacobson, Ravi Madduri, Benjamin McMahon, David W Oslin, Jodie Trafton, Swapnil Awasthi, Wade H Berrettini, Martin Bohus, Xiao Chang, Hsi-Chung Chen, Wei J Chen, Erik D Christensen, Scott Crow, Philibert Duriez, Alexis C Edwards, Fernando Fernández-Aranda, Hanga Galfalvy, Michael Gandal, Philip Gorwood, Yiran Guo, Jonathan D Hafferty, Hakon Hakonarson, Katherine A Halmi, Akitoyo Hishimoto, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S Kaplan, Walter H Kaye, Pamela K Keel, James L Kennedy, Minsoo Kim, Kelly L Klump, Daniel F Levey, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Christian R Marshall, James E Mitchell, Satoshi Okazaki, Ikuo Otsuka, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stephan Ripke, Stefan Roepke, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Anna Starnawska, Michael Strober, Mei-Hsin Su, Laura M Thornton, Janet Treasure, Erin B Ware, Hunna J Watson, Stephanie H Witt, D Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M Helena Azevedo, Nicholas Bass, Claiton H D Bau, Bernhard T Baune, Frank Bellivier, Klaus Berger, Joanna M Biernacka, Tim B Bigdeli, Elisabeth B Binder, Michael Boehnke, Marco P Boks, David L Braff, Richard Bryant, Monika Budde, Enda M Byrne, Wiepke Cahn, Enrique Castelao, Jorge A Cervilla, Boris Chaumette, Aiden Corvin, Nicholas Craddock, Srdjan Djurovic, Jerome C Foo, Andreas J Forstner, Mark Frye, Justine M Gatt, Ina Giegling, Hans J Grabe, Melissa J Green, Eugenio H Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Marian L Hamshere, Annette M Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A Jones, Lina Jonsson, René S Kahn, John R Kelsoe, Kenneth S Kendler, Stefan Kloiber, Karestan C Koenen, Manolis Kogevinas, Marie-Odile Krebs, Mikael Landén, Marion Leboyer, Phil H Lee, Douglas F Levinson, Calwing Liao, Jolanta Lissowska, Fermin Mayoral, Susan L McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Divya Mehta, Ingrid Melle, Philip B Mitchell, Esther Molina, Gunnar Morken, Caroline Nievergelt, Markus M Nöthen, Michael C O'Donovan, Roel A Ophoff, Michael J Owen, Carlos Pato, Michele T Pato, Brenda W J H Penninx, James B Potash, Robert A Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A Rouleau, Diego L Rovaris, Alan R Sanders, Peter R Schofield, Thomas G Schulze, Laura J Scott, Alessandro Serretti, Jianxin Shi, Lea Sirignano, Pamela Sklar, Olav B Smeland, Jordan W Smoller, Edmund J S Sonuga-Barke, Maciej Trzaskowski, Ming T Tsuang, Gustavo Turecki, Laura Vilar-Ribó, John B Vincent, Henry Völzke, James T R Walters, Cynthia Shannon Weickert, Thomas W Weickert, Myrna M Weissman, Leanne M Williams, Naomi R Wray, Clement C Zai, Esben Agerbo, Anders D Børglum, Gerome Breen, Ditte Demontis, Annette Erlangsen, Joel Gelernter, Stephen J Glatt, David M Hougaard, Hai-Gwo Hwu, Po-Hsiu Kuo, Cathryn M Lewis, Qingqin S Li, Chih-Min Liu, Nicholas G Martin, Andrew M McIntosh, Sarah E Medland, Ole Mors, Merete Nordentoft, Catherine M Olsen, David Porteous, Daniel J Smith, Eli A Stahl, Murray B Stein, Danuta Wasserman, Thomas Werge, David C Whiteman, Virginia Willour, Hilary Coon, Jean C Beckham, Nathan A Kimbrel, Douglas M Ruderfer
    OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
    Oct. 2023, The American journal of psychiatry, 180(10) (10), 723 - 738, English, International magazine
    Scientific journal

  • Ryota Shindo, Takaki Tanifuji, Satoshi Okazaki, Ikuo Otsuka, Toshiyuki Shirai, Kentaro Mouri, Tadasu Horai, Akitoyo Hishimoto
    Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.
    Sep. 2023, npj aging, 9(1) (1), 19 - 19, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 白井 寿行, 岡崎 賢志, 谷藤 貴紀, 大塚 郁夫, 毛利 健太朗, 菱本 明豊
    (一財)仁明会, Sep. 2023, 仁明会精神医学研究, 21(1) (1), 51 - 71, Japanese

  • 白井 寿行, 岡崎 賢志, 谷藤 貴紀, 大塚 郁夫, 毛利 健太朗, 菱本 明豊
    (一財)仁明会, Sep. 2023, 仁明会精神医学研究, 21(1) (1), 51 - 71, Japanese

  • うつ状態と空気嚥下症を呈した家族性地中海熱の1例
    節田 瑛里, 辻村 理司, 野口 信彦, 須田 顕, 吉見 明香, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2023, 精神神経学雑誌, 125(9) (9), 820 - 820, Japanese

  • 当院における高齢発症の摂食障害の3例
    苅谷 悠太, 野口 信彦, 辻村 理司, 吉見 明香, 須田 顕, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2023, 精神神経学雑誌, 125(9) (9), 823 - 823, Japanese

  • 岡村 泰, 村端 祐樹, 梅田 夕奈, 針間 博彦, 水野 雅文, 松永 寿人, 菱本 明豊
    (一社)日本社会精神医学会, Aug. 2023, 日本社会精神医学会雑誌, 32(3) (3), 268 - 268, Japanese

  • Hiraku Uchimura, Kaori Kanai, Masami Arai, Miyu Inoue, Akitoyo Hishimoto, Daiki Masukawa, Yoshio Goshima
    Methylphenidate (MPH) and methamphetamine (METH) are the current treatments of choice for attention deficit/hyperactivity disorder. We previously reported that METH induces the release of dopamine (DA) and of the neurotransmitter candidate L-3,4-dihydroxyphenylalanine (L-DOPA). In contrast, we here found that MPH increased the DA release while it did not affect the L-DOPA release from the dorsolateral striatum. Nevertheless, MPH-induced hyperlocomotion was reduced in Gpr143 (L-DOPA receptor) gene-deficient (Gpr143-/y) mice. The rewarding effect and increased c-fos expression induced by MPH were also attenuated in Gpr143-/y mice. Together, these findings suggest that GPR143 is involved in the acute and chronic actions of MPH.
    Jul. 2023, Journal of pharmacological sciences, 152(3) (3), 178 - 181, English, Domestic magazine
    Scientific journal

  • Naoki Hashimoto, Norio Yasui-Furukori, Naomi Hasegawa, Shuhei Ishikawa, Hikaru Hori, Hitoshi Iida, Kayo Ichihashi, Kenichiro Miura, Junya Matsumoto, Shusuke Numata, Fumitoshi Kodaka, Ryuji Furihata, Kazutaka Ohi, Kazuyoshi Ogasawara, Jun-Ichi Iga, Hiroyuki Muraoka, Hiroshi Komatsu, Masahiro Takeshima, Kiyokazu Atake, Mikio Kido, Toshinori Nakamura, Taishiro Kishimoto, Akitoyo Hishimoto, Toshiaki Onitsuka, Tsuyoshi Okada, Shinichiro Ochi, Tatsuya Nagasawa, Manabu Makinodan, Hiroki Yamada, Takashi Tsuboi, Hisashi Yamada, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    BACKGROUND: Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. METHODS: Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. RESULTS: For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. CONCLUSIONS: It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).
    Jun. 2023, BMC psychiatry, 23(1) (1), 473 - 473, English, International magazine
    Scientific journal

  • COVID-19流行開始1年後の大学病院職員の心理的影響調査(第2回) 流行初期の第1回調査と比較して
    井出 恵子, 浅見 剛, 野本 宗孝, 菱本 明豊
    (公社)日本精神神経学会, Jun. 2023, 精神神経学雑誌, (2023特別号) (2023特別号), S585 - S585, Japanese

  • Epigenetic clock解析により明らかとなった大うつ病性障害におけるDNAメチル化に基づくcystatin C値の上昇(Epigenetic clock analysis reveals increased cystatin C levels based on DNA methylation in major depressive disorder)
    谷藤 貴紀, 岡崎 賢志, 大塚 郁夫, 毛利 健太郎, 蓬莱 政, 新藤 良太, 白井 寿行, 菱本 明豊
    (一社)日本抗加齢医学会, Jun. 2023, 日本抗加齢医学会総会プログラム・抄録集, 23回, 252 - 252, English

  • 胎児性アルコールスペクトラム障害児におけるEpigenetic Clock解析(Epigenetic Clock Analysis in Children with Fetal Alcohol Spectrum Disorder)
    岡崎 賢志, 谷藤 貴紀, 大塚 郁夫, 蓬莱 政, 山木 愛久, 菱本 明豊
    (一社)日本抗加齢医学会, Jun. 2023, 日本抗加齢医学会総会プログラム・抄録集, 23回, 264 - 264, English

  • Masashi Hasegawa, Takaki Tanifuji, Satoshi Okazaki, Ikuo Otsuka, Toshiyuki Shirai, Ryota Shindo, Tadasu Horai, Kentaro Mouri, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Akitoyo Hishimoto
    BACKGROUND: One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A (MAOA) is an enzyme that degrades serotonin and is located on the X chromosome. A previous study indicated that the upstream (u) variable number of tandem repeat (VNTR) in the MAOA gene promoter may be associated with suicide. However, a meta-analysis showed that this polymorphism may not be related to suicide. According to a recent study, compared with the uVNTR, the distal (d)VNTR and the haplotypes of the two VNTRs modulate MAOA expression. METHODS: We examined the two VNTRs in the MAOA gene promoter in 1007 subjects who committed suicide and 844 healthy controls. We analyzed the two VNTRs using fluorescence-based polymerase chain reaction assays. We conducted a meta-analysis for the two VNTRs to update it. RESULTS: Our results demonstrated that neither the genotype-based associations nor allele/haplotype frequencies of the two VNTRs were significantly associated with suicide. In the meta-analysis, we did not indicate relationships between uVNTR and suicide nor did we identify articles analyzing dVNTR in suicide. CONCLUSION: Overall, we did not find a relationship between the two VNTRs in the MAOA promoter and suicide completion; thus, warranting further studies are required.
    May 2023, Neuropsychopharmacology reports, 43(3) (3), 338 - 345, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tsuyoshi Eiro, Tomoyuki Miyazaki, Mai Hatano, Waki Nakajima, Tetsu Arisawa, Yuuki Takada, Kimito Kimura, Akane Sano, Kotaro Nakano, Takahiro Mihara, Yutaro Takayama, Naoki Ikegaya, Masaki Iwasaki, Akitoyo Hishimoto, Yoshihiro Noda, Takahiro Miyazaki, Hiroyuki Uchida, Hideaki Tani, Nobuhiro Nagai, Teruki Koizumi, Shinichiro Nakajima, Masaru Mimura, Nozomu Matsuda, Kazuaki Kanai, Kazuhiro Takahashi, Hiroshi Ito, Yoji Hirano, Yuichi Kimura, Riki Matsumoto, Akio Ikeda, Takuya Takahashi
    The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.
    May 2023, Cell reports. Medicine, 4(5) (5), 101020 - 101020, English, International magazine
    Scientific journal

  • Yu-Han H. Hsu, Greta Pintacuda, Ruize Liu, Eugeniu Nacu, April Kim, Kalliopi Tsafou, Natalie Petrossian, William Crotty, Jung Min Suh, Jackson Riseman, Jacqueline M. Martin, Julia C. Biagini, Daya Mena, Joshua K.T. Ching, Edyta Malolepsza, Taibo Li, Tarjinder Singh, Tian Ge, Shawn B. Egri, Benjamin Tanenbaum, Caroline R. Stanclift, Annie M. Apffel, Steven A. Carr, Monica Schenone, Jake Jaffe, Nadine Fornelos, Hailiang Huang, Kevin C. Eggan, Kasper Lage, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chan, Eric Y.H. Chen, Wei Cheng, Eric FC. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O'Callaghan, Colm O'Dushlaine, F. Anthony O'Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O'Donovan, Hailiang Huang, Shengying Qin, Akira Sawa, Sibylle G. Schwab, Rene Kahn, Kyung Sue Hong, Wenzhao Shi, Ming Tsuang, Masanari Itokawa, Gang Feng, Jianjun Liu, Stephen J. Glatt, Nakao Iwata, Masashi Ikeda, Xiancang Ma, Jimmy Lee, Jinsong Tang, Yunfeng Ruan, Ruize Liu, Feng Zhu, Yasue Horiuchi, Byung Dae Lee, Eun-Jeong Joo, Woojae Myung, Kyooseob Ha, Hong-Hee Won, Ji Hyung Baek, Young Chul Chung, Sung-Wan Kim, Dieter B. Wildenauer, Agung Kusumawardhani, Wei J. Chen, Hai-Gwo Hwu, Kang Sim, Akitoyo Hishimoto, Ikuo Otsuka, Ichiro Sora, Tomoko Toyota, Takeo Yoshikawa, Hiroshi Kunugi, Kotaro Hattori, Sayuri Ishiwata, Shusuke Numata, Tetsuro Ohmori, Makoto Arai, Yuji Ozeki, Kumiko Fujii, Se Joo Kim, Heon-Jeong Lee, Yong Min Ahn, Se Hyun Kim, Kazufumi Akiyama, Kazutaka Shimoda, Makoto Kinoshita
    Elsevier BV, May 2023, iScience, 26(5) (5), 106701 - 106701
    Scientific journal

  • 救急科と連携し、身体合併症治療と並行して集中治療室で修正型電気けいれん療法を実施し症状改善を得た1例
    首藤 正茂, 服部 早紀, 野口 信彦, 田村 元, 吉見 明香, 須田 顕, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, May 2023, 精神神経学雑誌, 125(5) (5), 448 - 448, Japanese

  • Hidehito Miyazaki, Kousuke Hino, Tsubasa Ito, Takeru Abe, Munetaka Nomoto, Taku Furuno, Ichiro Takeuchi, Akitoyo Hishimoto
    BACKGROUND: Environmental factors such as meteorological and air pollution conditions have been identified as risk factors for suicide. This study aimed to clarify the relationship of the number of visits to the emergency department for suicide attempts with meteorological and air pollution conditions. METHODS: This cross-sectional study included patients who attempted suicide and were transported to Yokohama City University Medical Center from April 2005 to March 2022. The meteorological conditions recorded at the time of transport included mean atmospheric pressure, mean temperature, maximum temperature, minimum temperature, mean humidity, wind speed, and sunshine hours, and the air pollution conditions included SO2 (ppm), NO (ppm), NO2 (ppm), NOX (ppm), OX (ppm), CH4 (ppmC), NMHC (ppmC), THC (ppmC), SPM (μg/m3), and PM2.5 (μg/m3). Poisson regression analysis was used to examine the association between the number of suicide attempts and the meteorological and air pollution conditions. Subgroup analyses were conducted by classifying the subjects according to the means of suicide attempt; comparisons were performed using t-tests. RESULTS: The study included 1737 patients. Multivariate Poisson regression analyses revealed a significant positive relationship between the number of suicide attempts and SO2 levels and a significant negative relationship between the number of suicide attempts and NO levels. When subjects were divided by means of suicide attempt, different relationships with meteorological and air pollution conditions were observed. CONCLUSION: Meteorological and air pollution conditions are environmental factors that can enable a more detailed understanding of suicide behavior according to the means of suicide attempts.
    Apr. 2023, Journal of affective disorders, 333, 154 - 160, English, International magazine
    Scientific journal

  • Ikuo Otsuka, Hanga Galfalvy, Jia Guo, Masato Akiyama, Dan Rujescu, Gustavo Turecki, Akitoyo Hishimoto, J John Mann
    BACKGROUND: Suicidal behavior is moderately heritable and a consequence of a combination of the diathesis traits for suicidal behavior and suicide-related major psychiatric disorders. Here, we sought to examine shared polygenic effects between various psychiatric disorders/traits and suicidal behavior and to compare the shared polygenic effects of various psychiatric disorders/traits on non-fatal suicide attempt and suicide death. METHODS: We used our genotyped European ancestry sample of 260 non-fatal suicide attempters, 317 suicide decedents and 874 non-psychiatric controls to test whether polygenic risk scores (PRSs) obtained from large GWASs for 22 suicide-related psychiatric disorders/traits were associated with suicidal behavior. Results were compared between non-fatal suicide attempt and suicide death in a sensitivity analysis. RESULTS: PRSs for major depressive disorder, bipolar disorder, schizophrenia, ADHD, alcohol dependence, sensitivity to environmental stress and adversity, educational attainment, cognitive performance, and IQ were associated with suicidal behavior (Bonferroni-corrected p < 2.5 × 10-4). The polygenic effects of all 22 psychiatric disorders/traits had the same direction (p for binomial tests = 4.8 × 10-7) and were correlated (Spearman's ρ = 0.85) between non-fatal suicide attempters and suicide decedents. CONCLUSIONS: We found that polygenic effects for major psychiatric disorders and diathesis-related traits including stress responsiveness and intellect/cognitive function contributed to suicidal behavior. While we found comparable polygenic architecture between non-fatal suicide attempters and suicide decedents based on correlations with PRSs of suicide-related psychiatric disorders/traits, our analyses are limited by small sample size resulting in low statistical power to detect difference between non-fatal suicide attempt and suicide death.
    Apr. 2023, Psychological medicine, 53(6) (6), 2689 - 2697, English, International magazine
    Scientific journal

  • Takaki Tanifuji, Satoshi Okazaki, Ikuo Otsuka, Kentaro Mouri, Tadasu Horai, Ryota Shindo, Toshiyuki Shirai, Akitoyo Hishimoto
    Major depressive disorder (MDD) is a common mental illness and a major public health concern worldwide. Depression is associated with epigenetic changes that regulate gene expression, and analyzing these changes may help elucidate the pathophysiology of MDD. Genome-wide DNA methylation (DNAm) profiles can function as 'epigenetic clocks' that can help estimate biological aging. Here, we assessed biological aging in patients with MDD using various DNAm-based indicators of epigenetic aging. We used a publicly available dataset containing data obtained from the whole blood samples of MDD patients (n = 489) and controls (n = 210). We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and DNAm-based telomere length (DNAmTL). We also investigated seven DNAm-based age-predictive plasma proteins (including cystatin C) and smoking status, which are components of GrimAge. Following adjustment for confounding factors such as age and sex, patients with MDD showed no significant difference in epigenetic clocks and DNAmTL. However, DNAm-based plasma cystatin C levels were significantly higher in patients with MDD than controls. Our findings revealed specific DNAm changes predicting plasma cystatin C levels in MDD. These findings may help elucidate the pathophysiology of MDD, leading to the development of new biomarkers and medications.
    Apr. 2023, Psychiatry research, 322, 115103 - 115103, English, International magazine
    Scientific journal

  • Danmeng Zhang, Noriomi Eguchi, Satoshi Okazaki, Ichiro Sora, Akitoyo Hishimoto
    Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in early childhood and can persist to adulthood. It can affect many aspects of a patient's daily life, so it is necessary to explore the mechanism and pathological alterations. For this purpose, we applied induced pluripotent stem cell (iPSC)-derived telencephalon organoids to recapitulate the alterations occurring in the early cerebral cortex of ADHD patients. We found that telencephalon organoids of ADHD showed less growth of layer structures than control-derived organoids. On day 35 of differentiation, the thinner cortex layer structures of ADHD-derived organoids contained more neurons than those of control-derived organoids. Furthermore, ADHD-derived organoids showed a decrease in cell proliferation during development from day 35 to 56. On day 56 of differentiation, there was a significant difference in the proportion of symmetric and asymmetric cell division between the ADHD and control groups. In addition, we observed increased cell apoptosis in ADHD during early development. These results show alterations in the characteristics of neural stem cells and the formation of layer structures, which might indicate key roles in the pathogenesis of ADHD. Our organoids exhibit the cortical developmental alterations observed in neuroimaging studies, providing an experimental foundation for understanding the pathological mechanisms of ADHD.
    Mar. 2023, Stem cell reviews and reports, 19(5) (5), 1482 - 1491, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Saki Hattori, Akira Suda, Ikuko Kishida, Masatoshi Miyauchi, Yohko Shiraishi, Nobuhiko Noguchi, Taku Furuno, Takeshi Asami, Mami Fujibayashi, Natsuki Tsujita, Chie Ishii, Norio Ishii, Takashi Saeki, Tadashi Fukushima, Toshio Moritani, Yusuke Saigusa, Akitoyo Hishimoto
    BACKGROUND: Distinct oral atypical antipsychotics have different effects on autonomic nervous system (ANS) activity. Among them, oral aripiprazole has been linked to dysfunction of the ANS in schizophrenia. Long-acting injectable aripiprazole is a major treatment option for schizophrenia, but the effect of the aripiprazole formulation on ANS activity remains unclear. In this study, we compared ANS activity between oral aripiprazole and aripiprazole once-monthly (AOM) in schizophrenia. METHODS: Of the 122 patients with schizophrenia who participated in this study, 72 received oral aripiprazole and 50 received AOM as monotherapy. We used power spectral analysis of heart rate variability to assess ANS activity. RESULTS: Patients who received oral aripiprazole showed significantly diminished sympathetic nervous activity compared with those who received AOM. Multiple regression analysis revealed that the aripiprazole formulation significantly influenced sympathetic nervous activity. CONCLUSION: Compared with oral aripiprazole, AOM appears to have fewer adverse effects, such as sympathetic nervous dysfunction.
    Mar. 2023, BMC psychiatry, 23(1) (1), 135 - 135, English, International magazine
    Scientific journal

  • Takaki Tanifuji, Ikuo Otsuka, Toshio Atarashiya, Atsushi Kimura, Tadasu Horai, Satoshi Okazaki, Akitoyo Hishimoto
    Wiley, Mar. 2023, Psychiatry and Clinical Neurosciences Reports, 2(1) (1)
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshiaki Onitsuka, Tsuyoshi Okada, Naomi Hasegawa, Takashi Tsuboi, Jun-ichi Iga, Norio Yasui-Furukori, Naoki Yamada, Hikaru Hori, Hiroyuki Muraoka, Kazutaka Ohi, Kazuyoshi Ogasawara, Shinichiro Ochi, Masahiro Takeshima, Kayo Ichihashi, Kentaro Fukumoto, Hitoshi Iida, Hisashi Yamada, Ryuji Furihata, Manabu Makinodan, Yoshikazu Takaesu, Shusuke Numata, Hiroshi Komatsu, Akitoyo Hishimoto, Mikio Kido, Kiyokazu Atake, Hirotaka Yamagata, Saya Kikuchi, Naoki Hashimoto, Masahide Usami, Eiichi Katsumoto, Takeshi Asami, Chika Kubota, Junya Matsumoto, Kenichiro Miura, Yoji Hirano, Koichiro Watanabe, Ken Inada, Ryota Hashimoto
    Ovid Technologies (Wolters Kluwer Health), 2023, Journal of Clinical Psychopharmacology, 43(4) (4), 365 - 368
    Scientific journal

  • Masanobu Kogure, Nobuhisa Kanahara, Atsuhiro Miyazawa, Yuki Shiko, Ikuo Otsuka, Koichi Matsuyama, Masayuki Takase, Makoto Kimura, Hiroshi Kimura, Kiyomitsu Ota, Keita Idemoto, Masaki Tamura, Yasunori Oda, Taisuke Yoshida, Satoshi Okazaki, Fumiaki Yamasaki, Yusuke Nakata, Yoshinori Watanabe, Tomihisa Niitsu, Akitoyo Hishimoto, Masaomi Iyo
    BACKGROUND: Most genetic analyses that have attempted to identify a locus or loci that can distinguish patients with treatment-resistant schizophrenia (TRS) from those who respond to treatment (non-TRS) have failed. However, evidence from multiple studies suggests that patients with schizophrenia who respond well to antipsychotic medication have a higher dopamine (DA) state in brain synaptic clefts whereas patients with TRS do not show enhanced DA synthesis/release pathways. PATIENTS AND METHODS: To examine the contribution (if any) of genetics to TRS, we conducted a genetic association analysis of DA-related genes in schizophrenia patients (TRS, n = 435; non-TRS, n = 539) and healthy controls (HC: n = 489). RESULTS: The distributions of the genotypes of rs3756450 and the 40-bp variable number tandem repeat on SLC6A3 differed between the TRS and non-TRS groups. Regarding rs3756450, the TRS group showed a significantly higher ratio of the A allele, whereas the non-TRS group predominantly had the G allele. The analysis of the combination of COMT and SLC6A3 yielded a significantly higher ratio of the putative low-DA type (i.e., high COMT activity + high SLC6A3 activity) in the TRS group compared to the two other groups. Patients with the low-DA type accounted for the minority of the non-TRS group and exhibited milder psychopathology. CONCLUSION: The overall results suggest that (i) SLC6A3 could be involved in responsiveness to antipsychotic medication and (ii) genetic variants modulating brain DA levels may be related to the classification of TRS and non-TRS.
    2023, Frontiers in psychiatry, 14, 1334335 - 1334335, English, International magazine
    Scientific journal

  • Takashi Tsuboi, Yoshikazu Takaesu, Naomi Hasegawa, Shinichiro Ochi, Kentaro Fukumoto, Kazutaka Ohi, Hiroyuki Muraoka, Tsuyoshi Okada, Funitoshi Kodaka, Shun Igarashi, Hitoshi Iida, Hiroko Kashiwagi, Hikaru Hori, Kayo Ichihashi, Kazuyoshi Ogasawara, Naoki Hashimoto, Jun-Ichi Iga, Toshinori Nakamura, Masahide Usami, Tatsuya Nagasawa, Mikio Kido, Hiroshi Komatsu, Hirotaka Yamagata, Kiyokazu Atake, Ryuji Furihata, Saya Kikuchi, Tadasu Horai, Masahiro Takeshima, Yoji Hirano, Manabu Makinodan, Junya Matsumoto, Kenichiro Miura, Akitoyo Hishimoto, Shusuke Numata, Hisashi Yamada, Norio Yasui-Furukori, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.
    Jan. 2023, Psychiatry and clinical neurosciences, 77(1) (1), 30 - 37, English, International magazine
    Scientific journal

  • Sen Li, Ikuo Otsuka, Takaki Tanifuji, Satoshi Okazaki, Tadasu Horai, Motonori Takahashi, Takeshi Kondo, Yasuhiro Ueno, Akitoyo Hishimoto
    Past evidence has indicated increased ribosomal DNA (rDNA) content in the blood of patients with schizophrenia (SCZ) among European populations. Here, for the first time, we investigated the rDNA copy number (rDNAcn) of SCZ in East Asian populations as well as in blood and brain tissues. In this study, we measured 18S/28S rDNAcn in the peripheral blood of live participants (81 patients with SCZ and 98 healthy controls) and the dorsolateral prefrontal cortices (DLPFCs) of postmortem individuals (10 patients with SCZ and 23 non-psychiatric controls) in the Japanese population. Patients with SCZ had significantly increased 18S/28S rDNAcn in the blood compared to controls (p < 0.05). 18S rDNAcn was significantly increased in the brain of patients with SCZ compared to controls (p < 0.05). In conclusion, regarding the increased rDNAcn in the blood of patients with SCZ that was previously reported in Europeans, we successfully replicated this by using a different, ethnically East Asian, cohort. Additionally, we provide the first evidence of increased rDNAcn in the brain of patients with SCZ. These findings may help to elucidate the molecular underpinnings of SCZ pathophysiology related to ribosomal DNA abnormalities.
    2023, PloS one, 18(1) (1), e0280694, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshitaka Kyou, Norio Yasui-Furukori, Naomi Hasegawa, Kenta Ide, Kayo Ichihashi, Naoki Hashimoto, Hikaru Hori, Yoshihito Shimizu, Yayoi Imamura, Hiroyuki Muraoka, Hitoshi Iida, Kazutaka Ohi, Yuka Yasuda, Kazuyoshi Ogasawara, Shusuke Numata, Jun-Ichi Iga, Takashi Tsuboi, Shinichiro Ochi, Fumitoshi Kodaka, Ryuji Furihata, Toshiaki Onitsuka, Manabu Makinodan, Hiroshi Komatsu, Masahiro Takeshima, Chika Kubota, Akitoyo Hishimoto, Kiyokazu Atake, Hirotaka Yamagata, Mikio Kido, Tatsuya Nagasawa, Masahide Usami, Taishiro Kishimoto, Saya Kikuchi, Junya Matsumoto, Kenichiro Miura, Hisashi Yamada, Koichiro Watanabe, Ken Inada, Ryota Hahimoto
    BACKGROUND: Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions. METHODS: We used data from the "Effectiveness of Guidelines for Dissemination And Education in psychiatric treatment" (EGUIDE) project to investigate the presence or absence of PRN psychotropic medications at discharge for each drug category. We compared the PRN psychotropic prescription ratio at discharge by diagnosis for each drug category. The antipsychotic monotherapy ratio and no prescription ratio of other psychotropics for schizophrenia at discharge and the antidepressant monotherapy ratio and no prescription ratio of other psychotropics for major depressive disorder at discharge were calculated for each regular prescription, including PRN psychotropic medications, as quality indicators (QIs). Spearman's rank correlation test was performed for QI values of regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis. RESULTS: The PRN psychotropic prescription ratio at discharge was 28.7% for schizophrenia and 30.4% for major depressive disorder, with no significant differences by diagnosis. The prescription ratios of PRN antipsychotic medications and PRN antiparkinsonian medications were significantly higher for schizophrenia. The prescription ratios of PRN anxiolytic and hypnotic and PRN antidepressant medications were significantly higher for patients with major depressive disorder. For both schizophrenia and major depressive disorder, the QI was lower for discharge prescriptions, including PRN medications, than for regular prescriptions. QI values for regular prescriptions and the QI ratio were positively correlated. CONCLUSIONS: Considering PRN psychotropic medications, the monotherapy ratio and no prescription ratio of other psychotropics at discharge decreased in pharmacotherapy for schizophrenia and major depressive disorder. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.
    Dec. 2022, Annals of general psychiatry, 21(1) (1), 52 - 52, English, International magazine
    Scientific journal

  • Inada K, Fukumoto K, Hasegawa N, Yasuda Y, Yamada H, Hori H, Ichihashi K, Iida H, Ohi K, Muraoka H, Kodaka F, Ide K, Hashimoto N, Iga JI, Ogasawara K, Atake K, Takaesu Y, Nagasawa T, Komatsu H, Okada T, Furihata R, Kido M, Kikuchi S, Kubota C, Makinodan M, Ochi S, Takeshima M, Yamagata H, Matsumoto J, Miura K, Usami M, Kishimoto T, Onitsuka T, Katsumoto E, Hishimoto A, Numata S, Yasui- Furukori N, Watanabe K, Hashimoto R
    AIMS: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence-practice-gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'. METHODS: To establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared. RESULT: IFS points vary and ranged from 0 to100. The average pre-admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge. CONCLUSIONS: We developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia.
    Dec. 2022, Neuropsychopharmacol Rep, 42(4) (4), 502 - 509, English, International magazine
    [Refereed]
    Scientific journal

  • Hitoshi Iida, Tsuyoshi Okada, Kiyotaka Nemoto, Naomi Hasegawa, Shusuke Numata, Kazuyoshi Ogasawara, Kenichiro Miura, Junya Matsumoto, Hikaru Hori, Jun-Ichi Iga, Kayo Ichihashi, Naoki Hashimoto, Hisashi Yamada, Kazutaka Ohi, Norio Yasui-Furukori, Kentaro Fukumoto, Takashi Tsuboi, Masahide Usami, Ryuji Furihata, Yoshikazu Takaesu, Akitoyo Hishimoto, Hiroyuki Muraoka, Eiichi Katsumoto, Tatsuya Nagasawa, Shinichiro Ochi, Hiroshi Komatsu, Saya Kikuchi, Masahiro Takeshima, Toshiaki Onitsuka, Shinichiro Tamai, Chika Kubota, Ken Inada, Koichiro Watanabe, Hiroaki Kawasaki, Ryota Hashimoto
    To disseminate, educate, and validate psychiatric clinical practice guidelines, the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project was launched in 2016. In this study, we investigated whether the web-based courses offered by this project would be as effective as the face-to-face courses. We analyzed and compared survey answers about overall participant satisfaction with the course and answers regarding clinical knowledge of schizophrenia and major depressive disorder between 170 participants who took the web-based courses in 2020 and 689 participants who took the face-to-face courses from 2016 to 2019. The web-based course participants completed the survey questions about satisfaction with the web-based courses. The web-based courses were conducted using a combination of web services to make it as similar as possible to the face-to-face courses. The degree of satisfaction assessed by the general evaluation of the web-based courses was higher than what was expected from the face-to-face courses. The degree of satisfaction was similar for the courses on schizophrenia and major depressive disorder. In addition, there were no significant differences in overall satisfaction and clinical knowledge between web-based and face-to-face courses. In conclusion, the web-based courses on clinical practice guidelines provided by the EGUIDE project were rated as more satisfying than the face-to-face course that the participants expected to take and no differences in the effectiveness of either course. The results suggest that, after the COVID-19 pandemic, it would be possible to disseminate this educational material more widely by adopting web-based courses additionally face-to-face courses.
    Nov. 2022, Neuropsychopharmacology reports, 43(1) (1), 23 - 32, English, International magazine
    Scientific journal

  • Kentaro Fukumoto, Fumitoshi Kodaka, Naomi Hasegawa, Hiroyuki Muraoka, Hikaru Hori, Kayo Ichihashi, Yuka Yasuda, Hitoshi Iida, Kazutaka Ohi, Shinichiro Ochi, Kenta Ide, Naoki Hashimoto, Masahide Usami, Toshinori Nakamura, Hiroshi Komatsu, Tsuyoshi Okada, Tatsuya Nagasawa, Ryuji Furihata, Kiyokazu Atake, Mikio Kido, Saya Kikuchi, Hirotaka Yamagata, Taishiro Kishimoto, Manabu Makinodan, Tadasu Horai, Masahiro Takeshima, Chika Kubota, Takeshi Asami, Eiichi Katsumoto, Akitoyo Hishimoto, Toshiaki Onitsuka, Junya Matsumoto, Kenichiro Miura, Hisashi Yamada, Norio Yasui-Furukori, Koichiro Watanabe, Ken Inada, Kotaro Otsuka, Ryota Hashimoto
    AIM: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. METHODS: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. RESULTS: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10-3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). CONCLUSION: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.
    Nov. 2022, Neuropsychopharmacology reports, 43(1) (1), 33 - 39, English, International magazine
    Scientific journal

  • 小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 千葉 悠平, 阿部 紀絵, 井出 恵子, 吉見 明香, 菱本 明豊, 山中 太郎, 柾 晴美, 荒井 秀典
    (株)ワールドプランニング, Nov. 2022, 老年精神医学雑誌, 33(増刊II) (増刊II), 184 - 184, Japanese

  • Takaki Tanifuji, Ikuo Otsuka, Atsushi Kimura, Tadasu Horai, Satoshi Okazaki, Wataru Satake, Akitoyo Hishimoto
    Nov. 2022, Psychiatry and clinical neurosciences, 76(11) (11), 603 - 604, English, International magazine

  • Yukihiro Takemura, Takaki Tanifuji, Satoshi Okazaki, Yutaka Shinko, Ikuo Otsuka, Tadasu Horai, Toshiyuki Shirai, Katsuro Aso, Noriya Yamamoto, Akitoyo Hishimoto
    Methamphetamine (MA) is used worldwide and causes serious public health and social problems. MA affects the central nervous, cardiac, and immune systems, which causes neuropsychiatric and cardiovascular diseases and infection. Epigenetic changes, including DNA methylation (DNAm), are associated with various clinical phenotypes of MA abuse. DNAm is related to biological aging and health risks; hence, we aimed to assess the changes in biological aging in MA dependence using the DNAm age and DNA methylation-based telomere length (DNAmTL). We used five measures of DNAm age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAmTL, and DNAm-based age-predictive factors (plasma proteins and blood cell composition). We compared patients with MA dependence and healthy controls (n = 24 each) using the DNAm profiles obtained from whole-blood samples. Patients with MA dependence showed significant acceleration in PhenoAge and GrimAge, as well as a trend for significant acceleration in DNAmTL. Following adjustment for confounding factors, MA dependence was significantly associated with accelerations in PhenoAge, GrimAge, and DNAmTL, as well as alterations in DNAm-based age-predictive factors (beta-2-microglobulin, granulocytes, and naive cluster of differentiation 4+ T cells). Our results suggested an acceleration of biological aging and specific changes in the DNAm of age- predictive factors in MA dependence.
    Nov. 2022, Psychiatry research, 317, 114901 - 114901, English, International magazine
    Scientific journal

  • Tsuyoshi Okada, Hikaru Hori, Naomi Hasegawa, Atsunobu Murata, Yoshitaka Kyou, Fumitoshi Kodaka, Hitoshi Iida, Shinichiro Ochi, Yoshikazu Takaesu, Takashi Tsuboi, Jun-Ichi Iga, Kayo Ichihashi, Hiroyuki Muraoka, Ryuji Furihata, Norio Yasui-Furukori, Masahide Usami, Toshiaki Onitsuka, Kazuyoshi Ogasawara, Hiromi Tagata, Masahiro Takeshima, Kazutaka Ohi, Shusuke Numata, Naoki Hashimoto, Hiroki Yamada, Manabu Makinodan, Hiroshi Komatsu, Akitoyo Hishimoto, Hirotaka Yamagata, Mikio Kido, Chika Kubota, Kiyokazu Atake, Hisashi Yamada, Tatsuya Nagasawa, Junya Matsumoto, Kenichiro Miura, Ken Inada, Koichiro Watanabe, Shiro Suda, Ryota Hashimoto
    Oct. 2022, Journal of clinical psychopharmacology, English, International magazine
    [Refereed]
    Scientific journal

  • Takaki Tanifuji, Ikuo Otsuka, Satoshi Okazaki, Tadasu Horai, Ryuhei So, Kyoichi Shiroiwa, Kentaro Mouri, Motofumi Tanaka, Nobuko Ohmoto, Ichiro Sora, Midori Hirai, Takumi Fukumoto, Yonson Ku, Akitoyo Hishimoto
    Oct. 2022, Asian journal of psychiatry, 78, 103282 - 103282, English, International magazine

  • 認知症予防のエビデンスと社会実装に向けた挑戦 J-MINT PRIME神奈川モデルから考える社会実装への課題
    小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 千葉 悠平, 阿部 紀絵, 井出 恵子, 吉見 明香, 菱本 明豊, 山中 太郎, 柾 晴美, 荒井 秀典
    (一社)日本認知症学会, Oct. 2022, Dementia Japan, 36(4) (4), 713 - 713, Japanese

  • Yasushi Okamura, Yuki Murahashi, Yuna Umeda, Toshihiro Misumi, Takeshi Asami, Masanari Itokawa, Hirohiko Harima, Masafumi Mizuno, Hisato Matsunaga, Akitoyo Hishimoto
    (1) Background: Even though the comorbidity of obsessive-compulsive disorder (OCD) and a psychotic disorder (PD), such as schizophrenia, is being increasingly recognized, the impact of this comorbidity on the clinical presentation, including insight into obsessive-compulsive symptoms and the functioning of OCD, remains unclear. (2) Methods: To investigate clinical differences between OCD patients with and without PD, 86 Japanese outpatients who met the DSM-IV-TR criteria for OCD were recruited and divided into two groups: 28 OCD patients with PD, and 58 OCD patients without PD. The two groups were cross-sectionally compared in terms of their sociodemographic profiles and clinical characteristics, including the DSM-IV-TR insight specifier and the Global Assessment of Functioning (GAF). (3) Results: The results showed that OCD patients with PD scored lower on both the insight and GAF assessments. (4) Conclusions: The present study suggests that comorbid PD in OCD is a clinical entity.
    Sep. 2022, Healthcare (Basel, Switzerland), 10(10) (10), English, International magazine
    Scientific journal

  • Kiriko Minami, Takeshi Asami, Satoshi Tsujimura, Akira Suda, Keiko Ide, Akitoyo Hishimoto
    Sep. 2022, Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society, 22(6) (6), 886 - 889, English, International magazine

  • Yuriko Tanabe, Takeshi Asami, Asuka Yoshimi, Kie Abe, Yusuke Saigusa, Maya Hayakawa, Junichi Fujita, Keiko Ide, Akira Suda, Akitoyo Hishimoto
    AIM: The aim of this study was to conduct a 5-h training programme on anger-focused emotional management for nurses and verify its effectiveness. DESIGN: The study used a one-group pretest-posttest design. METHODS: Participants (N = 283) attended a programme comprising lectures and exercises. The Japanese version of the Buss-Perry Aggression Questionnaire was administered pre-, post- and 3-month posttraining. Regression analyses were used to assess the effects of the programme by gender. RESULTS: For the total aggression score, the difference between the pre- and posttraining scores was -2.827 points and remained at -1.602 points 3-month posttraining. Physical aggression scores decreased posttraining, but the scores increased after 3 months. There were statistically significant gender differences in hostility scores; pre-training scores were slightly higher for men than for women and lower for men after 3 months. Total and physical aggression scores were higher for men than for women. The training programme decreased aggression, and the effect persisted after 3 months.
    Sep. 2022, Nursing open, 10(2) (2), 998 - 1006, English, International magazine
    Scientific journal

  • Akitoyo Hishimoto, Norio Yasui-Furukori, Daisuke Sekine, Miyuki Matsukawa, Sakiko Yamada
    INTRODUCTION: Treatment continuation is essential for relapse prevention in patients with schizophrenia. The aim of this exploratory study was to compare the time to treatment discontinuation between patients with schizophrenia prescribed brexpiprazole (BRX group) and those prescribed other atypical antipsychotics (OAA group) in clinical settings in Japan using health insurance claims data. METHODS: De-identified data of working individuals with schizophrenia aged < 75 years and their dependents were assessed from April 2017 to May 2020 using a nationwide claims database. Cox proportional hazards models, adjusted for baseline patient variables, were used to compare the time to treatment discontinuation (primary outcome) for 180 days between BRX and OAA groups and to estimate the hazard ratio (HR) with 95% confidence interval (CI). The cumulative treatment continuation rates at 180 days were also estimated. Sensitivity and subgroup analyses were conducted for the primary outcome. RESULTS: The analysis included 978 and 4898 patients in the BRX and OAA groups, respectively. Patients in the BRX group were significantly less likely to discontinue treatment than those in the OAA group (HR 0.86, 95% CI 0.78-0.95; p = 0.0024). The cumulative treatment continuation rates were higher in the BRX group (45.9%, 95% CI 42.5-49.2]) than in the OAA group (39.5%, 95% CI 38.1-41.0; log-rank test, p < 0.0001). Based on patients matched by propensity score, the BRX group was significantly less likely to discontinue treatment than the OAA group (log-rank test, p = 0.0466). Similar results were obtained in sensitivity and subgroup analyses. CONCLUSION: This real-world study showed that patients in the BRX group were less likely to discontinue treatments than those in the OAA group. These findings suggest that BRX may contribute to treatment continuation among patients with schizophrenia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000044682.
    Sep. 2022, Advances in therapy, 39(9) (9), 4299 - 4314, English, International magazine
    Scientific journal

  • Yasuo Haruyama, Etsuko Miyagi, Gen Kobashi, Soichiro Obata, Takeshi Umazume, Asuka Yoshimi, Akitoyo Hishimoto, Kentaro Kurasawa, Yukio Suzuki, Tomoaki Ikeda, Tadashi Kimura, Hideto Yamada
    To investigate the relationships between communicative and critical health literacy (CCHL) and anxiety and depressive symptoms (ADs) in pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. A cross-sectional study was conducted and 5466 pregnant women responded in Japan in September 2020. A Kessler 6 scale (K6) score ≥ 10, an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13, and four CCHL groups were analyzed using a logistic regression model and trend test. The proportions of pregnant women with a K6 score ≥ 10 and EPDS score ≥ 13 were 13.5 and 15.4%, respectively. In comparisons with the low CCHL group, the adjusted odds ratio (95% CI) for anxiety symptoms was 0.770 (0.604-0.982) in the high CCHL group, while those for depressive symptoms were 0.777 (0.639-0.946), 0.665 (0.537-0.824), and 0.666 (0.529-0.838) in the lower, higher, and high CCHL groups (all p < 0.05), respectively, after adjustments for potential confounding factors, such as age, weeks of gestation, complications, history, number of children, marital status, education, employment, and income. Higher CCHL was associated with significantly lower adjusted odds ratios for anxiety (p for trend = 0.019) and depressive symptoms (p for trend < 0.001). These results suggest a relationship between CCHL and ADs in pregnant women during the COVID-19 pandemic.
    Aug. 2022, Scientific reports, 12(1) (1), 14042 - 14042, English, International magazine
    Scientific journal

  • Hiroyuki Muraoka, Fumitoshi Kodaka, Naomi Hasegawa, Norio Yasui-Furukori, Kentaro Fukumoto, Hiroko Kashiwagi, Hiromi Tagata, Hikaru Hori, Kiyokazu Atake, Hitoshi Iida, Kayo Ichihashi, Ryuji Furihata, Takashi Tsuboi, Masahiro Takeshima, Hiroshi Komatsu, Chika Kubota, Shinichiro Ochi, Yoshikazu Takaesu, Masahide Usami, Tatsuya Nagasawa, Manabu Makinodan, Toshinori Nakamura, Mikio Kido, Ikki Ueda, Hirotaka Yamagata, Toshiaki Onitsuka, Takeshi Asami, Akitoyo Hishimoto, Kazuyoshi Ogasawara, Eiichi Katsumoto, Kenichiro Miura, Junya Matsumoto, Kazutaka Ohi, Hisashi Yamada, Koichiro Watanabe, Ken Inada, Katsuji Nishimura, Ryota Hashimoto
    PURPOSE: In the treatment guidelines for major depressive disorder (MDD), the recommended treatment differs based on the severity. However, the type of treatment provided based on the severity of MDD in real-world clinical practice has not been investigated. In this study, we clarified the actual situation of MDD treatment in clinical practice and compared the treatment based on the severity of MDD. METHODS: We used data from 1484 patients with MDD at discharge from October 2016 to March 2020. RESULTS: The number of psychotropic prescriptions tended to be lower in those diagnosed with MDD in the severe group compared to in the non-severe group. There were significant differences among the three groups (mild, moderate/severe, and psychotic) in the percentage of patients who were not prescribed antipsychotics (p = 1.9 ×10-6), a combination of antipsychotics and antidepressants (p = 5.0 ×10-4), and the implementation rate of modified electroconvulsive therapy (m-ECT) (p = 3.4 ×10-9). The percentage of patients with a severe diagnosis who underwent m-ECT was higher, which corresponded to the severity. CONCLUSION: Our findings showed that the use of psychotropics decreased when the severity of MDD was diagnosed, and the rate of a combination of antipsychotics and antidepressants and the implementation rate of m-ECT increased with the severity. However, this study suggests that there is still an evidence-practice gap in the treatment of MDD in Japan, and guidelines are only partially adhered to in the treatment of depression.
    Aug. 2022, Asian journal of psychiatry, 74, 103174 - 103174, English, International magazine
    Scientific journal

  • Shinichiro Ochi, Hiromi Tagata, Naomi Hasegawa, Norio Yasui-Furukori, Jun-Ichi Iga, Hiroko Kashiwagi, Fumitoshi Kodaka, Hiroshi Komatsu, Takashi Tsuboi, Akira Tokutani, Shusuke Numata, Kayo Ichihashi, Toshiaki Onitsuka, Hiroyuki Muraoka, Hitoshi Iida, Kazutaka Ohi, Kiyokazu Atake, Taishiro Kishimoto, Hikaru Hori, Yoshikazu Takaesu, Masahiro Takeshima, Masahide Usami, Manabu Makinodan, Naoki Hashimoto, Michiko Fujimoto, Ryuji Furihata, Tatsuya Nagasawa, Hisashi Yamada, Junya Matsumoto, Kenichiro Miura, Mikio Kido, Akitoyo Hishimoto, Shu-Ichi Ueno, Koichiro Watanabe, Ken Inada, Ryota Hashimoto
    BACKGROUND: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Although antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. METHODS: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. RESULTS: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; p < 2.0 × 10 -16) and the ND-TRS without clozapine group (54.7%; p < 2.0 × 10 -16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; p = 1.1 × 10 -6) and the ND-TRS without clozapine group (17.0%; p = 5.9 × 10 -6). CONCLUSIONS: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.
    Jun. 2022, The international journal of neuropsychopharmacology, 25(10) (10), 818 - 826, English, International magazine
    Scientific journal

  • Yunfeng Ruan, Yen-Feng Lin, Yen-Chen Anne Feng, Chia-Yen Chen, Max Lam, Zhenglin Guo, Lin He, Akira Sawa, Alicia R Martin, Shengying Qin, Hailiang Huang, Tian Ge
    Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) have been conducted predominantly in individuals of European descent, the limited transferability of PRS reduces their clinical value in non-European populations, and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most remain underpowered. Here, we present a new PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations. PRS-CSx couples genetic effects across populations via a shared continuous shrinkage (CS) prior, enabling more accurate effect size estimation by sharing information between summary statistics and leveraging linkage disequilibrium diversity across discovery samples, while inheriting computational efficiency and robustness from PRS-CS. We show that PRS-CSx outperforms alternative methods across traits with a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes in simulations, and improves the prediction of quantitative traits and schizophrenia risk in non-European populations.
    May 2022, Nature genetics, 54(5) (5), 573 - 580, English, International magazine
    Scientific journal

  • 認知症予防の社会実装を考える J-MINT PRIME神奈川研究から社会実装を考える
    小田原 俊成, 水嶋 春朔, 齋藤 京子, 千葉 悠平, 阿部 紀絵, 吉見 明香, 井出 恵子, 山中 太郎, 柾 晴美, 菱本 明豊
    (一社)日本老年医学会, May 2022, 日本老年医学会雑誌, 59(Suppl.) (Suppl.), 72 - 72, Japanese

  • Hisashi Yamada, Mikuni Motoyama, Naomi Hasegawa, Kenichiro Miura, Junya Matsumoto, Kazutaka Ohi, Norio Yasui-Furukori, Shusuke Numata, Masahiro Takeshima, Nobuhiro Sugiyama, Tatsuya Nagasawa, Chika Kubota, Kiyokazu Atake, Takashi Tsuboi, Kayo Ichihashi, Naoki Hashimoto, Takahiko Inagaki, Yoshikazu Takaesu, Jun-Ichi Iga, Hikaru Hori, Toshiaki Onitsuka, Hiroshi Komatsu, Akitoyo Hishimoto, Kentaro Fukumoto, Michiko Fujimoto, Toshinori Nakamura, Kiyotaka Nemoto, Ryuji Furihata, Satoshi Yamamura, Hirotaka Yamagata, Kazuyoshi Ogasawara, Eiichi Katsumoto, Atsunobu Murata, Hitoshi Iida, Shinichiro Ochi, Manabu Makinodan, Mikio Kido, Taishiro Kishimoto, Yuka Yasuda, Masahide Usami, Taro Suwa, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    BACKGROUND: Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. AIMS: The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. METHOD: A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. RESULTS: All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. CONCLUSIONS: All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.
    Apr. 2022, BJPsych open, 8(3) (3), e83, English, International magazine
    Scientific journal

  • Satoshi Okazaki, Ryo Kimura, Ikuo Otsuka, Kiyotaka Tomiwa, Yasuko Funabiki, Masatoshi Hagiwara, Toshiya Murai, Akitoyo Hishimoto
    BACKGROUND: Williams syndrome (WS) is a rare genetic disorder caused by a microdeletion at the 7q11.23 region and is characterized by diverse symptoms encompassing physical and cognitive features. WS was reported to be associated to altered DNA methylation (DNAm) patterns. However, due to the limited information from long-term studies, it remains unclear whether WS accelerates aging. Genome-wide DNAm profiles can serve as "epigenetic clocks" to help estimate biological aging along with age-related markers, such as plasma proteins and telomere length. METHODS: We investigated GrimAge, DNAm-based telomere length (DNAmTL), and other epigenetic clocks in blood samples of 32 patients with WS and 32 healthy controls. RESULTS: We observed a significant acceleration in GrimAge, DNAmTL, and other epigenetic clocks in patients with WS as compared with those of controls. In addition, several GrimAge components, such as adrenomedullin, growth differentiation factor-15, leptin and plasminogen activator inhibitor-1, were altered in patients with WS. CONCLUSIONS: This study provides novel evidence supporting the hypothesis that WS may be associated to accelerated biological aging. A better understanding of the overall underlying biological effects of WS can provide new foundations for improved patient care; thus, long-term follow-up studies are still warranted.
    Apr. 2022, Journal of child psychology and psychiatry, and allied disciplines, 63(12) (12), 1553 - 1562, English, International magazine
    Scientific journal

  • Kazuyoshi Ogasawara, Shusuke Numata, Naomi Hasegawa, Masahito Nakataki, Manabu Makinodan, Kazutaka Ohi, Masahiro Takeshima, Takashi Tsuboi, Naoki Hashimoto, Toshiaki Onitsuka, Hiroyuki Muraoka, Hikaru Hori, Kayo Ichihashi, Takahiko Inagaki, Norio Yasui-Furukori, Akitoyo Hishimoto, Nobuhiro Sugiyama, Kentaro Fukumoto, Tatsuya Nagasawa, Junya Matsumoto, Yoshikazu Takaesu, Ryuji Furihata, Kiyotaka Nemoto, Toshinori Nakamura, Masahide Usami, Kenichiro Miura, Michiko Fujimoto, Hiromi Tagata, Hisashi Yamada, Hiroshi Komatsu, Shinichiro Ochi, Kiyokazu Atake, Eiichi Katsumoto, Mikio Kido, Taishiro Kishimoto, Taro Suwa, Satoshi Yamamura, Jun-Ichi Iga, Hitoshi Iida, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.
    Mar. 2022, Neuropsychopharmacology reports, 42(2) (2), 221 - 225, English, International magazine
    Scientific journal

  • Yutaka Shinko, Satoshi Okazaki, Ikuo Otsuka, Tadasu Horai, Saehyeon Kim, Takaki Tanifuji, Akitoyo Hishimoto
    BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a rare disorder characterized by neurodevelopmental delays, seizures, and diverse physical characteristics. The DNA methylation (DNAm) profile in NCBRS is significantly different. DNAm is linked to the biological aging of cells and the health risks associated with biological aging. In this study, we examined changes in biological ages in NCBRS to provide insights into the prognosis and health risks of NCBRS. METHODS: We used a publicly available dataset to examine biological aging in NCBRS using DNAm-based epigenetic ages, such as PhenoAge and GrimAge, as well as DNAm-based estimator of telomere length (DNAmTL). We investigated 12 cases, clinically diagnosed as NCBRS, and 27 controls. RESULTS: Compared to controls, NCBRS cases exhibited significantly accelerated PhenoAge and GrimAge as well as significantly shortened DNAmTL. CONCLUSION: These results suggest an acceleration of biological aging in NCBRS and provide insights into the prognosis and health risks of NCBRS.
    Mar. 2022, Molecular genetics & genomic medicine, 10(3) (3), e1876, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Junichi Fujita, Kumi Aoyama, Yusuke Saigusa, Hidehito Miyazaki, Yoshiko Aoki, Kazuya Asanuma, Yuichi Takahashi, Akitoyo Hishimoto
    ABSTRACT: Problematic Internet use (PIU) is common and likely to coexist with mental health problems among adolescents with school refusal behavior. To date, no study has revealed to what extent PIU relates to the daily burden compared with other mental health problems. This study has examined the association between daily difficulties and PIU among adolescents with school refusal behaviors.This cross-sectional study involved all first-visit patients, regardless of diagnosis, aged 10 to 18 years at 2 child/adolescent psychiatric outpatient clinics in Yokohama City, Japan, from April 2016 to March 2018. The Questionnaire-Children with Difficulties (QCD) were obtained from parents. Simultaneously, the severity of PIU was evaluated using the Internet Addiction Test and depressive and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 scale in the 2 weeks before the first-visit. From 684 first-visit patients, 227 with school refusal behaviors were enrolled in the study.PIU was observed in 40% of adolescents with school refusal behaviors. The QCD scores among patients with PIU were significantly lower than those in patients without PIU. Linear regression analysis revealed relationships between PIU and lower QCD scores throughout the day (except at night) and the total score of the day, after controlling for confounders such as depressive and anxiety symptoms.In conclusion, among adolescents with school refusal behaviors, PIU may affect their parent-assessed daily difficulties particularly experienced throughout the day.
    Feb. 2022, Medicine, 101(7) (7), e28916, English, International magazine
    Scientific journal

  • Niamh Mullins, JooEun Kang, Adrian I Campos, Jonathan R I Coleman, Alexis C Edwards, Hanga Galfalvy, Daniel F Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B Ware, Andrew W Bergen, Wade H Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M Fichter, Steven Gallinger, Stephen J Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S Kaplan, Walter H Kaye, Pamela K Keel, James L Kennedy, Kelly L Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J Magistretti, Christian R Marshall, James E Mitchell, Eric T Monson, Richard M Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M Thornton, Janet Treasure, Ming T Tsuang, Stephanie H Witt, D Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M Air, Martin Alda, Lars Alfredsson, Ole A Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M Helena Azevedo, Nicholas Bass, Claiton H D Bau, Bernhard T Baune, Frank Bellivier, Klaus Berger, Joanna M Biernacka, Tim B Bigdeli, Elisabeth B Binder, Michael Boehnke, Marco P Boks, Rosa Bosch, David L Braff, Richard Bryant, Monika Budde, Enda M Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J Edenberg, Ayman H Fanous, Jerome C Foo, Andreas J Forstner, Mark Frye, Janice M Fullerton, Justine M Gatt, Pablo V Gejman, Ina Giegling, Hans J Grabe, Melissa J Green, Eugenio H Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P Hamilton, Marian L Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A Jones, Lina Jonsson, René S Kahn, John R Kelsoe, Kenneth S Kendler, Stefan Kloiber, Karestan C Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H Lee, Douglas F Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M Nöthen, Michael C O'Donovan, Roel A Ophoff, Michael J Owen, Carlos Pato, Michele T Pato, Brenda W J H Penninx, Jonathan Pimm, Giorgio Pistis, James B Potash, Robert A Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A Rouleau, Diego L Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R Sanders, Peter R Schofield, Thomas G Schulze, Laura J Scott, Alessandro Serretti, Jianxin Shi, Stanley I Shyn, Lea Sirignano, Pamela Sklar, Olav B Smeland, Jordan W Smoller, Edmund J S Sonuga-Barke, Gianfranco Spalletta, John S Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B Vincent, Henry Völzke, James T R Walters, Cynthia Shannon Weickert, Thomas W Weickert, Myrna M Weissman, Leanne M Williams, Naomi R Wray, Clement C Zai, Allison E Ashley-Koch, Jean C Beckham, Elizabeth R Hauser, Michael A Hauser, Nathan A Kimbrel, Jennifer H Lindquist, Benjamin McMahon, David W Oslin, Xuejun Qin, Esben Agerbo, Anders D Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M Hougaard, Ronald C Kessler, Henry R Kranzler, Qingqin S Li, Nicholas G Martin, Andrew M McIntosh, Ole Mors, Merete Nordentoft, Catherine M Olsen, David Porteous, Robert J Ursano, Danuta Wasserman, Thomas Werge, David C Whiteman, Cynthia M Bulik, Hilary Coon, Ditte Demontis, Anna R Docherty, Po-Hsiu Kuo, Cathryn M Lewis, J John Mann, Miguel E Rentería, Daniel J Smith, Eli A Stahl, Murray B Stein, Fabian Streit, Virginia Willour, Douglas M Ruderfer
    BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
    Feb. 2022, Biological psychiatry, 91(3) (3), 313 - 327, English, International magazine
    Scientific journal

  • Takeshi Asami, Masao Takaishi, Ryota Nakamura, Asuka Yoshimi, Jun Konishi, Kumi Aoyama, Junichi Fujita, Hidehito Miyazaki, Yoshiko Aoki, Kazuya Asanuma, Saki Hattori, Akira Suda, Thomas J Whitford, Yoshio Hirayasu, Akitoyo Hishimoto
    Previous cross-sectional studies have reported that adolescent patients with anorexia nervosa (AN) showed global gray matter volume (GMV) reductions at the acute phase which were restored at the weight-recovered phase, compared with healthy controls (HC). However, few studies have investigated white matter volume (WMV) or cortical thickness in the context of AN, and results have been inconsistent. Voxel-based morphometry analyses for GM and WM, and cortical thickness analyses for GM were conducted in 31 adolescent patients with AN (vs. 18 HC) in the acute phase, and 16 patients with AN (vs. 13 HC) in the follow-up weight-recovered phase, over an approximately 1-year follow-up interval. At the acute phase, the AN patients showed significant reductions of GMVs and cortical thickness in widespread brain regions, compared with HC. Significant WMV reductions were identified in the bilateral superior longitudinal fascicle, superior thalamic radiation, corona radiata, and fornix, pons, and medulla in the patients. At the weight-recovered phase, the AN patients showed a significant GMV reduction in the left hippocampus, and a WMV reduction in the pons, compared with the HC. There was no difference in cortical thickness between two groups at the weight-recovered phase. In conclusion, the widespread volumetric reductions in GM and WM, and reduced cortical thickness observed in AN patients in the acute phase were not evident in the follow-up weight-recovered phase. The volume reductions observed in the hippocampus and pons in the weight-recovered phase could potentially reflect delayed neurogenesis or recovery from starvation in the AN patients.
    Jan. 2022, Brain imaging and behavior, 16(3) (3), 1372 - 1380, English, International magazine
    Scientific journal

  • Kayo Ichihashi, Yoshitaka Kyou, Naomi Hasegawa, Norio Yasui-Furukori, Yoshihito Shimizu, Hikaru Hori, Naoki Hashimoto, Kenta Ide, Yayoi Imamura, Hisashi Yamada, Shinichiro Ochi, Jun-Ichi Iga, Yoshikazu Takaesu, Kazutaka Ohi, Takashi Tsuboi, Hitoshi Iida, Hirotaka Yamagata, Akitoyo Hishimoto, Tadasu Horai, Masahide Usami, Manabu Makinodan, Tatsuya Nagasawa, Hiroshi Komatsu, Mikio Kido, Hiroyuki Muraoka, Kiyokazu Atake, Masahiro Takeshima, Chika Kubota, Takahiko Inagaki, Shinichiro Tamai, Taishiro Kishimoto, Ryuji Furihata, Junya Matsumoto, Kenichiro Miura, Ken Inada, Koichiro Watanabe, Kiyoto Kasai, Ryota Hashimoto
    BACKGROUND: Although several guidelines indicate that daily pharmacotherapy is an important part of the treatment of schizophrenia and major depressive disorder, there are few reports regarding pro re nata (PRN) prescriptions. The purpose of this study is to clarify the characteristics of patients receiving psychotropic PRN prescription for the treatment of schizophrenia and major depressive disorder. METHOD: We used data from 'the effectiveness of guideline for dissemination and education in psychiatric treatment' (EGUIDE) project to evaluate the presence or absence of psychotropic PRN prescription at the time of discharge, the age and sex of patients receiving PRN prescription for each diagnosis, and the association between PRN prescription and regular daily psychotropics. RESULTS: The psychotropic PRN prescription ratio was 29.9% among 2617 patients with schizophrenia and 31.1% among 1248 patients with major depressive disorder at discharge. In schizophrenia, the psychotropic PRN prescription ratio was 21.6% for patients aged 65 years or older, which was lower than that of all other age groups. In major depressive disorder, the psychotropic PRN prescription ratio was 34.2% for female patients, which was significantly higher than that for male patients (25.5%). In schizophrenia, there was an association between psychotropic PRN prescription and regular use of multiple psychotropic medications. CONCLUSIONS: Psychotropic PRN prescription was less common in elderly patients with schizophrenia and more common in female patients with major depressive disorder. In schizophrenia, psychotropic PRN prescription led to polypharmacy of psychotropics. Further studies are needed to accumulate evidence and to provide education on appropriate PRN prescriptions.
    Jan. 2022, Asian journal of psychiatry, 69, 103007 - 103007, English, International magazine
    Scientific journal

  • K Abe, Y Chiba, K Ide, A Yoshimi, T Asami, A Suda, T Odawara, A Hishimoto
    BACKGROUND: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. OBJECTIVES: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. DESIGN AND SETTING: Retrospective observational study using the data extracted from the Alzheimer's Disease Neuroimaging Initiative database. PARTICIPANTS: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI). MEASUREMENTS: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. RESULTS: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.
    2022, The journal of prevention of Alzheimer's disease, 9(2) (2), 331 - 337, English, International magazine
    Scientific journal

  • Keiko Ide, Takeshi Asami, Akira Suda, Asuka Yoshimi, Junichi Fujita, Yohko Shiraishi, Munetaka Nomoto, Masatoshi Miyauchi, Tomohide Roppongi, Taku Furuno, Kaori Watanabe, Tomoko Shimada, Tomoko Kaneko, Yusuke Saigusa, Kazumi Kubota, Hideaki Kato, Toshinari Odawara, Akitoyo Hishimoto
    The COVID-19 pandemic has been affecting the mental health of hospital workers. During the prolonged pandemic, hospital workers may experience much more severe psychological distress, leading to an increased risk of suicide. This study aimed to investigate changes in psychological effects on hospital workers over 12 months from the beginning of the pandemic and clarify factors associated with psychological distress and suicide-related ideation 1-year after the pandemic's beginning. These repeated, cross-sectional surveys collected demographic, mental health, and stress-related data from workers in 2 hospitals in Yokohama, Japan. The first survey, conducted in March-April 2020, contained the 12-item General Health Questionnaire (GHQ-12) assessing general distress and the Impact of Event Scale-Revised (IES-R) assessing event-related distress. In the second survey in March 2021, hospital workers at the same two hospitals were reassessed using the same questionnaire, and Item 9 of the Patient Health Questionnaire (PHQ-9) was added to assess their suicide-related ideation. The findings of the first and second surveys revealed that the average score of GHQ-12 (3.08 and 3.73, respectively), the IES-R total score (6.8 and 12.12, respectively), and the prevalence rates of severe general distress (35.0% and 44.0%, respectively) and severe event-related distress (7.0% and 17.1%, respectively) deteriorated. The second survey showed that 8.6% of the hospital workers were experiencing suicide-related ideation. Both the general and event-related distress were associated with suicide-related ideation. In these surveys, mental health outcomes among the hospital workers deteriorated over one year from the pandemic's beginning, and their severe psychological distress was the risk factor for the suicide-related ideation. Further studies are needed to compare the psychological effects on hospital workers during and after the prolonged pandemic and to explore appropriate measures to support hospital workers' mental health.
    2022, PloS one, 17(11) (11), e0277174, English, International magazine
    Scientific journal

  • Hikaru Hori, Norio Yasui-Furukori, Naomi Hasegawa, Jun-Ichi Iga, Shinichiro Ochi, Kayo Ichihashi, Ryuji Furihata, Yoshitaka Kyo, Yoshikazu Takaesu, Takashi Tsuboi, Fumitoshi Kodaka, Toshiaki Onitsuka, Tsuyoshi Okada, Atsunobu Murata, Hiroko Kashiwagi, Hitoshi Iida, Naoki Hashimoto, Kazutaka Ohi, Hisashi Yamada, Kazuyoshi Ogasawara, Yuka Yasuda, Hiroyuki Muraoka, Masahide Usami, Shusuke Numata, Masahiro Takeshima, Hirotaka Yamagata, Tatsuya Nagasawa, Hiromi Tagata, Manabu Makinodan, Mikio Kido, Eiichi Katsumoto, Hiroshi Komatsu, Junya Matsumoto, Chika Kubota, Kenichiro Miura, Akitoyo Hishimoto, Koichiro Watanabe, Ken Inada, Hiroaki Kawasaki, Ryota Hashimoto
    In several clinical guidelines for schizophrenia, long-term use of anticholinergic drugs is not recommended. We investigated the characteristics of the use of anticholinergics in patients with schizophrenia by considering psychotropic prescription patterns and differences among hospitals. A cross-sectional, retrospective prescription survey at the time of discharge was conducted on 2027 patients with schizophrenia from 69 Japanese hospitals. We examined the relations among psychotropic drug prescriptions regarding anticholinergic prescription. We divided the hospitals into three groups-low rate group (LG), medium rate group (MG), and high rate group (HG)-according to their anticholinergic prescription rates, and analyzed the relationship between anticholinergic prescription rates and antipsychotic prescription. Anticholinergic drugs were prescribed to 618 patients (30.5%), and the prescription rates were significantly higher for high antipsychotic doses, antipsychotic polypharmacy, and first-generation antipsychotics (FGAs) use. The anticholinergic prescription rate varied considerably among hospitals, ranging from 0 to 66.7%, and it was significantly higher in patients with antipsychotic monotherapy, antipsychotic polypharmacy, and normal and high doses of antipsychotics in HG than in those LG and MG. The anticholinergics prescription rate in patients with second-generation antipsychotic monotherapy in HG was also significantly higher than in those LG and MG; however, the difference was no longer significant in patients with FGA monotherapy. Conclusively, in addition to high antipsychotic doses, antipsychotic polypharmacy, and FGA use, hospital characteristics influence the prescribing of anticholinergic drugs.
    2022, Frontiers in psychiatry, 13, 823826 - 823826, English, International magazine
    Scientific journal

  • Satoshi Okazaki, Ryo Kimura, Ikuo Otsuka, Yasuko Funabiki, Toshiya Murai, Akitoyo Hishimoto
    BACKGROUND: Autism spectrum disorder (ASD) is characterized by impaired social communication and behavioral problems. An increased risk of premature mortality has been observed in individuals with ASD. Therefore, we hypothesized that biological aging is accelerated in individuals with ASD. Recently, several studies have established genome-wide DNA methylation (DNAm) profiles as 'epigenetic clocks' that can estimate biological aging. In addition, ASD has been associated with differential DNAm patterns. METHODS: We used two independent datasets from blood samples consisting of adult patients with high-functioning ASD and controls: the 1st cohort (38 ASD cases and 31 controls) and the 2nd cohort (6 ASD cases and 10 controls). We explored well-studied epigenetic clocks such as HorvathAge, HannumAge, SkinBloodAge, PhenoAge, GrimAge, and DNAm-based telomere length (DNAmTL). In addition, we investigated seven DNAm-based age-related plasma proteins, including plasminogen activator inhibitor-1 (PAI-1), and smoking status, which are the components of GrimAge. RESULTS: Compared to controls, individuals with ASD in the 1st cohort, but not in the 2nd cohort, exhibited a trend for increased GrimAge acceleration and a significant increase of PAI-1 levels. A meta-analysis showed significantly increased PAI-1 levels in individuals with ASD compared to controls. CONCLUSION: Our findings suggest there is no epigenetic age acceleration in the blood of individuals with ASD. However, this study provides novel evidence regarding increased plasma PAI-1 levels in individuals with high-functioning ASD. These findings suggest PAI-1 may be a biomarker for high-functioning ASD, however, larger studies based on epigenetic clocks and PAI-1 will be necessary to confirm these findings.
    2022, PloS one, 17(2) (2), e0263478, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Satoshi Okazaki, Shuken Boku, Yuichiro Watanabe, Ikuo Otsuka, Tadasu Horai, Ryo Morikawa, Atsushi Kimura, Naofumi Shimmyo, Takaki Tanifuji, Toshiyuki Someya, Akitoyo Hishimoto
    BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that promotes neurogenesis and neuroprotection. MIF is predominantly expressed in astrocytes in the brain. The serum MIF level and microsatellites/single nucleotide polymorphisms (SNPs) in the MIF gene promoter region are known to be associated with schizophrenia (SCZ). Interestingly, previous studies reported that hypoxia, an environmental risk factor for SCZ, induced MIF expression through binding of the hypoxia inducible factor (HIF)-1 to the hypoxia response element (HRE) in the MIF promoter. METHODS: We investigated the involvement of MIF in SCZ while focusing on the HIF pathway. First, we conducted an association study of the SNP rs17004038 (C>A) in the HRE of the MIF promoter between 1758 patients with SCZ and 1507 controls. Next, we investigated the effect of hypoxia on MIF expression in primary cultured astrocytes derived from neonatal mice forebrain. RESULTS: SNP rs17004038 was significantly associated with SCZ (p = 0.0424, odds ratio = 1.445), indicating that this SNP in the HRE of the MIF promoter was a genetic risk factor for SCZ. Hypoxia induced MIF mRNA expression and MIF protein production and increased HIF-1 binding to the MIF promoter, while the activity of the MIF promoter was suppressed by mutations in the HRE and by deletion of the HRE in astrocytes. CONCLUSION: These results suggest that SNP rs17004038 in the HRE of the MIF promoter was significantly associated with SCZ and may be involved in the pathophysiology of SCZ via suppression of hypoxia and HIF pathway-induced MIF expression.
    2022, PloS one, 17(3) (3), e0265738, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Saehyeon Kim, Satoshi Okazaki, Ikuo Otsuka, Yutaka Shinko, Tadasu Horai, Naofumi Shimmyo, Takashi Hirata, Naruhisa Yamaki, Takaki Tanifuji, Shuken Boku, Ichiro Sora, Akitoyo Hishimoto
    Metabolomics has been attracting attention in recent years as an objective method for diagnosing schizophrenia. In this study, we analyzed 378 metabolites in the serum of schizophrenia patients using capillary electrophoresis- and liquid chromatography-time-of-flight mass spectrometry. Using multivariate analysis with the orthogonal partial least squares method, we observed significantly higher levels of alanine, glutamate, lactic acid, ornithine, and serine and significantly lower levels of urea, in patients with chronic schizophrenia compared to healthy controls. Additionally, levels of fatty acids (15:0), (17:0), and (19:1), cis-11-eicosenoic acid, and thyroxine were significantly higher in patients with acute psychosis than in those in remission. Moreover, we conducted a systematic review of comprehensive metabolomics studies on schizophrenia over the last 20 years and observed consistent trends of increase in some metabolites such as glutamate and glucose, and decrease in citrate in schizophrenia patients across several studies. Hence, we provide substantial evidence for metabolic biomarkers in schizophrenia patients through our metabolomics study.
    Dec. 2021, Neuropsychopharmacology reports, 42(1) (1), 42 - 51, English, International magazine
    Scientific journal

  • Norio Yasui-Furukori, Hiroyuki Muraoka, Naomi Hasegawa, Shinichiro Ochi, Shusuke Numata, Hikaru Hori, Akitoyo Hishimoto, Toshiaki Onitsuka, Kazutaka Ohi, Naoki Hashimoto, Tatsuya Nagasawa, Yoshikazu Takaesu, Takahiko Inagaki, Hiromi Tagata, Takashi Tsuboi, Chika Kubota, Ryuji Furihata, Jun-Ichi Iga, Hitoshi Iida, Kenichiro Miura, Junya Matsumoto, Hisashi Yamada, Koichiro Watanabe, Ken Inada, Kazutaka Shimoda, Ryota Hashimoto
    BACKGROUND: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. METHODS: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study. RESULTS: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (rs  = 0.531, P = 1.032 × 10-4 ). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. CONCLUSION: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families.
    Dec. 2021, Neuropsychopharmacology reports, 42(1) (1), 3 - 9, English, International magazine
    Scientific journal

  • Atsuhiro Miyazawa, Nobuhisa Kanahara, Masanobu Kogure, Ikuo Otsuka, Satoshi Okazaki, Yoshinori Watanabe, Fumiaki Yamasaki, Yusuke Nakata, Yasunori Oda, Akitoyo Hishimoto, Masaomi Iyo
    BACKGROUND: GABAergic system dysfunction has been implicated in the etiology of schizophrenia and of cognitive impairments in particular. Patients with treatment-resistant schizophrenia (TRS) generally suffer from profound cognitive impairments in addition to severe positive symptoms, suggesting that GABA system dysfunction could be involved more closely in patients with TRS. METHODS AND RESULTS: In the present study, exome sequencing was conducted on fourteen TRS patients, whereby four SNPs were identified on GAD1, GABBR1 and GABBR2 genes. An association study for five SNPs including these 4 SNPs and rs3749034 on GAD1 as then performed among 357 patients with TRS, 682 non-TRS patients and 508 healthy controls (HC). The results revealed no significant differences in allelic and/or genetic distributions for any of the five SNPs. However, several subanalyses in comparisons between schizophrenia and HC groups, as well as between the three groups, showed nominal-level significance for rs3749034 on GAD1 and rs10985765/rs3750344 on GABBR2. In particular, in comparisons of female subjects, rigorous analysis for rs3749034 showed a statistical difference between the schizophrenia and HC groups and between the TRS and HC groups. CONCLUSIONS: Several positive results in subanalyses suggested that genetic vulnerability in the GABA system to schizophrenia or TRS could be affected by sex or sampling area, and overall, that rs3749034 on GAD1 and rs10985765 on GABBR2 could be related to TRS. In the present study, only a few SNPs were examined; it is possible that other important genetic variants in other regions of GABA-related genes were not captured in this preliminary study.
    Nov. 2021, Molecular biology reports, 49(3) (3), 2015 - 2024, English, International magazine
    Scientific journal

  • Ryuji Furihata, Rei Otsuki, Naomi Hasegawa, Takashi Tsuboi, Shusuke Numata, Norio Yasui-Furukori, Hiroko Kashiwagi, Hikaru Hori, Shinichiro Ochi, Hiroyuki Muraoka, Toshiaki Onitsuka, Hiroshi Komatsu, Masahiro Takeshima, Akitoyo Hishimoto, Tatsuya Nagasawa, Yoshikazu Takaesu, Toshinori Nakamura, Takeshi Asami, Kenichiro Miura, Junya Matsumoto, Kazutaka Ohi, Yuka Yasuda, Hitoshi Iida, Kazuyoshi Ogasawara, Naoki Hashimoto, Kayo Ichihashi, Hisashi Yamada, Koichiro Watanabe, Ken Inada, Ryota Hashimoto
    STUDY OBJECTIVES: To investigate the proportion of inpatients with schizophrenia and major depressive disorder prescribed hypnotic medication, and the association between such medication and the use of other antipsychotic agents. METHODS: This was a nationwide cross-sectional study performed as part of the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment' (EGUIDE) project. Data from 2146 inpatients with schizophrenia and 1031 inpatients with major depressive disorder were analyzed. All types and dosages of psychotropic drugs were recorded and the data at the time of discharge were analyzed. Associations between the use of hypnotic medication and other antipsychotic agents were evaluated using multivariate logistic regression analyses. RESULTS: The proportions of schizophrenia patients who were prescribed any and two or more hypnotic agents were 55.7% and 17.6%, respectively, and the corresponding proportions for patients with major depressive disorder were 63.6% and 22.6%, respectively. In schizophrenia patients, multivariate logistic regression analyses showed that two or more antipsychotics, anticholinergic drugs, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. In patients with major depressive disorder, multivariate logistic regression analyses revealed that two or more antidepressants, two or more antipsychotics, anxiolytics, and mood stabilizers/antiepileptic drugs were positively associated with the use of any hypnotic agent. CONCLUSIONS: Prescription of hypnotic agents was found to be highly frequent among inpatients with psychiatric disorders. Prescription of two or more main antipsychotic agents was commonly associated with the use of hypnotic medication for both schizophrenia and major depressive disorder.
    Nov. 2021, Sleep medicine, 89, 23 - 30, English, International magazine
    Scientific journal

  • Taishiro Kishimoto, Shotaro Kinoshita, Shogyoku Bun, Yasunori Sato, Momoko Kitazawa, Toshiaki Kikuchi, Mitsuhiro Sado, Akihiro Takamiya, Masaru Mimura, Takashi Nakamae, Yoshinari Abe, Tetsufumi Kanazawa, Yasuo Kawabata, Hiroaki Tomita, Koichi Abe, Akitoyo Hishimoto, Takeshi Asami, Akira Suda, Yoshinori Watanabe, Toru Amagai, Kei Sakuma, Hisashi Kida, Michitaka Funayama, Hiroshi Kimura, Aiko Sato, Shuichiro Fujiwara, Kiichiro Nagao, Naoya Sugiyama, Maki Takamiya, Hideyuki Kodama, Takaharu Azekawa
    INTRODUCTION: The COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. METHODS: The targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a "telepsychiatry group" (at least 50% of treatments to be conducted using telemedicine, with at least one face-to-face treatment [FTF] within six months) or an "FTF group" (all treatments to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. DISCUSSION: This study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. TRIAL REGISTRATION: jRCT1030210037, Japan Registry of Clinical Trials (jRCT).
    Oct. 2021, Contemporary clinical trials, 111, 106596 - 106596, English, International magazine
    Scientific journal

  • Keisuke Inoue, Tsuyoshi Eiro, Misato Semoto, Tomohide Roppongi, Munetaka Nomoto, Yuichi Takahashi, Akitoyo Hishimoto
    Oct. 2021, Clinical dysmorphology, 30(4) (4), 207 - 208, English, International magazine
    Scientific journal

  • 松沢病院の強迫症患者約85名の臨床的特徴 精神病性障害の併存や両者の鑑別に関する考察
    岡村 泰, 杉本 達哉, 頃安 英毅, 佐々木 亮, 村端 祐樹, 川瀬 愛, 梅田 夕奈, 根路銘 要太, 福田 陽明, 松本 光輔, 針間 博彦, 斎藤 正彦, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S614 - S614, Japanese

  • Soichiro Obata, Etsuko Miyagi, Yasuo Haruyama, Takeshi Umazume, Gen Kobashi, Asuka Yoshimi, Akitoyo Hishimoto, Kentaro Kurasawa, Yukio Suzuki, Tomoaki Ikeda, Tadashi Kimura, Hideto Yamada
    AIM: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. RESULTS: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557). CONCLUSIONS: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.
    Sep. 2021, The journal of obstetrics and gynaecology research, 47(9) (9), 2990 - 3000, English, International magazine
    Scientific journal

  • Naoki Hashimoto, Norio Yasui-Furukori, Naomi Hasegawa, Shuhei Ishikawa, Shusuke Numata, Hikaru Hori, Hitoshi Iida, Kayo Ichihashi, Ryuji Furihata, Atsunobu Murata, Takashi Tsuboi, Masahiro Takeshima, Yoshitaka Kyou, Hiroshi Komatsu, Chika Kubota, Shinichiro Ochi, Yoshikazu Takaesu, Masahide Usami, Tatsuya Nagasawa, Akitoyo Hishimoto, Kenichiro Miura, Junya Matsumoto, Kazutaka Ohi, Hisashi Yamada, Ken Inada, Koichiro Watanabe, Kazutaka Shimoda, Ryota Hashimoto
    BACKGROUND: Monopharmacy with antipsychotics and antidepressants is the first-line treatment for schizophrenia and major depressive disorder (MDD) in most clinical guidelines, while polypharmacy with psychotropic agents in the treatment of schizophrenia is common in clinical practice. There are no detailed data on the prescription patterns for inpatients with mental illness with reliable diagnoses made by treating psychiatrists. METHODS: We gathered prescription data at discharge from 2177 patients with schizophrenia and 1238 patients with MDD from October 2016 to March 2018. RESULTS: The patients with schizophrenia aged between 60 and 79 were prescribed lower doses of antipsychotics and hypnotics/anxiolytics than those aged between 40 and 59. There were significant differences between the prescription rate of antipsychotics in the patients with schizophrenia and that of antidepressants in the patients with MDD. The frequency of concomitant drugs such as anti-Parkinson drugs, anxiolytics/hypnotics and mood stabilizers in the subjects with schizophrenia prescribed antipsychotic polypharmacy was significantly higher than that with monotherapy. For the patients with schizophrenia, olanzapine, risperidone, aripiprazole, quetiapine, and blonanserin were the five most prescribed antipsychotics. For the patients with MDD, mirtazapine, duloxetine, escitalopram, trazodone and sertraline were the five most prescribed antidepressants. CONCLUSIONS: Our results showed the use of high doses of antipsychotics, high percentages of antipsychotic polypharmacy and concurrent use of hypnotics/anxiolytics in patients with schizophrenia. Notably, these data were collected before intensive instruction regarding the guidelines; therefore, we need to assess the change in the prescription pattern post guideline instruction.
    Sep. 2021, Asian journal of psychiatry, 63, 102744 - 102744, English, International magazine
    Scientific journal

  • Nao Toyohara, Junichi Fujita, Yasuyuki Okumura, Akira Suda, Saki Hattori, Yusuke Saigusa, Kumi Aoyama, Kazuya Asanuma, Yuichi Takahashi, Takashi Arai, Akitoyo Hishimoto
    BACKGROUND: Suicide remains one of the leading causes of death among adolescents. Although recent studies have suggested a strong association between auditory hallucinations and suicidal behaviors, little is known regarding the association between suicidal behaviors and visual hallucinations, which are also common among adolescent psychiatric patients. METHOD: A cross-sectional study of all first-time patients aged 10-15 years was conducted at three child and adolescent psychiatric outpatient facilities in Kanagawa Prefecture, Japan, from April 2015 to March 2018. Self-reported questionnaires were administered to evaluate auditory and visual hallucinations, suicide planning, and suicide attempts within the two weeks prior to the first visit. Our logistic regression model included three covariates (sex, age, and presence of major depressive episode) for adjustments. Among the 1285 respondents, 37 who had moderate or severe intellectual disability were excluded, leaving 1248 for analysis. RESULTS: Among the 1069 patients who completed questionnaire items on hallucinations, 230 (21.5%) experienced auditory or visual hallucinations. After controlling for all confounders, visual hallucinations, but not auditory hallucinations, were significantly associated with increased odds of suicide planning (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.5-4.1). In contrast, auditory hallucinations, but not visual hallucinations, were significantly associated with increased odds of suicide attempts (OR 2.8, 95% CI 1.3-6.1). No interaction effects were observed between suicidal behaviors and auditory or visual hallucinations. CONCLUSIONS: Clinicians should consider the prevalence of both auditory and visual hallucinations among young adolescent patients, with emphasis on auditory hallucinations, given their association with suicide attempts.
    Aug. 2021, Child and adolescent mental health, 27(4) (4), 335 - 342, English, International magazine
    Scientific journal

  • Keita Idemoto, Tomihisa Niitsu, Tatsuki Hata, Tamaki Ishima, Sumiko Yoshida, Kotaro Hattori, Tadasu Horai, Ikuo Otsuka, Hidenaga Yamamori, Shigenobu Toda, Yosuke Kameno, Kiyomitsu Ota, Yasunori Oda, Atsushi Kimura, Tasuku Hashimoto, Norio Mori, Mitsuru Kikuchi, Yoshio Minabe, Ryota Hashimoto, Akitoyo Hishimoto, Kazuyuki Nakagome, Kenji Hashimoto, Masaomi Iyo
    Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the pathophysiology of neuropsychiatric disorders. We examined serum GDNF levels in bipolar disorder (BD) patients and major depressive disorder (MDD) patients and their association with response to lithium therapy. We used a multicenter (six sites), exploratory, cross-sectional case-control design and recruited 448 subjects: 143 BD patients, 116 MDD patients, and 158 healthy controls (HCs). We evaluated the patients' clinical severity using the Clinical Global Impression (CGI), and responses to lithium therapy using the Alda scale. The serum GDNF levels were significantly decreased in the BD and MDD groups compared to the HCs, with no significant difference between the BD and MDD groups. After adjustment, the serum GDNF levels in the BD and MDD patients in remission or depressive states were decreased compared to the HC values. Lower serum GDNF levels in BD patients were associated with higher CGI and Alda scores (i.e., severe illness and good response to lithium therapy, respectively). Our findings suggest that the serum GDNF level may be a biomarker for both BD and MDD in remission or depressive states. The serum GDNF level may be associated with the lithium response of BD patients.
    Jul. 2021, Psychiatry research, 301, 113967 - 113967, English, International magazine
    Scientific journal

  • Shusuke Numata, Masahito Nakataki, Naomi Hasegawa, Yoshikazu Takaesu, Masahiro Takeshima, Toshiaki Onitsuka, Toshinori Nakamura, Reon Edagawa, Hiroaki Edo, Kenichiro Miura, Junya Matsumoto, Norio Yasui-Furukori, Taishiro Kishimoto, Hikaru Hori, Takashi Tsuboi, Yuka Yasuda, Ryuji Furihata, Hiroyuki Muraoka, Shinichiro Ochi, Tatsuya Nagasawa, Yoshitaka Kyou, Atsunobu Murata, Eiichi Katsumoto, Kazutaka Ohi, Akitoyo Hishimoto, Ken Inada, Koichiro Watanabe, Ryota Hashimoto
    BACKGROUND: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD). METHODS: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared. RESULTS: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group. CONCLUSIONS: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.
    Jun. 2021, Neuropsychopharmacology reports, 41(2) (2), 199 - 206, English, International magazine
    Scientific journal

  • Asaki Kumamoto, Yuhei Chiba, Akira Suda, Akitoyo Hishimoto, Akihiko Kase
    Epilepsy is known to comorbid with Alzheimer's disease. It can promote cognitive decline, and eventually worsen their prognosis and mortality. It is sometimes difficult to find a suitable drug because of the adverse effects. Perampanel has a unique mechanism of action that antagonizes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type glutamate receptor. Here, we report a case of severe dementia due to Alzheimer's disease with intractable epilepsy, which perampanel effected for controlling seizures with less adverse effects. The subject is an 89-year-old Japanese woman with severe dementia due to Alzheimer's disease and intractable myoclonic epilepsy. She also had psychiatric symptoms, such as circadian rhythm disorder and irritability. Valproic acid, lacosamide, or carbamazepine were prescribed, but none of them was effective. Shortly after perampanel started, however, myoclonus and these psychiatric symptoms improved. Moreover, it did not cause any obvious adverse effects, which made it possible to continue perampanel until the end of her life. Perampanel may be useful for controlling intractable epilepsy accompanied by Alzheimer's disease. It may also improve psychiatric symptoms with less adverse effect. Accumulation of studies is necessary to evaluate the effectiveness of perampanel on the epilepsy of Alzheimer's disease patients and further understand that mechanism.
    Jun. 2021, Journal of epilepsy research, 11(1) (1), 93 - 95, English, International magazine

  • Satoshi Okazaki, Shuken Boku, Ikuo Otsuka, Tadasu Horai, Atsushi Kimura, Naofumi Shimmyo, Naruhisa Yamaki, Akitoyo Hishimoto
    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and promotes neurogenesis and neuroprotection in brains. In addition, MIF has been identified as a potential marker of schizophrenia (SCZ). Our recent study also showed that serum MIF level is higher in SCZ and positively correlated with antipsychotic doses, and that MIF promoter polymorphisms are associated with SCZ. Here, we investigated the effects of antipsychotics such as clozapine on MIF expression in primary cultured astrocytes derived from neonatal mouse forebrain. MIF mRNA expression was estimated with quantitative reverse-transcription polymerase chain reaction. MIF protein concentration was measured with enzyme-linked immunosorbent assay. The histone acetylation of MIF promoter was examined with chromatin immunoprecipitation assay. As a result, common antipsychotics, especially clozapine, increased MIF mRNA expression in a dose-dependent manner. Clozapine increased MIF mRNA expression and protein concentration in a time-dependent manner. Moreover, clozapine increased the acetylation of histone H3 at lysine 27 residues (H3K27) in MIF promoter. In conclusion, we provide novel evidence that antipsychotics such as clozapine increases MIF expression via the acetylation of H3K27 in astrocytes, and that MIF may have a potential role for astrocytes in the action mechanisms of antipsychotics.
    Jan. 2021, Journal of psychiatric research, 135, 237 - 242, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kie Abe, Yuhei Chiba, Omi Katsuse, Yukitoshi Takahashi, Akira Suda, Saki Hattori, Ryusuke Yoshimi, Yohei Kirino, Misako Kunii, Asuka Yoshimi, Takeshi Asami, Akitoyo Hishimoto
    INTRODUCTION: Mild cognitive dysfunction has been implicated in a number of psychiatric diseases and affects social functioning. Although clinical criteria were recently proposed for autoimmune psychosis (AP), biomarkers have not yet been established for the severity and prognosis of cognitive dysfunction. We herein investigated the relationships between 3 types of serum antibodies and cognitive dysfunction in chronic psychiatric patients suspected of AP. METHODS: We included 31 patients suspected of AP and obtained information on their clinical characteristics. Three types of autoantibodies (the anti-N-methyl-D-aspartate receptor (anti-NMDAR Ab), anti-N-terminal of GluN1 (anti-GluN1-NT Ab), and anti-thyroid antibodies) were evaluated in serum. Cognitive function was assessed using Wechsler Adult Intelligence Scale-III. We examined the relationships between serum autoantibodies and cognitive dysfunction in patients using multiple regression models. RESULTS: Serum titers of anti-GluN1-NT Ab significantly contributed to the estimated score of working memory (B= -55.85, β= -0.46, p= 0.01), while no correlation was observed between the other 2 types of antibodies and cognitive function. CONCLUSIONS: The present results indicate the potential of serum anti-GluN1-NT Ab as a biomarker for the severity and prognosis of cognitive dysfunction underlying various psychiatric symptoms in patients with AP. The pathological significance of anti-GluN1-NT Ab needs to be verified in future studies.
    Jan. 2021, Neuroscience letters, 743, 135588 - 135588, English, International magazine
    Scientific journal

  • Takaki Tanifuji, Satoshi Okazaki, Ikuo Otsuka, Tadasu Horai, Yutaka Shinko, Saehyeon Kim, Ichiro Sora, Akitoyo Hishimoto
    Background: Monoamine oxidase-A (MAO-A) decomposes dopamine and serotonin, and decreased MAO-A expression increases monoamine levels and is related to the pathophysiology of schizophrenia. Previous studies have reported that variable number of tandem repeats (VNTR), namely, upstream (u)VNTR, and some single nucleotide polymorphisms (SNPs) in the MAOA gene are associated with schizophrenia. Methods: We investigated the two VNTRs and their related SNPs (rs6323 and rs1137070) in the MAOA gene promoter in 859 patients with schizophrenia and 826 healthy controls. Distal (d)VNTR and uVNTR were genotyped with fluorescence-based fragment polymerase chain reaction assays, and rs6323 and rs1137070 with TaqMan SNP genotyping assays. Results: Neither the genotype nor allelic frequency of the VNTRs or SNPs showed significant differences between the schizophrenia and control groups. On the other hand, analysis of the dVNTR-uVNTR-rs6323-rs1137070 haplotype showed significant association for nine repeats (9R)-3R-T-C in female patients (corrected p = 0.0006, odds ratio [confidence interval] = 2.17 [1.446-3.257]). Conclusion: Our findings provide novel evidence that MAOA gene polymorphisms are associated with an increased risk of developing schizophrenia in females.
    2021, Neuropsychiatric disease and treatment, 17, 3315 - 3323, English, International magazine
    Scientific journal

  • Hiroyuki Yamaguchi, Yuki Hashimoto, Genichi Sugihara, Jun Miyata, Toshiya Murai, Hidehiko Takahashi, Manabu Honda, Akitoyo Hishimoto, Yuichi Yamashita
    There has been increasing interest in performing psychiatric brain imaging studies using deep learning. However, most studies in this field disregard three-dimensional (3D) spatial information and targeted disease discrimination, without considering the genetic and clinical heterogeneity of psychiatric disorders. The purpose of this study was to investigate the efficacy of a 3D convolutional autoencoder (3D-CAE) for extracting features related to psychiatric disorders without diagnostic labels. The network was trained using a Kyoto University dataset including 82 patients with schizophrenia (SZ) and 90 healthy subjects (HS) and was evaluated using Center for Biomedical Research Excellence (COBRE) datasets, including 71 SZ patients and 71 HS. We created 16 3D-CAE models with different channels and convolutions to explore the effective range of hyperparameters for psychiatric brain imaging. The number of blocks containing two convolutional layers and one pooling layer was set, ranging from 1 block to 4 blocks. The number of channels in the extraction layer varied from 1, 4, 16, and 32 channels. The proposed 3D-CAEs were successfully reproduced into 3D structural magnetic resonance imaging (MRI) scans with sufficiently low errors. In addition, the features extracted using 3D-CAE retained the relation to clinical information. We explored the appropriate hyperparameter range of 3D-CAE, and it was suggested that a model with 3 blocks may be related to extracting features for predicting the dose of medication and symptom severity in schizophrenia.
    2021, Frontiers in neuroscience, 15, 652987 - 652987, English, International magazine
    Scientific journal

  • Keiko Ide, Takeshi Asami, Akira Suda, Asuka Yoshimi, Junichi Fujita, Munetaka Nomoto, Tomohide Roppongi, Kousuke Hino, Yuichi Takahashi, Kaori Watanabe, Tomoko Shimada, Toyoko Hamasaki, Emi Endo, Tomoko Kaneko, Michiko Suzuki, Kazumi Kubota, Yusuke Saigusa, Hideaki Kato, Toshinari Odawara, Hideaki Nakajima, Ichiro Takeuchi, Takahisa Goto, Michiko Aihara, Akitoyo Hishimoto
    The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that 'Feeling of being isolated and discriminated' was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.
    2021, PloS one, 16(1) (1), e0245294, English, International magazine
    Scientific journal

  • Keita Idemoto, Tamaki Ishima, Tomihisa Niitsu, Tatsuki Hata, Sumiko Yoshida, Kotaro Hattori, Tadasu Horai, Ikuo Otsuka, Hidenaga Yamamori, Shigenobu Toda, Yosuke Kameno, Kiyomitsu Ota, Yasunori Oda, Atsushi Kimura, Tasuku Hashimoto, Norio Mori, Mitsuru Kikuchi, Yoshio Minabe, Ryota Hashimoto, Akitoyo Hishimoto, Kazuyuki Nakagome, Masaomi Iyo, Kenji Hashimoto
    Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) due to overlapping depressive symptoms. This study investigated whether serum platelet-derived growth factor BB (PDGF-BB) is a differential diagnostic biomarker for BD and MDD. An initial SOMAscan proteomics assay of 1311 proteins in small samples from patients with BD and MDD and healthy controls (HCs) suggested that serum levels of PDGF-BB differed between BD and MDD. We then conducted a two-step, exploratory, cross-sectional, case-control study at our institute and five sites that included a total of 549 participants (157 with BD, 144 with MDD, and 248 HCs). Clinical symptoms were assessed using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. In the initial analysis at our institute, serum PDGF-BB levels in the MDD group (n = 36) were significantly lower than those in the BD (n = 39) and HC groups (n = 36). In the multicenter study, serum PDGF-BB levels in the MDD group were again significantly lower than those in the BD and HC groups, with no significant difference between the BD and HC groups. Treatment with sodium valproate was associated with significantly lower serum PDGF-BB levels in patients with BD. After controlling for confounding factors (sex, age, body mass index, clinical severity, and valproate medication), serum PDGF-BB levels were lower in the MDD group than in the BD group regardless of mood state. Our findings suggest that serum PDGF-BB may be a potential biomarker to differentiate BD and MDD.
    Dec. 2020, Journal of psychiatric research, 134, 48 - 56, English, International magazine
    Scientific journal

  • Satoshi Okazaki, Ikuo Otsuka, Yutaka Shinko, Tadasu Horai, Takashi Hirata, Naruhisa Yamaki, Ichiro Sora, Akitoyo Hishimoto
    BACKGROUND: Fetal alcohol spectrum disorder (FASD) is characterized by severe clinical impairment, considerable social burden, and high mortality and morbidity, which are due to various malformations, sepsis, and cancer. As >50% of deaths from FASD occur during the first year of life, we hypothesized that there is the acceleration of biological aging in FASD. Several recent studies have established genome-wide DNA methylation (DNAm) profiles as "epigenetic clocks" that can estimate biological aging, and FASD has been associated with differential DNAm patterns. Therefore, we tested this hypothesis using epigenetic clocks. METHODS: We investigated 5 DNAm-based measures of epigenetic age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and telomere length (DNAmTL) using 4 independent publicly available DNAm datasets; 2 datasets were derived from buccal epithelium, and the other 2 datasets were derived from peripheral blood. RESULTS: Compared with controls, children with FASD exhibited an acceleration of GrimAge in 1 buccal and 2 blood datasets. No significant difference was found in other DNAm ages and DNAmTL. Meta-analyses showed a significant acceleration of GrimAge in the blood samples but not in the buccal samples. CONCLUSIONS: This study provides novel evidence regarding accelerated epigenetic aging in children with FASD.
    Dec. 2020, Alcoholism, clinical and experimental research, 45(2) (2), 329 - 337, English, International magazine
    Scientific journal

  • Tadasu Horai, Shuken Boku, Satoshi Okazaki, Ikuo Otsuka, Woraphat Ratta-Apha, Kentaro Mouri, Naruhisa Yamaki, Takashi Hirata, Akitoyo Hishimoto
    MicroRNAs (miRNAs) have been investigated in neurodevelopmental and psychiatric disorders including schizophrenia (SZ). Previous studies showed miRNAs dysregulation in postmortem brain tissues and peripheral blood of SZ patients. These suggest that miRNAs may play a role in the pathophysiology of SZ and be a potential biomarker of SZ. Previous studies also showed that miRNAs regulated neurogenesis and that neurogenesis was involved in the pathophysiology of SZ. In addition, a recent study showed that miR-19a and 19b, enriched in neural progenitor cells (NPC) in adult hippocampus, were increased in human NPC derived from induced pluripotent stem cell derived from SZ patients. However, it remains unclear whether the levels of miR-19a and 19b are altered in peripheral blood of SZ patients and how miR-19a and 19b affects neurogenesis. To elucidate them, first we examined the levels of miR-19a and 19b in peripheral blood of SZ patients with quantitative RT-PCR and showed that the level of miR-19b, but not miR-19a, was significantly higher (miR-19a: p = 0.5733, miR-19b: p = 0.0038) in peripheral blood of SZ patients (N = 22) than that of healthy controls (N = 19). Next, we examined the involvement of miR-19b in proliferation and survival of mouse neonatal mice hippocampus-derived NPC with BrdU assay and TUNEL assay. The silencing of miR-19b significantly increased proliferation (N = 5, p = 0.0139), but not survival (N = 5, p = 0.9571), of neonatal mice hippocampus-derived NPC. These results suggest that the level of miR-19b in peripheral blood is a potential biomarker of schizophrenia and that the higher level of miR-19b may increase the vulnerability of SZ via attenuating proliferation of hippocampal NPC.
    Dec. 2020, Journal of psychiatric research, 131, 102 - 107, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Ryota Nakamura, Takeshi Asami, Asuka Yoshimi, Daiji Kato, Emi Fujita, Masao Takaishi, Kie Abe, Saki Hattori, Akira Suda, Kazumasa Shiozaki, Akihiko Kase, Yoshio Hirayasu, Akitoyo Hishimoto
    Sep. 2020, Schizophrenia research, 230, 101 - 103, English, International magazine
    Scientific journal

  • Hitoshi Iida, Junichi Iga, Naomi Hasegawa, Yuka Yasuda, Tomoya Yamamoto, Kenichiro Miura, Junya Matsumoto, Atsunobu Murata, Kazuyoshi Ogasawara, Hisashi Yamada, Hikaru Hori, Kayo Ichihashi, Naoki Hashimoto, Kazutaka Ohi, Norio Yasui-Furukori, Takashi Tsuboi, Toshinori Nakamura, Masahide Usami, Ryuji Furihata, Yoshikazu Takaesu, Kunihiro Iwamoto, Nobuhiro Sugiyama, Taishiro Kishimoto, Naohisa Tsujino, Hiroki Yamada, Akitoyo Hishimoto, Kiyotaka Nemoto, Kiyokazu Atake, Hiroyuki Muraoka, Eiichi Katsumoto, Satoru Oishi, Takahiko Inagaki, Fumiaki Ito, Yayoi Imamura, Mikio Kido, Tatsuya Nagasawa, Shusuke Numata, Shinichiro Ochi, Masaaki Iwata, Hidenaga Yamamori, Junichi Fujita, Toshiaki Onitsuka, Satoshi Yamamura, Manabu Makinodan, Michiko Fujimoto, Yoichiro Takayanagi, Kenji Takezawa, Hiroshi Komatsu, Kentaro Fukumoto, Shinichiro Tamai, Hirotaka Yamagata, Chika Kubota, Tadasu Horai, Ken Inada, Koichiro Watanabe, Hiroaki Kawasaki, Ryota Hashimoto
    Sep. 2020, Psychiatry and clinical neurosciences, 74(12) (12), 667 - 669, English, International magazine

  • Toshinori Chiba, Kentaro Ide, Jessica E Taylor, Shuken Boku, Hiroyuki Toda, Tetsufumi Kanazawa, Sumie Kato, Yuka Horiuchi, Akitoyo Hishimoto, Toru Maruyama, Taisuke Yamamoto, Miyako Shirakawa, Ichiro Sora, Mitsuo Kawato, Ai Koizumi
    Patients with posttraumatic stress disorder (PTSD) appear to manifest two opposing tendencies in their attentional biases and symptoms. However, whether common neural mechanisms account for their opposing attentional biases and symptoms remains unknown. We here propose a model in which reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) predicts synchronized alternations between emotional under- and overmodulatory states at the neural, behavioral, and symptom levels within the same patients. This reciprocal inhibition model predicts that when the amygdala is dominant, patients enter an emotional undermodulatory state where they show attentional bias toward threat and manifest re-experiencing symptoms. In contrast, when the vmPFC is dominant, patients are predicted to enter an emotional overmodulatory state where they show attentional bias away from threat and avoidance symptoms. To test the model, we performed a behavioral meta-analysis (total N = 491), analyses of own behavioral study (N = 20), and a neuroimaging meta-analysis (total N = 316). Supporting the model, we found the distributions of behavioral attentional measurements to be bimodal, suggesting alternations between the states within patients. Moreover, attentional bias toward threat was related to re-experiencing symptoms, whereas attentional bias away from threat was related with avoidance symptoms. We also found that the increase and decrease of activity in the left amygdala activity was related with re-experiencing and avoidance symptoms, respectively. Our model may help elucidate the neural mechanisms differentiating nondissociative and dissociative subtypes of PTSD, which usually show differential emotional modulatory levels. It may thus provide a new venue for therapies targeting each subtype.
    Jul. 2020, Molecular psychiatry, 26(9) (9), 5023 - 5039, English, International magazine
    Scientific journal

  • Kie Abe, Yuhei Chiba, Saki Hattori, Asuka Yoshimi, Takeshi Asami, Omi Katsuse, Akira Suda, Akitoyo Hishimoto
    OBJECTIVE: The present study investigated the effects of plasma matrix metalloproteinases (MMPs) on longitudinal changes in Alzheimer's disease (AD)-related biomarkers in cerebrospinal fluid (CSF), brain atrophy, and cognitive function in patients with mild cognitive impairment due to AD (MCI-AD). METHODS: We used data from the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4-positive patients with MCI-AD who were confirmed to have low Aβ42 and/or high phosphorylated-tau (p-tau) in CSF. We obtained baseline demographic data, plasma MMP levels, including MMP-1, -2, -7, -9, -10, and tissue inhibitor of MMP-1 (TIMP-1), longitudinal annual data on Aβ42, total tau, and p-tau in CSF, MRI-measured hippocampal volumes, and cognitive function evaluated by the Mini-Mental State Examination (MMSE) and AD Assessment Scale-11 (ADAS-11) over 4 years. We examined the effects of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampal volumes, and cognitive function using a linear mixed regression analysis. RESULTS: No significant differences were observed in baseline plasma MMP levels between MCI-AD patients and control subjects, except for MMP-10, which was significantly lower in MCI-AD than in controls. The baseline levels of MMPs did not correlate with longitudinal changes in CSF biomarkers. Declines in hippocampal volumes and cognitive function evaluated by MMSE and ADAS-11 were significantly faster in MCI-AD patients with high-MMP-9 levels at baseline than in those with middle and low MMP-9 levels at baseline. CONCLUSION: High plasma MMP-9 levels in MCI-AD patients might enhance neurodegeneration and cognitive decline.
    Jun. 2020, Journal of the neurological sciences, 416, 116989 - 116989, English, International magazine
    Scientific journal

  • Satoshi Okazaki, Shusuke Numata, Ikuo Otsuka, Tadasu Horai, Makoto Kinoshita, Ichiro Sora, Tetsuro Ohmori, Akitoyo Hishimoto
    There is high mortality among patients with bipolar disorder (BD). Studies have reported accelerated biological aging in patients with BD. Recently, Horvath and Hannum et al. independently developed DNA methylation (DNAm) profiles as "epigenetic clocks," which are the most accurate biological age estimate. This led to the development of two accomplished measures of epigenetic age acceleration (EAA) using blood samples, namely, intrinsic and extrinsic EAA (IEAA and EEAA, respectively). IEAA, which is based on Horvath's clock, is independent of blood cell counts and indicates cell-intrinsic aging. On the other hand, EEAA, which is based on Hannum's clock, is associated with age-dependent changes in blood cell counts and indicates immune system aging. Further, Lu et al. developed the "GrimAge" clock, which can strongly predict the mortality risk, and DNAm-based telomere length (DNAmTL). We used a DNAm dataset from whole blood samples obtained from 30 patients with BD and 30 healthy controls. We investigated Horvath EAA, IEAA, Hannum EAA, EEAA, Grim EAA, DNAmTL, and DNAm-based blood cell composition. Compared with controls, there was a decrease in Horvath EAA and IEAA in patients with BD. Further, there was a significant decrease in Horvath EAA and IEAA in patients with BD taking medication combinations of mood stabilizers (including lithium carbonate, sodium valproate, and carbamazepine) than in those taking no medication/monotherapy. This study provides novel evidence indicating decelerated epigenetic aging associated with mood stabilizers in patients with BD.
    May 2020, Translational psychiatry, 10(1) (1), 129 - 129, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Soichiro Maruyama, Shuken Boku, Satoshi Okazaki, Hiroki Kikuyama, Yoshito Mizoguchi, Akira Monji, Ikuo Otsuka, Ichiro Sora, Tetsufumi Kanazawa, Akitoyo Hishimoto, Hiroshi Yoneda
    AIM: Electroconvulsive therapy (ECT) is effective for psychiatric disorders. However, its action mechanism remains unclear. We previously reported that transcription factor 7 (TCF7) was increased in patients successfully treated with ECT. TCF7 regulates Wnt pathway, which regulates adult hippocampal neurogenesis. Adult hippocampal neurogenesis is involved in the pathophysiology of psychiatric disorders. Astrocytes play a role in adult hippocampal neurogenesis via neurogenic factors. Of astrocyte-derived neurogenic factors, leukemia inhibitory factor (LIF) and fibroblast growth factor 2 (FGF2) activate Wnt pathway. In addition, adenosine triphosphate (ATP), released from excited neurons, activates astrocytes. Therefore, we hypothesized that ECT might increase LIF and/or FGF2 in astrocytes. To test this, we investigated the effects of ATP and electric stimulation (ES) on LIF and FGF2 expressions in astrocytes. METHODS: Astrocytes were derived from neonatal mouse forebrain and administered ATP and ES. The mRNA expression was estimated with quantitative reverse-transcription polymerase chain reaction. Protein concentration was measured with ELISA. RESULTS: ATP increased LIF, but not FGF2, expression. Multiple ES, but not single, increased LIF expression. Knockdown of P2X2 receptor (P2X2R) attenuated ATP-induced increase of LIF mRNA expression. In contrast, P2X3 and P2X4 receptors intensified it. CONCLUSION: P2X2R may mediate ATP-induced LIF expression in astrocytes and multiple ES directly increases LIF expression in astrocytes. Therefore, both ATP/P2X2R and multiple ES-induced increases of LIF expression in astrocytes might mediate the efficacy of ECT on psychiatric disorders. Elucidating detailed mechanisms of ATP/P2X2R and multiple ES-induced LIF expression is expected to result in the identification of new therapeutic targets for psychiatric disorders.
    May 2020, Psychiatry and clinical neurosciences, 74(5) (5), 311 - 317, English, International magazine
    [Refereed]
    Scientific journal

  • Satoshi Hoya, Yuichiro Watanabe, Ayako Nunokawa, Ikuo Otsuka, Masako Shibuya, Hirofumi Igeta, Akitoyo Hishimoto, Toshiyuki Someya
    Whole-exome sequencing (WES) studies have shown that de-novo variants contribute to the genetic etiology of schizophrenia. WES studies of families with a monozygotic twin pair concordant or discordant for a disease may be fruitful for identifying de-novo pathogenic variants. Here, we performed WES in six individuals from one family (affected monozygotic twins, their unaffected parents, and two siblings) and identified three de-novo missense variants (CPT2 Ala283Thr, CPSF3 Val584Ile, and RNF148 Val210Ile) in the monozygotic twin pair concordant for schizophrenia. These three missense variants were not found in 1760 patients with schizophrenia or schizoaffective disorder or 1508 healthy controls. Our data do not support the role of the three missense variants in conferring risk for schizophrenia.
    Apr. 2020, Psychiatric genetics, 30(2) (2), 60 - 63, English, International magazine
    [Refereed]
    Scientific journal

  • Satoshi Okazaki, Ikuo Otsuka, Tadasu Horai, Takashi Hirata, Motonori Takahashi, Yasuhiro Ueno, Shuken Boku, Ichiro Sora, Akitoyo Hishimoto
    BACKGROUND: Studies suggest aberrant DNA methylation in victims of suicide. Recently, DNA methylation profiles have been developed for determining "epigenetic age," which is the most accurate estimate of biological age. Subsequently, two refined measures of epigenetic age acceleration have been expanded for blood samples as intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively). IEAA involves pure epigenetic aging independent of blood cell composition, whereas EEAA involves immunosenescence in association with blood cell composition. METHODS: We investigated epigenetic age acceleration using two independent DNA methylation datasets: a brain dataset from 16 suicide completers and 15 non-psychiatric controls and a blood dataset compiled using economical DNA pooling technique from 56 suicide completers and 60 living healthy controls. In the blood dataset, we considered IEAA and EEAA, as well as DNA methylation-based blood cell composition. RESULTS: There was no significant difference in universal epigenetic age acceleration between suicide completers and controls in both brain and blood datasets. Blood of suicide completers exhibited an increase in EEAA, but not in IEAA. We additionally found that suicide completers had more natural killer cells but fewer granulocytes compared to controls. CONCLUSION: This study provides novel evidence for accelerated extrinsic epigenetic aging in suicide completers and for the potential application of natural killer cells as a biomarker for suicidal behavior.
    Mar. 2020, Progress in neuro-psychopharmacology & biological psychiatry, 98, 109805 - 109805, English, International magazine
    [Refereed]
    Scientific journal

  • Yutaka Shinko, Ikuo Otsuka, Satoshi Okazaki, Tadasu Horai, Shuken Boku, Motonori Takahashi, Yasuhiro Ueno, Ichiro Sora, Akitoyo Hishimoto
    Suicide is a major health problem in the modern world. However, its physiological mechanisms have not been well elucidated yet. Immunological disturbances have been reported in psychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BP), and schizophrenia. Some studies have also suggested an association between immunological alterations especially neuroinflammation, and suicide. Chemokines play important roles in inflammation, and studies investigating chemokines in psychiatric diseases such as schizophrenia, MDD, and BP have reported chemokine dysregulations. However, there have been very few studies on the association between chemokines and suicide. We studied chemokine alterations in the postmortem brains of suicide completers and compared them to those of controls. We obtained brain tissue samples of the dorsolateral prefrontal cortex from 16 suicide completers and 23 controls. We examined the concentrations of chemokines and related substances in the brain tissue from these two groups using the Bio-Plex Pro™ Human Chemokine Panel 40-Plex. We performed multiple regression analysis with covariates. The levels of CCL1, CCL8, CCL13, CCL15, CCL17, CCL19, CCL20, CXCL11, and IL-10 were significantly decreased, whereas the IL-16 levels were significantly increased in the suicide completers after adjustment with the Benjamini-Hochberg method to control for type Ⅰ errors (Q < 0.05). The observed chemokine alterations might suggest the presence of suicide-specific immunological mechanisms.
    Jan. 2020, Journal of psychiatric research, 120, 29 - 33, English, International magazine
    [Refereed]
    Scientific journal

  • Ikuo Otsuka, Masato Akiyama, Osamu Shirakawa, Satoshi Okazaki, Yukihide Momozawa, Yoichiro Kamatani, Takeshi Izumi, Shusuke Numata, Motonori Takahashi, Shuken Boku, Ichiro Sora, Ken Yamamoto, Yasuhiro Ueno, Tatsushi Toda, Michiaki Kubo, Akitoyo Hishimoto
    Suicide is a significant public health problem worldwide, and several Asian countries including Japan have relatively high suicide rates on a world scale. Twin, family, and adoption studies have suggested high heritability for suicide, but genetics lags behind due to difficulty in obtaining samples from individuals who died by suicide, especially in non-European populations. In this study, we carried out genome-wide association studies combining two independent datasets totaling 746 suicides and 14,049 non-suicide controls in the Japanese population. Although we identified no genome-wide significant single-nucleotide polymorphisms (SNPs), we demonstrated significant SNP-based heritability (35-48%; P < 0.001) for completed suicide by genomic restricted maximum-likelihood analysis and a shared genetic risk between two datasets (Pbest = 2.7 × 10-13) by polygenic risk score analysis. This study is the first genome-wide association study for suicidal behavior in an East Asian population, and our results provided the evidence of polygenic architecture underlying completed suicide.
    Nov. 2019, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(12) (12), 2119 - 2124, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshikazu Takaesu, Koichiro Watanabe, Shusuke Numata, Masaaki Iwata, Noriko Kudo, Satoru Oishi, Takeya Takizawa, Kiyotaka Nemoto, Yuka Yasuda, Hiromi Tagata, Takashi Tsuboi, Naohisa Tsujino, Naoki Hashimoto, Yuki Matsui, Hikaru Hori, Hidenaga Yamamori, Nobuhiro Sugiyama, Taro Suwa, Taishiro Kishimoto, Akitoyo Hishimoto, Masahide Usami, Ryuji Furihata, Kunihiro Iwamoto, Hiroshige Fujishiro, Toshinori Nakamura, Kentaro Mizuno, Takahiko Inagaki, Eiichi Katsumoto, Hiroaki Tomita, Kazutaka Ohi, Hiroyuki Muraoka, Kiyokazu Atake, Hitoshi Iida, Tatsuya Nagasawa, Junichi Fujita, Satoshi Yamamura, Toshiaki Onitsuka, Atsunobu Murata, Yoichiro Takayanagi, Hokuto Noda, Yukiko Matsumura, Kenji Takezawa, Jun-Ichi Iga, Kayo Ichihashi, Kazuyoshi Ogasawara, Hisashi Yamada, Ken Inada, Ryota Hashimoto
    AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.
    Oct. 2019, Psychiatry and clinical neurosciences, 73(10) (10), 642 - 648, English, International magazine
    [Refereed]
    Scientific journal

  • Takashi Hirata, Ikuo Otsuka, Satoshi Okazaki, Kentaro Mouri, Tadasu Horai, Shuken Boku, Motonori Takahashi, Yasuhiro Ueno, Ichiro Sora, Osamu Shirakawa, Akitoyo Hishimoto
    A recent genome-wide association study (GWAS) for major depressive disorder (MDD) in Chinese women identified a single-nucleotide polymorphism (SNP), rs12415800, near the Sirtuin1 (SIRT1) gene as one of the top candidate loci. However, no study has shown a genetic association between SIRT1 and completed suicide, which is one of the most serious outcomes of MDD. In this study, 778 suicide completers and 760 controls in a Japanese population were genotyped for two SNPs in strong linkage disequilibrium (rs12415800 and rs4746720 in 3'UTR). We found significant associations between both SNPs and completed suicide among women aged ≥50 years. Additional analysis using postmortem brain tissues (10 suicide brains and 13 non-suicide brains) revealed the following: while SIRT1 gene expression in the prefrontal cortex did not differ between suicide and non-suicide brains, DNAJC12 gene expression, potentially implicated by the SNPs genotyped here, was significantly decreased in suicide brains (p = 0.003). In conclusion, regarding the genetic association of SIRT1 with MDD that was previously identified in women by the Chinese GWAS, we successfully validated our results using a female suicidal cohort in the same Asian population with the same direction of allelic effect.
    Aug. 2019, Psychiatry research, 278, 141 - 145, English, International magazine
    [Refereed]
    Scientific journal

  • Akitoyo Hishimoto, Olga Pletnikova, Doyle Lu Lang, Juan C Troncoso, Josephine M Egan, Qing-Rong Liu
    Following publication of the original article [1], the authors reported that Fig. 6 contains a mistake. The Fig. 6F is a duplicate of Fig. 6E of Braak 5.
    May 2019, Alzheimer's research & therapy, 11(1) (1), 39 - 39, English, International magazine
    [Refereed]

  • Akitoyo Hishimoto, Olga Pletnikova, Doyle Lu Lang, Juan C Troncoso, Josephine M Egan, Qing-Rong Liu
    BACKGROUND: Synaptic damage precedes neuron death in Alzheimer's disease (AD). Neurexins, NRXN1, NRXN2, and NRXN3, are presynaptic adhesion molecules that specify neuron synapses and regulate neurotransmitter release. Neurexins and postsynaptic neuroligins interact with amyloid beta oligomer (AβO) deposits in damaged synapses. NRXN3 gene variants have been associated with autism, addiction, and schizophrenia, however, not fully investigated in Alzheimer's disease. In the present study, we investigated an AD association of a 3'-splicing allele of rs8019381 that produces altered expression of transmembrane or soluble NRXN3 isoforms. METHODS: We carried out RT-PCR (reverse transcription polymerase chain reaction), PCR-RFLP (PCR and restriction fragment length polymorphism), Sanger sequencing, and in situ hybridization (ISH) assays for NRXN3 neuron expression and genotyping. Genetic associations were analyzed by χ2 tests, and ISH signals were analyzed by FISH v1.0 module of Indica Labs HALO software. RESULTS: We previously identified a functional haplotype in the 3' region of neurexin 3 (NRXN3) gene that alters the expression ratios between NRXN3 transmembrane and soluble isoforms. In this study, we found that expression and ratio of transmembrane and soluble NRXN3 isoforms were reduced in AD postmortem brains and inversely correlated with inflammasome component NLRP3 in AD brain regions. The splicing haplotype related to the transmembrane and soluble NRXN3 expression was associated with AD samples with P = 6.3 × 10-5 (odds ratio = 2.48) and interacted with APOE genotypes. CONCLUSIONS: We found that the SNP rs8019381 of NRXN3 that is located adjacent to splicing site #5 (SS#5) interacts with the APOE ε4 haplotype and alters NRXN3 transmembrane or soluble isoform expression in AD postmortem cortex. Dysregulation of presynaptic NRXN3 expression and splicing might increase neuron inflammation in AD brain.
    Mar. 2019, Alzheimer's research & therapy, 11(1) (1), 28 - 28, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Satoshi Okazaki, Ikuo Otsuka, Shusuke Numata, Tadasu Horai, Kentaro Mouri, Shuken Boku, Tetsuro Ohmori, Ichiro Sora, Akitoyo Hishimoto
    The accelerated aging hypothesis of schizophrenia (SCZ) has been proposed. DNA methylation profiles were developed for determining "epigenetic age." Here, we assessed intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively) in SCZ. We examined two independent cohorts of Japanese ancestry. The first cohort consisted of 80 patients with SCZ under long-term or repeated hospitalization and 40 controls, with the economical DNA pooling technique. The second cohort consisted of 24 medication-free patients with SCZ and 23 controls. Blood of SCZ subjects exhibited decreased EEAA in the first cohort (p = 0.0162), but not in the second cohort. IEAA did not differ in either cohort. We performed replication analyses using publicly available datasets from European ancestry (three blood and one brain datasets). One blood dataset showed increased EEAA in SCZ (p = 0.0228). Overall, our results provide evidence for decreased EEAA in SCZ associated with hospitalization in the Japanese population.
    Feb. 2019, NPJ schizophrenia, 5(1) (1), 4 - 4, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Naruhisa Yamaki, Sachio Matsushita, Sachiko Hara, Akira Yokoyama, Akitoyo Hishimoto, Susumu Higuchi
    Heavy drinking leads to premature aging and precipitates the onset of age-related diseases. Acetaldehyde (AcH), a toxic metabolite of ethanol, has been implicated in various types of cancer. However, whether alcohol accelerates biological aging at a cellular level is controversial and the mechanism involved is unclear. We addressed these questions by measuring telomere length (TL) in peripheral blood leukocytes of Japanese patients with alcohol dependence (AD) and examined the association between TL, genetic variants of alcohol dehydrogenase (ADH)1B and aldehyde dehydrogenase (ALDH)2, and other clinical characteristics. A total of 134 male AD patients and 121 age- and sex-matched healthy controls were evaluated. All patients received endoscopic screening for cancer of the upper aerodigestive tract (UADT). TL was almost 50% shorter in AD patients relative to controls. There were no significant differences in TL between AD patients with and without UADT cancer, and no associations between ADH1B and ALDH2 genotypes and TL. AD patients with thiamine (vitamin B1) deficiency at admission had significantly shorter TL than those with normal thiamine status. Although the exact mechanism underlying the shorter TL in AD patients remain unclear, our findings suggest that alcohol rather than AcH is associated with telomere shortening in AD, which may be accelerated by thiamine deficiency. Future studies should also focus on the association between telomere shortening and TD in the context of oxidative stress.
    Feb. 2019, Journal of psychiatric research, 109, 27 - 32, English, International magazine
    [Refereed]
    Scientific journal

  • Noa Tsujii, Ikuo Otsuka, Satoshi Okazaki, Masaya Yanagi, Shusuke Numata, Naruhisa Yamaki, Yoshihiro Kawakubo, Osamu Shirakawa, Akitoyo Hishimoto
    Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849-0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.
    2019, Frontiers in psychiatry, 10, 312 - 312, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshinori Chiba, Tetsufumi Kanazawa, Ai Koizumi, Kentarou Ide, Vincent Taschereau-Dumouchel, Shuken Boku, Akitoyo Hishimoto, Miyako Shirakawa, Ichiro Sora, Hakwan Lau, Hiroshi Yoneda, Mitsuo Kawato
    Background: Post-traumatic stress disorder (PTSD) is a neuropsychiatric affective disorder that can develop after traumatic life-events. Exposure-based therapy is currently one of the most effective treatments for PTSD. However, exposure to traumatic stimuli is so aversive that a significant number of patients drop-out of therapy during the course of treatment. Among various attempts to develop novel therapies that bypass such aversiveness, neurofeedback appears promising. With neurofeedback, patients can unconsciously self-regulate brain activity via real-time monitoring and feedback of the EEG or fMRI signals. With conventional neurofeedback methods, however, it is difficult to induce neural representation related to specific trauma because the feedback is based on the neural signals averaged within specific brain areas. To overcome this difficulty, novel neurofeedback approaches such as Decoded Neurofeedback (DecNef) might prove helpful. Instead of the average BOLD signals, DecNef allows patients to implicitly regulate multivariate voxel patterns of the BOLD signals related with feared stimuli. As such, DecNef effects are postulated to derive either from exposure or counter-conditioning, or some combination of both. Although the exact mechanism is not yet fully understood. DecNef has been successfully applied to reduce fear responses induced either by fear-conditioned or phobic stimuli among non-clinical participants. Methods: Follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted to compare DecNef effect with those of conventional EEG/fMRI-based neurofeedback on PTSD amelioration. To elucidate the possible mechanisms of DecNef on fear reduction, we mathematically modeled the effects of exposure-based and counter conditioning separately and applied it to the data obtained from past DecNef studies. Finally, we conducted DecNef on four PTSD patients. Here, we review recent advances in application of neurofeedback to PTSD treatments, including the DecNef. This review is intended to be informative for neuroscientists in general as well as practitioners planning to use neurofeedback as a therapeutic strategy for PTSD. Results: Our mathematical model suggested that exposure is the key component for DecNef effects in the past studies. Following DecNef a significant reduction of PTSD severity was observed. This effect was comparable to those reported for conventional neurofeedback approach. Conclusions: Although a much larger number of participants will be needed in future, DecNef could be a promising therapy that bypasses the unpleasantness of conscious exposure associated with conventional therapies for fear related disorders, including PTSD.
    2019, Frontiers in human neuroscience, 13, 233 - 233, English, International magazine
    [Refereed]

  • Hirofumi Igeta, Yuichiro Watanabe, Ryo Morikawa, Masashi Ikeda, Ikuo Otsuka, Satoshi Hoya, Masataka Koizumi, Jun Egawa, Akitoyo Hishimoto, Nakao Iwata, Toshiyuki Someya
    Purpose: Whole-exome sequencing (WES) of multiplex families is a promising strategy for identifying causative variations for common diseases. To identify rare recessive risk variations for schizophrenia, we performed a WES study in a consanguineous family with affected siblings. We then performed follow-up sequencing of SPATA7 in schizophrenia-affected families. In addition, we performed a case-control study to investigate association between SPATA7 variations and schizophrenia. Patients and methods: WES was performed on two affected siblings and their unaffected parents, who were second cousins, of a multiplex schizophrenia family. Subsequently, we sequenced the coding region of SPATA7, a potential risk gene identified by the WES analysis, in 142 affected offspring from 137 families for whom parental DNA samples were available. We further tested rare recessive SPATA7 variations, identified by WES and sequencing, for associations with schizophrenia in 2,756 patients and 2,646 controls. Results: Our WES analysis identified rare compound heterozygous missense SPATA7 variations, p.Asp134Gly and p.Ile332Thr, in both affected siblings. Sequencing SPATA7 coding regions from 137 families identified no rare recessive variations in affected offspring. In the case-control study, we did not detect the rare compound heterozygous SPATA7 missense variations in patients or controls. Conclusion: Our data does not support the role of the rare compound heterozygous SPATA7 missense variations p.Asp134Gly and p.Ile332Thr in conferring a substantial risk of schizophrenia.
    2019, Neuropsychiatric disease and treatment, 15, 2353 - 2363, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Naruhisa Yamaki, Ikuo Otsuka, Shusuke Numata, Masaya Yanagi, Kentaro Mouri, Satoshi Okazaki, Shuken Boku, Tadasu Horai, Tetsuro Ohmori, Osamu Shirakawa, Ichiro Sora, Akitoyo Hishimoto
    Numerous evidence indicated mitochondrial abnormalities in the pathophysiology of bipolar disorder (BD); however, it remains unclear whether aberrant mitochondrial DNA (mtDNA) copy number (cn) occur in BD due to the conflicting results in previous studies. Here, peripheral blood mtDNAcn in 69 BD patients and 54 controls were analysed via qPCR. BD patients had significantly lower mtDNAcn compared to controls (regardless of their BD type [BD I or II]). Meta-analysis for all previous BD-mtDNAcn studies combining our results with previously published studies failed to identify any significant association. Meanwhile, Asian-specific meta-analysis remarkably revealed lower mtDNAcn in BD patients.
    Nov. 2018, Psychiatry research, 269, 115 - 117, English, International magazine
    [Refereed]
    Scientific journal

  • Yuan Zhang, Akitoyo Hishimoto, Ikuo Otsuka, Yuichiro Watanabe, Shusuke Numata, Hidenaga Yamamori, Shuken Boku, Tadasu Horai, Toshiyuki Someya, Tetsuro Ohmori, Ryota Hashimoto, Ichiro Sora
    Several previous studies have investigated an association between leukocyte telomere length (LTL) and schizophrenia (SCZ). However, results have been largely inconsistent, partially due to the relatively small sample sizes in each study and heterogeneity caused by various uncontrolled confounders (e.g., duration of illness or hospitalization, lifetime antipsychotic dose, and LTL assay methods). Here, we investigate the association of LTL with SCZ with the quantitative polymerase chain reaction method in independent cohorts consisting of 1241 patients with SCZ and 1042 controls (the largest independent sample in this field). Furthermore, we examined whether duration of hospitalization and lifetime antipsychotic dose had an effect on LTL in SCZ. In all samples, we observed significantly longer LTL in patients with SCZ relative to controls. In subgroup analyses, we observed that longer telomeres in SCZ were only visible in elderly patients and not in patients under 50 years old. Moreover, significantly longer LTL in elderly patients with SCZ was only specific to those with long-term hospitalization, but not outpatients or those with short-term hospitalization. This may be because the former received more appropriate lifestyle management. Meanwhile, lifetime antipsychotic dose had no effect on LTL. Our findings suggest that consideration of the effect of age and duration of hospitalization on LTL may improve our understanding of controversial results obtained in previous studies of telomeres in SCZ.
    Aug. 2018, Journal of psychiatric research, 103, 161 - 166, English, International magazine
    [Refereed]
    Scientific journal

  • Satoshi Okazaki, Akitoyo Hishimoto, Ikuo Otsuka, Yuichiro Watanabe, Shusuke Numata, Shuken Boku, Naofumi Shimmyo, Makoto Kinoshita, Emiko Inoue, Tetsuro Ohmori, Toshiyuki Someya, Ichiro Sora
    BACKGROUND: Numerous studies have suggested that an immune system imbalance plays an important role in schizophrenia. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine. It plays multiple roles in various biological processes, including inflammation and neurogenesis. Furthermore, several exhaustive serum proteomic profiling studies have identified MIF as a potential biomarker of schizophrenia. Here, we investigate MIF protein levels in serum and postmortem prefrontal cortex in patients with schizophrenia and controls. Moreover, we investigate the association of two functional polymorphisms in the MIF gene promoter region (MIF-794CATT5-8 microsatellite and MIF-173G/C single-nucleotide polymorphism [SNP]) with schizophrenia. METHODS: We measured serum MIF levels with an enzyme-linked immunosorbent assay (ELISA) (51 patients vs. 86 controls) and postmortem brain MIF levels with a western blotting assay (18 patients vs. 22 controls). Subsequently, we genotyped the MIF-794CATT5-8 microsatellite with a fluorescence-based fragment assay and the MIF-173G/C SNP with a TaqMan SNP genotyping assay (1483 patients vs. 1454 controls). RESULTS: Serum MIF levels were significantly higher in patients with schizophrenia than in controls (p=0.00118), and were positively correlated with antipsychotic dose (Spearman's r=0.222, p=0.0402). In addition, an earlier age of onset was observed in patients with a high serum MIF level (≥40ng/mL) than those with a low serum MIF level (<40ng/mL) (p=0.0392). However, postmortem brain MIF levels did not differ between patients with schizophrenia and controls. The association study revealed that the CATT6-G haplotype was nominally significantly associated with schizophrenia (p=0.0338), and that the CATT6 allele and CATT6-G haplotype were significantly associated with female adolescent-onset schizophrenia (AsOS) (corrected p=0.0222 and p=0.0147, respectively). CONCLUSIONS: These results suggest that serum MIF level is a potential pharmacodynamic and/or monitoring marker of schizophrenia, and is related to a novel antipsychotic effect beyond dopamine antagonism. Furthermore, the MIF gene polymorphisms are associated with the risk for schizophrenia especially in adolescent females, and are potential stratification markers of schizophrenia. Further studies of MIF are warranted to elucidate the pathophysiology of schizophrenia and the effects of antipsychotics.
    Apr. 2018, Progress in neuro-psychopharmacology & biological psychiatry, 83, 33 - 41, English, International magazine
    [Refereed]
    Scientific journal

  • S Boku, T Izumi, S Abe, T Takahashi, A Nishi, H Nomaru, Y Naka, G Kang, M Nagashima, A Hishimoto, S Enomoto, G Duran-Torres, K Tanigaki, J Zhang, K Ye, S Kato, P T Männistö, K Kobayashi, N Hiroi
    Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.
    Apr. 2018, Molecular psychiatry, 23(4) (4), 985 - 992, English, International magazine
    [Refereed]
    Scientific journal

  • Resilience and suicide
    Ikuo Otsuka, Akitoyo Hishimoto
    Nova Science Publishers, Inc., Feb. 2018, Facilitating Resilience after PTSD: A Translational Approach, 177 - 198, English
    In book

  • Atsushi Kimura, Akitoyo Hishimoto, Ikuo Otsuka, Satoshi Okazaki, Shuken Boku, Tadasu Horai, Takeshi Izumi, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora
    Men have a higher rate of completed suicide than women, which suggests that sex chromosome abnormalities may be related to the pathophysiology of suicide. Recent studies have found an aberrant loss of chromosome Y (LOY) in various diseases; however, no study has investigated whether there is an association between LOY and suicide. The purpose of this study was to determine whether LOY occurs in men who completed suicide. Our study consisted of 286 male Japanese subjects comprised of 140 suicide completers without severe physical illness (130 post-mortem samples of peripheral blood and 10 brains) and 146 age-matched control subjects (130 peripheral blood samples from healthy individuals and 16 post-mortem brains). LOY was measured as the chromosome Y/chromosome X ratio of the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX). Regression analyses showed that LOY in the blood of suicide completers was significantly more frequent than that found in controls (odds ratio = 3.50, 95% confidence interval = 1.21-10.10), but not in the dorsolateral prefrontal cortex (DLPFC) region of brain. Normal age-dependent LOY in blood was found in healthy controls (r = -0.353, p < 0.001), which was not seen in suicide completers (r = -0.119, p = 0.177). DLPFC tissue had age-dependent LOY (B = -0.002, p = 0.015), which was independent of phenotype. To our knowledge, this is the first study demonstrating that LOY in blood is associated with suicide completion. In addition, our findings are the first to also indicate that age-dependent LOY may occur not only in blood, but also in specific brain regions.
    2018, PloS one, 13(1) (1), e0190667, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tadasu Horai, Akitoyo Hishimoto, Ikuo Otsuka, Tatsuhiro So, Kentaro Mouri, Naofumi Shimmyo, Shuken Boku, Noriaki Okishio, Ichiro Sora
    Background: Alcohol dependence induces low bone mineral density (BMD), predicting osteoporosis, while low and moderate alcohol consumption may even increase BMD. In recent years, undercarboxylated osteocalcin (ucOC) and tartrate-resistant acid phosphatase-5b (TRACP-5b), bone turnover markers, have gained special interest as useful indicators of low BMD. However, it remains unclear whether other alcohol-related variables (eg, duration of abstinence and continuous drinking) are linked to aberrant BMD. In addition, no previous study has investigated whether ucOC or TRACP-5b is clinically useful to predict low BMD not only in the general population, but also in alcohol-dependent subjects. Patients and methods: We recruited 275 male alcohol-dependent subjects and collected information about their drinking habits, comorbid diseases, smoking history and walking exercise behavior. BMD in each subject was determined by ultrasonography. Serum liver enzymes (AST, ALT, ALP, ChE, γ-GTP and LDH), ucOC and TRACP-5b were measured in all subjects. T-scores were calculated according to BMD for all subjects. Results: The mean T-scores of our subjects were negatively shifted compared to the general population (-0.75±1.36 SD). We divided our subjects into a normal BMD group (n=137) and a low BMD group (n=138) according to their T-scores (T-score ≥-1 SD, normal BMD; T-score <-1 SD, low BMD). Multivariate logistic regression analysis showed that body mass index (BMI) was negatively associated with low BMD (95% CI: 0.75-0.90). By contrast, long abstinence period (95% CI: 1.40-4.21), smoking (95% CI: 1.30-5.56), hypertension (95% CI: 1.04-3.76), lactate dehydrogenase (LDH) (95% CI: 1.00-1.01) and ucOC (95% CI: 1.04-1.22) were positively associated with low BMD. Conclusion: In alcohol-dependent males, smoking habits and higher ucOC are associated with low BMD. Our study suggests that smoking cessation may prevent lower BMD, and ucOC may predict lower BMD in alcohol-dependent individuals.
    2018, Neuropsychiatric disease and treatment, 14, 663 - 669, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Shuken Boku, Shin Nakagawa, Hiroyuki Toda, Akitoyo Hishimoto
    The monoamine hypothesis has been accepted as the most common hypothesis of major depressive disorder (MDD) for a long period because of its simplicity and understandability. Actually, most currently used antidepressants have been considered to act based on the monoamine hypothesis. However, an important problem of the monoamine hypothesis has been pointed out as follows: it fails to explain the latency of response to antidepressants. In addition, many patients with MDD have remained refractory to currently used antidepressants. Therefore, monoamine-alternate hypotheses are required to explain the latency of response to antidepressants. Such hypotheses have been expected to contribute to identifying hopeful new therapeutic targets for MDD. Past studies have revealed that the volume of the hippocampus is decreased in patients with MDD, which is likely caused by the failure of the hypothalamic-pituitary-adrenal axis and following elevation of glucocorticoids. Two hypotheses have been proposed to explain the volume of the hippocampus: (i) the neuroplasticity hypothesis; and (ii) the neurogenesis hypothesis. The neuroplasticity hypothesis explains how the hippocampal volume is decreased by the morphological changes of hippocampal neurons, such as the shortening length of dendrites and the decreased number and density of spines. The neurogenesis hypothesis explains how the hippocampal volume is decreased by the decrease of neurogenesis in the hippocampal dentate gyrus. These hypotheses are able to explain the latency of response to antidepressants. In this review, we first overview how the neuroplasticity and neurogenesis hypotheses have been developed. We then describe the details of these hypotheses.
    Jan. 2018, Psychiatry and clinical neurosciences, 72(1) (1), 3 - 12, English, International magazine
    [Refereed]
    Scientific journal

  • Takashi Hirata, Akitoyo Hishimoto, Ikuo Otsuka, Satoshi Okazaki, Shuken Boku, Atsushi Kimura, Tadasu Horai, Ichiro Sora
    Background: Life expectancy is 10-20 years lower in patients with schizophrenia than in the general population. In addition, men with schizophrenia have an earlier age at onset, more pronounced deficit symptoms, poorer course, and poorer response to antipsychotic medications than women. Recent studies have indicated that loss of chromosome Y (LOY) in peripheral blood is associated with an increased risk of all-cause mortality. In order to elucidate the pathophysiology of male-specific features, we investigated the association between LOY and schizophrenia. Materials and methods: The present study included 360 Japanese men (146 patients with schizophrenia vs 214 controls). The relative amount of Y chromosome was defined as the ratio of chromosome Y to chromosome X (Y/X ratio) based on the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX). Results: There was no significant difference in the frequency of LOY between the schizophrenia and control groups. However, longer duration of illness was associated with LOY after controlling for age and smoking status in the schizophrenia group (P=0.007, OR =1.11 [95% CI =1.03-1.19]). Conclusion: According to our results, schizophrenia may not have a remarkable effect on blood LOY; however, LOY may be associated with disease course in patients with schizophrenia.
    2018, Neuropsychiatric disease and treatment, 14, 2115 - 2122, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Takahiro Ito, Kazuhiro Yamamoto, Fuminori Ohsawa, Ikuo Otsuka, Akitoyo Hishimoto, Ichiro Sora, Midori Hirai, Ikuko Yano
    Background: Risperidone is mainly metabolized by cytochrome P450 (CYP) 2D6 in the liver. The gene encoding CYP2D6 is highly polymorphic. The average steady-state plasma concentration of risperidone active moiety is higher in the CYP2D6 intermediate metabolizers (IMs) compared with that in the extensive metabolizers (EMs). An association between drug-induced extrapyramidal symptoms scale (DIEPSS) score and CYP2D6 polymorphisms has not been reported to date. This study investigates the association of CYP2D6 polymorphisms with the severity of extrapyramidal symptoms in schizophrenia patients receiving risperidone therapy. Methods: Schizophrenia patients undergoing risperidone treatment were recruited for the study in the Kobe University Hospital. We evaluated extrapyramidal symptoms of schizophrenia using the DIEPSS. CYP2D6*10 and CYP2D6*14 were analyzed using TaqMan® assays, and CYP2D6*5 was analyzed using the long-PCR method. Patients with CYP2D6*1/*5, *1/*14, *5/*10, *10/*10, and *10/*14 were classified as IMs, and patients with CYP2D6*1/*1 and *1/*10 were classified as EMs. Patients with CYP2D6*5/*5, *5/*14, and *14/*14 were classified as poor metabolizers (PMs). Results: A total of 22 patients were included in the study. No patients were classified as PMs. The dose of risperidone (mg/day) was not significantly different between EMs (n = 15) and IMs (n = 7) (median with the interquartile range: 4.0 (2.0-6.0) vs. 4.0 (2.0-7.0) mg, p = 0.31). The age and disease duration of schizophrenia were not significantly different between the EMs and IMs. The DIEPSS score in the IMs was significantly higher than that in the EMs (median with the interquartile range: 5.0 (3.5-6.5) vs. 0.0 (0.0-3.0), p < 0.001). The multiple regression analysis showed that CYP2D6 IMs is a significant risk factor for the DIEPSS (p < 0.05). Conclusion: Special attentions should be paid to the onset of extrapyramidal symptoms in schizophrenia patients identified as CYP2D6 IM undergoing risperidone therapy.
    2018, Journal of pharmaceutical health care and sciences, 4, 28 - 28, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Satoshi Hoya, Yuichiro Watanabe, Akitoyo Hishimoto, Ayako Nunokawa, Naoshi Kaneko, Tatsuyuki Muratake, Naofumi Shinmyo, Ikuo Otsuka, Shujiro Okuda, Emiko Inoue, Hirofumi Igeta, Masako Shibuya, Jun Egawa, Naoki Orime, Ichiro Sora, Toshiyuki Someya
    Nov. 2017, Psychiatry and clinical neurosciences, 71(11) (11), 780 - 788, English, International magazine
    [Refereed]
    Scientific journal

  • Satoshi Hoya, Yuichiro Watanabe, Akitoyo Hishimoto, Ayako Nunokawa, Emiko Inoue, Hirofumi Igeta, Ikuo Otsuka, Masako Shibuya, Jun Egawa, Ichiro Sora, Toshiyuki Someya
    Aug. 2017, Psychiatry and clinical neurosciences, 71(8) (8), 562 - 568, English, International magazine
    [Refereed]
    Scientific journal

  • Ikuo Otsuka, Takeshi Izumi, Shuken Boku, Atsushi Kimura, Yuan Zhang, Kentaro Mouri, Satoshi Okazaki, Kyoichi Shiroiwa, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora, Akitoyo Hishimoto
    Jun. 2017, Scientific reports, 7(1) (1), 3176 - 3176, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Naruhisa Yamaki, Akitoyo Hishimoto, Ikuo Otsuka, Toru Sasada, Shuken Boku, Takeo Saito, Yuka Yasuda, Hidenaga Yamamori, Masashi Ikeda, Manabu Ikeda, Ichiro Sora, Nakao Iwata, Ryota Hashimoto
    Apr. 2017, Psychiatry and clinical neurosciences, 71(4) (4), 289 - 290, English, International magazine
    [Refereed]

  • Naofumi Shimmyo, Akitoyo Hishimoto, Ikuo Otsuka, Satoshi Okazaki, Shuken Boku, Kentaro Mouri, Tadasu Horai, Motonori Takahashi, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora
    2017, Neuropsychiatric disease and treatment, 13, 899 - 908, English, International magazine
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Satoshi Okazaki, Shuken Boku, Ikuo Otsuka, Kentaro Mouri, Shinsuke Aoyama, Kyoichi Shiroiwa, Ichiro Sora, Aiko Fujita, Yutaka Shirai, Osamu Shirakawa, Masahiro Kokai, Akitoyo Hishimoto
    BACKGROUND: Recent studies suggest that genomic abnormalities such as single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) may elevate the risk of schizophrenia. Such genomic abnormalities often occur during chromosomal DNA replication in the S phase of cell cycle. In addition, several studies showed that abnormal expressions of several cell cycle-related genes are associated with schizophrenia. Therefore, here we compared mRNA expression levels of cell cycle-related genes in peripheral blood cells between patients with schizophrenia and healthy controls. METHOD: mRNA expression levels of cell cycle-related genes in peripheral blood cells from patients with schizophrenia and healthy controls were measured with quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The discovery, replication and intervention studies with Q-RT-PCR were performed as follows: discovery (40 cases and 20 controls), replication (82 cases and 74 controls) and intervention (22 cases and 18 controls). RESULT: Nine genes were identified in the discovery and replication stages as schizophrenia-associated genes. Moreover, the combination of mRNA expression levels of CDK4, MCM7 and POLD4 was identified as a potential biomarker for schizophrenia with multivariate logistic regression analysis. The intervention stage revealed that the mRNA expression levels of these three genes were significantly decreased in the acute state of schizophrenia, and CDK4 was significantly recovered in the remission state of schizophrenia. CONCLUSION: The combination of mRNA expression levels of three cell cycle-related genes such as CDK4, MCM7 and POLD4 is expected to be a candidate for useful biomarkers for schizophrenia. Especially, the mRNA expression changes of CDK4 may be potential as both trait and state markers for schizophrenia.
    Oct. 2016, Progress in neuro-psychopharmacology & biological psychiatry, 70, 85 - 91, English, International magazine
    [Refereed]
    Scientific journal

  • 統合失調症薬物療法ガイドライン 維持期治療
    岸本 泰士郎, 伊藤 侯輝, 金沢 徹文, 竹内 啓善, 菱本 明豊
    (公社)日本精神神経学会, Jun. 2016, 精神神経学雑誌, (2016特別号) (2016特別号), S234 - S234, Japanese

  • [Biological review of completed suicide].
    Ikuo Otsuka, Ichiro Sora, Akitoyo Hishimoto
    Japanese Society of Neuropsychopharmacology, Jun. 2016, Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, 36(3) (3), 55 - 61, Japanese, Domestic magazine
    [Refereed]
    Scientific journal

  • Noriomi Eguchi, Akitoyo Hishimoto, Ichiro Sora, Masahiro Mori
    Mar. 2016, Neuroscience letters, 616, 170 - 6, English, International magazine
    [Refereed]
    Scientific journal

  • Akitoyo Hishimoto, Hiroko Nomaru, Kenny Ye, Akira Nishi, Jihyeon Lim, Jennifer T Aguilan, Edward Nieves, Gina Kang, Ruth Hogue Angeletti, Noboru Hiroi
    Mar. 2016, Biological psychiatry, 79(5) (5), 415 - 420, English, International magazine
    [Refereed]
    Scientific journal

  • Yuichiro Watanabe, Ayako Nunokawa, Masako Shibuya, Masashi Ikeda, Akitoyo Hishimoto, Kenji Kondo, Jun Egawa, Naoshi Kaneko, Tatsuyuki Muratake, Takeo Saito, Satoshi Okazaki, Ayu Shimasaki, Hirofumi Igeta, Emiko Inoue, Satoshi Hoya, Takuro Sugai, Ichiro Sora, Nakao Iwata, Toshiyuki Someya
    Jan. 2016, Psychiatry research, 235, 13 - 8, English, International magazine
    [Refereed]
    Scientific journal

  • Masaya Saito, Yoshihiko Yano, Hirotaka Hirano, Kenji Momose, Kentaro Mouri, Akitoyo Hishimoto, Masaru Yoshida, Takeshi Azuma
    2016, Cancer biomarkers : section A of Disease markers, 16(1) (1), 171 - 80, English, International magazine
    [Refereed]
    Scientific journal

  • Woraphat Ratta-Apha, Kentaro Mouri, Shuken Boku, Hiroki Ishiguro, Satoshi Okazaki, Ikuo Otsuka, Ichiro Sora, Tadao Arinami, Osamu Shirakawa, Akitoyo Hishimoto
    Dec. 2015, Psychiatry research, 230(2) (2), 424 - 9, English, International magazine
    [Refereed]
    Scientific journal

  • Ryuhei So, Tomoya Hirota, Yuki Yamamoto, Akitoyo Hishimoto, Christoph U. Correll
    Nov. 2015, GENERAL HOSPITAL PSYCHIATRY, 37(6) (6), 621, English
    [Refereed]
    Scientific journal

  • 統合失調症におけるCadherin13遺伝子多型解析(Association analysis of the Cadherin 13 gene with schizophrenia in the Japanese population)(英語)
    大塚郁夫, 渡部雄一郎, Hishimoto Akitoyo, 朴秀賢, 毛利健太朗, 白岩恭一, 岡崎賢志, 布川綾子, 白川治, 染矢俊幸, Ichiro Sora
    Sep. 2015, 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37回・45回, 201, Japanese
    Symposium

  • Woraphat Ratta-Apha, Shuken Boku, Kentaro Mouri, Satoshi Okazaki, Ikuo Otsuka, Ichiro Sora, Akitoyo Hishimoto, Yuichiro Watanabe, Ayako Nunokawa, Toshiyuki Someya, Osamu Shirakawa
    Sep. 2015, PSYCHIATRY RESEARCH, 229(1-2) (1-2), 627 - 628, English
    [Refereed]
    Scientific journal

  • 危険ドラッグの臨床症状への影響および遺伝子多型との関連の検討
    岡崎賢志, Hishimoto Akitoyo, 朴秀賢, 毛利健太朗, 竹村幸洋, 麻生克郎, 山本訓也, Ichiro Sora
    (一社)日本アルコール・アディクション医学会, Aug. 2015, 日本アルコール・薬物医学会雑誌, 50(4) (4), 230 - 230, Japanese
    Research society

  • アルコール・薬物依存症の神経生物学・遺伝学的研究の動向 若手精神科医を中心に 細胞接着因子と精神疾患
    Hishimoto Akitoyo, 大塚郁夫, 岡崎賢志, 朴秀賢
    (一社)日本アルコール・アディクション医学会, Aug. 2015, 日本アルコール・薬物医学会雑誌, 50(4) (4), 186 - 186, Japanese
    [Refereed]
    Scientific journal

  • Miwako Sakai, Yuichiro Watanabe, Toshiyuki Someya, Kazuaki Araki, Masako Shibuya, Kazuhiro Niizato, Kenichi Oshima, Yasuto Kunii, Hirooki Yabe, Junya Matsumoto, Akira Wada, Mizuki Hino, Takeshi Hashimoto, Akitoyo Hishimoto, Noboru Kitamura, Shuji Iritani, Osamu Shirakawa, Kiyoshi Maeda, Akinori Miyashita, Shin-ichi Niwa, Hitoshi Takahashi, Akiyoshi Kakita, Ryozo Kuwano, Hiroyuki Nawa
    Jul. 2015, MOLECULAR CYTOGENETICS, 8, 46, English
    [Refereed]
    Scientific journal

  • 血清マイクロRNAの定性的解析による統合失調症の診断・病態マーカーの探索
    Hishimoto Akitoyo, 毛利健太朗, 朴秀賢, 岡崎賢志, 白岩恭一, Ichiro Sora
    (公財)先進医薬研究振興財団, Mar. 2015, 先進医薬研究振興財団研究成果報告集, 2014年度(2014年度) (2014年度), 24 - 25, Japanese
    Research society

  • 反復性うつ病の入院治療中に多飲水行動を呈した1例
    小林 明美, 石丸 綾子, 笹田 徹, 白岩 恭一, 毛利 健太朗, 山本 泰司, 菱本 明豊, 田中 究, Ichiro Sora
    Feb. 2015, 精神神経学雑誌, 117(2号) (2号), 161, Japanese
    Research society

  • Shusuke Numata, Kazuo Ishii, Atsushi Tajima, Jun-ichi Iga, Makoto Kinoshita, Shinya Watanabe, Hidehiro Umehara, Manabu Fuchikami, Satoshi Okada, Shuken Boku, Akitoyo Hishimoto, Shinji Shimodera, Issei Imoto, Shigeru Morinobu, Tetsuro Ohmori
    Feb. 2015, EPIGENETICS, 10(2) (2), 135 - 141, English
    [Refereed]
    Scientific journal

  • Ikuo Otsuka, Yuichiro Watanabe, Akitoyo Hishimoto, Shuken Boku, Kentaro Mouri, Kyoichi Shiroiwa, Satoshi Okazaki, Ayako Nunokawa, Osamu Shirakawa, Toshiyuki Someya, Ichiro Sora
    2015, NEUROPSYCHIATRIC DISEASE AND TREATMENT, 11, 1381 - 1393, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • 神戸大学医学部附属病院におけるblonanserinの投与状況について
    白岩 恭一, 毛利 健太朗, 笹田 徹, 大塚 郁夫, 大本 暢子, Hishimoto Akitoyo, Ichiro Sora
    Nov. 2014, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集24回・44回, 174, Japanese
    [Refereed]
    Symposium

  • 慢性疼痛に対しduloxetineが奏効した4症例の検討
    大塚 郁夫, 白岩 恭一, 毛利 健太朗, 笹田 徹, Hishimoto Akitoyo, Ichiro Sora
    Aug. 2014, 臨床精神薬理, 17(8号) (8号), 1151 - 1156, Japanese
    [Refereed]
    Scientific journal

  • Hiroki Ishiguro, Frank S. Hall, Yasue Horiuchi, Takeshi Sakurai, Akitoyo Hishimoto, Martin Grumet, George R. Uhl, Emmanuel S. Onaivi, Tadao Arinami
    May 2014, ADDICTION BIOLOGY, 19(3) (3), 343 - 353, English
    [Refereed]
    Scientific journal

  • Satoshi Okazaki, Yuichiro Watanabe, Akitoyo Hishimoto, Toru Sasada, Kentaro Mouri, Kyoichi Shiroiwa, Noriomi Eguchi, Woraphat Ratta-Apha, Ikuo Otsuka, Ayako Nunokawa, Naoshi Kaneko, Masako Shibuya, Toshiyuki Someya, Osamu Shirakawa, Ichiro Sora
    Apr. 2014, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 50, 151 - 156, English
    [Refereed]
    Scientific journal

  • Yuichiro Watanabe, Masako Shibuya, Ayako Nunokawa, Naoshi Kaneko, Hirofumi Igeta, Jun Egawa, Toshiyuki Someya, Akitoyo Hishimoto, Kentaro Mouri, Ichiro Sora
    Mar. 2014, PSYCHIATRY RESEARCH, 215(3) (3), 801 - 802, English
    [Refereed]
    Scientific journal

  • SSRI/SNRI投与後に賦活症状によるものと考えられる自殺念慮・自殺行動が出現した5症例の検討
    Sasada Toru, 田中 究, Hishimoto Akitoyo
    Feb. 2014, 臨床精神薬理, 17(2号) (2号), 245 - 252, Japanese
    [Refereed]
    Scientific journal

  • Woraphat Ratta-apha, Akitoyo Hishimoto, Kentaro Mouri, Kyoichi Shiroiwa, Toru Sasada, Masakuni Yoshida, Satoshi Okazaki, Irwan Supriyanto, Migiwa Asano, Yasuhiro Ueno, Osamu Shirakawa, Ichiro Sora
    Jan. 2014, PSYCHIATRY RESEARCH, 215(1) (1), 249 - 251, English
    [Refereed]
    Scientific journal

  • Woraphat Ratta-apha, Akitoyo Hishimoto, Kentaro Mouri, Kyoichi Shiroiwa, Toru Sasada, Masakuni Yoshida, Irwan Supriyanto, Yasuhiro Ueno, Migiwa Asano, Osamu Shirakawa, Hideru Togashi, Yoshimi Takai, Ichiro Sora
    Dec. 2013, NEUROSCIENCE RESEARCH, 77(4) (4), 222 - 227, English
    [Refereed]
    Scientific journal

  • N Hiroi, T Takahashi, A Hishimoto, T Izumi, S Boku, T Hiramoto
    Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders.
    Nov. 2013, Molecular psychiatry, 18(11) (11), 1153 - 65, English, International magazine
    [Refereed]
    Scientific journal

  • 慢性疼痛へのセロトニン・ノルアドレナリン再取り込み阻害薬デュロキセチンの有効性
    大塚 郁夫, 白岩 恭一, 菱本 明豊, 毛利 健太朗, 笹田 徹, 曽良 一郎
    日本臨床精神神経薬理学会・日本神経精神薬理学会, Oct. 2013, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 170 - 170, Japanese

  • 精神病症状を伴う産後うつ病に高用量のquetiapineが奏効した1例
    山木 愛久, Mouri Kentaro, Shiroiwa Kyoichi, 田中 究, Hishimoto Akitoyo
    Oct. 2013, 臨床精神薬理, 16(10号) (10号), 1505 - 1509, Japanese
    [Refereed]
    Scientific journal

  • Woraphat Ratta-apha, Akitoyo Hishimoto, Masakuni Yoshida, Yasuhiro Ueno, Migiwa Asano, Osamu Shirakawa, Ichiro Sora
    Oct. 2013, PSYCHIATRY RESEARCH, 209(3) (3), 734 - 736, English
    [Refereed]
    Scientific journal

  • Brain Science 統合失調症の病態生理と皮質ニューロン・ネットワークの異常
    福武将映, Hishimoto Akitoyo
    科学評論社, Aug. 2013, 精神科, 23(2号) (2号), 211 - 217, Japanese
    [Refereed][Invited]
    Scientific journal

  • Shiroiwa Kyoichi, 田中 究, 大本 暢子, 平井 みどり, Hishimoto Akitoyo
    May 2013, 精神医学, 55(5号) (5号), 457 - 463, Japanese
    [Refereed]
    Scientific journal

  • 肝細胞癌の新規腫瘍マーカーNX-PVKA-Rはアルコールの影響を受けにくい
    斉藤 雅也, 瀬尾 靖, 矢野 嘉彦, Hishimoto Akitoyo, 百瀬 健次, 平野 仁崇, 東 健
    Apr. 2013, 肝臓, 54(Suppl.1) (Suppl.1), A243, Japanese
    Research society

  • 全般性不安障害を合併した大うつ病性障害にescitalopramの付加療法が著効した1例
    Hishimoto Akitoyo, Tanaka Kiwamu
    Feb. 2013, 臨床精神薬理, 16(2号) (2号), 237 - 243, Japanese
    [Refereed]
    Scientific journal

  • 双極I型障害の治療経過中にlamotrigine投与後、白血球減少および重度貧血をきたした1例
    Matsui Yusuke, Sasada Toru, Hishimoto Akitoyo, Tanaka Kiwamu
    Jan. 2013, 精神神経学雑誌, 115(1号) (1号), 107, Japanese
    Research society

  • Irwan Supriyanto, Yuichiro Watanabe, Kentaro Mouri, Kyoichi Shiroiwa, Woraphat Ratta-Apha, Masakuni Yoshida, Genki Tamiya, Toru Sasada, Noriomi Eguchi, Kenji Okazaki, Osamu Shirakawa, Toshiyuki Someya, Akitoyo Hishimoto
    Jan. 2013, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 40, 347 - 352, English
    [Refereed]
    Scientific journal

  • せん妄、抑うつ状態を呈し診断、治療に難渋した1例
    Shiroiwa Kyoichi, Hishimoto Akitoyo, Tanaka Kiwamu
    Sep. 2012, 精神神経学雑誌, 114(9号) (9号), 1103, Japanese
    Research society

  • Masakuni Yoshida, Kyoichi Shiroiwa, Kentaro Mouri, Hiroki Ishiguro, Irwan Supriyanto, Woraphat Ratta-Apha, Noriomi Eguchi, Satoshi Okazaki, Toru Sasada, Masaaki Fukutake, Takeshi Hashimoto, Toshiya Inada, Tadao Arinami, Osamu Shirakawa, Akitoyo Hishimoto
    Sep. 2012, SCHIZOPHRENIA RESEARCH, 140(1-3) (1-3), 185 - 191, English
    [Refereed]
    Scientific journal

  • NrCAM-regulating neural systems and addiction-related behaviors
    Hishimoto Akitoyo
    Jul. 2012, Addict Biol, 10(1111) (1111), 1369 - 1600, English
    [Refereed]
    Scientific journal

  • 気分障害の併存を認めた発作性運動誘発性舞踏アテトーゼの2例
    Sasada Toru, Hishimoto Akitoyo, Tanaka Kiwamu
    May 2012, 精神神経学雑誌, (2012特別) (2012特別), S - 433, Japanese
    Research society

  • SSRI/SNRI投与直後に自殺行動/念慮が惹起された5症例の検討
    Hishimoto Akitoyo
    Oct. 2011, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集21回・41回, 巻, , pp. 158-158, Japanese
    International conference proceedings

  • 抗リン脂質抗体症候群により幻覚妄想をきたした一例
    Hishimoto Akitoyo
    Aug. 2011, 精神神経学雑誌, 113巻, 8号, pp. 801-801, Japanese
    International conference proceedings

  • 再生不良性貧血による器質性精神障害を呈した一例
    Hishimoto Akitoyo
    (公社)日本精神神経学会, Jul. 2011, 精神神経学雑誌, 113(7) (7), 727 - 727, Japanese
    International conference proceedings

  • Huxing Cui, Irwan Supriyanto, Tohru Sasada, Kyoichi Shiroiwa, Masaaki Fukutake, Osamu Shirakawa, Migiwa Asano, Yasuhiro Ueno, Yasushi Nagasaki, Akitoyo Hishimoto
    Jun. 2011, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 35(4) (4), 1108 - 1111, English
    [Refereed]
    Scientific journal

  • Irwan Supriyanto, Toru Sasada, Masaaki Fukutake, Migiwa Asano, Yasuhiro Ueno, Yasushi Nagasaki, Osamu Shirakawa, Akitoyo Hishimoto
    Jan. 2011, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 35(1) (1), 252 - 256, English
    [Refereed]

  • A. Hishimoto, T. Sasada, M. Fukutake, K. Shiroiwa, I. Supriyanto, O. Shirakawa
    2011, EUROPEAN PSYCHIATRY, 26, English
    [Refereed]
    Scientific journal

  • これからのアルコール医療 細胞接着因子と精神疾患 最近の研究動向、アルコール・薬物依存研究について
    Hishimoto Akitoyo
    Aug. 2010, 日本アルコール・薬物医学会雑誌, 45巻, 4号, pp. 86-86, Japanese
    International conference proceedings

  • Huxing Cui, Naoki Nishiguchi, Masaya Yanagi, Masaaki Fukutake, Kentaro Mouri, Noboru Kitamura, Takeshi Hashimoto, Osamu Shirakawa, Akitoyo Hishimoto
    Aug. 2010, SCHIZOPHRENIA RESEARCH, 121(1-3) (1-3), 172 - 178, English
    [Refereed]
    Scientific journal

  • Huxing Cui, Irwan Supriyanto, Migiwa Asano, Yasuhiro Ueno, Yasushi Nagasaki, Naoki Nishiguchi, Osamu Shirakawa, Akitoyo Hishimoto
    Aug. 2010, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 34(6) (6), 992 - 996, English
    [Refereed]
    Scientific journal

  • A. Hishimoto, M. Fukutake, K. Mouri, Y. Nagasaki, M. Asano, Y. Ueno, N. Nishiguchi, O. Shirakawa
    Jul. 2010, GENES BRAIN AND BEHAVIOR, 9(5) (5), 498 - 502, English
    [Refereed]
    Scientific journal

  • 殺人未遂により鑑定入院となった妄想型統合失調症の一例
    Sasada Toru, Hishimoto Akitoyo, Tanaka Kiwamu
    Jul. 2010, 精神神経学雑誌, 112巻, 7号, pp. 685-685, Japanese
    International conference proceedings

  • リスペリドンにより持続勃起症をきたしアリピプラゾールに薬剤変更を行った統合失調症の二例
    Sasada Toru, Hishimoto Akitoyo, Yamamoto Yasuji
    (公社)日本精神神経学会, May 2010, 精神神経学雑誌, 巻, 2010特別, pp. S-330(2010特別) (2010特別), S - 330, Japanese
    International conference proceedings

  • Kyoichi Shiroiwa, Akitoyo Hishimoto, Kentaro Mouri, Masaaki Fukutake, Irwan Supriyanto, Naoki Nishiguchi, Osamu Shirakawa
    Mar. 2010, NEUROSCIENCE LETTERS, 472(3) (3), 194 - 198, English
    [Refereed]
    Scientific journal

  • Alexithymia and its relationships with eating behavior, self esteem, and body esteem in college women
    Keiko Sasai, Kiwamu Tanaka, Akitoyo Hishimoto
    2010, Kobe Journal of Medical Sciences, 56(6) (6), E231 - E238, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kentaro Mouri, Akitoyo Hishimoto, Masaaki Fukutake, Kyoichi Shiroiwa, Migiwa Asano, Yasushi Nagasaki, Yasuhiro Ueno, Osamu Shirakawa, Naoki Nishiguchi, Kiyoshi Maeda
    Nov. 2009, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 33(8) (8), 1546 - 1550, English
    [Refereed]

  • 頻回の自殺企図を伴ううつ病から遅発緊張病様の病態を呈した一例
    Hishimoto Akitoyo
    Nov. 2009, 精神神経学雑誌, 111巻, 11号, pp. 1436-1436, Japanese
    International conference proceedings

  • 精神科外来における統合失調症患者に対するblonanserinの使用経験
    Hishimoto Akitoyo, Fukutake Masaaki, Yamamoto Yasuji, Maeda Kiyoshi
    Sep. 2009, 臨床精神薬理, 12巻, 9号, pp. 1999-2009, Japanese
    [Refereed]
    Scientific journal

  • 意識障害が遷延したと考えられる統合失調症の1例
    Hishimoto Akitoyo, Taira Masaru
    Aug. 2009, 精神神経学雑誌, 111巻, 8号, pp. 992-992, Japanese
    International conference proceedings

  • Q. -R. Liu, C. -H. Pan, A. Hishimoto, C. -Y. Li, Z. -X. Xi, A. Llorente-Berzal, M. -P. Viveros, H. Ishiguro, T. Arinami, E. S. Onaivi, G. R. Uhl
    Jul. 2009, GENES BRAIN AND BEHAVIOR, 8(5) (5), 519 - 530, English
    [Refereed]
    Scientific journal

  • 双極性I型障害にaripiprazoleが奏功した1症例
    Hishimoto Akitoyo, Sasada Toru
    May 2009, 精神神経学雑誌, 巻, 2009特別, pp. S-238, Japanese
    International conference proceedings

  • AripiprazoleとMilnacipranの併用療法が有効であったFTD合併が疑われる大うつ病性障害の一例
    Hishimoto Akitoyo, Sasada Toru
    May 2009, 精神神経学雑誌, 巻, 2009特別, pp. S-236, Japanese
    International conference proceedings

  • Association study of RGS2 gene polymorphisms with panic disorder in Japanese
    Kentaro Mouri, Akitoyo Hishimoto, Masaaki Fukutake, Naoki Nishiguchi, Osamu Shirakawa, Kiyoshi Maeda
    2009, Kobe Journal of Medical Sciences, 55(5) (5), E116 - E121, English
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Masaaki Fulcutake, Akitoyo Hishimoto, Naoki Nishiguchi, Hideyuki Nushida, Yasuhiro Ueno, Osamu Shirakawa, Kiyoshi Maeda
    Aug. 2008, PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 32(6) (6), 1428 - 1433, English
    [Refereed]

  • A. Hishimoto, H. Cui, K. Mouri, H. Nushida, Y. Ueno, K. Maeda, O. Shirakawa
    Mar. 2008, JOURNAL OF NEURAL TRANSMISSION, 115(3) (3), 531 - 536, English
    [Refereed]
    Scientific journal

  • Akitoyo Hishimoto, Qing-Rong Liu, Tomas Drgon, Olga Pletnikova, Donna Walther, Xu-Guang Zhu, Juan C. Troncoso, George R. Uhl
    Dec. 2007, HUMAN MOLECULAR GENETICS, 16(23) (23), 2880 - 2891, English
    [Refereed]
    Scientific journal

  • A. Hishimoto, O. Shirakawa, N. Nishiguchi, T. Hashimoto, M. Yanagi, H. Nushida, Y. Ueno, K. Maeda
    Dec. 2006, JOURNAL OF NEURAL TRANSMISSION, 113(12) (12), 1915 - 1920, English
    [Refereed]
    Scientific journal

  • 「食」から見た会食恐怖症
    Hishimoto Akitoyo
    Apr. 2005, 治療の声, 6巻, 1号, pp. 81-88, Japanese
    [Refereed]
    Scientific journal

  • A Hishimoto, O Shirakawa, N Nishiguchi, S Aoyama, H Ono, T Hashimoto, K Maeda
    Oct. 2004, PSYCHIATRY AND CLINICAL NEUROSCIENCES, 58(5) (5), 579 - 581, English
    [Refereed]
    Scientific journal

  • S Matsushita, K Suzuki, M Murayama, N Nishiguchi, A Hishimoto, A Takeda, O Shirakawa, S Higuchi
    Jul. 2004, AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 128B(1) (1), 114 - 117, English
    [Refereed]
    Scientific journal

  • Sachio Matsushita, Kenji Suzuki, Masanobu Murayama, Naoki Nishiguchi, Akitoyo Hishimoto, Aya Takeda, Osamu Shirakawa, Susumu Higuchi
    Jul. 2004, American Journal of Medical Genetics - Neuropsychiatric Genetics, 128(1) (1), 114 - 117, English
    [Refereed]
    Scientific journal

  • Association Study between Temperament-related Functional Gene Polymorphisms and Completed Suicides.
    白川治, 小野久江, 青山慎介, 菱本明豊, 岡村健二, 柳雅也, 主田英之, 上野易弘, 前田潔
    (公財)先進医薬研究振興財団, Mar. 2003, 精神薬療研究年報, (35) (35), 88 - 92, Japanese

  • Treatment of depression seen in the case. From the viewpoint of the psychiatrist. Present conditions of the medical care for depression. General specialty and psychiatry.
    菱本明豊, 白川治
    エルゼビア・ジャパン(株), Feb. 2003, 臨床と薬物治療, 22(2) (2), 78 - 82, Japanese

■ MISC
  • 自殺のエピジェネティクス
    岡崎賢志, 大塚郁夫, 谷藤貴紀, 白井寿行, 毛利健太朗, 菱本明豊
    2024, 日本臨床精神神経薬理学会プログラム・抄録集, 34th (CD-ROM)

  • アルコール依存症でのエピゲノム年齢加速
    白井寿行, 岡崎賢志, 大塚郁夫, 南陽香, 岡田将平, 宮地真生, 蓬莱政, 毛利健太朗, 菱本明豊
    2024, 日本精神科診断学会プログラム・抄録集, 43rd

  • 未治療のうつ病患者におけるエピジェネティック年齢の加速とDNAメチル化に基づくナチュラルキラー細胞の減少
    岡崎賢志, 新藤良太, 谷藤貴紀, 大塚郁夫, 白井寿行, 毛利健太朗, 蓬莱政, 菱本明豊
    2024, 日本精神科診断学会プログラム・抄録集, 43rd

  • 日本人の自殺既遂者における,マクロファージ遊走阻害因子(MIF)の低酸素応答因子における遺伝子研究
    宮地真生, 白井寿行, 岡崎賢志, 谷藤貴紀, 大塚郁夫, 岡田将平, 新藤良太, 蓬莱政, 毛利健太郎, 高橋玄倫, 近藤武史, 上野易弘, 菱本明豊
    2024, 日本生物学的精神医学会(Web), 46th

  • メタンフェタミン依存症におけるエピゲノムワイド関連研究
    白井寿行, 岡崎賢志, 谷藤貴紀, 大塚郁夫, 蓬莱政, 毛利健太朗, 麻生克郎, 山本訓也, 菱本明豊
    2024, 日本生物学的精神医学会(Web), 46th

  • DNAメチル化に代表される後天的遺伝子修飾と精神疾患の解明
    白井寿行, 岡崎賢志, 大塚郁夫, 谷藤貴紀, 宮地真生, 岡田将平, 蓬莱政, 毛利健太朗, 菱本明豊
    2024, 統合失調症研究(CD-ROM), 13(1) (1)

  • 持続性抗精神病注射薬剤(LAI)と経口抗精神病薬の併用薬の状況 日本における実態調査
    鬼塚 俊明, 岡田 剛史, 長谷川 尚美, 坪井 貴嗣, 伊賀 淳一, 古郡 規雄, 山田 直輝, 堀 輝, 村岡 寛之, 大井 一高, 小笠原 一能, 越智 紳一郎, 竹島 正浩, 市橋 香代, 福本 健太郎, 飯田 仁志, 山田 恒, 降籏 隆二, 牧之段 学, 高江洲 義和, 沼田 周助, 小松 浩, 菱本 明豊, 木戸 幹雄, 阿竹 聖和, 山形 弘隆, 菊地 紗耶, 橋本 直樹, 宇佐美 政英, 勝元 榮一, 浅見 剛, 久保田 智香, 松本 純弥, 三浦 健一郎, 平野 羊嗣, 渡邊 衡一郎, 稲田 健, 橋本 亮太
    (公社)日本精神神経学会, Jun. 2023, 精神神経学雑誌, 12(2023特別号) (2023特別号), S684 - S684, Japanese

  • 【私のクリニカルクエスチョン】統合失調症とパーキンソン病を合併した22q11.2欠失症候群に対する維持電気けいれん療法(ECT)の治療選択
    谷藤 貴紀, 菱本 明豊
    (株)アークメディア, Feb. 2023, 臨床精神医学, 52(2) (2), 171 - 174, Japanese

  • 菱本 明豊
    (株)先端医学社, Feb. 2023, Depression Strategy, 13(1) (1), 5 - 8, Japanese

  • 消化器内科での治療から減酒外来へつながり断酒会につなぐことが出来た一例
    若杉慶嗣, 宮内雅利, 須田顕, 須田顕, 戸井田真木, 戸井田真木, 野口信彦, 上松太郎, 鈴木妙実, 杉本彩, 古野拓, 古野拓, 菱本明豊
    2023, 日本アルコール関連問題学会大会プログラム・抄録集, 45th

  • 一般精神科診療所に通う患者のアルコール問題調査
    宮内雅利, 須田顕, 須田顕, 戸井田真紀, 戸井田真紀, 戸井田真紀, 野口信彦, 若杉慶嗣, 上松太郎, 鈴木妙実, 杉本彩, 古野拓, 菱本明豊
    2023, 日本アルコール関連問題学会大会プログラム・抄録集, 45th

  • Investigation of Medication for Dialysis Patients with Delirium: Impact of Liaison Team Intervention
    野口信彦, 服部早紀, 渡邊香織, 藤田英美, 須田顕, 浅見剛, 菱本明豊
    2023, 日本臨床精神神経薬理学会プログラム・抄録集, 33rd

  • A case of psychiatric symptoms caused by limbic encephalitis of neurosyphilis successfully treated with blonanserin patch
    玉井佳菜子, 服部早紀, 野口信彦, 須田顕, 浅見剛, 菱本明豊, 菱本明豊
    2023, 日本臨床精神神経薬理学会プログラム・抄録集, 33rd

  • Effects of AOM versus PP on autonomic nervous system activity in schizophrenic patients
    服部早紀, 須田顕, 岸田郁子, 宮内雅利, 野口信彦, 白石洋子, 浅見剛, 藤林真美, 辻田那月, 石井千恵, 石井紀夫, 佐伯隆史, 佐伯隆史, 福島端, 森谷敏夫, 菱本明豊, 菱本明豊
    2023, 日本臨床精神神経薬理学会プログラム・抄録集, 33rd

  • 【不安症再考】不安症の形態画像研究
    浅見 剛, 佐々木 亮, 菱本 明豊
    (有)科学評論社, Jan. 2023, 精神科, 42(2) (2), 189 - 194, Japanese

  • 菱本 明豊
    (株)メディカルレビュー社, Dec. 2022, Depression Journal, 10(3) (3), 88 - 89, Japanese

  • 新型コロナウイルス感染症に対する推奨外投薬後にステロイド精神病を発症した1例
    戸井田 真木, 日野 耕介, 長谷川 花, 杉山 直也, 菱本 明豊
    (公社)日本精神神経学会, Nov. 2022, 精神神経学雑誌, 124(11) (11), 818 - 818, Japanese

  • 熱海土石流災害の支援活動により治療再開に至った統合失調症の治療中断例
    山下 大翔, 野口 信彦, 長谷川 花, 菱本 明豊, 杉山 直也
    (公社)日本精神神経学会, Nov. 2022, 精神神経学雑誌, 124(11) (11), 820 - 820, Japanese

  • 児童青年期の自殺企図者に併存する精神病症状の6ヵ月追跡調査
    藤田 純一, 宮崎 秀仁, 浅沼 和哉, 太田 陽, 戸代原 奈央, 青山 久美, 高橋 雄一, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O20 - 2, Japanese

  • 子どものこころ専門医研修をはじめた小児科医のコンサルテーション・リエゾン症例を通した学び
    太田 陽, 深津 英希, 藤田 純一, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O21 - 2, Japanese

  • ゲーム障害に対する集団精神療法 自閉症に関する予備調査
    浅沼 和哉, 青山 久美, 藤田 純一, 古賀 大吉, 宮崎 秀仁, 青木 芳子, 宇賀神 北斗, 武越 百恵, 重井 和真, 深津 英希, 太田 陽, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O22 - 1, Japanese

  • 新型コロナウイルス感染症に対する推奨外投薬後にステロイド精神病を発症した1例
    戸井田 真木, 日野 耕介, 長谷川 花, 杉山 直也, 菱本 明豊
    (公社)日本精神神経学会, Nov. 2022, 精神神経学雑誌, 124(11) (11), 818 - 818, Japanese

  • 熱海土石流災害の支援活動により治療再開に至った統合失調症の治療中断例
    山下 大翔, 野口 信彦, 長谷川 花, 菱本 明豊, 杉山 直也
    (公社)日本精神神経学会, Nov. 2022, 精神神経学雑誌, 124(11) (11), 820 - 820, Japanese

  • 認知症予防のエビデンスと社会実装に向けた挑戦 J-MINT PRIME神奈川モデルから考える社会実装への課題
    小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 千葉 悠平, 阿部 紀絵, 井出 恵子, 吉見 明香, 菱本 明豊, 山中 太郎, 柾 晴美, 荒井 秀典
    (株)ワールドプランニング, Nov. 2022, 老年精神医学雑誌, 33(増刊II) (増刊II), 184 - 184, Japanese

  • 児童青年期の自殺企図者に併存する精神病症状の6ヵ月追跡調査
    藤田 純一, 宮崎 秀仁, 浅沼 和哉, 太田 陽, 戸代原 奈央, 青山 久美, 高橋 雄一, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O20 - 2, Japanese

  • 子どものこころ専門医研修をはじめた小児科医のコンサルテーション・リエゾン症例を通した学び
    太田 陽, 深津 英希, 藤田 純一, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O21 - 2, Japanese

  • ゲーム障害に対する集団精神療法 自閉症に関する予備調査
    浅沼 和哉, 青山 久美, 藤田 純一, 古賀 大吉, 宮崎 秀仁, 青木 芳子, 宇賀神 北斗, 武越 百恵, 重井 和真, 深津 英希, 太田 陽, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, O22 - 1, Japanese

  • コロナ禍の摂食障害患者に併存する抑うつ・不安症状に関する調査
    重井 和真, 宮崎 秀仁, 武越 百恵, 浅沼 和哉, 藤田 純一, 菱本 明豊
    (一社)日本児童青年精神医学会, Nov. 2022, 日本児童青年精神医学会総会抄録集, 63回, P8 - 9, Japanese

  • コロナ禍における自殺関連問題 コロナ禍における急性期総合病院での自殺未遂者対応
    宮崎 秀仁, 日野 耕介, 野本 宗孝, 古野 拓, 菱本 明豊
    (一社)日本総合病院精神医学会, Oct. 2022, 総合病院精神医学, 34(Suppl.) (Suppl.), S - 77, Japanese

  • 認知症予防のエビデンスと社会実装に向けた挑戦 J-MINT PRIME神奈川モデルから考える社会実装への課題
    小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 千葉 悠平, 阿部 紀絵, 井出 恵子, 吉見 明香, 菱本 明豊, 山中 太郎, 柾 晴美, 荒井 秀典
    (一社)日本認知症学会, Oct. 2022, Dementia Japan, 36(4) (4), 713 - 713, Japanese

  • 知的障害を合併したてんかん患者における、抗精神病薬併用例の臨床的特徴の検討
    白石 洋子, 川瀬 真琴, 西田 拡人, 新井 めぐみ, 許 博陽, 高石 政男, 堀 岳人, 佐倉 義久, 山口 隆之, 古荘 竜, 梶原 智, 菱本 明豊
    (一社)日本てんかん学会, Aug. 2022, てんかん研究, 40(2) (2), 482 - 482, Japanese

  • 強迫性障害とカタトニアの判別に苦慮した児童症例
    青木 芳子, 武越 百恵, 藤田 純一, 菱本 明豊
    (公社)日本精神神経学会, Jun. 2022, 精神神経学雑誌, 124(6) (6), 419 - 419, Japanese

  • 抗体介在性自己免疫性脳炎と精神医学 自己免疫性脳炎治療後の精神科における長期経過について
    千葉 悠平, 阿部 紀絵, 服部 早紀, 伊倉 崇浩, 斎藤 知之, 須田 顕, 藤城 弘樹, 勝瀬 大海, 西野 精治, 菱本 明豊
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 448, Japanese

  • 生成系深層学習を使った精神疾患脳構造画像変換の検討
    山口 博行, 清水 正彬, 杉原 玄一, 菱本 明豊, 本田 学, 山下 祐一
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 541, Japanese

  • メンタルケアにおける自律神経バイオマーカーの利用 自律神経活動指標を用いた抗精神病薬の副作用およびリワークプログラムの効果の検証
    服部 早紀, 須田 顕, 岸田 郁子, 宮内 雅利, 古野 拓, 白石 洋子, 野口 信彦, 藤林 真美, 辻田 那月, 石井 千恵, 石井 紀夫, 森谷 敏夫, 菱本 明豊
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 628, Japanese

  • 松沢病院における強迫性障害と統合失調症の併存例23名の臨床的特徴
    岡村 泰, 杉本 達哉, 頃安 英毅, 佐々木 亮, 村端 祐樹, 川瀬 愛, 梅田 夕奈, 根路銘 要太, 福田 陽明, 松本 光輔, 針間 博彦, 菱本 明豊, 水野 雅文
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 369, Japanese

  • COVID-19流行前後での救命救急センターに入院となった自殺企図者の臨床的特徴と対応
    宮崎 秀仁, 日野 耕介, 伊藤 翼, 六本木 知秀, 野本 宗孝, 古野 拓, 菱本 明豊
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 524, Japanese

  • パニック症における視床下部の容積減少
    佐々木 亮, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, Apr. 2022, 精神神経学雑誌, 124(4付録) (4付録), S - 637, Japanese

  • Effects of OA versus AOM on autonomic nervous system activity in schizophrenic patients
    服部早紀, 須田顕, 岸田郁子, 岸田郁子, 宮内雅利, 古野拓, 白石洋子, 野口信彦, 藤林真美, 辻田那月, 石井千恵, 石井紀夫, 佐伯隆史, 佐伯隆史, 福島端, 森谷敏夫, 菱本明豊
    2022, 日本生物学的精神医学会(Web), 44th

  • Vitamins and psychiatric symptoms : relevance and clinical applications : A review
    佐々木 亮, 浅見 剛, 菱本 明豊
    科学評論社, Dec. 2021, 精神科 = Psychiatry, 39(6) (6), 650 - 655, Japanese

  • Biological prospects of suicide for clinical application
    大塚 郁夫, 菱本 明豊
    医歯薬出版, Oct. 2021, 医学のあゆみ, 279(1) (1), 29 - 34, Japanese

  • 吉見 明香, 加藤 大慈, 菱本 明豊
    (株)医学書院, Oct. 2021, 精神医学, 63(10) (10), 1453 - 1461, Japanese

  • 多因子生活習慣介入による認知症予防 地域在住高齢者に対する多因子介入による認知症予防の取り組み
    小田原 俊成, 水嶋 春朔, 齋藤 京子, 鈴木 裕子, 櫻井 孝, 千葉 悠平, 阿部 紀恵, 吉見 明香, 井出 恵子, 菱本 明豊, 山中 太郎, 柾 晴美, 荒井 秀典
    (一社)日本認知症学会, Oct. 2021, Dementia Japan, 35(4) (4), 571 - 571, Japanese

  • 大学病院における精神医学教育の役割 大学病院における精神医学教育は如何に医療者の持つスティグマを軽減できるのか?
    菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S273 - S273, Japanese

  • 抗体介在性自己免疫性脳炎と精神疾患 免疫性精神病と甲状腺抗体陽性の精神科疾患患者におけるバイオマーカーとしての自己抗体について
    千葉 悠平, 阿部 紀絵, 斎藤 知之, 勝瀬 大海, 高橋 幸利, 須田 顕, 服部 早紀, 吉見 明香, 浅見 剛, 西野 精治, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S295 - S295, Japanese

  • 救命救急センターに搬送される自殺企図者に対する精神科医の役割 救命救急センターを拠点とする自殺未遂者対応 近年の傾向およびCOVID-19流行がもたらした変化
    日野 耕介, 宮崎 秀仁, 伊藤 翼, 野本 宗孝, 古野 拓, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S410 - S410, Japanese

  • 慢性自己免疫性精神病患者における抗GluN1-NT抗体と認知機能障害に関する探索的調査
    阿部 紀絵, 千葉 悠平, 勝瀬 大海, 高橋 幸利, 服部 早紀, 吉見 明香, 須田 顕, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S580 - S580, Japanese

  • 免疫性精神病患者の免疫療法後の長期的予後と脳微細構造の変化について
    千葉 悠平, 阿部 紀絵, 勝瀬 大海, 高橋 幸利, 須田 顕, 服部 早紀, 吉見 明香, 浅見 剛, 西野 精治, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S581 - S581, Japanese

  • 松沢病院の強迫症患者約85名の臨床的特徴 精神病性障害の併存や両者の鑑別に関する考察
    岡村 泰, 杉本 達哉, 頃安 英毅, 佐々木 亮, 村端 祐樹, 川瀬 愛, 梅田 夕奈, 根路銘 要太, 福田 陽明, 松本 光輔, 針間 博彦, 斎藤 正彦, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2021, 精神神経学雑誌, (2021特別号) (2021特別号), S614 - S614, Japanese

  • 亜急性に前頭葉機能低下症状が出現し、ビタミンB12欠乏の関与が疑われた1例
    佐々木 亮, 服部 早紀, 政岡 数紀, 浅見 剛, 菱本 明豊
    (公社)日本精神神経学会, Aug. 2021, 精神神経学雑誌, 123(8) (8), 528 - 528, Japanese

  • 抗精神病薬使用中のてんかん患者における薬剤選択の実態調査
    許 博陽, 山口 隆之, 新井 めぐみ, 西田 拡人, 辻村 理司, 白石 洋子, 堀 岳人, 佐倉 義久, 古荘 竜, 梶原 智, 菱本 明豊
    (一社)日本てんかん学会, Jul. 2021, てんかん研究, 39(2) (2), 422 - 422, Japanese

  • COVID-19が精神科にもたらした心理学的影響 COVID-19パンデミックが流行初期に病院職員にもたらした心理的影響
    井出 恵子, 浅見 剛, 野本 宗孝, 菱本 明豊
    日本うつ病学会・日本認知療法・認知行動療法学会, Jul. 2021, 日本うつ病学会総会・日本認知療法・認知行動療法学会プログラム・抄録集, 18回・21回, 187 - 187, Japanese

  • Neurobiological abnormalities in suicide
    大塚 郁夫, 菱本 明豊
    アークメディア, Jun. 2021, 臨床精神医学 = Japanese journal of clinical psychiatry, 50(6) (6), 577 - 583, Japanese

  • COVID-19 and psychiatric treatment viewed from university hospitals
    浅見 剛, 佐々木 亮, 吉見 明香, 六本木 知秀, 野本 宗孝, 古野 拓, 菱本 明豊
    科学評論社, Jun. 2021, 精神科 = Psychiatry, 38(6) (6), 641 - 644, Japanese

  • Bipolar disorder and suicide : Tips to prevent suicide
    日野 耕介, 菱本 明豊
    星和書店, May 2021, 精神科治療学, 36(5) (5), 513 - 518, Japanese

  • GENETIC STUDY OF SUICIDE
    菱本 明豊
    横浜市立大学医学会, Apr. 2021, 横浜医学 = YOKOHAMA MEDICAL JOURNAL, 72(2) (2), 83 - 87, Japanese

  • 自殺のゲノム研究の現況と臨床応用の可能性
    菱本 明豊, 大塚 郁夫, 須田 顕, 服部 早紀
    (公社)日本小児科学会, Feb. 2021, 日本小児科学会雑誌, 125(2) (2), 195 - 195, Japanese

  • 井出恵子, 加藤英明, 菱本明豊
    メディカル・サイエンス・インターナショナル, 2021, Intensivist, 13(3) (3), 451 - 459, Japanese

  • 著しい血小板減少をきたした神経性やせ症の1例
    山本 浩世, 吉田 晴久, 千葉 直子, 西田 拡人, 浅見 剛, 菱本 明豊
    神奈川県医師会, Jan. 2021, 神奈川医学会雑誌, 48(1) (1), 43 - 43, Japanese

  • 児童神経性やせ症における体重変化に伴う脳構造の変化
    加藤 南実, 浅見 剛, 小西 潤, 六本木 知秀, 野本 宗孝, 青山 久美, 平安 良雄, 菱本 明豊
    神奈川県医師会, Jan. 2021, 神奈川医学会雑誌, 48(1) (1), 45 - 46, Japanese

  • 精神科における生物学的研究の意義 自殺予防の視点から
    菱本 明豊
    神奈川県医師会, Jan. 2021, 神奈川医学会雑誌, 48(1) (1), 46 - 46, Japanese

  • COVID-19パンデミックが精神科にもたらしたもの 横浜市立大学附属病院の経験
    井出 恵子, 浅見 剛, 菱本 明豊
    (株)先端医学社, Jan. 2021, 精神科Resident, 2(1) (1), 65 - 67, Japanese

  • コロナ時代の社会不安障害を考える
    菱本 明豊
    (一社)日本総合病院精神医学会, Nov. 2020, 総合病院精神医学, 32(Suppl.) (Suppl.), S - 127, Japanese

  • ベランパネルの増量により精神病症状が出現した一例
    清登 健太, 中村 亮太, 野本 宗孝, 六本木 知秀, 古野 拓, 菱本 明豊
    (一社)日本総合病院精神医学会, Nov. 2020, 総合病院精神医学, 32(Suppl.) (Suppl.), S - 142, Japanese

  • 長期の経過を辿った摂食障害の一例
    有賀 直庸, 木谷 卓矢, 六本木 智秀, 野本 宗孝, 古野 拓, 菱本 明豊
    (一社)日本総合病院精神医学会, Nov. 2020, 総合病院精神医学, 32(Suppl.) (Suppl.), S - 162, Japanese

  • 横浜市立大学附属病院でのCovid-19感染症に対するこころのケアチームの活動について
    若月 智詞, 服部 早紀, 須田 顕, 浅見 剛, 井出 恵子, 政岡 数紀, 高石 政男, 寺山 慧, 渡邊 香織, 島田 朋子, 友田 安政, 島崎 志紀子, 粟竹 正幸, 菱本 明豊
    (一社)日本総合病院精神医学会, Nov. 2020, 総合病院精神医学, 32(Suppl.) (Suppl.), S - 199, Japanese

  • 自殺未遂患者への中長期的な心理支援を行ない社会復帰に至った一症例
    伊藤 翼, 日野 耕介, 檜垣 はる香, 野本 宗孝, 六本木 知秀, 菱本 明豊
    (一社)日本総合病院精神医学会, Nov. 2020, 総合病院精神医学, 32(Suppl.) (Suppl.), S - 207, Japanese

  • 自殺関連事象を伴う児童・青年期の適応障害患者のストレス因と援助希求に関する調査
    宮崎 秀仁, 藤田 純一, 青木 芳子, 青山 久美, 浅沼 和哉, 戸井田 真木, 菱本 明豊
    (一社)日本児童青年精神医学会, Oct. 2020, 日本児童青年精神医学会総会抄録集, 61回, O - 34, Japanese

  • 児童精神科外来初診患者におけるIGDS-J高値患者の特徴
    浅沼 和哉, 青山 久美, 戸井田 真木, 宮崎 秀仁, 藤田 純一, 高橋 雄一, 菱本 明豊
    (一社)日本児童青年精神医学会, Oct. 2020, 日本児童青年精神医学会総会抄録集, 61回, P - 45, Japanese

  • ADに起因するMCIの進行に対するマトリクスメタロプロテイナーゼの影響(Effects of matrix metalloproteinase on disease progression in MCI due to AD)
    阿部 紀絵, 千葉 悠平, 服部 早紀, 吉見 明香, 井出 恵子, 浅見 剛, 須田 顕, 菱本 明豊
    (一社)日本認知症学会, Oct. 2020, Dementia Japan, 34(4) (4), 499 - 499, English

  • Effects of matrix metalloproteinase on disease progression in MCI due to AD(和訳中)
    阿部 紀絵, 千葉 悠平, 服部 早紀, 吉見 明香, 井出 恵子, 浅見 剛, 須田 顕, 菱本 明豊
    (一社)日本認知症学会, Oct. 2020, Dementia Japan, 34(4) (4), 499 - 499, English

  • Otsuka Ikuo, Hishimoto Akitoyo
    Japanese Society of Biological Psychiatry, Sep. 2020, Japanese Journal of Biological Psychiatry, 31(3) (3), 134 - 140, Japanese

  • 統合失調症罹患同胞対・両親の全エクソームシーケンスおよびSPATA7遺伝子リシーケンスと関連解析
    井桁 裕文, 渡部 雄一郎, 森川 亮, 池田 匡志, 大塚 郁夫, 保谷 智史, 小泉 暢大栄, 江川 純, 菱本 明豊, 岩田 仲生, 染矢 俊幸
    (公社)日本精神神経学会, Sep. 2020, 精神神経学雑誌, (2020特別号) (2020特別号), S306 - S306, Japanese

  • 神経免疫学と精神医学の狭間で 精神科医が遭遇することがある、慢性〜亜急性経過の自己免疫性脳炎と、その治療後の長期経過について
    千葉 悠平, 阿部 紀絵, 服部 早紀, 伊倉 崇浩, 斎藤 知之, 須田 顕, 藤城 弘樹, 勝瀬 大海, 西野 精治, 菱本 明豊
    (公社)日本精神神経学会, Sep. 2020, 精神神経学雑誌, (2020特別号) (2020特別号), S359 - S359, Japanese

  • 統合失調症患者の退院前作業療法における余暇活動支援の効果
    胡 友恵, 菱本 明豊, 南 陽香, 橋本 健志, 四本 かやの
    (一社)日本作業療法士協会, Sep. 2020, 日本作業療法学会抄録集, 54回, OH - 8, Japanese

  • 大塚 郁夫, 菱本 明豊
    日本生物学的精神医学会, Sep. 2020, 日本生物学的精神医学会誌, 31(3) (3), 134 - 140, Japanese

  • メタボローム解析による統合失調症血液バイオマーカーの探究
    金 世賢, 岡崎 賢志, 大塚 郁夫, 新光 穣, 木村 敦, 蓬莱 政, 新名 尚史, 平田 尚士, 谷藤 貴紀, 山木 愛久, 青山 慎介, 菱本 明豊, 曽良 一郎
    日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会, Aug. 2020, 日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集, 50回・42回・4回, 190 - 190, Japanese

  • 気分障害のバイオマーカーとしての血清中血小板由来増殖因子(PDGF-BB)に関する多施設共同研究
    井手本 啓太, 石間 環, 新津 富央, 畑 達記, 小田 靖典, 木村 敦史, 亀野 陽亮, 蓬莱 政, 山森 英長, 戸田 重誠, 菱本 明豊, 橋本 亮太, 中込 和幸, 伊豫 雅臣, 橋本 謙二
    日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会, Aug. 2020, 日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集, 50回・42回・4回, 197 - 197, Japanese

  • 自殺完遂者の死後脳におけるケモカインの変化
    新光 穣, 大塚 郁夫, 岡崎 賢志, 蓬莱 政, 朴 秀賢, 高橋 玄倫, 上野 易弘, 曽良 一郎, 菱本 明豊
    日本神経精神薬理学会・日本生物学的精神医学会・日本精神薬学会, Aug. 2020, 日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集, 50回・42回・4回, 197 - 197, Japanese

  • Cell adhesion molecules and neuropsychiatric disorders
    菱本 明豊
    星和書店, May 2020, 臨床精神薬理 = Japanese journal of clinical psychopharmacology, 23(5) (5), 528 - 530, Japanese

  • うつ病モデル動物における扁桃体FKBP5の発現様式
    鹿内 浩樹, Ghebreab Robel, 吉田 隆行, 菱本 明豊, 吉岡 充弘, 泉 剛
    日本臨床精神神経薬理学会・日本神経精神薬理学会, Oct. 2019, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 29回・49回, 260 - 260, Japanese

  • 余暇活動への介入により健康状態の自己評価が向上した統合失調患者の事例
    胡 友恵, 菱本 明豊, 南 陽香, 橋本 健志, 四本 かやの
    (一社)日本作業療法士協会, Sep. 2019, 日本作業療法学会抄録集, 53回, OH - 4, Japanese

  • 統合失調症患者におけるBrexpiprazoleの使用経験
    菱本 明豊, 青山 慎介, 大塚 郁夫, 朴 秀賢, 蓬莱 政, 木村 敦, 新名 尚史, 山木 愛久, 曽良 一郎
    (公社)日本精神神経学会, Jun. 2019, 精神神経学雑誌, (2019特別号) (2019特別号), S409 - S409, Japanese

  • 鑑別と診断に苦慮した遷延するアルコール離脱せん妄の一例
    長妻 渉, 新名 尚史, 塚本 亮, 木村 敦, 蓬莱 政, 大塚 郁夫, 青山 慎介, 菱本 明豊, 曽良 一郎
    (公社)日本精神神経学会, Jun. 2019, 精神神経学雑誌, (2019特別号) (2019特別号), S484 - S484, Japanese

  • 統合失調症患者の脳内ゲノムにおけるコピー数変異の評価
    坂井 美和子, 渡部 雄一郎, 染矢 俊幸, 荒木 一明, 澁谷 雅子, 新里 和弘, 大島 健一, 國井 泰人, 矢部 博興, 松本 純弥, 和田 明, 日野 瑞城, 橋本 健志, 菱本 明豊, 北村 登, 入谷 修司, 白川 治, 前田 潔, 宮下 哲典, 丹羽 真一, 高橋 均, 柿田 明美, 桑野 良三, 那波 宏之
    (公社)日本精神神経学会, Jun. 2019, 精神神経学雑誌, (2019特別号) (2019特別号), S603 - S603, Japanese

  • 統合失調症におけるマクロファージ遊走阻止因子(MIF)の血清濃度増加と遺伝子多型関連解析
    岡崎 賢志, 大塚 郁夫, 渡部 雄一郎, 朴 秀賢, 新名 尚史, 平田 尚士, 蓬莱 政, 染矢 俊幸, 曽良 一郎, 菱本 明豊
    (公社)日本精神神経学会, Jun. 2019, 精神神経学雑誌, (2019特別号) (2019特別号), S441 - S441, Japanese

  • 統合失調症患者の脳内ゲノムにおけるコピー数変異の評価
    坂井 美和子, 渡部 雄一郎, 染矢 俊幸, 荒木 一明, 澁谷 雅子, 新里 和弘, 大島 健一, 國井 泰人, 矢部 博興, 松本 純弥, 和田 明, 日野 瑞城, 橋本 健志, 菱本 明豊, 北村 登, 入谷 修司, 白川 治, 前田 潔, 宮下 哲典, 丹羽 真一, 高橋 均, 柿田 明美, 桑野 良三, 那波 宏之
    (公社)日本精神神経学会, Jun. 2019, 精神神経学雑誌, (2019特別号) (2019特別号), S603 - S603, Japanese

  • うつ病の診断で加療中に、著しい嚥下機能障害と非典型的な亜昏迷様症状を呈し診断に苦慮した1例
    塚本 亮, 木村 敦, 新名 尚史, 蓬莱 政, 大塚 郁夫, 田宮 裕子, 青山 慎介, 朴 秀賢, 菱本 明豊, 曽良 一郎
    (公社)日本精神神経学会, Mar. 2019, 精神神経学雑誌, 121(3) (3), 233 - 233, Japanese

  • 気分障害のバイオマーカーとしての血清中グリア細胞株由来神経栄養因子(GDNF)に関する多施設共同研究
    井手本啓太, 新津富央, 畑達記, 小田靖典, 木村敦史, 橋本佐, 亀野陽亮, 蓬莱政, 山森英長, 山森英長, 山森英長, 戸田重誠, 戸田重誠, 菱本明豊, 橋本亮太, 橋本亮太, 中込和幸, 橋本謙二, 伊豫雅臣, 伊豫雅臣
    2019, 日本うつ病学会総会プログラム・抄録集, 16th

  • mtDNA copy number raises the potential of left frontopolar hemodynamic responses for distinguishing BD from MDD
    菱本明豊, 辻井農亜, 大塚郁夫, 岡崎賢志, 柳雅也, 沼田周助, 山木愛久, 川久保善宏, 白川治
    2019, 日本うつ病学会総会プログラム・抄録集, 16th

  • アルコール依存症にアルコール性心筋症が合併し、断酒により心機能が改善した症例
    塚本 亮, 菱本 明豊, 青山 慎介, 朴 秀賢, 田宮 裕子, 大塚 郁夫, 松山 賢一, 木村 敦, 蓬莱 政, 曽良 一郎
    (公社)日本精神神経学会, Jan. 2019, 精神神経学雑誌, 121(1) (1), 68 - 68, Japanese

  • 統合失調症治療ガイドラインの使い方(第3回) 維持期治療
    樽谷精一郎, 金沢徹文, 竹内啓善, 伊藤侯輝, 岸本泰士郎, Hishimoto Akitoyo
    星和書店, Jul. 2018, 臨床精神薬理, 21(7) (7), 965 - 968, Japanese
    [Refereed][Invited]

  • 自殺者死後脳およびうつ病モデルにおけるグルココルチコイド阻害因子FKBP5の検討
    泉 剛, Ghebreab Robel, 吉田 隆行, 大塚 郁夫, 菱本 明豊, 吉岡 充弘
    (公財)先進医薬研究振興財団, Mar. 2018, 先進医薬研究振興財団研究成果報告集, 2017年度, 4 - 8, Japanese

  • 自殺者死後脳およびうつ病モデルにおけるグルココルチコイド阻害因子FKBP5の検討
    泉 剛, Ghebreab Robel, 吉田 隆行, 大塚 郁夫, 菱本 明豊, 吉岡 充弘
    (公財)先進医薬研究振興財団, Mar. 2018, 先進医薬研究振興財団研究成果報告集, 2017年度, 4 - 8, Japanese

  • 全身性エリテマトーデス加療中に急性精神病状態を呈し診断に難渋した症例
    塚本亮, 松山賢一, Hishimoto Akitoyo, 青山慎介, 朴秀賢, 田宮裕子, 大塚郁夫, 木村敦, 蓬莱政, Ichiro Sora
    (公社)日本精神神経学会, Mar. 2018, 精神神経学雑誌, 120(3) (3), 232 - 232, Japanese
    [Refereed]
    Meeting report

  • 自殺既遂者におけるテロメア異常短縮(Shorter telomere length in suicide completers)
    大塚 郁夫, 菱本 明豊, 泉 剛, 朴 秀賢, 木村 敦, 張 園, 毛利 健太朗, 岡崎 賢志, 高橋 玄倫, 上野 易弘, 白川 治, 曽良 一郎
    日本生物学的精神医学会・日本神経精神薬理学会, Sep. 2017, 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, 39回・47回, 156 - 156, English

  • 日本人自殺既遂者におけるMIF遺伝子プロモーター領域機能的多型の関連解析(Association study of MIF promoter polymorphosms with suicide completers in the Japanese population)
    新名 尚史, 菱本 明豊, 大塚 郁夫, 岡崎 賢志, 朴 秀賢, 毛利 健太朗, 蓬莱 政, 江口 典臣, 木村 敦, 山木 愛久, 平田 尚士, 高橋 玄倫, 上野 易弘, 白川 治, 曽良 一郎
    日本生物学的精神医学会・日本神経精神薬理学会, Sep. 2017, 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, 39回・47回, 190 - 190, English

  • PDCD11遺伝子の稀な変異と統合失調症の発症リスク 罹患同胞対家系の全エクソーム解析、ターゲットリシーケンス、および症例・対照研究
    保谷 智史, 渡部 雄一郎, 菱本 明豊, 布川 綾子, 金子 尚史, 村竹 辰之, 新名 尚史, 大塚 郁夫, 奥田 修二郎, 井上 絵美子, 井桁 裕文, 澁谷 雅子, 江川 純, 折目 直樹, 曽良 一郎, 染矢 俊幸
    日本生物学的精神医学会・日本神経精神薬理学会, Sep. 2017, 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, 39回・47回, 177 - 177, Japanese

  • 抗NMDA受容体脳炎回復期の精神症状に対して修正型電気痙攣療法を施行した一例
    金 世賢, 青山 慎介, 大塚 郁夫, 宋 慎平, 朴 秀賢, 菱本 明豊, 曽良 一郎
    (公社)日本精神神経学会, Jun. 2017, 精神神経学雑誌, (2017特別号) (2017特別号), S485 - S485, Japanese

  • Copy Number Variation of 22q11.2 Genes Arrests the Developmental Maturation of Working Memory Capacity and Adult Hippocampal Neurogenesis
    Noboru Hiroi, Shuken Boku, Seiji Abe, Takeshi Izumi, Tomohisa Takahashi, Akira Nishi, Hiroko Nomaru, Yasuhiko Naka, Gina Kang, Akitoyo Hishimoto, Kenji Tanigaki, Jinghang Zhang, Kenny Ye, Shigeki Kato, Pekka Mannisto, Kazuto Kobayashi
    May 2017, BIOLOGICAL PSYCHIATRY, 81(10) (10), S14 - S14, English
    Summary international conference

  • 染色体22q11.2領域のコピー数増加は作業記憶の発達と成体海馬神経細胞新生を抑制する
    朴秀賢, 泉剛, 阿部誠二, 高橋知久, 菱本明豊, 谷垣健二, 加藤成樹, 小林和人, 廣井昇
    2017, 日本神経精神薬理学会プログラム・抄録集, 47th, 156, Japanese

  • The risk factors of low bone mineral density in male alcoholic patients: cross-sectional study
    Tadasu Horai, Shunken Boku, Noriomi Eguchi, Akitoyo Hishimoto, Atsushi Kimura, Kentaro Mori, Naofumi Shinmyo, Ichiro Sora
    Jun. 2016, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 164 - 164, English
    Summary international conference

  • Possible role of CDH13 in nicotine dependence: Investigations on mouse neural progenitors and schizophrenia patients
    Ikuo Otsuka, Akitoyo Hishimoto, Shuken Boku, Satoshi Okazaki, Kentaro Mouri, Ichiro Sora
    Jun. 2016, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 160 - 160, English
    Summary international conference

  • 自殺既遂の生物学的研究
    Otsuka Ikuo, Ichiro Sora, 菱本明豊
    (一社)日本神経精神薬理学会, Jun. 2016, 日本神経精神薬理学雑誌, 36(3号) (3号), 55 - 61, Japanese
    [Refereed]

  • 【依存症の分子病態解析】 報酬系にかかわる受容体と薬物依存
    Ichiro Sora, 菱本明豊
    金芳堂, Jan. 2016, 脳21, 19(1号) (1号), 9 - 12, Japanese
    [Refereed]

  • 【急性薬物中毒 精神疾患を持つ患者の自殺企図へのアプローチ】 この患者ではどう対応する?エキスパートが教えるココがポイント! うつ病治療中で賦活症候群が疑われる患者
    木村敦, Hishimoto Akitoyo
    Oct. 2015, 薬局, 66(11号) (11号), 2790 - 2794, Japanese
    Introduction other

  • 統合失調症における細胞周期関連遺伝子に着目した3段階mRNA発現解析(A three-stage mRNA expression study to identify cell cycle-related genes associated with schizophrenia)
    岡崎 賢志, 菱本 明豊, 朴 秀賢, 毛利 健太朗, 白岩 恭一, 大塚 郁夫, 白井 豊, 藤田 愛子, 白川 治, 湖海 正尋, 曽良 一郎
    日本生物学的精神医学会・日本神経精神薬理学会, Sep. 2015, 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, 37回・45回, 172 - 172, English

  • 統合失調症の薬物治療ガイドライン (第3章)「維持期治療」
    岸本 泰士郎, 伊藤 侯輝, 金沢 徹文, 竹内 啓善, 菱本 明豊
    日本生物学的精神医学会・日本神経精神薬理学会, Sep. 2015, 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, 37回・45回, 107 - 107, Japanese

  • 統合失調症のニコチン依存におけるCadherin 13の役割
    大塚郁夫, Hishimoto Akitoyo, 渡部雄一郎, 朴秀賢, 笠原好之, Ichiro Sora
    (一社)日本アルコール・アディクション医学会, Aug. 2015, 日本アルコール・薬物医学会雑誌, 50(4号) (4号), 207 - 207, Japanese
    [Refereed]
    Meeting report

  • Identification of Chromosomal Segments and Specific Individual Genes Critical for Schizophrenia-related Phenotypes in Mouse Models of 22q11.2 Copy Number Variants
    Noboru Hiroi, Takeshi Hiramoto, Shuken Boku, Tomohisa Takahashi, Takeshi Izumi, Gina Kang, Akitoyo Hishimoto
    May 2014, BIOLOGICAL PSYCHIATRY, 75(9) (9), 139S - 139S, English
    Summary international conference

  • Over-expression of Tbx1 or COMT in the Mouse Hippocampus Partially Recapitulates Behavioral Phenotypes of 22q11.2 Duplication
    Shuken Boku, Takeshi Izumi, Tomohisa Takahashi, Gina Kang, Akitoyo Hishimoto, Shigeki Kato, Kazuto Kobayashi, Kenji Tanigaki, Takeshi Hiramoto, Noboru Hiroi
    May 2014, BIOLOGICAL PSYCHIATRY, 75(9) (9), 38S - 38S, English
    Summary international conference

  • 統合失調症におけるIL-19遺伝子の発現量的形質遺伝子座(eQTL)におけるハプロタイプ解析
    岡崎 賢志, 渡部 雄一郎, 大塚 郁夫, 吉田 正邦, 白岩 恭一, 毛利 健太朗, ウォラパット・ラッタアーパー, イルワン・スプリヤント, 江口 典臣, 笹田 徹, 福武 将映, 布川 綾子, 染矢 俊幸, 白川 治, 菱本 明豊, 曽良 一郎
    日本臨床精神神経薬理学会・日本神経精神薬理学会, Oct. 2013, 日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集, 23回・43回, 230 - 230, Japanese

  • Brain Science 統合失調症の病態生理と皮質ニューロン・ネットワークの異常(解説)
    福武 将映, Hishimoto Akitoyo
    科学評論社, Aug. 2013, 精神科, 23(2) (2), 211 - 217, Japanese
    [Refereed]
    Introduction scientific journal

  • 総合病院における他科入院患者への精神科リエゾン・コンサルテーションの現状 2
    上月遥, 川添文子, 磯部昌憲, 磯部昌憲, 大谷恭平, 高宮靜男, 白岩恭一, 大塚郁夫, 菱本明豊, 曽良一郎, 河野将英, 岡村健二, 北村登, 松石邦隆, 見野耕一
    2013, 総合病院精神医学, 25(Supplement) (Supplement)

  • 総合病院における他科入院患者への精神科リエゾン・コンサルテーションの現状 1
    川添文子, 上月遥, 河村麻美子, 石川慎一, 大谷恭平, 高宮静男, 長谷川雅史, 白岩恭一, 大塚郁夫, 菱本明豊, 曽良一郎
    2013, 総合病院精神医学, 25(Supplement) (Supplement)

  • ALCOHOL AND ALDEHYDE DEHYDROGENASE POLYMORPHISMS AND RISK FOR SUICIDE
    A. Hishimoto, M. Fukutake, K. Mouri, K. Shiroiwa, T. Sasada, Y. Nagasaki, M. Asano, Y. Ueno, O. Shirakawa
    Sep. 2012, ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 36, 50A - 50A, English
    Summary international conference

  • 台灣生物精神醫學會に参加して
    菱本 明豊
    25 Jun. 2011, 日本生物学的精神医学会誌 = Japanese journal of biological psychiatry, 22(2) (2), 139 - 140, Japanese

  • Synaptic cell adhesion molecules and neuropsychiatric disorders
    HISHIMOTO Akitoyo, ISHIGURO Hiroki
    日本生物学的精神医学会 ; 2010-, 25 Jun. 2010, 日本生物学的精神医学会誌 = Japanese journal of biological psychiatry, 21(2) (2), 97 - 104, Japanese

  • 【死後脳研究 その病態と課題】 細胞接着因子と精神疾患
    Hishimoto Akitoyo
    Jun. 2010, 日本生物学的精神医学会誌, 21巻, 2号, pp. 97-104, Japanese
    Introduction scientific journal

  • Neurobiology of alcohol dependence
    HISHIMOTO Akitoyo
    日本生物学的精神医学会 ; 2010-, 25 Mar. 2010, 日本生物学的精神医学会誌 = Japanese journal of biological psychiatry, 21(1) (1), 39 - 46, Japanese

  • 【薬物依存の分子病態】 アルコール依存の生物学
    Hishimoto Akitoyo
    Mar. 2010, 日本生物学的精神医学会誌, 21巻, 1号, pp. 39-46, Japanese
    Introduction scientific journal

  • ALCOHOL AND ALDEHYDE DEHYDROGENASE POLYMORPHISMS AND RISK FOR SUICIDE
    A. Hishimoto, K. Mouri, M. Fukutake, K. Shiroiwa
    2010, EUROPEAN PSYCHIATRY, 25, English
    Summary international conference

  • 【精神科における診断面接】 病歴の取り方
    Hishimoto Akitoyo
    科学評論社, Jul. 2009, 精神科, 15巻, 1号, pp. 16-24(1) (1), 10 - 15, Japanese
    Introduction scientific journal

  • 【精神医学症候群 器質・症状性精神障害など】 脳器質性・症状性精神障害 人格・行動の障害 器質性人格障害
    Hishimoto Akitoyo
    Oct. 2003, 日本臨床, 巻, 別冊精神医学症候群III, pp. 227-231, Japanese
    Introduction scientific journal

  • A novel polymorphism in the coding region of the DAP-1 gene (hDLG-and PSD-95 associated protein4 gene): Analysis of association with schizophrenia
    S Aoyama, O Shirakawa, A Hishimoto, K Yamamoto, H Hattori, H Ono, Hashimoto, I, Y Kajimoto, K Maeda
    Mar. 2003, SCHIZOPHRENIA RESEARCH, 60(1) (1), 93 - 93, English
    Summary international conference

  • 孫殺害に至ったCapgras症状群の1症例
    岸 睦久, 菱本 明豊, 見野 耕一, 山口 直彦, 橋本 健志, 金 光洙, 田中 究, 白川 治, 前田 潔
    九州精神神経学会, Aug. 1999, 九州神経精神医学, 45(2) (2), 141 - 141, Japanese

  • Serotonin transporter and serotonin 2A receptor gene polymorphisms in suicide victims
    NISHIGUCHI Naoki, MATSUSHITA Sachio, HIGUCHI Susumu, NISHIMURA Akiyoshi, NUSHIDA Hideyuki, TATSUNO Yoshitsugu, HISHIMOTO Akitoyo, HOSAKA Takaaki, MATSUISHI Kunitaka, ONO Hisae, SHIRAKAWA Osamu
    25 Dec. 1997, 日本神経精神薬理学雑誌 = Japanese journal of psychopharmacology, 17(6) (6), 308 - 308, Japanese

■ Books And Other Publications
  • Facilitating Resilience after PTSD: A Translational Approach. / Resilience and Suicide.
    OtsukaI, Hishimoto Akitoyo
    Others, Nova Science Publishers., 2018, English
    Scholarly book

  • 認知機能とカルシウム / 認知症治療薬によるカルシウム制御を介した神経障害抑制
    中村祐, Hishimoto Akitoyo, 吉山容正
    Others, 医薬ジャーナル社, 2015, Japanese
    Scholarly book

  • 精神疾患診断のための脳形態・機能検査法 / 自殺のバイオマーカー
    Hishimoto Akitoyo
    Others, 新興医学出版社, Feb. 2012, Japanese
    Scholarly book

  • 脳バンク精神疾患の謎を解くために / 精神疾患研究におけるブレインバンクの必要性
    Hishimoto Akitoyo
    Joint work, 光文社, May 2011, Japanese
    General book

  • 子どもの不安障害と抑うつ 子どもの心の診療シリーズ 4 / 自殺の生物学
    Hishimoto Akitoyo
    Joint work, 中山書店, Aug. 2010, Japanese
    Scholarly book

  • ブロナンセリン100の報告 / 統合失調症の再発再燃例へのブロナンセリンの効果
    Hishimoto Akitoyo
    Joint work, 星和書店, 2009, Japanese
    Scholarly book

■ Lectures, oral presentations, etc.
  • ベンゾジアゼピン系薬と修正型電気けいれん療法（ｍECT）が奏功せずメマンチンが有効であった遅発性緊張病の１例
    新谷 敏夫, HISHIMOTO AKITOYO, 谷藤 貴紀, KIMURA ATSUSHI, SHINMYOU NAOFUMI, HOURAI TADASU, OTSUKA IKUO, AOYAMA SHINSUKE, SORA ICHIRO
    第124回 近畿精神神経学会, Feb. 2019, Japanese, 近畿精神神経学会, 和歌山, Domestic conference
    Oral presentation

  • Electric stimulation increases expression of leukemia inhibitory factor in astrocytes via adenosine triphosphate receptor P2X2
    BOKU SHUKEN, 丸山 総一郎, 岡﨑 賢志, 菊山 裕貴, 溝口 義人, 門司 晃, 金沢 徹文, HISHIMOTO AKITOYO, 米田 博
    ACNP 2018, Dec. 2018, English, Florida, International conference
    Poster presentation

  • The cell cycle-related genes as biomarkers for schizophrenia
    岡﨑 賢志, BOKU SHUKEN, OTSUKA IKUO, 江口 典臣, SORA ICHIRO, HISHIMOTO AKITOYO
    Neuroscience 2018 Annual Meeting, Nov. 2018, English, San Diego, International conference
    Poster presentation

  • Whole-exome sequencing in a consanguineous multiplex family with schizophrenia and a case-control study
    井桁 裕文, 渡部 雄一郎, 保谷 智史, 池田 匡志, HISHIMOTO AKITOYO, 布川 綾子, 井上 絵美子, SORA ICHIRO, 岩田 仲生, 染矢 俊幸
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • Treatment in schizophrenia in the light of subjective evaluation
    HISHIMOTO AKITOYO
    The 40th Annual Meeting of Japanease Society of Biolojical Psychiatry・The 61th Annual Meeting of Japanease Society for Neurochemistry, Sep. 2018, English, Kobe, International conference
    Public discourse

  • Rare FBXO18 variations and risk of schizophrenia
    渡部 雄一郎, 保谷 智史, HISHIMOTO AKITOYO, 布川 綾子, 井上 絵美子, 井桁 裕文, OTSUKA IKUO, 澁谷 雅子, SORA ICHIRO
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • Mosaic loss of chromosome Y in peripheral blood and its risk variants in men with schizophrenia
    平田 尚士, 岡﨑 賢志, OTSUKA IKUO, BOKU SHUKEN, AOYAMA SHINSUKE, 江口 典臣, KIMURA ATSUSHI, HOURAI TADASU, SORA ICHIRO, HISHIMOTO AKITOYO
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • Mitochondrial DNA copy number of peripheral blood in bipolar disorder:the present study and a meta-analysis
    山木 愛久, OTSUKA IKUO, 毛利 健太朗, BOKU SHUKEN, 沼田 周助, 柳 雅也, 大森 哲郎, 白川 治, SORA ICHIRO, HISHIMOTO AKITOYO
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • Loss of chromosome Y in blood, but not in brain, of suicide completers
    OTSUKA IKUO, 岡﨑 賢志, KIMURA ATSUSHI, HOURAI TADASU, 泉 剛, Motonori Takahashi, Yasuhiro Ueno, 白川 治, SORA ICHIRO, HISHIMOTO AKITOYO
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia
    岡﨑 賢志, OTSUKA IKUO, 渡部 雄一郎, 沼田 周助, BOKU SHUKEN, SHINMYOU NAOFUMI, 大森 哲郎, 染矢 俊幸, SORA ICHIRO, HISHIMOTO AKITOYO
    WFSBP Asia Pacific Regional Congress of Biological Psychiatry 2018 KOBE, Sep. 2018, English, Kobe, International conference
    Poster presentation

  • ALCOHOL-RELATED POLYMORPHISMS AND RISK FOR SUICIDE IN THE JAPANEASE POPULATION
    OTSUKA IKUO, HISHIMOTO AKITOYO
    ISBRA2018, Sep. 2018, English, Kyoto, International conference
    Oral presentation

  • うつ病の診断で加療中に、著しい嚥下機能障害と非定型的な亜昏迷様症状を呈し診断に苦慮した１例
    塚本 亮, KIMURA ATSUSHI, SHINMYOU NAOFUMI, HOURAI TADASU, OTSUKA IKUO, TAMIYA HIROKO, AOYAMA SHINSUKE, BOKU SHUKEN, HISHIMOTO AKITOYO, SORA ICHIRO
    第123回近畿精神神経学会, Aug. 2018, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • 統合失調症症状とパーキンソン症状を合併した22ｑ11.2欠失症候群に対し修正型電気けいれん療法が奏功した１例
    谷藤 貴紀, HISHIMOTO AKITOYO, KIMURA ATSUSHI, 佐竹 渉, SORA ICHIRO
    第114回日本精神神経学会学術総会, Jun. 2018, Japanese, 日本精神神経学会, 神戸, Domestic conference
    Oral presentation

  • 自殺の生物学的研究の現状と課題
    HISHIMOTO AKITOYO
    第24回（通算45回）日本精神神経科診療所協会学術研究会, Jun. 2018, Japanese, 日本精神神経科診療所協会, 淡路, Domestic conference
    Public symposium

  • ステージを考えた統合失調症薬物療法
    HISHIMOTO AKITOYO
    第24回（通算45回）日本精神神経科診療所協会学術研究会, Jun. 2018, Japanese, 日本精神神経科診療所協会, 淡路, Domestic conference
    Public discourse

  • アルコール依存症にアルコール性心筋症が合併し、断酒により心機能が改善した症例
    塚本 亮, Hishimoto Akitoyo, Aoyama Shinsuke, Boku Shuken, Tamiya Hiroko, Otsuka Ikuo, Matsuyama Kenichi, Ichiro Sora
    第122回近畿精神神経学会, Feb. 2018, Japanese, 近畿精神神経学会, 京都, Domestic conference
    Oral presentation

  • 統合失調症患者における錐体外路症状発現に及ぼすCYP2D6遺伝子多型の影響
    伊藤 雄大, 山本 和宏, 西岡 達也, 久米 学, 槇本 博雄, Otsuka Ikuo, Hishimoto Akitoyo, Ichiro Sora, Hirai Midori, Yano Ikuko
    第27回日本医療薬学会年会, Nov. 2017, Japanese, 日本医療薬学会, 千葉, Domestic conference
    Oral presentation

  • 双極性感情障害におけるテロメア長・ミトコンドリア DNA コピー数の解析
    山木 愛久, Otsuka Ikuo, 岡崎 賢志, Boku Shuken, Hishimoto Akitoyo
    第36回躁うつ病の薬理・生物学的研究懇話会, Oct. 2017, Japanese, 東京, Domestic conference
    Oral presentation

  • SIRT1 遺伝子と自殺
    平田 尚士, Otsuka Ikuo, 岡崎 賢志, 山木 愛久, Boku Shuken, Hishimoto Akitoyo
    第36回躁うつ病の薬理・生物学的研究懇話会, Oct. 2017, Japanese, 東京, Domestic conference
    Oral presentation

  • Aberrant Telomere Length and Mitochondria DNA Copy Number in Suicide Completers
    Otsuka Ikuo, Takeshi Izumi, Boku Shuken, Atsushi Kimura, Yuan Zhang, Kentaro Mouri, Satoshi Okazaki, Kyoichi Shiroiwa, Takahashi Motonori, Ueno Yasuhiro, Osamu Shirakawa, Ichiro Sora, Hishimoto Akitoyo
    25th World Congress of Psychiatric Genetics, Oct. 2017, English, オーランド, アメリカ, International conference
    Oral presentation

  • 日本人自殺既遂者におけるMIF遺伝子プロモーター領域機能的多型の関連解析
    新名 尚史, Hishimoto Akitoyo, Otsuka Ikuo, 岡崎 賢志, Boku Shuken, 毛利 健太朗, 蓬莱 政, 江口 典臣, 木村 敦, 山木 愛久, 平田 尚士, Takahashi Motonori, Ueno Yasuhiro, 白川 治, Ichiro Sora
    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会, Sep. 2017, Japanese, 日本生物学的精神医学会・日本神経精神薬理学会, 札幌, Domestic conference
    Poster presentation

  • 染色体22ｑ11.2領域のコピー数増加は作業記憶の発達と成体海馬神経細胞新生を抑制する
    Boku Shuken, 泉 剛, 阿部 誠二, 高橋 和久, Hishimoto Akitoyo, 谷垣 健二, 加藤 成樹, 小林 和人, 廣井 昇
    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会, Sep. 2017, Japanese, 日本生物学的精神医学会・日本神経精神薬理学会, 札幌, Domestic conference
    Oral presentation

  • 自殺既遂者におけるテロメア異常短縮
    Otsuka Ikuo, Hishimoto Akitoyo, 泉 剛, Boku Shuken, 木村 敦, 張 園, 毛利 健太朗, 岡崎 賢志, Takahashi Motonori, Ueno Yasuhiro, 白川 治, Ichiro Sora
    第39回日本生物学的精神医学会・第47回日本神経精神薬理学会 合同年会, Sep. 2017, Japanese, 日本生物学的精神医学会・日本神経精神薬理学会, 札幌, Domestic conference
    Oral presentation

  • 全身性エリテマトーデス加療中に急性精神病状態を呈し診断に難渋した症例
    塚本 亮, Matsuyama Kenichi, Hishimoto Akitoyo, Aoyama Shinsuke, Boku Shuken, Tamiya Hiroko, Otsuka Ikuo, Ichiro Sora
    第121回近畿精神神経学会, Aug. 2017, Japanese, 近畿精神神経学会, 滋賀, Domestic conference
    Oral presentation

  • 抗NMDA受容体脳炎回復期の精神症状に対して修正型電気痙攣療法を施行した一例
    金 世賢, Aoyama Shinsuke, Otsuka Ikuo, 宋 慎平, Boku Shuken, Hishimoto Akitoyo, Ichiro Sora
    第113回日本精神神経学会学術総会, Jun. 2017, Japanese, 日本精神神経学会, 名古屋, Domestic conference
    Oral presentation

  • 当院の電気けいれん療法における実績と報告
    加賀野井, 秀和, 白川 治, Aoyama Shinsuke, Boku Shuken, Otsuka Ikuo, Hishimoto Akitoyo, Ichiro Sora
    第120回近畿精神神経学会, Feb. 2017, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • 神戸大学医学部附属病院における精神科ショートケア開設後の現状と課題
    神志那 武, Tamiya Hiroko, Boku Shuken, 村瀬 裕美, 渕脇 綾乃, 干飯 雅昭, Hishimoto Akitoyo, Ichiro Sora
    第120回近畿精神神経学会, Feb. 2017, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • 視神経膠腫治療の経過中に幻覚妄想、精神運動興奮を認めた下垂体機能低下症の1例
    内田 杏子, Matsuyama Kenichi, 毛利 健太朗, Aoyama Shinsuke, Hishimoto Akitoyo, Ichiro Sora
    第120回近畿精神神経学会, Feb. 2017, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • 自殺者におけるテロメア・ミトコンドリア異常
    Otsuka Ikuo, 泉 剛, 木村 敦, 張 園, 岡﨑 賢志, 新名 尚史, 山木 愛久, Boku Shuken, Hishimoto Akitoyo
    第35回躁うつ病の薬理・生化学的研究懇話会, Nov. 2016, Japanese, 躁うつ病の薬理・生化学的研究会, 山口, Domestic conference
    Oral presentation

  • 統合失調症罹患同胞対・両親3家系のエクソーム解析および3段階関連解析
    布川 綾子, 渡部 雄一郎, 澁谷 雅子, 池田 匡志, Hishimoto Akitoyo, 近藤 健治, 江川 純, 金子 尚史, 村竹 辰之, 齋藤 竹生, 岡﨑 賢志, 島崎 愛夕, 井桁 裕文, 井上 絵美子, 保谷 智史, 須貝 拓朗, Ichiro Sora, 岩田 仲生, 染矢 俊幸
    第38回日本生物学的精神医学会・第59回日本神経化学大会 合同年会, Sep. 2016, Japanese, 日本生物学的精神医学会, 福岡, Domestic conference
    Oral presentation

  • Molecular histochemistry identifies peptidomic organaization and reorganaization along striatal projection units.
    Hishimoto Akitoyo, Hiroko Nomaru, Kenny Kenny, Akira Nishi, Jihyeon Lim, Jennifer T Aguilan, Edward Nieves, Gina Kang, Ruth H Angeletti, Noboru Hiroi
    第38回日本生物学的精神医学会・第59回日本神経化学大会 合同年会, Sep. 2016, English, 日本生物学的精神医学会, 福岡, Domestic conference
    Oral presentation

  • 統合失調症におけるニコチン依存へのCadherin13の役割
    Ichiro Sora, Otsuka Ikuo, Boku Shuken, 岡﨑 賢志, 森屋 由紀, 久保 有美子, 笠原 好之, Hishimoto Akitoyo
    第31回平成17年度助成研究発表会（喫煙科学研究財団）, Jul. 2016, Japanese, 喫煙科学研究財団, 東京, Domestic conference
    Oral presentation

  • 男性アルコール依存症患者における骨密度減少のリスクファクターに関する横断研究
    蓬莱 政, Hishimoto Akitoyo, 毛利 健太朗, Boku Shuken, 江口 典臣, 新名 尚史, 木村 敦, Ichiro Sora
    第46回日本神経精神薬理学会, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, International conference
    Oral presentation

  • 好中球減少にてクロザピンを一時中止したのち再投与した統合失調症の一例
    Otsuka Ikuo, 笹田 徹, Hishimoto Akitoyo, Ichiro Sora
    第46回日本神経精神薬理学会, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, International conference
    Oral presentation

  • ニコチン依存症におけるCDH13の役割：マウス神経前駆細胞と統合失調症臨床サンプルを用いた解析
    Otsuka Ikuo, Hishimoto Akitoyo, Boku Shuken, 岡﨑 賢志, 毛利 健太朗, Ichiro Sora
    第46回日本神経精神薬理学会, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, International conference
    Oral presentation

  • The risk factors of low bone minerak density in male alcoholic patients: cross-sectional study
    Tadasu Horai, Boku Shuken, Noriomi Eguchi, Hishimoto Akitoyo, Atsushi Kimura, Kentaro Mori, Naofumi Shinmyo, Ichiro Sora
    30th CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Jul. 2016, English, CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Seoul, Korea, International conference
    Poster presentation

  • QOLに焦点を当てた統合失調症の薬物治療～アリピプラゾール持続性注射剤の使用経験から～
    Hishimoto Akitoyo
    第46回日本神経精神薬理学会, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, International conference
    Public symposium

  • Possible role of CDH13 in nicotine dependence: investigations on mouse neural progenitors and schizophrenia patients
    Otsuka Ikuo, Hishimoto Akitoyo, Boku Shuken, Satoshi Okazaki, Kentaro Mouri, Ichiro Sora
    30th CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Jul. 2016, English, CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Seoul, Korea, International conference
    Poster presentation

  • KIF17の脳内タンパク減少とミスセンス変異は統合失調症と関連する
    Hishimoto Akitoyo, 毛利 健太朗, ラッタアッパワラパット, Boku Shuken, Ichiro Sora
    第46回日本神経精神薬理学会, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, International conference
    Oral presentation

  • A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia
    Hishimoto Akitoyo, Boku Shuken, Hiroki Ishiguro, Kentaro Mori, Woraphat Ratta-apha, Ichiro Sora
    30th CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Jul. 2016, English, CINP WORLD CONGRESS OF NEUROPSYCHOPHAMACOLOGY, Seoul, Korea, International conference
    Poster presentation

  • 統合失調症におけるDNAテロメア短縮とミトコンドリアDNAコピー数の解析
    Otsuka Ikuo, Hishimoto Akitoyo, Boku Shuken, 岡﨑 賢志, 毛利 健太朗, 蓬莱 政, Ichiro Sora
    第11回ICG 第7回COCORO合同会議, Jun. 2016, Japanese, COCORO, 東京, Domestic conference
    Oral presentation

  • 維持期治療
    岸本 泰士郎, 伊藤 侯輝, 金沢 徹文, 竹内 啓善, Hishimoto Akitoyo
    第112回日本精神神経学会学術総会, Jun. 2016, Japanese, 日本精神神経学会, 千葉, Domestic conference
    Public symposium

  • アルコール・薬物依存、行動嗜癖
    Hishimoto Akitoyo
    第112回日本精神神経学会学術総会, Jun. 2016, Japanese, 日本精神神経学会, 千葉, Domestic conference
    Oral presentation

  • The biological aspects of suicidal behavior in addiction
    Hishimoto Akitoyo
    第7回国際自殺予防学会アジア・太平洋地域大会・第40回日本自殺予防学会総会, May 2016, English, 日本自殺予防学会, 東京, Domestic conference
    Oral presentation

  • 自閉症スペクトラム障害を合併した摂食障害の1例
    奥小路 明子, Tamiya Hiroko, Mouri Kentaro, Sasada Toru, Hishimoto Akitoyo, Ichiro Sora
    第118回近畿精神神経学会, Feb. 2016, Japanese, 近畿精神神経学会, 奈良, Domestic conference
    Oral presentation

  • 統合失調症のニコチン依存におけるCadherin13の役割
    大塚 郁夫, Hishimoto Akitoyo, 渡部 雄一郎, Boku Shuken, 笠原 好之, Ichiro Sora
    平成27年度アルコール・薬物依存関連問題学会合同学術総会, Oct. 2015, Japanese, アルコール・薬物依存関連問題学会、日本依存性神経精神科学会, 神戸, Domestic conference
    Oral presentation

  • 細胞接着因子と精神疾患
    Hishimoto Akitoyo, 大塚 郁夫, 岡﨑 賢志, Boku Shuken
    平成27年度アルコール・薬物依存関連問題学会合同学術総会, Oct. 2015, Japanese, アルコール・薬物依存関連問題学会、日本依存性神経精神科学会, 神戸, Domestic conference
    [Invited]
    Nominated symposium

  • 危険ドラッグの臨床症状にへの影響および遺伝子多形との関連の検討
    岡﨑 賢志, Hishimoto Akitoyo, Boku Shuken, Mouri Kentaro, 竹村 幸洋, 麻生 克郎, 山本 訓也, Ichiro Sora
    平成27年度アルコール・薬物依存関連問題学会合同学術総会, Oct. 2015, Japanese, アルコール・薬物依存関連問題学会、日本依存性神経精神科学会, 神戸, Domestic conference
    Oral presentation

  • 統合失調症における細胞周期関連遺伝子に着目した3段階mRNA発現解析
    岡﨑 賢志, Hishimoto Akitoyo, Boku Shuken, Mouri Kentaro, Shiroiwa Kyoichi, 大塚 郁夫, 白井 豊, 藤田 愛子, 白川 治, 湖海 正尋, Ichiro Sora
    第37回日本生物学的精神医学会・第45回日本神経精神薬理学会, Sep. 2015, Japanese, 日本生物学的精神医学会・日本神経精神薬理学会, 東京, Domestic conference
    Oral presentation

  • 統合失調症におけるCadherin13遺伝子多形解析
    大塚 郁夫, 渡部 雄一郎, Hishimoto Akitoyo, Boku Shuken, Mouri Kentaro, Shiroiwa Kyoichi, 岡﨑 賢志, 布川 綾子, 白川 治, 染矢 俊幸, Ichiro Sora
    第37回日本生物学的精神医学会・第45回日本神経精神薬理学会, Sep. 2015, Japanese, 日本生物学的精神医学会・日本神経精神薬理学会, 東京, Domestic conference
    Oral presentation

  • 自殺感受性遺伝子の中枢神経における機能解析
    Hishimoto Akitoyo, Boku Shuken, 泉 剛, Ichiro Sora, 白川 治
    第34回躁うつ病の薬理・生化学的研究懇話会, Sep. 2015, Japanese, 薬理・生化学的研究懇話会, 淡路島, Domestic conference
    Oral presentation

  • 向精神薬まるわかり徹底解剖 「薬理学根拠に基づく抗うつ薬の使い方」
    Hishimoto Akitoyo
    第25回日本サイコオンコロジー学会総会, Sep. 2015, Japanese, 日本サイコオンコロジー学会, 広島, Domestic conference
    Public symposium

  • 災害派遣精神医療チームDPAT（Disaster Psychiatric Assistance Team）の災害支援のあり方
    井上 貴裕, Aoyama Shinsuke, Mouri Kentaro, Boku Shuken, Hishimoto Akitoyo, Ichiro Sora
    第117回近畿精神神経学会, Jul. 2015, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • Early life stress attenuates the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter
    Boku Shuken, 戸田 裕之, Hishimoto Akitoyo, Mouri Kentaro, 岡崎 賢志, 廣井 昇, 中川 伸, 久住 一郎
    The International College of Neuropsychopharmacology 2015, Jun. 2015, English, The International College of Neuropsychopharmacology, DUBRIN, Irish, International conference
    Poster presentation

  • 神戸大学医学部附属病院におけるblonanserinの投与状況について
    Shiroiwa Kyoichi, Mouri Kentaro, Sasada Toru, 大塚 郁夫, 大本 暢子, Hishimoto Akitoyo, Ichiro Sora
    第24回日本臨床精神神経薬理学会/第44回日本神経精神薬理学会, Nov. 2014, Japanese, 名古屋, Domestic conference
    Poster presentation

  • Over-expression of Tbx1 or COMT in the mouse hippocampus partially recapitulates behavioral phenotypes of 22q11.2 duplication
    Boku Shuken, Takeshi Izumi, Tomohisa Takahashi, Gina Kang, Hishimoto Akitoyo, Akira Nishi, Shigeki Kato, Kazuto Kobayashi, Kenji Tanigaki, Takeshi Hiramoto, Noboru Hiroi
    The 44th annual meeting of the Society for Neuroscience, Nov. 2014, English, Washington DC, USA, International conference
    Poster presentation

  • 統合失調症とＨＬＡ-ＤＲＢ1*04の遺伝子関連解析
    岡﨑 賢志, Hishimoto Akitoyo, 渡部 雄一郎, ラッタアーパーウォラパット, Mouri Kentaro, Shiroiwa Kyoichi, Sasada Toru, 江口 典臣, 大塚郁夫, 布川 綾子, 澁谷 雅子, 染矢 俊幸, Ichiro Sora
    第36回日本生物学的精神医学会・第57回日本神経化学大会 合同年会, Sep. 2014, Japanese, 日本生物学的精神医学会・日本神経化学大会, 奈良, Domestic conference
    Poster presentation

  • マイクロＲＮＡ138-2遺伝子の稀な変異と統合失調症の関連
    渡部 雄一郎, Hishimoto Akitoyo, 澁谷 雅子, 布川 綾子, 金子 尚史, 井桁 裕文, 江川 純, Mouri Kentaro, Ichiro Sora, 染矢 俊幸
    第36回日本生物学的精神医学会・第57回日本神経化学大会 合同年会, Sep. 2014, Japanese, 日本生物学的精神医学会・日本神経化学大会, 奈良, Domestic conference
    Poster presentation

  • Specific circulating micro-RNA in acute and chronic schizophorenia.
    Hishimoto Akitoyo, W.Ratta-apha, Satoshi Okazaki, Mouri Kentaro, Shiroiwa Kyoichi, Sasada Toru, Ikuo Otsuka, Noriomi Eguchi, Ichiro Sora
    The 16th World Cogress of Psychiatry, Sep. 2014, English, Madrid, Spain, International conference
    Poster presentation

  • 反復性うつ病の入院治療中に多飲水行動を呈した1例
    小林 明美, 石丸 綾子, Sasada Toru, Shiroiwa Kyoichi, Mouri Kentaro, Yamamoto Yasuji, Hishimoto Akitoyo, Tanaka Kiwamu, Ichiro Sora
    第115回近畿精神神経学会, Jul. 2014, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • 総合病院における他科入院患者への精神科リエゾン・コンサルテーションの現状2
    上月 遥, 川添 文子, 磯部 昌憲, 大谷 恭平, 高宮 静男, Shiroiwa Kyoichi, 大塚 郁夫, Hishimoto Akitoyo, Ichiro Sora, 河野 将英, 岡村 健二, 北村 登, 松石 邦隆, 見野 耕一
    第26回日本総合病院精神医学会総会, Nov. 2013, Japanese, 京都, Domestic conference
    Oral presentation

  • 総合病院における他科入院患者への精神科リエゾン・コンサルテーションの現状1
    川添 文子, 上月 遥, 河村 麻美子, 石川 慎一, 大谷 恭平, 高宮 静男, 長谷川 雅史, Shiroiwa Kyoichi, 大塚 郁夫, Hishimoto Akitoyo, Ichiro Sora
    第26回日本総合病院精神医学会総会, Nov. 2013, Japanese, 京都, Domestic conference
    Oral presentation

  • 慢性疼痛へのセロトニン・ノルアドレナリン再取り込み阻害薬デュロキセチンの有効性
    大塚 郁夫, Shiroiwa Kyoichi, Hishimoto Akitoyo, Mouri Kentaro, Sasada Toru, Ichiro Sora
    第23回日本臨床精神神経薬理学会、第43回日本神経精神薬理学会, Oct. 2013, Japanese, 沖縄, Domestic conference
    Oral presentation

  • 統合失調症におけるIL-19遺伝子の発現量的形質遺伝子座(eQTL）におけるハプロタイプ解析
    岡﨑 賢志, 渡部 雄一郎, 大塚 郁夫, 吉田 正邦, Shiroiwa Kyoichi, Mouri Kentaro, ウォラパット ラッタアーパー, イルワン スプリヤント, 江口 典臣, Sasada Toru, 福武 将映, 布川 綾子, 染矢 俊幸, 白川 治, Hishimoto Akitoyo, Ichiro Sora
    第23回日本臨床精神神経薬理学会、第43回日本神経精神薬理学会, Oct. 2013, Japanese, 沖縄, Domestic conference
    Oral presentation

  • Association study of BDNF with completed suicide in the Japanese population.
    Hishimoto Akitoyo, ウォラパット ラッタアッパ, Shiroiwa Kyoichi, Ichiro Sora
    American Society of Human Genetics 2013, Oct. 2013, English, Boston, USA, International conference
    Poster presentation

  • 罪業妄想を呈した産褥期うつ病にquetiapineの高容量投与が奏功した1例
    山木 愛久, Matsui Yusuke, Tamiya Hiroko, Tanaka Kiwamu, Hishimoto Akitoyo
    第112回近畿精神神経学会, Feb. 2013, Japanese, 近畿精神神経学会, 和歌山, Domestic conference
    Oral presentation

  • せん妄が蔓延化し、治療に難渋したアルコール依存症の一例
    長谷川 雅史, 松山 賢一, Shiroiwa Kyoichi, Matsui Yusuke, Hishimoto Akitoyo, Tanaka Kiwamu
    第112回近畿精神神経学会, Feb. 2013, Japanese, 近畿精神神経学会, 和歌山, Domestic conference
    Oral presentation

  • Haplotypes in the expression quantitative trait locus of interleukin-1βgene are associated with schizophrenia
    Yoshida Masaru, Shiroiwa Kyoichi, Mouri Kentaro, Sasada Toru, H. Ishiguro, T.Inada, T.Arinami, O.Shirakawa, Hishimoto Akitoyo
    ASHG(American Society of Human Genetics), Nov. 2012, English, サンフランシスコ, International conference
    Poster presentation

  • Association and Expression analysis of DISC1 gene in schizophrenia and completed suicide
    ウォラパット ラッタアッパ, Mouri Kentaro, Irwan Supriyanto, 福武 将映, Sasada Toru, Shiroiwa Kyoichi, 吉田 正邦, 江口 典臣, 岡崎 賢志, 浅野 水辺, 長崎 靖, Ueno Yasuhiro, 白川 治, Hishimoto Akitoyo
    第34回日本生物学的精神医学会, Sep. 2012, English, 日本生物学的精神医学会, 神戸, Domestic conference
    Poster presentation

  • Association study between the eQTL of theIL1B gene polymorphism and completed suicide
    岡崎 賢志, 吉田 正邦, Shiroiwa Kyoichi, Mouri Kentaro, Woraphat Ratta-apha, Irwan Supriyanto, 江口 典臣, Sasada Toru, 福武 将映, 浅野 水辺, 長崎 靖, Ueno Yasuhiro, 白川 治, Hishimoto Akitoyo
    第34回日本生物学的精神医学会, Sep. 2012, Japanese, 日本生物学的精神医学会, 神戸, Domestic conference
    Poster presentation

  • Haplotaypes in the eQTL of the 1L1B gene are associated wth schizophrenia
    吉田 正邦, Shiroiwa Kyoichi, Mouri Kentaro, Irwan Supriyanto, Woraphat Ratta-apha, 江口 典臣, 岡崎 賢志, Sasada Toru, 福武 将映, 稲田 俊也, 石黒 浩毅, 有波 忠雄, 白川 治, Hishimoto Akitoyo
    第34回日本生物学的精神医学会, Sep. 2012, Japanese, 日本生物学的精神医学会, 神戸, Domestic conference
    Oral presentation

  • 双極I型障害の治療経過中にLamotrigine 投与後、白血球減少および重度貧血をきたした一症例
    荒賀 哲也, Matsui Yusuke, Sasada Toru, Hishimoto Akitoyo, Tanaka Kiwamu
    第111回近畿精神神経学会, Jul. 2012, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • The mental world of autism spectrum disorder through the experience of psychological interview and examination for a case
    Iwamoto Noriko, Matsui Yusuke, A.Tamaoka, E.Honaga, Hishimoto Akitoyo, Tanaka Kiwamu
    iacapap (20th World Congress), Jul. 2012, English, パリ, International conference
    Poster presentation

  • Changes of behavioral problems of children at a children's home in Japan, accompanied by the downsizing.
    Tanaka Kiwamu, 万代 ツルエ, 岩本 直子, Matsui Yusuke, Kitayama Shinji, 補永 栄子, 玉岡 文子, Hishimoto Akitoyo
    The 20th World "INTERNATIONAL ASSOCIATION FOR CHILD AND ADOLESCENT PSYCHIATRY AND ALLIED PROFESSIONS Congress", Jul. 2012, English, INTERNATIONAL ASSOCIATION FOR CHILD AND ADOLESCENT PSYCHIATRY AND ALLIED PROFESSIONS, Paris, In Japan, many of abused and orphaned children are settled at Children's homes (Jidou-yougo-shisetsu) for custody and care. These homes are running on the residential and collective care, and embrace a large number of children. And psychologically traum, International conference
    Poster presentation

  • The Use of Aripiprazole in Serotonin Reuptake Inhibitor Resistant Obsessive-Compulsive Disorder:A 12-month,Prospective,Naturalistic Study
    Hishimoto Akitoyo, Aoyama Shinsuke, Tanaka Kiwamu
    28th CINP World Congress of Neuropsychopharmacology, Jun. 2012, English, The International College Of Neuropsychopharmacology, ストックホルム, International conference
    Poster presentation

  • 気分障害の併存を認めた発作性運動誘発性舞踏アテトーゼの2例
    Sasada Toru, 山田 隆平, Hishimoto Akitoyo, 影山 恭史, Tanaka Kiwamu
    The 108th Annual Meeting of the Japanese Society of Psychiatry and Neurology, May 2012, Japanese, Japanese Society of Psychiatry and Neurology, 札幌, Domestic conference
    Oral presentation

  • せん妄、抑うつ状態を呈し診断、治療に難渋した1例
    荒賀哲也, 松山賢一, Shiroiwa Kyoichi, Hishimoto Akitoyo, Tanaka Kiwamu
    第110回近畿精神神経学会, Feb. 2012, Japanese, 近畿精神神経学会, 京都, Domestic conference
    Oral presentation

  • 一般身体科領域におけmirtazapineの使用実態調査（せん妄症例を中心に）
    Shiroiwa Kyoichi, Shiroiwa Kyoichi, 福武将映, 福武 将映, 大本 暢子, 大本暢子, Hirai Midori, Hirai Midori, Tanaka Kiwamu, Tanaka Kiwamu, Hishimoto Akitoyo, Hishimoto Akitoyo
    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会, Oct. 2011, Japanese, 日本臨床精神神経薬理学会, 東京, Domestic conference
    Oral presentation

  • SSRI/SNRI投与直後に自殺行動/念慮が惹起された5症例の検討
    Sasada Toru, Tamiya Hiroko, Tanaka Kiwamu, Hishimoto Akitoyo
    第21回日本臨床精神神経薬理学会・第41回日本神経精神薬理学会合同年会, Oct. 2011, Japanese, 日本臨床精神神経薬理学会, 東京, Domestic conference
    Oral presentation

  • Polymorphisms in a potential promoter region of the EP1 gene are associated with young suicide completers in the Japanese population
    Hishimoto Akitoyo, Sasada Toru, 福武将映, Shiroiwa Kyoichi, イルワンスプリヤント, 白川治
    WFSBP Congress2011, May 2011, English, 世界生物学的精神医学会, プラハ, チェコ, International conference
    Poster presentation

  • Association of FKBP5 gene haplotypes with completed suicide in Japanese population
    Hishimoto Akitoyo, Sasada Toru, 福武 将映, Shiroiwa Kyoichi, イルワン・スプリヤント, 白川治
    19th European Congress Psychiatry-EPA2011, Mar. 2011, English, European Psychiatric association, ウィーン, オーストリア, International conference
    Oral presentation

  • 抗リン脂質抗体症候群により幻覚妄想をきたした一例
    松山 賢一, 長谷川 典子, Sasada Toru, Tamiya Hiroko, Hishimoto Akitoyo
    第108回近畿精神神経学会, Dec. 2010, Japanese, 近畿精神神経学会, 京都, Domestic conference
    Oral presentation

  • 自殺とBDNF遺伝子多型との相関研究
    吉田 正邦, Shiroiwa Kyoichi, イルワン スプリヤント, 江口 典臣, 福武 将映, Sasada Toru, Hishimoto Akitoyo
    第32回日本生物学的精神医学会, Oct. 2010, Japanese, 日本生物学的精神医学会, 福岡, Domestic conference
    Poster presentation

  • A genetic variation of NOS1is associated with schizophrenia and NOS1 expression in the brain
    Hishimoto Akitoyo, 崔虎星, 西口 直希, 柳 雅也, 福武 将映, Mouri Kentaro, 北村 登, Hashimoto Takeshi, 白川 治
    第32回日本生物学的精神医学会, Oct. 2010, Japanese, 日本生物学的精神医学会, 福岡, Domestic conference
    Oral presentation

  • A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain
    Hishimoto Akitoyo
    Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology 2010 Fall Meeting, Sep. 2010, English, Society of Biological Psychiatry, 台湾, 中国, International conference
    Oral presentation

  • 再生不良性貧血による器質製精神障害を呈した一例
    佐々木 彩, 岡﨑 賢志, Tamiya Hiroko, Hishimoto Akitoyo, Yamamoto Yasuji
    第107回近畿精神神経学会, Aug. 2010, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • リスペリドンにより持続勃起症をきたしアリピプラゾールに薬剤変更を行った統合失調症の二例
    Sasada Toru, 高橋 優, 岡崎 賢志, 福武 将映, Tamiya Hiroko, Hishimoto Akitoyo, Yamamoto Yasuji, 前田 潔
    第106回日本精神神経学会学術総会, May 2010, Japanese, 日本精神神経学会, 広島, Domestic conference
    Oral presentation

  • 意識障害が遷延したと考えられる統合失調症の１例
    Hishimoto Akitoyo, Fukutake Masaaki, Taira Masaru, Tamiya Hiroko, Tanaka Kiwamu, Maeda Kiyoshi
    第104回近畿精神神経学会, Feb. 2009, Japanese, 近畿精神神経学会, 大阪, Domestic conference
    Oral presentation

  • Neurexin3:differential expression in and and association with Alzheimer disease
    Hishimoto Akitoyo
    第１６回精神科遺伝学世界会議, Oct. 2008, English, ＷＣＰＧ, 大阪, International conference
    Oral presentation

  • NRXN1:Novel mRNA Transcripts,Differential Expression in and Association with Alzheimer Disease
    Hishimoto Akitoyo, Maeda Kiyoshi
    2sd WFSBP Asia-Pacific Congress and 30th Annual Meeting of JSBP・第２回アジア・太平洋生物学的精神医学会・第３０回日本生物学的精神医学会, Sep. 2008, English, ＷＦＳＢＰ, 富山, International conference
    Poster presentation

  • ASSOCIATION STUDY BETWEEN THE EPS8 GENE SINGLE NUCLEOTIDE POLYMORPHISMS AND ALCOHOL DEPENDENCE
    Hishimoto Akitoyo
    第43回日本アルコール・薬物医学会、第２０回日本アルコール精神医学会、第１１回ニコチン・薬物依存研究フォーラム、第２８回アルコール医学生物学研究会, Sep. 2008, English, 横浜, International conference
    Oral presentation

■ Research Themes
  • エンドカンナビノイドシステムが介在するうつ病の易罹患性とストレス脆弱性を検証する
    石黒 浩毅, 堀内 泰江, 須原 義智, 菱本 明豊, 山下 純
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 山梨大学, 01 Apr. 2023 - 31 Mar. 2026

  • ポリジェニックリスクスコアを用いた自殺リスクの予測と遺伝学的解明
    菱本 明豊, 秋山 雅人, 曳野 圭子, 大塚 郁夫
    日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 横浜市立大学, 01 Apr. 2021 - 31 Mar. 2024
    自殺についての遺伝学的知見の獲得は、自殺者試料の収集が困難なため世界的に大幅に遅れている。申請者らは国内唯一・世界最大規模の自殺者DNA試料とゲノムワイド関連解析（genome-wide association study; GWAS）データを有し、GWASデータから算出できる個人ごとの自殺ポリジェニックリスクスコア（polygenic risk score; PRS）が、個人の自殺リスクを予測できる可能性を見出した。本研究では、自殺者/自殺未遂者試料の追加GWASを実施し計1,800例の日本人自殺者/自殺未遂者（及び20,000例の非自殺者）のGWASデータを用いることで、①日本人集団において自殺PRSがどの程度の確度で自殺リスクを予測できるか、②アジア人種において各精神疾患や喫煙・飲酒・身長・体重などの様々なヒト表現型がどの程度自殺と遺伝的リスクを共有しているか、の2点を精細に検討する。R3年度末までに約400例の自殺関連試料の追加収集・大部分のGWASデータ取得を実施し、次年度以降の解析に向けて順調に準備を進めることができた。

  • A worldwide study of genetic factor for suicide
    菱本 明豊
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Yokohama City University, 27 Oct. 2020 - 31 Mar. 2024
    世界的に深刻な社会問題である「自殺」には強い遺伝要因が存在するとされる。しかしながら、自殺者試料の収集が極めて困難なことから、相応の規模のゲノム解析の実施が難しく、うつ病や統合失調症など他の精神科領域の表現型に比して、自殺の遺伝学的知見の獲得は大幅に遅れている。申請者らは、世界最大規模の自殺者DNA試料とそれら大半のゲノムワイド関連解析（genome-wide association study; GWAS）データを有し、2019年には世界で初めて「自殺完遂」のポリジェニック効果を報告した。本申請では、そうした経験・強みを生かし、白人自殺GWASを世界で初めて施行するなど自殺研究の世界的中核機関であるコロンビア大学精神科Mannらのグループと組んで、最近立ち上がった世界初の「国際自殺遺伝学コンソーシアム（以下、自殺コンソーシアム）」の拡張（特にアジア人コホートのサンプル増加への貢献）を目指す。自殺は例えば欧米とアジアでは、企図手段や並存精神疾患の割合などが大きく異なることも報告されている。自殺コンソーシアムの発展によって、自殺GWASのサンプルサイズ増加と多人種のデータ取得が可能となり、自殺リスクについての人類共通の遺伝因子の発見や、人種間の遺伝因子の差異、自殺と他のヒト表現型との遺伝的関連の精細なマッピングなど、これまで困難とされていた自殺の遺伝要因についての遺伝統計学的知見を産出中である。特に東アジア人集団の自殺行動GWASのスケールアップに注力している。

  • Boku Shuken
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), 神戸大学, 01 Apr. 2018 - 31 Mar. 2021
    First, we performed the microarray analysis to identify miRNAs altered by early life stress in rats serum and hippocampus and identified a lot of such miRNAs. Next, we examined the levels of these miRNAs in serum of human subjects with mood disorders and showed that the levels of some miRNAs are altered in serum of human subjects compared with healthy controls. These miRNAs are expected to work as a biomarker of mood disorders.
    Competitive research funding

  • Mouri Kentaro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2018 - 31 Mar. 2021
    For the students with suicide high-risk and non-suicidal healthy students, gDNA from peripheral blood, MWAS-based telomere length by using Infinium Human Methylation 450K BeadChip, suicide-attempt history, and various suicide-related clinical scales such as HAMD17, SRS18 and C-SSRS were obtained. We found shorter MWAS-based telomeres in young suicidal subjects compared to the healthy group. We also identified the association between suicide risk in women after middle age and rs12415800 related to SIRT1 gene which is well-known to be related to telomere dynamics.
    Competitive research funding

  • Hishimoto Akitoyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2017 - 31 Mar. 2020, Principal investigator
    Our GWAS identified significant polygenicity for Japanese suicide. We found aberrant changes of various telomere-related factors (telomere length, DNA-methylation aging, methylation status of TERT promoter, mtDNAcn, SIRT1 SNP, and chemokine levels) in suicides, which may contribute to the establishment of "biomarker for suicide risk". We observed that the direction of the relationships between the oxy-Hb changes of the left frontopolar region and mtDNAcn was opposite in bipolar disorder (BD) and major depressive disorder (MDD), which may suggest the potential Potential as Diagnostic Marker for Distinguishing BD From MDD. By using mouse neural stem cells and stress-model rats, we indicated that stress can reduce TERT and some anti-depressant drugs may rescue stress-induced TERT reduction.
    Competitive research funding

  • IZUMI TAKESHI, KOBAYASHI kazuto, NAKAGAWA shin, BOKU shunken, HISHIMOTO akitoyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), 01 Apr. 2016 - 31 Mar. 2019
    We investigated the effect of repeated restraint stress (RS) (3 hr/day) on depression-like behaviors using forced swimming test (FST) in rats. Moreover, we assessed the effect of repeated RS on the serum corticosterone by EIA, and on the GR and FKBP5 (inhibitory factor of GR) in the mPFC, hippocampus and amygdala by Western blotting. We performed above these assessments 2 weeks after repeated stress. Seven times RS significantly increased depression-like behavior, and it was antagonized by previous 14 days repeated administration of escitalopram (10 mg/kg), a SSRI. Serum corticosterone was increased by seven times RS. Protein level of GR was not changed, but that of FKBP5 was increased in the amygdala by seven times RS. Hyperactivity of HPA axis and increased FKBP5 in the amygdala may be related to RS-induced depression-like behavior. Besides, FKBP5 was significantly decreased in the frontal cortex of the suicide completer’s postmortem brain sample compared to normal control.

  • Sora Ichiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2019
    To investigate the pathogenesis and new effective treatments of attention deficit hyperactivity disorder (AD/HD), we analysed telencephalon organoids including cerebral cortex-like structures. We induced telencephalon organoids from iPS cells derived from control and AD/HD individuals by SFEBq method (Kadoshima 2013, Eguchi 2018). The analysis of cerebral cortex-like structures revealed AD/HD showed thinner cortical plate, the layer of neuron than controls.Previous study using MRI reported AD/HD showed delayed maturation of cerebral cortex (Shaw 2007).Our result indicates early development of cerebral cortex is delayed in AD/HD, that might be consistent with previous report using MRI which reported AD/HD showed delayed maturation of cerebral cortex (Shaw 2007). It suggests that our telencepharon organoids might be available as biological model of AD/HD. Further investigation is needed to establish the model.
    Competitive research funding

  • Sora Ichiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research, Grant-in-Aid for Challenging Exploratory Research, Kobe University, 01 Apr. 2016 - 31 Mar. 2018
    Factors related to the differentiation and induction of the nigrostriatal dopamine neuron (A9) and the mesolimbic dopamine neuron (A10) were analized with SDIA（Stromal cell Derived Inducing Activity）method. As a result of examining differentiation and induction to dopaminergic neurons with SDIA method in various periods, it was found that Otx 2 and Sox 6 are expressed in about 3 weeks. Cells in which Otx 2 and Sox 6 are overlappingly expressed were not observed. Culture with dopamine neurons by SDIA method was thought to differentiate into and induce the nigrostriatal dopamine neuron (A9) and the mesolimbic dopamine neuron (A10) in about 3 weeks.
    Competitive research funding

  • Boku Shuken, Murai Toshiya, Furuyashiki Tomoyuki, Izumi Takeshi, Toda Hiroyuki, Hiroi Noboru
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2015 - 31 Mar. 2018
    1. We showed that some miRNA-related molecules may be involved in early life stress-induced increase of DNA methylation in adult hippocampal neural stem cell. 2. We showed that early life stress remarkably increased DNA methylation of gene region X with genome-wide analysis of DNA methylation. In addition, we showed that DNA methylation of gene region X may be associated with stress sensibility with behavioral analysis. 3. We are showing that DNA methylation may be associated with the assessment scale for early life stress in human subjects.
    Competitive research funding

  • Hishimoto Akitoyo, Watanabe Masahiko, Kusumi Ichiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2014 - 31 Mar. 2017, Principal investigator
    The genetic research of complete suicide is behind other mental problems because it is extremely difficult to obtain tissue samples of completed suicide. Under the difficult situation, we performed a GWAS using 500 samples of suicide completers, and found two candidates of suicide-related gene; PTCHD3 and RAB18. Here, we investigated the function of these candidate genes in chronic stressed rats and mouse neural stem cells. Stressed rats showed higher PTCHD3 expression in prefrontal cortex and hippocampus, and lower RAB18 expression in amygdala. In mouse neural stem cells with RAB18 knockdown, cell proliferation and survival were significantly increased compared to controls. Our results suggest aberrant expression of these suicide-related genes may be associated with brain abnormalities in stress conditons. Replication GWAS of suicide completers and further in vivo and in vitro analyses are needed in future studies.
    Competitive research funding

  • （AMED）脳脊髄液サンプルを用いたうつ病バイオマーカーの開発/うつ病患者の臨床評価と脳脊髄液サンプル収集
    菱本 明豊
    国立研究開発法人国立精神・神経医療研究センター, 長寿・障害総合研究事業, 2017, Principal investigator
    Competitive research funding

  • （AMED）脳脊髄液サンプルを用いたうつ病バイオマーカーの開発/被験者の精神医学的評価と脳脊髄液サンプル収集
    菱本 明豊
    長寿科学研究開発事業, 2016, Principal investigator
    Competitive research funding

  • （AMED）血液バイオマーカーを用いたうつ病と双極性障害の鑑別診断法の開発に関する研究
    菱本 明豊
    国立研究開発法人日本医療研究開発機構, 難治性疾患実用化研究事業, 2016, Principal investigator
    Competitive research funding

  • HISHIMOTO Akitoyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 2011 - 2012
    We explored the differential expression of stress-related genes in the postmortem brains of suicide victims and conducted genetic associations of the candidate genes of suicide and schizophrenia. Although we found no evidence of expression difference of stress-related genes such as CRH, we found significant reduced expression of BDNF and DISC1 immunoreactivity in the suicide victims. In addition, we found significant genetic association of DISC1 and EP1 with suicide and schizophrenia. Our findings suggest that suicidal behavior is involved in the genetic vulnerability and that certain polymorphisms might be useful for a biomarker of suicidal behavior.

  • SASADA Toru, HISHIMOTO Akitoyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 2010 - 2012
    Since it was expected that heterogeneity in "depressed state" was large, first of all, we focused on the schizophrenia group. Several literatures reported there was an association between low cholesterolemia and impulsivity.In our study, between suicide and non-suicide attempt group, a significant difference was notseen by the serum total cholesterol level and positive symptoms (conceptual disorganization, hostility and excitement), negative symptoms,and anxiety and depression of PANSS. On the other hand, in the suicide attempt group, the male's serum total cholesterol level was low as compared with the woman, and the psychiatric manifestation suited the high tendency generally. We are going to continue the analysis to multi-biomarker searchby means of metabolome analys and examine about the possibility of early picking up ofsuicide risk, and suicide re-plan prevention in psychiatric disorder patients.

  • KONISHI Junya, FUJII Masahiko, SUGIMURA Kazuro, HISHIMOTO Akitoyo, OHNO Yoshiharu
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 2010 - 2012
    Abnormality of the synaptic transmission in nerve cells is pointed out than cerebrocortical abnormality for schizophrenia. Therefore it wasdifficult to catch clinical condition by the normal radiographic studies. We triedanalysis with the high-angular diffusion tensor imaging. As a result, we could depict white matter abnormality in right frontal lobe, and a utility of the high-angular diffusion tensor imaging for mental disorder such as schizophrenia was suggested.
    Competitive research funding

  • 菱本 明豊
    学術研究助成基金助成金／若手研究(B), 2011, Principal investigator
    Competitive research funding

  • HISHIMOTO Akitoyo
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 2009 - 2010, Principal investigator
    We explored a positive association of suicidal behavior with certain haplotypes of FKBP5 gene which regulates the hypothalamo-pituitary-adrenal axis in stress response. We additionally explored associations of suicidal behavior with polymorphisms of ALDH2 and NOS1 genes. We also found a positive association of schizophrenia with polymorphisms of NOS1 gene. Our findings suggest that suicidal behavior is involved in the genetic vulnerability and that certain polymorphisms might be useful for a biomarker of suicidal behavior.
    Competitive research funding

  • 笹田 徹
    科学研究費補助金／基盤研究(C), 2010
    Competitive research funding

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