Updated on 2022/04/04

写真a

 
INADA Toshiya
 
Organization
Graduate School of Medicine Department of Clinical Psychiatry Endowed Chair Designated professor
Title
Designated professor
Contact information
メールアドレス
Profile
Graduated from Keio University School of Medicine in Tokyo, Japan, in 1984. After the completion of his internship at Keio University Hospital (1984-1985), he worked as a clinical psychiatrist at Sakuragaoka Memorial Hospital in Tokyo (1985-1989). From 1989 to 1991, he had been working as a postdoctoral fellow in the Department of Pharmacology and Toxicology at the University of Mississippi Medical Center. After he returned to Japan, he had been working as Associate Director at the National Institute of Mental Health, National Center of Neurology and Psychiatry (1994-2002), as Associate Professor, Department of Psychiatry and Psychobiology, Nagoya University, Graduate School of Medicine (2002-2005), as Professor at the Teikyo University School of Medicine and as Head at the Department of Psychiatry, Teikyo University Chiba Medical Center (2005-2007), as Vice President (2008-2015), and President (2015-2016), Seiwa Hospital, Institute of Neuropsychiatry, Tokyo. He returned to Nagoya University, Graduate School of Medicine in June 2016 and he has been working as Associate Professor, Department of Psychiatry and Psychobiology since then. He received the Rafaelsen Fellowship Award from the 19th Collegium Internationale Neuro-Psychopharmacologicum (CINP) meeting in 1994 and the Paul Janssen Research Encouragement Award from the 18th Japanese Society of Clinical Neuropsychopharmacology meeting in 2008. His major research topics include Psychotropics, Clinical psychopharmacology, Molecular Psychopharmacology, Extrapyramidal side effects of antipsychotics. He has been an opinion leader on these fields.
He developed a new rating scale for drug-induced extrapyramidal symptoms scale (DIEPSS) in 1994 when he had been working as visiting scientist at McLean Hospital, Department of Psychiatry, Harvard Medical School, Boston. The DIEPSS is now translated into more than 22 languages and is widely used in the clinical trials of the psychotropic agents in the treatment of psychoses conducted in Asia. Current his academic activity includes: Japanese Society of Psychiatric Rating Scales (President, Representative trustee), Japanese Society of Psychiatric and Behavioral Genetics (Trustee), Japanese Society of Neuropsychopharmacology (Councilor), Japanese Society of Geriatric Psychiatry (Councilor), Japanese Society of Biological Psychiatry (Councilor), Japanese Society of Clinical Neuropsychopharmacology (Councilor), Japanese Society of Schizophrenia (Councilor), Japanese Society of Depression (Councilor).

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Degree 1

  1. M.D., Ph.D. ( 1993.7   Keio University ) 

Research Interests 30

  1. 気分障害

  2. 抗うつ薬

  3. 総合失調症

  4. 抗精神病薬

  5. 思考障害

  6. 幻覚妄想

  7. 奇異な行動

  8. マイクロサテライト

  9. ハロペリドール

  10. ハプロタイプ

  11. ドパミントランスポーター

  12. ドパミン

  13. クロモグラニン

  14. MTHFR

  15. homocystein

  16. Hardy-Weinbergの平衡法則

  17. DRD4

  18. DRD3

  19. DRD2

  20. D6S287

  21. CYP2D6

  22. 第5番染色体

  23. depression

  24. 陰性症状

  25. 関連研究

  26. 錐体外路症状

  27. 遺伝子多型

  28. 遺伝子

  29. 遅発性ジスキネジア

  30. 血中濃度

Research Areas 1

  1. Life Science / Psychiatry

Research History 5

  1. Nagoya University   Graduate School of Medicine Endowed Chairs Department of Mental Health   Designated professor

    2021.4

  2. Nagoya University Graduate School of Medicine   Professor

    2021.4

  3. Nagoya University Graduate School of Medicine   Psychiatry and Psychobiology   Associate professor

    2016.6 - 2021.3

  4. Seiwa Hospital, Institute of Neuropsychiatry   Psychiatry   President

    2015 - 2016

  5. Institute of Neuropsychiatry   Vice president

    2008 - 2016

Professional Memberships 1

  1. 公益社団法人日本精神神経学会

Awards 2

  1. 日本臨床精神神経薬理学会研究論文学会奨励賞

    2008.10   第18回日本臨床精神神経薬理学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  2. Rafaelsen fellowship Award

    1994.6   第19回国際神経精神薬理学会  

    稲田俊也

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    Award type:Award from international society, conference, symposium, etc.  Country:United States

 

Papers 50

  1. Network Analysis-Based Disentanglement of the Symptom Heterogeneity in Asian Patients with Schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics

    Choi Joonho, Yoon Hyung-Jun, Park Jae Hong, Nakagami Yukako, Kubota Chika, Inada Toshiya, Kato Takahiro A., Yang Shu-Yu, Lin Sih-Ku, Chong Mian-Yoon, Avasthi Ajit, Grover Sandeep, Kallivayalil Roy Abraham, Tanra Andi Jaylangkara, Chee Kok Yoon, Xiang Yu-Tao, Sim Kang, Javed Afzal, Tan Chay Hoon, Sartorius Norman, Kanba Shigenobu, Shinfuku Naotaka, Park Yong Chon, Park Seon-Cheol

    JOURNAL OF PERSONALIZED MEDICINE   Vol. 12 ( 1 )   2022.1

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    Language:Japanese   Publisher:Journal of Personalized Medicine  

    The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis.

    DOI: 10.3390/jpm12010033

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  2. The trigger and data acquisition system of the FASER experiment

    Abreu H., Mansour E. Amin, Antel C., Ariga A., Ariga T., Bernlochner F., Boeckh T., Boyd J., Brenner L., Cadoux F., Casper D. W., Cavanagh C., Chen X., Coccaro A., Debieux S., Dmitrievsky S., Dozen C., Favre Y., Fellers D., Feng J. L., Ferrere D., Gamberini E., Galantay E. K., Gibson S., Gonzalez-Sevilla S., Gornushkin Y., Gwilliam C., Hsu S-C, Hu Z., Iacobucci G., Inada T., Jakobsen S., Johnson E., Kajomovitz E., Kling F., Kose U., Kuehn S., Lefebvre H., Levinson L., Li K., Liu J., Magliocca C., McFayden J., Milanesio M., Meehan S., Mladenov D., Moretti T., Munker M., Nakamura M., Nakano T., Nessi M., Neuhaus F., Nevay L., Otono H., Pandini C., Pang H., Paolozzi L., Petersen B., Pietropaolo F., Prim M., Queitsch-Maitland M., Resnati F., Rizzi C., Rokujo H., Ruiz-Cholis E., Salfeld-Nebgen J., Sato O., Scampoli P., Schmieden K., Schott M., Sfyrla A., Shively S., Sipos R., Spencer J., Takubo Y., Tarannum N., Theiner O., Torrence E., Tufanli S., Vasina S., Vormwald B., Wang D.

    JOURNAL OF INSTRUMENTATION   Vol. 16 ( 12 )   2021.12

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    Language:Japanese   Publisher:Journal of Instrumentation  

    The FASER experiment is a new small and inexpensive experiment that is placed 480 meters downstream of the ATLAS experiment at the CERN LHC. FASER is designed to capture decays of new long-lived particles, produced outside of the ATLAS detector acceptance. These rare particles can decay in the FASER detector together with about 500-1000 Hz of other particles originating from the ATLAS interaction point. A very high efficiency trigger and data acquisition system is required to ensure that the physics events of interest will be recorded. This paper describes the trigger and data acquisition system of the FASER experiment and presents performance results of the system acquired during initial commissioning.

    DOI: 10.1088/1748-0221/16/12/P12028

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  3. First neutrino interaction candidates at the LHC

    Abreu Henso, Afik Yoav, Antel Claire, Arakawa Jason, Ariga Akitaka, Ariga Tomoko, Bernlochner Florian, Boeckh Tobias, Boyd Jamie, Brenner Lydia, Cadoux Franck, Casper David W., Cavanagh Charlotte, Cerutti Francesco, Chen Xin, Coccaro Andrea, D'Onofrio Monica, Dozen Candan, Favre Yannick, Fellers Deion, Feng Jonathan L., Ferrere Didier, Gibson Stephen, Gonzalez-Sevilla Sergio, Gwilliam Carl, Hsu Shih-Chieh, Hu Zhen, Iacobucci Giuseppe, Inada Tomohiro, Ismail Ahmed, Jakobsen Sune, Kajomovitz Enrique, Kling Felix, Kose Umut, Kuehn Susanne, Lefebvre Helena, Levinson Lorne, Li Ke, Liu Jinfeng, Magliocca Chiara, McFayden Josh, Meehan Sam, Mladenov Dimitar, Nakamura Mitsuhiro, Nakano Toshiyuki, Nessi Marzio, Neuhaus Friedemann, Nevay Laurie, Otono Hidetoshi, Pandini Carlo, Pang Hao, Paolozzi Lorenzo, Petersen Brian, Pietropaolo Francesco, Prim Markus, Queitsch-Maitland Michaela, Resnati Filippo, Rokujo Hiroki, Sabate-Gilarte Marta, Salfeld-Nebgen Jakob, Sato Osamu, Scampoli Paola, Schmieden Kristof, Schott Matthias, Sfyrla Anna, Shively Savannah, Spencer John, Takubo Yosuke, Theiner Ondrej, Torrence Eric, Trojanowski Sebastian, Tufanli Serhan, Vormwald Benedikt, Wang Di, Zhang Gang

    PHYSICAL REVIEW D   Vol. 104 ( 9 )   2021.11

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    Language:Japanese   Publisher:Physical Review D  

    FASERν at the CERN Large Hadron Collider (LHC) is designed to directly detect collider neutrinos for the first time and study their cross sections at TeV energies, where no such measurements currently exist. In 2018, a pilot detector employing emulsion films was installed in the far-forward region of ATLAS, 480 m from the interaction point, and collected 12.2 fb-1 of proton-proton collision data at a center-of-mass energy of 13 TeV. We describe the analysis of this pilot run data and the observation of the first neutrino interaction candidates at the LHC. This milestone paves the way for high-energy neutrino measurements at current and future colliders.

    DOI: 10.1103/PhysRevD.104.L091101

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  4. A Call for a Rational Polypharmacy Policy: International Insights From Psychiatrists

    Nakagami Yukako, Hayakawa Kohei, Horinouchi Toru, Pereira-Sanchez Victor, Tan Marcus P. J., Park Seon-Cheol, Park Yong Chon, Moon Seok Woo, Choi Tae Young, Avasthi Ajit, Grover Sandeep, Kallivayalil Roy Abraham, Rai Yugesh, Shalbafan Mohammadreza, Chongsuksiri Pavita, Udomratn Pichet, Kathriarachchi Samudra T., Xiang Yu-Tao, Sim Kang, Javed Afzal, Chong Mian-Yoon, Tan Chay-Hoon, Lin Shih-Ku, Inada Toshiya, Murai Toshiya, Kanba Shigenobu, Sartorius Norman, Shinfuku Naotaka, Kato Takahiro A.

    PSYCHIATRY INVESTIGATION   Vol. 18 ( 11 ) page: 1058 - 1067   2021.11

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    Language:Japanese   Publisher:Psychiatry Investigation  

    Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate. Methods We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide. Results The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively). Conclusion Policy on polypharmacy may influence psychiatrists’ decision-making. Thus, policies considering rational polypharmacy should be established.

    DOI: 10.30773/pi.2021.0169

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  5. Factors associated with the severity of delirium. International journal

    Masako Tachibana, Toshiya Inada, Masaru Ichida, Shihori Kojima, Mayumi Shioya, Kazuki Wakayama, Norio Ozaki

    Human psychopharmacology   Vol. 36 ( 5 ) page: e2787   2021.9

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:WILEY  

    BACKGROUND: Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors. METHODS: A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale-revised-98 (DRS-R-98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium. RESULTS: Intensive care unit admission (p = 0.003), use of benzodiazepines (p = 0.01), dementia (p = 0.02), and older age (p = 0.045) were all positively associated the severity of delirium, while use of β-blockers (p = 0.001) was negatively associated with the severity of delirium. CONCLUSIONS: Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.

    DOI: 10.1002/hup.2787

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  6. Genome wide study of tardive dyskinesia in schizophrenia

    Lim Keane, Lam Max, Zai Clement, Tay Jenny, Karlsson Nina, Deshpande Smita N., Thelma B. K., Ozaki Norio, Inada Toshiya, Sim Kang, Chong Siow-Ann, Lencz Todd, Liu Jianjun, Lee Jimmy

    TRANSLATIONAL PSYCHIATRY   Vol. 11 ( 1 ) page: 351   2021.6

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    Language:Japanese   Publisher:Translational Psychiatry  

    Tardive dyskinesia (TD) is a severe condition characterized by repetitive involuntary movement of orofacial regions and extremities. Patients treated with antipsychotics typically present with TD symptomatology. Here, we conducted the largest GWAS of TD to date, by meta-analyzing samples of East-Asian, European, and African American ancestry, followed by analyses of biological pathways and polygenic risk with related phenotypes. We identified a novel locus and three suggestive loci, implicating immune-related pathways. Through integrating trans-ethnic fine mapping, we identified putative credible causal variants for three of the loci. Post-hoc analysis revealed that SNPs harbored in TNFRSF1B and CALCOCO1 independently conferred three-fold increase in TD risk, beyond clinical risk factors like Age of onset and Duration of illness to schizophrenia. Further work is necessary to replicate loci that are reported in the study and evaluate the polygenic architecture underlying TD.

    DOI: 10.1038/s41398-021-01471-y

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  7. The ubiquitination-deubiquitination cycle on the ribosomal protein eS7A is crucial for efficient translation

    Takehara Yuka, Yashiroda Hideki, Matsuo Yoshitaka, Zhao Xian, Kamigaki Akane, Matsuzaki Tetsuo, Kosako Hidetaka, Inada Toshifumi, Murata Shigeo

    ISCIENCE   Vol. 24 ( 3 )   2021.3

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  8. Students' emotions, teachers' first language (L1)/target language (tl) use and english proficiency improvement

    Inada T., Inada T.

    International Medical Journal   Vol. 28 ( 2 ) page: 163 - 166   2021

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    Language:Japanese   Publisher:International Medical Journal  

    Objective: The aim of this study was to investigate whether a teacher's language choice in task-based English communicative classes could affect students' enjoyment, anxiety, and English proficiency improvement. Design: Two groups: English-only (EE group) and with some legitimate Japanese support (EJ group) were created and their enjoyment, anxiety and English proficiency improvement were compared. Methods: The questionnaire ninety-two students took twice (at the entry and at the end) was used to measure the levels of students enjoyment and anxiety. The change between the term tests' scores was used to measure the levels of students' English proficiency improvement. Results: The levels of enjoyment significantly increased in the EE group, and each student's score from the midterm to the final exam significantly increased in the EJ group. Conclusion: Japanese support instruction might contribute to English proficiency improvement of basic to low intermedi-ate-level students.

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  9. Teachers' First Language (L1)/Target Language (TL) Use, Students’ Emotions and English Proficiency Improvement. Reviewed

    稲田 俊也

    International Medical Journal   Vol. 28 (2)   page: 163 - 166   2021

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  10. Design and production of segment mirrors for the Large-Sized Telescopes of the Cherenkov Telescope Array

    Inada T., Fukami S., Noda K., Chikawa M., Kagaya M., Katagiri H., Mazin D., Obara K., Okumura A., Saito T., Teshima M., Yamamoto T., Yoshida T., Vovk I.

    Proceedings of SPIE - The International Society for Optical Engineering   Vol. 11451   2020

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    Language:Japanese   Publisher:Proceedings of SPIE - The International Society for Optical Engineering  

    CTA (Cherenkov Telescope Array) is a project for the next generation of the ground-based gamma-ray observatory. CTA will cover a wide energy range, 20 GeV and 300 TeV, by 3 types of the telescopes whose diameters are different. The Large-Sized Telescopes (LSTs) of the CTA are designed to cover the lowest energy range. We are working on mirrors for 4 LSTs which will be built at La Palma, Spain. The parabolic primary mirror of CTA-LST is 23 m diameter and its focal length is 28 m. The primary mirror consists of 198 segmented mirrors. Total effective reflective area is about 370 m2. Each mirror has a hexagonal shape of 1.51 m side-by-side size. It has a sandwich structure which consists of aluminum honeycomb (60 mm thickness) and two glass surfaces (2.7 mm) and the total weight is about 47 kg. We used a sputtering deposition technique to coat in the surface with 5 layer. The coated layers protect the surface for long operation such as 10 years at outside with a reflectance degradation of less than 1 % a year. The reflectance of the mirror reaches about 92 % at 400 nm and its resolution is 0.5 mrad in diameter that contains the 80 % light reflected by the mirror. The production technique based on cold slumping gave us the stable its production. We report on the design of the segment mirror and the production of about 950 hexagonal 2 m2 mirrors to achieve the parabolic shape of the optical system for 4 LSTs.

    DOI: 10.1117/12.2562111

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  11. Is frequent use of English outside class related to the degree of Foreign language classroom anxiety?

    Inada T., Inada T.

    International Medical Journal   Vol. 26 ( 6 ) page: 505 - 509   2019.12

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    Language:Japanese   Publisher:International Medical Journal  

    Objective: Among researchers, there is some controversy about the most effective way of learning English from the viewpoint of the affective domain. The purpose of the present study was to investigate the potential relationship between students frequent use of English outside class and the degree of foreign language classroom anxiety (FLCA). Methods: A questionnaire including 45 five-point Likert scale items on the relationship between Japanese use and FLCA in task-based English classes was administered to 257 Japanese students attending a language-oriented university. Results: Increased use of English outside class was significantly related to lower FLCA, higher risk-taking, less preference to use Japanese, and higher enthusiasm. Additionally, lower FLCA was related to longer hours of English study (grammar, reading, listening and/or writing) at home and study abroad experience. Conclusions: The present results suggest that frequent use of English out of class with high enthusiasm may be useful for Japanese college students to have lower FLCA.

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  12. Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

    Watanabe H., Ozasa N., Morimoto T., Shiomi H., Bingyuan B., Suwa S., Nakagawa Y., Izumi C., Kadota K., Ikeguchi S., Hibi K., Furukawa Y., Kaji S., Suzuki T., Akao M., Inada T., Hayashi Y., Nanasato M., Okutsu M., Kametani R., Sone T., Sugimura Y., Kawai K., Abe M., Kaneko H., Nakamura S., Kimura T.

    PLoS ONE   Vol. 13 ( 8 )   2018.8

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    Background Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). Methods and results In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) 40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3 ±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06) Conclusion Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. Trial registration CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

    DOI: 10.1371/journal.pone.0199347

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  13. Prediction of thrombotic and bleeding events after percutaneous coronary intervention: CREDO-Kyoto thrombotic and bleeding risk scores

    Natsuaki M., Morimoto T., Yamaji K., Watanabe H., Yoshikawa Y., Shiomi H., Nakagawa Y., Furukawa Y., Kadota K., Ando K., Akasaka T., Hanaoka K.I., Kozuma K., Tanabe K., Morino Y., Muramatsu T., Kimura T., Matsuda M., Mitsuoka H., Fujiwara H., Takatsu Y., Taniguchi R., Nohara R., Murakami T., Takeda T., Nobuyoshi M., Iwabuchi M., Tatami R., Shirotani M., Kita T., Ehara N., Kato H., Eizawa H., Ishii K., Tanaka M., Lee J.D., Nakano A., Takizawa A., Takahashi M., Horie M., Takashima H., Tamura T., Takahashi M., Tei C., Hamasaki S., Kambara H., Doi O., Kaburagi S., Mitsudo K., Miki S., Mizoguchi T., Ogawa H., Sugiyama S., Hattori R., Aoyama T., Araki M., Urasawa K., Koshida R., Hirokami M., Yamashita T., Nagashima M., Nozaki Y., Igarashi K., Furuya J., Yoshimachi F., Sakamoto Y., Nakamura A., Fukui S., Itoh T., Inoue N., Takizawa K., Katahira Y., Nakano T., Kato A., Yamamoto Y., Tada T., Takeishi Y., Nakazato K., Kijima M., Ujiie Y., Komatsu N., Ishida G., Ota Y., Honda A., Muto M., Ishikawa T., Komatsu T., Shimizu M., Uehara Y., Ogawa T., Ogawa K., Daida H., Miyauchi K., Sumiyoshi T., Asano R., Yamasaki M., Yajima J., Funada R., Taniwaki M., Ogawa M.

    Journal of the American Heart Association   Vol. 7 ( 11 )   2018.6

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    Language:Japanese   Publisher:Journal of the American Heart Association  

    Background--Prediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention. Methods and Results--We developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) and NEXT (Nobori Biolimus-Eluting Versus Xience/Promus Everolimus-Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3-year incidence of thrombotic events than a score that was intermediate (2-3, n=1178) or low (0-1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P < 0.0001). A high bleeding risk score (≥3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1-2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P < 0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%). Conclusions--CREDO-Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.

    DOI: 10.1161/JAHA.118.008708

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  14. Drug-induced akathisia

    Inada T.

    Brain and Nerve   Vol. 69 ( 12 ) page: 1417 - 1424   2017.12

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    Language:Japanese   Publisher:Brain and Nerve  

    Akathisia consists of subjective inner restlessness, such as awareness of the inability to remain seated, restless legs, fidgetiness, and the desire to move constantly, and of objective increased motor phenomena, such as body rocking, shifting from foot to foot, stamping in place, crossing and uncrossing legs, pacing around. Although the broad definition of akathisia includes the inner and motor restlessness observed in patients with idiopathic Parkinson's disease, post-encephalitic parkinsonism, and restless legs syndrome, here we exclusively focus on the narrow definition of antipsychotic-induced akathisia. The most reliable treatment for acute akathisia is the reduction or the withdrawal of antipsychotic medication. However, this is often not possible because it may worsen the patients' mental condition. Various pharmacological agents have been used for the treatment of this condition. These include anticholinergic agents (e.g., biperiden and trihexyphenidyl), benzodiazepines, beta-adrenoceptor blockers (e.g., propranolol), and serotonin 2A receptor antagonists (e.g., mianserin, cyproheptadine, and mirtazapine).

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  15. The ReACT Trial: Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial

    Shiomi H., Morimoto T., Kitaguchi S., Nakagawa Y., Ishii K., Haruna Y., Takamisawa I., Motooka M., Nakao K., Matsuda S., Mimoto S., Aoyama Y., Takeda T., Murata K., Akao M., Inada T., Eizawa H., Hyakuna E., Awano K., Shirotani M., Furukawa Y., Kadota K., Miyauchi K., Tanaka M., Noguchi Y., Nakamura S., Yasuda S., Miyazaki S., Daida H., Kimura K., Ikari Y., Hirayama H., Sumiyoshi T., Kimura T., Kimura K., Hibi K., Kataoka K., Miyazaki S., Yasuda S., Ishii M., Momona E., Nakamura S., Takizawa A., Nanasato M.

    JACC: Cardiovascular Interventions   Vol. 10 ( 2 ) page: 109 - 117   2017.1

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    Objectives The purpose of this study was to evaluate long-term clinical impact of routine follow-up coronary angiography (FUCAG) after percutaneous coronary intervention (PCI) in daily clinical practice in Japan. Background The long-term clinical impact of routine FUCAG after PCI in real-world clinical practice has not been evaluated adequately. Methods In this prospective, multicenter, open-label, randomized trial, patients who underwent successful PCI were randomly assigned to routine angiographic follow-up (AF) group, in which patients were to receive FUCAG at 8 to 12 months after PCI, or clinical follow-up alone (CF) group. The primary endpoint was defined as a composite of death, myocardial infarction, stroke, emergency hospitalization for acute coronary syndrome, or hospitalization for heart failure over a minimum of 1.5 years follow-up. Results Between May 2010 and July 2014, 700 patients were enrolled in the trial among 22 participating centers and were randomly assigned to the AF group (n = 349) or the CF group (n = 351). During a median of 4.6 years of follow-up (interquartile range [IQR]: 3.1 to 5.2 years), the cumulative 5-year incidence of the primary endpoint was 22.4% in the AF group and 24.7% in the CF group (hazard ratio: 0.94; 95% confidence interval: 0.67 to 1.31; p = 0.70). Any coronary revascularization within the first year was more frequently performed in AF group than in CF group (12.8% vs. 3.8%; log-rank p < 0.001), although the difference between the 2 groups attenuated over time with a similar cumulative 5-year incidence (19.6% vs. 18.1%; log-rank p = 0.92). Conclusions No clinical benefits were observed for routine FUCAG after PCI and early coronary revascularization rates were increased within routine FUCAG strategy in the current trial. (Randomized Evaluation of Routine Follow-up Coronary Angiography After Percutaneous Coronary Intervention Trial [ReACT]; NCT01123291)

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  16. Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial)

    Tanigawa Nobuhiko, Yamaue Hiroki, Ohyama Shigekazu, Sakuramoto Shinichi, Inada Takao, Kodera Yasuhiro, Kitagawa Yuko, Omura Kenji, Terashima Masanori, Sakata Yuh, Nashimoto Atsushi, Yamaguchi Toshiharu, Chin Keisho, Nomura Eiji, Lee San-Woong, Takeuchi Masahiro, Fujii Masashi, Nakajima Toshifusa

    GASTRIC CANCER   Vol. 19 ( 2 ) page: 350 - 360   2016.4

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    Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755

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  17. Autistic traits as predictors of persistent depression. International journal

    Kanako Ishizuka, Tomomi Ishiguro, Norio Nomura, Toshiya Inada

    European archives of psychiatry and clinical neuroscience   Vol. 272 ( 2 ) page: 211 - 216   2022.3

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    Persistent depression has been suggested to be associated with autistic traits in people of working age. This study aimed to clarify which autistic characteristics at the initial visit were associated with persistent depression at the 12 week follow-up in a primary care setting. Newly depressed outpatients aged 24-59 years with no history of autism were asked to complete the 50-item autism spectrum quotient (AQ) and the Beck depression inventory (BDI) at baseline and 12 week follow-up (N = 123, males: 48%, age: 37.7 ± 9.15 years). Nearly 40% of participants had an AQ score ≥ 26. Significant differences were observed between the group with remitted depression (N = 43) and those with persistent depression (N = 80) in educational years and AQ "attention switching" and "attention to detail" subscale scores. In addition, a statistically significant decrease in the total AQ and the "communication" and "imagination" scores were observed in the remitted group, while no such change was observed in the group with persistent depression. It remains unclear whether the self-perceived severity of communication and imagination traits in persistent depression was due to the state of persistent depression or a kind of premorbid autistic trait. The results suggest that high levels of autistic traits are frequently present in adults with depression. High "attention switching" and "attention to detail" scores in AQ screening at the first visit might predict the persistence of depressive symptoms after 12 weeks in adults with depression, while total AQ scores, especially for "communication" and "imagination" items, might be state-dependent.

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  18. Risk factors for inducing violence in patients with delirium. International journal

    Masako Tachibana, Toshiya Inada, Masaru Ichida, Norio Ozaki

    Brain and behavior   Vol. 11 ( 8 ) page: e2276   2021.8

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    BACKGROUND: Violence in patients with delirium may occur suddenly and unpredictably in a fluctuating state of consciousness. Although various factors are involved, appropriate assessment and early response to factors related to violence in delirium are expected to prevent dangerous and distressing acts of violence against patients, their families and medical staff, and minimize the use of physical restraint and excessive drug sedation. METHODS: Subjects were 601 delirium cases referred to the department of psychiatry over the course of 5 years at a general hospital. The demographic, clinical, and pharmacological variables of patients with violence (n = 189) were compared with those of patients without violence (n = 412). Logistic regression analysis was applied to determine whether any specific individual factors were associated with violence. RESULTS: Current smoker status (p < .0005), older age (p < .0005), male gender (p = .004), and use of intensive care units (p = .043) were identified as factors associated with violence in patients with delirium. CONCLUSIONS: Screening tools for violence in patients with delirium and adequate management may assist in better outcomes for patients and medical staff. Further research should evaluate the usefulness of nicotine replacement treatment for the prevention of violence during nicotine withdrawal, including whether it is safe for elderly inpatients with a high incidence of delirium in clinical practice.

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  19. 評価尺度を用いた抑うつ症状の重症度評価

    稲田 俊也, 岩本 邦弘, 香月 あすか

    臨床精神薬理   Vol. 24 ( 8 ) page: 775 - 779   2021.8

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    うつ病・うつ状態を評価するために様々な評価尺度が開発されている。なかでもハミルトンうつ病評価尺度やモンゴメリ・アスベルグうつ病評価尺度は精神科領域で広く使用されている。これらの尺度は、主としてうつ病患者の経時的な重症度の推移を評価する際に用いられ、臨床試験等における薬剤の有効性や臨床研究における改善や寛解等を示す指標として用いられている。一方で、特定の精神疾患を対象としてうつ状態を評価する目的で開発された評価尺度として、認知症患者を対象としたコーネル認知症抑うつ尺度、統合失調症患者を対象とした統合失調症カルガリー抑うつ尺度、双極性うつ病患者を対象とした双極性うつ病評価尺度などがある。このほか、抑うつ症状を1ポイントで評価する目的で開発された標準化うつ病臨床転帰尺度や、精神症状全般を評価する尺度の中に含まれるうつ状態に関連した評価項目について概観する。(著者抄録)

  20. 【評価尺度を用いた抑うつ症状の重症度評価】双極性うつ病における抑うつ症状の評価尺度

    岩本 邦弘, 稲田 俊也

    臨床精神薬理   Vol. 24 ( 8 ) page: 795 - 802   2021.8

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    軽躁・躁病エピソードの既往が聴取されなければ、うつ病エピソードで受診する双極性うつ病の患者を単極性うつ病と鑑別することは容易ではない。両者は薬剤選択などの治療方針が異なり、双極性うつ病では抗うつ薬治療による気分変動や急速交代化など診断の遅れに伴う難治化をもたらすことから正しく評価する必要がある。さらに、双極性障害は病相が変化することから、治療経過中の症状モニタリングと臨機応変な治療方針の決定も欠かせない。現在、うつ病評価尺度のほとんどは単極性うつ病を評価するために考案された尺度であり、双極性うつ病を対象に用いる評価ツールとしては限界がある。本稿では、双極性うつ病を検出し、そのうつ症状の重症度を評価するために開発されたBipolar Depression Rating Scale(双極性うつ病評価尺度)の開発経緯や尺度について概説する。(著者抄録)

  21. Factors affecting hallucinations in patients with delirium. International journal

    Masako Tachibana, Toshiya Inada, Masaru Ichida, Norio Ozaki

    Scientific reports   Vol. 11 ( 1 ) page: 13005 - 13005   2021.6

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    Delirium develops through a multifactorial process and include multiple subtypes with different pathological factors. To refine the treatment and care for delirium, a more detailed examination of these subtypes is needed. Therefore, this study aimed to explore the factors affecting delirium in cases in which hallucinations are conspicuous. In total, 602 delirium cases referred to the psychiatry department at a general hospital between May 2015 and August 2020 were enrolled. The Delirium Rating Scale-revised-98 was used to assess perceptual disturbances and hallucinations in patients with delirium. Multiple regression analysis was applied to determine whether individual factors were associated with the hallucinations. A total of 156 patients with delirium (25.9%) experienced hallucinations, with visual hallucinations being the most common subtype. Alcohol drinking (p < 0.0005), benzodiazepine withdrawal (p = 0.004), and the use of angiotensin II receptor blockers (p = 0.007) or dopamine receptor agonists (p = 0.014) were found to be significantly associated with hallucinations in patients with delirium. The four factors detected in this study could all be reversible contributing factors derived from the use of or withdrawal from exogenous substances.

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  22. Depressive mood changes are associated with self-perceptions of ADHD characteristics in adults. International journal

    Kanako Ishizuka, Tomomi Ishiguro, Norio Nomura, Toshiya Inada

    Psychiatry research   Vol. 300   page: 113893 - 113893   2021.6

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    Subjective attention deficit/hyperactivity disorder (ADHD) symptoms seen in adult depressive patients have often become a pathophysiological topic in recent years. Screening questionnaires are widely used for detecting ADHD; however, the risk of misdiagnosis exists. The present study examined whether self-perceptions of ADHD-related characteristics were consistent regardless of changes in the severity of depressive symptoms. Between April to October 2018, newly diagnosed depressed outpatients aged 24-59 years with good social functioning and without a history of ADHD were asked to fill out the Adult ADHD Self-Report Scale version 1.1 (ASRS) and the Beck Depression Inventory (BDI) at baseline (n = 726) and 12-week follow-up (n = 202). A statistically significant correlation was found between a change in BDI and ASRS scores (score at baseline minus score at the endpoint; r = .57). In addition, the higher the rate of improvement in BDI, the lower the frequency of positive screening for ADHD by ASRS. This study showed that subjective ADHD symptoms were correlated with depressive states. Diagnostic evaluation of comorbid ADHD using self-report scales in a primary care setting should be made with caution.

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  23. Significant decrease in delirium referrals after changing hypnotic from benzodiazepine to suvorexant. International journal

    Masako Tachibana, Toshiya Inada, Masaru Ichida, Shihori Kojima, Takafumi Arai, Keiko Naito, Norio Ozaki

    Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society   Vol. 21 ( 3 ) page: 324 - 332   2021.5

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    BACKGROUND: The use of benzodiazepines (BZDs) causes delirium, especially in elderly people. For this reason, suvorexant has been recommended as the first-line hypnotic in elderly patients. The aim of this study was to determine whether the first-line use of suvorexant, instead of BZDs, decreases referrals for delirium in elderly patients. METHODS: Since May 2016 at Nagoya Ekisaikai Hospital, suvorexant has been recommended as the first-line hypnotic instead of BZDs. In May 2017, suvorexant was adopted as the first-line hypnotic. The number of delirium cases referred to psychiatry was compared among three consecutive periods: period A (May 2015-April 2016), during which BZDs were mainly used for insomnia; period B (May 2016-April 2017), during which the use of suvorexant was recommended instead of BZDs; and period C (May 2017-April 2018), during which suvorexant was principally adopted as the first-line hypnotic for insomnia. Potential confounding factors that may affect the development of delirium were also examined during the three periods. RESULTS: The number of delirium referral cases in elderly patients in each period decreased, from 133 in period A to 86 in period B and 53 in period C. The rate of delirium referral cases decreased significantly every year (P = 9.02 × 10-10 ). Almost no significant confounding factors other than hypnotics were detected during the three periods. CONCLUSION: The referrals for delirium in elderly patients decreased significantly after the hypnotic was changed from BZDs to suvorexant.

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  24. Peripheral biomarkers of attention-deficit hyperactivity disorder: Current status and future perspective. International journal

    Nagahide Takahashi, Kanako Ishizuka, Toshiya Inada

    Journal of psychiatric research   Vol. 137   page: 465 - 470   2021.5

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    Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. Since the diagnosis of ADHD is defined by operational diagnostic criteria consisting of several clinical symptoms, a number of heterogeneous mechanisms have been considered to be implicated in its pathophysiology. Although no clinically reliable biomarkers are available for the diagnosis of ADHD, several plausible candidate biomarkers have been proposed based on recent advances in biochemistry and molecular biology. This review article summarizes potential peripheral biomarkers associated with ADHD, mainly from recently published case-control studies. These include 1) biochemical markers: neurotransmitters and their receptors, neurotrophic factors, serum electrolytes, and inflammation markers; 2) genetic and epigenetic markers: microRNA, mRNA expression, and peripheral DNA methylation; 3) physiological markers: eye movement and electroencephalography. It also discusses the limitations and future directions of these potential biomarkers for application in clinical practice.

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  25. Dyskinesia is most centrally situated in an estimated network of extrapyramidal syndrome in Asian patients with schizophrenia: findings from research on Asian psychotropic prescription patterns for antipsychotics. International journal

    Seon-Cheol Park, Gyung-Mee Kim, Takahiro A Kato, Mian-Yoon Chong, Shih-Ku Lin, Shu-Yu Yang, Ajit Avasthi, Sandeep Grover, Roy Abraham Kallivayalil, Yu-Tao Xiang, Kok Yoon Chee, Andi Jayalangkara Tanra, Chay Hoon Tan, Kang Sim, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park, Toshiya Inada

    Nordic journal of psychiatry   Vol. 75 ( 1 ) page: 9 - 17   2021.1

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    BACKGROUND: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology. AIMS: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. METHODS: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. RESULTS: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clusters - extrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. CONCLUSIONS: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.

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  26. Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder. International journal

    Hidekazu Kato, Itaru Kushima, Daisuke Mori, Akira Yoshimi, Branko Aleksic, Yoshihiro Nawa, Miho Toyama, Sho Furuta, Yanjie Yu, Kanako Ishizuka, Hiroki Kimura, Yuko Arioka, Keita Tsujimura, Mako Morikawa, Takashi Okada, Toshiya Inada, Masahiro Nakatochi, Keiko Shinjo, Yutaka Kondo, Kozo Kaibuchi, Yasuko Funabiki, Ryo Kimura, Toshimitsu Suzuki, Kazuhiro Yamakawa, Masashi Ikeda, Nakao Iwata, Tsutomu Takahashi, Michio Suzuki, Yuko Okahisa, Manabu Takaki, Jun Egawa, Toshiyuki Someya, Norio Ozaki

    Translational psychiatry   Vol. 10 ( 1 ) page: 421 - 421   2020.12

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    Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

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  27. Support vector machine-based classification of schizophrenia patients and healthy controls using structural magnetic resonance imaging from two independent sites International journal

    Maeri Yamamoto, Epifanio Bagarinao, Itaru Kushima, Tsutomu Takahashi, Daiki Sasabayashi, Toshiya Inada, Michio Suzuki, Tetsuya Iidaka, Norio Ozaki

    PLOS ONE   Vol. 15 ( 11 ) page: e0239615   2020.11

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    Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.

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  28. Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility. International journal

    Yoshihiro Nawa, Hiroki Kimura, Daisuke Mori, Hidekazu Kato, Miho Toyama, Sho Furuta, Yanjie Yu, Kanako Ishizuka, Itaru Kushima, Branko Aleksic, Yuko Arioka, Mako Morikawa, Takashi Okada, Toshiya Inada, Kozo Kaibuchi, Masashi Ikeda, Nakao Iwata, Michio Suzuki, Yuko Okahisa, Jun Egawa, Toshiyuki Someya, Fumichika Nishimura, Tsukasa Sasaki, Norio Ozaki

    Human genome variation   Vol. 7 ( 1 ) page: 37 - 37   2020.11

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    Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.

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  29. Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia. International journal

    Kanako Ishizuka, Tomoyuki Yoshida, Takeshi Kawabata, Ayako Imai, Hisashi Mori, Hiroki Kimura, Toshiya Inada, Yuko Okahisa, Jun Egawa, Masahide Usami, Itaru Kushima, Mako Morikawa, Takashi Okada, Masashi Ikeda, Aleksic Branko, Daisuke Mori, Toshiyuki Someya, Nakao Iwata, Norio Ozaki

    Journal of neurodevelopmental disorders   Vol. 12 ( 1 ) page: 25 - 25   2020.9

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    BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.

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  30. ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk. International journal

    Mariko Sekiguchi, Akira Sobue, Itaru Kushima, Chenyao Wang, Yuko Arioka, Hidekazu Kato, Akiko Kodama, Hisako Kubo, Norimichi Ito, Masahito Sawahata, Kazuhiro Hada, Ryosuke Ikeda, Mio Shinno, Chikara Mizukoshi, Keita Tsujimura, Akira Yoshimi, Kanako Ishizuka, Yuto Takasaki, Hiroki Kimura, Jingrui Xing, Yanjie Yu, Maeri Yamamoto, Takashi Okada, Emiko Shishido, Toshiya Inada, Masahiro Nakatochi, Tetsuya Takano, Keisuke Kuroda, Mutsuki Amano, Branko Aleksic, Takashi Yamomoto, Tetsushi Sakuma, Tomomi Aida, Kohichi Tanaka, Ryota Hashimoto, Makoto Arai, Masashi Ikeda, Nakao Iwata, Teppei Shimamura, Taku Nagai, Toshitaka Nabeshima, Kozo Kaibuchi, Kiyofumi Yamada, Daisuke Mori, Norio Ozaki

    Translational psychiatry   Vol. 10 ( 1 ) page: 247 - 247   2020.7

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    Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

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  31. Validation and factor structure of the Japanese version of the inventory to diagnose depression, lifetime version for pregnant women. International journal

    Chika Kubota, Toshiya Inada, Yukako Nakamura, Tomoko Shiino, Masahiko Ando, Branko Aleksic, Aya Yamauchi, Mako Morikawa, Takashi Okada, Masako Ohara, Maya Sato, Satomi Murase, Setsuko Goto, Atsuko Kanai, Norio Ozaki

    PloS one   Vol. 15 ( 6 ) page: e0234240   2020.6

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    INTRODUCTION: A history of major depressive disorder before pregnancy is one risk factor for peripartum depression. Therefore, the purpose of the present study was to examine the validation and factor structure of the Japanese version of the Inventory to Diagnose Depression, Lifetime version (IDDL) for pregnant women. METHODS: The study participants were 556 pregnant women. Factor analysis was performed to identify the factor structure, construct validity was examined based on the results of the factor analysis, and reliability was examined using Cronbach's α coefficient. RESULTS: Based on the results of the factor analysis of the IDDL, a bifactor model composed of a single general dimension along with the following five factors was extracted: (1) depression, anxiety, and irritability (items 1, 2, 8-10, and 19-21); (2) retardation, decreased concentration, indecisiveness, and insomnia (items 4, 11, 12, and 17); (3) decrease in appetite/significant weight loss (items 13 and 14); (4) increase in appetite/significant weight gain (items 15 and 16); and (5) diminished interest, pleasure, and libido (items 5-7). Cronbach's α coefficients for these five factors were as follows: 0.910, 0.815, 0.780, 0.683, and 0.803, respectively. CONCLUSIONS: The reliability, construct validity, and factor structure of the Japanese version of the IDDL were confirmed in pregnant women.

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  32. The Risk Factors Predicting Suicidal Ideation Among Perinatal Women in Japan. International journal

    Chika Kubota, Toshiya Inada, Tomoko Shiino, Masahiko Ando, Maya Sato, Yukako Nakamura, Aya Yamauchi, Mako Morikawa, Takashi Okada, Masako Ohara, Branko Aleksic, Satomi Murase, Setsuko Goto, Atsuko Kanai, Norio Ozaki

    Frontiers in psychiatry   Vol. 11   page: 441 - 441   2020.5

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    Introduction: The aim of the present study was to elucidate the foreseeable risk factors for suicidal ideation among Japanese perinatal women. Methods: This cohort study was conducted in Nagoya, Japan, from July 2012 to March 2018. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was conducted at four time points: early pregnancy, late pregnancy, 5 days postpartum, and 1 month postpartum. A total of 430 women completed the questionnaires. A logistic regression analysis was performed using the presence of suicidal ideation on the EPDS as an objective variable. The explanatory variables were age, presence of physical or mental disease, smoking and drinking habits, education, hospital types, EPDS total score in early pregnancy, bonding, and quality and amount of social support, as well as the history of major depressive disorder (MDD). Results: The rate of participants who were suspected of having suicidal ideation at any of the four time points was 11.6% (n=52), with the highest (n=25, 5.8%) at late pregnancy. For suicidal ideation, education level (OR: 1.19; 95% CI: 1.00-1.41; p=0.047), EPDS total points in the pregnancy period (OR: 1.25; 95% CI: 1.16-1.34; p < 0.000), a history of MDD (OR: 2.16; 95% CI: 1.00-4.79; p=0.049), and presence of mental disease (OR: 2.39; 95% CI: 1.00-5.70; p=0.049) were found to be risk factors for suicidal ideation. Age [odds ratio (OR): 0.88; 95% confidence interval (CI): 0.80-0.95; p=.002] and quality of social support (OR: 0.77; 95% CI: 0.60-0.99; p=.041) were found to be protective factors. Conclusion: Based on these results, effective preventive interventions, such as increasing the quality of social support and confirming the history of depression, should be carried out in pregnant depressive women at the early stage of the perinatal period.

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  33. A Single Medical Marker for Diagnosis of Methamphetamine Addiction - DNA Methylation of SHATI/NAT8L Promoter Sites from Patient Blood Reviewed International journal

    Kusui Yuka, Daisuke Nishizawa, Junko Hasegawa, Kyosuke Uno, Hajime Miyanishi, Hiroshi Ujike, Norio Ozaki, Toshiya Inada, Nakao Iwata, Ichiro Sora, Masaomi Iyo, Mitsuhiko Yamada, Naoki Kondo, Moo-Jun Won, Nobuya Naruse, Kumi Uehara-Aoyama, Kazutaka Ikeda, Atsumi Nitta

    CURRENT PHARMACEUTICAL DESIGN   Vol. 26 ( 2 ) page: 260 - 264   2020

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    Background: Methamphetamine (METH) is one of the most widely distributed psychostimulants worldwide. Despite active counter measures taken by different countries, neither overall usage of METH nor the frequency of repeat users has reduced over the past decade. METH induces abuse and dependence as it acts on the central nervous system and temporarily stimulates the brain. The recidivism rate for abuse of stimulants in Japan is very high and therefore prevention of repeated usage is paramount. However, we lack information about the relationship between METH users and genomic changes in humans in Japan, which would provide important information to aid such efforts.Objective: Shati/Nat8l is a METH-inducible molecule and its overexpression has protective effects on the brain upon METH usage. Here we investigated the effect of METH usage on DNA methylation rates at the promoter site of SHATI/NAT8L. We used DNA samples from human METH users, who are usually difficult to recruit in Japan.Methods: We measured DNA methylation at SHATI/NAT8L promoter sites by pyrosequencing method using 193 samples of METH users and 60 samples of healthy subjects. In this method, DNA methylation is measured by utilizing the property that only non-methylated cytosine changes to urasil after bisulfite conversion.Results: We found that the rate of DNA methylation at six CpG islands of SHATI/NAT8L promoter sites is significantly higher in METH users when compared to healthy subjects.Conclusion: These results suggest that the DNA methylation rate of SHATI/NAT8L promotor regions offers a new diagnostic method for METH usage.

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  34. Relationship Between Body Mass Index and Extrapyramidal Symptoms in Asian Patients with Schizophrenia: The Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP). International journal

    Seon-Cheol Park, Adarsh Tripathi, Ajit Avasthi, Sandeep Grover, Andi J Tanra, Takahiro A Kato, Toshiya Inada, Kok Yoon Chee, Mian-Yoon Chong, Shu-Yu Yang, Sih-Ku Lin, Kang Sim, Yu-Tao Xiang, Afzal Javed, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park

    Psychiatria Danubina   Vol. 32 ( 2 ) page: 176 - 186   2020

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    BACKGROUND: Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. SUBJECTS AND METHODS: Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight pre-obese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. RESULTS: In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. CONCLUSION: Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

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  35. Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test-retest reliability Reviewed International journal

    Bernhard Weidle, Ashmita Chaulagain, Kenneth Stensen, Branko Aleksic, Norbert Skokauskas, Toshiya Inada

    NORDIC JOURNAL OF PSYCHIATRY   Vol. 73 ( 8 ) page: 546 - 550   2019.11

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    Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test-retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 +/- 16.3 years (range 18-80) at the time of video recording. Inter-rater agreement was assessed with five raters and test-retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test-retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test-retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.

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  36. Cannabis use correlates with aggressive behavior and long-acting injectable antipsychotic treatment in Asian patients with schizophrenia. Reviewed International journal

    Seon-Cheol Park, Hong Seok Oh, Adarsh Tripathi, Roy Abraham Kallivayalil, Ajit Avasthi, Sandeep Grover, Andi Jayalangkara Tanra, Shigenobu Kanba, Takahiro A Kato, Toshiya Inada, Kok Yoon Chee, Mian-Yoon Chong, Shih-Ku Lin, Kang Sim, Yu-Tao Xiang, Chay Hoon Tan, Afzal Javed, Norman Sartorius, Naotaka Shinfuku, Yong Chon Park

    Nordic journal of psychiatry   Vol. 73 ( 6 ) page: 323 - 330   2019.8

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    Background: Although cannabis use has been linked with schizophrenia in a dose-response pattern, to our knowledge, the relationship between cannabis and schizophrenia has rarely been reported in Asian population. Aim: We compared the clinical characteristics and psychotropic prescription patterns between cannabis users and non-users among Asian patients with schizophrenia. Moreover, we aimed to identify the independent correlates of cannabis use in these subjects. Methods: We performed the analysis of the data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), a collaborative consortium survey used to collate the prescription patterns for antipsychotic and other psychotropic medications in patients with schizophrenia in Asia. We included 132 schizophrenia patients in the group of lifetime cannabis use and 1756 in the group that had never used cannabis. A binary logistic model was fitted to detect the clinical correlates of lifetime cannabis use. Results: Adjusting for the effects of age, sex, geographical region, income group, duration of untreated psychosis, and Charlson comordity index level, a binary logistic regression model revealed that lifetime cannabis use was independently associated with aggressive behavior [adjusted odds ratio (aOR) = 1.582, 95% confidence interval (CI) = 1.006-2.490, p = .047] and with long-acting injectable antipsychotic treatment (aOR = 1.796, 95% CI = 1.444-2.820, p = .001). Conclusion: Our findings indicate a close link between lifetime cannabis use and aggressive behavior. The use of long-acting, injectable antipsychotics preferentially treats the aggressive behavior cannabis users among patients with schizophrenia in Asia, especially, the South or Southeast Asia.

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  37. Relation Between Perinatal Depressive Symptoms, Harm Avoidance, and a History of Major Depressive Disorder: A Cohort Study of Pregnant Women in Japan. Reviewed International journal

    Chika Kubota, Toshiya Inada, Tomoko Shiino, Masahiko Ando, Branko Aleksic, Aya Yamauchi, Maya Sato, Masako Ohara, Satomi Murase, Mako Morikawa, Yukako Nakamura, Takashi Okada, Setsuko Goto, Atsuko Kanai, Norio Ozaki

    Frontiers in psychiatry   Vol. 10   page: 515 - 515   2019.7

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    Introduction: The relationship between perinatal depressive symptoms, harm avoidance (HA), and a history of major depressive disorder (MDD) was examined in a prospective cohort study. Methods: This study was conducted from May 1, 2011, to December 31, 2016. A history of MDD was evaluated using the Inventory to Diagnose Depression, Lifetime version during pregnancy. Depressive state and HA were evaluated during pregnancy and at 1 month postnatal using the Edinburgh Postnatal Depression Scale (EPDS) and Temperament and Character Inventory, respectively. The relationship between these variances was examined using structural equation modeling. Results: A total of 338 participants with complete data were included in the present study. Pregnant women with compared with those without a history of MDD were observed to have a significantly higher intensity of HA and more severe depressive symptoms in both the prenatal and postnatal periods. A history of MDD affected the severity of depressive symptoms [standardized path coefficient (SPC) = 0.25, p < 0.001] and the intensity of HA during pregnancy (SPC = 0.36, p < 0.001). The intensity of HA during pregnancy affected that at 1 month postnatal (SPC = 0.78, p < 0.001), while the severity of depressive symptoms as assessed by the EPDS during pregnancy affected that at 1 month postnatal (SPC = 0.41, p < 0.001). The SPC for perinatal HA to postnatal depressive symptoms (SPC = 0.13, p = 0.014) was significant and higher than that for perinatal depressive symptoms to postnatal HA (SPC = 0.06, p = 0.087). Conclusion: The present results suggest that early intervention in pregnant women with a history of MDD or a high intensity of HA is important to prevent postnatal depressive symptoms.

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  38. Application of eye trackers for understanding mental disorders: Cases for schizophrenia and autism spectrum disorder. Reviewed International journal

    Emiko Shishido, Shiori Ogawa, Seiko Miyata, Maeri Yamamoto, Toshiya Inada, Norio Ozaki

    Neuropsychopharmacology reports   Vol. 39 ( 2 ) page: 72 - 77   2019.6

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    Studies of eye movement have become an essential tool of basic neuroscience research. Measures of eye movement have been applied to higher brain functions such as cognition, social behavior, and higher-level decision-making. With the development of eye trackers, a growing body of research has described eye movements in relation to mental disorders, reporting that the basic oculomotor properties of patients with mental disorders differ from those of healthy controls. Using discrimination analysis, several independent research groups have used eye movements to differentiate patients with schizophrenia from a mixed population of patients and controls. Recently, in addition to traditional oculomotor measures, several new techniques have been applied to measure and analyze eye movement data. One research group investigated eye movements in relation to the risk of autism spectrum disorder several years prior to the emergence of verbal-behavioral abnormalities. Research on eye movement in humans in social communication is therefore considered important, but has not been well explored. Since eye movement patterns vary between patients with mental disorders and healthy controls, it is necessary to collect a large amount of eye movement data from various populations and age groups. The application of eye trackers in the clinical setting could contribute to the early treatment of mental disorders.

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  39. 睡眠薬としてのスボレキサント導入前後におけるせん妄コンサルテーション件数の推移

    立花 昌子, 稲田 俊也, 市田 勝, 兒嶋 しほり, 新井 孝文, 内藤 桂子, 尾崎 紀夫

    精神神経学雑誌   ( 2019特別号 ) page: S621 - S621   2019.6

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  40. Stable factor structure of the Edinburgh Postnatal Depression Scale during the whole peripartum period: Results from a Japanese prospective cohort study. Reviewed International journal

    Chika Kubota, Toshiya Inada, Yukako Nakamura, Tomoko Shiino, Masahiko Ando, Branko Aleksic, Aya Yamauchi, Mako Morikawa, Takashi Okada, Masako Ohara, Maya Sato, Satomi Murase, Setsuko Goto, Atsuko Kanai, Norio Ozaki

    Scientific reports   Vol. 8 ( 1 ) page: 17659 - 17659   2018.12

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    Early detection of perinatal depression is an urgent issue. Our study aimed to examine the construct validity and factor structure of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) from a prospective cohort study from pregnancy to postpartum. A total of 1075 women completed all items of the EPDS at four time points: early pregnancy, late pregnancy, 5 days postpartum and 1 month postpartum. The participants were randomly divided into two sample sets. The first sample set (n = 304) was used for exploratory factor analysis, and the second sample set (n = 771) was used for confirmatory factor analysis. As a result, the Cronbach's alpha coefficients of the EPDS items were 0.762, 0.740, 0.765 and 0.772 at the four time points. From the confirmatory factor analysis of the EPDS in a sample set of Japanese women from pregnancy to postpartum, the following three factors were detected: depression (items 7, 9), anxiety (items 4, 5) and anhedonia (items 1, 2). In conclusion, the EPDS is a useful rating scale, and its factor structure is consistently stable during the whole peripartum period.

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  41. Assessment of a glyoxalase I frameshift variant, p.P122fs, in Japanese patients with schizophrenia. Reviewed International journal

    Kanako Ishizuka, Hiroki Kimura, Itaru Kushima, Toshiya Inada, Yuko Okahisa, Masashi Ikeda, Nakao Iwata, Daisuke Mori, Branko Aleksic, Norio Ozaki

    Psychiatric genetics   Vol. 28 ( 5 ) page: 90 - 93   2018.10

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    Enhanced carbonyl stress has been observed in a subgroup of patients with schizophrenia. Glyoxalase I, which is encoded by GLO1, is an enzyme that protects against carbonyl stress. In this study, we focused on the association between rare genetic variants of GLO1 and schizophrenia. First, we identified one heterozygous frameshift variant, p.P122fs, in 370 Japanese schizophrenia cases with allele frequencies of up to 1% by exon-targeted mutation screening of GLO1. We then performed an association analysis on 1282 cases and 1764 controls with this variant. The variant was found in three cases and eight controls. There was no statistically significant association between p.P122fs in GLO1 and schizophrenia (P=0.25). This frameshift variant in GLO1 might occur at near-polymorphic frequencies in the Japanese population, although further investigations using larger samples and biological analyses are needed to exclude the possibility of a low-penetrance genetic risk associated with this variant.

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  42. Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. Reviewed International journal

    Itaru Kushima, Branko Aleksic, Masahiro Nakatochi, Teppei Shimamura, Takashi Okada, Yota Uno, Mako Morikawa, Kanako Ishizuka, Tomoko Shiino, Hiroki Kimura, Yuko Arioka, Akira Yoshimi, Yuto Takasaki, Yanjie Yu, Yukako Nakamura, Maeri Yamamoto, Tetsuya Iidaka, Shuji Iritani, Toshiya Inada, Nanayo Ogawa, Emiko Shishido, Youta Torii, Naoko Kawano, Yutaka Omura, Toru Yoshikawa, Tokio Uchiyama, Toshimichi Yamamoto, Masashi Ikeda, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Toshiyuki Someya, Yuichiro Watanabe, Jun Egawa, Ayako Nunokawa, Masanari Itokawa, Makoto Arai, Mitsuhiro Miyashita, Akiko Kobori, Michio Suzuki, Tsutomu Takahashi, Masahide Usami, Masaki Kodaira, Kyota Watanabe, Tsukasa Sasaki, Hitoshi Kuwabara, Mamoru Tochigi, Fumichika Nishimura, Hidenori Yamasue, Yosuke Eriguchi, Seico Benner, Masaki Kojima, Walid Yassin, Toshio Munesue, Shigeru Yokoyama, Ryo Kimura, Yasuko Funabiki, Hirotaka Kosaka, Makoto Ishitobi, Tetsuro Ohmori, Shusuke Numata, Takeo Yoshikawa, Tomoko Toyota, Kazuhiro Yamakawa, Toshimitsu Suzuki, Yushi Inoue, Kentaro Nakaoka, Yu-Ichi Goto, Masumi Inagaki, Naoki Hashimoto, Ichiro Kusumi, Shuraku Son, Toshiya Murai, Tempei Ikegame, Naohiro Okada, Kiyoto Kasai, Shohko Kunimoto, Daisuke Mori, Nakao Iwata, Norio Ozaki

    Cell reports   Vol. 24 ( 11 ) page: 2838 - 2856   2018.9

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    Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders.

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  43. Aberrant functional connectivity between the thalamus and visual cortex is related to attentional impairment in schizophrenia Reviewed International journal

    Maeri Yamamoto, Itaru Kushima, Ryohei Suzuki, Aleksic Branko, Naoko Kawano, Toshiya Inada, Tetsuya Iidaka, Norio Ozaki

    PSYCHIATRY RESEARCH-NEUROIMAGING   Vol. 278   page: 35 - 41   2018.8

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    Resting-state (rs) functional magnetic resonance imaging (fMRI) studies have revealed dysfunctional thalamocortical functional connectivity (FC) in schizophrenia. However, the relationship between thalamocortical FC and cognitive impairment has not been thoroughly investigated. We hypothesized that aberrant thalamocortical FC is related to attention deficits in schizophrenia. Thirty-eight patients with schizophrenia and 38 matched healthy controls underwent rs-fMRI and task fMRI while performing a Flanker task. We observed decreased left thalamic activation in patients with schizophrenia using task fMRI to determine the thalamic seed. A seed-based analysis using this seed was performed in the whole brain to assess differences in thalamocortical FC between the groups. Significantly worse performance was observed in the patient group. The rs-fMRI analysis revealed significantly increased FC between the left thalamus seed and the occipital cortices/postcentral gyri in patients when compared to controls. In the patient group, significant positive correlations were observed between the degree of FC from the left thalamus to the bilateral occipital gyri, which correspond to the visual cortex, and the Flanker effect. No significant correlation was detected in the control group. These results indicate that aberrant FC between the left thalamus and the visual cortex is related to attention deficits in schizophrenia.

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  44. A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder Reviewed

    Ikeda M, Takahashi A, Kamatani Y, Okahisa Y, Kunugi H, Mori N, Sasaki T, Ohmori T, Okamoto Y, Kawasaki H, Shimodera S, Kato T, Yoneda H, Yoshimura R, Iyo M, Matsuda K, Akiyama M, Ashikawa K, Kashiwase K, Tokunaga K, Kondo K, Saito T, Shimasaki A, Kawase K, Kitajima T, Matsuo K, Itokawa M, Someya T, Inada T, Hashimoto R, Inoue T, Akiyama K, Tanii H, Arai H, Kanba S, Ozaki N, Kusumi I, Yoshikawa T, Kubo M, Iwata N

    Mol Psychiatry   Vol. 23 ( 3 ) page: 639 - 647   2018.3

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    © The Author(s) 2018. Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

    DOI: 10.1038/mp.2016.259

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  45. [Drug-Induced Akathisia]. Reviewed

    Toshiya Inada

    Brain and nerve = Shinkei kenkyu no shinpo   Vol. 69 ( 12 ) page: 1417 - 1424   2017.12

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    Akathisia consists of subjective inner restlessness, such as awareness of the inability to remain seated, restless legs, fidgetiness, and the desire to move constantly, and of objective increased motor phenomena, such as body rocking, shifting from foot to foot, stamping in place, crossing and uncrossing legs, pacing around. Although the broad definition of akathisia includes the inner and motor restlessness observed in patients with idiopathic Parkinson's disease, post-encephalitic parkinsonism, and restless legs syndrome, here we exclusively focus on the narrow definition of antipsychotic-induced akathisia. The most reliable treatment for acute akathisia is the reduction or the withdrawal of antipsychotic medication. However, this is often not possible because it may worsen the patients' mental condition. Various pharmacological agents have been used for the treatment of this condition. These include anticholinergic agents (e.g., biperiden and trihexyphenidyl), benzodiazepines, beta-adrenoceptor blockers (e.g., propranolol), and serotonin 2A receptor antagonists (e.g., mianserin, cyproheptadine, and mirtazapine).

    DOI: 10.11477/mf.1416200927

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  46. A novel rare variant R292H in RTN4R affects growth cone formation and possibly contributes to schizophrenia susceptibility

    Kimura H., Fujita Y., Kawabata T., Ishizuka K., Wang C., Iwayama Y., Okahisa Y., Kushima I., Morikawa M., Uno Y., Okada T., Ikeda M., Inada T., Branko A., Mori D., Yoshikawa T., Iwata N., Nakamura H., Yamashita T., Ozaki N.

    TRANSLATIONAL PSYCHIATRY   Vol. 7   2017.8

  47. Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) Serbian Language version: Inter-rater and Test-retest Reliability Reviewed

    Ami Peljto, Ljubica Zamurovic, Milica Pejovic Milovancevic, Branko Aleksic, Dusica Lecic Tosevski, Toshiya Inada

    SCIENTIFIC REPORTS   Vol. 7 ( 1 ) page: 8105   2017.8

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    Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) is developed in the era of second-generation antipsychotics and is suitable for evaluation of the low incidence of extrapyramidal symptoms occurring in the treatment of atypical antipsychotics, as well as the relationship between personal and social functioning. The study was carried out at the Institute of Mental Health in Serbia in 2015 Study used the 127 DIEPSS video clips material, recorded from 1987 till 2015. Four raters performed the assessment simultaneously, individually rating one assigned item immediately after seeing the video clip. For the purpose of evaluating test-retest reliability the second assessment of the same material was performed nine months after the first assessment. Inter-rater reliability was high for each individual item, with ICCs ranging from 0.769 to 0.949. The inter-rater reliability was highest for akathisia item and lowest for dyskinesia. The test-retest reliability was high for each individual item, with ICCs ranging from 0.713 to 0.935. The test-retest reliability was highest for bradykinesia item and lowest for dystonia. The Serbian version of DIEPSS has high level of inter-rater and test-retest reliability. High values of concordance rates (ICC &gt; 0.7) for each evaluated individual item suggest that items of DIEPSS are well defined.

    DOI: 10.1038/s41598-017-08706-3

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  48. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders

    Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, Okahisa Y, Egawa J, Usami M, Kushima I, Uno Y, Okada T, Ikeda M, Aleksic B, Mori D, Someya To, Yoshikawa T, Iwata N, Nakamura H, Yamashita T, Ozaki N

    TRANSLATIONAL PSYCHIATRY   Vol. 7 ( 8 ) page: e1184 - e1184   2017.8

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    Language:Japanese   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1038/tp.2017.173

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    Other Link: http://www.nature.com/articles/tp2017173

  49. Use of a Spin Strategy Can Result in Unreliable Research Findings RESPONSE Reviewed

    Yoshio Yamanouchi, Tsuruhei Sukegawa, Ataru Inagaki, Toshiya Inada, Takashi Yoshio, Reiji Yoshimura, Nakao Iwata

    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY   Vol. 20 ( 7 ) page: 548 - 549   2017.7

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    Language:Japanese   Publisher:OXFORD UNIV PRESS  

    DOI: 10.1093/ijnp/pyx020

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  50. Identification of a rare variant in CHD8 that contributes to schizophrenia and autism spectrum disorder susceptibility Reviewed

    Hiroki Kimura, Chenyao Wang, Kanako Ishizuka, Jingrui Xing, Yuto Takasaki, Itaru Kushima, Branko Aleksic, Yota Uno, Takashi Okada, Masashi Ikeda, Daisuke Mori, Toshiya Inada, Nakao Iwata, Norio Ozaki

    SCHIZOPHRENIA RESEARCH   Vol. 178 ( 1-3 ) page: 104 - 106   2016.12

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    Language:Japanese   Publisher:ELSEVIER SCIENCE BV  

    DOI: 10.1016/j.schres.2016.08.023

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Books 11

  1. 精神医学テキスト 改訂第4版 -精神障害の理解と治療のために-・精神症状評価尺度の使い方

    稲田俊也( Role: Contributor)

    南江堂  2017.3  ( ISBN:978-4-524-25942-7

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    Language:Japanese Book type:Textbook, survey, introduction

  2. 小児の向精神薬治療ガイド : 世界の添付文書が示す小児への使い方

    稲田 俊也, 萩倉 美奈子, 遠藤 洋

    じほう  2017  ( ISBN:9784840749725

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    CiNii Books

  3. OPRS-IV 客観的精神科評価尺度ガイド 観察者による精神科領域の症状評価尺度 第4版

    稲田俊也,岩本邦弘,山本暢朋( Role: Edit)

    株式会社じほう  2016.6  ( ISBN:978-4-8407-4848-3

  4. OPRS-IV客観的精神科評価尺度ガイド

    稲田 俊也, 岩本 邦弘, 山本 暢朋

    じほう  2016  ( ISBN:9784840748483

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  5. HAMDを使いこなす. ハミルトンうつ病評価尺度(HAMD)の解説と利用の手引き.

    稲田俊也, 佐藤康一, 山本暢朋, 稲垣 中, 八木剛平, 中根允文( Role: Edit)

    星和書店  2014.4  ( ISBN:978-4-7911-0870-1

  6. YMRSを使いこなす 改訂版 ヤング躁病評価尺度日本語版 (YMRS-J) による躁病の臨床評価.

    稲田俊也,稲垣 中,中谷真樹,堀 宏治,樋口輝彦,岩本邦弘( Role: Edit)

    株式会社じほう  2012.6  ( ISBN:978-4-8407-4342-6

  7. DIEPSSを使いこなす 改訂版 薬原性錐体外路症状の評価と診断 –DIEPSSの解説と利用の手引き-.

    稲田俊也( Role: Sole author)

    星和書店  2012.3  ( ISBN:978-4-7911-0802-2

  8. Dystonia - The many facets. Dystonia secondary to use of antipsychotic agents.

    Nobutomo YAMAMOTO, Toshiya INADA( Role: Joint author)

    InTech, Rijeka, Croatia  2012  ( ISBN:978-953-51-0329-5

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  9. ひと目でわかる向精神薬の薬効比較 : エビデンス・グラフィックバージョン 2003 [第2巻]

    稲田 俊也, 笹田 和見

    じほう  ( ISBN:4840731187

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  10. ひと目でわかる向精神薬の薬効比較 : エビデンス・グラフィックバージョン 第4巻 Part2 抗不安剤・睡眠薬

    稲田 俊也, 笹田 和見

    じほう  ( ISBN:4840734402

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    CiNii Books

  11. ひと目でわかる向精神薬の薬効比較 : エビデンス・グラフィックバージョン 第3巻 Part1 抗精神病薬・抗うつ薬

    稲田 俊也, 笹田 和見

    じほう  ( ISBN:4840732957

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MISC 11

  1. Severe and long-lasting neuropsychiatric symptoms after mild respiratory symptoms caused by COVID-19: A case report.

    Jozuka R, Kimura H, Uematsu T, Fujigaki H, Yamamoto Y, Kobayashi M, Kawabata K, Koike H, Inada T, Saito K, Katsuno M, Ozaki N

    Neuropsychopharmacology reports   Vol. 42 ( 1 ) page: 114 - 119   2022.3

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    Language:English   Publisher:Neuropsychopharmacology Reports  

    Background: Coronavirus disease 2019 (COVID-19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID-19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID-19 remain poorly understood. Here, we present a case of COVID-19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms. Case presentation: A 55-year-old female with COVID-19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post-COVID-19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained. Conclusions: This case suggests the importance of both recognizing that even apparently mild COVID-19-related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long-term course of COVID-19-related neuropsychiatric symptoms in the future.

    DOI: 10.1002/npr2.12222

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  2. Historical transition and current topics on the treatment of tardive dyskinesia

    稲田 俊也, 山本 暢朋

    臨床精神薬理 = Japanese journal of clinical psychopharmacology   Vol. 22 ( 9 ) page: 933 - 944   2019.9

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    Language:Japanese   Publisher:星和書店  

  3. エジンバラ産後うつ病自己評価表の周産期における因子不変性

    久保田 智香, 稲田 俊也, 椎野 智子, 安藤 昌彦, 山内 彩, 大原 聖子, 佐藤 真耶, 森川 真子, 岡田 俊, 中村 由嘉子, 尾崎 紀夫

    精神神経学雑誌   ( 2019特別号 ) page: S453 - S453   2019.6

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    Language:Japanese   Publisher:(公社)日本精神神経学会  

  4. MRI構造画像を用いたサポートベクターマシンによる統合失調症患者と健常者の判別法の検討

    山本真江里, EPIFANIO Bagarinao, 久島周, 久島周, 高橋努, 笹林大樹, 鈴木道雄, ALEKSIC Branko, 稲田俊也, 稲田俊也, 飯高哲也, 尾崎紀夫

    日本生物学的精神医学会(Web)   Vol. 41st   2019

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  5. Dose equivalence of psychotropic drugs(Part 27)Dose equivalence of novel antidepressants(2)Venlafaxine

    稲垣 中, 稲田 俊也

    臨床精神薬理   Vol. 21 ( 4 ) page: 547 - 562   2018.4

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  6. 統合失調症発症に強い影響を及ぼす、頻度の低い稀な遺伝子変異を22q11.2欠失領域に存在するミエリン関連遺伝子のRTN4Rに同定した

    木村 大樹, 藤田 幸, 川端 猛, 石塚 佳奈子, Wang Chenyao, 岩山 佳美, 岡久 祐子, 久島 周, 宇野 洋太, 岡田 俊, 森川 真子, 森 大輔, 池田 匡志, 稲田 俊也, Aleksic Branko, 吉川 武男, 岩田 仲生, 中村 春木, 山下 俊英, 尾崎 紀夫

    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   Vol. 39回・47回   page: 190 - 190   2017.9

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    Language:Japanese   Publisher:日本生物学的精神医学会・日本神経精神薬理学会  

  7. 統合失調症発症に強い影響を及ぼす、頻度の低い稀な遺伝子変異を22q11.2欠失領域に存在するミエリン関連遺伝子のRTN4Rに同定した

    木村 大樹, 尾崎 紀夫, 藤田 幸, 川端 猛, 石塚 佳奈子, Wang Chenyao, 岩山 佳美, 岡久 祐子, 久島 周, 森川 真子, 宇野 洋太, 岡田 俊, 森 大輔, 池田 匡志, 稲田 俊也, Aleksic Branko, 吉川 武男, 岩田 仲生, 中村 春木, 山下 俊英

    精神神経学雑誌   ( 2017特別号 ) page: S622 - S622   2017.6

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  8. Dose equivalence of psychotropic drugs(Part 26)Dose equivalence of novel antipsychotics : asenapine

    稲垣 中, 稲田 俊也

    臨床精神薬理   Vol. 20 ( 1 ) page: 89 - 97   2017.1

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  9. A novel rare variant R292H in RTN4R affects growth cone 2 formation and possibly contributes to Schizophrenia susceptibility

    Hiroki Kimura, Yuki Fujita, Takeshi Kawabata, Kanako Ishizuka, Chenyao Wang, Yoshimi Iwayama, Yuko Okahisa, Itaru Kushima, Mako Morikawa, Yota Uno, Takashi Okada, Masashi Ikeda, Toshiya Inada, Aleksic Branko, Daisuke Mori, Takeo Yoshikawa, Nakao Iwata, Haruki Nakamura, Toshihide Yamashita, Norio Ozaki

    Translational Psychiatry     page: in print   2017

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  10. The problem of high dose polypharmacy of antipsychotic in a viewpoint of safety correction

    助川 鶴平, 山之内 芳雄, 稲垣 中, 稲田 俊也, 吉尾 隆, 吉村 玲児, 岩田 仲生

    臨床精神薬理   Vol. 19 ( 10 ) page: 1463 - 1469   2016.10

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  11. 精神科臨床評価 特定の精神障害に関連したもの 躁病 Invited

    岩本邦弘, 稲田俊也

    臨床精神医学   Vol. 44 ( 増刊 ) page: 375-84   2016.1

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KAKENHI (Grants-in-Aid for Scientific Research) 11

  1. 新規評価尺度による大うつ病性障害の臨床評価に関する研究.

    2009.4 - 2012.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  2. 総合失調症とメチレンテトラヒドロ葉酸還元酵素遺伝子との関連研究.

    2006.4 - 2008.3

    科学研究費補助金  基盤研究(C)

  3. クロモグラニンB遺伝子多型の各種精神疾患の病態生理に及ぼす影響についての研究

    2003.4 - 2005.3

    科学研究費補助金  基盤研究(C)

    稲田 俊也

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    Authorship:Principal investigator 

  4. 第5番および第6番染色体上のDNAマーカーを用いた精神分裂病の遺伝子関連研究.

    2001.4 - 2003.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  5. 第19番および第20番染色体上のDNAマーカーを用いた精神分裂病の遺伝子関連研究.

    1999.4 - 2001.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Principal investigator 

  6. 精神分裂病患者における精神症状および薬原性錐体外路症状発症と関連する遺伝子の検索.

    1997.4 - 1999.3

    科学研究費補助金  奨励研究(A)

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    Authorship:Principal investigator 

  7. ドパミンD4遺伝子多型の精神症候学的意義についての検討.

    1996.4 - 1997.3

    科学研究費補助金  奨励研究(A)

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    Authorship:Principal investigator 

  8. 精神分裂病患者における個別精神症状などの早期発見に関する分子生物学的研究.

    1995.4 - 1996.3

    科学研究費補助金  奨励研究(A)

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    Authorship:Principal investigator 

  9. 遅発性ジスキネジアに脆弱性をもつ精神分裂病患者の早期発見に関する分子生物学的研究.

    1994.4 - 1995.3

    科学研究費補助金  症例研究(A)

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    Authorship:Principal investigator 

  10. 海馬破壊ラットにおけるメタンフェタミン反復投与による増感現象形成についての研究.

    1993.4 - 1994.3

    科学研究費補助金  奨励研究(A)

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    Authorship:Principal investigator 

  11. 深層学習・人工知能技術を用いた音声認識システムによるうつ病重症度推定機器の開発

    Grant number:19K08071  2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    稲田 俊也

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    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    本研究は,うつ病の重症度を評価する目的で自らが開発したモンゴメリ・アスベルグうつ病評価尺度構造化面接をベースとして行った実際の面接場面で集積した録音データを用いて,申請者が定義した重症度評点,書き起こしたテキストファイルと音声ファイルの3点セットのデータとして抽出し,深層学習モデル用の学習データとして集積することによって試作したうつ病の重症度評点を推定するAI(人工知能)うつ病重症度評点推定機器を,実臨床で使用できるレベルにまで各項目の重症度評価の精度を高める手法として,臨床評価面接データの更なる集積による学習の強化以外に,精神科の臨床面接の分野でどのような工夫が必要であるかを検討する。
    本研究は,研究代表者らが開発し,2004年に公表したモンゴメリ・アスベルグうつ病評価尺度(MADRS)構造化面接(SIGMA)に含まれるうつ病の重症度を評価するための質問文をベースに,AI(人工知能)での重症度評価に適した質問文となるように改定し,被験者からの回答を実際の評価面接場面で収録した音声データをもとに,①研究代表者が定義した被験者の回答例に対する重症度評点,②書き起こしたテキストファイル,③被験者が回答した音声WAVファイルの3点セットのデータとして抽出し,これらを深層学習モデル用の学習データとして集積し,うつ病の重症度評点を推定するAI(人工知能)うつ病重症度評点推定機器の中核部分となるプログラムを作成し,最終的にはこのAI評価システムを用いて実臨床においてうつ病の重症度評価を行えるようにすることである。本年度は昨年度に引き続き,これまでに試作したAI機器の精度を高めるための深層学習モデル用のデータの集積をすすめるとともに,AI機器の精度を高めるための音声認識や自然言語処理の手法についての改良や新たな技術の追加,重症度評価のためのアルゴリズムの改良やAI評点を導く試作機器プログラムの改変を繰り返し行った。具体的には,学習用のデータを集積して,重症度評点を推測する精度を高める過程で,それぞれの質問文に対する回答から評点を推定するモデルの性能を評価して,モデル構造や活性化関数のチューニングを行うなどのプログラミングの改良を行うとともに,臨床面接の手法としては,被験者からの回答で音声認識が不完全であった箇所はマニュアルで評価者が入力して修正できるように改良したり,質問文をよみ上げた直後に被験者が回答できるような工夫を加えたり,矛盾する回答に対して追加の質問文を行ったりするなど,AI面接のアルゴリズムの再構築についても検討を行った。
    初年度の時点で完成した試作システムと比較した場合,パソコンやタブレットでの画面上の見た目はそれほど変わりがないものの評価精度を高めるための様々な工夫を加えた結果,AIうつ病重症度推定システムを用いた重症度評価の評点と熟練した精神科医による重症度評点との評価者・評価機器間の一致率は,昨年度集積したデータのみで解析した場合よりも今年度集積したデータを加えて実施した場合,有意とは言えないものの上昇傾向にあることから,AIうつ病重症度推定システムの精度は順調に向上しつつとあると考えている。しかし,被験者の回答がこれまでの学習内容になかった場合の評価者・評価機器間の評点の一致率が依然として低いため,さらなる症例追加で学習を繰り返すことや,自然言語処理システムのさらなる改良が必要と思われる。
    来年度も昨年度や今年度に引き続き,これまでに試作したAI機器の精度を高めるための深層学習モデル用のデータの集積をすすめるとともに,AI機器の精度を高めるための音声認識や自然言語処理の手法についての改良や新たな技術の追加,重症度評価のためのアルゴリズムの改良やAI評点を導く試作機器プログラムの改変を繰り返し行う予定である。来年度は最終年度であるため、AIうつ病重症度推定システムの精度がどの程度向上したかを実証するため,今年度までに集積したデータと,来年度集積したデータを用いて,AIうつ病重症度推定システムを用いた重症度評価の評点と熟練した精神科医による重症度評点との評価者・評価機器間の一致率を算出し、実臨床で使用できるレベルにまで向上しているかどうかを評価するとともに,特許性のない既存の音声認識技術や自然言語処理手法を用いたAIうつ病重症度推定システムで評価した場合の評価精度(熟練した精神科医による評価との一致率)を算出し,今後,精度を画期的に高めることができるような特許性のある技術を追加したAIうつ病重症度推定システムとの比較ができるコントロールデータとして国際誌に公表する。

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