Investigation of biomarkers for early intervention of schizophrenia focusing on neural oscillations

• Project/Area Number: 18K07588
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: The University of Tokyo
• Principal Investigator: KIRIHARA Kenji 東京大学, バリアフリー支援室, 准教授 (80553700)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 統合失調症 / 脳波 / 聴性定常反応 / 神経オシレーション / 思春期 / 精神病 / ハイリスク / オシレーション / ASSR / 早期支援 / 発達

Outline of Final Research Achievements

In early stages of schizophrenia, 40 Hz auditory steady-state response (ASSR) was reduced while neither spontaneous gamma oscillations nor gamma-band harmonic response was reduced. In schizophrenia, 40 Hz ASSR was correlated with plasma levels of D-serine. Healthy control subjects showed correlation between 40 Hz ASSR and white matter while patients with schizophrenia did not show the correlation. These findings suggest that 40 Hz ASSR may be a useful biomarker for early intervention of schizophrenia. We did not find longitudinal change of 40 Hz ASSR and correlation with psychological indexes in adolescents.

Academic Significance and Societal Importance of the Research Achievements

本研究では、γオシレーションが統合失調症の早期段階で変化しており、NMDA受容体機能や白質統合性と関連することを明らかにした。本研究の結果は、統合失調症の早期段階における病態生理を明らかにすることに役立つ。また、本研究で示唆が得られたγオシレーションの生物学的メカニズムを解明することで、統合失調症の早期支援に有用な新規治療法の開発に役立つことが期待される。本研究では思春期発達におけるγオシレーションの変化を認めなかったため、この点については今後のさらなる研究が必要である。

Research Products

• [Journal Article] Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia. (2024)
  • Author(s): D. Koshiyama， R. Nishimura， K. Usui， M. Fujioka， M. Tada， K. Kirihara， T. Araki， S. Kawakami， N. Okada， S. Koike， H. Yamasue， O. Abe and K. Kasai
  • Journal Title: Schizophrenia (Heidelb). Volume: 10 Issue: 1 Pages: 32-32
  • DOI: 10.1038/s41537-024-00454-4
  • Peer Reviewed / Open Access
• [Journal Article] Gamma‐band harmonic responses for beta‐band auditory steady‐state response are intact in patients with early stage schizophrenia (2023)
  • Author(s): Tada Mariko、Kirihara Kenji、Nagai Tatsuya、Koike Shinsuke、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Neuropsychopharmacology Reports Volume: 44 Issue: 1 Pages: 240-245
  • DOI: 10.1002/npr2.12392
  • Peer Reviewed / Open Access
• [Journal Article] Alterations of auditory-evoked gamma oscillations are more pronounced than alterations of spontaneous power of gamma oscillation in early stages of schizophrenia (2023)
  • Author(s): Tada Mariko、Kirihara Kenji、Koshiyama Daisuke、Nagai Tatsuya、Fujiouka Mao、Usui Kaori、Satomura Yoshihiro、Koike Shinsuke、Sawada Kingo、Matsuoka Jun、Morita Kentaro、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Translational Psychiatry Volume: 13 Issue: 1 Pages: 218-218
  • DOI: 10.1038/s41398-023-02511-5
  • Peer Reviewed / Open Access
• [Journal Article] Criticality in the Healthy Brain (2022)
  • Author(s): Shi Jifan、Kirihara Kenji、Tada Mariko、Fujioka Mao、Usui Kaori、Koshiyama Daisuke、Araki Tsuyoshi、Chen Luonan、Kasai Kiyoto、Aihara Kazuyuki
  • Journal Title: Frontiers in Network Physiology Volume: 1 Pages: 1-9
  • DOI: 10.3389/fnetp.2021.755685
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The association between clinical symptoms and later subjective quality of life in individuals with ultra‐high risk for psychosis and recent‐onset psychotic disorder: A longitudinal investigation (2022)
  • Author(s): Usui Kaori、Kirihara Kenji、Tada Mariko、Fujioka Mao、Koshiyama Daisuke、Tani Motoko、Tsuchiya Maiko、Morita Susumu、Kawakami Shintaro、Kanehara Akiko、Morita Kentaro、Satomura Yoshihiro、Koike Shinsuke、Suga Motomu、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: - Issue: 11 Pages: 1-8
  • DOI: 10.1111/pcn.13359
  • Peer Reviewed / Open Access
• [Journal Article] Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans (2021)
  • Author(s): Tada Mariko、Kirihara Kenji、Ishishita Yohei、Takasago Megumi、Kunii Naoto、Uka Takanori、Shimada Seijiro、Ibayashi Kenji、Kawai Kensuke、Saito Nobuhito、Koshiyama Daisuke、Fujioka Mao、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Cerebral Cortex Volume: 31 Issue: 10 Pages: 4518-4532
  • DOI: 10.1093/cercor/bhab103
  • Peer Reviewed / Open Access
• [Journal Article] Gamma-Band Auditory Steady-State Response as a Neurophysiological Marker for Excitation and Inhibition Balance: A Review for Understanding Schizophrenia and Other Neuropsychiatric Disorders. (2020)
  • Author(s): Tada M, Kirihara K, Koshiyama D, Fujioka M, Usui K, Uka T, Komatsu M, Kunii N, Araki T, Kasai K.
  • Journal Title: Clin EEG Neuroscience Volume: in press Issue: 4 Pages: 234-243
  • DOI: 10.1177/1550059419868872
  • Peer Reviewed / Open Access
• [Journal Article] Reduced Auditory Mismatch Negativity Reflects Impaired Deviance Detection in Schizophrenia (2020)
  • Author(s): Koshiyama Daisuke、Kirihara Kenji、Tada Mariko、Nagai Tatsuya、Fujioka Mao、Usui Kaori、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Schizophrenia Bulletin Volume: - Issue: 4 Pages: 937-946
  • DOI: 10.1093/schbul/sbaa006
  • Peer Reviewed / Open Access
• [Journal Article] A Predictive Coding Perspective on Mismatch Negativity Impairment in Schizophrenia (2020)
  • Author(s): Kirihara Kenji、Tada Mariko、Koshiyama Daisuke、Fujioka Mao、Usui Kaori、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Frontiers in Psychiatry Volume: 11 Pages: 1-8
  • DOI: 10.3389/fpsyt.2020.00660
  • Peer Reviewed / Open Access
• [Journal Article] Translatability of Scalp EEG Recordings of Duration-Deviant Mismatch Negativity Between Macaques and Humans: A Pilot Study (2020)
  • Author(s): Tada Mariko、Suda Yuki、Kirihara Kenji、Koshiyama Daisuke、Fujioka Mao、Usui Kaori、Araki Tsuyoshi、Kasai Kiyoto、Uka Takanori
  • Journal Title: Frontiers in Psychiatry Volume: 11 Pages: 874-874
  • DOI: 10.3389/fpsyt.2020.00874
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mismatch negativity (MMN) as a tool for translational investigations into early psychosis: A review (2019)
  • Author(s): Tada Mariko、Kirihara Kenji、Mizutani Shunsuke、Uka Takanori、Kunii Naoto、Koshiyama Daisuke、Fujioka Mao、Usui Kaori、Nagai Tatsuya、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: International Journal of Psychophysiology Volume: 145 Pages: 5-14
  • DOI: 10.1016/j.ijpsycho.2019.02.009
  • Peer Reviewed / Open Access
• [Journal Article] Gamma-band auditory steady-state response is associated with plasma levels of d-serine in schizophrenia: An exploratory study (2019)
  • Author(s): Koshiyama Daisuke、Kirihara Kenji、Tada Mariko、Nagai Tatsuya、Fujioka Mao、Usui Kaori、Koike Shinsuke、Suga Motomu、Araki Tsuyoshi、Hashimoto Kenji、Kasai Kiyoto
  • Journal Title: Schizophrenia Research Volume: 208 Pages: 467-469
  • DOI: 10.1016/j.schres.2019.02.012
  • Peer Reviewed / Open Access
• [Journal Article] Electrophysiological evidence for abnormal glutamate-GABA association following psychosis onset (2018)
  • Author(s): Koshiyama Daisuke、Kirihara Kenji、Tada Mariko、Nagai Tatsuya、Fujioka Mao、Ichikawa Eriko、Ohta Kazusa、Tani Motoko、Tsuchiya Maiko、Kanehara Akiko、Morita Kentaro、Sawada Kingo、Matsuoka Jun、Satomura Yoshihiro、Koike Shinsuke、Suga Motomu、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Translational Psychiatry Volume: 8 Issue: 1 Pages: 211-211
  • DOI: 10.1038/s41398-018-0261-0
  • Peer Reviewed / Open Access
• [Journal Article] Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: A longitudinal investigation (2018)
  • Author(s): Koshiyama Daisuke、Kirihara Kenji、Tada Mariko、Nagai Tatsuya、Fujioka Mao、Ichikawa Eriko、Ohta Kazusa、Tani Motoko、Tsuchiya Maiko、Kanehara Akiko、Morita Kentaro、Sawada Kingo、Matsuoka Jun、Satomura Yoshihiro、Koike Shinsuke、Suga Motomu、Araki Tsuyoshi、Kasai Kiyoto
  • Journal Title: Clinical Neurophysiology Volume: 129 Issue: 11 Pages: 2268-2275
  • DOI: 10.1016/j.clinph.2018.08.007
  • Peer Reviewed
• [Presentation] 統合失調症の早期段階におけるtranslatable brain markerとしてのミスマッチ陰性電位 (2023)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、國井尚人、宇賀貴紀、笠井清登
  • Organizer: 第119回日本精神神経学会学術総会
• [Presentation] 統合失調症の早期段階におけるバイオマーカーとしてのミスマッチ陰性電位 (2023)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、笠井清登
  • Organizer: 第53回日本臨床神経生理学会学術大会
• [Presentation] 統合失調症における脳予測性の障害：臨床脳波研究 (2022)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、笠井清登
  • Organizer: NEURO2022
• [Presentation] Mismatch negativity as a biological marker in early stages of psychosis (2022)
  • Author(s): Kenji Kirihara, Mariko Tada, Daisuke Koshiyama, Mao Fujioka, Kaori Usui, Ryoichi Nishimura, Tsuyoshi Araki, Kiyoto Kasai
  • Organizer: The 9th Mismatch Negativity conference（MMN 2022）
  • Int'l Joint Research
• [Presentation] 統合失調症の早期段階におけるミスマッチ陰性電位 (2022)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、笠井清登
  • Organizer: 第52回日本臨床神経生理学会学術大会
• [Presentation] 脳予測性の視点からみたミスマッチ陰性電位 (2021)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、笠井清登
  • Organizer: 第5回MMN研究会
• [Presentation] 統合失調症におけるtranslatable brain markerとしてのミスマッチ陰性電位 (2021)
  • Author(s): 切原賢治、多田真理子、越山太輔、藤岡真生、臼井香、西村亮一、荒木剛、笠井清登
  • Organizer: 第51回日本臨床神経生理学会学術大会
• [Presentation] 統合失調症における聴性定常反応：早期段階および分子レベルでの検討 (2019)
  • Author(s): 切原 賢治, 多田 真理子, 越山 太輔, 藤岡 真生, 臼井 香, 荒木 剛, 笠井 清登
  • Organizer: 第49回日本臨床神経生理学会学術大会
• [Presentation] MMN in human adolescence and in early psychosis (2018)
  • Author(s): Daisuke Koshiyama, Kenji Kirihara, Mariko Tada, Tatsuya Nagai, Mao Fujioka, Kaori Usui, Shinsuke Koike, Motomu Suga, Tsuyoshi Araki, Kiyoto Kasai
  • Organizer: 第41回日本神経科学大会