Neural basis of subjective and objective well- and ill-being in mood disorders

• Project/Area Number: 17H04244
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: The University of Tokyo
• Principal Investigator: Kasai Kiyoto 東京大学, 医学部附属病院, 教授 (80322056)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 気分障害 / 自覚 / 他覚 / うつ / MRI / NIRS / ウェルビーイング / イルビーイング / 脳画像 / 脳神経疾患

Outline of Final Research Achievements

We conducted resting-state functional MRI connectivity analysis in mood disorders and found that subjective ill-being was associated with elevated functional connectivity between frontopolar cortex and precuneus. We also developed a method to measure resting-state functional connectivity using near-infrared spectroscopy (NIRS) and applied the technique to major depressive disorder. We observed that objective ill-being was associated with decreased functional connectivity between the dorsolateral prefrontal cortex and the parietal cortex. In another study, cognitive function predicted subjective well-being in mood disorder patients. Finally, we found that the combination of MRI and NIRS yielded a 76% accuracy rate for the classification of mood disorders from healthy controls. Taken together, our findings suggest that different brain networks subserve well- and ill-being in mood disorders, and the combination of MRI and NIRS may be a promising biomarker for the aid of diagnosis.

Academic Significance and Societal Importance of the Research Achievements

本研究はイルビーイングの自覚・他覚的側面やそれらのかい離の脳神経基盤を解明した点、精神科臨床でこれまで対象としてきたイルビーイングだけでなく、ウェルビーイングについても統合的に検討した点であると考えられる。本研究の成果は、自覚・他覚イルビーイングのかい離とその脳基盤の同定により、気分障害の脳機能・構造にもとづく層別化を可能とし、治療法選択バイオマーカーとして実用化する道を開くことにつながるものと思われる。また、ウェルビーイングとイルビーイングが単なる正負の鏡像関係ではなく、独立した脳基盤を持つことを示すことで、精神疾患のリカバリー支援にも脳科学的な示唆を与えた。

Research Products

• [Int'l Joint Research] Harvard Medical School/UCSD(米国)
• [Int'l Joint Research] Seoul National University(韓国)
• [Int'l Joint Research] 北京大学(中国)
• [Int'l Joint Research] ソウル大学(韓国)
• [Int'l Joint Research] ジョンズホプキンス大学(米国)
• [Journal Article] Resting-state EEG beta band power predicts quality of life outcomes in patients with depressive disorders: A longitudinal investigation (2020)
  • Author(s): Koshiyama Daisuke、Kirihara Kenji、Usui Kaori、Tada Mariko、Fujioka Mao、Morita Susumu、Kawakami Shintaro、Yamagishi Mika、Sakurada Hanako、Sakakibara Eisuke、Satomura Yoshihiro、Okada Naohiro、Kondo Shinsuke、Araki Tsuyoshi、Jinde Seichiro、Kasai Kiyoto
  • Journal Title: J Affect Disord Volume: 265 Pages: 416-422
  • DOI: 10.1016/j.jad.2020.01.030
  • Peer Reviewed
• [Journal Article] Brain morphological and functional features in cognitive subgroups of schizophrenia (2020)
  • Author(s): Yasuda Y., Okada N., Nemoto K., Fukunaga M., Yamamori H., Ohi K., Koshiyama D., Kudo N., Shiino T., Morita S., Morita K., Azechi H., Fujimoto M., Miura K., Watanabe Y., Kasai K., Hashimoto R.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 74(3) Pages: 191-203
  • DOI: 10.1111/pcn.12963
  • NAID: 120007132757
  • Peer Reviewed / Open Access
• [Journal Article] Severity-dependent and -independent brain regions of major depressive disorder: A long-term longitudinal near-infrared spectroscopy study (2019)
  • Author(s): Satomura Yoshihiro、Sakakibara Eisuke、Takizawa Ryu、Koike Shinsuke、Nishimura Yukika、Sakurada Hanako、Yamagishi Mika、Shimojo Chie、Kawasaki Shingo、Okada Naohiro、Matsuoka Jun、Kinoshita Akihide、Jinde Seiichiro、Kondo Shinsuke、Kasai Kiyoto
  • Journal Title: Journal of Affective disorder Volume: 243 Pages: 249-254
  • DOI: 10.1016/j.jad.2018.09.029
  • Peer Reviewed
• [Journal Article] Genetic influences on prefrontal activation during a verbal fluency task in children: A twin study using near-infrared spectroscopy (2018)
  • Author(s): Sakakibara E, Takizawa R, Kawakubo Y, Kuwabara H, Kono T, Hamada K, Okuhata S, Eguchi S, Ishii-Takahashi A, Kasai K
  • Journal Title: Brain and Behavior Volume: 8(6)
  • DOI: 10.1002/brb3.980
  • NAID: 120006496949
  • Peer Reviewed / Open Access
• [Journal Article] Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder (2018)
  • Author(s): Kamiya K., Okada N., Sawada K., Watanabe Y., Irie R., Hanaoka S., Suzuki Y., Koike S., Mori H., Kunimatsu A., Hori M., Aoki S., Kasai K., Abe O.
  • Journal Title: NMR Biomed Volume: 31
  • DOI: 10.1002/nbm.3938
  • Peer Reviewed / Open Access
• [Journal Article] Deficient neural activity subserving decision-making during reward waiting time in intertemporal choice in adult attention-deficit hyperactivity disorder (2018)
  • Author(s): Todokoro A., Tanaka S. C., Kawakubo Y., Yahata N., Ishii-Takahashi A., Nishimura Y., Kano Y., Ohtake F., Kasai K.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: - Pages: 580-590
  • DOI: 10.1111/pcn.12668
  • Peer Reviewed / Open Access
• [Journal Article] Genetic influences on prefrontal activation during a verbal fluency task in children: A twin study using near-infrared spectroscopy (2018)
  • Author(s): Sakakibara E, Takizawa R, Kawakubo Y, Kuwabara H, Kono T, Hamada K, Okuhata S, Eguchi S, Ishii-Takahashi A, Kasai K
  • Journal Title: Brain Behav Volume: in press
  • NAID: 120006496949
  • Peer Reviewed
• [Journal Article] Association between mismatch negativity and global functioning is specific to duration deviance in early stages of psychosis (2018)
  • Author(s): Koshiyama Daisuke, Kirihara Kenji, Tada Mariko, Nagai Tatsuya, Fujioka Mao, Koike Shinsuke, Suga Motomu, Araki Tsuyoshi, Kasai Kiyoto
  • Journal Title: Schizophr Res Volume: - Pages: 30607-30607
  • DOI: 10.1016/j.schres.2017.09.045
  • Peer Reviewed / Open Access
• [Journal Article] Role of subcortical structures on cognitive and social function in schizophrenia (2018)
  • Author(s): Koshiyama D., Fukunaga M., Okada N., Yamashita F., Yamamori H., Yasuda Y., Fujimoto M., Ohi K., Fujino H., Watanabe Y., Kasai K., Hashimoto R.
  • Journal Title: Scientific Reports Volume: 8 Pages: 1183-1183
  • DOI: 10.1038/s41598-017-18950-2
  • Peer Reviewed / Open Access
• [Journal Article] Subcortical association with memory performance in schizophrenja : a structural magnetic resonance imaging study (2018)
  • Author(s): Koshiyama D., Fukunaga M., Okada N., Yamashita F., Yamamori H., Yasuda Y., Fujimoto M., Ohi K., Fujino H., Watanabe Y., Kasai K., Hashimoto R.
  • Journal Title: Transl Psychiatry Volume: 8 Pages: 1-11
  • DOI: 10.1038/s41398-017-0069-3
  • Peer Reviewed / Open Access
• [Journal Article] Application of functional near infrared spectroscopy as supplementary examination for diagnosis of clinical stages of psychosis spectrum (2017)
  • Author(s): Koike S., Satomura Y., Kawasaki S., Nishimura Y., Kinoshita A., Sakurada H., Yamagishi M., Ichikawa E., Matsuoka J., Okada N., Takizawa R., Kasai K.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 71 Pages: 794-806
  • DOI: 10.1111/pcn.12551
  • Peer Reviewed / Open Access
• [Journal Article] Duration and frequency mismatch negativity shows no progressive reduction in early stages of psychosis (2017)
  • Author(s): Koshiyama D, Kirihara K, Tada M, Nagai T, Koike S, Suga M, Araki T, Kasai K
  • Journal Title: Schizophr Res Volume: 印刷中 Pages: 32-38
  • DOI: 10.1016/j.schres.2017.03.015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased Occipital Gyrification and Development of Psychotic Disorders in Individuals With an At-Risk Mental State : A Multicenter Study (2017)
  • Author(s): Sasabayashi D., Takayanagi Y., Takahashi T., Koike S., Yamasue H., Katagiri N., Sakuma A., Obara C., Nakamura M., Furuichi A., Kido M., Nishikawa Y., Noguchi K., Matsumoto K., Mizuno M., Kasai K., Suzuki M.
  • Journal Title: Biological Psychiatry Volume: 82 Pages: 737-745
  • DOI: 10.1016/j.biopsych.2017.05.018
  • Peer Reviewed / Open Access
• [Journal Article] Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis (2017)
  • Author(s): Nagai Tatsuya, Kirihara Kenji, Tada Mariko, Koshiyama Daisuke, Koike Shinsuke, Suga Motomu, Araki Tsuyoshi, Hashimoto Kenji, Kasai Kiyoto
  • Journal Title: Sci Rep Volume: 7 Pages: 2258-2258
  • DOI: 10.1038/s41598-017-02267-1
  • Peer Reviewed / Open Access
• [Journal Article] Identifying neurocognitive markers for outcome prediction of global functioning in ultra-high-risk for psychosis and first episode psychosis. (2017)
  • Author(s): Sawada K, Kanehara A, Eguchi S, Tada M, Satomura Y, Suga M, Koike S, Kasai K
  • Journal Title: Psychiatry Clin Neurosci Volume: 印刷中 Pages: 318-327
  • DOI: 10.1111/pcn.12522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Using translatable brain markers to understand pathophysiology of early psychosis. (2019)
  • Author(s): Kasai K
  • Organizer: International symposium on redox in psychosis risk.
  • Int'l Joint Research / Invited
• [Presentation] 東大病院こころの検査プログラム参加患者の転帰調査． (2019)
  • Author(s): 櫻田華子、山岸美香、金原明子、岡村由美子、里村嘉弘、榊原英輔、松岡潤、岡田直大、小池進介、神出誠一郎、近藤伸介、笠井清登．
  • Organizer: 第23回日本精神保健・予防学会学術集会
• [Presentation] The difference in brain activity of the prefrontal cortex between schizophrenia, bipolar disorder, and major depression. (2018)
  • Author(s): Koike S, Sakakibara E, Satomura Y, Sakurada H, Yamagishi M, Matsuoka J, Okada N, Kasai K
  • Organizer: WFSBP Asia Pacific Regional Congress of Biological Psychiatry
  • Int'l Joint Research
• [Presentation] 成人を対象としたウェルビーイングの評価尺度に関する文献レビュー：精神保健サービスのアウトカム評価の視点から (2018)
  • Author(s): 千葉理恵、宮本有紀、山口創生、西大輔、島津明人、近藤伸介、笠井清登
  • Organizer: 第13回日本統合失調症学会
• [Presentation] リカバリープロセス尺度日本語版の開発 (2018)
  • Author(s): 金原明子、小竹理紗、宮本有紀、熊倉陽介、森田健太郎、石浦朋子、清水希実子、藤枝由美子、安藤俊太郎、近藤伸介、笠井清登
  • Organizer: 第13回日本統合失調症学会
• [Presentation] Neuroimaging and neurophysiological investigations into schizophrenia (2017)
  • Author(s): Kasai K
  • Organizer: 1st International Symposium of International Research Center for Neurointelligence
  • Int'l Joint Research / Invited
• [Presentation] Development of a framework of recovery for mental health service users in Japan (2017)
  • Author(s): Kanehara A, Kumakura Y, Kanata S, Fujieda Y, Koike H, Morita K, Yamaguchi S, Miyamoto Y, Nochi M, Fukuda M, Kasai K
  • Organizer: 6th European Conference on Schizophrenia Research
  • 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と認知機能・全般的社会適応レベルとの相関関係 (2017)
  • Author(s): 越山太輔、切原賢治、多田真理子、永井達哉、藤岡真生、小池進介、菅心、荒木剛、笠井清登
  • Organizer: 第39回日本生物学的精神医学会
• [Remarks] 東京大学精神医学教室ホームページ
  • URL: http://npsy.umin.jp/
• [Remarks] 東大精神科ホームページ
  • URL: http://npsy.umin.jp/