Basic research on elucidation of neurocircuit pathology of depression and its remodeling mechanism

• Project/Area Number: 15H02552
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Hiroshima University
• Principal Investigator: Yamawaki Shigeto 広島大学, 医歯薬保健学研究科, 特任教授 (40230601)
• Co-Investigator(Kenkyū-buntansha): 淵上 学 広島大学, 医歯薬保健学研究科(医), 助教 (40403571) ; 吉野 敦雄 広島大学, 医歯薬保健学研究科(医), 特任助教 (90633727)
• Co-Investigator(Renkei-kenkyūsha): Okamoto Yasumasa 広島大学, 大学院医歯薬保健学研究科(医), 教授 (70314763) ; Okada Go 広島大学, 大学院医歯薬保健学研究科(医), 講師 (10457286) ; Hashimoto Koichi 広島大学, 大学院医歯薬保健学研究科(医), 教授 (00303272) ; Morioka Norimitsu 広島大学, 大学院医歯薬保健学研究科(薬), 教授 (20346505) ; Yamawaki Yosuke 広島大学, 大学院医歯薬保健学研究科(歯), 助教 (90584061)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥41,990,000 (Direct Cost: ¥32,300,000、Indirect Cost: ¥9,690,000); Fiscal Year 2017: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2015: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
• Keywords: Depression / うつ病 / リアルタイムfMRI / 前頭前野 / 脳神経疾患

Outline of Final Research Achievements

The purpose of the present study is to reveal the distinctive neural activities in the pathophysiology of depression and to develop the new treatment which re-models neural circuit. Our outcomes were as follows: 1) the identification of depressive-specific human functional connectivity such as the prefrontal cortex and anterior cingulate cortex, 2) the identification of behavioral changes by neural activities in the rat prefrontal cortex, 3) the association between behavioral changes in the rat and electrophysiological changes in the rat prefrontal cortex, and 4) based on the above outcomes, the development of neurofeedback treatment and the improvement of functional connectivity between the prefrontal cortex and anterior cingulate cortex by its treatment. More work is needed to further modify the methodology of neurofeedback.

Research Products

• [Int'l Joint Research] Hadasah-Hebrew University Medical Center(Israel)
• [Journal Article] Effects of behavioral activation on the neural basis of other perspective self referential processing in subthreshold depression: An fMRI study. (2017)
  • Author(s): Shiota, S., Okamoto, Y., Okada, G., Takagaki, K., Takamura, M., Mori, A., Yokoyama, S., Nishiyama, Y., Jinnin, R., Hashimoto, R., & Yamawaki, S.
  • Journal Title: Psychological Medicine Volume: 47 Issue: 5 Pages: 877-888
  • DOI: 10.1017/s0033291716002956
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disrupted Brain Activation and Deactivation Pattern during Semantic Verbal Fluency Task in Patients with Major Depression. (2017)
  • Author(s): Takamura M, Okamoto Y, Okada G, Toki S, Yamamoto T, Yamamoto O, Jitsuiki H, Yokota N, Tamura T, Kurata A, Kaichi Y, Akiyama Y, Awai K, Yamawaki S
  • Journal Title: Neuropsychobiology Volume: 74 Issue: 2 Pages: 69-77
  • DOI: 10.1159/000453399
  • Peer Reviewed
• [Journal Article] Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices. (2017)
  • Author(s): Yoshimura S, Okamoto Y, Matsunaga M, Onoda K, Okada G, Kunisato Y, Yoshino A, Ueda K, Suzuki SI, Yamawaki S.
  • Journal Title: J Affect Disord Volume: 208 Pages: 610-614
  • DOI: 10.1016/j.jad.2016.10.017
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased amygdala reactivity following early life stress: a potential resilience enhancer role. (2017)
  • Author(s): Yamamoto T, Toki S, Siegle GJ, Takamura M, Takaishi Y, Yoshimura S, Okada G, Matsumoto T, Nakao T, Muranaka H, Kaseda Y, Murakami T, Okamoto Y, Yamawaki S
  • Journal Title: BMC psychiatry Volume: 17 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s12888-017-1201-x
  • NAID: 120006814094
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regional brain functions in the resting state indicative of potential differences between depression and chronic pain (2017)
  • Author(s): Yoshino Atsuo、Okamoto Yasumasa、Doi Mitsuru、Otsuru Naofumi、Okada Go、Takamura Masahiro、Ichikawa Naho、Yokoyama Satoshi、Yamashita Hidehisa、Yamawaki Shigeto
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 3003-3003
  • DOI: 10.1038/s41598-017-03522-1
  • Peer Reviewed / Open Access
• [Journal Article] Patients with major depressive disorder exhibit reduced reward size coding in the striatum (2017)
  • Author(s): Takamura Masahiro、Okamoto Yasumasa、Okada Go、Toki Shigeru、Yamamoto Tetsuya、Ichikawa Naho、Mori Asako、Minagawa Hideaki、Takaishi Yoshiyuki、Fujii Yasutaka、Kaichi Yoko、Akiyama Yuji、Awai Kazuo、Yamawaki Shigeto
  • Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry Volume: 79 Pages: 317-323
  • DOI: 10.1016/j.pnpbp.2017.07.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identifying melancholic depression biomarker using whole-brain functional connectivity (2017)
  • Author(s): Ichikawa N, Lisi G, Yahata N, Okada G, Takamura M, Yamada M, Suhara T, Hashimoto R, Yamada T, Yoshihara Y, Takahashi H, Kasai K, Kato N, Yamawaki S, Kawato M, Morimoto J, Okamoto Y
  • Journal Title: ArXiv Volume: -
  • Peer Reviewed
• [Journal Article] Differential effects of chronic stress in young-adult and old female mice: cognitive-behavioral manifestations and neurobiological correlates (2017)
  • Author(s): Lotan A、Lifschytz T、Wolf G、Keller S、Ben-Ari H、Tatarsky P、Pillar N、Oved K、Sharabany J、Merzel T K、Matsumoto T、Yamawaki Y、Mernick B、Avidan E、Yamawaki S、Weller A、Shomron N、Lerer B
  • Journal Title: Molecular Psychiatry Volume: - Issue: 6 Pages: 1432-1445
  • DOI: 10.1038/mp.2017.237
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 精神医療に求められるエビデンス：脳科学に基づく新たな診療・治療法の開発～うつ病を例として (2018)
  • Author(s): 山脇成人
  • Organizer: ヘルスデーターサイエンス研究所セミナー
  • Invited
• [Presentation] 医療ビックデータ時代における精神疾患の革新的診断・治療法の開発 (2018)
  • Author(s): 山脇成人
  • Organizer: 日本製薬工業協会 医療健康分野のビックデータ活用研究会
  • Invited
• [Presentation] こころの脳科学イノベーション うつ病医療からモノづくりまで (2017)
  • Author(s): 山脇成人, 岡本泰昌, 岡田剛, 吉野敦雄, 淵上学, 岡田怜, 山下英尚, 町野彰彦, 志々田一宏, 小早川誠, 神人蘭
  • Organizer: 第113回日本精神神経学会
  • Invited
• [Presentation] 精神医学の新たな社会貢献～脳とこころの化学の産学官連携～ (2017)
  • Author(s): 山脇成人
  • Organizer: 第113回日本精神神経学会
  • Invited
• [Presentation] 5cmルールでのrTMSの施行は適切か? Resting fMRIの知見から (2017)
  • Author(s): 横山仁史, 岡本泰昌, 岡田剛, 高村真広, 市川奈穂, 柴崎千代, 吉野敦雄, 山脇成人
  • Organizer: 第14回日本うつ病学会総会・第17回日本認知療法・認知行動療法学会
• [Presentation] こころの科学としての精神医学：その現状と展望 (2017)
  • Author(s): 山脇成人
  • Organizer: 第6回日本精神科医学会学術大会
  • Invited
• [Presentation] 精神・神経疾患の診断・治療法開発に向けた取り組みと現状の課題～うつ病を例として～ (2017)
  • Author(s): 山脇成人
  • Organizer: 文部科学省 科学技術・学術政策研究所講演会
  • Invited
• [Presentation] 脳科学を応用したネガティブ感性（うつ病）とポジティブ感性（ワクワク感）の可視化技術開発 (2017)
  • Author(s): 山脇成人
  • Organizer: 技術情報協会セミナー
  • Invited
• [Presentation] 脳とこころの科学から見た「うつ」と「希望」 (2017)
  • Author(s): 山脇成人
  • Organizer: 第28回日本緑内障学会
  • Invited
• [Presentation] Depressive rumination reduced by realtime fMRI neurofeedback of the posterior cingulate cortex (PCC) activity (2017)
  • Author(s): Ichikawa, N., Takamura, M., Okada, G., Yokoyama, S., Shibasaki, C., Yoshino, A., Matsumoto, Y., Araki, J., Koura, T., Sumiya, Y., Okamoto, Y. & Yamawaki, S
  • Organizer: Real-time Functional Imaging and Neurofeedback Conference 2017
  • Int'l Joint Research
• [Presentation] A classifier of melancholic depression with whole-brain resting-state connectivity (2017)
  • Author(s): Ichikawa, N., Lisi, G., Yahata, N., Okada, G., Takamura, M., Hashimoto, R., Yamada, T., Yamada, M., Suhara, T., Moriguchi, S., Mimura, M., Yoshihara, Y., Takahashi, H., Kasai, K., Kato, N., Yamawaki, S., Seymour, B., Kawato, M., Morimoto, J. & Okamoto, Y
  • Organizer: Real-time Functional Imaging and Neurofeedback Conference 2017
  • Int'l Joint Research
• [Presentation] Deactivation of DMN nodes during DLPFC fMRI neurofeedback (2017)
  • Author(s): Takamura, M, Okamoto, Y, Ichikawa, N, Okada, G, Yoshino, A, Shibasaki, C, Yamawaki, S.
  • Organizer: Real-time Functional Imaging and Neurofeedback Conference 2017
  • Int'l Joint Research
• [Remarks]
  • URL: https://www.nature.com/articles/mp2017237