Development of discrimination between mono-polar and bipolar depression by utilizing positron emission tomography with serotonergic triple tracers

• Project/Area Number: 18H02748
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Yamasue Hidenori 浜松医科大学, 医学部, 教授 (80436493)
• Co-Investigator(Kenkyū-buntansha): 横倉 正倫 浜松医科大学, 医学部, 助教 (00529399) ; 間賀田 泰寛 浜松医科大学, 光尖端医学教育研究センター, 教授 (20209399) ; 尾内 康臣 浜松医科大学, 光尖端医学教育研究センター, 教授 (40436978) ; 亀野 陽亮 浜松医科大学, 医学部, 助教 (40537255)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2018: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: うつ病 / 脳画像研究 / PET / MRI / 認知行動療法 / 専門外来 / 双極性障害 / セロトニン / 脳画像 / 単極性うつ病 / 双極性うつ病 / セロトニン受容体 / セロトニントランスポーター

Outline of Final Research Achievements

The current study registered and analyzed healthy controls and patients with medication free major depression who had written consent to participate in the present study during the study period and met the inclusion and exclusion criteria. Head positron emission tomography (PET) to measure activated microglia and serotonin transporter, resting state functional MRI to measure resting state function connectivity and 1H-Magnetic Resonance Spectroscopy by MEGA-PRESS to measure GABA and glutamate concentrations in the medial prefrontal cortex, and clinical evaluation were performed in the study participants. By analyzing the obtained data, it was found that the molecular pathology in the brain regions such as the right caudate and the subgenual anterior cingulate cortex plays a role in the pathophysiology of major depression.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、うつ病における神経炎症仮説とモノアミノ仮説相互の関係に初めて迫るもので、うつ病の脳分子病態解明や新たな治療標的の創出に結びつくことが期待される。うつ病は生涯有病率20%という頻度の高い疾患で若年成人から中高年に好発するため、生産人口を直撃して社会的な影響も大きい。一方で現状でのうつ病治療薬はモノアミン仮説に立脚したものに限定されており、多くの治療抵抗性症例が生じて当事者および家族そして社会全体への困難が生じている。本研究によって神経炎症仮説さらにはそのモノアミン仮説との相互作用に立脚した新たな治療標的が示されることで、治療抵抗性症例の治療に結びつく新たな治療薬の開発が期待される。

Research Products

• [Journal Article] Individual psychotherapy using psychological first aid for frontline nurses at high risk of psychological distress during the COVID-19 pandemic. (2021)
  • Author(s): Kameno Y, Hanada A, Asai D, Naito Y, Kuwabara H, Enomoto N, Yamasue H.
  • Journal Title: Psychiatry and Clinical Neuroscience Volume: 75 Pages: 25-27
  • DOI: 10.1111/pcn.13170
  • Peer Reviewed
• [Journal Article] White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals (2020)
  • Author(s): Koshiyama D., Fukunaga M., Okada N., Morita K., Nemoto K., Usui K., Yamamori H., Yasuda Y., Fujimoto M., Kudo N., Azechi H., Watanabe Y., Hashimoto N., Narita H., Kusumi I., Ohi K., Shimada T., Kataoka Y., Yamamoto M., Ozaki N., Okada G., Okamoto Y., Harada K., Matsuo K., Yamasue H., Abe O., Hashimoto R., Takahashi T., Hori T., Nakataki M., Onitsuka T., Holleran L., Jahanshad N., van Erp T. G. M.,
  • Journal Title: Molecular Psychiatry Volume: 25 Pages: 883-895
  • DOI: 10.1038/s41380-019-0553-7
  • NAID: 120006980539
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Subcortical Brain Volume Abnormalities in Individuals With an At-risk Mental State (2020)
  • Author(s): Sasabayashi Daiki、Takayanagi Yoichiro、Takahashi Tsutomu、Katagiri Naoyuki、Sakuma Atsushi、Obara Chika、Katsura Masahiro、Okada Naohiro、Koike Shinsuke、Yamasue Hidenori、Nakamura Mihoko、Furuichi Atsushi、Kido Mikio、Nishikawa Yumiko、Noguchi Kyo、Matsumoto Kazunori、Mizuno Masafumi、Kasai Kiyoto、Suzuki Michio
  • Journal Title: Schizophr Bull Volume: - Pages: 834-45
  • DOI: 10.1093/schbul/sbaa011
  • Peer Reviewed / Open Access
• [Journal Article] In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study (2020)
  • Author(s): Yokokura Masamichi、Takebasashi Kiyokazu、Takao Akiyo、Nakaizumi Kyoko、Yoshikawa Etsuji、Futatsubashi Masami、Suzuki Katsuaki、Nakamura Kazuhiko、Yamasue Hidenori、Ouchi Yasuomi
  • Journal Title: Mol Psychiatry Volume: - Pages: 12-12
  • DOI: 10.1038/s41380-020-0784-7
  • Peer Reviewed / Open Access
• [Journal Article] Acute oxytocin effects in inferring others' beliefs and social emotions in people at clinical high risk for psychosis. (2020)
  • Author(s): Schmidt A, Davies C, Paloyelis Y, Meyer N, De Micheli A, Ramella-Cravaro V, Provenzani U, Aoki Y, Rutigliano G, Cappucciati M, Oliver D, Murguia S, Zelaya F, Allen P, Shergill S, Morrison P, Williams S, Taylor D, Borgwardt S, Yamasue H, McGuire P, Fusar-Poli P.
  • Journal Title: Translational Psychiatry Volume: 10 Pages: 203-203
  • DOI: 10.1038/s41398-020-00885-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Machine-learning classification using neuroimaging data in schizophrenia, autism, ultra-high risk and first-episode psychosis (2020)
  • Author(s): Yassin Walid、Nakatani Hironori、Zhu Yinghan、Kojima Masaki、Owada Keiho、Kuwabara Hitoshi、Gonoi Wataru、Aoki Yuta、Takao Hidemasa、Natsubori Tatsunobu、Iwashiro Norichika、Kasai Kiyoto、Kano Yukiko、Abe Osamu、Yamasue Hidenori、Koike Shinsuke
  • Journal Title: Translational Psychiatry Volume: 10 Pages: 1-11
  • DOI: 10.1038/s41398-020-00965-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 妊娠後期に緊張病を発症した双極性障害の1例 (2020)
  • Author(s): 金子信也、宇佐美梨奈、亀野陽亮、桑原斉、山末英典
  • Organizer: 第178回東海精神神経学会
• [Presentation] 医師と脳科学者の協働でこころの発達を健やかに (2019)
  • Author(s): 山末英典
  • Organizer: 日本医療研究開発機構脳とこころの研究課 第4回公開シンポジウム
  • Invited
• [Presentation] 自閉スペクトラム症、うつ病、PTSDについての浜松医大での取り組み (2018)
  • Author(s): 山末英典
  • Organizer: 静岡県精神神経科診療所協会
  • Invited
• [Book] うつ病に対する経頭蓋直流電気刺激法：有効性と安全性」〈講座 精神疾患の臨床〉「気分障害(気分症)」 (2020)
  • Author(s): 亀野陽亮、山末英典
  • Total Pages: 504
  • Publisher: 中山書店
  • ISBN: 452174821X
• [Book] 「治療抵抗性うつ病に対する脳深部刺激術：有効性と安全性」〈講座 精神疾患の臨床〉「気分障害(気分症)」 (2020)
  • Author(s): 山末英典、杉山憲嗣
  • Total Pages: 504
  • Publisher: 中山書店
  • ISBN: 452174821X
• [Book] 気分症群 (2020)
  • Author(s): 亀野陽亮、山末英典
  • Total Pages: 504
  • Publisher: 中山書店
  • ISBN: 9784521748214
• [Remarks] うつ病の認知行動療法専門外来「気分障害のPET研究について」
  • URL: https://www.hama-med.ac.jp/hos/departments/psychiatry/post.html