Endophenotype integrated analysis of brain imaging and cognitive function in adolescent obsessive-compulsive disorder.

• Project/Area Number: 19K08076
• 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: Kyushu University
• Principal Investigator: Murayama Keitaro 九州大学, 大学病院, 助教 (20645981)
• Co-Investigator(Kenkyū-buntansha): 中尾 智博 九州大学, 大学病院, 講師 (50423554) ; 樋渡 昭雄 九州大学, 医学研究院, 准教授 (30444855) ; 山下 洋 九州大学, 大学病院, 学術研究員 (20253403)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 強迫性障害 / エンドフェノタイプ / 脳画像研究 / 神経心理機能 / 脳大域ネットワーク / 安静時機能的MRI / 反応抑制障害 / 小脳 / 安静時脳機能画像 / 反応抑制機能 / 大域脳ネットワーク / 安静時fMRI / 強迫症 / 認知機能 / 脳機能画像 / 安静時脳機能的結合 / 児童思春期 / 脳画像

Outline of Research at the Start

強迫性障害（obsessive-compulsive disorder:OCD）の半数は児童思春期に発症する。この児童思春期発症OCDは成人期発症OCDとの臨床的異種性から、これまでの臨床研究では成人OCDと区別されて報告さてきた。
本研究では、特に児童思春期のOCD患者とその第一度近親者（両親や同胞）を対象とし脳画像解析と神経心理機能検査を用いて、endophenotype（中間表現型）の調査を行うことで児童思春期OCDの臨床的な異種性だけではなく、脳画像と神経心理検査という客観的な指標を用いた生物学的異種性を明らかにすることが目的である。

Outline of Final Research Achievements

The aim of this study was to investigate whether patients with obsessive-compulsive disorder in childhood and adolescence and their relatives have abnormalities in similar intrinsic brain networks. However, the recruitment of child and adolescent patients and their relatives did not proceed, and the number of the subjects required for imaging and neuropsychological test analysis was not reached. Therefore, we investigated whether there were abnormalities in the intrinsic brain network and neuropsychological functions in adult patients with OCD and their relatives.
The results revealed that not only OCD patients but also their relatives had common abnormalities in their intrinsic brain networks. In addition, we found that cognitive dysfunction in OCD patients is related to abnormalities in the large intrinsic brain networks.

Academic Significance and Societal Importance of the Research Achievements

強迫性障害は脳の線条体や眼窩前頭皮質、視床といった部位がその病態に強く関与していることが報告されてきた。近年では、脳の様々な部位が機能的に結合し、いくつかの大域的なネットワークを構成していることが分かっている。本研究では、強迫性障害の患者がその脳ネットワークに異常があるということに加えて患者の家族にもそのような異常があることを明らかにした。つまり、脳ネットワークの異常が強迫性障害のエンドフェノタイプ（中間表現型）であることを示唆することができたといえる。

Research Products

• [Journal Article] Alterations of default mode and cingulo-opercular salience network and frontostriatal circuit: A candidate endophenotype of obsessive-compulsive disorder (2022)
  • Author(s): Tomiyama H, Murayama K, Nemoto K, Hasuzawa S, Mizobe T, Kato K, Matsuo A, Ohono A, Kang M, Togao O, Hiwatashi A, Ishigami K, Nakao T.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 116 Pages: 110516-110516
  • DOI: 10.1016/j.pnpbp.2022.110516
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant resting-state cerebellar-cerebral functional connectivity in unmedicated patients with obsessive-compulsive disorder. (2021)
  • Author(s): Murayama K, Tomiyama H, Tsuruta S, Ohono A, Kang M, Hasuzawa S, Mizobe T, Kato K, Togao O, Hiwatashi A, Nakao T
  • Journal Title: Frontiers in Psychiatry Volume: in press
  • DOI: 10.3389/fpsyt.2021.659616
  • Peer Reviewed / Open Access
• [Journal Article] Increased functional connectivity between presupplementary motor area and inferior frontal gyrus associated with the ability of motor response inhibition in obsessive-compulsive disorder. (2021)
  • Author(s): Tomiyama H, Murayama K, Nemoto K, Tomita M, Hasuzawa S, Mizobe, T, Kato K, Ohno A, Tsuruta S, Hiwatashi A, Nakao T
  • Journal Title: Human Brain Mapping Volume: Nov 24 Issue: 3 Pages: 974-984
  • DOI: 10.1002/hbm.25699
  • Peer Reviewed / Open Access
• [Journal Article] Dysfunction between dorsal caudate and salience network associated with impaired cognitive flexibility in obsessive-compulsive disorder: A resting-state fMRI study (2019)
  • Author(s): Tomiyama H, Nakao T, Murayama K, Nemoto K, Ikari K, Yamada S, Kuwano M, Hasuzawa S, Togao O, Hiwatashi A, Kanba S
  • Journal Title: Neuroimage: Clinical Volume: 24 Pages: 102004-102004
  • DOI: 10.1016/j.nicl.2019.102004
  • NAID: 120007132840
  • Peer Reviewed / Open Access
• [Presentation] 強迫症患者と第一度親族における意思決定機能~意思決定機能は強迫症におけるエンドフェノタイプなのか？ (2021)
  • Author(s): 村山桂太郎、豊見山泰史、大野愛哉、蓮澤優、溝部太郎、加藤研太、Kang Mingi、松尾陽、中尾智博
  • Organizer: 第13回日本不安症学会学術大会
• [Presentation] 強迫症患者における感覚現象の有無による認知機能の差異. (2021)
  • Author(s): 村山桂太郎、豊見山泰史、Kang Mingi、蓮澤優、溝部太郎、加藤研、松尾陽、大野愛哉, 中尾智博.
  • Organizer: 日本認知・行動療法学会第47回大会
• [Presentation] A biological investigation of OCD and hoarding disorder by neuroimaging methods. (2019)
  • Author(s): Tomiyama H, Nakao T, Murayama K
  • Organizer: 6th Congress of Asian College of Neuropsychopharmacology
  • Int'l Joint Research / Invited
• [Presentation] s there abnormal functional connectivity between the cerebellum and the cerebrum networks in un-medicated patients with obsessive-compulsive disorder? (2019)
  • Author(s): Keitaro Murayama, Tomohiro Nakao, Hirofumi Tomiyama, Sae Tsuruta, Aikana Ohno, Suguru Hasuzawa Shigenobu Kanba
  • Organizer: 18th International Forum on Mood and Anxiety Disorders
  • Int'l Joint Research