Identification of a biomarker for pathophysiology of schizophrenia using Kv3.1/3.2 gene mutations

• Project/Area Number: 17K10320
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kindai University
• Principal Investigator: YANAGI Masaya 近畿大学, 医学部, 講師 (10418775)
• Co-Investigator(Kenkyū-buntansha): 白川 治 近畿大学, 医学部, 教授 (40243307) ; 細見 史治 近畿大学, 医学部, 助教 (40580783) ; 川久保 善宏 近畿大学, 医学部, 助教 (40716429)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 統合失調症 / 前頭前野 / 聴性定常反応 / 安静時脳血流 / NIRS / 前頭葉 / 脳波 / ガンマオシレーション / Kv3.1 / Kv3.2 / ASSR

Outline of Final Research Achievements

We measured the auditory steady state response (ASSR) using electroencephalography (EEG) and the cerebral blood flow at rest using near-infrared spectroscopy（NIRS）to identify a biomarker for the pathophysiology of the prefrontal cortex in schizophrenia. In the analysis of the cerebral blood flow during resting-state, we applied the methods of the amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF), which have been used in fMRI studies to quantify the resting-state blood flow, to the NIRS data. We found that both ALFF and fALFF were decreased in the medial prefrontal cortex of the chronic patients with schizophrenia, and that the ALFF was negatively associated with the symptoms of auditory hallucinations in the patients.

Academic Significance and Societal Importance of the Research Achievements

従来PETやfMRIなどの大掛かりな設備が必要であった安静時脳血流の測定を、簡便な検査手技であるNIRSを用いておこなえることが示されたことは、安静時脳血流測定法の臨床現場への有用性を高めることができる点において有意義である。また、検査課題への取り組みに難を抱えやすい統合失調症患者にとって、こうした負担の少ない検査を用いて病態研究に用いることができることは、今後のバイオマーカー開発にとって有用なものとなる。

Research Products

• [Journal Article] Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia (2019)
  • Author(s): Hosomi Fumiharu、Yanagi Masaya、Kawakubo Yoshihiro、Tsujii Noa、Ozaki Satoshi、Shirakawa Osamu
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 5283-5283
  • DOI: 10.1038/s41598-019-41739-4
  • Peer Reviewed / Open Access
• [Journal Article] Repetition of verbal fluency task attenuates the hemodynamic activation in the left prefrontal cortex: Enhancing the clinical usefulness of near-infrared spectroscopy. (2018)
  • Author(s): Kawakubo Y, Yanagi M, Tsujii N, Shirakawa O.
  • Journal Title: PLoS One. Volume: 13 Issue: 3 Pages: e0193994-e0193994
  • DOI: 10.1371/journal.pone.0193994
  • Peer Reviewed / Open Access
• [Presentation] NIRSを用いた統合失調症前頭葉の安静時脳血流測定 (2019)
  • Author(s): 柳雅也
  • Organizer: 第41回日本生物学的精神医学会
  • Invited
• [Presentation] 統合失調症における自発的脳活動のNIRSを用いた検討 (2019)
  • Author(s): 細見史治、柳雅也、川久保善宏、土屋有希、廣瀬智之、三川和歌子、辻井農亜、尾崎哲、白川治
  • Organizer: 第41回日本生物学的精神医学会
• [Presentation] A preliminarilystudy of near-infrared spectroscopy to measure a resting state activity in prefrontal cortex of schizophrenia (2018)
  • Author(s): 柳 雅也, 細見 史治,川久保 義宏, 土屋 有希, 廣瀬 智之, 三川 和歌子, 辻井 農亜, 尾崎 哲、白川 治
  • Organizer: 第40回日本生物学的精神医学会
• [Presentation] Measuring the resting-state activity of the medial prefrontal cortex in schizophrenic patient using near-infrared spectroscopy (2018)
  • Author(s): 細見史治、柳雅也、川久保善宏、石田静香、尾崎哲、白川治
  • Organizer: WFSBP (World Federation of Societies of Biological Psychiatry) 2018 KOBE
  • Int'l Joint Research
• [Presentation] Near‐Infrared Spectroscopy（NIRS）を用いた安静時脳血流賦活の測定 (2017)
  • Author(s): 細見史治 柳雅也 川久保善宏 土屋有希 広瀬知之 三川和歌子 辻井農亜 白川治
  • Organizer: 日本生物学的精神医学会