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Brain glutathione, structure, and blood flow in patients with schizophrenia

Research Project

Project/Area Number 15K09826
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Psychiatric science
Research InstitutionKyoto University

Principal Investigator

Yoshihara Yujiro  京都大学, 医学研究科, 特定助教 (00529464)

Co-Investigator(Kenkyū-buntansha) 杉原 玄一  京都大学, 医学研究科, 助教 (70402261)
Research Collaborator URAYAMA Shin-Ichi  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsグルタチオン / MRスペクトロスコピー / 統合失調症 / 日内変動 / グルタミン酸 / スペクトロスコピー
Outline of Final Research Achievements

There are two hypotheses of schizophrenia, that are glutamatergic dysfunction and impaired glutathione synthesis. Glutamate is an excitatory neurotransmitter, while glutathione is an antioxidant. Previous MR spectroscopy studies about brain glutamate and glutathione in vivo had inconsistent results. In addition, it is not clear whether glutathione and glutamate have daily fluctuations. The current MR spectroscopy study with healthy subjects measuring the two metabolites in the posterior cingulate 6 times a day showed larger fluctuation range than that of repeated scans. Next, our study comparing the two metabolites between patients with schizophrenia and healthy controls on the same time before breakfast showed no significant differences. This result of the comparative test did not support two hypotheses. We have the necessities of searching factors to affect variations of healthy individuals and testing two metabolites in brain different regions using high magnetic field.

Academic Significance and Societal Importance of the Research Achievements

統合失調症は、幻覚や妄想、社会的引きこもりなどの症状により社会的な損失は大きい。新規治療薬や病態解明が待たれている状況である。グルタチオンの前駆物質であるN-アセチルシステインも期待される薬であるが脳内グルタチオンの障害は明確でない。一方、グルタミン酸障害仮説も依然、脳内グルタミン酸のエビデンスが十分とは言えない状況である。今回の研究で脳内グルタチオンとグルタミン酸がある程度の範囲で日内変動が存在することが明らかになり、後部帯状回では二つの物質に患者と健常者では差がないことが判明した。今回の結果を基に、統合失調症の二つの物質のMRスペクトロスコピーによる次のステップの病態解明が可能となった。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Open Access: 4 results,  Peer Reviewed: 4 results)

  • [Journal Article] Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias2019

    • Author(s)
      Yamashita Ayumu、... Okamoto Yasumasa、Tanaka Saori C.、Kawato Mitsuo、Yamashita Okito、Imamizu Hiroshi
    • Journal Title

      PLOS Biology

      Volume: 17 Issue: 4 Pages: e3000042-e3000042

    • DOI

      10.1371/journal.pbio.3000042

    • NAID

      120006734932

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overlapping but asymmetrical relationships between schizophrenia and autism revealed by brain connectivity2018

    • Author(s)
      Yujiro Yoshihara, Giuseppe Lisi, Noriaki Yahata, Hidehiko Takahash, et al.
    • Journal Title

      biorxiv

      Volume: -

    • DOI

      10.1101/403212

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] Effect of phase-encoding direction on group analysis of resting-state functional magnetic resonance imaging2018

    • Author(s)
      Mori Yasuo、Miyata Jun、Isobe Masanori、Son Shuraku、Yoshihara Yujiro、Aso Toshihiko、Kouchiyama Takanori、Murai Toshiya、Takahashi Hidehiko
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 72 Issue: 9 Pages: 683-691

    • DOI

      10.1111/pcn.12677

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A prediction model of working memory across health and psychiatric disease using whole-brain functional connectivity2018

    • Author(s)
      Yamashita Masahiro、Yoshihara Yujiro、Hashimoto Ryuichiro、Yahata Noriaki、Ichikawa Naho、Sakai Yuki、Yamada Takashi、Matsukawa Noriko、Okada Go、Tanaka Saori C、Kasai Kiyoto、Kato Nobumasa、Okamoto Yasumasa、Seymour Ben、Takahashi Hidehiko、Kawato Mitsuo、Imamizu Hiroshi
    • Journal Title

      eLife

      Volume: 7

    • DOI

      10.7554/elife.38844

    • NAID

      120006549308

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Additive Effect of Cigarette Smoking on Gray Matter Abnormalities in Schizophrenia2017

    • Author(s)
      Yokoyama Naoto、Sasaki Hitoshi、Mori Yasuo、Ono Miki、Tsurumi Kousuke、Kawada Ryosaku、Matsumoto Yukiko、Yoshihara Yujiro、Sugihara Genichi、Miyata Jun、Murai Toshiya、Takahashi Hidehiko
    • Journal Title

      Schizophr Bull.

      Volume: 1 Pages: 1-10

    • DOI

      10.1093/schbul/sbx092

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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