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Stress, depression, and suicide - molecular basis of the downward spiral

Research Project

Project/Area Number 17H04249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionYokohama City University (2019)
Kobe University (2017-2018)

Principal Investigator

Hishimoto Akitoyo  横浜市立大学, 医学研究科, 教授 (50529526)

Co-Investigator(Kenkyū-buntansha) 泉 剛  北海道医療大学, 薬学部, 教授 (60312360)
白川 治  近畿大学, 医学部, 教授 (40243307)
曽良 一郎  神戸大学, 医学研究科, 教授 (40322713)
朴 秀賢  神戸大学, 医学研究科, 講師 (60455665)
辻井 農亜  近畿大学, 医学部, 准教授 (90460914)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywords自殺 / テロメア / ミトコンドリア / DNAメチル化 / バイオマーカー / テロメア短縮 / ストレス / 神経科学
Outline of Final Research Achievements

Our GWAS identified significant polygenicity for Japanese suicide. We found aberrant changes of various telomere-related factors (telomere length, DNA-methylation aging, methylation status of TERT promoter, mtDNAcn, SIRT1 SNP, and chemokine levels) in suicides, which may contribute to the establishment of "biomarker for suicide risk". We observed that the direction of the relationships between the oxy-Hb changes of the left frontopolar region and mtDNAcn was opposite in bipolar disorder (BD) and major depressive disorder (MDD), which may suggest the potential Potential as Diagnostic Marker for Distinguishing BD From MDD. By using mouse neural stem cells and stress-model rats, we indicated that stress can reduce TERT and some anti-depressant drugs may rescue stress-induced TERT reduction.

Academic Significance and Societal Importance of the Research Achievements

申請者らは本研究課題にて、気分障害や自殺に関連するバイオマーカーを既に多数同定し、今後、抗うつ作用や抗自殺作用とテロメア動態の関連を提示する論文を準備中である。COVID-19による様々な社会不安・ストレスにより、世界各国で今後数年に渡り自殺の増加が懸念される今だからこそ、自殺予防のバイオマーカーや創薬につながる生物学的機序を解明しようとする申請者らの研究は、社会に必ず貢献できると考える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (25 results)

All 2020 2019 2018

All Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 17 results,  Open Access: 15 results) Presentation (7 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Decelerated Epigenetic Aging Associated With Mood Stabilizers in the Blood of Patients With Bipolar Disorder.2020

    • Author(s)
      Okazaki S, Numata S, Otsuka I, Horai T, Kinoshita M, Sora I, Ohmori T, Hishimoto A.
    • Journal Title

      Translational Psychiatry

      Volume: 10 Issue: 1 Pages: 129-129

    • DOI

      10.1038/s41398-020-0813-y

    • NAID

      120006850492

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-exome Sequencing in a Family With a Monozygotic Twin Pair Concordant for Schizophrenia and a Follow-Up Case-Control Study of Identified De-Novo Variants.2020

    • Author(s)
      Hoya S, Watanabe Y, Nunokawa A, Otsuka I, Shibuya M, Igeta H, Hishimoto A, Someya T.
    • Journal Title

      Psychiatric Genetics

      Volume: 30 Issue: 2 Pages: 60-63

    • DOI

      10.1097/ypg.0000000000000250

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ATP and Repetitive Electric Stimulation Increases Leukemia Inhibitory Factor Expression in Astrocytes: A Potential Role for Astrocytes in the Action Mechanism of Electroconvulsive Therapy2020

    • Author(s)
      Maruyama S, Boku S, Okazaki S, Kikuyama H, Mizoguchi Y, Monji A, Otsuka I, Sora I, Kanazawa T, Hishimoto A, Yoneda H.
    • Journal Title

      Psychiatry Clin Neurosci .

      Volume: . Issue: 5 Pages: 12986-12986

    • DOI

      10.1111/pcn.12986

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accelerated Extrinsic Epigenetic Aging and Increased Natural Killer Cells in Blood of Suicide Completers2020

    • Author(s)
      Okazaki S, Otsuka I, Horai T, Hirata T, Takahashi M, Ueno Y, Boku S, Sora I, Hishimoto A.
    • Journal Title

      Prog Neuropsychopharmacol Biol Psychiatry .

      Volume: 98 Pages: 109805-109805

    • DOI

      10.1016/j.pnpbp.2019.109805

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemokine Alterations in the Postmortem Brains of Suicide Completers2020

    • Author(s)
      Shinko Y, Otsuka I, Okazaki S, Horai T, Boku S, Takahashi M, Ueno Y, Sora I, Hishimoto A.
    • Journal Title

      J Psychiatr Res .

      Volume: 120 Pages: 29-33

    • DOI

      10.1016/j.jpsychires.2019.10.008

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association studies identify polygenic effects for completed suicide in the Japanese population.2019

    • Author(s)
      Otsuka I, Akiyama M, Shirakawa O, Okazaki S, Momozawa Y, Kamatani Y, Izumi T, Numata S, Takahashi M, Boku S, Sora I, Yamamoto K, Ueno Y, Toda T, Kubo M, Hishimoto A
    • Journal Title

      Neuropsychopharmacology

      Volume: 44 Issue: 12 Pages: 2119-2124

    • DOI

      10.1038/s41386-019-0506-5

    • NAID

      120007027666

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Major depressive disorder-associated SIRT1 locus affects the risk for suicide in women after middle age.2019

    • Author(s)
      Hirata T, Otsuka I, Okazaki S, Mouri K, Horai T, Boku S, Takahashi M, Ueno Y, Sora I, Shirakawa O, Hishimoto A.
    • Journal Title

      Psychiatry Res

      Volume: 278 Pages: 141-145

    • DOI

      10.1016/j.psychres.2019.06.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial DNA copy number raises the potential of left frontopolar hemodynamic response as a diagnostic marker for distinguishing bipolar disorder from major depressive disorder.2019

    • Author(s)
      Tsujii N, Otsuka I, Okazaki S, Yanagi M, Numata S, Yamaki N, Kawakubo Y, Shirakawa O, Hishimoto A.
    • Journal Title

      Frontiers in Psychiatry

      Volume: in press

    • NAID

      120006869526

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neurexin 3 transmembrane and soluble isoform expression and splicing haplotype are associated with neuron inflammasome and Alzheimer's disease.2019

    • Author(s)
      Hishimoto A, Pletnikova O, Lang DL, Troncoso JC, Egan JM, Liu QR.
    • Journal Title

      Alzheimer's Research & Therapy

      Volume: 11 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s13195-019-0475-2

    • NAID

      120006604676

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic clock analysis of blood samples from Japanese schizophrenia patients.2019

    • Author(s)
      Okazaki S, Otsuka I, Numata S, Horai T, Mouri K, Boku S, Ohmori T, Sora I, Hishimoto A.
    • Journal Title

      NPJ Schizophrenia

      Volume: 5 Issue: 1 Pages: 4-4

    • DOI

      10.1038/s41537-019-0072-1

    • NAID

      120006629323

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study.2018

    • Author(s)
      Ito T, Yamamoto K, Ohsawa F, Otsuka I, Hishimoto A, Sora I, Hirai M, Yano I.
    • Journal Title

      Journal of Pharmaceutical Health Care and Sciences

      Volume: 4 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s40780-018-0126-y

    • NAID

      120006543322

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Telomere shortening in alcohol dependence: Roles of alcohol and acetaldehyde.2018

    • Author(s)
      Yamaki N, Matsushita S, Hara S, Yokoyama A, Hishimoto A, Higuchi S.
    • Journal Title

      Journal of Psychiatric Research

      Volume: 109 Pages: 27-32

    • DOI

      10.1016/j.jpsychires.2018.11.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of chromosome Y loss in men with schizophrenia.2018

    • Author(s)
      Hirata T, Hishimoto A, Otsuka I, Okazaki S, Boku S, Kimura A, Horai T, Sora I.
    • Journal Title

      Neuropsychiatr Dis Treat.

      Volume: 14 Pages: 2115-2122

    • DOI

      10.2147/ndt.s172886

    • NAID

      120006510199

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondrial DNA copy number of peripheral blood in bipolar disorder: The present study and a meta-analysis.2018

    • Author(s)
      Yamaki N, Otsuka I, Numata S, Yanagi M, Mouri K, Okazaki S, Boku S, Horai T, Ohmori T, Shirakawa O, Sora I, Hishimoto A.
    • Journal Title

      Psychiatry Research

      Volume: 269 Pages: 115-117

    • DOI

      10.1016/j.psychres.2018.08.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longer telomeres in elderly schizophrenia are associated with long-term hospitalization in the Japanese population.2018

    • Author(s)
      Zhang Y, Hishimoto A, Otsuka I, Watanabe Y, Numata S, Yamamori H, Boku S, Horai T, Someya T, Ohmori T, Hashimoto R, Sora I.
    • Journal Title

      J Psychiatr Res

      Volume: 103 Pages: 161-166

    • DOI

      10.1016/j.jpsychires.2018.05.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia.2018

    • Author(s)
      Okazaki S, Hishimoto A, Otsuka I, Watanabe Y, Numata S, Boku S, Shimmyo N, Kinoshita M, Inoue E, Ohmori T, Someya T, Sora I.
    • Journal Title

      Prog Neuropsychopharmacol Biol Psychiatry.

      Volume: 83 Pages: 33-41

    • DOI

      10.1016/j.pnpbp.2018.01.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of chromosome Y in blood, but not in brain, of suicide completers2018

    • Author(s)
      Kimura A, Hishimoto A, Otsuka I, Okazaki S, Boku S, Horai T, Izumi T, Takahashi M, Ueno Y, Shirakawa O, Sora I
    • Journal Title

      PLoS One

      Volume: 13 Issue: 1 Pages: e0190667-e0190667

    • DOI

      10.1371/journal.pone.0190667

    • NAID

      120006382347

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Loss of chromosome Y in blood, but not in brain, of suicide completers.2018

    • Author(s)
      Otsuka I, Okazaki S, Kimura A, Horai T, Izumi T, Takahashi M, Ueno Y, Shirakawa O, Sora I, Hishimoto A.
    • Organizer
      WFSBP Asia Pacific Regional Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mitochondrial DNA copy number of peripheral blood in bipolar disorder:the present study and a meta-analysis.2018

    • Author(s)
      Yamaki N, Otsuka I, Mouri K, Boku S, Numata S, Yanagi M, Ohmori T, Shirakawa O, Sora I, Hishimoto A.
    • Organizer
      WFSBP Asia Pacific Regional Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mosaic loss of chromosome Y in peripheral blood and its risk variants in men with schizophrenia.2018

    • Author(s)
      Hirata T, Okazaki S, Otsuka I, Boku S, Aoyama S, Eguchi N, Kimura A, Horai T, Sora I, Hishimoto A.
    • Organizer
      WFSBP Asia Pacific Regional Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia.2018

    • Author(s)
      Okazaki S, Otsuka I, Watanabe Y, Numata S, Boku S, Shimmyo N, Ohmori T, Someya T, Sora I, Hishimoto A.
    • Organizer
      WFSBP Asia Pacific Regional Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ALCOHOL-RELATED POLYMORPHISMS AND RISK FOR SUICIDE IN THE JAPANESE POPULATION.2018

    • Author(s)
      Otsuka I, Hishimoto A.
    • Organizer
      The 19th Congress of the International Society for Biomedical Research on Alcoholism.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ABERRANT TELOMERES IN ALCOHOL DEPENDENCE, MOOD DISORDER AND SUICIDEABERRANT TELOMERES IN ALCOHOL DEPENDENCE, MOOD DISORDER AND SUICIDE.2018

    • Author(s)
      Yamaki N, Hishimoto A.
    • Organizer
      The 19th Congress of the International Society for Biomedical Research on Alcoholism.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The cell cycle-related genes as biomarkers for schizophrenia.2018

    • Author(s)
      Okazaki S, Boku S, Otsuka I, Eguchi N, Sora I, Akitoyo Hishimoto A.
    • Organizer
      Neuroscience 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] Facilitating Resilience After PTSD: A Translational Approach2018

    • Author(s)
      Ikuo Otsuka, Akitoyo Hishimoto(分担執筆)
    • Total Pages
      243
    • Publisher
      Nova Science Pub Inc
    • ISBN
      1536130974
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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