Interventions of gut bacteria to develop preventive methods for depression.

• Project/Area Number: 18K15484
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kobe University
• Principal Investigator: Horai Tadasu 神戸大学, 医学部附属病院, 講師 (90817826)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 腸内細菌 / ストレス反応性 / DEX-CRH負荷試験 / うつ病 / ストレス反応生

Outline of Final Research Achievements

We started the study and tried to obtain informed consent from depressed patients who were outpatients or hospitalized at our hospital, but we could not obtain informed consent. Most of them were afraid of taking steroids or intravenous CRH. In addition, due to the spread of the coronavirus disease 2019 (COVID-19), the number of eligible patients has decreased significantly, both in terms of first visit patients and inpatients. It is extremely difficult to include both patients and healthy subjects in the study at this time, and we will attempt to recruit patients and healthy control again as soon as the COVID-19 settles down.
We have also conducted several biological studies on mood disorders and schizophrenia.

Academic Significance and Societal Importance of the Research Achievements

本研究は、腸内細菌叢プロファイルと個人のストレス反応性との関連、うつ病の回復や重症化に関連する腸内細菌叢のタイプ・腸内細菌の種類の同定、腸内細菌がうつ病の発症に影響を与える生物学的機序の解明を目的とする研究であった。現在の精神医学は依然としてその診断は臨床症状からの診断が中心で、画像所見や血液検査などの客観的な診断方法は確立されていない。それゆえに本研究で腸内細菌からうつ病の診断や各個人のストレス反応性が解明される可能性があり、学術的にも社会的にも非常に大きな意義をもつものであった。今後も患者の組み入れを継続し、新たな精神疾患の診断法・治療法の発展に寄与したい。

Research Products

• [Journal Article] Platelet-derived growth factor BB: A potential diagnostic blood biomarker for differentiating bipolar disorder from major depressive disorder. (2021)
  • Author(s): Idemoto K, Ishima T, Niitsu T, Hata T, Yoshida S, Hattori K, Horai T, Otsuka I, Yamamori H, Toda S, Kameno Y, Ota K, Oda Y, Kimura A, Hashimoto T, Mori N, Kikuchi M, Minabe Y, Hashimoto R, Hishimoto A, Nakagome K, Iyo M, Hashimoto K.
  • Journal Title: J Psychiatr Res Volume: 134 Pages: 48-56
  • DOI: 10.1016/j.jpsychires.2020.12.051
  • Peer Reviewed / Open Access
• [Journal Article] Unmet needs of patients with major depressive disorder ? Findings from the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ project: A nationwide dissemination, education, and evaluation study (2020)
  • Author(s): Iida Hitoshi、Iga Junichi、Hasegawa Naomi、（45番目）Fujimoto Michiko、et al.
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 74 Issue: 12 Pages: 667-669
  • DOI: 10.1111/pcn.13143
  • Peer Reviewed / Open Access
• [Journal Article] miR-19b is elevated in peripheral blood of schizophrenic patients and attenuates proliferation of hippocampal neural progenitor cells (2020)
  • Author(s): Horai T, Boku S, Okazaki S, Otsuka I, Ratta-Apha W, Mouri K, Yamaki N, Hirata T, Hishimoto A.
  • Journal Title: J Psychiatr Res . Volume: 131 Pages: 102-107
  • DOI: 10.1016/j.jpsychires.2020.09.006
  • NAID: 120006952760
  • Peer Reviewed
• [Journal Article] Chemokine Alterations in the Postmortem Brains of Suicide Completers (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Accelerated Extrinsic Epigenetic Aging and Increased Natural Killer Cells in Blood of Suicide Completers (2020)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research