Analysis of aberrant methylation on CpG island of X chromosome in male schizophrenia

• Project/Area Number: 16K19765
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Kobe University
• Principal Investigator: Otsuka Ikuo 神戸大学, 医学部附属病院, 助教 (40722880)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 統合失調症 / X染色体 / DNAメチル化 / 性差

Outline of Final Research Achievements

Each CpG methylation status of CpG island A in 40 male schizophrenia (SCZ) patients and 40 healthy males (as "replication cohort") were analysed by MassARRAY; I revealed that approximately 30% of male SCZ have aberrant higher methylation of CpG island A. In addition, I investigated the association between TAF1 gene expression and methylation status of CpG island A using data from replication cohort. As in vitro study, I have been trying CRISPR-Cas experiments using male-derived neural stem cells and iPSC-derived neural cells in order to further clarify the biological importance of aberrant methylation of CpG island A.

Academic Significance and Societal Importance of the Research Achievements

統合失調症の有病率や重症度に性差があることはよく知られているが、その生物学的機序は不明であり、統合失調症とX染色体領域のメチル化異常に着目した研究はほとんどない。本解析を遂行できれば、世界に先駆けて統合失調症の病態や性差に関する生物学的異常の一部をDNAメチル化という可塑性（治療可能性）のある現象を通して解明することにつながり、統合失調症領域における今後の診断・治療の発展に大きな貢献ができると考える。

Research Products

• [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
  • 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] 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
  • Peer Reviewed / Open Access
• [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
• [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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Loss of chromosome Y in blood, but not in brain, of suicide completers (2018)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The cell cycle-related genes as biomarkers for schizophrenia. (2018)
  • Author(s): Okazaki S, Boku S, Otsuka I, Eguchi N, Sora I, Hishimoto A.
  • Organizer: Neuroscience 2018 Annual Meeting
  • 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
  • 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
  • Int'l Joint Research