Telomere length and mitochondrial DNA copy number in blood and brain of suicide completers

Research Project

Project/Area Number	16K19766
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Psychiatric science
Research Institution	Kobe University
Principal Investigator	Shiroiwa Kyoichi 神戸大学, 医学研究科, 医学研究員 (00420852)
Research Collaborator	Otsuka Ikuo
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	自殺 / テロメア / ミトコンドリア / バイオマーカー
Outline of Final Research Achievements	Short telomere length (TL) and alterations of mitochondrial DNA copy number (mtDNAcn) occur in individuals under psychological stress, and with various psychiatric diseases. However, no study has examined whether aberrant TL or mtDNAcn occur in completed suicide. TL and mtDNAcn in samples from suicide completers (508 peripheral bloods; 20 brains) and controls (peripheral bloods from 535 healthy individuals; 25 post-mortem brains) were analysed by qPCR. Suicide completers had significantly shorter TL and higher mtDNAcn of bloods with age-dependent differences (shorter TL was more remarkably in young suicides; higher mtDNAcn more so in elderly suicides). The normal age-related decline of TL and mtDNAcn were significantly altered in suicide completers. Furthermore, shorter TL and lower mtDNAcn of post-mortem prefrontal cortex were seen in suicide completers compared to controls. This study shows the first association of aberrant telomeres and mtDNA content with suicide completion.
Academic Significance and Societal Importance of the Research Achievements	テロメア長短縮は精神疾患やストレスの簡便かつ有用なバイオマーカーになりうることからも大きな注目を集めている。自殺とテロメア、さらにはミトコンドリアとの関連について、大規模な自殺既遂者サンプルを用いた解析が可能な研究機関は世界的に見ても非常に稀少である。本研究成果は、末梢血テロメア長やテロメア長制御遺伝子の発現、ミトコンドリアDNAコピー数を用いた自殺リスクの判定や、生物学的異常に基づいた合理的な創薬などにつながる可能性があり、今後の自殺予防に関する生物学的知見として高い学術的意義を有すると考えられる。