Aberrant telomere length and mitochondrial DNA copy number in suicide completers.
Aberrant telomere length and mitochondrial DNA copy number in suicide completers.
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DOI：
10.1038/s41598-017-03599-8
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发表时间：
2017-06-09
影响因子：
4.6
通讯作者：
Hishimoto A
中科院分区：
文献类型：
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作者：
Otsuka I;Izumi T;Boku S;Kimura A;Zhang Y;Mouri K;Okazaki S;Shiroiwa K;Takahashi M;Ueno Y;Shirakawa O;Sora I;Hishimoto A
短端粒长度（TL）发生在心理应激和各种精神疾病的个体中。最近的研究也报道了在几种神经精神疾病下线粒体DNA拷贝数（mtDNA Acn）的改变。然而，没有研究检查是否异常TL或mtDNAcn发生在完成自杀，精神疾病的最严重的结果之一。采用定量聚合酶链反应分析了528例无严重身体疾病的自杀完成者（508例外周血; 20例脑）和560例对照组（535例健康人外周血; 25例死后脑）的尸检样本中的TL和mtDNA。自杀完成者外周血TL显著缩短，mtDNAc n显著升高，且存在性别和年龄依赖性差异（女性/青年自杀者TL缩短更显著，男性/老年自杀者mtDNAc n升高更显著）。自杀完成者的TL和mtDNA的正常年龄相关性下降显著改变。此外，与对照组相比，自杀完成者的TL较短，死后前额叶皮层的mtDNA含量较低。这项研究首次显示了异常端粒和mtDNA含量与自杀完成的关联。我们的研究结果表明，对端粒缩短和线粒体功能障碍的进一步研究可能有助于阐明自杀相关病理生理学的分子基础。
Short telomere length (TL) occurs in individuals under psychological stress, and with various psychiatric diseases. Recent studies have also reported mitochondrial DNA copy number (mtDNAcn) alterations under several neuropsychiatric conditions. However, no study has examined whether aberrant TL or mtDNAcn occur in completed suicide, one of the most serious outcomes of mental illnesses. TL and mtDNAcn in post-mortem samples from 528 suicide completers without severe physical illness (508 peripheral bloods; 20 brains) and 560 samples from control subjects (peripheral bloods from 535 healthy individuals; 25 post-mortem brains) were analysed by quantitative polymerase chain reaction. Suicide completers had significantly shorter TL and higher mtDNAcn of peripheral bloods with sex/age-dependent differences (shorter TL was more remarkably in female/young suicides; higher mtDNAcn more so in male/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. Our results indicate that further research on telomere shortening and mitochondrial dysfunction may help elucidate the molecular underpinnings of suicide-related pathophysiology.