Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Sci Rep. 2017 Jun 9;7(1):3176. doi: 10.1038/s41598-017-03599-8.
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.
短端粒长度(TL)存在于心理压力下的个体和各种精神疾病患者中。最近的研究还报告了在几种神经精神疾病下线粒体 DNA 拷贝数(mtDNAcn)的改变。然而,还没有研究检查过在精神疾病最严重的后果之一的完成自杀者中是否存在异常的 TL 或 mtDNAcn。通过定量聚合酶链反应分析了来自 528 名无严重躯体疾病的自杀完成者(508 名外周血;20 名脑)的死后样本和 560 名对照样本(535 名健康个体的外周血;25 名死后脑)的 TL 和 mtDNAcn。自杀完成者的 TL 明显较短,外周血的 mtDNAcn 较高,存在性别/年龄依赖性差异(女性/年轻自杀者的 TL 较短;男性/老年自杀者的 mtDNAcn 较高)。TL 和 mtDNAcn 的正常年龄相关下降在自杀完成者中明显改变。此外,与对照组相比,自杀完成者的死后前额皮质的 TL 较短,mtDNAcn 较低。这项研究首次显示了异常端粒和 mtDNA 含量与自杀完成之间的关联。我们的研究结果表明,进一步研究端粒缩短和线粒体功能障碍可能有助于阐明与自杀相关的病理生理学的分子基础。