National Center for PTSD at VA Boston Healthcare System,Boston,MA 02130,USA.
Pharmacogenomics Analysis Laboratory,Research Service, Central Arkansas Veterans Healthcare System,Little Rock,AR,USA.
Psychol Med. 2019 Apr;49(5):791-800. doi: 10.1017/S0033291718001411. Epub 2018 Jun 13.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
创伤后应激障碍(PTSD)和应激/创伤暴露与相对于实际年龄的 DNA 甲基化年龄的进展相关。然而,缺乏关于 DNA 甲基化年龄与更广泛的精神障碍之间的关联的纵向研究。本研究的目的是检验 PTSD、抑郁、广泛性焦虑和酒精使用障碍是否预测 DNA 甲基化年龄随时间的加速(即表观遗传时钟的进展速度或加速率)。
对 179 名参加过伊拉克/阿富汗战争的退伍军人进行了全基因组 DNA 甲基化和一系列全面的精神症状和诊断评估,这些退伍军人在大约 2 年的时间内完成了两次评估。量化了两个 DNA 甲基化年龄指数(Horvath 和 Hannum),每个指数都是一组全基因组 DNA 甲基化探针的加权指数。表观遗传时钟的速度被定义为评估之间 DNA 甲基化年龄随时间的变化。
分析显示,第 1 次评估时的酒精使用障碍(p=0.001)和 PTSD 回避和麻木症状(p=0.02)与 Horvath(而非 Hannum)的细胞衰老指数的表观遗传时钟的加速率相关。
这是第一项表明创伤后病理与表观遗传时钟的加速率呈纵向相关的研究。研究结果表明,加速的细胞衰老可能是应激相关精神病理学的共同生物学后果,这对识别应激相关细胞衰老的机制和开发减缓其速度的干预措施具有重要意义。