Mehta Divya, Bruenig Dagmar, Lawford Bruce, Harvey Wendy, Carrillo-Roa Tania, Morris Charles P, Jovanovic Tanja, Young Ross McD, Binder Elisabeth B, Voisey Joanne
School of Psychology and Counselling, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
Neurobiol Stress. 2018 Apr 7;8:112-119. doi: 10.1016/j.ynstr.2018.04.001. eCollection 2018 Feb.
Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males). Primary measures included the Clinician Administered PTSD Scale for DSM-5 and the Connor-Davidson Resilience Scale (CD-RISC). DNAm age prediction was performed using the validated epigenetic clock calculator. Veterans with PTSD had increased PTSD symptom severity (P-value = 3.75 × 10) and lower CD-RISC scores (P-value = 7.5 × 10) than veterans without PTSD. DNAm age was significantly correlated with the chronological age (P-value = 3.3 × 10), but DNAm age acceleration was not different between the PTSD and non-PTSD groups (P-value = 0.24). Evaluating potential protective factors, we found that DNAm age acceleration was significantly associated with CD-RISC resilience scores in veterans with PTSD, these results remained significant after multiple testing correction (P-value = 0.023; r = 0.32). This finding was also replicated in an independent trauma-exposed civilian cohort (P-value = 0.02; r = 0.23). Post-hoc factor analyses revealed that this association was likely driven by "self-efficacy" items within the CD-RISC (P-value = 0.015; r = 0.35). These results suggest that among individuals already suffering from PTSD, some aspects of increased resilience might come at a biological cost.
加速的表观遗传衰老，即DNA甲基化预测年龄（DNAm年龄）与实际年龄之间的差异，与多种疾病相关。本研究调查了表观遗传衰老与创伤后应激障碍（PTSD）的风险及保护因素之间的关系。对211名个体进行了全基因组DNA甲基化分析，其中包括经历过战斗的澳大利亚退伍军人（发现队列，n = 96名男性）和来自格雷迪创伤项目的受过创伤的平民男性（复制队列，n = 115名男性）。主要测量指标包括用于《精神疾病诊断与统计手册》第5版的临床医生管理的PTSD量表和康纳-戴维森韧性量表（CD-RISC）。使用经过验证的表观遗传时钟计算器进行DNAm年龄预测。与没有PTSD的退伍军人相比，患有PTSD的退伍军人的PTSD症状严重程度更高（P值 = 3.75 × 10），CD-RISC得分更低（P值 = 7.5 × 10）。DNAm年龄与实际年龄显著相关（P值 = 3.3 × 10），但PTSD组和非PTSD组之间的DNAm年龄加速情况没有差异（P值 = 0.24）。在评估潜在保护因素时，我们发现患有PTSD的退伍军人中，DNAm年龄加速与CD-RISC韧性得分显著相关，经过多次检验校正后，这些结果仍然显著（P值 = 0.023；r = 0.32）。这一发现也在一个独立的受过创伤的平民队列中得到了重复验证（P值 = 0.02；r = 0.23）。事后因素分析表明，这种关联可能是由CD-RISC中的“自我效能感”项目驱动的（P值 = 0.015；r = 0.35）。这些结果表明，在已经患有PTSD的个体中，恢复力增强的某些方面可能会付出生物学代价。
