Evaluating the impact of trauma and PTSD on epigenetic prediction of lifespan and neural integrity
Evaluating the impact of trauma and PTSD on epigenetic prediction of lifespan and neural integrity
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DOI：
10.1038/s41386-020-0700-5
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发表时间：
2020-05-07
影响因子：
7.6
通讯作者：
Smith, Alicia K.
中科院分区：
文献类型：
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作者：
Katrinli, Seyma;Stevens, Jennifer;Smith, Alicia K.
创伤后应激障碍（PTSD）是一些人在创伤暴露后出现的一种衰弱性障碍。创伤和创伤后应激障碍与细胞加速衰老有关。本研究评估了创伤和创伤后应激障碍对创伤平民寿命的表观遗传预测因子加速GrimAge的影响。本研究包括218名患有当前PTSD的个体，427名没有任何PTSD病史的创伤暴露对照组，以及209名有终生PTSD病史但未被归类为当前PTSD病例的被试。创伤事件量表（TEI）和临床创伤后应激障碍量表（CAPS）分别用于测量终身创伤负担和创伤后应激障碍。使用MethylationEPIC或HumanMethylation450 BeadChips检测全血DNA。使用甲基化年龄计算器计算GrimAge估计值。采用MRI t1加权结构图像评估69例女性受试者的皮质厚度。采用多元回归模型检验创伤暴露、PTSD、皮质厚度和GrimAge加速之间的关系。终生创伤负担（p = 0.03）、当前创伤后应激障碍（p = 0.02）和终生创伤后应激障碍（p = 0.005）与GrimAge加速相关，表明预测寿命较短。与终生PTSD的关联在独立队列中得到了验证（p = 0.04）。在MRI亚样本中，GrimAge加速还与右侧外侧眶额皮质（p(adj) = 0.03）和右侧后扣带（p(adj) = 0.04）的皮质萎缩有关，这些大脑区域与情绪调节和威胁调节有关。我们的研究结果表明，终身创伤和创伤后应激障碍可能会导致更高的表观遗传死亡风险。我们还证明了创伤后应激障碍相关脑区皮质萎缩与预期寿命缩短之间的关系。
Post-traumatic stress disorder (PTSD) is a debilitating disorder that develops in some people following trauma exposure. Trauma and PTSD have been associated with accelerated cellular aging. This study evaluated the effect of trauma and PTSD on accelerated GrimAge, an epigenetic predictor of lifespan, in traumatized civilians. This study included 218 individuals with current PTSD, 427 trauma-exposed controls without any history of PTSD and 209 subjects with lifetime PTSD history who are not categorized as current PTSD cases. The Traumatic Events Inventory (TEI) and Clinician-Administered PTSD Scale (CAPS) were used to measure lifetime trauma burden and PTSD, respectively. DNA from whole blood was interrogated using the MethylationEPIC or HumanMethylation450 BeadChips. GrimAge estimates were calculated using the methylation age calculator. Cortical thickness of 69 female subjects was assessed by using T1-weighted structural MRI images. Associations between trauma exposure, PTSD, cortical thickness, and GrimAge acceleration were tested with multiple regression models. Lifetime trauma burden (p = 0.03), current PTSD (p = 0.02) and lifetime PTSD (p = 0.005) were associated with GrimAge acceleration, indicative of a shorter predicted lifespan. The association with lifetime PTSD was replicated in an independent cohort (p = 0.04). In the MRI sub sample, GrimAge acceleration also associated with cortical atrophy in the right lateral orbitofrontal cortex (p(adj) = 0.03) and right posterior cingulate (p(adj) = 0.04), brain areas associated with emotion-regulation and threat-regulation. Our findings suggest that lifetime trauma and PTSD may contribute to a higher epigenetic-based mortality risk. We also demonstrate a relationship between cortical atrophy in PTSD-relevant brain regions and shorter predicted lifespan.