The Biological Cost of External and Internal Resilience Factors in Trauma Survivors

项目摘要/摘要 全世界超过70%的人至少经历过一次创伤性事件和一个重要的子集 会发展成创伤后应激障碍(PTSD)。创伤的生物代价明显体现在过度的“磨损”上。 对生物系统的破坏会加速神经和细胞过程的衰老。例如， 患有创伤后应激障碍的人的大脑似乎比没有创伤后应激障碍的同龄人年长1-2岁。创伤 暴露也会通过积累DNA甲基化来改变基因表达。DNA甲基化水平 随着年龄的增长，这种“表观遗传时钟”会被创伤性事件加速。尽管如此 对于创伤后应激障碍的负面影响，大多数暴露在创伤中的人不会患上创伤后应激障碍。某些个人强项 或者，社会环境资源增加了克服创伤影响的可能性。这些恢复力 这些因素可能有助于缓冲与创伤相关的大脑加速老化和表观遗传衰老。然而，可能会有 与这些因素相关的隐藏的生物成本，特别是对于经历了更严重 严重的创伤后症状。该项目测试在创伤幸存者中，内部资源是否有 与外部资源相比，生物成本明显更高。使用大型纵向数据集( Aurora研究)从美国各地的急救部门招募的创伤受伤个人 我们将测试外部韧性(作为更高的收入)、内部和外部弹性之间的关系 恢复力(在Connor-Davidson恢复力量表上得分较高)和加速大脑 (脑老化；目标1)和表观遗传老化(表观遗传老化；目标2)。我们预计BrainAGE和EPAGE将在 复原力因素与未来创伤后应激障碍症状(伤后6个月)的关系。重要的是，我们 预计个人的急性创伤后应激障碍症状(受伤后2周)将缓和这些关系。 具有更严重的2周创伤后应激障碍症状和更高的内部韧性的参与者将显示出更大的大脑年龄 而症状相似且外部韧性较高的参与者将表现出更典型的 衰老模式。在目标3中，我们将在南方地区测试BrainAGE、PTSD和弹性因素之间的关系 非洲有反复创伤暴露的妇女队列，以评估推广能力。这所学校的培训目标是 奖学金旨在加深申请者在以下方面的知识和技能：1)高级神经成像分析， 2)神经精神病学研究的表观基因组学方法，3)创伤后应激障碍的临床理解，4)培养 流行病学精神病学研究的能力，以及5)科学交流和有效指导。 这些结果将为创伤后应激障碍的治疗和预防提供参考。通过更好地了解弹性是如何 从生物学上讲，药物疗法可能会被开发出来，以增强内源性的弹性。 机械装置。此外，这些发现可能会通过以下方式在公共卫生层面上改善创伤后干预 说明临床医生和政策制定者应针对的弹性因素的类型。

PROJECT SUMMARY/ABSTRACT Over 70% of individuals world-wide have been exposed to at least one traumatic event and a significant subset will develop posttraumatic stress disorder (PTSD). The biological cost of trauma is evident in the excessive “wear and tear” on biological systems which can accelerate aging of neural and cellular processes. For example, the brains of individuals with PTSD appear 1-2 years older than same-aged counterparts without PTSD. Trauma exposure also modifies gene expression through the accumulation of DNA methylation. DNA methylation levels increase with chronological age but this “epigenetic clock” is accelerated by traumatic events. Despite these negative effects, the majority of trauma-exposed individuals do not develop PTSD. Certain individual strengths or socioenvironmental resources increase the likelihood of overcoming the impact of trauma. These resilience factors may help buffer against trauma-related accelerated brain and epigenetic aging. However, there may be hidden biological costs associated with these factors, especially for individuals who experience more severe symptoms acutely post-trauma. This project tests whether, in trauma survivors, internal resources have a significantly higher biological cost compared to external resources. Using a large longitudinal dataset (the AURORA study) of traumatically injured individuals recruited from Emergency Departments across the United States, we will test the associations between external resilience (operationalized as higher income), internal resilience (operationalized as higher scores on the Connor-Davidson Resilience Scale), and accelerated brain (brainAGE; Aim 1) and epigenetic aging (epiAGE; Aim 2). We anticipate that brainAGE and epiAGE will mediate the relationship between resilience factors and future PTSD symptoms (6-months post-injury). Importantly, we anticipate an individual’s acute PTSD symptoms (2-weeks post-injury) will moderate these relationships. Participants with more severe 2-week PTSD symptoms and higher internal resilience will show greater brainAGE and epiAGE whereas participants with similar symptoms and higher external resilience will display more typical aging patterns. In Aim 3, we will test the relationship between brainAGE, PTSD, and resilience factors in a South African cohort of women with recurrent trauma exposure to evaluate generalizability. The training goals of this fellowship were designed to further the applicant’s knowledge and skills in: 1) advanced neuroimaging analyses, 2) epigenomic approaches for neuropsychiatric research, 3) clinical understanding of PTSD, 4) cultural competency in epidemiologic psychiatric research, and 5) scientific communication and effective mentorship. These results will inform the treatment and prevention of PTSD. By better understanding how resiliency is promoted biologically, pharmacological therapeutics may be developed that boost the endogenous resilience mechanisms. In addition, the findings may improve post-trauma interventions at a public health level by illustrating the types of resilience factors that clinicians and policy makers should target.