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

创伤幸存者外部和内部复原因素的生物成本

• 批准号: 10748472
• 负责人: Elisabeth Kathleen Webb
• 金额: $ 6.91万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748472
• 关键词: 2 year old; Acceleration; Accident and Emergency department; Acute Post Traumatic Stress Disorder; Age; Aging; Biological; Biological Aging; Blood specimen; Brain; Buffers; Cell physiology; Chronology; Clinical; Cognitive; Communication; DNA Methylation; Data; Data Set; Development; Disease; Early Intervention; Emotional; Epigenetic Process; Exposure to; Family; Fellowship; Future; Gene Expression; Genetic; Goals; Health Status; Income; Individual; Injury; Intervention; Knowledge; Longevity; Machine Learning; Magnetic Resonance Imaging; Measures; Mediating; Mediation; Mentorship; Outcome; Participant; Pattern; Policy Maker; Population; Post-Traumatic Stress Disorders; Predisposition; Prevention; Process; Psychiatric epidemiology; Public Health; Recovery; Recurrence; Research; Research Personnel; Resources; Risk; Sampling; Social Environment; South Africa; South African; Stress; Survivors; Symptoms; System; Techniques; Testing; Therapeutic; Thick; Training; Trauma; Traumatic injury; United States; Woman; Work; acute symptom; adverse outcome; aged; biological systems; clinical training; cohort; cost; cost comparison; cultural competence; design; epigenomics; experience; gray matter; improved; interest; longitudinal dataset; machine learning model; multimodal data; neural; neuroimaging; neuropsychiatry; new therapeutic target; novel therapeutic intervention; pharmacologic; post-trauma; post-traumatic symptoms; prevent; provider factors; psychologic; recruit; resilience; resilience factor; resilience scale; skills; social; stressor; trauma exposure; traumatic event

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.

项目总结/摘要 全世界超过70%的人至少经历过一次创伤性事件， 会患上创伤后应激障碍创伤的生物学代价在过度的“磨损”中是显而易见的。 和撕裂”的生物系统，可以加速老化的神经和细胞过程。比如说 患有PTSD的个体的大脑比没有PTSD的同龄人大1-2岁。创伤 暴露还通过DNA甲基化的积累改变基因表达。DNA甲基化水平 随着实际年龄的增长而增加，但这种“表观遗传时钟”会因创伤事件而加速。尽管有这些 尽管有负面影响，但大多数创伤暴露个体不会发展为PTSD。某些个人优势 或社会环境资源增加了克服创伤影响的可能性。这些韧性 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老化。然而， 与这些因素相关的隐藏生物成本，特别是对于经历更严重 创伤后的急性症状这个项目测试，在创伤幸存者，内部资源是否有一个 与外部资源相比，生物成本明显较高。使用大型纵向数据集（ AURORA研究）的创伤受伤的个人招募从急诊科在美国 在美国，我们将测试外部弹性（可操作为更高的收入），内部弹性和内部弹性之间的关联。 韧性（具体表现为康纳-戴维森韧性量表的较高分数）和大脑加速 （brainAGE; Aim 1）和表观遗传衰老（epiAGE; Aim 2）。我们预计brainAGE和epiAGE将介导 恢复力因素与未来PTSD症状（受伤后6个月）之间的关系。重要的是我们 预期个体的急性PTSD症状（受伤后2周）将缓和这些关系。 具有更严重的2周PTSD症状和更高内部弹性的参与者将显示更大的brainAGE 和epiAGE，而具有类似症状和较高外部弹性的参与者将显示出更典型的 老化模式在目标3中，我们将在南方地区测试脑年龄、创伤后应激障碍和恢复力因素之间的关系。 评估普遍性的复发性创伤暴露的非洲妇女队列。本次培训的目标 奖学金旨在促进申请人在以下方面的知识和技能：1）先进的神经成像分析， 2)神经精神病学研究的表观基因组方法，3）PTSD的临床理解，4）文化 流行病学精神病学研究的能力，和5）科学沟通和有效的指导。 这些结果将为PTSD的治疗和预防提供信息。通过更好地理解弹性是如何 生物学促进的药理学疗法可以被开发出来，以增强内源性恢复力。 机制等此外，这些发现可能会改善公共卫生层面的创伤后干预， 说明了临床医生和政策制定者应该瞄准的弹性因素的类型。