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.

项目概要/摘要 全球超过 70% 的人至少经历过一次创伤事件，并且其中很大一部分人曾经历过 会发展为创伤后应激障碍（PTSD）。创伤的生物成本在过度的“磨损”中显而易见 和撕裂”对生物系统的影响，可以加速神经和细胞过程的衰老。例如， 患有 PTSD 的人的大脑比没有 PTSD 的同龄人要老 1-2 岁。创伤 暴露还通过 DNA 甲基化的积累来改变基因表达。 DNA甲基化水平 随着实际年龄的增长，这种“表观遗传时钟”会因创伤事件而加速。尽管有这些 负面影响，大多数遭受创伤的人不会患上创伤后应激障碍（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加速大脑和表观遗传衰老。然而，可能有 与这些因素相关的隐性生物成本，特别是对于经历更严重的个体 外伤后出现急性症状。该项目测试了创伤幸存者的内部资源是否具有 与外部资源相比，生物成本显着更高。使用大型纵向数据集（ AURORA 研究）针对从美国各地急诊科招募的外伤人员 国家，我们将测试外部弹性（可操作为更高的收入）与内部弹性之间的关联 复原力（在康纳戴维森复原力量表上表现为更高的分数）和加速的大脑 （brainAGE；目标 1）和表观遗传衰老（epiAGE；目标 2）。我们预计 BrainAGE 和 epiAGE 将介导 复原力因素与未来 PTSD 症状（受伤后 6 个月）之间的关系。重要的是，我们 预计一个人的急性创伤后应激障碍症状（受伤后两周）会缓和这些关系。 具有更严重的 2 周 PTSD 症状和更高的内部复原力的参与者将表现出更高的 BrainAGE 和 epiAGE 而具有相似症状和较高外部复原力的参与者将表现出更典型的 老化模式。在目标 3 中，我们将测试南方地区的 BrainAGE、PTSD 和复原力因素之间的关系 非洲经常遭受创伤的妇女队列评估普遍性。本次培训目标 奖学金旨在进一步提高申请人在以下方面的知识和技能：1）高级神经影像分析， 2) 神经精神病学研究的表观基因组方法，3) 对 PTSD 的临床理解，4) 文化 流行病学精神病学研究的能力，以及 5) 科学沟通和有效的指导。 这些结果将为创伤后应激障碍的治疗和预防提供信息。通过更好地理解弹性是如何 在生物学上促进，可以开发药理学疗法来增强内源性恢复力 机制。此外，研究结果可能会改善公共卫生层面的创伤后干预措施 说明临床医生和政策制定者应瞄准的复原力因素类型。