Models of Risk for PTSD

描述（由申请人提供）：本申请旨在识别创伤后应激障碍（PTSD）和/或重度抑郁症（MDD）急性创伤后风险的认知和神经生物学标志物。此外，还概述了候选人获得必要培训的计划，以发展一个独立的研究项目，重点是了解创伤后应激障碍和重度抑郁症的风险标记和机制。候选人之前在生活压力、情绪障碍和创伤后应激障碍研究方面的训练使他能够磨练许多实现这一目标所需的技能。然而，他需要额外的培训，指导和五个关键领域的经验：(1)昼夜交感神经系统（SNS）和下丘脑-垂体-肾上腺（HPA）活动；(2) SNS和HPA对应激的反应性；(3) PTSD的神经生物学风险标志物；(4) PTSD和MDD的认知危险因素；(5)纵向设计研究创伤后应激障碍和/或重度抑郁症的发病和病程的应对和神经内分泌轨迹。我们制定了一个全面的培训大纲，包括实践教学经验、正式课程、独立阅读、研讨会、网络研讨会、指导会议和与这五个关键领域的专家咨询。拟议的研究将在60名最近暴露于人际暴力（IPV）的妇女和40名未暴露于人际暴力的妇女的样本中，使用四波数据收集（暴露于IPV后1个月内，以及初步评估后1、3和6个月），调查从人际暴力（IPV）暴露到创伤后应激障碍和/或重度抑郁症的纵向途径。虽然女性在遭受创伤后患PTSD和/或重度抑郁症的可能性是男性的两倍，但这种风险增加的机制尚不清楚。识别这些疾病的高风险个体对于制定有效的早期干预计划至关重要。HPA和SNS系统是应对压力或创伤的主要防线。患有创伤后应激障碍的个体在创伤后HPA系统活动减少，SNS活动增加。横断面研究表明，创伤后HPA和SNS活动的逐渐分化可能有助于PTSD的维持，但缺乏纵向研究来支持这一假设。虽然PTSD和重度抑郁症经常同时发生，但重度抑郁症症状在创伤暴露后HPA和SNS功能模式中的作用尚未被描述。本研究的主要目的是(a)检查社交网络和HPA每日输出的渐进式差异是否与随着时间的推移而出现的更高水平的PTSD症状有关，以及(b)确定PTSD风险较高的女性是否未能适应其对社会心理压力任务的皮质醇反应。次要目标是检查同时发生的重度抑郁症症状对HPA/SNS系统的日分泌和反应性的作用。应对策略等社会心理因素也可能决定PTSD和/或重度抑郁症的风险，并可能影响SNS/HPA功能。结果将确定与PTSD和/或重度抑郁症风险相关的认知和神经生物学因素，这些因素可用于开发更“个性化”的早期干预计划。

DESCRIPTION (provided by applicant): This application seeks to identify cognitive and neurobiological markers of risk for posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) in the acute aftermath of trauma. In addition, a plan is outlined for the candidate to acquire the necessary training to develop an independent program of research focused on understanding markers and mechanisms of risk for PTSD and MDD. The candidate's prior training in life stress, mood disorders and PTSD research has allowed him to hone many skills necessary for achieving this goal. However, he requires additional training, mentoring and experience in five key areas: (1) diurnal sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) activity; (2) SNS and HPA reactivity to stress; (3) neurobiological risk markers for PTSD; (4) cognitive risk factors for PTSD and MDD; and (5) longitudinal designs to study coping and neuroendocrine trajectories for the onset and course of PTSD and/or MDD. A comprehensive training plain has been developed that includes hands-on didactic experiences, formal coursework, independent readings, seminars, webinars, mentoring meetings and consultation with experts in these five key areas. The proposed study will investigate longitudinal pathways leading from interpersonal violence (IPV) exposure to PTSD and/or MDD in a sample of 60 women recently exposed to IPV and 40 non-exposed women using four waves of data collection (within 1 month after exposure to IPV, and at 1, 3, and 6 months following the initial assessment). Although women are twice as likely as men to develop PTSD and/or MDD after exposure to trauma, the mechanisms underlying this increased risk remain unclear. Identifying individuals at elevated risk for these disorders is critical for developing effective early intervention programs. The HPA and SNS systems serve as main lines of defense in responding to stress or trauma. Individuals who develop PTSD have reduced activity in the HPA system and increased activity in the SNS following trauma. Cross-sectional studies suggest that a progressive divergence of HPA and SNS activity following trauma may contribute to the maintenance of PTSD, but there is scant longitudinal research to support this hypothesis. Although PTSD and MDD frequently co-occur, the role of MDD symptoms in the patterns of HPA and SNS function following trauma-exposure has not yet been described. The primary aims of the proposed study are to (a) examine whether a progressive divergence in SNS and HPA daily output is associated with higher levels of PTSD symptoms over time, and (b) to determine whether women at greater risk for PTSD fail to habituate in terms of their cortisol responses to a psychosocial stress task. Secondary goals will examine the role of co-occurring MDD symptoms on diurnal secretion and reactivity of HPA/SNS systems. Psychosocial factors such as coping strategies may also determine the risk for PTSD and/or MDD and may influence SNS/HPA function. Results will identify cognitive and neurobiological factors associated with risk for PTSD and/or MDD that could be used to develop more "personalized" early intervention programs.