The Intergenerational Transmission of Trauma from Terror: A Developmental Perspec

描述（由申请人提供）：拟议的工作解决了NIMH计划公告PA-07-312的一个关键目标，该计划旨在“加强对与暴力和创伤相关的精神病理学病因学的科学理解”。2006年夏天，近4000枚导弹落在以色列北部，财产和人员遭受的损失，以及恐怖时期许多家庭在防空洞的限制，创造了一个独特的“自然主义”实验室，用于评估暴露在有限的恐怖时期造成的创伤后应激障碍的影响。在此背景下，我们将检查在战争时期居住在北方的孕妇的胎儿健康和行为以及出生参数，并测试胎儿和分娩措施的基因和环境调节作用。我们将研究两组：(1)150名妇女，她们是在“战争”中遭受袭击的城市的居民，由于暴露在袭击中，她们完全符合创伤后应激障碍（PTSD）的标准；(2)150名来自同一队列的妇女，没有表现出PTSD的症状。这项研究将是第一个检查患有创伤后应激障碍的孕妇胎儿健康和行为的研究，也是第一个测试基于基因的脆弱性和基因x环境的研究。该研究探讨了恐怖诱发的PTSD对胎儿发育的影响，与PTSD相关的生物事件从母亲到胎儿的潜在传播，以及可能加剧胎儿风险的环境和遗传因素。本研究的具体目的是：目的1。母亲创伤后应激障碍会对胎儿健康和行为产生不利影响。假设1认为，与未患PTSD的母亲相比，暴露于恐怖环境中并患有PTSD的母亲的胎儿会表现出较差的健康状况（胎儿生长发育迟缓、非典型反应性、心率调节和躯干/肢体运动的挑战以及并发症）和较差的出生/新生儿参数（出生体重、头围、分娩时胎龄和并发症）。我们还预测了整个样本中创伤后应激症状与结果测量之间的关联。目标2。心理社会压力和母亲抑郁预测胎儿健康、行为、应激反应和调节。假设2认为，在患有创伤后应激障碍的女性中，社会心理压力源（生活事件，慢性压力源）和母亲抑郁会增加胎儿的风险。假设3预测，在全样本中，心理社会压力和母亲抑郁会调节母亲创伤后应激障碍的影响。目标3。与胎儿/新生儿结局相关的候选基因分析。我们将评估后代基因型（由一系列候选基因索引）与胎儿/新生儿结局之间的关系。假设4预测，这些基因的变异将对婴儿的结局产生主要影响。假设5预测，我们将发现基因-环境的相互作用如下：a)假设4中涉及的风险变异将调节母亲的创伤后应激障碍和母亲的社会心理压力对胎儿/新生儿结局的影响（即，我们希望观察到基因-环境的相互作用）。

DESCRIPTION (provided by applicant): The proposed work addresses a key goal of NIMH Program Announcement PA-07-312, which seeks to enhance scientific understanding about the etiology of psychopathology related to violence and trauma". The almost 4000 missiles that fell within Northern Israel in the summer of 2006, the damage suffered by property and persons, and the confinement of many families in bomb shelters during the terror period created a unique 'naturalistic' laboratory for assessing the effects of PTSD caused by exposure to a circumscribed period of terror. Within this context, we will examine the health and behavior of fetuses and birth parameters of pregnant women who were residents of the North at the time of the war and test for gene and environmental moderation of fetal and birth measures. We will study two groups: (1) 150 women who are residents of cities attacked during the "war" and who meet full criteria for posttraumatic stress disorder (PTSD) as a result of their exposure to attacks, and (2) 150 women from the same cohort, who show no symptoms of PTSD. The study will be the first study to examine fetal health and behavior in pregnant women with PTSD and the first study to test for gene-based vulnerabilities and Gene x Environment on these measures. The study speaks to the impact of terror induced PTSD on fetal development, the potential transmission of biological events associated with PTSD from mother to fetus, and environmental and genetic factors that may exacerbate fetal risk. The specific aims of the study are: Aim 1. Fetal health and behavior will be adversely affected by maternal PTSD. Hypothesis 1 asserts that fetuses of mothers exposed to terror and suffer from PTSD will show signs of poorer health (stunted fetal growth measures, atypical reactivity and regulation of heart rate and torso/limb movement to challenge, and complications) and poorer birth/neonatal parameters (birth weight, head circumference, gestational age at delivery, and complications) than women who were exposed to terror, but who do not develop PTSD. We also predict an association between posttraumatic stress symptoms and outcome measures, across the sample. Aim 2. Psychosocial stresses and maternal depression predict fetal health, behavior, and stress reactivity and regulation. Hypothesis 2 posits that, among women with PTSD, psychosocial stressors (life events, chronic stressors) and maternal depression will add significant risk to their fetus. Hypothesis 3 predicts that, in the full sample, psychosocial stress and maternal depression will moderate the effects of maternal PTSD. Aim 3. Analyses of candidate gene associations with fetal/neonatal outcomes. We will evaluate the association between offspring's genotype (indexed by a battery of candidate genes) and fetal/neonatal outcomes. Hypothesis 4 predicts that variants of these genes will have main effects on infant outcomes. Hypothesis 5 predicts we will find gene-environment interactions as follows: a) risk variants implicated in hypothesis 4 will moderate the impact that mothers' PTSD and mother's psychosocial stress each have on fetal/neonatal outcomes (i.e., we expect to observe gene-environment interactions). PUBLIC HEALTH RELEVANCE PARAGRAPH: The violence outside the home, as experienced in some US communities (sporadic and frequent) can affect anyone near by. Information regarding the relation between exposure to violence and PTSD on fetal development and birth outcome is important for understanding the processes that can promote developmental risk in communities with such violence. In this regard, the distribution of adverse reproductive health outcomes in the US and other developed nations is characterized by large racial/ethic disparities (Anachebe 2003). In the US, an almost two-fold disparity persists in the rate of premature birth between African American and non-Hispanic White women, even after accounting for obstetric, socio demographic, and behavioral risk factors (Collins & Hammond 1996; MacDorman et al 2002); and it has been suggested that differences in risk may be related to variations in stress and stress physiology (Wadwa et al 2001). The results of the proposed study, which examines genetic and environmental risk in relation to fetal health, can further understanding of individual differences in psycho- neuroendocrine processes that underlie or contribute to the risk of pre maturity and adverse neurodevelopment, and both represent major public health issues in the US.