The Intergenerational Transmission of Trauma from Terror: A Developmental Perspec

描述(由申请人提供)：拟议的工作涉及NIMH计划公告PA-07-312的一个关键目标，该目标旨在加强对与暴力和创伤有关的精神病理学的病因学的科学理解“。2006年夏天落在以色列北部境内的近4000枚导弹、财产和人员遭受的损失以及恐怖时期许多家庭被限制在防空洞内，为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创造了一个独特的“自然主义”实验室。在这一背景下，我们将检查胎儿的健康和行为，以及战争期间身为北方居民的孕妇的生育参数，并测试胎儿和生育措施的基因和环境适宜性。我们将研究两组：(1)150名因遭受攻击而符合创伤后应激障碍(PTSD)完全标准的城市居民，以及(2)来自同一队列的150名没有创伤后应激障碍症状的女性。这项研究将是第一项检查患有创伤后应激障碍孕妇的胎儿健康和行为的研究，也是第一项测试这些措施的基于基因的脆弱性和基因x环境的研究。这项研究涉及恐怖导致的创伤后应激障碍对胎儿发育的影响，与创伤后应激障碍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.母体创伤后应激障碍会对胎儿的健康和行为产生不利影响。假设1认为，与那些遭受恐怖威胁但没有患上创伤后应激障碍的母亲相比，暴露在恐怖环境中并患有创伤后应激障碍的母亲的胎儿将表现出更差的健康迹象(胎儿发育迟缓、异常反应和心率调节、躯干/肢体运动，以及并发症)，以及更差的出生/新生儿参数(出生体重、头围、分娩时的孕周和并发症)。我们还预测了整个样本中创伤后应激症状和结果指标之间的联系。目的2.心理社会压力和母亲抑郁可以预测胎儿的健康、行为、应激反应和调节。假设2假设，在患有创伤后应激障碍的女性中，心理社会应激源(生活事件、慢性应激源)和母亲抑郁将显著增加其胎儿的风险。假设3预测，在整个样本中，心理社会压力和母亲抑郁将缓和母亲创伤后应激障碍的影响。目的3.分析候选基因与胎儿/新生儿结局的关系。我们将评估后代的基因型(由一组候选基因索引)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与环境的交互作用如下：a)假设4中涉及的风险变量将缓和母亲的创伤后应激障碍和母亲的心理社会应激对胎儿/新生儿结局的影响(即，我们期望观察基因与环境的交互作用)。 公共卫生相关段落：家庭外的暴力，就像美国一些社区所经历的(零星和频繁的)，可以影响到附近的任何人。关于暴露于暴力和创伤后应激障碍对胎儿发育和出生结局的关系的信息，对于理解在有这种暴力的社区中促进发育风险的过程是重要的。在这方面，不利的生殖健康结果在美国和其他发达国家的分布以巨大的种族/伦理差异为特征(Anachebe 2003)。在美国，即使考虑了产科、社会人口和行为风险因素，非裔美国人和非西班牙裔白人妇女的早产率仍然存在近两倍的差异(Collins&Hammond 1996；MacDorman等人2002年)；而且有人提出风险的差异可能与压力和压力生理学的变化有关(Wadwa等人2001)。这项拟议的研究考察了与胎儿健康相关的遗传和环境风险，其结果可以进一步了解心理神经内分泌过程中的个体差异，这些过程是早产和不利神经发育风险的基础或促成因素，两者都代表着美国的主要公共卫生问题。

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.