Neuropsychological and genomic signatures of violence exposure in childhood

描述（由申请人提供）：如何在早期生活中发生的压力经历对几十年后的健康状况有如此强大的直接影响？这些经验何时以及如何成为生物嵌入？为了解决这个问题，我们跟踪了1994-95年出生的2,232对双胞胎（E风险研究）。该队列在环境和表型方面都得到了很好的表征，在出生、2、5、7、10、12和18岁时进行了评估，并有一个专门的生物库。我们的研究重点是暴露于暴力，人类压力的最常见和最严重的来源之一。我们开始通过汇编儿童和青少年暴力暴露的累积档案，包括虐待儿童，性虐待，家庭暴力，同伴受害，约会暴力和传统犯罪。然后，我们测试的假设，即年轻人谁是暴露于暴力在童年和青春期将，由年轻的成年，表现出受损的神经心理功能，端粒侵蚀，差异表达和表观遗传调控的基因参与协调的压力反应和调节免疫和炎症反应。这项研究的一个关键需要是将暴力暴露与相关的风险因素，包括贫困，父母的心理健康和遗传责任分开。对E-Risk队列的分析将通过以下方式隔离暴力暴露的这些影响：（a）比较暴力暴露不一致的双胞胎的心理生物学结果;（B）研究心理生物学结果的个体内变化，将每个孩子作为他或她自己的对照;以及最终（c）确定减轻暴力暴露的生物学嵌入的保护因素。E-Risk研究将是第一个主要的纵向发展队列研究，汇集了对多种暴力暴露和多种压力生物标志物的详细评估，以描述暴力暴露儿童可能获得持久的疾病脆弱性的机制。

DESCRIPTION (provided by applicant): How do stressful experiences that happen in early life have such powerful direct effects on poor health decades later? When and how do these experiences become biologically embedded? To address this question, we are following a 1994-95 birth cohort of 2,232 twins (the E-Risk Study). The cohort is well- characterized, environmentally and phenotypically, with assessments at birth, 2,5,7,10,12, and 18 years, and has a dedicated biobank. Our research focuses on exposure to violence, one of the most common and severe sources of human stress. We begin by compiling cumulative dossiers of violence exposure in childhood and adolescence, including child maltreatment, sexual abuse, domestic violence, peer victimization, dating violence, and conventional crime. We then test the hypothesis that young people who are exposed to violence in childhood and adolescence will, by young adulthood, show compromised neuropsychological functioning, telomere erosion, and differential expression and epigenetic regulation of genes involved in the coordination of the stress response and the regulation of immune and inflammatory reactions. A key need in this research is for violence exposure to be disentangled from associated risk factors, including poverty, parents' mental health, and genetic liability. Analyses with the E-Risk cohort will isolat these effects of violence exposure by (a) comparing twins who are discordant for violence exposure on their psychobiological outcomes, (b) studying within-individual changes in psychobiological outcomes, using each child as his or her own control, and ultimately (c) identifying protective factors that mitigate biological embedding of exposure to violence. The E- Risk Study will be the first major developmental-longitudinal cohort study to bring together detailed assessments of multiple kinds of exposure to violence and multiple stress biomarkers, in order to characterize the mechanisms through which violence-exposed children may acquire lasting vulnerability to disease.