Neuropsychological and genomic signatures of violence exposure in childhood

描述（由申请人提供）：早期生活中发生的压力经历如何对几十年后的健康状况产生如此强大的直接影响？这些经历何时以及如何在生物学上根深蒂固？为了解决这个问题，我们追踪了1994-95年出生的2232对双胞胎（E-Risk Study）。该队列具有良好的特征、环境和表型，在出生、2、5、7、10、12和18岁时进行评估，并有专门的生物库。我们的研究重点是暴露于暴力，这是人类压力最常见和最严重的来源之一。我们首先收集儿童和青少年时期暴力暴露的累积档案，包括儿童虐待、性虐待、家庭暴力、同伴受害、约会暴力和传统犯罪。然后，我们测试了一个假设，即在童年和青少年时期遭受暴力的年轻人，在成年后会表现出神经心理功能受损、端粒侵蚀、参与协调应激反应、免疫和炎症反应调节的基因的差异表达和表观遗传调节。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分开，包括贫困、父母的心理健康和遗传责任。E-Risk队列分析将通过(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部变化，使用每个孩子作为自己的对照，并最终(c)确定减轻暴力暴露的生物嵌入的保护因素，从而隔离暴力暴露的这些影响。E-风险研究将是第一个主要的发展纵向队列研究，汇集了多种暴力暴露和多种压力生物标志物的详细评估，以确定暴力暴露儿童可能获得持久疾病脆弱性的机制。

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.