Neuropsychological and genomic signatures of violence exposure in childhood

儿童时期暴力暴露的神经心理学和基因组特征

基本信息

批准号：
8858661
负责人：
AVSHALOM CASPI
金额：
$ 53.75万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8858661
关键词：
18 year old Accounting Address Adolescence Adolescent Adult Adverse effects Affect Age Behavioral Mechanisms Biological Biological Markers Birth Blood Cell division Child Child Abuse and Neglect Childhood Chromatin Structure Chromosomes Chronic Chronic Disease Chronic stress Clinical Cohort Studies Crime DNA DNA Methylation DNA Sequence Data Data Analyses Data Collection Dementia Development Disease Domestic Violence Environmental Risk Factor Epigenetic Process Exposure to Functional disorder Funding Gene Cluster Gene Expression Gene Expression Profiling Genes Genetic Genomics Great Britain Health Human Immune Immune system Individual Infection Inflammation Inflammatory Inflammatory Response Length Life Life Cycle Stages Life Experience Life Stress Link Longitudinal Studies Major Depressive Disorder Measures Mediating Medical Research Mental Health Methods Molecular Molecular Profiling Neurosecretory Systems Non-Insulin-Dependent Diabetes Mellitus Outcome Parents Positioning Attribute Poverty Publishing Reaction Reading Regulation Research Risk Risk Factors Sexual abuse Short-Term Memory Socioeconomic Status Source Stress Surveys System Telomere Shortening Testing Time Tissue Sample Tissues Twin Multiple Birth Update Variant Violence Vocabulary Youth biobank biological adaptation to stress cardiovascular disorder risk cohort dating violence differential expression effective intervention epigenetic regulation epigenomics executive function experience fitness human tissue indexing mental function neuropsychological pathogen peer victimization perceptual organization processing speed protein structure psychobiologic response skills telomere young adult

项目摘要

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.

描述（由申请人提供）：早年发生的压力经历如何对几十年后的健康状况不佳产生如此强大的直接影响？这些经历何时以及如何融入生物学？为了解决这个问题，我们对 1994-95 年出生的 2,232 名双胞胎进行了追踪（E-Risk 研究）。该队列具有良好的特征、环境和表型特征，在出生、2、5、7、10、12 和 18 岁时进行了评估，并拥有专门的生物库。我们的研究重点是暴力，这是人类压力最常见和最严重的来源之一。我们首先编制童年和青少年时期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，我们检验了这样的假设：在童年和青少年时期遭受暴力的年轻人，到了成年早期，会表现出神经心理功能受损、端粒侵蚀以及参与协调应激反应和调节的基因的差异表达和表观遗传调控。免疫和炎症反应。这项研究的一个关键需求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倾向。 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) 比较暴力暴露对其心理生物学结果不一致的双胞胎，(b) 研究个体内心理生物学结果的变化，将每个孩子作为他或她的孩子自己的控制，并最终 (c) 确定减轻暴力暴露的生物嵌入的保护因素。 E-风险研究将是第一个主要的发展纵向队列研究，汇集对多种暴力暴露和多种压力生物标志物的详细评估，以描述遭受暴力的儿童可能获得持久的疾病脆弱性的机制。