Longitudinal examination of DNA methylation in maltreated children

受虐待儿童 DNA 甲基化的纵向检查

基本信息

批准号：
10002336
负责人：
Stephanie Hart Parade
金额：
$ 54.45万
依托单位：
EMMA PENDLETON BRADLEY HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10002336
关键词：
5 year old Address Adult Affect Affective Age Allergic rhinitis Anxiety Asthma Basic Science Biological Blood Pressure Cell Differentiation process Child Child Abuse and Neglect Child Health Childhood Chronic Chronic Disease Cognitive Cost efficiency DNA DNA Methylation Data Data Analyses Development Disease Endocrine system Epigenetic Process Exposure to Fetal Development Functional disorder Funding Genes Glucocorticoids Goals Gold Health Health behavior Inflammatory Intervention Knowledge Link Literature Longevity Lung Measures Mediating Mediator of activation protein Medical Mental disorders Metabolic Methylation Modeling Moods National Institute of Child Health and Human Development Neurosecretory Systems Obesity Outcome Pattern Physiological Public Health Pulmonary function tests Regulation Research Risk Risk Factors Role Saliva Sampling Signal Transduction Stress System Time Time Study United States Work biobehavior biological adaptation to stress biopsychosocial cognitive task cost design early childhood early life adversity follow-up high risk immune system function individual variation longitudinal course longitudinal design maltreated children maltreatment middle childhood physical conditioning pre-clinical prospective protective factors public health relevance resilience

项目摘要

Project Summary/Abstract Childhood maltreatment is a major risk factor for the development of psychiatric disorders as well as chronic and severe physical health problems across the lifespan. Emerging evidence suggests that epigenetic processes represent key mechanisms underlying the biobehavioral encoding of early adversity, and childhood maltreatment is associated with epigenetic changes in the genes that regulate the child stress response including neuroendocrine and immune system functioning. DNA methylation is a critical epigenetic process that regulates cell differentiation very early in fetal development and is responsive to environmental influences, including childhood maltreatment. Yet a basic understanding of how methylation longitudinally changes over time has yet to be achieved, with little knowledge of how childhood maltreatment affects these developmental trajectories. Likewise, although recent work suggests that methylation of stress sensitive genes contributes to child health outcomes, it is unknown how methylation longitudinally contributes to child health and behavior over time. The goals of the proposed research are: 1) to examine stability and change in methylation of glucocorticoid- and inflammatory-signaling genes from early to middle childhood; 2) to determine if childhood maltreatment is associated with stability and change in methylation over time; and 3) to investigate if methylation of glucocorticoid- and inflammatory-signaling genes is a mechanism linking childhood maltreatment to psychiatric outcomes, health outcomes, and pre-clinical indicators of malfunctioning in metabolic, inflammatory, and endocrine systems. Two hundred well-characterized, very high-risk, maltreated and non-maltreated children will participate. Assessments of early adversity, including childhood maltreatment, and child biopsychosocial health will be captured in early childhood (3 to 5 years) and middle childhood (9 to 11 years). Saliva DNA will be collected from children at each assessment to assess methylation of glucocorticoid- and inflammatory-signaling genes. Data analysis will focus on modeling longitudinal stability and change in methylation over time, as well as examining maltreatment as a predictor of stability and change in methylation. Methylation will also be examined as a mediator of the influence of maltreatment on child health outcomes. Understanding the longitudinal course of methylation across childhood will inform the basic science of epigenetic processes, as well as refinement of interventions to enhance resilience among children with early adversity.

项目概要/摘要童年虐待是精神疾病和慢性疾病发展的主要危险因素以及一生中严重的身体健康问题。新出现的证据表明表观遗传过程代表了早期逆境和童年的生物行为编码的关键机制虐待与调节儿童应激反应的基因的表观遗传变化有关包括神经内分泌和免疫系统功能。 DNA 甲基化是一个关键的表观遗传过程在胎儿发育的早期调节细胞分化并对环境影响做出反应，包括童年时期的虐待。然而对甲基化如何纵向变化的基本了解时间尚未到来，人们对儿童虐待如何影响这些发育知之甚少。轨迹。同样，尽管最近的研究表明压力敏感基因的甲基化有助于儿童健康结果，尚不清楚甲基化如何纵向影响儿童健康和行为随着时间的推移。拟议研究的目标是：1）检查甲基化的稳定性和变化儿童早期至中期的糖皮质激素和炎症信号基因； 2）判断是否童年虐待与甲基化随时间的稳定性和变化有关； 3）调查是否糖皮质激素和炎症信号基因的甲基化是联系童年的机制对精神结果、健康结果和临床前功能障碍指标的虐待代谢、炎症和内分泌系统。 200 个特征明确、风险极高、受到虐待的人未受虐待的儿童将参加。对早期逆境的评估，包括儿童期虐待，儿童生物心理社会健康将在幼儿期（3 至 5 岁）和中期（9 至 5 岁） 11 年）。每次评估时都会收集儿童的唾液 DNA，以评估糖皮质激素和炎症信号基因。数据分析将重点关注纵向稳定性建模甲基化随时间的变化，以及检查虐待作为稳定性和变化的预测因子在甲基化中。还将检查甲基化作为虐待对儿童健康影响的中介因素结果。了解童年时期甲基化的纵向过程将为基础科学提供信息表观遗传过程的研究，以及改进干预措施以增强早期患有早期疾病的儿童的复原力逆境。