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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.

项目总结/文摘