Longitudinal examination of DNA methylation in maltreated children

受虐待儿童 DNA 甲基化的纵向检查

• 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
• 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

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.

项目摘要/摘要 儿童虐待是发展精神疾病和慢性病的主要危险因素 以及整个生命周期的严重身体健康问题。新兴证据表明表观遗传 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 在胎儿发育中很早就调节细胞分化，并对环境影响有反应， 包括童年时期的虐待。然而，对甲基化如何纵向改变的基本了解 时间尚未实现，几乎不了解童年虐待如何影响这些发展 轨迹。同样，尽管最近的工作表明，应激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对儿童健康和行为做出贡献 随着时间的推移。拟议研究的目标是：1）检查稳定性和甲基化的变化 糖皮质激素和炎性信号基因从童年早期至中期； 2）确定是否童年 虐待与稳定性和甲基化变化有关。 3）调查是否 糖皮质激素和炎性信号基因的甲基化是一种联系儿童期的机制 虐待精神病结果，健康结果和临床前指标 代谢，炎症和内分泌系统。两百个特征良好的，非常高风险，虐待 和未熟食的孩子将参加。评估早期逆境，包括儿童虐待， 和儿童生物心理社会健康将在幼儿（3至5年）和中年时期（9至 11年）。每次评估时，将从儿童中收集唾液DNA，以评估 糖皮质激素和炎症信号基因。数据分析将着重于建模纵向稳定性 随着时间的流逝，甲基化的变化，并检查虐待作为稳定和变化的预测指标 在甲基化中。甲基化也将作为虐待对儿童健康影响的调解人进行检查 结果。了解整个儿童甲基化的纵向过程将为基础科学提供信息 表观遗传过程以及干预措施的完善，以增强早期儿童的韧性 逆境。