Longitudinal examination of DNA methylation in maltreated children

项目摘要/摘要 儿童期虐待是导致精神障碍和慢性精神疾病的主要危险因素。 以及一生中严重的身体健康问题。新出现的证据表明，表观遗传学 过程代表了早期逆境和童年的生物行为编码的关键机制 虐待与调节儿童压力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 在胎儿发育的早期就调节细胞分化，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理解 时间尚未达到，对童年虐待如何影响这些发育还知之甚少。 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 从儿童早期到中期的糖皮质激素和炎症信号基因；2)确定儿童时期 虐待与甲基化的稳定性和随时间的变化有关；以及3)调查 糖皮质激素和炎症信号基因的甲基化是连接儿童的一种机制 虐待对精神结果、健康结果和临床前功能障碍指标的影响 代谢、炎症和内分泌系统。两百人特征良好，风险很高，受到虐待 而未受虐待的儿童将参与其中。对早期逆境的评估，包括童年虐待， 儿童的生物心理社会健康将在儿童早期(3至5岁)和儿童中期(9至5岁)获得。 11年)。将在每次评估时从儿童身上收集唾液DNA，以评估 糖皮质激素和炎症信号基因。数据分析将侧重于对纵向稳定性进行建模 以及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素 在甲基化中。甲基化也将作为虐待对儿童健康影响的中介进行检查。 结果。了解儿童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，以及改进干预措施，以提高早产儿的复原力 逆境。

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.