Longitudinal examination of DNA methylation in maltreated children

项目概要/摘要 儿童期虐待是发展精神障碍和慢性精神病的主要危险因素。 和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， 在胎儿发育的非常早期调节细胞分化并且对环境影响有反应， 包括童年虐待然而，对甲基化如何纵向变化的基本理解 时间尚未实现，对儿童虐待如何影响这些发展的了解甚少。 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，甲基化如何纵向有助于儿童健康和行为尚不清楚 随着时间本研究的目标是：1）检测甲基化的稳定性和变化， 糖皮质激素和炎症信号基因从早期到中期的儿童; 2）以确定是否儿童 虐待与甲基化随时间的稳定性和变化有关;以及3）调查是否 糖皮质激素和炎症信号基因的甲基化是儿童期 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。200个特征鲜明的高风险的被虐待的 未受虐待的儿童将参加。对早期逆境的评估，包括童年虐待， 和儿童生物心理社会健康将在幼儿期（3至5岁）和幼儿期（9至10岁） 11年）。在每次评估时，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。数据分析将侧重于纵向稳定性建模 随着时间的推移，甲基化的变化，以及检查虐待作为稳定和变化的预测因素， 甲基化。甲基化也将被视为虐待对儿童健康影响的中介 结果。了解整个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，以及完善干预措施，以提高儿童的复原力， 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.