Tyrka Audrey R, Ridout Kathryn K, Parade Stephanie H
Butler Hospital.
Brown University Alpert Medical School.
Dev Psychopathol. 2016 Nov;28(4pt2):1319-1331. doi: 10.1017/S0954579416000870. Epub 2016 Oct 3.
Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects. We present recent evidence related to epigenetic regulation of genes involved in hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed.
幼儿期经历对发育有着持久影响,包括患精神疾病的风险。研究这些关联的生物学基础发现,童年期虐待会对生理应激反应以及下丘脑-垂体-肾上腺轴的活动产生影响。越来越多的文献支持这样一种假说,即环境暴露通过表观遗传机制介导其生物学效应。甲基化被认为是表观遗传变化最稳定的形式,它可能是早期生活暴露产生持久影响的一种机制。我们展示了近期有关童年期逆境后下丘脑-垂体-肾上腺轴调节相关基因(即糖皮质激素受体基因,核受体亚家族3,C组成员1 [NR3C1])和FK506结合蛋白51基因(FKBP5)的表观遗传调控以及与精神疾病风险关联的证据。文中还讨论了对干预措施发展及未来研究的启示。