Tyrka Audrey R, Ridout Kathryn K, Parade Stephanie H, Paquette Alison, Marsit Carmen J, Seifer Ronald
Butler Hospital.
Brown University Alpert Medical School.
Dev Psychopathol. 2015 Nov;27(4 Pt 2):1637-45. doi: 10.1017/S0954579415000991.
A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families participated in this study, including 69 with child welfare documentation of moderate to severe maltreatment in the past 6 months. The children, who ranged in age from 3 to 5 years, were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors; and a composite variable assessed the number exposures to these adversities. Methylation of two sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p < .05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p < .05). FKBP5 alters glucocorticoid receptor responsiveness, and FKBP5 gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.
越来越多的证据表明，应激反应系统的改变可能是童年期虐待改变精神病理学风险的一种机制。FK506结合蛋白51（FKBP5）与糖皮质激素受体结合，并改变其对应激信号作出反应的能力。本研究的目的是在一组贫困学龄前儿童样本中，研究FKBP5基因（FKBP5）的甲基化以及FKBP5基因变异与童年期虐待的关系。174个家庭参与了本研究，其中69个家庭有过去6个月中存在中度至重度虐待的儿童福利记录。这些年龄在3至5岁之间的儿童种族和民族各异。通过结构化记录审查和家庭访谈来评估虐待史、其他创伤和背景生活应激源；一个综合变量评估了接触这些逆境的次数。通过亚硫酸氢盐焦磷酸测序法测量FKBP5第7内含子中两个位点的甲基化。受虐待儿童在两个CpG位点的甲基化水平均显著较低（p < 0.05）。终生背景应激暴露显示其中一个位点的甲基化水平有降低的趋势，并且与FKBP5多态性存在相互作用的趋势。一个综合逆境变量也与其中一个位点较低的甲基化水平相关（p < 0.05）。FKBP5改变糖皮质激素受体反应性，并且FKBP5基因甲基化可能是幼儿不良暴露产生生物行为效应的一种机制。
