Cordero María I, Stenz Ludwig, Moser Dominik A, Rusconi Serpa Sandra, Paoloni-Giacobino Ariane, Schechter Daniel Scott
Department of Psychology, Manchester Metropolitan University, Manchester, United Kingdom.
Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Geneva, Switzerland.
Front Psychiatry. 2022 Aug 19;13:919820. doi: 10.3389/fpsyt.2022.919820. eCollection 2022.
Interpersonal violent (IPV) experiences when they begin in childhood and continue in various forms during adulthood often lead to chronic post-traumatic stress disorder (PTSD) that is associated in multiple studies with hypocortisolism and lower percentage of methylation of the promoter region of the gene coding for the glucocorticoid receptor (NR3C1). This prospective, longitudinal study examined the relationship of NR3C1 methylation among mothers with IPV-related PTSD and their toddlers and then looked at the relationship of maternal NR3C1 methylation and child psychopathology at school age.
Forty-eight mothers were evaluated for life-events history and post-traumatic stress disorder structured clinical interview when their children were ages 12-42 months (mean age 26.7 months, SD 8.8). Their children's psychopathology in terms of internalizing symptoms and externalizing behaviors was evaluated using the Child Behavior Checklist at ages 5-9 years (mean age 7 years, SD 1.1). Percentage of methylation for the NR3C1 gene promoter region was assessed from DNA extracted from maternal and child saliva using bisulfite pyrosequencing. Data analysis involved parametric and non-parametric correlations and multiple linear and logistic regression modeling.
Logistic regression models using child NR3C1 methylation as the dependent variable and maternal NR3C1 methylation and PTSD group status as predictors, as well as the interaction indicated that all three of these significantly predicted child NR3C1 methylation. These findings remained significant when controlling for child age, sex and maternal child abuse history. Overall, maternal NR3C1 methylation when children were toddlers was negatively and significantly associated with child externalizing behavior severity at school age.
We found that correlations between mothers and their children of NR3C1 methylation levels overall and at all individual CpG sites of interest were significant only in the IPV-PTSD group. The latter findings support that NR3C1 methylation in mothers positively and statistically significantly correlates with NR3C1 methylation in their children only in presence of IPV-PTSD in the mothers. This maternal epigenetic signature with respect to this glucocorticoid receptor is significantly associated with child behavior that may well pose a risk for intergenerational transmission of violence and related psychopathology.
人际暴力（IPV）经历若始于童年并在成年期以各种形式持续存在，往往会导致慢性创伤后应激障碍（PTSD），多项研究表明，这种障碍与皮质醇分泌不足以及编码糖皮质激素受体（NR3C1）的基因启动子区域甲基化比例降低有关。这项前瞻性纵向研究考察了患有与IPV相关PTSD的母亲及其幼儿中NR3C1甲基化之间的关系，随后研究了母亲的NR3C1甲基化与学龄期儿童精神病理学之间的关系。
48名母亲在其孩子12至42个月大时（平均年龄26.7个月，标准差8.8）接受了生活事件史和创伤后应激障碍结构化临床访谈评估。在孩子5至9岁时（平均年龄7岁，标准差1.1），使用儿童行为检查表对其孩子的内化症状和外化行为方面的精神病理学进行评估。使用亚硫酸氢盐焦磷酸测序法从母亲和孩子唾液中提取的DNA评估NR3C1基因启动子区域的甲基化百分比。数据分析涉及参数和非参数相关性以及多元线性和逻辑回归建模。
以儿童NR3C1甲基化为因变量、母亲NR3C1甲基化和PTSD组状态为预测变量的逻辑回归模型以及交互作用表明，这三者均显著预测了儿童NR3C1甲基化。在控制儿童年龄、性别和母亲虐待儿童史后，这些发现仍然显著。总体而言，孩子幼儿期时母亲的NR3C1甲基化与孩子学龄期外化行为严重程度呈负相关且具有显著性。
我们发现，母亲及其孩子的NR3C1甲基化水平总体上以及在所有感兴趣的单个CpG位点上的相关性仅在IPV-PTSD组中显著。后一项发现支持，仅在母亲存在IPV-PTSD的情况下，母亲的NR3C1甲基化与其孩子的NR3C1甲基化呈正相关且具有统计学显著性。这种关于糖皮质激素受体的母亲表观遗传特征与儿童行为显著相关，这很可能会为暴力及相关精神病理学的代际传播带来风险。
