BACKGROUND Genetic variation and epigenetic mechanisms involving the stress-related gene FKBP5 have been implicated in the intergenerational transmission of trauma-related effects in adult offspring of trauma-exposed caregivers, but these processes have not been fully explored in postpartum women and their newborn infants. METHODS Women recruited from a prenatal care clinic during their third trimester of pregnancy (N = 114) completed a battery of instruments assessing adverse childhood experiences (ACEs), adversity in adulthood, posttraumatic stress disorder (PTSD) symptoms, negative emotional state, and emotion dysregulation. FKBP5 rs1360780 genotype and intron 7 methylation were derived from saliva collected from postpartum mothers and their newborn infants within 24 h of delivery. RESULTS Allele-specific associations of methylation with maternal ACEs and prenatal trauma-related symptoms were evident; however, relations differed between mothers and newborns. In mothers carrying the stress sensitive T-allele (CT and TT genotypes), maternal FKBP5 methylation negatively correlated with threat-based ACEs and maternal PTSD symptoms during pregnancy, but not deprivation-based ACEs. In infants homozygous for the C allele (CC genotype), infant FKBP5 methylation positively correlated with maternal threat-based ACEs and prenatal PTSD symptom severity, but not deprivation-based ACEs or adversity in adulthood. CONCLUSIONS Our results provide evidence that links maternal threat-based ACEs and trauma-related symptoms during pregnancy with allele-specific epigenetic patterns in postpartum women and their newborn infants. These findings provide mechanistic insight into the potential intergenerational impact of ACEs and the effect of maternal PTSD symptoms during pregnancy.

中文翻译：

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产后妇女及其新生儿的不良童年经历、创伤后压力和 FKBP5 甲基化模式

背景 涉及压力相关基因 FKBP5 的遗传变异和表观遗传机制与创伤暴露照料者成年后代的创伤相关效应的代际传递有关，但这些过程尚未在产后妇女及其新生儿中得到充分探索。方法 在妊娠晚期 (N = 114) 从产前保健诊所招募的妇女完成了一系列评估童年不良经历 (ACE)、成年期逆境、创伤后应激障碍 (PTSD) 症状、负面情绪状态和情绪的工具失调。FKBP5 rs1360780 基因型和内含子 7 甲基化来自产后母亲及其新生儿在分娩后 24 小时内收集的唾液。结果 甲基化与母体 ACE 和产前创伤相关症状的等位基因特异性关联是明显的；然而，母亲和新生儿之间的关系不同。在携带压力敏感 T 等位基因（CT 和 TT 基因型）的母亲中，母亲 FKBP5 甲基化与妊娠期间基于威胁的 ACE 和母亲 PTSD 症状呈负相关，但与基于剥夺的 ACE 呈负相关。在 C 等位基因（CC 基因型）纯合婴儿中，婴儿 FKBP5 甲基化与基于母体威胁的 ACE 和产前 PTSD 症状严重程度呈正相关，但与基于剥夺的 ACE 或成年期逆境无关。结论 我们的研究结果提供了证据，将基于母体威胁的 ACE 和怀孕期间的创伤相关症状与产后妇女及其新生儿的等位基因特异性表观遗传模式联系起来。