Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes.

中文翻译：

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糖皮质激素和盐皮质激素受体 DNA 甲基化在产前抑郁和婴儿应激调节中的作用

了解支持母体和后代心理健康之间关系的胎儿编程途径需要探索表观遗传变异在早期发育中的潜在作用。参与压力反应调节的两个基因，糖皮质激素和盐皮质激素受体（NR3C1 和 NR3C2）一直是了解压力暴露和心理健康结果的重点。数据来自 Mercy Pregnancy Emotional Wellbeing Study (MPEWS) 的 236 名孕妇，这是一个选定的妊娠队列，在妊娠早期招募。使用 DSM-IV 的结构化临床访谈 (SCID-IV) 和爱丁堡产后抑郁量表 (EPDS) 的重复测量来测量抑郁。测量了抗抑郁药的使用、压力事件和焦虑症状。在胎盘和婴儿口腔样本中测量了 NR3C1 和 NR3C2 DNA 甲基化。在整个任务的重复唾液样本中测量婴儿皮质醇。该研究发现，母亲早孕抑郁症和症状与胎盘组织中 NR3C2 CpG_24 的较低 DNA 甲基化有关。对于 NR3C1 的 DNA 甲基化，抑郁症或抗抑郁药的使用没有显着差异。产前抑郁症与 12 个月时婴儿皮质醇反应性较低有关。胎盘样本中 NR3C2 中 CpG_24 位点的 DNA 甲基化抑制了早期母体抑郁症状与婴儿皮质醇反应性之间的关系。这些发现表明产前抑郁症、NR3C2 DNA 甲基化和婴儿皮质醇反应之间存在关系，为特定的胎儿编程途径提供支持。