Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5 × 106 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

中文翻译：

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依恋不安全和童年逆境的表观遗传特征为围产期抑郁症发病机制中的角色转变提供了证据。

早年的逆境和不安全的依恋方式是围产期抑郁症的已知危险因素。然而，连接这些经历的生物学途径尚未阐明。我们假设与这些现象相关的 DNA 甲基化模式的重叠可以识别重要的基因和途径。具体来说，我们希望区分围产期抑郁症的异位负荷假设和角色转换假设。我们对参与围产期抑郁症纵向前瞻性研究的 54 名女性的 5 × 106 个个体 CG 二核苷酸的甲基化模式进行了大规模分析，使用基于聚类的显着性标准来控制多重比较。我们确定了 1580 个区域，其中甲基化密度与童年逆境有关，3个甲基化密度与不安全依恋风格相关，6个甲基化密度与围产期抑郁症相关。观察到较短的端粒与童年创伤有关，但与围产期抑郁或依恋不安全无关。对催产素受体基因中甲基化密度的详细分析揭示了与围产期抑郁症和不安全依恋方式相关的类似 DNA 甲基化模式，而童年创伤与该基因中独特的甲基化模式相关。临床上，依恋风格仅在妊娠期和产后早期与抑郁症密切相关，而童年逆境与抑郁症的关联是不随时间变化的。我们得出的结论是，与童年逆境相关的广泛的 DNA 甲基化特征和减少的端粒长度可能表明跨多个身体系统的异位负荷增加，而围产期抑郁和依恋不安全可能是更窄的表型，在 CNS 之外具有更有限的 DNA 甲基化特征，并且没有明显的关联端粒长度，或者，通过扩展，异位负荷。相比之下，在催产素受体基因内发现与围产期抑郁和依恋不安全感匹配的 DNA 甲基化模式与围产期是为了构建母子关系而激活现有依恋模式的理论相一致，并且这种激活可能部分通过催产素受体基因的特定甲基化模式发生。