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Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

ABSTRACT: 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.

SUBMITTER: Robakis TK

PROVIDER: S-EPMC7026105 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

Robakis Thalia K TK Zhang Siming S Rasgon Natalie L NL Li Tongbin T Wang Tao T Roth Marissa C MC Humphreys Kathryn L KL Gotlib Ian H IH Ho Marcus M Khechaduri Arineh A Watson Katherine K Roat-Shumway Siena S Budhan Vena V VV Davis Kasey N KN Crowe Susan D SD Ellie Williams Katherine K Urban Alexander E AE

Translational psychiatry 20200203 1

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 ...[more]

PMID: 32066670

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Project description:Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3-5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth.

Project description:This study introduced the novel concept of Centeredness, a measure of the emotional atmosphere of the family of origin and a target adult individual's perception of feeling safe, accepted, and supported from childhood primary caregivers and other family members. This study developed a Centeredness scale for adult respondents and tested hypotheses that higher levels of overall Centeredness would predict lower levels of depression and anxiety symptoms; suicidal thoughts and behaviors (STBs); and aggressive behavior; and higher levels of life satisfaction. Predictive effects of Centeredness were compared against attachment-related anxiety and avoidance, and adverse and benevolent childhood experiences (ACEs and BCEs). Participants were recruited via the Prolific-Academic (Pro-A) survey panel into two large independent samples of US young adults aged 19-35 years [Sample 1 (test sample), N = 548, 53.5% female, 2.2% gender non-conforming, 68.3% White, recruited before the pandemic; Sample 2 (replication sample), N = 1,198, 56.2% female, 2.3% gender non-conforming, 66.4% White; recruited during the pandemic]. Participants completed the novel Centeredness scale, which showed strong psychometric properties, and standardized, publicly available assessments of childhood experiences and mental health outcomes. Centeredness was the only variable that significantly predicted each mental health outcome across both samples. BCEs predicted all outcomes except aggressive behavior in the test sample. Centeredness and BCEs were also the only two variables that significantly predicted a dimensional mental health composite in both samples. Neither attachment-related anxiety and avoidance nor ACEs were as broadly predictive. The Centeredness scale assesses emotional aspects of childhood family relationships with individuals of diverse backgrounds and family compositions. Clinical and cultural implications are discussed.Supplementary informationThe online version contains supplementary material available at 10.1007/s42844-023-00089-x.

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Dataset Information

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

Publications

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression.

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