Highlights Non-human animal research shows stress alters amygdala–medial prefrontal cortex (mPFC) connectivity. It is unclear how prenatal stress may alter human infant connectivity. Prenatal stress was associated with decreased amygdala–mPFC functional connectivity. Prenatal stress was associated with increased amygdala–mPFC structural connectivity. This work provides insight into how stress contributes to neurodevelopmental risk.

Experiences of psychosocial neglect affect the developing brain and may place individuals at increased risk for anxiety. The majority of research in this area has focused on children who have experienced severe psychosocial deprivation; it is not clear whether typical variation in neglect experienced in community samples would have the same neurobiological consequences as those documented in extreme samples. The present study examined the associations among self-reported childhood neglect, amygdala volume, and anxiety symptoms in a community sample of 138 adolescents ages 9-15 years (43% male). Linear mixed modeling yielded a three-way interaction of neglect, sex, and brain hemisphere, reflecting a significant positive association between neglect and right amygdala volume in boys. Additional analyses indicated that right amygdala volume significantly mediated the association between neglect and anxiety symptoms in boys. These findings are consistent with previous reports of larger amygdala volumes in previously institutionalized children, and with documented associations between caregiving deprivation and anxiety symptoms. The results suggest that the effects of childhood neglect on limbic structures are sex-specific and lateralized, and provide support for a neural mechanism relating childhood neglect to later difficulties in emotional functioning.

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 × 10 6 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.

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