Abstract
BACKGROUND: Maternal childhood maltreatment (CM) has been associated with subsequent difficult infant temperament. Further, maternal CM and maladaptive infant outcomes have each been linked, separately, to increased methylation in umbilical cord blood of CpG sites in genes related to the stress response and inflammatory markers. Researchers have not yet examined the nature of the interactions of these factors or whether DNA methylation (DNAm) mediates or moderates the association of maternal CM with infant temperament. OBJECTIVE: We tested whether DNAm mediates or moderates the association between maternal CM and infant temperament. PARTICIPANTS AND SETTING: Longitudinal data from 144 mother-infant dyads were analyzed. METHODS: DNAm in umbilical cord blood, history of maternal CM, and infant temperament were assessed at age three months. Principal components analysis identified one methylation component with CpG sites related to the following hypothalamic-pituitary-adrenal (HPA) axis genes: ADRA1B, CRHBP, CREBBP, HSD11B1, HTR2A, NCOR2, and NR3C1. RESULTS: Higher DNAm levels were associated with stronger effects of maternal CM, driven in particular by maternal childhood abuse, on difficult infant temperament. CONCLUSIONS: These findings highlight the complexity of the relations among maternal CM, epigenetic modifications to the stress response, and infant temperament. Infants of mothers who experienced more CM, particularly abuse, exhibited more difficult temperament, a relation that was moderated by heightened methylation of HPA-axis-related CpG sites related to CM. This methylation pattern may reflect an elevated stress response that is altered by maternal CM, suggesting a fetal programming formulation that should be tested more explicitly and systematically in future research.