Oxytocin Receptor Genetic and Epigenetic Variation, Early Life Adversity, and Breastfeeding Outcomes: A Three-Manuscript Dissertation

Abstract

Background: Suboptimal breastfeeding (BF) contributes to increased disease burden for both infants and lactating parents. Although social factors influencing formula supplementation and premature weaning are well documented, the physiological mechanisms underlying disrupted lactation remain less understood. Because BF is a biosocial process shaped by both biological and social forces, this dissertation applies a biosocial framework to examine how oxytocin system function relates to BF outcomes within the context of maternal early life adversity. The purpose of this dissertation was to investigate associations between oxytocin receptor (OXTR) genetic and epigenetic variation and BF outcomes, and to evaluate how early adverse experiences may modify these relationships. Three cohesive manuscripts collectively address this objective. Methods: Manuscript 1 is a scoping review conducted using PRISMA guidelines to synthesize existing research on oxytocin and OXTR genetic and epigenetic variation in relation to postpartum outcomes, including maternal mental health, maternal behavior, and BF. Manuscripts 2 and 3 draw on secondary data from a randomized controlled trial led by PI Dr. Aleeca Bell (NIH R01NR018828), examining mother–infant synchrony among women with childhood adversity. Manuscript 2 uses a cross-sectional design to assess relationships between adverse childhood experiences, OXTR genetic and DNA methylation variations, and exclusive BF at 1 month postpartum through moderation models. Manuscript 3 employs longitudinal mixed-effects models to test whether BF exposure at 2 months postpartum predicts OXTR methylation, and whether these associations differ by genotype. Results: Across studies, this dissertation identified gene × environment interactions involving OXTR variations that influence maternal postpartum outcomes, with BF emerging as the least studied outcome in the literature. In the empirical analyses, higher adversity exposure combined with the GG genotype at rs53576 was associated with greater likelihood of exclusive BF at 1 month. Additionally, higher BF exposure at 2 months postpartum was associated with increasedmethylation among GG individuals but decreased methylation among A-carriers. These findings suggest differential susceptibility to social and biological exposures, highlighting that OXTR genotype may shape maternal physiological responsiveness during both early life and the perinatal period. Conclusions: Together, these three manuscripts demonstrate that OXTR genetic and epigenetic variation is associated with BF outcomes and may represent a mechanistic pathway linking early life adversity, lactation physiology, and maternal adaptation. This work underscores BF as a biosocial phenomenon and supports further investigation to identify individuals at increased risk for suboptimal lactation outcomes and to inform targeted, biologically informed interventions.