<p>The present study aims to examine psychological and epigenetic influences on the journey to parenthood for first-time parents. Prior work suggests that one in five new parents will experience elevated depressive symptoms in the postpartum period which has been shown to have downstream consequences on the quality of parent-infant bonding. More research is needed to explore the biological underpinnings of postpartum depressive symptoms and parent-infant bonding to inform prevention efforts. Sixty-six expectant parents from diverse sociocultural backgrounds participated during the antepartum period and through six months postpartum. Psychological measures were collected via a secure online platform and the epigenetic modification of the oxytocin system (oxytocin receptor gene methylation) was assayed from passive drool saliva collection that was completed in-person. Expectant parents with higher levels of oxytocin receptor gene methylation during the antepartum period were more likely to endorse high stress and conflict in the parent-infant relationship and higher levels of postpartum depressive symptoms. An epigenetic modification of the oxytocin system may play a role in risk for postpartum depressive symptoms and challenges in the parent-infant relationship. More research is needed to understand the biological underpinnings of risk for postpartum depressive symptoms and challenging parent-infant relationships, particularly those factors that may be most responsive to prevention and intervention efforts.</p>