One of the major contributions of developmental psychology is the demonstration that early caregiving experiences within the normative range (i.e., sensitive caregiving) not only contribute to offspring’s mental and physical health disparities, but also that such associations are enduring over the life course. Research by the PIs and others has identified brain mechanisms by which key maternal risk factors—depressive symptoms and attachment insecurity—undermine caregiving behavior. However, given evidence documenting significant change in the maternal brain over the transition to motherhood, there is a critical gap as to whether this transition serves as a sensitive period during which maternal neural responding to infants is particularly impacted by maternal depressive symptoms and insecurity that pose risk for caregiving behavior and infant adjustment. Moreover, the majority of research has focused exclusively on mother-driven effects, limiting understanding of the significance of infant characteristics for the maternal brain. Additionally, research on the maternal brain primarily comprises samples of European-ancestry women, thus, little is known about whether such processes operate similarly in families of color. Therefore, this R01 application seeks to programmatically investigate whether maternal psychological risk undermines maternal sensitivity and, in turn, infant adjustment via negatively impacting change in maternal brain responding to infants over the transition to motherhood. Further, we will test the role of infant characteristics (i.e., negative emotionality) in moderating this pathway. Critically, we include a racially/ethnically diverse sample of 400 women to explore moderation of our findings by maternal race/ethnicity. We further propose to identify person (parenting/emotion beliefs) and community (kinship/social support) factors that may impact their neural adaptation to motherhood. We will examine maternal risk factors (depressive symptoms, attachment insecurity), person and community factors, and brain responding to infant cues prenatally (3rd trimester) and postnatally (4 and 8 months). Postnatal assessments will include caregiving behavior (4, 8, and 12 months), infant negative emotionality (4 and 8 months), and infant adjustment (12 months), including attachment security and behavior problems. Our approach is innovative given its intergenerational, prospective, multi-level, and multi-time point design and the racial and ethnic diversity in the maternal sample enrolled. Our findings will inform models of the changing maternal brain from pregnancy to the postpartum period and how maternal depression and attachment insecurity may pose risk for maternal caregiving and infant adjustment as a function of infant negative emotionality and maternal race/ethnicity. Furthermore, our approach will allow for more targeted intervention strategies for women during their transition to motherhood to optimize mother and child well-being.