Trajectories of Positive Valence Systems Function and Postpartum Depression Risk - PROJECT SUMMARY Postpartum depression (PPD) is prevalent and associated with negative outcomes for both mothers and infants. PPD emerges during a period of psychosocial and neurobiological change, and there is a critical need for integrated research on trajectories of risk processes. Low activation of RDoC’s positive valence systems (PVS) prospectively predicts depressive symptoms outside of the peripartum period and may be particularly relevant for driving social motivation in mother–infant relationships. PVS function is reliably and objectively measured at the neural level, but very little research has examined brain function across pregnancy. Critically, psychosocial and neurobiological changes occurring across the peripartum period, including acute stress and elevated cortisol, are also known to impact PVS function. These disparate lines of research support the scientific premise of low PVS function as a key risk process in PPD and highlight the need to consider multimethod trajectories of change in PVS function as predictors of PPD, rather than relying on single measures and time points. We developed safe, feasible, and robust methods for repeatedly assessing reward- related brain function across the peripartum period, which we will combine with ecological momentary assessment of positive affect to chart trajectories of PVS function across the peripartum. For comparison, similar measures of negative valence systems (NVS) function will also be collected. We will recruit 300 pregnant women in their 2nd trimester (at least 50% classified as high risk for PPD) for an intensive longitudinal study with follow-up assessments conducted every 10 weeks through 25 weeks postpartum (4 lab and 2 virtual assessments). PVS function will be assessed from 15 weeks gestation to 5 weeks postpartum. Hair samples will allow for retrospective assessment of cortisol and other hormones to be estimated from conception through birth, and acute stress and birth trauma will be measured through gold-standard interviews. At 15 weeks postpartum, mothers and infants will participate in an observed free play interaction to assess mutual enjoyment. Depressive symptoms and diagnoses will be assessed from 15 weeks gestation through 25 weeks postpartum. This innovative study will advance understanding of the role of PVS function in PPD, including examining PVS function as a prospective predictor of PPD, comparing both baseline functioning vs. trajectories of change and PVS vs. NVS as predictors of depression (Specific Aim 1). We will also test PVS function across peripartum as a predictor of new mothers’ experiences of enjoyment in interactions with infants and examine low mutual enjoyment as a mechanism of the effects of low PVS function on PPD (Specific Aim 2). Finally, we will test longitudinal associations between acute stressors, cortisol levels, and subsequent PVS function, providing unique insight into the psychosocial and neurobiological processes shaping PVS function, and ultimately, depression risk (Specific Aim 3). The study will advance understanding of the dynamic interplay of processes impacting PVS and inform effective timing and targets for intervention to reduce the burden of PPD.