PROJECT SUMMARY/ABSTRACT Background: Nearly 20% of women in the United States experience clinically significant depressive symptoms during pregnancy or the postpartum period. Although treatments exist for depressive symptoms such as antidepressants and psychotherapy, many women remain under- or un-treated due to concerns about stigma, side effects, and costs, particularly marginalized women (minority, low socioeconomic status). Further, the standard depression treatments do not address social connectedness, which is a potentially modifiable factor involved in depressive symptoms. A focus on adequate symptom management through safe, non- pharmacologic, accessible therapies that address social connectedness during pregnancy in marginalized women is an urgent clinical and research priority. Preliminary Data: Preliminary evidence from our research team shows a promising pathway for addressing social connectedness in the context of perinatal depression: we have piloted the “Mindful Moms” intervention in a NICHD-funded study (R15HD086835, Kinser); the 12- week intervention involves a brief motivating discussion about symptom self-management plus group-based mindful physical activity (prenatal yoga) sessions. Study findings provide support of protocol feasibility and intervention acceptability, with qualitative findings leading us to hypothesize that social connectedness plays as a key role in symptom management. Also, we have identified epigenetic patterns uniquely related to postpartum depression; we will evaluate the similarity of these DNA methylation patterns related to social connectedness and postpartum depression, as an exploration of mechanisms of social connectedness. Study Design: Using a conceptual framework based upon Individual and Family Self-Management Theory, the overall goal of this two-arm longitudinal randomized controlled trial is to evaluate the effects and mechanisms of this self-management approach in marginalized women with depressive symptoms (n=200), compared to an active control. The first Specific Aim is to evaluate effects by group on depressive symptom severity, anxiety, and perceived stress over time. The second Specific Aim is to understand the role of social connectedness as a moderator of the effects of group assignment on depressive symptoms. The third Specific Aim is to identify genome-wide DNA methylation patterns associated with levels of perceived social connectedness. Potential Impact: The successful completion of our aims will provide important insights into social connectedness as a mechanism to decrease depressive symptoms in a largely understudied, historically marginalized population of women. Further, if proven efficacious, “Mindful Moms” may be a low-cost, sustainable, and translatable option for intervention in perinatal depressive symptoms.