PROJECT SUMMARY The proposed R61/R33 phased study aims to elucidate the physiological stress mechanisms underlying effects of a mindfulness program designed to target youth at risk for externalizing, affective and traumatic stress disorders by virtue of significant environmental disadvantage. Adolescents for each phase will be recruited from schools serving high poverty neighborhoods in Baltimore City where adversity and experiences of trauma and maltreatment are common. The intervention is currently being implemented in a few Baltimore City schools and other settings by the Holistic Life Foundation, Inc. (HLF), a non-profit organization with a lengthy track record of providing mindfulness-based programming (breath work and meditation) to impoverished youth. Both empirical and anecdotal reports of significant change in emotion regulation have been reported with this intervention, yet similar to most mindfulness programs, mechanisms of effects have not yet been delineated, particularly in disadvantaged youth. Our primary mechanism of interest is stress physiology, as measured by heart rate variability (HRV) and skin conductance response (SCR) during acute stress, a central component of emotion regulation and implicated in relevant clinical syndromes (e.g., externalizing behaviors, affective disorders).To identify the characteristics of youth that predict intervention response (moderation) and the stress-related pathways through which positive outcomes are achieved (mediation), we propose to conduct two RCTs with the ultimate goal to maximally improve externalizing behaviors and affective and traumatic disorders in at-risk youth. In the R61, we will intensively measure mechanistic effects of the mindfulness program to establish its effects in a conceptually appropriate population. Students in 4 Baltimore City High Schools will be randomized to treatment and active control conditions (N=160 students) and assessed at baseline, post-intervention and follow-up. Stress physiological profiles that improve in response to intervention will be identified. In the R33, we will conduct a larger RCT (8 schools, N=240) with assignment either to the mindfulness program or the mindfulness program plus an enhancement?HRV biofeedback?shown to independently exert effects on stress responses. Comparisons will be made between conditions and then a mediation model will be applied to the intervention condition exhibiting maximal effects to determine whether positive change in stress physiology explains improvements in outcomes. This sequence of studies will characterize participants who are maximally impacted by mindfulness and will differentiate between treatment conditions, leading to more efficient and effective targeting and scaling. In so doing, this research will break new ground in the rapidly growing field of youth mindfulness-based interventions by identifying key physiological mechanisms of effect for common mindfulness practices.