Reward Responsiveness as a Prevention Target in Youth At Risk for Anhedonia

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PROJECT SUMMARY Anhedonia, a core symptom of depression and other forms of psychopathology characterized by loss of interest or pleasure, is associated with a range of negative health outcomes, including suicide risk, and poor treatment response. Low activation of positive valence systems, particularly low reward responsiveness (RR), is a key brain-behavioral process underlying anhedonia. Critically, there is growing evidence that low RR is observable in children at risk for anhedonia due to maternal symptomatology and reflects a vulnerability for the later emergence of anhedonia and depression. Thus, targeting RR in high-risk children is critically needed to prevent the development of anhedonia, alter risk trajectories, and mitigate the tremendous health burden of anhedonia-related psychopathology. Combining principles from adult positive affect treatment and family cognitive behavioral preventive interventions, we developed an innovative, neuroscience-informed dyadic preventive intervention, Family Promoting Positive Emotions (F-PPE), for 8- to 12-year-old children and mothers with a history of major depressive disorder with anhedonia. F-PPE is designed to specifically target RR in children, assessed at the neural level using well-validated electroencephalogram methods. The first phase of the project (R61) will focus on target engagement, testing whether F-PPE increases child neural RR relative to an active comparison. Children (N=60) will complete neural measures of RR pre-intervention, 4- weeks into the intervention to determine dose effects, and post-intervention (8 weeks). Biological mother-child dyads will be randomized to F-PPE or a psychoeducation preventive intervention comparison. Target engagement will be defined as an increase in neural RR in the F-PPE relative to psychoeducation group with at least a medium effect size (d > .40). Change in the target at 4 weeks will be examined to determine dose effects and integrated with participant feedback to refine F-PPE for the R33 phase. The R33 phase will be a replication and extension to clinical outcomes with 100 biological mother-child dyads. Dyads will again be randomized to F-PPE or a comparable number of psychoeducation sessions. In addition to neural RR, ecological momentary assessment of real-world experiences of interest and pleasure and clinical symptoms of anhedonia will be assessed pre- and post-intervention and at a 6-month follow-up assessment. We will examine effects of F-PPE on momentary experiences of interest/pleasure and symptoms of anhedonia across the longitudinal follow-up and test change in RR as a mechanism of clinical effects of F-PPE. These projects will take critical next steps in translating developmental affective neuroscience research to prevention and moving towards precision medicine to reduce the burden of anhedonia and associated psychopathologies.