Comparing reward learning among adolescents and adults with MDD and using reward-related neurobiology to predict future reward-related learning

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PROJECT SUMMARY The number of mental health concerns and emergency visits for suspected suicide attempts in youth during 2021 has led to a declared national emergency by the American Academy of Child and Adolescent Psychiatry. The consequences of major depressive disorder (MDD) onset during adolescence are substantial. Adolescents with MDD are at higher risk for suicidality, the second leading cause of death in this age group, and for developing additional mental health disorders in adulthood. Despite considerable efforts, efficacy of gold- standard treatment for MDD remains low. For these reasons, research has aimed to identify early neurobiological markers related to depression onset and severity. Progress in the field of neuroimaging has identified aberrant reward circuitry (i.e., dampened activation in the reward system in anticipation or receipt of reward) as a potential endophenotype for depression. However, reward processing is not limited to hedonics, and depression may be better characterized by how diminished hedonics impact other aspects of the reward system, such as reward learning. Previous literature supports the notion that MDD is associated with dampened reward-learning behavior in adults; however, less is known about how adolescent reward-learning behavior may be impacted by MDD. Of note, studying reward dysfunction and reward learning during adolescence is critical due to heightened reward sensitivity and ongoing neuroplasticity occurring during this time. The goal of this proposal is to examine how reward learning is impacted by MDD in adolescence, as well as how neurobiological mechanisms of reward responsivity and reward circuitry predict future reward-learning behavior in adulthood. The first aim is to be the first study to compare reward-learning behavior among adolescents and adults with and without MDD. Then, capitalizing on an existing dataset, the second aim is to assess the associations between adolescent neurobiological reward responsivity, resting-state functional connectivity (rsFC) of the reward system, and task- based functional connectivity and future reward learning. Filling the gap in our understanding of how reward learning is impacted by MDD in adolescents and how neurobiological mechanisms of reward circuitry relate to future reward-driven behavior may further our understanding of risk for depression and help to inform early prevention efforts. Improved understanding of these mechanisms also may help to inform individualized treatment strategies for youth based on individual neurobiology and behavior.