Behavioral and neural mechanisms of reward responsivity across normative and at-risk adolescent development

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Depression is a major public health concern, ranking as a leading contributor of disease burden in adults and adolescents. A promising etiological mechanism for understanding the development of depression is low responsivity to rewards. Diminished reward responsivity during adolescence prospectively predicts depression onset and is associated with increased symptom severity. Given the prominent role of diminished responsivity to reward in the emergence and course of depression, reward response may be a critical target for treatment, particularly during the adolescent period when the prevalence of depression onset spikes, when reward responsivity among affected youth is markedly attenuated, and when the reward system may be particularly plastic, and, thus, theoretically more amenable to intervention. Before interventions can be realized, however, a more thorough understanding of developing reward responsivity is needed. While it is known that reward responsivity undergoes dramatic change across normative adolescent development, very little is known about the behavioral or neural mechanisms underlying these changes, either in healthy development or in adolescents with an increased risk for depression. The proposed research will use existing project data, while extending the initial aims of the parent R01, by further probing the developing reward-related phenotype in terms of (1) behavioral dimensions of reward responsivity, and (2) hierarchically maturing reward circuitry. Across two aims, the mechanisms underlying developing reward responsivity will be examined using a symptom-level approach, longitudinal design, and comparison of adolescents with and without a family history of depression (at-risk and normative groups). Specifically, Aim 1 will use computational modeling to examine developmental trajectories of distinct dimensions of reward responsivity across normative development and in relation to the etiology of depression symptoms. As computational modeling allows behavioral responses to be understood in more mechanistic terms, the findings of this research will lay the foundation for understanding how dysregulation of specific aspects of reward responsivity lead to depression onset. Aim 2 will examine how microstructure development in the superolateral branch of the medial forebrain bundle, a recently identified reward-related white matter tract, changes across healthy adolescent development and in those at-risk for depression. While broad white matter disruptions have been linked to depression generally, the proposed project will seek to demonstrate a specific functional-structural relationship between reward responsivity and microstructure in a white matter tract with high theoretical relevance. Further, as strong evidence suggests neural circuitry matures hierarchically (from subcortical to cortical), the proposed project will examine how reward responsivity changes in relation to developing microstructure in successively maturating segments of the tract. Across both aims, the proposed research has great promise to elucidate novel mechanisms underlying the etiology of depression, laying the foundation for therapeutics that target diminished reward responsivity during the highly plastic adolescent period.