Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project


Randy P Auerbach, David Pagliaccio, Nicholas A Hubbard, Isabelle Frosch, Rebecca Kremens, Elizabeth Cosby, Robert Jones, Viviana Siless, Nicole Lo, Aude Henin, Stefan G Hofmann, John DE Gabrieli, Anastasia Yendiki, Susan Whitfield-Gabrieli, and Diego A Pizzagalli. 2022. “Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project.” J Am Acad Child Adolesc Psychiatry, 61, 2, Pp. 308-320.


OBJECTIVE: Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth. METHOD: The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14- to 17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n = 129) or no lifetime history of mental disorders (n = 64). In addition, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period. RESULTS: Our findings highlighted considerable convergence. Relative to healthy youth, depressed-anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed-anxious youth). Subgroup analyses comparing anxious-only, depressed-anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time. CONCLUSION: Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed-anxious adolescents. In the current hypothesis-driven analyses, however, only reduced nucleus accumbens volume predicted depressive symptoms over time. An important next step will be to clarify why structural alterations have an impact on reward-related processes and associated symptoms.