Reward function as an outcome predictor in youth with mood and anxiety symptoms

•Anhedonia, but not irritability, predicted follow-up depression and suicidality.•Activation in left angular gyrus during PPE predicted future depression severity.•dACC, right insula & bilateral operculum activation during PPE predicted anhedonia.•Reward dysfunction is a potential biobehavioral predictor for adolescent depression. Adolescent depression varies considerably in its course. However, there remain no biobehavioral predictors of illness trajectory, and follow-up studies in depressed youth are sparse. Here, we sought to examine whether reward function would predict future clinical outcomes in adolescents with depressive symptoms. We utilized the reward flanker fMRI task to assess brain function during distinct reward processes of anticipation, attainment, and positive prediction error (PPE, i.e. receiving uncertain rewards). Subjects were 29 psychotropic-medication-free adolescents with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two participants (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined baseline symptom severity measures as predictors of follow-up clinical outcomes. Whole-brain analyses examined relationships between neural reward processes and follow-up outcomes. Clinically, anhedonia, but not irritability, predicted future depression and suicidal ideation. Among reward processes, only baseline neural activation during PPE correlated with follow-up depression and anhedonia severity. Specifically, activation in the left angular gyrus—a component of the default mode network—was associated with future depression, while activation in the dorsal anterior cingulate, operculum, and left insula—key salience and pain network regions—was associated with future anhedonia, even when controlling for baseline anhedonia. The small sample size and variable follow-up intervals limit the generalizability of conclusions. This research suggests that reward dysfunction, indexed by anhedonia, may predict worse clinical trajectories in depressed youth. Adolescents presenting with significant anhedonia should be carefully monitored for illness progression.