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

Abstract Background: Adolescent depression varies considerably in the course. However, there are no biobehavioral predictors of illness trajectories, 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). Methods: Subjects were 29 psychotropic-medication-free participants with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two adolescents (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined symptom severity as predictors for follow-up clinical outcomes. Whole-brain analyses examined the relationships between neural reward processes and follow-up outcomes. Results: Clinically, anhedonia, but not irritability, predicted future depression and suicidal ideations. Among reward processes, only neural activation during PPE was correlated with future depression and anhedonia severity. Specifically, activation in the left angular gyrus—a component of default mode network—was associated with future depression, while activation in the dorsal anterior cingulate, operculum and left insula—key regions within the salience and pain networks—was associated with future anhedonia, even when controlling baseline anhedonia. Limitations: Small sample size and variability in follow-up intervals limit the generalizability of conclusions. Conclusions: This research suggests the anhedonia and reward dysfunction may predict a worse course in adolescent depression. The adolescents with anhedonia should be monitored more carefully for a longer period.