The Role of Reward-Related Brain Activity in Response to Treatment and Later Depression Severity: Data from a Randomized Controlled Trial in Early Adolescents with Anxiety Disorders

Alterations in reward-related brain activity have been linked to response to psychological treatment in adolescents with anxiety disorders. However, it remains unknown whether these effects are driven by reward anticipation or feedback, which reflect different functional roles in motivated behavior, or whether brain activity changes as a function of treatment response. The current study investigated these questions in the context of a randomized controlled trial of cognitive-behavioral therapy (CBT) for anxiety disorders in adolescents. This study used an fMRI paradigm to investigate reward-related brain activity in youth aged 9-14 with anxiety disorders (ANX; N = 133; 57 female) before and after 16 weeks of CBT or an active comparison (child-centered therapy, CCT). Age- and sex-matched healthy comparison (HC) youth (N = 38; 17 female) completed scans on a similar timeline. A subset of ANX youth completed a 2-year follow-up assessment of depressive symptoms. At pretreatment, ANX compared to HC youth demonstrated reduced brain activity in reward-related regions (e.g. dorsal striatum, thalamus) during reward anticipation, and elevated activity in angular gyrus, PCC and inferior frontal gyrus during reward feedback. Reduced pretreatment activation in the precuneus/cuneus and pre-to-post reductions in left angular gyrus corresponded with treatment response. Finally, pre-to-post increases in posterior cingulate cortex (PCC) corresponded with increased depressive symptoms at 2 years. Our results suggest that reward-related brain activity outside of striatal reward regions, including PCC, precuneus and angular gyrus, plays a role in treatment response in youth with anxiety disorders. Trial registration: ClinicalTrials.gov NCT00774150.