Reward-related neural predictors and mechanisms of symptom change in cognitive behavioral therapy for depressed adolescent girls

Abstract Background Approximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pre-treatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive vs. poor outcome to CBT may have important clinical implications (e.g., informing treatment recommendations). Emerging evidence suggests that neural reward responsiveness represents one promising predictor. Method Adolescents with major depressive disorder (n = 36) received CBT and completed a reward task at three timepoints (pre-treatment, mid-treatment and post-treatment) while 128-channel electroencephalogram (EEG) data were acquired. Healthy control participants (n = 29) completed the same task at three corresponding timepoints. Analyses focused on event-related potentials (ERPs) linked to two stages of neural processing: initial response to rewards (reward-related positivity [RewP]) and later, elaborative processing (late positive potential [LPP]). Moreover, time-frequency analyses decomposed the RewP into two constituent components: reward-related delta and loss-related theta activity. Results Multilevel modeling revealed that greater pre-treatment reward responsiveness, as measured by the LPP to rewards, predicted greater depressive symptom change. In addition, a Group x Condition x Time interaction emerged for theta activity to losses, reflecting normalization of theta power in the MDD group from baseline to post-treatment. Conclusions An ERP measure of sustained (LPP)—but not initial (RewP)—reward responsiveness predicted symptom improvement, which may help inform which depressed adolescents are most likely to benefit from CBT. In addition to alleviating depression, successful CBT may attenuate underlying neural (theta) hypersensitivity to negative outcomes in depressed youth.