Christian A Webb1, Randy P Auerbach2, Erin Bondy3, Colin H Stanton3, Lindsay Appleman3, Diego A Pizzagalli3. 1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. Electronic address: cwebb@mclean.harvard.edu. 2. Department of Psychiatry, Columbia University, New York, New York; Division of Clinical Developmental Neuroscience, Sackler Institute, New York, New York. 3. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts.
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 pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus 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. METHODS: Adolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity. RESULTS: Multilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment. CONCLUSIONS: An event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-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 youths.
BACKGROUND: Approximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus 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. METHODS: Adolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity. RESULTS: Multilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment. CONCLUSIONS: An event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-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 youths.
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