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Response Inhibition and Predicting Response to Pharmacological and Cognitive Behavioral Therapy Treatments for Major Depressive Disorder: A Canadian Biomarker Integration Network for Depression Study

Dhami, P., Quilty, L. C., Schwartzmann, B., Uher, R., Allen, T. A., Kloiber, S., Lam, R. W., MacQueen, G., Frey, B. N., Milev, R., Müller, D. J., Strother, S. C., Blier, P., Soares, C. N., Parikh, S. V., Turecki, G., Foster, J. A., Rotzinger, S., Kennedy, S. H., & Farzan, F.

Background
Major depressive disorder (MDD) is associated with various cognitive impairments, including response inhibition. Deficits in response inhibition may also underlie poor antidepressant treatment response. Recent studies revealed that the neurobiological correlates of response inhibition can predict response to pharmacological treatments. However, the generalizability of this finding to first-line nonpharmacological treatments, particularly cognitive behavioral therapy, remains to be investigated.

Methods
Data from two independent treatment protocols were combined, one in which 65 patients with MDD underwent treatment with escitalopram, and the other in which 41 patients with MDD underwent a course of cognitive behavioral therapy. A total of 25 healthy control subjects were also recruited. Neural correlates of response inhibition were captured by participants completing a Go/NoGo task during electroencephalography recording. Response inhibition–related measures of interest included the amplitudes of the N2 and P3 event-related potentials.

Results
Pretreatment P3 amplitude, which has been linked to both the motor and cognitive aspects of response inhibition, was a significant predictor of change in depressive symptoms following escitalopram and cognitive behavioral therapy treatment. A greater pretreatment P3 amplitude was associated with a greater reduction in depressive severity. In addition, the pretreatment P3 amplitude was found to be significantly greater at baseline in remitters than in nonremitters and healthy control subjects.

Conclusions
The integrity of response inhibition may be critical for a successful course of pharmacological or psychological treatment for MDD. Electrophysiological correlates of response inhibition may have utility as a general prognostic marker of treatment response in MDD. Future studies may investigate the benefit of preceding first-line treatments with interventions that improve response inhibition in MDD.

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