Brain response to emotional faces in anxiety and depression: neural predictors of cognitive behavioral therapy outcome and predictor-based subgroups following therapy.

Abstract

Neuroimaging studies have shown variance in brain response to emotional faces predicts cognitive behavioral therapy (CBT) outcome. An important next step is to determine if individual differences in neural predictors of CBT response represent distinct patient groups. In total, 90 patients with internalizing disorders completed a face-matching task during functional magnetic resonance imaging before and after 12 weeks of CBT and 45 healthy controls completed the task before and after 12 weeks. Patients exhibiting a pre-to-post CBT >50% reduction in symptom severity on two measures were considered treatment responders. Regions of interest (ROIs) for angry, fearful, and happy faces were submitted to receiver operating characteristic (ROC) curve analysis. Significant ROIs were then submitted to decision tree analysis to classify responder/non-responder subgroups. Psychophysiological interactions (PPI) were used to explore functional connectivity in the region(s) that delineated subgroups. A total of 51 patients were treatment responders and ROC curve results were significant for all face types though specific regions varied. Decision tree results revealed superior occipital response to angry faces identified patient subgroups such that the subgroup with 'high' occipital activity had more responders than the 'low' occipital subgroup. Following CBT, the high, relative to low, occipital subgroup was less symptomatic. Controls exhibited stable superior occipital activation over time. Whole-brain PPI showed reduced baseline superior occipital-postcentral gyrus functional connectivity in responders compared to non-responders. Preliminary findings indicate patients characterized by relatively more pre-treatment superior occipital gyrus engagement to angry faces and reduced superior occipital-postcentral gyrus connectivity, relative to non-responders, may represent a phenotype likely to benefit from CBT.