Impact of Cognitive Behavioral Therapy for Social Anxiety Disorder on the Neural Dynamics of Cognitive Reappraisal of Negative Self-Beliefs: Randomized Clinical Trial.

IMPORTANCE Cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) is thought to enhance cognitive reappraisal in patients with SAD. Such improvements should be evident in cognitive reappraisal-related prefrontal cortex responses. OBJECTIVE To determine whether CBT for SAD modifies cognitive reappraisal-related prefrontal cortex neural signal magnitude and timing when implementing cognitive reappraisal with negative self-beliefs. DESIGN Randomized clinical trial of CBT for SAD vs wait-list control group during a study that enrolled patients from 2007 to 2010. SETTING University psychology department. PARTICIPANTS Seventy-five patients with generalized SAD randomly assigned to CBT or wait list. INTERVENTION Sixteen sessions of individual CBT for SAD. MAIN OUTCOME MEASURES Negative emotion ratings and functional magnetic resonance imaging blood oxygen-level dependent signal when reacting to and cognitively reappraising negative self-beliefs embedded in autobiographical social anxiety situations. RESULTS During reactivity trials, compared with wait list, CBT produced (1) greater reduction in negative emotion ratings and (2) greater blood oxygen-level dependent signal magnitude in the medial prefrontal cortex. During cognitive reappraisal trials, compared with wait list, CBT produced (3) greater reduction in negative emotion ratings, (4) greater blood oxygen level-dependent signal magnitude in the dorsolateral and dorsomedial prefrontal cortex, (5) earlier temporal onset of dorsomedial prefrontal cortex activity, and (6) greater dorsomedial prefrontal cortex-amygdala inverse functional connectivity. CONCLUSIONS AND RELEVANCE Modulation of cognitive reappraisal-related brain responses, timing, and functional connectivity may be important brain changes that contribute to the effectiveness of CBT for social anxiety. This study demonstrates that clinically applied neuroscience investigations can elucidate neurobiological mechanisms of change in psychiatric conditions. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00380731.