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Original Investigation |

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

Philippe R. Goldin, PhD1; Michal Ziv, PhD1; Hooria Jazaieri, MA1; Kevin Hahn, BS1; Richard Heimberg, PhD2; James J. Gross, PhD1
[+] Author Affiliations
1Department of Psychology, Stanford University, Stanford, California
2Department of Psychology, Temple University, Philadelphia, Pennsylvania
JAMA Psychiatry. 2013;70(10):1048-1056. doi:10.1001/jamapsychiatry.2013.234.
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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.

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Figure 1.
Consolidated Standards of Reporting Trials Diagram for a Randomized Clinical Trial of Individual Cognitive Behavioral Therapy (I-CBT) vs Wait List (WL)
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Figure 2.
Experimental Design

Components and structure of 1 autobiographical social situation trial. After each negative self-belief (NSB), participants provide a negative emotion rating from 1 = not negative to 5 = extremely negative.

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Figure 3.
Changes in Negative Emotion Intensity Ratings

Changes in negative emotion intensity ratings for react negative self-beliefs and cognitive reappraisal of negative self-beliefs in patients with social anxiety disorder before and after individual cognitive behavioral therapy (I-CBT) vs wait list (WL). Negative emotion ratings after the offset of each stimulus were provided by participants in response to “How negative do you feel?” (1 = not at all, 2 = slightly, 3 = moderately, 4 = very much, and 5 = extreme). Error bars = standard error of the mean.aP < .05.bP < .001.

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Figure 4.
Changes in Brain Responses

Changes in brain responses in the dorsomedial prefrontal cortex (DMPFC) and left dorsolateral prefrontal cortex (DLPFC) a priori cognitive reappraisal–related prefrontal cortical brain regions of interest in patients with social anxiety disorder before and after individual cognitive-behavioral therapy (I-CBT) vs wait list (WL). The dot represents the spherical region of interest mask used in the analysis. Blood oxygen level–dependent (BOLD) signal represents before to after I-CBT and WL change scores in BOLD signal responses.aP < .05.

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Figure 5.
Blood Oxygen Level–Dependent (BOLD) Signal Time Series

Blood oxygen level–dependent signal time series in the dorsomedial prefrontal cortex (A) and left dorsolateral prefrontal cortex (B) during reappraise negative self-beliefs vs read neutral statements. I-CBT indicates individual cognitive-behavioral therapy and WL, wait list.

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Figure 6.
Differential Between-Group Baseline to Posttreatment Change

Differential between-group baseline to posttreatment change in dorsomedial prefrontal cortex–seeded context-dependent functional connectivity of cognitive reappraisal vs react negative self-beliefs. 1 Indicates medial prefrontal cortex; 2, right dorsomedial prefrontal cortex; 3, right middle frontal gyrus; 4, dorsomedial prefrontal cortex seed; 5, left hippocampus; and 6, left amygdala. For the whole-brain analysis, thresholding consisted of a per-voxel P < .005 and cluster volume threshold of 263 mm3 or more. Within the amygdala search region, thresholding consisted of a per-voxel P < .03 and cluster volume threshold of 160 mm3 or more.

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