Abstract
BackgroundAberrant amygdala-prefrontal interactions at rest and during emotion processing are implicated in the pathophysiology of generalized social anxiety disorder (gSAD), a common disorder characterized by fears of potential scrutiny. Cognitive behavioral therapy (CBT) is first-line psychotherapy for gSAD and other anxiety disorders. While CBT is generally effective, there is a great deal of heterogeneity in treatment response. To date, predictors of success in CBT for gSAD include reduced amygdala reactivity and increased activity in prefrontal regulatory regions (e.g., anterior cingulate cortex, “ACC”) during emotion processing. However, studies have not examined whether tonic (i.e., at rest) coupling of amygdala and these prefrontal regions also predict response to CBT.ResultsTwenty-one patients with gSAD participated in resting-state functional magnetic resonance imaging (fMRI) before 12 weeks of CBT. Overall, symptom severity was significantly reduced after completing CBT; however, the patients varied considerably in degree of symptom change. Whole-brain voxel-wise findings showed symptom improvement after CBT was predicted by greater right amygdala-pregenual ACC (“pgACC”) connectivity and greater left amygdala-pgACC coupling encompassing medial prefrontal cortex. In support of their predictive value, area under receiver operating characteristic curve was significant for the left and right amygdala-pgACC in relation to treatment responders.ConclusionsImprovement after CBT was predicted by enhanced resting-state bilateral amygdala-prefrontal coupling in gSAD. Preliminary results suggest baseline individual differences in a fundamental circuitry that may underlie emotion regulation contributed to variation in symptom change after CBT. Findings offer a new approach towards using a biological measure to foretell who will most likely benefit from CBT. In particular, the departure from neural predictors based on illness-relevant stimuli (e.g., socio-emotional stimuli in gSAD) permits the development of biomarkers that reflect commonalities in the neurobiology of anxiety and mood disorders.
Highlights
Aberrant amygdala-prefrontal interactions at rest and during emotion processing are implicated in the pathophysiology of generalized social anxiety disorder, a common disorder characterized by fears of potential scrutiny
Similar pregenual anterior cingulate cortex (pgACC) results were observed for the left amygdala [(10, 52, −2), z = 3.30, volume = 928 mm3; r = 0.66, p < 0.001] though here the cluster extended to the medial prefrontal cortex volume = 712 mm3 (Figure 1)
Even though the medication was stable before the study and remained unchanged during the study, and these participants did not serve as outliers in a priori findings as indicated by scatterplots, any influence it may have had on other outcomes cannot be ruled out
Summary
Aberrant amygdala-prefrontal interactions at rest and during emotion processing are implicated in the pathophysiology of generalized social anxiety disorder (gSAD), a common disorder characterized by fears of potential scrutiny. Predictors of success in CBT for gSAD include reduced amygdala reactivity and increased activity in prefrontal regulatory regions Studies have not examined whether tonic (i.e., at rest) coupling of amygdala and these prefrontal regions predict response to CBT. Cognitive behavioral therapy (CBT) is empirically supported psychotherapy for generalized social anxiety disorder (gSAD), a common, debilitating illness marked by excessive fears of negative evaluation by others [1]. Findings from neuroimaging studies indicate heterogeneity in treatment outcome may relate in part to brain regions implicated in the pathophysiology of gSAD that are utilized by CBT. Findings suggest phasic hyper-reactive amygdala responses to external information involve tonic disturbances in core amygdala-prefrontal circuitry [8] and that individual differences in such circuitry may factor into the likelihood of benefiting from CBT
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