Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:83-91. doi: 10.1016/j.pnpbp.2013.05.004. Epub 2013 May 10.


Cognitive behavioral therapy (CBT) is "gold standard" psychotherapy for social anxiety disorder (SAD). Cognitive models posit that preferential processing of threat mediates excessive forms of anxiety, which is supported by exaggerated amygdala, insula, and cortical reactivity to threatening socio-emotional signals in SAD. However, little is known about neural predictors of CBT success or the mechanisms by which CBT exerts its therapeutic effects. Functional magnetic resonance imaging (fMRI) was conducted during responses to social signals of threat (fearful/angry faces) against positive signals (happy faces) in 14 patients with SAD before and after 12 weeks of CBT. For comparison, 14 healthy control (HC) participants also underwent two fMRI scans, 12 weeks apart. Whole-brain voxel-wise analyses showed therapeutic success was predicted by enhanced pre-treatment activation to threatening faces in higher-order visual (superior and middle temporal gyrus), cognitive, and emotion processing areas (dorsal anterior cingulate cortex, dorsomedial prefrontal cortex). Moreover, a group by time interaction was revealed in prefrontal regions (dorsomedial, medial gyrus) and insula. The interaction was driven by relatively greater activity during threat processing in SAD, which significantly reduced after CBT but did not significantly predict response to CBT. Therefore, pre-treatment cortical hyperactivity to social threat signals may serve as a prognostic indicator of CBT success in SAD. Collectively, CBT-related brain changes involved a reduction in activity in insula, prefrontal, and extrastriate regions. Results are consistent with cognitive models, which associate decreases in threat processing bias with recovery.

Keywords: ACC; BDI; BOLD; Beck Depression Inventory; Brain imaging; CBT; CGI-I; Clinical Global Impression-Improvement; DSM-IV; Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision; Emotional faces; Generalized social anxiety; HC; LSAS; Liebowitz Social Anxiety Scale; PFC; Treatment; anterior cingulate cortex; blood-oxygen-level-dependent; cognitive behavioral therapy; fMRI; functional magnetic resonance imaging; gSAD; generalized Social Anxiety Disorder; healthy controls; prefrontal cortex.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anxiety Disorders / physiopathology*
  • Anxiety Disorders / therapy*
  • Brain / physiopathology*
  • Brain Mapping
  • Cognitive Behavioral Therapy*
  • Endophenotypes*
  • Facial Expression
  • Fear / physiology*
  • Female
  • Humans
  • Male
  • Severity of Illness Index
  • Social Behavior*