Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia

Biol Psychiatry. 2013 Feb 15;73(4):329-36. doi: 10.1016/j.biopsych.2012.10.003. Epub 2012 Nov 17.


Background: Generalized social phobia (gSP), also known as generalized social anxiety disorder, is characterized by excessive fear of scrutiny by others and pervasive avoidance of social interactions. Pathophysiologic models of gSP implicate exaggerated reactivity of the amygdala and insula in response to social evaluative threat, making them plausible targets for treatment. Although selective serotonin reuptake inhibitor (SSRI) treatment is known to be an effective treatment, little is known about the mechanism through which these agents exert their anxiolytic effects at a brain level in gSP.

Methods: We acquired functional magnetic resonance imaging data of brain response to social signals of threat (fearful/angry faces) in 21 gSP patients before and after they completed 12 weeks of open-label treatment with the SSRI sertraline. For comparison, 19 healthy control (HC) subjects also underwent two functional magnetic resonance imaging scans, 12 weeks apart.

Results: Whole-brain voxelwise analysis of variance revealed significant Group×Time interactions in the amygdala and the ventral medial prefrontal cortex. Follow-up analyses showed that treatment in gSP subjects reduced amygdala reactivity to fearful faces (which was exaggerated relative to HCs before treatment) and enhanced ventral medial prefrontal cortex activation to angry faces (which was attenuated relative to HCs before treatment). However, these brain changes were not significantly related to social anxiety symptom improvement.

Conclusions: SSRI treatment response in gSP is associated with changes in a discrete limbic-paralimbic brain network, representing a neural mechanism through which SSRIs may exert their actions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Attention / drug effects
  • Attention / physiology
  • Brain Mapping
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology
  • Cues
  • Emotions / drug effects
  • Emotions / physiology
  • Fear / drug effects
  • Fear / physiology
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Limbic System / drug effects*
  • Limbic System / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Phobic Disorders / drug therapy*
  • Phobic Disorders / physiopathology
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Sertraline / pharmacology
  • Sertraline / therapeutic use*


  • Serotonin Uptake Inhibitors
  • Sertraline