Have No Fear: The Neural Basis of Anxiolytic Drug Action in Generalized Social Phobia

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for anxiety disorders such as social phobia. Despite widespread use of SSRIs over the last 20 years, our understanding of how these treatments correct the disabling psychological symptoms seen in anxiety disorders is still in its infancy. Neuropsychological models highlight a key role for corticolimbic neural circuitry in anxiety, in which excessive reactivity to threat at the level of the amygdala is left unchecked by cortical systems, which usually regulate excessive or inappropriate responses to these cues. This model has been widely supported by experimental evidence across a number of anxiety disorders, shown as an imbalance in activity and/or reduced connectivity across amygdala-medial prefrontal cortex networks believed to govern our responses to a potential environmental threat ( 1 Kim M.J. Loucks R.A. Palmer A.L. Brown A.C. Solomon K.M. Marchante A.N. Whalen P.J. The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety. Behav Brain Res. 2011; 223: 403-410 Crossref PubMed Scopus (597) Google Scholar ). In this issue of Biological Psychiatry, Phan et al. ( 2 Phan KL, Coccaro EF, Angstadt M, Kreger KJ, Mayberg HS, Liberzon I, Stein MB (2013): Corticolimbic brain reactivity to social signals of threat before and after sertraline treatment in generalized social phobia. Biol Psychiatry 73:329–336. Google Scholar ) present evidence that a 12 week SSRI treatment with sertraline normalizes aberrant threat responses in this corticolimbic circuit in generalized social phobia, revealing a potentially relevant neuropsychological mechanism of anxiolytic drug action. Corticolimbic Brain Reactivity to Social Signals of Threat Before and After Sertraline Treatment in Generalized Social PhobiaBiological PsychiatryVol. 73Issue 4PreviewGeneralized 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. Full-Text PDF