Corticolimbic Brain Reactivity to Social Signals of Threat Before and After Sertraline Treatment in Generalized Social Phobia

doi:10.1016/j.biopsych.2012.10.003

Biological Psychiatry

Volume 73, Issue 4, 15 February 2013, Pages 329-336

https://doi.org/10.1016/j.biopsych.2012.10.003 Get rights and content

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.

Section snippets

Subjects

Twenty-one untreated (e.g., unmedicated and not in psychotherapy) gSP and 19 HC volunteers participated in this study. This study was conducted at the University of Chicago (gSP n = 12; HC n = 14) and at the University of Michigan (gSP n = 9; HC n = 5). Each subject underwent a screening evaluation involving structured clinical interviews and assessments by trained clinicians and semistructured medical and psychiatric interviews with the study psychiatrist (K.L.P.). All subjects were

Treatment Effects on Social Anxiety Severity

After 12 weeks of sertraline treatment, social anxiety severity, as indexed by the LSAS score, dropped significantly from a mean (SD) of 82.29 (13.02) to 44.71 (25.44; t = 7.24, p<.001), nearly a 50% reduction and similar to previous SSRI trials in gSP (2). The large effect size observed here may be due in part to the entry criteria, which excluded previous failure of response to sertraline or other SSRI. At PostTx, two-thirds of the gSP group (14 of 21) were considered to be “Responders” as

Discussion

The goal of this study was to examine the effect of treatment on brain responses to social signals of threat (angry, fearful faces) in patients with gSP in the context of an open-label 12-week clinical trial of the SSRI sertraline, a Food and Drug Administration–approved, evidence-based treatment for gSP (2). As predicted, we observed that SSRI treatment in gSP subjects reduced left amygdala reactivity to fearful faces, which had been exaggerated relative to HCs before treatment. Second, we

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Archival ReportCorticolimbic Brain Reactivity to Social Signals of Threat Before and After Sertraline Treatment in Generalized Social Phobia

Background

Methods

Results

Conclusions

Section snippets

Subjects

Treatment Effects on Social Anxiety Severity

Discussion

Lancet

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychol

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Eur J Pharmacol

Trends Cogn Sci

Neuroimage

Neuroimage

Prog Neuropsychopharmacol Biol Psychiatry

J Neurosci Methods

Trends Cogn Sci

Trends Cogn Sci

Psychiatry Res

J Affect Disord

Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication

Arch Gen Psychiatry

Social fears and social phobia in the USA: Results from the National Comorbidity Survey Replication

Psychol Med

Clinical practice. Social anxiety disorder

N Engl J Med

Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia

Am J Psychiatry

The amygdala: Vigilance and emotion

Mol Psychiatry

The neurocircuitry of fear, stress, and anxiety disorders

Neuropsychopharmacology

Recent advances in the neurobiology of anxiety disorders: Implications for novel therapeutics

Am J Med Genet C Semin Med Genet

Archival Report
Corticolimbic Brain Reactivity to Social Signals of Threat Before and After Sertraline Treatment in Generalized Social Phobia