Neural response to eye contact and paroxetine treatment in generalized social anxiety disorder

Generalized social anxiety disorder (GSAD) is characterized by excessive fears of scrutiny and negative evaluation, but neural circuitry related to scrutiny in GSAD has been little studied. In this study, 16 unmedicated adults with GSAD and 16 matched healthy comparison (HC) participants underwent functional magnetic resonance imaging to assess neural response to viewed images of faces simulating movement into eye contact versus away from eye contact. GSAD patients were then treated for 8 weeks with paroxetine, and 15 patients were re-imaged. At baseline, GSAD patients had elevated neural response to eye contact in parahippocampal cortex, inferior parietal lobule, supramarginal gyrus, posterior cingulate and middle occipital cortex. During paroxetine treatment, symptomatic improvement was associated with decreased neural response to eye contact in regions including inferior and middle frontal gyri, anterior cingulate, posterior cingulate, precuneus and inferior parietal lobule. Both the magnitude of GSAD symptom reduction with paroxetine treatment and the baseline comparison of GSAD vs. HCs were associated with neural processing of eye contact in distributed networks that included regions involved in self-referential processing. These findings demonstrate that eye contact in GSAD engages neurocircuitry consistent with the heightened self-conscious emotional states known to characterize GSAD patients during scrutiny.