Karleyton C. Evans

Corticolimbic circuitry has been implicated in generalized social anxiety disorder (gSAD) by several neuroimaging symptom provocation studies. However, there are limited data regarding resting state or treatment effects on regional cerebral metabolic rate of glucose uptake (rCMRglu). Given evidence for anxiolytic effects conferred by tiagabine, a γ-aminobutyric acid (GABA) reuptake inhibitor, the present [¹⁸F] fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) study sought to (1) compare resting rCMRglu between healthy control (HC) and pretreatment gSAD cohorts, (2) examine pre- to post-tiagabine treatment rCMRglu changes in gSAD, and (3) determine rCMRglu predictors of tiagabine treatment response. Fifteen unmedicated individuals with gSAD and ten HCs underwent a baseline (pretreatment) resting-state ¹⁸FDG-PET scan. Twelve of the gSAD individuals completed an open, 6-week, flexible dose trial of tiagabine, and underwent a second (posttreatment) resting-state ¹⁸FDG-PET scan. Compared to the HC subjects, individuals with gSAD demonstrated less pretreatment rCMRglu within the anterior cingulate cortex and ventral medial prefrontal cortex (vmPFC) at baseline. Following tiagabine treatment, vmPFC rCMRglu increased significantly in the gSAD group. Further, the magnitude of treatment response was inversely correlated with pretreatment rCMRglu within vmPFC. Taken together the present findings converge with neuroimaging findings from studies of social cognition in healthy individuals and symptom provocation in gSAD to support a role for the vmPFC in the pathophysiology of gSAD. Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC.

Neuroimaging studies using angry or contemptuous human facial photographic stimuli have suggested amygdala hyper-responsivity in social anxiety disorder (SAD). We sought to determine if an angry “schematic face” (simple line drawing) would evoke exaggerated amygdalar responses in SAD patients compared with healthy control (HC) subjects. Angry, happy, and neutral schematic faces were overtly presented to matched cohorts of 11 SAD and 11 HC subjects for passive viewing, whereas brain functional magnetic resonance imaging signal was measured at 1.5 Tesla. Voxel-wise analyses were performed using a random effects model in SPM99. Compared with HC subjects, SAD patients exhibited exaggerated responses in the right amygdala for the Angry versus Neutral contrast. The findings of exaggerated amygdala responses to angry schematic faces in SAD converge with results from earlier neuroimaging studies and illustrate the potential utility of schematic faces for probing amygdala function in psychiatric disorders. One prospective advantage of schematic faces is that they may minimize confounds related to gender, age, or race effects. However, extending earlier findings in healthy subjects, schematic faces appear more effective for probing amygdala responses to arousal-based (Angry versus Neutral) as opposed to valence-based (Angry versus Happy) contrasts. Depression and Anxiety 0:1–10, 2007. Published 2007 Wiley-Liss, Inc.