An FDG-PET study of GABAergic treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder

Abstract

1001

Objectives: Cortico-limbic circuitry has been implicated in generalized social anxiety disorder (gSAD), yet resting state and treatment-related regional cerebral metabolic rates of glucose uptake (rCMRglu) remain unknown. Given reported anxiolytic effects of tiagabine, a GABA reuptake inhibitor, the present fluorodeoxyglucose-positron emission tomography (FDG-PET) study sought to: compare resting rCMRglu between healthy control (HC) and pre-treatment gSAD cohorts, examine pre-/post-tiagabine rCMRglu in gSAD, determine rCMRglu predictors of treatment response.

Methods: Pre-treatment resting state FDG-PET scans were acquired in 15 gSAD and 10 HC. Post-treatment scans were acquired in the gSAD cohort after an open, 6-week, tiagabine trial. Objective hypotheses were tested via voxel-wise SPM5 analyses.

Results: Reduced pre-treatment rCMRglu was observed within anterior cingulate and ventral medial prefrontal cortices (vmPFC) in gSAD compared to HC. Increased vmPFC rCMRglu was observed in gSAD at post-treatment and the magnitude of treatment response was inversely correlated with pre-treatment vmPFC rCMRglu.

Conclusions: The present findings converge with lesion studies and gSAD symptom provocation neuroimaging studies to implicate vmPFC pathophysiology in gSAD. Given the pharmacology of tiagabine, these findings suggest its therapeutic effects in gSAD may be mediated by vmPFC GABAergic modulation.

Research Support: Supported by an investigator-initiated grant from Cephalon.