DECREASED BRAIN GABA(A)-BENZODIAZEPINE RECEPTOR-BINDING IN PANIC DISORDER - PRELIMINARY-RESULTS FROM A QUANTITATIVE PET STUDY

Background: Positron emission tomography (PET)! allows the measurement of benzodiazepine-gamma-aminobutyric acid, (GABA,) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand tha t labels the benzodiazepine site on the GABAA receptor, and fully quan titative, high-sensitivity PET to test the hypothesis that central ben zodiazepine site binding is decreased in medication-free patients with panic disorder. Methods: We compared 7 patients with panic disorder w ho had been off medication for at least 6 months and who had never abu sed alcohol with 8 healthy controls. The resulting parametric voxel-by -voxel maps were analyzed by voxel-based and region of interest-based methods using both parametric and nonparametric statistics. Results: T he major finding was that there is a global reduction in benzodiazepin e site binding throughout the brain in patients with panic disorder co mpared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In a ddition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought I:o be esse ntial in the central mediation of anxiety. Conclusion: These results m ust be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GAB A(A), receptor and demonstrate that decreased flumazenil binding at th is site may underlie panic disorder.