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Preliminary Results From a Quantitative PET Study

Andrea L. Malizia, MBBS, MRCPsych; Vincent J. Cunningham, PhD; Caroline J. Bell, MBBChir, MRCPsych; Peter F. Liddle, PhD, MBBS, FRCPsych; Terry Jones, PhD, DSc(Hon); David J. Nutt, MBBS, DM, MRCP, FRCPsych

Arch Gen Psychiatry. 1998;55:715-720.

Background  Positron emission tomography (PET) allows the measurement of benzodiazepine–-aminobutyric acid_A (GABA_A) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand that labels the benzodiazepine site on the GABA_A receptor, and fully quantitative, high-sensitivity PET to test the hypothesis that central benzodiazepine site binding is decreased in medication-free patients with panic disorder.

Methods  We compared 7 patients with panic disorder who had been off medication for at least 6 months and who had never abused 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  The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In addition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought to be essential in the central mediation of anxiety.

Conclusion  These results must be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GABA_A receptor and demonstrate that decreased flumazenil binding at this site may underlie panic disorder.

From the Cyclotron Unit, Medical Research Council, Clinical Research Centre, Hammersmith Hospital, London, England (Drs Malizia, Cunningham, Liddle, and Jones); Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, England (Drs Malizia, Bell, and Nutt); and Department of Psychiatry, University of British Columbia, Vancouver (Dr Liddle). Dr Malizia is now with the Clinical Pharmacology Unit, SmithKline Beecham Pharmaceuticals, Harlow, England.

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