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 acidA (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.


CONCLUSIONS
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.
Malizia
A L
AL
Cyclotron Unit, Medical Research Council, Clinical Research Centre, Hammersmith Hospital, London, England.
Cunningham
V J
VJ
Bell
C J
CJ
Liddle
P F
PF
Jones
T
T
Nutt
D J
DJ
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005442:Flumazenil; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D010555:Personality Inventory; D011963:Receptors, GABA-A / Q000378:metabolism*; D012737:Sex Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid