Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study

The central benzodiazepine receptor (cBZr) has long been implicated in anxi ety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a pos sibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced , namely changes in the concentration or properties of the latter, and chan ges in the GABAA complex conformation, which contains the cBZr. Neither pos tmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure bot h the density and affinity of the cBZr in multiple brain regions in unmedic ated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr paramet ers and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 :1; mean age: 39 years), prospectively recruited using DSM III -R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of C-11-flu mazenil (at high and low specific radioactivity) and previously validated b y us, we estimated the B-max, K-d and bound :free (B/F) ratios in 11 neocor tical areas and in the cerebellum. Before and after the PET session, anxiet y scores from Spielberger's and Covi's scales were obtained. There was no s tatistically significant difference in B-max, K-d or B/F-values between the two groups for any region. Across the two groups, there were only a few ma rginally significant anxiety-score-PET correlations, suggesting chance find ings. This is the first fully quantitative study to report on the relations hips between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cer ebellum in this sample. These findings, if confirmed by studies on larger s amples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of an xiety.