Cerebral benzodiazepine receptor binding and distribution in generalized anxiety disorder: a fractal analysis

Abstract

Data obtained from animal and human brain imaging studies indicate that frontal cortex and medial temporal lobe are involved in experiencing and controlling fear and anxiety. We tested the hypothesis that benzodiazepine receptor binding is decreased in the left temporal pole and increased in the right prefrontal area among patients suffering from anxiety. We studied 10 drug-naive female patients with generalized anxiety disorder (GAD) and 10 age- and gender-matched healthy controls with MRI and with SPET by using a new ¹²³I-labelled specific benzodiazepine receptor radioligand, NNC 13-8241. Blindly analyzed results showed that the benzodiazepine receptor binding of [¹²³I]NNC 13-8241 was significantly decreased in the left temporal pole among patients with GAD when compared with age- and sex-matched healthy controls. This hemispheric asymmetry was studied further with a fractal analysis of the SPET images. The fractal dimension of the left hemispheric benzodiazepine receptor binding in patients with GAD was significantly higher than that of controls (1.28 ± 0.09 and 1.17 ± 0.07, respectively), whereas the intercept was decreased by 43 ± 23% reflecting more homogeneous cerebral benzodiazepine receptor density distribution in patients with GAD. The finding is analogous to the decreased heterogeneity of myocardial blood flow observed in patients with ischemic heart disease. The results are consistent with the general hypothesis that high regional heterogeneity of perfusion, metabolism and receptor density is necessary to maintain adaptation ability in the living organism.