Reduced serotonin-1A receptor binding in social anxiety disorder

Background: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). Methods: Using PET and [carbonyl-C-11]WAY- 100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HQ. A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. Results: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p=.234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p =.003). There was also a more than 20% lower 5-HT1A BP of SAD patients in the anterior cingulate cortex (p =.004), insula (p =.003), and dorsal raphe nuclei (p =.030). Conclusions: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A, binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.