Neurobiological evidence implicates the amygdala as well as serotonergic 
(serotonin, 5-HT) signaling via postsynaptic 5-HT(2A) receptors as essential 
substrates of anxiety behaviors. Assuming a functional interdependence of these 
substrates, we hypothesized that a low-fear behavioral phenotype due to 
bilateral lesion of the amygdala would be associated with significant 5-HT(2A) 
receptor changes. Thus, we used [(18)F]altanserin positron emission tomography 
(PET) referenced to radioligand plasma levels and corrected for partial volume 
effects to quantify the spatial distribution of 5-HT(2A) receptor binding 
potential (BP(P)) in a rare patient with Urbach-Wiethe disease and selective 
bilateral amygdala calcification damage relative to 10 healthy control subjects. 
Consistent with our a priori hypothesis, we observed a 70% global decrease in 
5-HT(2A) receptor BP(P) in the Urbach-Wiethe patient relative to controls. Thus, 
brain abnormalities in this patient are not restricted to the amygdala, but 
extend to overall 5-HT neurotransmission via 5-HT(2A) receptors. Our findings 
provide important insights into the molecular architecture of human anxiety 
behaviors and suggest the 5-HT(2A) receptor as a promising pharmacological 
target to control pathological anxiety.