Journal
SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
Volume 4, Issue 1, Pages 79-84Publisher
OXFORD UNIV PRESS
DOI: 10.1093/scan/nsn039
Keywords
Amygdala; fear; anxiety; serotonin; 5-HT2A receptor; PET; Urbach-Wiethe disease
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Funding
- German Federal Ministry for Education and Research [01GI9934]
- Deutsche Forschungsgemeinschaft (DFG
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Neurobiological evidence implicates the amygdala as well as serotonergic (serotonin, 5-HT) signaling via postsynaptic 5-HT2A 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-HT2A receptor changes. Thus, we used [F-18]altanserin positron emission tomography (PET) referenced to radioligand plasma levels and corrected for partial volume effects to quantify the spatial distribution of 5-HT2A receptor binding potential (BPP) in a rare patient with UrbachWiethe 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-HT2A receptor BPP in the UrbachWiethe 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-HT2A receptors. Our findings provide important insights into the molecular architecture of human anxiety behaviors and suggest the 5-HT2A receptor as a promising pharmacological target to control pathological anxiety.
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