Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage.
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.
Hurlemann
René
R
Brain Imaging Center West, Research Center Juelich, Juelich, Germany. renehurlemann@me.com
Schlaepfer
Thomas E
TE
Matusch
Andreas
A
Reich
Harald
H
Shah
Nadim J
NJ
Zilles
Karl
K
Maier
Wolfgang
W
Bauer
Andreas
A
D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging* / Q000473:pathology*; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007650:Ketanserin / Q000031:analogs & derivatives; D008065:Lipoid Proteinosis of Urbach and Wiethe / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; C071983:altanserin; D007650:Ketanserin