Abstract |
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.
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Authors | René Hurlemann, Thomas E Schlaepfer, Andreas Matusch, Harald Reich, Nadim J Shah, Karl Zilles, Wolfgang Maier, Andreas Bauer |
Journal | Social cognitive and affective neuroscience
(Soc Cogn Affect Neurosci)
Vol. 4
Issue 1
Pg. 79-84
(Mar 2009)
ISSN: 1749-5024 [Electronic] England |
PMID | 19015089
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Fluorine Radioisotopes
- Radiopharmaceuticals
- Receptor, Serotonin, 5-HT2A
- Serotonin
- altanserin
- Ketanserin
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Topics |
- Adult
- Amygdala
(diagnostic imaging, pathology)
- Fluorine Radioisotopes
- Humans
- Image Processing, Computer-Assisted
- Ketanserin
(analogs & derivatives)
- Lipoid Proteinosis of Urbach and Wiethe
(diagnostic imaging, pathology, psychology)
- Magnetic Resonance Imaging
- Male
- Neuropsychological Tests
- Positron-Emission Tomography
- Radiopharmaceuticals
- Receptor, Serotonin, 5-HT2A
(physiology)
- Serotonin
(physiology)
- Synaptic Transmission
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