TY  - JOUR
AU  - Hurlemann, R.
AU  - Schlaepfer, T.E.
AU  - Matusch, A.
AU  - Reich, H.
AU  - Shah, J. N.
AU  - Zilles, K.
AU  - Maier, W.
AU  - Bauer, A.
TI  - Reduced 5-HT2A receptor signaling following selective bilateral amygdala damage
JO  - Social cognitive and affective neuroscience
VL  - 4
SN  - 1749-5016
CY  - Oxford
PB  - Oxford Univ. Press
M1  - PreJuSER-1420
SP  - 97 - 84
PY  - 2009
N1  - The authors are grateful to M. X. Cohen and M. Wagner for helpful comments on an earlier version of the manuscript. In addition, the authors wish to thank H. H. Coenen, J. Ermert, S. Grafmuller, K. Hamacher, M. Lang, B. Palm, S. Rehbein, E. Wabbels (Institute of Nuclear Chemistry), D. Elmenhorst, S. Sihver, M. Vogeling (Molecular Neuroimaging Group), H. Herzog, S. Schaden, L. Tellmann, E. Theelen (PET Instrumentation Group), B. Elghahwagi, P. Engels, G. Oefler and A.-M. Oros-Peusquens (MRI Instrumentation Group, Research Center Juelich). This work was supported by the German Federal Ministry for Education and Research (BMBF) (01GI9934); Deutsche Forschungsgemeinschaft (DFG) (Klinische Forschergruppe 112 to A. B.); International Consortium for Brain Mapping (ICBM). These authors contributed equally to this work.
AB  - 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.
KW  - Adult
KW  - Amygdala: pathology
KW  - Amygdala: radionuclide imaging
KW  - Fluorine Radioisotopes: diagnostic use
KW  - Humans
KW  - Image Processing, Computer-Assisted
KW  - Ketanserin: analogs & derivatives
KW  - Ketanserin: diagnostic use
KW  - Lipoid Proteinosis of Urbach and Wiethe: pathology
KW  - Lipoid Proteinosis of Urbach and Wiethe: psychology
KW  - Lipoid Proteinosis of Urbach and Wiethe: radionuclide imaging
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Neuropsychological Tests
KW  - Positron-Emission Tomography
KW  - Radiopharmaceuticals: diagnostic use
KW  - Receptor, Serotonin, 5-HT2A: physiology
KW  - Serotonin: physiology
KW  - Synaptic Transmission
KW  - Fluorine Radioisotopes (NLM Chemicals)
KW  - Radiopharmaceuticals (NLM Chemicals)
KW  - Receptor, Serotonin, 5-HT2A (NLM Chemicals)
KW  - Serotonin (NLM Chemicals)
KW  - Ketanserin (NLM Chemicals)
KW  - altanserin (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19015089
C2  - pmc:PMC2656878
UR  - <Go to ISI:>//WOS:000264398000008
DO  - DOI:10.1093/scan/nsn039
UR  - https://juser.fz-juelich.de/record/1420
ER  -