Journal Article

PreJuSER-1420

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reduced 5-HT2A receptor signaling following selective bilateral amygdala damage

Hurlemann, R. ; Schlaepfer, T. E. ; Matusch, A.FZJ* ; Reich, H. ; Shah, J. N.FZJ* ; Zilles, K.FZJ* ; Maier, W. ; Bauer, A.FZJ*

2009
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/scan/nsn039

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.

Keyword(s): Adult (MeSH) ; Amygdala: pathology (MeSH) ; Amygdala: radionuclide imaging (MeSH) ; Fluorine Radioisotopes: diagnostic use (MeSH) ; Humans (MeSH) ; Image Processing, Computer-Assisted (MeSH) ; Ketanserin: analogs & derivatives (MeSH) ; Ketanserin: diagnostic use (MeSH) ; Lipoid Proteinosis of Urbach and Wiethe: pathology (MeSH) ; Lipoid Proteinosis of Urbach and Wiethe: psychology (MeSH) ; Lipoid Proteinosis of Urbach and Wiethe: radionuclide imaging (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Male (MeSH) ; Neuropsychological Tests (MeSH) ; Positron-Emission Tomography (MeSH) ; Radiopharmaceuticals: diagnostic use (MeSH) ; Receptor, Serotonin, 5-HT2A: physiology (MeSH) ; Serotonin: physiology (MeSH) ; Synaptic Transmission (MeSH) ; Fluorine Radioisotopes ; Radiopharmaceuticals ; Receptor, Serotonin, 5-HT2A ; Serotonin ; Ketanserin ; altanserin ; J ; Amygdala (auto) ; fear (auto) ; anxiety (auto) ; serotonin (auto) ; 5-HT2A receptor (auto) ; PET (auto) ; Urbach-Wiethe disease (auto)

Note: 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.

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Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)

Appears in the scientific report 2009

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