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000001420 0247_ $$2DOI$$a10.1093/scan/nsn039
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000001420 084__ $$2WoS$$aNeurosciences
000001420 084__ $$2WoS$$aPsychology
000001420 084__ $$2WoS$$aPsychology, Experimental
000001420 1001_ $$0P:(DE-HGF)0$$aHurlemann, R.$$b0
000001420 245__ $$aReduced 5-HT2A receptor signaling following selective bilateral amygdala damage
000001420 260__ $$aOxford$$bOxford Univ. Press$$c2009
000001420 300__ $$a97 - 84
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000001420 440_0 $$019361$$aSocial Cognitive and Affective Neuroscience$$v4$$x1749-5016$$y1
000001420 500__ $$aThe 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.
000001420 520__ $$aNeurobiological evidence implicates the amygdala as well as serotonergic (serotonin, 5-HT) signaling via postsynaptic 5-HT(2A) receptors as essential substrates of anxiety behaviors. Assuming a functional interdependence of these substrates, we hypothesized that a low-fear behavioral phenotype due to bilateral lesion of the amygdala would be associated with significant 5-HT(2A) receptor changes. Thus, we used [(18)F]altanserin positron emission tomography (PET) referenced to radioligand plasma levels and corrected for partial volume effects to quantify the spatial distribution of 5-HT(2A) receptor binding potential (BP(P)) in a rare patient with Urbach-Wiethe disease and selective bilateral amygdala calcification damage relative to 10 healthy control subjects. Consistent with our a priori hypothesis, we observed a 70% global decrease in 5-HT(2A) receptor BP(P) in the Urbach-Wiethe patient relative to controls. Thus, brain abnormalities in this patient are not restricted to the amygdala, but extend to overall 5-HT neurotransmission via 5-HT(2A) receptors. Our findings provide important insights into the molecular architecture of human anxiety behaviors and suggest the 5-HT(2A) receptor as a promising pharmacological target to control pathological anxiety.
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000001420 65320 $$2Author$$aAmygdala
000001420 65320 $$2Author$$afear
000001420 65320 $$2Author$$aanxiety
000001420 65320 $$2Author$$aserotonin
000001420 65320 $$2Author$$a5-HT2A receptor
000001420 65320 $$2Author$$aPET
000001420 65320 $$2Author$$aUrbach-Wiethe disease
000001420 650_2 $$2MeSH$$aAdult
000001420 650_2 $$2MeSH$$aAmygdala: pathology
000001420 650_2 $$2MeSH$$aAmygdala: radionuclide imaging
000001420 650_2 $$2MeSH$$aFluorine Radioisotopes: diagnostic use
000001420 650_2 $$2MeSH$$aHumans
000001420 650_2 $$2MeSH$$aImage Processing, Computer-Assisted
000001420 650_2 $$2MeSH$$aKetanserin: analogs & derivatives
000001420 650_2 $$2MeSH$$aKetanserin: diagnostic use
000001420 650_2 $$2MeSH$$aLipoid Proteinosis of Urbach and Wiethe: pathology
000001420 650_2 $$2MeSH$$aLipoid Proteinosis of Urbach and Wiethe: psychology
000001420 650_2 $$2MeSH$$aLipoid Proteinosis of Urbach and Wiethe: radionuclide imaging
000001420 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000001420 650_2 $$2MeSH$$aMale
000001420 650_2 $$2MeSH$$aNeuropsychological Tests
000001420 650_2 $$2MeSH$$aPositron-Emission Tomography
000001420 650_2 $$2MeSH$$aRadiopharmaceuticals: diagnostic use
000001420 650_2 $$2MeSH$$aReceptor, Serotonin, 5-HT2A: physiology
000001420 650_2 $$2MeSH$$aSerotonin: physiology
000001420 650_2 $$2MeSH$$aSynaptic Transmission
000001420 650_7 $$00$$2NLM Chemicals$$aFluorine Radioisotopes
000001420 650_7 $$00$$2NLM Chemicals$$aRadiopharmaceuticals
000001420 650_7 $$00$$2NLM Chemicals$$aReceptor, Serotonin, 5-HT2A
000001420 650_7 $$050-67-9$$2NLM Chemicals$$aSerotonin
000001420 650_7 $$074050-98-9$$2NLM Chemicals$$aKetanserin
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000001420 7001_ $$0P:(DE-HGF)0$$aSchlaepfer, T.E.$$b1
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000001420 7001_ $$0P:(DE-HGF)0$$aReich, H.$$b3
000001420 7001_ $$0P:(DE-Juel1)131794$$aShah, J. N.$$b4$$uFZJ
000001420 7001_ $$0P:(DE-Juel1)131714$$aZilles, K.$$b5$$uFZJ
000001420 7001_ $$0P:(DE-HGF)0$$aMaier, W.$$b6
000001420 7001_ $$0P:(DE-Juel1)131672$$aBauer, A.$$b7$$uFZJ
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