Reduced 5-HT2A receptor signaling following selective bilateral amygdala damage

René Hurlemann, Thomas E. Schlaepfer, Andreas Matusch, Harald Reich, Nadim J. Shah, Karl Zilles, Wolfgang Maier, Andreas Bauer

Research output: Contribution to journalArticle

Abstract

Neurobiological evidence implicates the amygdala as well as serotonergic (serotonin, 5-HT) signaling via postsynaptic 5-HT2A 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-HT2A receptor changes. Thus, we used [18F]altanserin positron emission tomography (PET) referenced to radioligand plasma levels and corrected for partial volume effects to quantify the spatial distribution of 5-HT2A receptor binding potential (BPP) 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-HT2A receptor BPP 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-HT2A receptors. Our findings provide important insights into the molecular architecture of human anxiety behaviors and suggest the 5-HT2A receptor as a promising pharmacological target to control pathological anxiety.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalSocial cognitive and affective neuroscience
Volume4
Issue number1
DOIs
StatePublished - Apr 3 2009

    Fingerprint

Keywords

  • 5-HT receptor
  • Amygdala
  • Anxiety
  • Fear
  • PET
  • Serotonin
  • Urbach-Wiethe disease

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience

Cite this