Reduced serotonin-1A receptor binding in social anxiety disorder.

Abstract

BACKGROUND:

Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD).

METHODS:

Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed.

RESULTS:

We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030).

CONCLUSIONS:

The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.

• Authors: Rupert R Lanzenberger, Markus Mitterhauser, Christoph Spindelegger, Wolfgang Wadsak, Nikolas Klein, Leonhard-Key Mien, Alexander Holik, Trawat Attarbaschi, Nilufar Mossaheb, Julia Sacher, Thomas Geiss-Granadia, Kurt Kletter, Siegfried Kasper, Johannes Tauscher
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 61 Issue 9 Pg. 1081-9 (May 01 2007) ISSN: 0006-3223 [Print] United States
• PMID: 16979141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Pyridines
• Serotonin Antagonists
• Receptor, Serotonin, 5-HT1A
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide

Topics

• Adult
• Brain (diagnostic imaging)
• Brain Chemistry (physiology)
• Humans
• Magnetic Resonance Imaging
• Male
• Phobic Disorders (diagnostic imaging, metabolism, psychology)
• Piperazines
• Positron-Emission Tomography
• Psychiatric Status Rating Scales
• Pyridines
• Receptor, Serotonin, 5-HT1A (metabolism)
• Serotonin Antagonists