Reduced serotonin-1A receptor binding in social anxiety disorder.
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.
Lanzenberger
Rupert R
RR
Department of General Psychiatry, Medical University of Vienna, Vienna, Austria. rupert.lanzenberger@meduniwien.ac.at
Mitterhauser
Markus
M
Spindelegger
Christoph
C
Wadsak
Wolfgang
W
Klein
Nikolas
N
Mien
Leonhard-Key
LK
Holik
Alexander
A
Attarbaschi
Trawat
T
Mossaheb
Nilufar
N
Sacher
Julia
J
Geiss-Granadia
Thomas
T
Kletter
Kurt
K
Kasper
Siegfried
S
Tauscher
Johannes
J
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010698:Phobic Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D010879:Piperazines; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide