Elsevier

Biological Psychiatry

Volume 61, Issue 9, 1 May 2007, Pages 1081-1089
Biological Psychiatry

Original article
Reduced Serotonin-1A Receptor Binding in Social Anxiety Disorder

https://doi.org/10.1016/j.biopsych.2006.05.022Get rights and content

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-HT1A 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.

Section snippets

Subjects

Fourteen medication-free male outpatients with social anxiety disorder and 18 healthy male control subjects were scanned with PET. Two patients were excluded from analysis: one because of drug consumption prior to the scan, discovered afterwards, and the second because of missing structural magnetic resonance imaging (MRI). Details of subject characteristics including psychometric assessment results are given in Table 1. All healthy subjects and most of the patients were recruited from the

Comparison Between SAD Patients and Healthy Control Subjects

The multivariate ANOVA revealed a significant reduction of 5-HT1A BP in SAD patients compared with healthy control subjects (p = .041; Pillai’s Trace). Including age and radiochemical variables as covariates in the multivariate ANOVA, we found a highly significant reduction in 5-HT1A binding in the amygdala (p = .003; −21.4%, uncorrected for multiple comparison, post hoc t test), in the anterior cingulate cortex (p = .004; −23.8%), and in the insula (p = .003; −28.0%), and a significant

Discussion

We have demonstrated a significantly lower 5-HT1A receptor binding potential in male patients suffering from SAD than in an age-matched healthy control group. Significant 5-HT1A BP reductions (corrected for multiple tests) were found in the amygdala (−21.4%), the anterior cingulate cortex (−23.8%), and insula (−28.0%), indicating alterations in limbic and paralimbic areas of SAD patients. The reduction was most prominent in the raphe nuclei (−36.4%) but did not survive correction for multiple

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