1. ¹Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria
2. ²Department of Nuclear Medicine, Medical University Vienna, Vienna, Austria
3. ³Department of Inorganic Chemistry, University of Vienna, Vienna, Austria
4. ⁴Department of Pharmaceutical Technology, University of Vienna, Vienna, Austria

Correspondence: Professor S Kasper, Department of Psychiatry and Psychotherapy, Medical University Vienna, MUV, AKH, Waehringer Guertel 18-20, Wien A-1090, Austria. E-mail: sci-biolpsy@meduniwien.ac.at

⁵These authors contributed equally to this work.

Received 23 July 2007; Revised 14 February 2008; Accepted 18 February 2008; Published online 25 March 2008.

Abstract

There is an increasing interest in the underlying mechanisms of the antidepressant and anxiolytic treatment effect associated with changes in serotonergic neurotransmission after treatment with selective serotonin (5-HT) reuptake inhibitors (SSRIs) in humans. The 5-HT_1A receptor is known to play a crucial role in the pathophysiology of affective disorders, and altered 5-HT_1A receptor binding has been found in anxiety patients. SSRI treatment raises the 5-HT level in the synaptic cleft and might change postsynaptic receptor densities. Therefore, our study in patients suffering from anxiety disorders investigated the effects of long-term treatment with escitalopram on the 5-HT_1A receptor. A longitudinal positrone emission tomography (PET) study in 12 patients suffering from anxiety disorders was conducted. Two dynamic PET scans were performed applying the selective 5-HT_1A receptor antagonist [carbonyl-¹¹C]WAY-100635. Eight regions of interest were defined a priori (orbitofrontal cortex, amygdala, hippocampus, subgenual cortex, anterior and posterior cingulate cortex, dorsal raphe nucleus and cerebellum as reference). After the baseline PET scan, patients were administered escitalopram (average dose of 11.26.0 mg day^-1) for a minimum of 12 weeks. A second PET scan was conducted after 10927 days. 5-HT_1A receptor binding potentials in 12 patients were assessed by PET applying the Simplified Reference Tissue Model.There was a significant reduction in the 5-HT_1A receptor binding potential after a minimum of 12 weeks of escitalopram treatment in the hippocampus (P=0.006), subgenual cortex (P=0.017) and posterior cingulate cortex (P=0.034). The significance of the hippocampus region survived the Bonferroni-adjusted threshold for multiple comparisons. These PET data in humans in vivo demonstrate a reduction of the 5-HT_1A binding potential after SSRI treatment.