1. ¹Department of Biological Psychiatry, Medical University of Vienna, Vienna, Austria
2. ²Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria
3. ³Department of Neurochemistry, Ludwig Maximilians University, Munich, Germany
4. ⁴Department for Medical Statistics, Medical University of Vienna, Vienna, Austria;
5. ⁵Department of Transfusion Medicine, Medical University of Vienna, Vienna, Austria

Correspondence: Dr M Willeit, Department of Biological Psychiatry, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria. Tel: +43 1 40 400 3543; Fax: +43 1 40 400 3099; E-mail: matthaeus.willeit@meduniwien.ac.at; Dr HH Sitte, Center for Biomolecular Medicine and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Währinger Strasse 13a, Vienna A-1090, Austria. Tel: +43 1 4277 64123; Fax: +43 1 4277 9641; E-mail: harald.sitte@meduniwien.ac.at

⁶These authors contributed equally to this work.

Received 2 March 2007; Revised 20 June 2007; Accepted 6 August 2007; Published online 19 September 2007.

Abstract

Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case–control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.