Enhanced serotonin transporter function during depression in seasonal affective disorder.

萧条(经济学) 5-羟色胺能 抗抑郁药 重性抑郁障碍 神经科学 舍曲林 西酞普兰 医学 焦虑 5-羟色胺受体
作者
Matthäus Willeit,Harald H. Sitte,N. Thierry,Klaus G. Michalek,Nicole Praschak-Rieder,Peter Zill,Dietmar Winkler,Werner Brannath,Michael B. Fischer,Brigitta Bondy,Siegfried Kasper,Ernst A. Singer
出处
期刊:Neuropsychopharmacology [Springer Nature]
卷期号:33 (7): 1503-1513 被引量:78
标识
DOI:10.1038/sj.npp.1301560
摘要

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 (rho=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.

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