Enhanced serotonin transporter function during depression in seasonal affective disorder.
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.
Willeit
Matthäus
M
Department of Biological Psychiatry, Medical University of Vienna, Vienna, Austria. matthaeus.willeit@meduniwien.ac.at
Sitte
Harald H
HH
Thierry
Nikolaus
N
Michalek
Klaus
K
Praschak-Rieder
Nicole
N
Zill
Peter
P
Winkler
Dietmar
D
Brannath
Werner
W
Fischer
Michael B
MB
Bondy
Brigitta
B
Kasper
Siegfried
S
Singer
Ernst A
EA
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D003863:Depression / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010789:Phototherapy / Q000379:methods; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D016574:Seasonal Affective Disorder / Q000150:complications* / Q000235:genetics; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014439:Tyramine / Q000494:pharmacology / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014439:Tyramine