Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

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 tyramineinduced, 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 ¼ 0.014) and outward (p ¼ 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 (r ¼ 0.421, p ¼ 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.

Abnormal Hypothalamic Response to Light in Seasonal Affective Disorder

“…This discrepancy cannot be attributed to the sample of patients, because SIGHSAD scores, depression, and seasonality levels were similar to those reported in previous studies on SAD (e.g., [19,46]), including those investigating retinal sensitivity (9,54). It should be noted, however, that it is the seasonal change in rod retinal sensitivity that has been most reported to be abnormal in SAD, whereas differences between patients and control subjects were not systematically detected in fall/winter (54 -56).…”

“…The locus coeruleus and dorsal raphe nucleus are implicated in reward regulation and depression (44) and constitute an important source of norepinephrine and serotonin, respectively. Interestingly, serotonin levels seem to be influenced by season and bright sunlight (45), and altered serotonin receptor functions have been described in SAD (2,3,46). Animal data also showed that complete light deprivation reduced noradrenergic projections from the locus coeruleus to the prefrontal cortex (47), which is essential for cognition (48).…”

Regulation of Serotonin Transport in Human Platelets by Tyrosine Kinase Syk

“…It should be noted that conflicting results have been reported on the efflux pathways of serotonin from the platelet cytosol into the extracellular compartment, mainly based on the different inhibitory effect shown by imipramine and fluoxetine on this process [18,21,23]. Interestingly, it has been recently reported that not only the inward but also the outward transport of serotonin is enhanced in depressed patients suffering seasonal affective disorders [58].…”

Do mood disorders play a role in pig welfare?

“…SAD is a form of depression most often associated with seasonal reductions in daylight, with remission linked to a subsequent seasonal increase in daylight. It has, indeed, been shown that winter-SAD may respond to brightlight therapy (Lewy et al, 1989;Willeit et al, 2008). These authors have recently demonstrated that changes in mood are associated with alterations in the efficiency of the serotonin (5-hydroxytryptamine) transporter in the patients' blood platelets.…”