The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior.
The purpose of this study was to determine whether -1438G/A, a polymorphism in the 5-HT2A promoter, is associated with SAD and seasonality, and whether it has additive effects with 5-HTTLPR on seasonality.
The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.
Molecular genetic research: two genetic variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT2A-1438G/A gene promoter polymorphisms, are associated with SAD; the former but not the latter polymorphism is related to seasonality.
Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample.
An association between the presence of PMDD and family history (P=0.0029) and 5-HTTLPR long/short allele-heterozygosity (P=0.033) was found in females with SAD.
These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.
The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality.
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.
SLC6A4 provided strong and consistent evidence of association with the PD and PD+SAD groups, with the most significant association in both groups being at rs140701 (chi(2)=10.72, P=0.001 with PD and chi(2)=8.59, P=0.003 in the PD+SAD group).
Female S' carriers with SAD, in turn, displayed robustly increased 5-HTT levels in the ventral striatum (bilaterally), right orbitofrontal cortex, middle frontal gyrus (bilaterally), extending to the left supramarginal gyrus, left precentral gyrus and left postcentral gyrus during winter compared to female S' carriers without SAD.
We conclude that resilience to SAD is associated with a global downregulation of SERT levels in winter which serves to keep 5-HT levels across seasons.