Seasonality and winter-type seasonal depression are associated with the rs731779 polymorphism of the serotonin-2A receptor gene

Seasonal Affective Disorder (SAD), seasonality and increased sensitivity to the fluctuation of seasons in biological and psychological parameters can manifest to varying degrees across a normal population. The serotonin-2A (5-HT2A) receptor gene has long been suggested as a candidate for the genetic basis of this phenomenon. We hypothesized that functional sequence variation in this gene could contribute to seasonality and the development of winter- and/or summer-type seasonal depression. Seasonality was measured by the self-rating Global Seasonality Score (GSS) of the Seasonal Pattern Assessment Questionnaire, and SAD by the Seasonal Health Questionnaire (SHQ). We analysed associations between GSS or SAD scores and 5-HTR2A receptor gene polymorphisms rs731779, rs985934 and rs6311, in 609 individuals. People carrying the GG genotype of rs731779 were six times more likely to manifest winter or summer SAD compared to GT or TT genotypes (OR = 6.47), and the chance of having winter-type SAD was almost nine-fold (OR = 8.7) with the GG genotype. GG subjects of rs731779 also scored significantly higher on the GSS scale compared to carriers of the T allele. In the haplotype analysis subjects carrying the G allele of rs731779 scored higher on the GSS scale, while the presence of the T allele leads to lower scores. These results suggest that variations in the 5-HTR2A gene play a significant role in the development of seasonality and especially in winter-type SAD. The fact that the above polymorphism showed association not only with clinical SAD but also seasonality symptoms in a general population provides evidence for the spectrum nature of this connection.