Association between seasonal affective disorder and the 5-HT2A promoter polymorphism, -1438G/A

Genes involved in serotonin metabolism are good candidates for the pathogen esis of seasonal affective disorder (SAD). A functional variant in the sero tonin transporter promoter, 5-HTTLPR, has recently been shown to be associa ted with SAD and seasonality. The purpose of this study was to determine wh ether -1438G/A, a polymorphism in the 5-HT2A promoter, is associated with S AD and seasonality, and whether it has additive effects with 5-HTTLPR on se asonality, Sixty-seven individuals with SAD and 69 normal volunteers, all s creened with the SCID and diagnosed according to DSM-III-R criteria, were g enotyped for the -1438G/A 5-HT2A promoter polymorphism. All had been previo usly genotyped for 5-HTTLPR and had been assessed for seasonality by the Gl obal Seasonality Scale. There was a significant increase in the frequency o f the -1438A variant allele of the 5-HT2A promoter polymorphism in SAD pati ents (0.47) compared to matched controls (0.36) (P < 0.01), The difference in genotype distribution was also significant (P < 0.05). We found no assoc iation between the -1438G/A polymorphism and seasonality scores, and there was no additive effect with 5-HTTLPR on seasonality, In conclusion, we have shown that the -1438G/A 5-HT2A promoter variant is associated with SAD but not with seasonality. We suggest that the association may instead be with the depressive symptoms of SAD, However, these results should be treated wi th caution until replicated because of the possibility of false-positive fi ndings in case-control association studies.