Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder

Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT).1 the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression.2,3 We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. the three 5-httlpr genotypes were also differentially distributed in patients and controls (P < 0.03). the sad patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean ± s.d. = 15.3 ± 2.8 vs 17.1 ± 3.4 respectively; P < 0.02). 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.