Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants.

A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats. In this study, we investigated the antidepressant response to fluvoxamine in individuals carrying different *l and *s variants according to the Nakamura findings. Two hundred and twenty-eight patients affected by bipolar disorder and major depression were administered a daily dose of fluvoxamine up to 300 mg and evaluated at baseline and weekly thereafter until week 7, using the 21-item Hamilton Rating Scale for Depression. We found a marginally significant difference in genotype and allele (P=0.04, data not shown) distribution (*l and *s traditional variants) according to diagnosis (bipolar disorder vs. major depression). We confirmed a better and faster response in our depressed patients bearing the *l variant, but we also found significant differences in response among *l carriers according to the type of *l allele. In fact, 16F *l carriers showed only a partial response, while 16D *l carriers showed a marginally significantly better response than 16A *l allele carriers. These results, although very preliminary, can represent a further step toward a better understanding of the molecular genetics of antidepressant response.