Association study of the serotonin transporter promoter polymorphism and mirtazapine antidepressant response in major depressive disorder

Abstract

Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants, and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR). Mirtazapine has a dual-action profile, combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes. The goal of this study was to elucidate whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder (MDD). One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment. The severity of depression was assessed with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction. Our results showed that responses at the 2nd and 4th weeks were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers. These results support our hypothesis that the response to noradrenergic and specific serotonergic antidepressants is significantly associated with the 5-HTTLPR polymorphism.