Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine

Rationale: A 44-base-pair insertion/deletion polymorphism in the promoter r egion of the human serotonin (5-HT) transporter (5-HTT) gene gives rise to a biallelic polymorphism designated long (I) and short (s). The s variant i s associated with a lower expression of 5-HTT sites and a reduced efficienc y of 5-HT reuptake. Objective: The aim of the present study was to determin e whether the increase in brain 5-HT function produced by acute 5-HT reupta ke blockade is influenced by the 5-HTT promoter l/s polymorphism. Methods: We measured the increase in plasma prolactin that follows acute administrat ion of the tricyclic antidepressant clomipramine as an index of 5-HT neurot ransmission in 14 healthy female subjects (7 with ss genotype and 7 with II genotype) using a placebo-controlled crossover design. Results: Clomiprami ne-induced prolactin release was significantly greater in subjects with the II genotype. Conclusion: Our findings suggest that acute 5-HT reuptake blo ckade produces a greater increase in 5-HT neurotransmission in subjects wit h the II genotype than in those with an ss genotype. These results are cons istent with clinical data indicating that subjects with an ss genotype may have a poorer therapeutic response to selective serotonin reuptake inhibito r (SSRI) monotherapy.