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RATIONALE: A 44-base-pair insertion/deletion polymorphism in the promoter region of the human serotonin (5-HT) transporter (5-HTT) gene gives rise to a bi-allelic polymorphism designated long (l) and short (s). The s variant is associated with a lower expression of 5-HTT sites and a reduced efficiency of 5-HT reuptake. OBJECTIVE: The aim of the present study was to determine whether the increase in brain 5-HT function produced by acute 5-HT reuptake blockade is influenced by the 5-HTT promoter l/s polymorphism. METHODS: We measured the increase in plasma prolactin that follows acute administration of the tricyclic antidepressant clomipramine as an index of 5-HT neurotransmission in 14 healthy female subjects (7 with ss genotype and 7 with ll genotype) using a placebo-controlled crossover design. RESULTS: Clomipramine-induced prolactin release was significantly greater in subjects with the ll genotype. CONCLUSION: Our findings suggest that acute 5-HT reuptake blockade produces a greater increase in 5-HT neurotransmission in subjects with the ll genotype than in those with an ss genotype. These results are consistent with clinical data indicating that subjects with an ss genotype may have a poorer therapeutic response to selective serotonin reuptake inhibitor (SSRI) monotherapy.

Type

Journal article

Journal

Psychopharmacology (Berl)

Publication Date

05/2000

Volume

150

Pages

120 - 122

Keywords

Adult, Analysis of Variance, Carrier Proteins, Clomipramine, Female, Genotype, Humans, Male, Membrane Glycoproteins, Membrane Transport Proteins, Middle Aged, Nerve Tissue Proteins, Polymorphism, Genetic, Prolactin, Promoter Regions, Genetic, Serotonin Plasma Membrane Transport Proteins, Serotonin Uptake Inhibitors