Serotonin transporter promoter polymorphism is associated with attenuated prolactin response to fenfluramine

Disturbances in central serotonin (5-HT) function may have a role in impulsive aggression in patients with a wide range of psychiatric diagnoses. The underlying mechanism, however, remains unknown. There are several naturally occurring mutations in the 5-HT signaling pathway that may underlie differences in 5-HT function and responsivity to drugs that affect 5-HT functioning. In the present study, we examined the relationship between polymorphisms in the promoter region of the gene coding for the neuronal 5-HT transporter, fenfluramine-induced prolactin release, and aggressive impulsivity (as measured by Barratt Impulsivity Scale, Buss-Durkee Hostility Inventory, and Brown-Goodwin Aggression Scale scores), in a group of abstinent alcoholic patients and healthy volunteers. We report here that possession of the short variant of the 5-HT transporter promoter polymorphism was associated with a blunting of overall central 5-HT function, as measured by fenfluramine-induced prolactin release. We found no relationship between aggressive, hostile, or impulsive traits and fenfluramine-induced prolactin release or between these traits and polymorphisms in the 5-HT transporter promoter. Thus, we have shown that a 5-HT transporter promoter genotype, which has previously been associated with anxiety-based behaviors, alters an in vivo measure of central 5-HT function (fenfluramine-induced prolactin release), providing an important mechanism for linkage between a gene, physiological function, and behavior. Published 2001 Wiley-Liss, Inc.