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.
Reist
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Department of Psychiatry, Long Beach Veterans Affairs Medical Center, Long Beach, California, USA. creist@uci.edu
Mazzanti
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Vu
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Tran
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Goldman
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D000328:Adult; D000374:Aggression; D000483:Alleles; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005277:Fenfluramine / Q000494:pharmacology*; D005787:Gene Frequency; D005838:Genotype; D006791:Hostility; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000097:blood / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D002352:Carrier Proteins; D004247:DNA; D005277:Fenfluramine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011388:Prolactin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human