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


CONCLUSIONS
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.
Whale
R
R
University Department of Psychiatry, Warneford Hospital, Oxford, UK.
Quested
D J
DJ
Laver
D
D
Harrison
P J
PJ
Cowen
P J
PJ
D000328:Adult; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics; D002997:Clomipramine / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects* / 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*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D002352:Carrier Proteins; D002997:Clomipramine; 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