TY - JOUR
T1 - Moderation of antidepressant response by the serotonin transporter gene
AU - Huezo-Diaz, Patricia
AU - Uher, Rudolf
AU - Smith, Rebecca
AU - Rietschel, Marcella
AU - Henigsberg, Neven
AU - Marušič, Andrej
AU - Mors, Ole
AU - Maier, Wolfgang
AU - Hauser, Joanna
AU - Souery, Daniel
AU - Placentino, Anna
AU - Zobel, Astrid
AU - Larsen, Erik Roj
AU - Czerski, Piotr M.
AU - Gupta, Bhanu
AU - Hoda, Farzana
AU - Perroud, Nader
AU - Farmer, Anne
AU - Craig, Ian
AU - Aitchison, Katherine J.
AU - McGuffin, Peter
PY - 2009/7
Y1 - 2009/7
N2 - Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene. Aims: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). Method: The 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome. Conclusions: The effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5′ end of the serotonin transporter gene.
AB - Background: There have been conflicting reports on whether the length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) moderates the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs). We hypothesised that the pharmacogenetic effect of 5-HTTLPR is modulated by gender, age and other variants in the serotonin transporter gene. Aims: To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor). Method: The 5-HTTLPR and 13 additional markers across the serotonin transporter gene were genotyped in 795 adults with moderate-to-severe depression treated with escitalopram or nortriptyline in the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Results: The 5-HTTLPR moderated the response to escitalopram, with long-allele carriers improving more than short-allele homozygotes. A significant three-way interaction between 5-HTTLPR, drug and gender indicated that the effect was concentrated in males treated with escitalopram. The single-nucleotide polymorphism rs2020933 also influenced outcome. Conclusions: The effect of 5-HTTLPR on antidepressant response is SSRI specific conditional on gender and modulated by another polymorphism at the 5′ end of the serotonin transporter gene.
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U2 - 10.1192/bjp.bp.108.062521
DO - 10.1192/bjp.bp.108.062521
M3 - Article
C2 - 19567893
AN - SCOPUS:67650882530
SN - 0007-1250
VL - 195
SP - 30
EP - 38
JO - British Journal of Psychiatry
JF - British Journal of Psychiatry
IS - 1
ER -
