Moderation of antidepressant response by the serotonin transporter gene

Patricia Huezo-Diaz; Rudolf Uher; Rebecca Smith; Marcella Rietschel; Neven Henigsberg; Andrej Marusic; Ole Mors; Wolfgang Maier; Joanna Hauser; Daniel Souery; Anna Placentino; Astrid Zobel; Erik Roj Larsen; Piotr M. Czerski; Bhanu Gupta; Farzana Hoda; Nader Perroud; Anne Farmer; Ian Craig; Katherine J. Aitchison; Peter McGuffin

doi:10.1192/bjp.bp.108.062521

Moderation of antidepressant response by the serotonin transporter gene

Patricia Huezo-Diaz, Rudolf Uher, Rebecca Smith, Marcella Rietschel, Neven Henigsberg, Andrej Marusic, Ole Mors, Wolfgang Maier, Joanna Hauser, Daniel Souery, Anna Placentino, Astrid Zobel, Erik Roj Larsen, Piotr M. Czerski, Bhanu Gupta, Farzana Hoda, Nader Perroud, Anne Farmer, Ian Craig, Katherine J. AitchisonPeter McGuffin

Social Genetic & Developmental Psychiatry

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

Abstract

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 mode rate-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.

Original language	English
Pages (from-to)	30 - 38
Number of pages	9
Journal	British Journal of Psychiatry
Volume	195
Issue number	1
DOIs	https://doi.org/10.1192/bjp.bp.108.062521
Publication status	Published - Jul 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1192/bjp.bp.108.062521

Cite this

Huezo-Diaz, P., Uher, R., Smith, R., Rietschel, M., Henigsberg, N., Marusic, A., Mors, O., Maier, W., Hauser, J., Souery, D., Placentino, A., Zobel, A., Larsen, E. R., Czerski, P. M., Gupta, B., Hoda, F., Perroud, N., Farmer, A., Craig, I., ... McGuffin, P. (2009). Moderation of antidepressant response by the serotonin transporter gene. British Journal of Psychiatry, 195(1), 30 - 38. https://doi.org/10.1192/bjp.bp.108.062521

@article{5d3b817b65ed4c53906a8b7c336acdc7,

title = "Moderation of antidepressant response by the serotonin transporter gene",

abstract = "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 mode rate-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.",

author = "Patricia Huezo-Diaz and Rudolf Uher and Rebecca Smith and Marcella Rietschel and Neven Henigsberg and Andrej Marusic and Ole Mors and Wolfgang Maier and Joanna Hauser and Daniel Souery and Anna Placentino and Astrid Zobel and Larsen, {Erik Roj} and Czerski, {Piotr M.} and Bhanu Gupta and Farzana Hoda and Nader Perroud and Anne Farmer and Ian Craig and Aitchison, {Katherine J.} and Peter McGuffin",

year = "2009",

month = jul,

doi = "10.1192/bjp.bp.108.062521",

language = "English",

volume = "195",

pages = "30 -- 38",

journal = "British Journal of Psychiatry",

issn = "1472-1465",

publisher = "Cambridge University Press",

number = "1",

}

Huezo-Diaz, P, Uher, R, Smith, R, Rietschel, M, Henigsberg, N, Marusic, A, Mors, O, Maier, W, Hauser, J, Souery, D, Placentino, A, Zobel, A, Larsen, ER, Czerski, PM, Gupta, B, Hoda, F, Perroud, N, Farmer, A , Craig, I , Aitchison, KJ & McGuffin, P 2009, 'Moderation of antidepressant response by the serotonin transporter gene', British Journal of Psychiatry, vol. 195, no. 1, pp. 30 - 38. https://doi.org/10.1192/bjp.bp.108.062521

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 - Marusic, 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 mode rate-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 mode rate-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.

U2 - 10.1192/bjp.bp.108.062521

DO - 10.1192/bjp.bp.108.062521

M3 - Article

SN - 1472-1465

VL - 195

SP - 30

EP - 38

JO - British Journal of Psychiatry

JF - British Journal of Psychiatry

IS - 1

ER -

Moderation of antidepressant response by the serotonin transporter gene

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this