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.
  
  
  OBJECTIVE
  To test the hypothesis that the 5-HTTLPR differently influences response to escitalopram (an SSRI) compared with nortriptyline (a noradrenaline reuptake inhibitor).
  
  
  METHODS
  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.
authors: Institute of Psychiatry, King's College London, UK.
authors: Patricia
authors: P
authors: Huezo-Diaz
authors: Rudolf
authors: R
authors: Uher
authors: Rebecca
authors: R
authors: Smith
authors: Marcella
authors: M
authors: Rietschel
authors: Neven
authors: N
authors: Henigsberg
authors: Andrej
authors: A
authors: Marusic
authors: Ole
authors: O
authors: Mors
authors: Wolfgang
authors: W
authors: Maier
authors: Joanna
authors: J
authors: Hauser
authors: Daniel
authors: D
authors: Souery
authors: Anna
authors: A
authors: Placentino
authors: Astrid
authors: A
authors: Zobel
authors: Erik Roj
authors: ER
authors: Larsen
authors: Piotr M
authors: PM
authors: Czerski
authors: Bhanu
authors: B
authors: Gupta
authors: Farzana
authors: F
authors: Hoda
authors: Nader
authors: N
authors: Perroud
authors: Anne
authors: A
authors: Farmer
authors: Ian
authors: I
authors: Craig
authors: Katherine J
authors: KJ
authors: Aitchison
authors: Peter
authors: P
authors: McGuffin
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D015283:Citalopram / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D009661:Nortriptyline; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors