title: The serotonin transporter promoter polymorphism (5-HTTLPR) affects the relation between antidepressant serum concentrations and effectiveness in major depression.
abstract: BACKGROUND
  Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5-HTTLPR and SSRI serum concentrations.
  
  
  METHODS
  49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly.
  
  
  RESULTS
  Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r² = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31).
  
  
  CONCLUSIONS
  In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany. dreimueller@psychiatrie.klinik.uni-mainz.de
authors.forename: N
authors.initials: N
authors.lastname: Dreimüller
authors.forename: A
authors.initials: A
authors.lastname: Tadić
authors.forename: A
authors.initials: A
authors.lastname: Dragicevic
authors.forename: K
authors.initials: K
authors.lastname: Boland
authors.forename: B
authors.initials: B
authors.lastname: Bondy
authors.forename: K
authors.initials: K
authors.lastname: Lieb
authors.forename: G
authors.initials: G
authors.lastname: Laux
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: M J
authors.initials: MJ
authors.lastname: Müller
authors.forename: M L
authors.initials: ML
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: J
authors.initials: J
authors.lastname: Röschke
authors.forename: P
authors.initials: P
authors.lastname: Zill
authors.forename: C
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human