title: Serotonin transporter genotype interacts with paroxetine plasma levels to influence depression treatment response in geriatric patients.
abstract: OBJECTIVE
  To investigate whether variable antidepressant response may be influenced by an interaction between the serotonin transporter promoter polymorphism (5-HTTLPR) and antidepressant concentration.
  
  
  METHODS
  Elderly subjects with depression treated with paroxetine (n = 110) were genotyped and assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect analysis of repeated measures was used.
  
  
  RESULTS
  There was an interaction between early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement over 12 weeks (F(18,59.5) = 1.8, p < 0.05), as well as main effects of both paroxetine concentration (F(68,55.3) = 2.4, p < 0.005) and genotype (F(2,74.2) = 5.7, p < 0.005). Paroxetine concentrations were correlated with change in HAMD scores after 2 weeks of treatment in subjects with the short (s) allele (r = 0.31, p < 0.05) but not in subjects homozygous for the long (l) allele.
  
  
  CONCLUSIONS
  The results demonstrate a concentration-response relation for paroxetine in late-life depression and support the hypothesis for both a direct main effect and a moderating influence of 5-HTTLPR alleles on this concentration-response relation.
authors.affiliation: NIMH Advanced Center in Interventions and Services Research for Late-Life Mood Disorders and the John A. Hartford Foundation Center of Excellence in Geriatric Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. lotrichfe@upmc.edu
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Margaret
authors.initials: M
authors.lastname: Kirshner
authors.forename: Robert F
authors.initials: RF
authors.lastname: Ferrell
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds Iii
mesh_terms: D000368:Aged; D000483:Alleles; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood* / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human