title: Initial conditions of serotonin transporter kinetics and genotype: influence on SSRI treatment trial outcome.
abstract: BACKGROUND
  Fifty-one patients with major depression were classified for 5-HTT promoter region polymorphism and platelet 5-HTT kinetics before treatment with fluoxetine, and then examined for treatment outcome.
  
  
  METHODS
  Dose was stratified from 1.25 mg to 40 mg per day to allow for the possibility that one genotype could express a lower-dose fluoxetine response. A repeated-measures analysis of variance of 24-item Hamilton depression change through baseline, 1-week placebo lead-in, and 6, 12, and 18 weeks treatment was done to test a genotype effect on outcome.
  
  
  RESULTS
  Genotype had a significant effect on outcome (F = 4.7, p <.02), with the initial affinity constant (K(m)) (F = 11.9, p =.001), and dose (F = 6.0, p <.02) being significant covariates on outcome as well. The gene effect, however, was complex in that the 5-HTT promoter region insertion showed two effects: both a placebo response effect (F = 4, p <.025), and a drug dose response effect (r =.40, p <.01). The long allele group was more responsive to placebo, as well as more responsive to drug dose than was the short allele group.
  
  
  CONCLUSIONS
  This is the first study to examine the antidepressant dose-response relationship to 5-HTT kinetics and genetics. The findings indicate that both the initial affinity and genotype of 5-HTT may contribute in unique ways to the variation in the outcome of depression treatment trials.
authors: Department of Psychiatry, Veterans Administration Hospital, The Medical College of Georgia, Augusta, Georgia 30912-3800, USA.
authors: Jeffrey L
authors: JL
authors: Rausch
authors: Maria E
authors: ME
authors: Johnson
authors: You-Jun
authors: YJ
authors: Fei
authors: Jun Qing
authors: JQ
authors: Li
authors: Nitin
authors: N
authors: Shendarkar
authors: Henry Mac
authors: HM
authors: Hobby
authors: Vadivel
authors: V
authors: Ganapathy
authors: Fred H
authors: FH
authors: Leibach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D005473:Fluoxetine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human