Initial conditions of serotonin transporter kinetics and genotype: Influence on SSRI treatment trial outcome

Jeffrey L. Rausch, Maria E. Johnson, You Jun Fei, Jun Qing Li, Nitin Sudhakar Shendarkar, Henry McCager Hobby, Vadivel Ganapathy, Fred H. Leibach

Research output: Contribution to journalArticle

194 Citations (Scopus)

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 (Km) (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.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalBiological Psychiatry
Volume51
Issue number9
DOIs
StatePublished - May 1 2002

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Genotype
Fluoxetine
Genetic Promoter Regions
Alleles
Placebos
Placebo Effect
Pharmaceutical Preparations
Antidepressive Agents
Analysis of Variance
Blood Platelets
Therapeutics
Genes

Keywords

  • 5-HT transport kinetics
  • 5-HTT
  • Antidepressants
  • Depression
  • Dose
  • Fluoxetine
  • Genetics
  • SERT
  • SSRI
  • Serotonin
  • Serotonin transporter
  • Treatment response

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Initial conditions of serotonin transporter kinetics and genotype : Influence on SSRI treatment trial outcome. / Rausch, Jeffrey L.; Johnson, Maria E.; Fei, You Jun; Li, Jun Qing; Shendarkar, Nitin Sudhakar; Hobby, Henry McCager; Ganapathy, Vadivel; Leibach, Fred H.

In: Biological Psychiatry, Vol. 51, No. 9, 01.05.2002, p. 723-732.

Research output: Contribution to journalArticle

Rausch, JL, Johnson, ME, Fei, YJ, Li, JQ, Shendarkar, NS, Hobby, HM, Ganapathy, V & Leibach, FH 2002, 'Initial conditions of serotonin transporter kinetics and genotype: Influence on SSRI treatment trial outcome', Biological Psychiatry, vol. 51, no. 9, pp. 723-732. https://doi.org/10.1016/S0006-3223(01)01283-5
Rausch, Jeffrey L. ; Johnson, Maria E. ; Fei, You Jun ; Li, Jun Qing ; Shendarkar, Nitin Sudhakar ; Hobby, Henry McCager ; Ganapathy, Vadivel ; Leibach, Fred H. / Initial conditions of serotonin transporter kinetics and genotype : Influence on SSRI treatment trial outcome. In: Biological Psychiatry. 2002 ; Vol. 51, No. 9. pp. 723-732.
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AU - Shendarkar, Nitin Sudhakar

AU - Hobby, Henry McCager

AU - Ganapathy, Vadivel

AU - Leibach, Fred H.

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N2 - 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 (Km) (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.

AB - 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 (Km) (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.

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KW - Treatment response

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