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Psychopharmacology

, Volume 174, Issue 4, pp 525–529 | Cite as

The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder

  • L. Kathryn Durham
  • Suzin M. Webb
  • Patrice M. Milos
  • Cathryn M. Clary
  • Albert B. SeymourEmail author
Original Investigation

Abstract

Rationale

A common polymorphism (5HTTLPR) within the promoter region of the serotonin transporter gene (LSC6A4) has been shown to influence response time as well as overall response to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder. We hypothesized that a similar effect in response time to sertraline would be observed and that no effect on response time would be seen in a placebo arm.

Objectives

We tested the hypothesis that subjects homozygous for the long allele at the 5HTTLPR polymorphism would respond more rapidly to sertraline than subjects carrying one or two copies of the short allele.

Methods

HAM-D and CGI-I responses to sertraline and placebo were measured weekly in the context of an 8-week, placebo-controlled study in elderly depressed subjects. Genotyping of the 5HTTLPR polymorphism was performed to test for correlations with response at each week in the sertraline and placebo groups (n=206).

Results

Subjects homozygous for the long allele of 5HTTLPR showed a significant increase in response at week 1 and week 2, as assessed by the CGI-I scale compared with subjects carrying one or two copies of the short allele (P=0.01 at both weeks). No significant difference was observed in the placebo group.

Conclusions

These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs.

Keywords

5HTTLPR Genotype Sertraline Placebo Major depressive disorder 

Notes

Acknowledgements

The authors would like to extend their thanks to the individuals who donated DNA samples to this study. In addition, we would like to thank Paul Feeney, Jack Ostroff, and Michael Swietek for orchestrating the collection and anonymization of the samples, and Penny Cohen-Dellolio for her efforts in coordinating and monitoring the clinical sites.

References

  1. Arias B, Catalan R, Gasto C, Imaz ML, Gutierrez B, Pintor L Fananas L (2001) Genetic variability in the promoter region of the serotonin transporter gene is associated with clinical remission of major depression after long term treatment with cetalopram. World federation of societies of biological psychiatry, vol 2. The World Journal of Biological Psychiatry, Berlin, p 9SGoogle Scholar
  2. Collier DA, Stober G, Li T, Heils A, Catalano M, Debella D, Arranz MJ, Murray RM, Vallada HP, Bengel D, Muller CR, Roberts GW, Smeraldi E, Kirov G, Sham P, Lesch KP (1996) A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1:453–460PubMedGoogle Scholar
  3. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedGoogle Scholar
  4. Guy W (1976) ECDEU assessment manual for psychopharmacology, revised edn. US Department of Health, Education, and Welfare, WashingtonGoogle Scholar
  5. Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296PubMedGoogle Scholar
  6. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624PubMedGoogle Scholar
  7. Kim DK, Lim SW, Lee S, Sohn SE, Kim S, Hahn CG, Carroll BJ (2000) Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 11:215–219PubMedGoogle Scholar
  8. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenbert BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531PubMedGoogle Scholar
  9. Nakamura M, Ueno S, Sano A, Tanabe H (2000) The human serotonin transporter gene-linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 5:32–38CrossRefPubMedGoogle Scholar
  10. Pollock BG, Ferrell, RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF III, Kupfer DJ (2000) Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 23:587–590CrossRefPubMedGoogle Scholar
  11. Ramamoorthy S, Bauman AL, Moore KR, Han K, Yang-Geng T, Chang AS, Ganapathy V, Blakely RD (1993) Antidepressant and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci USA 90:2542–2546PubMedGoogle Scholar
  12. Rausch JL, Johnson ME, Fei Y, Li JQ, Shendarkar N, Hobby HM, Ganapathy V, Leibach RH (2002) Initial conditions of serotonin transporter kinetics and genotype: influence of SSRI treatment trial outcome. Biol Psychiatry 51:723–732Google Scholar
  13. Schneider LS, Nelson JC, Clary CM, Newhouse P, Krishnan KRR, Shiovita T, Weihs K (2003) An eight-week, multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry 160:1277–1285CrossRefPubMedGoogle Scholar
  14. Smeraldi E, Zanardi R, Benedetti F, Dibella D, Perez J, Catalano M (1998) Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 3:508–511PubMedGoogle Scholar
  15. Whyte EM, Pollock BG, Wagner WR, Mulsant BH, Ferrell RD, Mazumdar S, Reynolds CF III (2001) Influence of serotonin-transporter-linked promoter region polymorphism on platelet activation in geriatric depression. Am J Psychiatry 158:2074–2076CrossRefPubMedGoogle Scholar
  16. Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H, Shimizu T, Itoh K, Inoue K, Tezuka T, Suzuki T, Ohkubo T, Sugawara K, Otani K (2002) Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 26:383–386Google Scholar
  17. Zanardi R, Benedetti F, Dibella D, Catalano M, Smeraldi E (2000) Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. Clin Psychopharmacol 20:105–107CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • L. Kathryn Durham
    • 1
  • Suzin M. Webb
    • 2
  • Patrice M. Milos
    • 2
  • Cathryn M. Clary
    • 3
  • Albert B. Seymour
    • 2
    Email author
  1. 1.Biostatistical ApplicationsPfizer Global Research and DevelopmentGrotonUSA
  2. 2.Discovery PharmacogenomicsPfizer Global Research and Development, MS-8118D-3006GrotonUSA
  3. 3.Pfizer Global PharmaceuticalsNew YorkUSA

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