Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Feature Review
  • Published:

Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review

Abstract

Large differences in clinical response to selective serotonin reuptake inhibitors (SSRIs) are observed in depressive patients with different genotypes. Quantification of these differences is needed to decide if genetic testing prior to antidepressant treatment is useful. We conducted a systematic review of the literature on the influence of polymorphisms in the serotonin transporter gene (SERTPR (or 5-HTTLPR) and STin2) on SSRI response. Studies were identified by the use of MEDLINE, EmBase and PsycINFO, references of articles, reviews and information from pharmaceutical companies. Nine studies assessing the influence of SERTPR or STin2 on treatment response were included. Outcome was expressed as the percentage of decrease in depression score (HAM-D or MADRS) or as the percentage of responders (≥50% reduction on the depression scale). Both study methodologies and study outcomes showed large heterogeneity. Weighted mean decreases in depression score for patients with the s/s, s/l and l/l genotypes were 35.4, 46.3 and 48.0% at week 4, respectively, and 53.9, 54.6 and 48.3% at week 6. Among Caucasian patients, both mean decrease in depression score and response rate were lowest in the s/s group, while among Asian patients, results were inconsistent. Weighted response rates were 36.1% for the 10/12 genotype of the STin2 polymorphism and 80.7% for the 12/12 genotype (χ2=27.8, P<0.001) (only Asians). The available evidence points to a less favourable response to SSRI treatment among Caucasian patients with the SERTPR s/s genotype and among (Asian) patients with the STin2 10/12 genotype. In view of the scarcity and heterogeneity of the studies, however, current information is insufficiently reliable as a basis for implementing genetic testing in the diagnostic work-up of the depressive patient.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lotrich FE, Pollock BG, Ferrell RE . Polymorphism of the serotonin transporter: implications for the use of selective serotonin reuptake inhibitors. Am J Pharmacogenom 2001; 1 (3): 153–164.

    Article  CAS  Google Scholar 

  2. Middlemiss DN, Price GW, Watson JM . Serotonergic targets in depression. Curr Opin Pharmacol 2002; 2 (1): 18–22.

    Article  CAS  Google Scholar 

  3. Lesch KP . Serotonergic gene expression and depression: implications for developing novel antidepressants. J Affect Disord 2001; 62 (1–2): 57–76.

    Article  CAS  Google Scholar 

  4. Lesch KP . Variation of serotonergic gene expression: neurodevelopment and the complexity of response to psychopharmacologic drugs. Eur Neuropsychopharmacol 2001; 11 (6): 457–474.

    Article  CAS  Google Scholar 

  5. Veenstra-VanderWeele J, Anderson G, Cook E . Pharmacogenetics and the serotonin system: initial studies and future directions. Eur Jo Pharmacol 2000; 410: 165–181.

    Article  CAS  Google Scholar 

  6. Steimer W, Muller B, Leucht S, Kissling W . Pharmacogenetics: a new diagnostic tool in the management of antidepressive drug therapy. Clin Chim Acta 2001; 308: 33–41.

    Article  CAS  Google Scholar 

  7. Mundo E, Walker M, Cate T, Macciardi F, Kennedy JL . The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings. Arch Gen Psychiatry 2001; 58 (6): 539–544.

    Article  CAS  Google Scholar 

  8. Serretti A, Zanardi R, Rossini D, Cusin C, Lilli R, Smeraldi E . Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity. Mol Psychiatry 2001; 6 (5): 586–592.

    Article  CAS  Google Scholar 

  9. Zanardi R, Seretti A, Rossini D, Franchini L, Cusin C, Lattuada E et al. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 2001; 50: 323–330.

    Article  CAS  Google Scholar 

  10. Minov C, Baghai TC, Schule C, Zwanzger P, Schwarz MJ, Zill P et al. Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression. Neurosci Lett 2001; 303 (2): 119–122.

    Article  CAS  Google Scholar 

  11. Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E . Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. J Clin Psychopharmacol 2000; 20 (1): 105–107.

    Article  CAS  Google Scholar 

  12. Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ et al. Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 2002; 7 (10): 1115–1119.

    Article  CAS  Google Scholar 

  13. Rausch JL, Johnson ME, Fei YJ, Li JQ, Shendarkar N, Mac Hobby H et al. Initial conditions of serotonin transporter kinetics and genotype: influence on ssri treatment trial outcome. Biol Psychiatry 2002; 51 (9): 723–732.

    Article  CAS  Google Scholar 

  14. Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H et al. Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26 (2): 383–386.

    Article  CAS  Google Scholar 

  15. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23 (5): 587–590.

    Article  CAS  Google Scholar 

  16. Smeraldi E, Zanardi R, Benedetti F, Di Bella D, Perez J, Catalano M . Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 1998; 3 (6): 508–511.

    Article  CAS  Google Scholar 

  17. Kim DK, Lim SW, Lee S, Sohn SE, Kim S, Hahn CG et al. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 2000; 11 (1): 215–219.

    Article  CAS  Google Scholar 

  18. Ito K, Yoshida K, Sato K, Takahashi H, Kamata M, Higuchi H et al. A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine. Psychiatry Res 2002; 111 (2–3): 235.

    Article  CAS  Google Scholar 

  19. Hooijer C, Zitman FG, Griez E, van Tilburg W, Willemse A, Dinkgreve MA . The Hamilton Depression Rating Scale (HDRS); changes in scores as a function of training and version used. J Affect Disord 1991; 22 (1–2): 21–29.

    Article  CAS  Google Scholar 

  20. Stimpson N, Agrawal N, Lewis G . Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression. Systematic review. Br J Psychiatry 2002; 181: 284–294.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K M Smits.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smits, K., Smits, L., Schouten, J. et al. Influence of SERTPR and STin2 in the serotonin transporter gene on the effect of selective serotonin reuptake inhibitors in depression: a systematic review. Mol Psychiatry 9, 433–441 (2004). https://doi.org/10.1038/sj.mp.4001488

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001488

Keywords

This article is cited by

Search

Quick links