Skip to main content
SpringerLink
Log in

Serotonin Transporter Gene: A New Polymorphism May Affect Response to Antidepressant Treatments in Major Depressive Disorder

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and Objectives

Several gene variants have been related to major depressive disorder (MDD) treatment outcomes; however, few studies have investigated a possible different effect on pharmacotherapy and brief psychotherapy response.

Methods

A total of 137 MDD patients were randomized to either interpersonal counseling (IPC; n = 40) or antidepressant pharmacological treatment (n = 97). Outcomes were remission, response, and symptom improvement at week 8. Five genetic variants were investigated (5HTR2A rs6314, BDNF rs6265, SLC6A4 rs8076005, CREB1 rs2253206, and TPH2 rs11179023) as possible modulators of outcomes.

Results

The LC6A4 rs8076005 AA genotype and A allele were associated with response rate in the antidepressant group (p = 0.015 and 0.005, respectively) and in the whole sample (p = 0.03 and 0.02, respectively). In the IPC group a non-significant trend in the same direction was observed. The TPH2 rs11179023 A allele showed a marginal association with symptom improvement in the IPC group only. Other gene variants did not impact on outcomes in any treatment group.

Conclusion

Our study suggests that rs8076005 in the SLC6A4 gene may be a modulator of antidepressant response, especially when pharmacological treatment is used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, et al. Disability and quality of life impact of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl. 2004;420:38–46.

    PubMed  Google Scholar 

  2. World Health Organization. The global burden of disease: 2004 update. Genova: World Health Organization; 2008.

    Google Scholar 

  3. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Wardren D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28–40.

    Article  PubMed  Google Scholar 

  4. Cuijpers P, Sibrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF 3rd. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry. 2013;12:137–48.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Unutzer J, Park M. Strategies to improve the management of depression in primary care. Prim Care. 2012;39:415–31.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Crisafulli C, Fabbri C, Porcelli S, Drago A, Spina E, De Ronchi D, Serretti A. Pharmacogenetics of antidepressants. Front Pharmacol. 2011;2:6. doi:10.3389/fphar.2011.00006.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Porcelli S, Drago A, Fabbri C, Gibiino S, Catali R, Serretti A. Pharmacogenetics of antidepressant response. J Psychiatry Neurosci. 2011;36:87–113.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Porcelli S, Fabbri C, Spina E, Serretti A, De Ronchi D. Genetic polymorphisms of cytochrome P450 enzymes and antidepressant metabolism. Expert Opin Drug Metab Toxicol. 2011;7:1101–15.

    Article  PubMed  CAS  Google Scholar 

  9. Narasimhan S, Lohoff FW. Pharmacogenetics of antidepressant drugs: current clinical practice and future directions. Pharmacogenomics. 2012;13:441–64.

    Article  PubMed  CAS  Google Scholar 

  10. Burnet PW, Eastwood SL, Lacey K, Harrison PJ. The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain. Brain Res. 1995;676:157–68.

    Article  PubMed  CAS  Google Scholar 

  11. Kusumi I, Koyama T, Yamashita I. Serotonin-induced platelet intracellular calcium mobilization in depressed patients. Psychopharmacology. 1994;113:322–7.

    Article  PubMed  CAS  Google Scholar 

  12. Tomiyoshi R, Kamei K, Muraoka S, Muneoka K, Takigawa M. Serotonin-induced platelet intracellular Ca2+ responses in untreated depressed patients and imipramine responders in remission. Biol Psychiatry. 1999;45:1042–8.

    Article  PubMed  CAS  Google Scholar 

  13. Ozaki N, Manji H, Lubierman V, Lu SJ, Lappalainen J, Rosenthal NE, Goldman D. A naturally occurring amino acid substitution of the human serotonin 5-HT2A receptor influences amplitude and timing of intracellular calcium mobilization. J Neurochem. 1997;68:2186–93.

    Article  PubMed  CAS  Google Scholar 

  14. Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP. Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry. 2004;9:879–89.

    Article  PubMed  CAS  Google Scholar 

  15. Wilkie MJ, Smith G, Day RK, Matthews K, Smith D, Blackwood D, Reid IC, Wolf CR. Polymorphisms in the SLC6A4 and HTR2A genes influence treatment outcome following antidepressant therapy. Pharmacogenomics J. 2009;9:61–70.

    Article  PubMed  CAS  Google Scholar 

  16. Porcelli S, Fabbri C, Serretti A. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol. 2012;22:239–58.

    Article  PubMed  CAS  Google Scholar 

  17. Su S, Zhao J, Bremner JD, Miller AH, Tang W, Bouzyk M, Snieder H, Novik O, Afzal N, Goldberg J, Vaccarino V. Serotonin transporter gene, depressive symptoms and interleukin-6. Circ Cardiovasc Genet. 2009;2:614–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Zill P, Banghai TC, Zwanzger P, Schule C, Eser D, Rupprecht R, Moller HJ, Bondy B, Ackenheil M. SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol Psychiatry. 2004;9:1030–6.

    Article  PubMed  CAS  Google Scholar 

  19. Garriock HA, Allen JJ, Delgado P, Nahaz Z, Kling MA, Carpenter L, Burke M, Burke W, Schwartz T, Marangell LB, Husain M, Erickson RP, Moreno FA. Lack of association of TPH2 exon XI polymorphisms with major depression and treatment resistance. Mol Psychiatry. 2005;10:976–7.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB, Schwartz DA, Krishnan KR, Caron MG. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron. 2005;45:11–6.

    Article  PubMed  CAS  Google Scholar 

  21. Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J, Enoch MA, Virkkunen M, Goldman D. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch Gen Psychiatry. 2005;62:1109–18.

    Article  PubMed  CAS  Google Scholar 

  22. Bicalho MA, Pimenta GJ, Neves FS, Correa H, de Moraes EN, Da Marco L, Romano-Silva MA. Genotyping of the G1463A (Arg441His) TPH2 polymorphism in a geriatric population of patients with major depression. Mol Psychiatry. 2006;11:799–800.

    Article  PubMed  CAS  Google Scholar 

  23. Delorme R, Durand CM, Betancur C, Wagner M, Ruhrmann S, Grabe HJ, Nygren G, Gillberg C, Leboyer M, Bourgeron T, Courtet P, Jollant F, Buresi C, Aubry JM, Baud P, Bondolfi G, Bertschy G, Perroud N, Malafosse A. No human tryptophan hydroxylase-2 gene R441H mutation in a large cohort of psychiatric patients and control subjects. Biol Psychiatry. 2006;60:202–3.

    Article  PubMed  CAS  Google Scholar 

  24. Van Den Bogaert A, Sleegers K, De Zutter S, Heyrman L, Norrback KF, Adolfsson R, Van Broeckhoven C, Del-Favero J. Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population. Arch Gen Psychiatry. 2006;63:1103–10.

    Article  Google Scholar 

  25. Gizatullin R, Zaboli G, Jonsson EG, Asperg M, Leopardi R. The tryptophan hydroxylase (TPH) 2 gene unlike TPH-1 exhibits no association with stress-induced depression. J Affect Disord. 2008;107:175–9.

    Article  PubMed  CAS  Google Scholar 

  26. Haghighi F, Bach-Mizrachi H, Huang YY, Arango V, Shi S, Dwork AJ, Rosoklija G, Sheng HT, Morozova I, Ju J, Russo JJ, Mann JJ. Genetic architecture of the human tryptophan hydroxylase 2 gene: existence of neural isoforms and relevance for major depression. Mol Psychiatry. 2008;13:813–20.

    Article  PubMed  CAS  Google Scholar 

  27. Mann JJ, Currier D, Murphy L, Huang YY, Galfalvy H, Brent D, Greenhill L, Oquendo M. No association between a TPH2 promoter polymorphism and mood disorders or monoamine turnover. J Affect Disord. 2008;106:117–21.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Illi A, Setala-Soikkeli E, Vikki M, Poutanen O, Huhtala H, Mononen N, Lehtimaki T, Leinonen E, Kampan O. 5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression. Neuroreport. 2009;20:1125–8.

    PubMed  CAS  Google Scholar 

  29. Tsai SJ, Hong CJ, Liou YJ, Yu YW, Chen TJ, Hou SJ, Yen FC. Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response. Prog Neuropsychopharmocol Biol Psychiatry. 2009;33:637–41.

    Article  CAS  Google Scholar 

  30. Claes S, Myint AM, Domschke K, Del-Favero J, Entrich K, Engelborghs S, De Deyn P, Mueller N, Baune B, Rothermundt M. The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes. Psychiatry Res. 2011;188:355–60.

    Article  PubMed  CAS  Google Scholar 

  31. Serretti A, Chiesa A, Porcelli S, Han C, Patkar AA, Lee SJ, Park MH, Pae CU. Influence of TPH2 variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia. Psychiatry Res. 2011;189:26–32.

    Article  PubMed  CAS  Google Scholar 

  32. Shen X, Wu Y, Qian M, Wang X, Hou Z, Liu Y, Sun J, Zhong H, Yang J, Lin M, Li L, Liang L, Guan T, Shen Z, Yuan Y. Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population. J Affect Disord. 2011;133:619–24.

    Article  PubMed  CAS  Google Scholar 

  33. Gao J, Pan Z, Jiao Z, Li F, Zhao G, Wei Q, Pan F, Evangelou E. TPH2 gene polymorphisms and major depression: a meta-analysis. Plos One. 2012;7:e36721. doi:10.1371/journal.pone.0036721.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Quesseveur G, David DJ, Gaillard MC, Pla P, Wu MV, Nguyen HT, Nicolas V, Auregan G, David I, Dranovsky A, Hantraye P, Hen R, Gardier AM, Deglon N, Guiard BP. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Transl Psychiatry. 2013;3:e253. doi:10.1038/tp.2013.30.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29:261–5.

    Article  PubMed  CAS  Google Scholar 

  36. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112:257–69.

    Article  PubMed  CAS  Google Scholar 

  37. Ozan E, Okur H, Eker C, Eker OD, Gonul AS, Akarsu N. The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels. Brain Res Bull. 2010;81:61–5.

    Article  PubMed  CAS  Google Scholar 

  38. Zou YF, Ye DQ, Feng XL, Su H, Pan FM, Liao FF. Meta-analysis of BDNF val66met polymorphism association with treatment response in patients with major depressive disorder. Eur Neuropsychopharmacol. 2010;20:535–44.

    Article  PubMed  CAS  Google Scholar 

  39. Kato M, Serretti A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry. 2010;15:473–500.

    Article  PubMed  CAS  Google Scholar 

  40. Niitsu T, Fabbri C, Bentini F, Serretti A. Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2013;45:183–94.

    Article  PubMed  CAS  Google Scholar 

  41. Mayr B, Montminy M. Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol. 2001;2:599–609.

    Article  PubMed  CAS  Google Scholar 

  42. Lonze BE, Ginty DD. Function and regulation of CREB family transcription factors in the nervous system. Neuron. 2002;35:605–23.

    Article  PubMed  CAS  Google Scholar 

  43. Zubenko GS, Hughes HB, Stiffler JS, Zubenko WN, Kaplan BB. Genome survey for susceptibility loci for recurrent, early-onset, major depression: results at 10 cM resolution. Am J Med Genet. 2002;114:413–22.

    Article  PubMed  Google Scholar 

  44. Zubenko GS, Hughes HB III, Stiffler JS, Zubenko WN, Kaplan BB. D2S2944 identifies a likely susceptibility locus for recurrent, early-onset, major depression in women. Mol Psychiatry. 2002;7:460–7.

    Article  PubMed  CAS  Google Scholar 

  45. Rankinen T, Argyropoulos G, Rice T, Rao DC, Bouchard C. CREB1 is a strong genetic predictor of the variation in exercise heart rate response to regular exercise: the HERITAGE Family Study. Circ Cardiovasc Genet. 2010;3:294–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Juhasz G, Dunham JS, Mckie S, Thomas E, Downey D, Chase D, Lloyd-Williams K, Toth ZG, Platt H, Mekli K, Payton A, Elliott R, Williams SR, Anderson IM, Deakin JF. The CREB1-BDNF-NTRK2 pathway in depression: multiple gene–cognition–environment interactions. Biol Psychiatry. 2011;69:762–71.

    Article  PubMed  CAS  Google Scholar 

  47. Serretti A, Chiesa A, Calati R, Massat I, Linotte S, Kasper S, Lecrubier Y, Antonijevic I, Forray C, Snyder L, Bollen J, Zohar J, De Ronchi D, Souery D, Mendlewicz J. A preliminary investigation of the influence of CREB1 gene on treatment resistance in major depression. J Affect Disord. 2011;128:56–63.

    Article  PubMed  CAS  Google Scholar 

  48. Serretti A, Fabbri C, Pellegrini S, Porcelli S, Politi P, Bellino S, Menchetti M, Mariotti V, Demi C, Martinelli V, Cappucciati M, Bozzatello P, Brignolo E, Brambilla P, Pae CU, Balestrieri M, De Ronchi D. No effect of serotoninergic gene variants on response to interpersonal counseling and antidepressants in major depression. Psychiatry Investig. 2013;10:180–9.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Judd FK, Piterman L, Cockram AM, McCall L, Weissman MM. A comparative study of venlafaxine with a focused education and psychotherapy program versus venlafaxine alone in the treatment of depression in general practice. Hum Psychopharmacol. 2001;16:423–8.

    Article  PubMed  CAS  Google Scholar 

  50. Oranta O, Luutonen S, Salokangas RK, Vahlberg T, Leino-Kilpi H. The outcomes of interpersonal counselling on depressive symptoms and distress after myocardial infarction. Nord J Psychiatry. 2010;64:78–86.

    Article  PubMed  Google Scholar 

  51. Weissman M. Interpersonal counselling for stress and distress in primary care: a treatment manual. New York: Columbia University; 1988.

    Google Scholar 

  52. Menchetti M, Bortolotti B, Rucci P, Scocco P, Bombi A, Berardi D, et al. Depression in primary care: interpersonal counseling vs selective serotonin reuptake inhibitors. The DEPICS study. A multicenter randomized controlled trial. Relationale and design. BMC Psychiatry. 2010;10:97. doi:10.1186/1471-244X-10-97.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Guy W. Dosage record and treatment emergent symptom scale [DOTES]. In: US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH Psychopharmocology Research Branch, Division of Extramural Research Programs, editors. ECDEU Assessment manual for psychopharmacology. Revised. Rockville: National Institute of Mental Health; 1976. pp. 223–244.

  54. Frommberger UH, Bauer J, Haselbeuer P, Fraulin A, Riemann D, Berger M. Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci. 1997;247:228–33.

    Article  PubMed  CAS  Google Scholar 

  55. Lanquilon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000;22:370–9.

    Article  Google Scholar 

  56. Yoshimura R, Hori H, Ikenouchi-Sugita A, Uneme-Nakano W, Ueda N, Nakamura J. Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:722–6.

    Article  PubMed  CAS  Google Scholar 

  57. Wray NR, James MR, Gordon SD, Dumenil T, Ryan L, Coventry WL, Statham DJ, Pergadia ML, Madden PA, Heath AC, Montgomery GW, Martin NG. Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiatry. 2009;66:468–76.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  58. Tzvetkov MV, Brockmoller J, Roots I, Kirchheiner J. Common genetic variations in human brain-specific tryptophan hydroxylase-2 and response to antidepressant treatment. Pharmacogenet Genomics. 2008;18:495–506.

    Article  PubMed  CAS  Google Scholar 

  59. Minov C, Baghai TC, Schule C, Zwanzger P, Schwarz MJ, Zill P, Rupprecht R, Bondy B. Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression. Neurosci Lett. 2001;303:119–22.

    Article  PubMed  CAS  Google Scholar 

  60. Tsai SJ, Cheng CY, Yu YW, Chen TJ, Hong CJ. Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Am J Med Genet B Neuropsychiatr Genet. 2003;123B:19–22.

    Article  PubMed  Google Scholar 

  61. Wilkie MJ, Smith D, Reid IC, Day RK, Matthews K, Wolf CR, Blackwood D, Smith G. A splice site polymorphism in the G-protein beta subunit influences antidepressant efficacy in depression. Pharmacogenet Genomics. 2007;17:207–15.

    Article  PubMed  CAS  Google Scholar 

  62. Kang RH, Chang HS, Wong ML, Choi MJ, Park JY, Lee HY, Jung IK, Joe SH, Kim L, Kim SH, Kim YK, Han CS, Ham BJ, Lee HJ, Ko YU, Lee MS, Lee MS. Brain-derived neurotrophic factor gene polymorphisms and mirtazapine responses in Koreans with major depression. J Psychopharmacol. 2010;24:1755–63.

    Article  PubMed  CAS  Google Scholar 

  63. Licinio J, Dong C, Wong ML. Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. Arch Gen Psychiatry. 2009;66:488–97.

    Article  PubMed  CAS  Google Scholar 

  64. Domschke K, Lawford B, Laje G, Berger K, Young R, Morris P, Deckert J, Arolt V, McMahon FJ, Baune BT. Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant response. Int J Neuropsychopharmacol. 2010;13:93–101.

    Article  PubMed  CAS  Google Scholar 

  65. Kocabas NA, Antonijevic I, Faghel C, Forray C, Kasper S, Lecrubier Y, Linotte S, Massat I, Mendlewicz J, Noro M, Montogomery S, Oswald P, Snyder L, Zohar J, Souery D. Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder. Int Clin Psychopharmacol. 2011;26:1–10.

    Article  PubMed  Google Scholar 

  66. Yoshimura R, Kishi T, Suzuki A, Uneme-Nakano W, Ikenouchi-Sugita A, Hori H, Otani K, Iwata N, Nakamura J. The brain-derived neurotrophic factor (BDNF) polymorphism val66met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1022–5.

    Article  PubMed  CAS  Google Scholar 

  67. Musil R, Zill P, Seemuller F, Bondy B, Obermeier M, Spellmann I, Bender W, Adli M, Heuser I, Zeiler J, Gaebel W, Maier W, Rietschel M, Rujescu D, Schennach R, Moller HJ, Riedel M. No influence of brain-derived neurotrophic factor (BDNF) polymorphisms on treatment response in a naturalistic sample of patients with major depression. Eur Arch Psychiatry Clin Neurosci. 2013;263:405–12.

    Article  PubMed  Google Scholar 

  68. Tsuchimine S, Yasui-Furukori N, Nakagami T, Sato Y, Kaneko S. DRD3 but not BDNF, genotype affects treatment response to paroxetine in major depressive disorder: a preliminary study. J Clin Psychopharmacol. 2012;32:724–6.

    Article  PubMed  Google Scholar 

  69. Xu G, Lin K, Rao D, Dang Y, Ouyang H, Mai G, Zhang M. Brain-derived neurotrophic factor gene polymorphism (Val66Met) and the early response to antidepressant in Chinese Han population. Psychiatr Genet. 2012;22:214–5.

    Article  PubMed  CAS  Google Scholar 

  70. Brunoni AR, Kemp AH, Shiozawa P, Cordeiro Q, Valiengo LC, Goulart AC, Coprerski B, Lotufo PA, Brunori D, Perez AB, Fregni F, Bensenor IM. Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: implications for the serotonergic system. Eur Neuropsychopharmcol. 2013;23:1530–40.

    Article  CAS  Google Scholar 

  71. Murphy GM Jr, Sarginson JE, Ryan HS, O’Hara R, Schatzberg AF, Lazzeroni LC. BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression. Pharmacogenet Genomics. 2013;23:301–13.

    Article  PubMed  CAS  Google Scholar 

  72. Verhagen M, van der Meij A, van Deurzen PAM, Janzing JGE, Arias-Vasquez A, Buitelaar JK, Franke B. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry. 2010;15:260–71.

    Article  PubMed  CAS  Google Scholar 

  73. Koch JM, Hinze-Selch D, Stingele K, Huchzermeier C, Goder R, Seeck-Hirschner M, Aldenhoff JB. Changes in CREB Phosphorylation and BDNF plasma levels during psychotherapy of depression. Psychother Psychosom. 2009;78:187–92.

    Article  PubMed  Google Scholar 

  74. Koch JM, Kell S, Hinze-Selch D, Aldenhoff JB. Changes in CREB-phosphorylation during recovery from major depression. J Psychiatr Res. 2002;36:369–75.

    Article  PubMed  Google Scholar 

  75. Crisafulli C, Shim DS, Andrisano C, Pae CU, Chiesa A, Han C, Patkar AA, Lee SJ, Serretti A, De Ronchi D. Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder. Psychiatry Res. 2012;198:39–46.

    Article  PubMed  CAS  Google Scholar 

  76. Levenson JC, Wallace ML, Fournier JC, Rucci P, Frank E. The role of personality pathology in depression treatment outcome with psychotherapy and pharmacotherapy. J Counsult Clin Psychol. 2012;80:719–29.

    Article  Google Scholar 

Download references

Acknowledgments

The study was funded by MIUR (2008XWR4SB).

Disclosure statement

Dr Serretti is, or has been, a consultant/speaker for Abbott, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lily, GlaxoSmithkline, Janssen, Lundbeck, Pfizer, Sanofi, and Servier. Yoshihiko Matsumoto, Chiara Fabbri, Silvia Pellegrini, Stefano Porcelli, Pierluigi Politi, Silvio Bellino, Caterina Iofrida, Veronica Mariotti, Erika Melissari, Marco Menchetti, Valentina Martinelli, MarcoCappucciati, Paola Bozzatello, Elena Brignolo, Paolo Brambilla, and Matteo Balestrieri have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Biomedical and Neuromotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy

    Yoshihiko Matsumoto, Chiara Fabbri, Stefano Porcelli & Alessandro Serretti

  2. Department of Surgical, Medical, Molecular Pathology and of Critical Area, University of Pisa, Pisa, Italy

    Silvia Pellegrini, Caterina Iofrida, Veronica Mariotti & Erika Melissari

  3. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy

    Pierluigi Politi, Valentina Martinelli & Marco Cappucciati

  4. Neuroscience Department, Turin University, Turin, Italy

    Silvio Bellino, Paola Bozzatello & Elena Brignolo

  5. Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan

    Yoshihiko Matsumoto

  6. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

    Marco Menchetti

  7. Unit of Psychiatry, Department of Experimental and Clinical Medical Sciences (DISM), ICBN, University of Udine, Udine, Italy

    Paolo Brambilla & Matteo Balestrieri

  8. Department of Psychiatry and Behavioral Sciences, UT Houston Medical School, Houston, TX, USA

    Paolo Brambilla

Authors
  1. Yoshihiko Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Fabbri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Pellegrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stefano Porcelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pierluigi Politi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Silvio Bellino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Caterina Iofrida
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Veronica Mariotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Erika Melissari
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Marco Menchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Valentina Martinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Marco Cappucciati
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Paola Bozzatello
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Elena Brignolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Paolo Brambilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Matteo Balestrieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alessandro Serretti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Serretti.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsumoto, Y., Fabbri, C., Pellegrini, S. et al. Serotonin Transporter Gene: A New Polymorphism May Affect Response to Antidepressant Treatments in Major Depressive Disorder. Mol Diagn Ther 18, 567–577 (2014). https://doi.org/10.1007/s40291-014-0110-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-014-0110-7

Keywords

Search

Navigation