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.

  • Original Article
  • Published:

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

The Pharmacogenomics Journal volume 4, pages 267–273 (2004)Cite this article

Abstract

We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (⩾1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Goodwin F, Jamison K . Manic-depressive Illness. Oxford University Press: New York 1990.

    Google Scholar 

  2. Schou M . Lithium Treatment of Manic Depressive Illness. A Practical Guide. Karger: Basal 1989.

    Google Scholar 

  3. Maj M, Arena F, Lovero N, Pirozzi R, Kemali D . Factors associated with response to lithium prophylaxis in DSM III major depression and bipolar disorder. Pharmacopsychiatry 1985; 18: 309–313.

    CAS  PubMed  Google Scholar 

  4. Maj M, Pirozzi R, Starace F . Previous pattern of course of the illness as a predictor of response to lithium prophylaxis in bipolar patients. J Affect Disord 1989; 17: 237–241.

    CAS  PubMed  Google Scholar 

  5. OConnell RA, Mayo JA, Flatow L, Cuthbertson BO, Brien BE . Outcome of bipolar disorder on long-term treatment with lithium. Br J Psychiatry 1991; 159: 123–129.

    CAS  Google Scholar 

  6. Abou-Saleh MT . Who responds to prophylactic lithium therapy? Br J Psychiatry 1993; 21(Suppl 21): 20–26.

    Article  Google Scholar 

  7. Franchini L, Zanardi R, Smeraldi E, Gasperini M . Early onset of lithium prophylaxis as a predictor of good long-term outcome. Eur Arch Psychiatry Clin Neurosci 1999; 249: 227–230.

    CAS  PubMed  Google Scholar 

  8. Serretti A, Lattuada E, Franchini L, Smeraldi E . Melancholic features and response to lithium prophylaxis in mood disorders. Depression Anxiety 2000; 11: 73–79.

    Article  CAS  PubMed  Google Scholar 

  9. Mendlewicz J, Fieve RR, Stallone F, Fleiss JL . Genetic history as a predictor of lithium response in manic-depressive illness. Lancet 1972; 1: 599–600.

    CAS  PubMed  Google Scholar 

  10. Maj M, Del Vecchio M, Starace F, Pirozzi R, Kemali D . Prediction of affective psychoses response to lithium prophylaxis. The role of socio-demographic, clinical, psychological and biological variables. Acta Psychiatrica Scand 1984; 69: 37–44.

    Article  CAS  Google Scholar 

  11. Grof P, Alda M, Grof E, Zvolsky P, Walsh M . Lithium response and genetics of affective disorders. J Affect Disord 1994; 32: 85–95.

    CAS  PubMed  Google Scholar 

  12. Abou-Saleh MT, Coppen A . Who responds to prophylactic lithium? J Affect Disord 1986; 10: 115–125.

    Article  CAS  PubMed  Google Scholar 

  13. Mendlewicz J . Prediction of treatment outcome: family and twin studies in lithium prophylaxis and the question of lithium red blood cell/plasma ratio. In: Cooper TB, Gershon S, Kline NS, Schou M (eds). Litium Controversis and Unresolved Issues. Excerpta Medica: Amsterdam, 1979.

    Google Scholar 

  14. Nylander PO, Engstrom C, Nordqvist-Karlsson B, Astrom M . Family history of affective disorders and the significance for prophylactic effect of lithium treatment. Biol Psychiatry 1999; 45: 1079–1081.

    Article  CAS  PubMed  Google Scholar 

  15. Morabito A, Gasperini M, Macciardi F, Smeraldi E . Possible relationship between outcome in primary affective disorders treated with lithium and family history. Adv Biochem Psychopharmacol 1982; 32: 157–163.

    CAS  PubMed  Google Scholar 

  16. Smeraldi E, Petroccione A, Gasperini M, Macciardi F, Orsini A . The search for genetic homogeneity in affective disorders. J Affect Disord 1984; 7: 99–107.

    Article  CAS  PubMed  Google Scholar 

  17. Smeraldi E, Petroccione A, Gasperini M, Macciardi F, Orsini A, Kidd KK . Outcomes on lithium treatment as a tool for genetic studies in affective disorders. J Affect Disord 1984; 6: 139–151.

    Article  CAS  PubMed  Google Scholar 

  18. Cavazzoni P, Alda M, Turecki G, Rouleau G, Grof E, Martin R et al. Lithium-responsive affective disorders: no association with the tyrosine hydroxylase gene. Psychiatry Res 1996; 64: 91–96.

    Article  CAS  PubMed  Google Scholar 

  19. Turecki G, Alda M, Grof P, Martin R, Cavazzoni PA, Duffy A et al. No association between chromosome-18 markers and lithium-responsive affective disorders. Psychiatry Res 1996; 63: 17–23.

    Article  CAS  PubMed  Google Scholar 

  20. Alda M . Pharmacogenetics of lithium response in bipolar disorder. J Psychiatry Neurosci 1999; 24: 154–158.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Dunner DL, Fleiss JL, Fieve RR . Lithium carbonate prophylaxis failure. Br J Psychiatry 1976; 129: 40–44.

    Article  CAS  PubMed  Google Scholar 

  22. Misra PC, Burns BH . ‘Lithium non-responders’ in a lithium clinic. Acta Psychiatrica Scand 1977; 55: 32–40.

    Article  CAS  Google Scholar 

  23. Strober M, Morrell W, Burroughs J, Lampert C, Danforth H, Freeman R . A family study of bipolar I disorder in adolescence. Early onset of symptoms linked to increased familial loading and lithium resistance. J Affect Disord 1988; 15: 255–268.

    Article  CAS  PubMed  Google Scholar 

  24. Engstrom C, Astrom M, Nordqvist-Karlsson B, Adolfsson R, Nylander PO . Relationship between prophylactic effect of lithium therapy and family history of affective disorders. Biol Psychiatry 1997; 42: 425–433.

    Article  CAS  PubMed  Google Scholar 

  25. Coryell W, Akiskal H, Leon AC, Turvey C, Solomon D, Endicott J . Family history and symptoms levels during treatment for bipolar I affective disorder. Biol Psychiatry 2000; 47: 1034–1042.

    Article  CAS  PubMed  Google Scholar 

  26. Grof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M et al. Is response to prophylactic lithium a familial trait? Int J Neuropsychopharmacol 2000; 3: 339.

    Article  Google Scholar 

  27. Carli M, Afkhami-Dastjerdian S, Reader TA . Effects of a chronic lithium treatment on cortical serotonin uptake sites and 5-HT1A receptors. Neurochem Res 1997; 22: 427–435.

    Article  CAS  PubMed  Google Scholar 

  28. Carli M, Reader TA . Regulation of central serotonin transporters by chronic lithium: an autoradiographic study. Synapse 1997; 27: 83–89.

    Article  CAS  PubMed  Google Scholar 

  29. El-Mallakh S . Litihum: Actions and Mechanisms. American Psychiatric Press: Washington, DC 1996.

    Google Scholar 

  30. Pei Q, Leslie RA, Grahame-Smith DG, Zetterstrom TS . 5-HT efflux from rat hippocampus in vivo produced by 4-aminopyridine is increased by chronic lithium administration. Neuroreport 1995; 6: 716–720.

    Article  CAS  PubMed  Google Scholar 

  31. Sharp T, Bramwell SR, Lambert P, Grahame-Smith DG . Effect of short- and long-term administration of lithium on the release of endogenous 5-HT in the hippocampus of the rat in vivo and in vitro. Neuropharmacology 1991; 30: 977–984.

    Article  CAS  PubMed  Google Scholar 

  32. Baptista TJ, Hernandez L, Burguera JL, Burguera M, Hoebel BG . Chronic lithium administration enhances serotonin release in the lateral hypothalamus but not in the hippocampus in rats. A microdialysis study. J Neur Trans—Gen Sect 1990; 82: 31–41.

    Article  CAS  Google Scholar 

  33. Odagaki Y, Koyama T, Matsubara S, Matsubara R, Yamashita I . Effects of chronic lithium treatment on serotonin binding sites in rat brain. J Psychiatric Res 1990; 24: 271–277.

    Article  CAS  Google Scholar 

  34. Goodwin GM . The effects of antidepressant treatments and lithium upon 5-HT1A receptor function. Prog Neuro-Psychopharmacol Biol Psychiatry 1989; 13: 445–451.

    Article  CAS  Google Scholar 

  35. Artigas F, Sarrias MJ, Martinez E, Gelpi E, Alvarez E, Udina C . Increased plasma free serotonin but unchanged platelet serotonin in bipolar patients treated chronically with lithium. Psychopharmacology 1989; 99: 328–332.

    Article  CAS  PubMed  Google Scholar 

  36. Hotta I, Yamawaki S, Segawa T . Long-term lithium treatment causes serotonin receptor down-regulation via serotonergic presynapses in rat brain. Neuropsychobiology 1986; 16: 19–26.

    Article  CAS  PubMed  Google Scholar 

  37. Treiser SL, Cascio CS, O'Donohue TL, Thoa NB, Jacobowitz DM, Kellar KJ . Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science 1981; 213: 1529–1531.

    Article  CAS  PubMed  Google Scholar 

  38. Price LH, Charney DS, Delgado PL, Heninger GR . Lithium and serotonin function: implications for the serotonin hypothesis of depression. Psychopharmacology 1990; 100: 3–12.

    Article  CAS  PubMed  Google Scholar 

  39. Cassidy F, Murry E, Carroll BJ . Tryptophan depletion in recently manic patients treated with lithium. Biol Psychiatry 1998; 43: 230–232.

    Article  CAS  PubMed  Google Scholar 

  40. Chaouloff F, Gunn SH, Young JB . Serotonin does not mediate the adrenal catecholamine-releasing effect of acute lithium administration in rats. Psychoneuroendocrinology 1992; 17: 135–144.

    Article  CAS  PubMed  Google Scholar 

  41. Lacaille JC, Cloutier S, Reader TA . Lithium reduced synaptic transmission and increased neuronal excitability without altering endogenous serotonin, norepinephrine and dopamine in rat hippocampal slices in vitro. Prog Neuro-Psychopharmacol Biol Psychiatry 1992; 16: 397–412.

    Article  CAS  Google Scholar 

  42. Manji HK, Hsiao JK, Risby ED, Oliver J, Rudorfer MV, Potter WZ . The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry 1991; 48: 505–512.

    Article  CAS  PubMed  Google Scholar 

  43. Collier D, Stöber G, Li T, Heils A, Catalano M, Di Bella D et al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1996; 1: 453–460.

    CAS  PubMed  Google Scholar 

  44. Collier DA, Arranz MJ, Sham P, Battersby S, Vallada H, Gill P et al. The serotonin transporter is a potential susceptibility factor for bipolar affective disorder. Neuroreport 1996; 7: 1675–1679.

    Article  CAS  PubMed  Google Scholar 

  45. Rees M, Norton N, Jones I, McCandless F, Scourfield J, Holmans P et al. Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT). Mol Psychiatry 1997; 2: 398–402.

    Article  CAS  PubMed  Google Scholar 

  46. Bellivier F, Laplanche JL, Leboyer M, Feingold J, Bottos C, Allilaire JF et al. Serotonin transporter gene and manic depressive illness: an association study. Biol Psychiatry 1997; 41: 750–752.

    Article  CAS  PubMed  Google Scholar 

  47. Mendes de Oliveira JR, Otto PA, Vallada H, Lauriano V, Elkis H, Lafer B et al. Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia. Am J Med Genet 1998; 81: 225–227.

    Article  CAS  PubMed  Google Scholar 

  48. Furlong RA, Ho L, Walsh C, Rubinsztein JS, Jain S, Paykel ES et al. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. Am J Med Genet 1998; 81: 58–63.

    Article  CAS  PubMed  Google Scholar 

  49. Hoehe MR, Wendel B, Grunewald I, Chiaroni P, Levy N, Morris-Rosendahl D et al. Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. Am J Med Genet 1998; 81: 1–3.

    Article  CAS  PubMed  Google Scholar 

  50. Esterling LE, Yoshikawa T, Turner G, Badner JA, Bengel D, Gershon ES et al. Serotonin transporter (5-HTT) gene and bipolar affective disorder. Am J Med Genet 1998; 81: 37–40.

    Article  CAS  PubMed  Google Scholar 

  51. Gutierrez B, Arranz MJ, Collier DA, Valles V, Guillamat R, Bertranpetit J et al. Serotonin transporter gene and risk for bipolar affective disorder—an association study in a Spanish population. Biol Psychiatry 1998; 43: 843–847.

    Article  CAS  PubMed  Google Scholar 

  52. Oruc L, Verheyen GR, Furac I, Jakovljevic M, Ivezic S, Raeymaekers P et al. Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorder. Am J Med Genet 1997; 74: 504–506.

    Article  CAS  PubMed  Google Scholar 

  53. Ewald H, Flint T, Degn B, Mors O, Kruse TA . A functional variant of the serotonin transporter gene in families with bipolar affective disorder. J Affect Disord 1998; 48: 135–144.

    Article  CAS  PubMed  Google Scholar 

  54. Kelsoe J, Remick R, Sadovnick A, Kristbjarnarson H, Flodman P, Spence M et al. Genetic linkage study of bipolar disorder and the serotonin transporter. Am J Med Genet 1996; 67: 215–217.

    Article  CAS  PubMed  Google Scholar 

  55. Lenzinger E, Neumeister A, Praschak-Rieder N, Fuchs K, Gerhard E, Willeit M et al. Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene? Psychiatry Res 1999; 85: 241–246.

    Article  CAS  PubMed  Google Scholar 

  56. Mundo E, Walker M, Tims H, Macciardi F, Kennedy JL . Lack of linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and bipolar disorder. Am J Med Genet 2000; 96: 379–383.

    Article  CAS  PubMed  Google Scholar 

  57. Ospina-Duque J, Duque C, Carvajal-Carmona L, Ortiz-Barrientos D, Soto I, Pineda N et al. An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia. Neurosci Lett 2000; 292: 199–202.

    Article  CAS  PubMed  Google Scholar 

  58. Saleem Q, Ganesh S, Vijaykumar M, Reddy YC, Brahmachari SK, Jain S . Association analysis of 5HT transporter gene in bipolar disorder in the Indian population. Am J Med Genet 2000; 96: 170–172.

    Article  CAS  PubMed  Google Scholar 

  59. Lesch K, Bengel D, Heils A, Sabol S, Greenberg B, Petri S et al. Association of anxiety-related traits with a polymorphismin the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1530.

    Article  CAS  PubMed  Google Scholar 

  60. Serretti A, Lilli R, Mandelli L, Lorenzi C, Smeraldi E . Serotonin transporter gene associated with lithium prophylaxis in mood disorders. Pharmacogenom J 2001; 1: 71–77.

    Article  CAS  Google Scholar 

  61. Serretti A, Lilli R, Smerladi E . Pharmacogenetics in affective disorders. Eur J Pharmacol 2002; 438: 117–128.

    Article  CAS  PubMed  Google Scholar 

  62. Del Zompo M, Ardau R, Palmas MA, Bocchetta A, Reina A, Piccardi MP . Lithium response: association study with two candidate genes. Mol Psychiatry 1999; 4(Suppl 1): s66–s67.

    Google Scholar 

  63. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association: Washington, DC 1994.

  64. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM . Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry 1982; 39: 879–883.

    Article  CAS  PubMed  Google Scholar 

  65. W.M.A. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997; 277: 925–926.

  66. Lahiri DK, Nurnberger JIJ . A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucl Acid Res 1991; 19: 5444.

    Article  CAS  Google Scholar 

  67. Erdfelder E, Faul F, Buchner A . GPOWER: A general power analysis program. Behav Res Methods Instrum Comput 1996; 28: 1–11.

    Article  Google Scholar 

  68. Cohen J . Statistical Power Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates: Hillsdale, NJ 1988.

    Google Scholar 

  69. Rosenthal N, Mazzanti C, Barnett R, Hardin T, Turner E, Lam G et al. Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder. Mol Psychiatry 1998; 3: 175–177.

    Article  CAS  PubMed  Google Scholar 

  70. Flory JD, Manuck SB, Ferrell RE, Dent KM, Peters DG, Muldoon MF . Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism. Mol Psychiatry 1999; 4: 93–96.

    Article  CAS  PubMed  Google Scholar 

  71. Ohara K, Nagai M, Suzuki Y, Ochiai M . Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene. Psychiatry Res 1998; 81: 277–279.

    Article  CAS  PubMed  Google Scholar 

  72. Matsushita S, Muramatsu T, Kimura M, Shirakawa O, Mita T, Nakai T et al. Serotonin transporter gene regulatory region polymorphism and panic disorder. Mol Psychiatry 1997; 2: 390–392.

    Article  CAS  PubMed  Google Scholar 

  73. Serretti A, Lilli R, Lorenzi C, Gasperini M, Smeraldi E . Tryptophan hydroxylase gene and response to lithium prophylaxis in mood disorders. J Psychiatric Res 1999; 33: 371–377.

    Article  CAS  Google Scholar 

  74. Turecki G, Grof P, Cavazzoni P, Duffy A, Grof E, Ahrens B et al. Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder. Mol Psychiatry 1998; 3: 534–538.

    Article  CAS  PubMed  Google Scholar 

  75. Lovlie R, Berle JO, Stordal E, Steen VM . The phospholipase C-gamma1 gene (PLCG1) and lithium-responsive bipolar disorder: re-examination of an intronic dinucleotide repeat polymorphism. Psychiatr Genet 2001; 11: 41–43.

    Article  CAS  PubMed  Google Scholar 

  76. Steen VM, Lovlie R, Osher Y, Belmaker RH, Berle JO, Gulbrandsen AK . The polymorphic inositol polyphosphate 1-phosphatase gene as a candidate for pharmacogenetic prediction of lithium-responsive manic-depressive illness. Pharmacogenetics 1998; 8: 259–268.

    CAS  PubMed  Google Scholar 

  77. Washizuka S, Ikeda A, Kato N, Kato T . Possible relationship between mitochondrial DNA polymorphisms and lithium response in bipolar disorder. Int J Neuropsychopharmacol 2003; 6: 421–424.

    Article  CAS  PubMed  Google Scholar 

  78. Smeraldi E, Benedetti F, Zanardi R . Serotonin transporter promoter genotype and illness recurrence in mood disorders. Eur Neuropsychopharmacol 2002; 12: 73–75.

    Article  CAS  PubMed  Google Scholar 

  79. Gasperini M, Scherillo P, Manfredonia MG, Franchini L, Smeraldi E . A study of relapses in subjects with mood disorder on lithium treatment. Eur Neuropsychopharmacol 1993; 3: 103–110.

    Article  CAS  PubMed  Google Scholar 

  80. Franchini L, Gasperini M, Smeraldi E . A 24-month follow-up study of unipolar subjects: a comparison between lithium and fluvoxamine. J Affect Disord 1994; 32: 225–231.

    Article  CAS  PubMed  Google Scholar 

  81. Hamilton S, Slager S, Kraft J, McGrath P, Knowles J . Genetic Analysis of the Serotonin Transporter in the Treatment of Depression, Pharmacogenetics in Psychiatry Meeting 2003, Green tab: New York.

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

    Article  CAS  PubMed  Google Scholar 

  83. Zanardi R, Serretti 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  PubMed  Google Scholar 

  84. 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: 586–592.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  87. 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: 587–590.

    Article  CAS  PubMed  Google Scholar 

  88. Muller-Oerlinghausen B . Does effective lithium prophylaxis result in a symptom-free state of manic-depressive illness? Some thoughts on the fine-tuning of mood stabilization. Comp Psychiatry 2000; 41: 26–31.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, San Raffaele Institute, Vita-Salute University, Milano, Italy

    A Serretti, L Mandelli, C Lorenzi, C Ploia & E Smeraldi

  2. Department of Psychiatry, Eginition Hospital, Athens University Medical School, Athens, Greece

    P N Malitas, B Alevizos, C Nikolaou, F Boufidou & G N Christodoulou

Authors
  1. A Serretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P N Malitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Mandelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Lorenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Ploia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Alevizos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Nikolaou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F Boufidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G N Christodoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E Smeraldi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Serretti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Serretti, A., Malitas, P., Mandelli, L. et al. Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders. Pharmacogenomics J 4, 267–273 (2004). https://doi.org/10.1038/sj.tpj.6500252

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500252

Keywords

This article is cited by

Search

Advanced search

Quick links