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American Journal of Pharmacogenomics

, Volume 5, Issue 1, pp 45–52 | Cite as

Monoamine Oxidase A and Tryptophan Hydroxylase Gene Polymorphisms

Are They Associated with Bipolar Disorder?
  • Martin Preisig
  • François Ferrero
  • Alain Malafosse
Genomics in Health and Disease

Abstract

Most of the candidate gene studies in bipolar disorder have focused on the major neurotransmitter systems that are influenced by drugs used in the treatment of this disorder. The monoamine oxidase A (MAOA) and the tryptophan hydroxylase (TPH1, TPH2) genes are two of the candidates that have been tested in a series of association studies using unrelated or family-based controls. This review summarizes the existing association studies regarding these genes. Most of these studies were based on the unrelated case-control design with samples of 50 to 600 subjects. Regarding MAOA, three meta-analyses with partially overlapping samples supported a modest effect of this gene in bipolar disorder in female Caucasians. However, as several studies could not replicate these findings, more work is necessary to demonstrate unequivocally the involvement of MAOA in bipolar disorder and establish the biological mechanism underlying the genetic association. With respect to TPH1 and TPH2, the majority of studies did not provide evidence for an association between these genes and bipolar disorder. The genes are more likely to be related to suicidal behavior than to bipolar disorder.

Keywords

Bipolar Disorder Suicidal Behavior Bipolar Patient Tryptophan Hydroxylase MAOA Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by grants 32-40677.94, 32-47315.96, 31-53849.98, and 32-66793.01 from the Swiss National Foundation.

The authors have provided no information on conflicts of interest directly relevant to the content of this review.

References

  1. 1.
    Gershon ES, Hamovit J, Guroff JJ, et al. A family study of schizoaffective, bipolar I, bipolar II, unipolar and normal control probands. Arch Gen Psychiatry 1982; 39: 1157–67PubMedCrossRefGoogle Scholar
  2. 2.
    Tsuang MT, Faraone SV, Fleming JA. Familial transmission of major affective disorders: is there evidence supporting the distinction between unipolar and bipolar disorders? Br J Psychiatry 1985; 146: 268–71PubMedCrossRefGoogle Scholar
  3. 3.
    Maier W, Hallmayer J, Minges J, et al. Morbid risks in relatives of affective, schizoaffective, and schizophrenic patients: results of a family study. In: Marneros A, Tsuang T, editors. Affective and schizoaffective disorders: similarities and differences. Berlin: Springer, 1990: 201–7CrossRefGoogle Scholar
  4. 4.
    Mendlewicz J, Rainer JD. Adoption study supporting genetic transmission in manic depressive illness. Nature 1977; 268: 327–9PubMedCrossRefGoogle Scholar
  5. 5.
    Wender PH, Kety SS, Rosenthal D, et al. Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 1986; 30: 121–8CrossRefGoogle Scholar
  6. 6.
    Bertelsen A, Harvard B, Hauge M. A Danish twin study of manic-depressive disorders. Br J Psychiatry 1977; 130: 330–51PubMedCrossRefGoogle Scholar
  7. 7.
    Benkelfat C. Serotoninergic mechanisms in psychiatric disorders: new research tool, new ideas. Int Clin Psychopharmacol 1993; 8Suppl. 2: 53–6PubMedCrossRefGoogle Scholar
  8. 8.
    Jacobs BL, Fornal CA. Serotonin and behavior: a general hypothesis. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York: Raven Press, 1995: 461–9Google Scholar
  9. 9.
    Maes M, Meltzer HY. The serotoninergic hypothesis of major depression. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York: Raven Press, 1995: 933–44Google Scholar
  10. 10.
    Craddock N, Davé S, Greening J. Association studies of bipolar disorder. Bipolar Disord 2001; 3: 284–98PubMedCrossRefGoogle Scholar
  11. 11.
    Van Praag H, Korf J, Puite J. 5-Hydroxyindoleacetic acid levels in the cerebrospinal fluid of depressive patients treated with probenecid. Nature 1970; 225: 1259–60PubMedCrossRefGoogle Scholar
  12. 12.
    Briley MS, Langer SZ, Raiman R, et al. Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients. Science 1980; 209: 303–5PubMedCrossRefGoogle Scholar
  13. 13.
    Owens MJ, Nemeroff CB. Role of serotonin in pathophysiology of depression: focus on the serotonin transporter. Clin Chem 1994; 40: 288–95PubMedGoogle Scholar
  14. 14.
    Scott N, Reading H, Loundon J. Studies on human platelets in affective disorders. Psychopharmacology 1979; 60: 131–5PubMedCrossRefGoogle Scholar
  15. 15.
    Ozelius L, Hsu YP, Bruns G, et al. Human monoamine oxidase gene MAOA Chromosome position Xp21-p11 and DNA polymorphism. Genomics 1988; 3: 53–8PubMedCrossRefGoogle Scholar
  16. 16.
    Lan NC, Heinzmann C, Gal A, et al. Human monoamine oxidase A and B genes map to Xp11.23 and are deleted in a patient with Norrie disease. Genomics 1989; 4: 552–9PubMedCrossRefGoogle Scholar
  17. 17.
    Brunner HG, Nelen MR, van Zandvoort P, et al. X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization and evidence for disturbed monoamine metabolism. Am J Hum Genet 1993; 52: 1032–9PubMedGoogle Scholar
  18. 18.
    Brunner HG, Nelen M, Breakefield XO, et al. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 1993; 262: 578–80PubMedCrossRefGoogle Scholar
  19. 19.
    Lim LC, Powell J, Sham P, et al. Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder. Am J Med Genet 1995; 60: 325–31PubMedCrossRefGoogle Scholar
  20. 20.
    Black GCM, Chen ZY, Craig IW, et al. Dinucleotide repeat polymorphism at the MAOA locus. Nucleic Acids Res 1991; 19: 689PubMedGoogle Scholar
  21. 21.
    Hinds HL, Hendriks RW, Craig IW, et al. Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif. Genomics 1992; 13: 896–7PubMedCrossRefGoogle Scholar
  22. 22.
    Hotamisligil GS, Breakfield XO. Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet 1991; 49: 383–92PubMedGoogle Scholar
  23. 23.
    Preisig M, Bellivier F, Fenton BT, et al. Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multi-center study. Am J Psychiatry 2000; 157: 948–55PubMedCrossRefGoogle Scholar
  24. 24.
    Craddock N, Daniels J, Roberts E, et al. No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphism. Am J Med Genet 1995; 60: 322–4PubMedCrossRefGoogle Scholar
  25. 25.
    Kawada Y, Hattori M, Dai XY, et al. Possible association between monoamine oxidase A gene and bipolar affective disorder. Am J Hum Genet 1995; 56: 335–6PubMedGoogle Scholar
  26. 26.
    Nöthen MM, Eggermann K, Albus M, et al. Association analysis of the monoamine oxidase A gene in bipolar affective disorder by using family-based internal controls. Am J Hum Genet 1995; 57: 977–8Google Scholar
  27. 27.
    Rubinsztein DC, Leggo J, Goodburn S, et al. Genetic association between monoamine oxidase A microsatellite and RFLP alleles and bipolar affective disorder: analysis and meta-analysis. Hum Mol Gen 1996; 5: 779–82PubMedCrossRefGoogle Scholar
  28. 28.
    Parsian A, Todd RD. Genetic association between monoamine oxidase and manicdepressive illness: comparison of relative risk and haplotype relative risk data. Am J Med Genet 1997; 74: 475–9PubMedCrossRefGoogle Scholar
  29. 29.
    Muramatsu T, Matsushita S, Kanba S, et al. Monoamine oxidase gene polymorphisms and mood disorder. Am J Med Genet 1997; 74: 494–6PubMedCrossRefGoogle Scholar
  30. 30.
    Kunugi H, Ishida S, Kato T, et al. A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders. Mol Psychiatry 1999; 4: 393–5PubMedCrossRefGoogle Scholar
  31. 31.
    Furlong RA, Ho L, Rubinsztein JS, et al. Analysis of the monoamine oxidase A (MAOA) gene in bipolar affective disorder by association studies, metaanalyses, and sequencing of the promoter. Am J Med Genet 1999; 88: 398–406PubMedCrossRefGoogle Scholar
  32. 32.
    Turecki G, Grof P, Cavazzoni P, et al. MAOA: association and linkage studies with lithium responsive bipolar disorder. Psychiatr Genet 1999; 9: 13–6PubMedCrossRefGoogle Scholar
  33. 33.
    Lin S, Jiang S, Wu X, et al. Association analysis between mood disorder and monoamine oxidase gene. Am J Med Genet 2000; 96: 12–4PubMedCrossRefGoogle Scholar
  34. 34.
    Syagailo YV, Stöber G, Gässle M, et al. Association analysis of functional monoamine oxidase A gene promoter polymorphism in psychiatric disorders. Am J Med Genet 2001; 105: 168–71PubMedCrossRefGoogle Scholar
  35. 35.
    Serretti A, Cristina S, Lilli R, et al. Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. Am J Med Genet 2002; 114: 361–9PubMedCrossRefGoogle Scholar
  36. 36.
    Cusin C, Serretti A, Lattuada E, et al. Association study of MAO-A, COMT, 5HT2A, DRD2 and DRD4 polymorphisms with illness time course in mood disorders. Am J Med Genet 2002; 114: 380–90PubMedCrossRefGoogle Scholar
  37. 37.
    Ho LW, Furlong RA, Rubinsztein JS, et al. Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder. Am J Med Genet 2000; 96: 36–42PubMedCrossRefGoogle Scholar
  38. 38.
    Craig SP, Boularan S, Darmon N, et al. Localization of human tryptophan hydroxylase (TPH) to chromosome 11p15.3p14 by in situ hybridization. Cytogenet Cell Genet 1991; 56: 157–9PubMedCrossRefGoogle Scholar
  39. 39.
    Nielsen DA, Jenkins GL, Stefanisco KM, et al. Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7. Brain Res Mol Brain Res 1997; 45: 145–8PubMedCrossRefGoogle Scholar
  40. 40.
    Boularan S, Darmon M, Ganem Y, et al. Complete coding sequence of human tryptophan hydroxylase. Nucleic Acids Res 1990; 18: 4257CrossRefGoogle Scholar
  41. 41.
    Abbar M, Courtet P, Amadeo S, et al. Suicidal behaviors and the tryptophan hydroxylase gene. Arch Gen Psychiatry 1995; 51: 846–9CrossRefGoogle Scholar
  42. 42.
    Walther DJ, Peter JU, Bashammakh S, et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 2003; 299: 76PubMedCrossRefGoogle Scholar
  43. 43.
    Sugden D. Comparison of circadian expression of tryptophan hydroxylase isoform mRNA in the rat pineal gland using real-time PCR. J Neurochem 2003; 86: 1308–11PubMedCrossRefGoogle Scholar
  44. 44.
    Nurnberger JI, Adkins S, Lahiri DK, et al. Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry 2000; 57: 572–9PubMedCrossRefGoogle Scholar
  45. 45.
    Nielsen DA, Goldman D, Virkkunen M, et al. Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch Gen Psychiatry 1994; 51: 34–8PubMedCrossRefGoogle Scholar
  46. 46.
    Nielsen DA, Virkkunen M, Lappalainen J, et al. A tryptophan hydroxylase gene marker for suicidality and alcoholism. Arch Gen Psychiatry 1998; 55: 593–602PubMedCrossRefGoogle Scholar
  47. 47.
    Bellivier F, Leboyer M, Courtet P, et al. Association between the tryptophan hydroxylase gene and manic-depressive illness. Arch Gen Psychiatry 1998; 55: 33–7PubMedCrossRefGoogle Scholar
  48. 48.
    Serretti A, Lilli R, Lorenzi C, et al. Tryptophan hydroxylase gene and major psychoses. Psychiatry Res 2001; 103: 79–86PubMedCrossRefGoogle Scholar
  49. 49.
    Rotondo A, Mazzanti C, Dell’Osso L, et al. Catechol O-methyltransferase, serotonin transporter and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder. Am J Psychiatry 2002; 159: 23–9PubMedCrossRefGoogle Scholar
  50. 50.
    Kirov G, Owen MJ, Jones I, et al. Tryptophan hydroxylase gene and manicdepressive illness. Arch Gen Psychiatry 1999; 56: 98–9PubMedCrossRefGoogle Scholar
  51. 51.
    McQuillin A, Lawrence J, Kalsi G, et al. No allelic association between bipolar affective disorder and the tryptophan hydroxylase gene. Arch Gen Psychiatry 1999; 56: 99–101PubMedCrossRefGoogle Scholar
  52. 52.
    Furlong RA, Ho L, Rubinsztein JS, et al. No association of the tryptophan hydroxylase gene with bipolar affective disorder, unipolar affective disorder, or suicidal behavior in major affective disorder. Am J Med Genet 1998; 81: 245–7PubMedCrossRefGoogle Scholar
  53. 53.
    Han L, Nielsen DA, Rosenthal NE, et al. No coding variant of tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive: compulsive disorder, anorexia nervosa, and alcoholism. Biol Psychiatry 1999; 45: 615–9PubMedCrossRefGoogle Scholar
  54. 54.
    Vincent JB, Massellis M, Lawrence J, et al. Genetic association analysis of serotonin system genes in bipolar affective disorder. Am J Psychiatry 1999; 156: 136–8PubMedGoogle Scholar
  55. 55.
    Tsai SJ, Hong CJ, Wang YC. Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors. Neuro Report 1999; 10: 3773–5Google Scholar
  56. 56.
    Rietschel M, Schorr A, Albus M, et al. Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls. Am J Med Genet 2000; 96: 310–1PubMedCrossRefGoogle Scholar
  57. 57.
    Souery D, Van Gestel S, Massat I, et al. Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study. Biol Psychiatry 2001; 49: 405–9PubMedCrossRefGoogle Scholar
  58. 58.
    Cusin C, Serretti A, Lattuada E, et al. Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders. J Psychiatr Res 2001; 35: 217–23PubMedCrossRefGoogle Scholar
  59. 59.
    White K, Shih J, Fong T, et al. Elevated plasma monoamine oxidase activity in patients with non-endogenous depression. Am J Psychiatry 1980; 137: 1258–9PubMedGoogle Scholar
  60. 60.
    von Knorring L, Perris C, Oreland L, et al. Morbidity risk for psychiatric disorders in families of probands with affective disorders divided according to levels of platelet MAO activity. Psychiatr Res 1985; 15: 271–9CrossRefGoogle Scholar
  61. 61.
    Gershon ES, Targum SD, Leckman JF. Platelet monoamine oxidase MAO activity and genetic vulnerability to bipolar BP affective illness. Psychopharmacol Bull 1979; 15: 27–30PubMedGoogle Scholar
  62. 62.
    Pandey GN, Dorus L, Shaughnessy R, et al. Reduced platelet MAO activity and vulnerability to psychiatric disorders. Psychiatry Res 1980; 2: 315–21PubMedCrossRefGoogle Scholar
  63. 63.
    Bellivier F, Chaste P, Maolafosse A. Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis. Am J Med Genet 2004; 124B: 87–91PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Martin Preisig
    • 1
  • François Ferrero
    • 2
  • Alain Malafosse
    • 2
  1. 1.University Department of Adult PsychiatryPrilly-LausanneSwitzerland
  2. 2.Department of PsychiatryUniversity Hospital of GenevaGenevaSwitzerland

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