5-ht2c receptor and mao-a interaction analysis: no association with suicidal behaviour in bipolar patients

  • Vincenzo De Luca
  • Subi Tharmaligam
  • John Strauss
  • James L. Kennedy
ORIGINAL PAPER

Abstract

The serotonin 2C (HTR2C) receptor has been implicated in suicide-related behaviours, however there are not many studies to date about HTR2C and suicidality. We studied HTR2C haplotypes in suicide attempters, where our sample composed of 306 families with at least one member affected by bipolar disorder. HTR2C (Cys23Ser and a common STR in the promoter) variants were analyzed with respect to attempter status and the severity of suicidal behaviour. The X-linked haplotype analysis in relation to suicide attempt did not reveal any significant association. Furthermore, we performed a particular gene-gene interaction for the X-linked serotonergic genes (HTR2C and MAOA), and found no association among this intergenic haplotype combination and suicidal behaviour in bipolar disorder.

Keywords

suicide 5-ht2c bipolar disorder MAO-A X-linked haplotype 

References

  1. 1.
    APA (1994) Diagnostic and statistical manual of mental disorders, 4th edn (DSM-IV). APA, Washington, DCGoogle Scholar
  2. 2.
    Arango V, Ernsberger P, Marzuk PM, Chen JS, Tierney H, Stanley M, Reis DJ, Mann JJ (1990) Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47:1038–1047PubMedGoogle Scholar
  3. 3.
    Asberg M, Traskman L, Thoren P (1976) 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 33:1193–1197PubMedGoogle Scholar
  4. 4.
    Canetto SS, Sakinofsky I (1998) The gender paradox in suicide. Suicide Life Threat Behav 28:1–23PubMedGoogle Scholar
  5. 5.
    Chen YW, Dilsaver SC (1996) Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry 39:896–899PubMedCrossRefGoogle Scholar
  6. 6.
    Dalton EJ, Cate-Carter TD, Mundo E, Parikh SV, Kennedy JL (2003) Suicide risk in bipolar patients: the role of co-morbid substance use disorders. Bipolar Disord 5:58–61PubMedCrossRefGoogle Scholar
  7. 7.
    De Luca V, Tharmalingam S, Sicard T, Kennedy JL (2005) Gene-gene interaction between MAOA and COMT in suicidal behavior. Neurosci Lett 383:151–154PubMedCrossRefGoogle Scholar
  8. 8.
    De Luca V, Wang H, Squassina A, Wong GW, Yeomans J, Kennedy JL (2004) Linkage of M5 muscarinic and alpha7-nicotinic receptor genes on 15q13 to schizophrenia. Neuropsychobiology 50:124–127PubMedCrossRefGoogle Scholar
  9. 9.
    Deckert J, Meyer J, Catalano M, Bosi M, Sand P, DiBella D, Ortega G, Stober G, Franke P, Nothen MM, Fritze J, Maier W, Beckmann H, Propping P, Bellodi L, Lesch KP (2000) Novel 5′-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder. Int J Neuropsychopharmacol 3:321–325PubMedCrossRefGoogle Scholar
  10. 10.
    Drysdale CM, McGraw DW, Stack CB, Stephens JC, Judson RS, Nandabalan K, Arnold K, Ruano G, Liggett SB (2000) Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 97:10483–10488PubMedCrossRefGoogle Scholar
  11. 11.
    Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (2002) High activity-related allele of MAO-A gene associated with depressed suicide in males. Neuroreport 13:1195–1198PubMedCrossRefGoogle Scholar
  12. 12.
    Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121PubMedCrossRefGoogle Scholar
  13. 13.
    Gutierrez B, Arias B, Papiol S, Rosa A, Fananas L (2001) Association study between novel promoter variants at the 5-HT2C receptor gene and human patients with bipolar affective disorder. Neurosci Lett 309:135–137PubMedCrossRefGoogle Scholar
  14. 14.
    Jamison KR (2000) Suicide and bipolar disorder. J Clin Psychiatry 61(Suppl 9):47–51PubMedGoogle Scholar
  15. 15.
    Joiner TE Jr, Brown JS, Wingate LR (2005) The psychology and neurobiology of suicidal behavior. Annu Rev Psychol 56:287–314PubMedCrossRefGoogle Scholar
  16. 16.
    Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444PubMedCrossRefGoogle Scholar
  17. 17.
    Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D (1995) Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). Genomics 27:274–279PubMedCrossRefGoogle Scholar
  18. 18.
    Mann JJ (1995) The fourth generation of progress. Raven Press, New YorkGoogle Scholar
  19. 19.
    Mann JJ (1998) The neurobiology of suicide. Nat Med 4:25–30PubMedCrossRefGoogle Scholar
  20. 20.
    Mann JJ, Brent DA, Arango V (2001) The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system. Neuropsychopharmacology 24:467–477PubMedCrossRefGoogle Scholar
  21. 21.
    McGuffin P, Marusic A, Farmer A (2001) What can psychiatric genetics offer suicidology? Crisis 22:61–65PubMedGoogle Scholar
  22. 22.
    Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E (2001) RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology 24:478–491PubMedCrossRefGoogle Scholar
  23. 23.
    Nordstrom P, Samuelsson M, Asberg M, Traskman-Bendz L, Aberg-Wistedt A, Nordin C, Bertilsson L (1994) CSF 5-HIAA predicts suicide risk after attempted suicide. Suicide Life Threat Behav 24:1–9PubMedGoogle Scholar
  24. 24.
    Okada M, Northup JK, Ozaki N, Russell JT, Linnoila M, Goldman D (2004) Modification of human 5-HT(2C) receptor function by Cys23Ser, an abundant, naturally occurring amino-acid substitution. Mol Psychiatry 9:55–64PubMedCrossRefGoogle Scholar
  25. 25.
    Pooley EC, Houston K, Hawton K, Harrison PJ (2003) Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes. Psychol Med 33:775–783PubMedCrossRefGoogle Scholar
  26. 26.
    Roy A (1993) Genetic and biologic risk factors for suicide in depressive disorders. Psychiatr Q 64:345–358PubMedCrossRefGoogle Scholar
  27. 27.
    Rydin E, Asberg M, Edman G, Schalling D (1990) Violent and nonviolent suicide attempts–a controlled Rorschach study. Acta Psychiatr Scand 82:30–39PubMedCrossRefGoogle Scholar
  28. 28.
    Serretti A, Mandelli L, Giegling I, Schneider B, Hartmann AM, Schnabel A, Maurer K, Moller HJ, Rujescu D (2007) HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers. Am J Med Genet B Neuropsychiatr Genet 144:291–299Google Scholar
  29. 29.
    Sherif F, Marcusson J, Oreland L (1991) Brain gamma-aminobutyrate transaminase and monoamine oxidase activities in suicide victims. Eur Arch Psychiatry Clin Neurosci 241:139–144PubMedCrossRefGoogle Scholar
  30. 30.
    Stack S (2000) Suicide: a 15-year review of the sociological literature. Part I: cultural and economic factors. Suicide Life Threat Behav 30:145–162PubMedGoogle Scholar
  31. 31.
    Stefulj J, Buttner A, Kubat M, Zill P, Balija M, Eisenmenger W, Bondy B, Jernej B (2004) 5HT-2C receptor polymorphism in suicide victims. Association studies in German and Slavic populations. Eur Arch Psychiatry Clin Neurosci 254:224–227PubMedGoogle Scholar
  32. 32.
    WHO (2005) Burden of mental and behavioural disorders: suicideGoogle Scholar
  33. 33.
    Xie E, Zhu L, Zhao L, Chang LS (1996) The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant. Genomics 35:551–561PubMedCrossRefGoogle Scholar
  34. 34.
    Yuan X, Yamada K, Ishiyama-Shigemoto S, Koyama W, Nonaka K (2000) Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes. Diabetologia 43:373–376PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Vincenzo De Luca
    • 1
  • Subi Tharmaligam
    • 1
  • John Strauss
    • 1
  • James L. Kennedy
    • 1
  1. 1.Dept. of PsychiatryUniversity of TorontoTorontoCanada

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