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Parent of origin effect and allelic expression imbalance of the serotonin transporter in bipolar disorder and suicidal behaviour

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Suicide and suicidal behaviour are a major health concern worldwide particularly in patients with mood disorders. Family, adoption and twin studies show that genetics influences suicidal behaviour. The serotonin transporter (5HTT) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since 5HTT binding is decreased in the brain of suicide completers. Because the effect of genomic imprinting in the 5HTT gene on suicidal behaviour has not been investigated, we analysed the parent-of-origin effect (POE) of four 5HTT markers and the differential expression of the 5HTT G2651T (rs1042173) alleles in suicide attempters affected by bipolar disorder. We performed a family based association study and ETDT/QTDT analyses of the rs25531, HTTLPR, VNTR-2 and G2651T polymorphisms in 312 nuclear families with at least one subject affected by bipolar disorder. The main outcomes investigated in this study are bipolar disorder diagnosis, suicide attempts, suicidal behaviour severity and age at onset of bipolar disorder. We also compared the allele-specific mRNA levels in lymphoblastoid cells from 13 bipolar suicide attempters and 8 bipolar non-suicide attempters. Allele 2651T was transmitted significantly more often to bipolar patients (P = 0.042). There was no significant difference between maternal and paternal transmission ratios. Furthermore, there was no significant difference in the ratio of T/G-specific mRNA expression between bipolar attempters and non-attempters. These data do not support a role for differential allelic expression of 5HTT for suicidal behaviour in bipolar disorder. Small sample size and the fact that RNA was obtained from lymphoblastoid cell lines were some of the limitations of this study.

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References

  1. Anguelova M, Benkelfat C, Turecki G (2003) A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I affective disorders. Mol Psychiatry 8:574–591

    Article  PubMed  CAS  Google Scholar 

  2. Altamura AC, Dell’Osso B, Berlin HA, Buoli M, Bassetti R, Mundo E (2010) Duration of untreated illness and suicide in bipolar disorder: a naturalistic study. Eur Arch Psychiatry Clin Neurosci 260:385–391

    Article  PubMed  Google Scholar 

  3. Caspi A, Sugden K, Moffitt TE et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  PubMed  CAS  Google Scholar 

  4. 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 39:896–899

    Article  PubMed  CAS  Google Scholar 

  5. Cho HJ, Meira-Lima I, Cordeiro Q et al (2005) Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis. Mol Psychiatry 10:771–781

    Article  PubMed  CAS  Google Scholar 

  6. Contreras J, Hare L, Camarena B et al (2009) The serotonin transporter 5-HTTPR polymorphism is associated with current and lifetime depression in persons with chronic psychotic disorders. Acta Psychiatr Scand 119:117–127

    Article  PubMed  CAS  Google Scholar 

  7. Hegerl U, Mergl R, Havers I, Schmidtke A, Lehfeld H, Niklewski G, Althaus D (2010) Sustainable effects on suicidality were found for the Nuremberg alliance against depression. Eur Arch Psychiatry Clin Neurosci 260:401–406

    Article  PubMed  Google Scholar 

  8. Kato T, Winokur G, Coryell W et al (1996) Parent-of-origin effect in transmission of bipolar disorder. Am J Med Genet 67:546–550

    Article  PubMed  CAS  Google Scholar 

  9. Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B (2005) The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 62:529–535

    Article  PubMed  CAS  Google Scholar 

  10. Goodwin FK, Jaminson KR (1990) Manic depressive illness. Oxford University Press, New York

    Google Scholar 

  11. Li D, He L (2007) Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behaviour. Mol Psychiatry 12:47–54

    Article  PubMed  Google Scholar 

  12. Lim JE, Papp A, Pinsonneault J, Sadee W, Saffen D (2006) Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR. Mol Psychiatry 11:649–662

    Article  PubMed  CAS  Google Scholar 

  13. Lonnqvist JK, Henriksson MM, Isometsa ET, Marttunen MJ, Heikkinen ME, Aro HM, Kuoppasalmi KI (1995) Mental disorders and suicide prevention. Psychiatry Clin Neurosci 49(Suppl 1):S111–S116

    Article  PubMed  Google Scholar 

  14. Lopez JF, Chalmers DT, Vazquez DM, Watson SJ, Akil H (1994) Serotonin transporter mRNA in rat brain is regulated by classical antidepressants. Biol Psychiatry 35:287–290

    Article  PubMed  CAS  Google Scholar 

  15. Lucki I (1998) The spectrum of behaviours influenced by serotonin. Biol Psychiatry 44:151–162

    Article  PubMed  CAS  Google Scholar 

  16. Müller DJ, de Luca V, Sicard T, King N, Strauss J, Kennedy JL (2006) Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study. Br J Psychiatry 189:317–323

    Article  PubMed  Google Scholar 

  17. Neumaier JF, Root DC, Hamblin MW (1996) Chronic fluoxetine reduces serotonin transporter mRNA and 5-HT1B mRNA in a sequential manner in the rat dorsal Raphe nucleus. Neuropsychopharmacology 15:515–522

    Article  PubMed  CAS  Google Scholar 

  18. Risch N, Herrell R, Lehner T et al (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301:2462–2471

    Article  PubMed  CAS  Google Scholar 

  19. Schloss P, Williams DC (1998) The serotonin transporter: a primary target for antidepressant drugs. J Psychopharmacol 12:115–121

    Article  PubMed  CAS  Google Scholar 

  20. Schulze TG, Muller DJ, Krauss H et al (2002) Further evidence for age of onset being an indicator for severity in bipolar disorder. J Affect Disord 68:343–345

    Article  PubMed  Google Scholar 

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Acknowledgments

National Alliance for Research on Schizophrenia and Depression (Young Investigator to VDL), American Foundation for Suicide Prevention (Pilot Gant to VDL) and Canadian Institutes of Health Research (Fellowship #93967 to RPS and Clinician-Scientist Phase II fellowship to AHCW).

Conflict of interest

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Authors and Affiliations

  1. Neurobiology of Schizophrenia Section, Neuroscience Department, Centre for Addiction and Mental Health Toronto, Toronto, ON, Canada

    Crystal Pinto, Diane Lioult, Mawahib Semeralul, Albert H. Wong & Vincenzo De Luca

  2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Crystal Pinto, Renan P. Souza, James L. Kennedy, Jerry J. Warsh, Albert H. Wong & Vincenzo De Luca

  3. Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health Toronto, Toronto, ON, Canada

    Renan P. Souza, James L. Kennedy & Vincenzo De Luca

  4. Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    Jerry J. Warsh & Albert H. Wong

  5. Cellular and Molecular Pathophysiology Section, Neuroscience Department, Centre for Addiction and Mental Health Toronto, Toronto, ON, Canada

    Jerry J. Warsh

  6. Centre for Addiction and Mental Health, 250 College Street, Room 711, Toronto, ON, M5T 1R8, Canada

    Albert H. Wong

Authors
  1. Crystal Pinto
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  2. Renan P. Souza
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  3. Diane Lioult
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  4. Mawahib Semeralul
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  5. James L. Kennedy
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  6. Jerry J. Warsh
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  7. Albert H. Wong
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  8. Vincenzo De Luca
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Corresponding author

Correspondence to Albert H. Wong.

Additional information

A. Wong and V. De Luca have contributed equally to the preparation of this manuscript.

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Pinto, C., Souza, R.P., Lioult, D. et al. Parent of origin effect and allelic expression imbalance of the serotonin transporter in bipolar disorder and suicidal behaviour. Eur Arch Psychiatry Clin Neurosci 261, 533–538 (2011). https://doi.org/10.1007/s00406-011-0192-8

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  • DOI: https://doi.org/10.1007/s00406-011-0192-8

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