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Family-Based Association Analysis of Serotonin Genes in Pathological Gambling Disorder: Evidence of Vulnerability Risk in the 5HT-2A Receptor Gene

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Abstract

Pathological gambling (PG) has become a growing public health problem in many countries around the world. PG is an impulse control disorder and its behavior and psychopathology present similarities with substance abuse disorders. Evidence from twin studies supports a significant genetic predisposition to PG, but the precise genetic loci still remain unclear. The present study investigates the allele and genotype distribution of polymorphisms of the serotonin transporter, serotonin receptor 1B and 2A genes in 140 sib-pairs discordant for the diagnosis of PG. A significant association of the C/C genotype of the serotonin receptor 2A T102C (rs 6313) polymorphism and the PG phenotype was observed [OR = 1.7 (1.1–3.4)]. This preliminary result is consistent with the hypothesis that the serotonin system is associated with addiction behavior and similar results have been reported for nicotine and alcohol dependence.

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References

  • A.P.A. (1980) Diagnostic and statistical manual of mental disorders, 3rd edition (DSM-III). American Psychiatric Association, Washington

    Google Scholar 

  • A.P.A. (1994) Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). American Psychiatric Association, Washington

    Google Scholar 

  • Bergevin T, Gupta R, Derevensky J, Kaufman F (2006) Adolescent gambling: understanding the role of stress and coping. J Gambl Stud 22(2):195–208

    Article  PubMed  Google Scholar 

  • Black DW, Repertinger S, Gaffney GR, Gabel J (1998) Family history and psychiatric comorbidity in persons with compulsive buying: preliminary findings. Am J Psychiatry 155:960–963

    PubMed  CAS  Google Scholar 

  • Black DW, Monahan PO, Temkit M, Shaw M (2006) A family study of pathological gambling. Psychiatry Res 141:295–303

    Article  PubMed  Google Scholar 

  • Blanco C, Moreyra P, Nunes EV, Saiz-Ruiz J, Ibanez A (2001) Pathological gambling: addiction or compulsion? Semin Clin Neuropsychiatry 6:167–176

    Article  PubMed  CAS  Google Scholar 

  • Cardinal RN (2006) Neural systems implicated in delayed and probabilistic reinforcement. Neural Netw 19:1277–12301

    Article  PubMed  Google Scholar 

  • 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 

  • Chambers RA, Potenza MN (2003) Neurodevelopment, impulsivity, and adolescent gambling. J Gambl Stud 19:53–84

    Article  PubMed  Google Scholar 

  • Comings DE, Gade-Andavolu R, Gonzalez N et al (2001) The additive effect of neurotransmitter genes in pathological gambling. Clin Genet 60:107–116

    Article  PubMed  CAS  Google Scholar 

  • Cook EH Jr, Courchesne R, Lord C et al (1997) Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 2:247–250

    Article  PubMed  Google Scholar 

  • Crockford DN, Goodyear B, Edwards J, Quickfall J, El-Guebaly N (2005) Cue-induced brain activity in pathological gamblers. Biol Psychiatry 58:787–795

    Article  PubMed  Google Scholar 

  • Da Silva Lobo DS, Vallada HP, Knight J et al (2007) Dopamine genes and pathological gambling in discordant sib-pairs. J Gambl Stud 23:421–433

    Article  PubMed  Google Scholar 

  • Do Prado-Lima PA, Chatkin JM, Taufer M et al (2004) Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction. Am J Med Genet B Neuropsychiatr Genet 128:90–93

    Article  Google Scholar 

  • Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121

    Article  PubMed  Google Scholar 

  • Dudbridge F (2006) UNPHASED user guide. Technical report 2006/5. MRC Biostatistics Unit, Cambridge

    Google Scholar 

  • Goodman A (2008) Neurobiology of addiction. An integrative review. Biochem Pharmacol 75:266–322

    Article  PubMed  CAS  Google Scholar 

  • Goudriaan AE, Oosterlaan J, De Beurs E, Van Den Brink W (2004) Pathological gambling: a comprehensive review of biobehavioral findings. Neurosci Biobehav Rev 28:123–141

    Article  PubMed  Google Scholar 

  • Hawi Z, Segurado R, Conroy J et al (2005) Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. Am J Hum Genet 77:958–965

    Article  PubMed  CAS  Google Scholar 

  • Hwu HG, Chen CH (2000) Association of 5HT2A receptor gene polymorphism and alcohol abuse with behavior problems. Am J Med Genet 96:797–800

    Article  PubMed  CAS  Google Scholar 

  • Jakubczyk A, Wrzosek M, Lukaszkiewicz J et al (2012) The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients. J Psychiatr Res 46:44–49

    Article  PubMed  Google Scholar 

  • 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 

  • Knight RT, Staines WR, Swick D, Chao LL (1999) Prefrontal cortex regulates inhibition and excitation in distributed neural networks. Acta Psychol (Amst) 101:159–178

    Article  CAS  Google Scholar 

  • Lange C, Laird NM (2002) Power calculations for a general class of family-based association tests: dichotomous traits. Am J Hum Genet 71:575–584

    Article  PubMed  CAS  Google Scholar 

  • Lappalainen J, Dean M, Charbonneau L et al (1995) Mapping of the serotonin 5-HT1D beta autoreceptor gene on chromosome 6 and direct analysis for sequence variants. Am J Med Genet 60:157–161

    Article  PubMed  CAS  Google Scholar 

  • Laurin N, Feng Y, Ickowicz A et al (2007) No preferential transmission of paternal alleles at risk genes in attention-deficit hyperactivity disorder. Mol Psychiatry 12:226–229

    Article  PubMed  CAS  Google Scholar 

  • Lesch KP, Bengel D, Heils A et al (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531

    Article  PubMed  CAS  Google Scholar 

  • Lobo DS, Kennedy JL (2006) The genetics of gambling and behavioral addictions. CNS Spectr 11:931–939

    PubMed  Google Scholar 

  • Nakamura T, Matsushita S, Nishiguchi N et al (1999) Association of a polymorphism of the 5HT2A receptor gene promoter region with alcohol dependence. Mol Psychiatry 4:85–88

    Article  PubMed  CAS  Google Scholar 

  • Nicodemus KK, Liu W, Chase GA, Tsai YY, Fallin MD (2005) Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms. BMC Genet 6(Suppl 1):S78

    Article  PubMed  Google Scholar 

  • Perez De Castro I, Ibanez A, Saiz-Ruiz J, Fernandez-Piqueras J (1999) Genetic contribution to pathological gambling: possible association between a functional DNA polymorphism at the serotonin transporter gene (5-HTT) and affected men. Pharmacogenetics 9:397–400

    PubMed  CAS  Google Scholar 

  • Petry NM, Stinson FS, Grant BF (2005) Comorbidity of DSM-IV pathological gambling and other psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 66:564–574

    Article  PubMed  Google Scholar 

  • Potenza MN, Leung HC, Blumberg HP et al (2003a) An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers. Am J Psychiatry 160:1990–1994

    Article  PubMed  Google Scholar 

  • Potenza MN, Steinberg MA, Skudlarski P et al (2003b) Gambling urges in pathological gambling: a functional magnetic resonance imaging study. Arch Gen Psychiatry 60:828–836

    Article  PubMed  Google Scholar 

  • Puig MV, Celada P, Artigas F (2004) Serotonergic control of prefrontal cortex. Rev Neurol 39:539–547

    PubMed  CAS  Google Scholar 

  • Shaffer HJ, Hall MN (2001) Updating and refining prevalence estimates of disordered gambling behaviour in the United States and Canada. Can J Public Health 92:168–172

    PubMed  CAS  Google Scholar 

  • Slutske WS, Eisen S, True WR et al (2000) Common genetic vulnerability for pathological gambling and alcohol dependence in men. Arch Gen Psychiatry 57:666–673

    Article  PubMed  CAS  Google Scholar 

  • Smoller JW, Biederman J, Arbeitman L et al (2006) Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD. Biol Psychiatry 59:460–467

    Article  PubMed  CAS  Google Scholar 

  • Stein DJ, Fan J, Fossella J, Russell VA (2007) Inattention and hyperactivity-impulsivity: psychobiological and evolutionary underpinnings of ADHD. CNS Spectr 12:190–196

    PubMed  Google Scholar 

  • Taber JI, Mccormick RA, Ramirez LF (1987) The prevalence and impact of major life stressors among pathological gamblers. Int J Addict 22:71–79

    PubMed  CAS  Google Scholar 

  • Tanabe J, Thompson L, Claus E et al (2007) Prefrontal cortex activity is reduced in gambling and nongambling substance users during decision-making. Hum Brain Mapp 28:1276–1286

    Article  PubMed  Google Scholar 

  • Warren JT Jr, Peacock ML, Rodriguez LC, Fink JK (1993) An MspI polymorphism in the hyman serotonin receptor gene (HTR2): detection by DGGE and RFLP analysis. Hum Mol Genet 2:338

    Article  PubMed  CAS  Google Scholar 

  • White MJ, Young RM, Morris CP, Lawford BR (2011) Cigarette smoking in young adults: the influence of the HTR2A T102C polymorphism and punishment sensitivity. Drug Alcohol Depend 114:140–146

    PubMed  CAS  Google Scholar 

  • Wing JK, Babor T, Brugha T et al (1990) SCAN. Schedules for clinical assessment in neuropsychiatry. Arch Gen Psychiatry 47:589–593

    Article  PubMed  CAS  Google Scholar 

  • Yucel M, Lubman DI (2007) Neurocognitive and neuroimaging evidence of behavioural dysregulation in human drug addiction: implications for diagnosis, treatment and prevention. Drug Alcohol Rev 26:33–39

    Article  PubMed  Google Scholar 

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Acknowledgments

We would like to acknowledge the São Paulo Research Funding Agency (government agency, FAPESP, projects 02/026537; 02/00009-3) for financial support. We thank Dr Elizabete Miracca from the Programme of Genetics and Pharmacogenetics (ProGene) at Institute of Psychiatry, University of São Paulo for genotyping supervision and the Gambling Outpatient Unit group in São Paulo for help with data collection.

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Authors and Affiliations

  1. Department and Institute of Psychiatry (LIM 23), University of Sao Paulo Medical School, Rua Dr Ovídio Pires de Campos 785, 05403-010, São Paulo, SP, Brazil

    David Wilson, Daniela Sabbatini da Silva Lobo, Hermano Tavares, Valentim Gentil & Homero Vallada

  2. Centre for Addiction and Mental Health, Neurogenetics Section, University of Toronto, Toronto, ON, Canada

    Daniela Sabbatini da Silva Lobo

Authors
  1. David Wilson
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  2. Daniela Sabbatini da Silva Lobo
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  3. Hermano Tavares
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  4. Valentim Gentil
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  5. Homero Vallada
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Correspondence to Homero Vallada.

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Wilson, D., da Silva Lobo, D.S., Tavares, H. et al. Family-Based Association Analysis of Serotonin Genes in Pathological Gambling Disorder: Evidence of Vulnerability Risk in the 5HT-2A Receptor Gene. J Mol Neurosci 49, 550–553 (2013). https://doi.org/10.1007/s12031-012-9846-x

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  • DOI: https://doi.org/10.1007/s12031-012-9846-x

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