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ADHD Diagnosis May Influence the Association between Polymorphisms in Nicotinic Acetylcholine Receptor Genes and Tobacco Smoking

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Abstract

Polymorphisms in the CHRNA5–CHRNA3–CHRNB4 gene cluster have been shown to be involved in tobacco smoking susceptibility. Considering that attention deficit/hyperactivity disorder (ADHD) not only increases the risk but may also influence the molecular mechanisms of tobacco smoking, we analyzed the association between polymorphisms in the nicotinic acetylcholine receptor genes and tobacco smoking among individuals with or without ADHD. The sample included 1,118 subjects divided into four groups according to smoking status and ADHD diagnosis. Our results demonstrate that the minor alleles of two polymorphisms (rs578776 and rs3743078) in the CHRNA3 gene are associated with an increased risk of tobacco smoking only among patients with ADHD. These alleles have been shown in previous studies to be protective factors for smoking in subjects without ADHD. These findings add to existing evidence that ADHD may exert an important modifying effect on the genetic risk of smoking and should be considered in tobacco smoking association studies.

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References

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington: American Psychiatric Press.

    Google Scholar 

  • Aubin, H. J., Rollema, H., Svensson, T. H., & Winterer, G. (2012). Smoking, quitting, and psychiatric disease: A review. Neuroscience and Biobehavioral Reviews, 36(1), 271–284.

    Article  PubMed  Google Scholar 

  • Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2005). Haploview: Analysis and visualization of LD and haplotype maps. Bioinformatics, 21(2), 263–265.

    Article  CAS  PubMed  Google Scholar 

  • Bidwell, L. C., Garrett, M. E., McClernon, F. J., Fuemmeler, B. F., Williams, R. B., Ashley-Koch, A. E., et al. (2012). A preliminary analysis of interactions between genotype, retrospective ADHD symptoms, and initial reactions to smoking in a sample of young adults. Nicotine and Tobacco Research, 14(2), 229–233.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bierut, L. J., Stitzel, J. A., Wang, J. C., Hinrichs, A. L., Grucza, R. A., Xuei, X., et al. (2008). Variants in nicotinic receptors and risk for nicotine dependence. American Journal of Psychiatry, 165(9), 1163–1171.

    Article  PubMed Central  PubMed  Google Scholar 

  • Broms, U., Wedenoja, J., Largeau, M. R., Korhonen, T., Pitkaniemi, J., Keskitalo-Vuokko, K., et al. (2012). Analysis of detailed phenotype profiles reveals CHRNA5–CHRNA3–CHRNB4 gene cluster association with several nicotine dependence traits. Nicotine and Tobacco Research, 14(6), 720–733.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bukstein, O. G. (2012). Attention deficit hyperactivity disorder and substance use disorders. Current Topics in Behavioral Neurosciences, 9, 145–172.

    Article  PubMed  Google Scholar 

  • Chen, X., Chen, J., Williamson, V. S., An, S. S., Hettema, J. M., Aggen, S. H., et al. (2009). Variants in nicotinic acetylcholine receptors α5 and α3 increase risks to nicotine dependence. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 150B(7), 926–933.

    Article  CAS  Google Scholar 

  • David, S. P., Hamidovic, A., Chen, G. K., Bergen, A. W., Wessel, J., Kasberger, J. L., et al. (2012). Genome-wide meta-analyses of smoking behaviors in African Americans. Translational Psychiatry, 2, e119.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2002). Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition (SCID-I/P). New York: Biometrics Research.

    Google Scholar 

  • Freathy, R. M., Ring, S. M., Shields, B., Galobardes, B., Knight, B., Weedon, M. N., et al. (2009). A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5–CHRNA3–CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy. Human Molecular Genetics, 18(15), 2922–2927.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Furberg, H., Kim, Y., Dackor, J., Boerwinkle, E., Franceschini, N., Ardissino, D., et al. (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics, 42(5), 441–447.

    Article  CAS  Google Scholar 

  • Glass, K., & Flory, K. (2010). Why does ADHD confer risk for cigarette smoking? A review of psychosocial mechanisms. Clinical Child and Family Psychology Review, 13(3), 291–313.

    Article  PubMed  Google Scholar 

  • Gotti, C., & Clementi, F. (2004). Neuronal nicotinic receptors: From structure to pathology. Progress in Neurobiology, 74(6), 363–396.

    Article  CAS  PubMed  Google Scholar 

  • Gotti, C., Clementi, F., Fornari, A., Gaimarri, A., Guiducci, S., Manfredi, I., et al. (2009). Structural and functional diversity of native brain neuronal nicotinic receptors. Biochemical Pharmacology, 78(7), 703–711.

    Article  CAS  PubMed  Google Scholar 

  • Gould, T.J., Leach, P.T. (2013). Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning. Neurobiology of Learning and Memory, doi: 10.1016/j.nlm.2013.08.004.

  • Grevet, E. H., Bau, C. H., Salgado, C. A., Ficher, A., Victor, M. M., Garcia, C., et al. (2005). Interrater reliability for diagnosis in adults of attention deficit hyperactivity disorder and oppositional defiant disorder using K-SADS-E. Arquivos de Neuro-Psiquiatria, 63(2A), 307–310.

    Article  PubMed  Google Scholar 

  • Grucza, R. A., Wang, J. C., Stitzel, J. A., Hinrichs, A. L., Saccone, S. F., Saccone, N. L., et al. (2008). A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence. Biological Psychiatry, 64(11), 922–929.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K. O. (1991). The Fagerstrom test for nicotine dependence: A revision of the Fagerstrom tolerance Questionnaire. British Journal of Addiction, 86(9), 1119–1127.

    Article  CAS  PubMed  Google Scholar 

  • Hindorff, L. A., MacArthur, J., Morales, J., Junkins, H. A., Hall, P. N., Klemm, A. K., & Manolio, T. A. (2013, May). A catalog of published genome-wide association studies. www.genome.gov/gwastudies. Accessed 9 May 2013.

  • Hutchison, K. E., Stallings, M., McGeary, J., & Bryan, A. (2004). Population stratification in the candidate gene study: Fatal threat or red herring? Psychological Bulletin, 130(1), 66–79.

    Article  PubMed  Google Scholar 

  • Kalil, K. L., Bau, C. H., Grevet, E. H., Sousa, N. O., Garcia, C. R., Victor, M. M., et al. (2008). Smoking is associated with lower performance in WAIS-R Block Design scores in adults with ADHD. Nicotine and Tobacco Research, 10(4), 683–688.

    Article  PubMed  Google Scholar 

  • Kapoor, M., Wang, J. C., Bertelsen, S., Bucholz, K., Budde, J. P., Hinrichs, A., et al. (2012). Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking. PLoS One, 7(3), e33513.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kessler, R. C., Adler, L., Ames, M., Demler, O., Faraone, S., Hiripi, E., et al. (2005). The World Health Organization adult ADHD Self-Report Scale (ASRS): A short screening scale for use in the general population. Psychological Medicine, 35(2), 245–256.

    Article  PubMed  Google Scholar 

  • Lahiri, D. K., & Nurnberger, J. I, Jr. (1991). A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Research, 19(19), 5444.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee, C. T., Fuemmeler, B. F., McClernon, F. J., Ashley-Koch, A., & Kollins, S. H. (2013). Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood. Addictive Behaviors, 38(11), 2683–2689.

    Article  PubMed  Google Scholar 

  • Liu, J. Z., Tozzi, F., Waterworth, D. M., Pillai, S. G., Muglia, P., Middleton, L., et al. (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics, 42(5), 436–440.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marques-Vidal, P., Kutalik, Z., Paccaud, F., Bergmann, S., Waeber, G., Vollenweider, P., et al. (2011). Variant within the promoter region of the CHRNA3 gene associated with FTN dependence is not related to self-reported willingness to quit smoking. Nicotine and Tobacco Research, 13(9), 833–839.

    Article  CAS  PubMed  Google Scholar 

  • Martin-Soelch, C. (2013). Neuroadaptive changes associated with smoking: Structural and functional neural changes in nicotine dependence. Brain Sciences, 3, 159–176.

    Article  Google Scholar 

  • Mayhew, K. P., Flay, B. R., & Mott, J. A. (2000). Stages in the development of adolescent smoking. Drug and Alcohol Dependence, 59(Suppl 1), S61–S81.

    Article  PubMed  Google Scholar 

  • McClernon, F. J., Fuemmeler, B. F., Kollins, S. H., Kail, M. E., & Ashley-Koch, A. E. (2008). Interactions between genotype and retrospective ADHD symptoms predict lifetime smoking risk in a sample of young adults. Nicotine and Tobacco Research, 10(1), 117–127.

    Article  PubMed  Google Scholar 

  • McClernon, F. J., & Kollins, S. H. (2008). ADHD and smoking: From genes to brain to behavior. Annals of the New York Academy of Sciences, 1141, 131–147.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mercadante, M. T., Asbahar, F., Rosário, M. C., Ayres, A. M., Karman, L., Ferrari, M. C., et al. (1995). K-SADS, entrevista semi-estruturada para diagnóstico em psiquiatria da infância, versão epidemiológica. São Paulo: FMUSP.

    Google Scholar 

  • Mihailescu, S., & Drucker-Colin, R. (2000). Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Archives of Medical Research, 31(2), 131–144.

    Article  CAS  PubMed  Google Scholar 

  • Mitchell, J.T., McIntyre, E.M., McClernon, F.J., Kollins, S.H. (2013). Smoking motivation in adults with attention-deficit/hyperactivity disorder using the Wisconsin inventory of smoking dependence motives. Nicotine and Tobacco Research, doi: 10.1093/ntr/ntt144.

  • Morisano, D., Bacher, I., Audrain-McGovern, J., & George, T. P. (2009). Mechanisms underlying the comorbidity of tobacco use in mental health and addictive disorders. Canadian Journal of Psychiatry, 54(6), 356–367.

    Google Scholar 

  • Potter, A. S., Newhouse, P. A., & Bucci, D. J. (2006). Central nicotinic cholinergic systems: A role in the cognitive dysfunction in attention-deficit/hyperactivity disorder? Behavioural Brain Research, 175(2), 201–211.

    Article  CAS  PubMed  Google Scholar 

  • Saccone, N. L., Saccone, S. F., Hinrichs, A. L., Stitzel, J. A., Duan, W., Pergadia, M. L., et al. (2009a). Multiple distinct risk loci for nicotine dependence identified by dense coverage of the complete family of nicotinic receptor subunit (CHRN) genes. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 150B(4), 453–466.

    Article  CAS  Google Scholar 

  • Saccone, N. L., Wang, J. C., Breslau, N., Johnson, E. O., Hatsukami, D., Saccone, S. F., et al. (2009b). The CHRNA5–CHRNA3–CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African–Americans and in European–Americans. Cancer Research, 69(17), 6848–6856.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Salzano, F. M., & Bortolini, M. C. (2002). The evolution and genetics of Latin American populations. Cambridge: Cambridge University Press.

    Google Scholar 

  • Santos, N. P., Ribeiro-Rodrigues, E. M., Ribeiro-Dos-Santos, A. K., Pereira, R., Gusmao, L., Amorim, A., et al. (2010). Assessing individual interethnic admixture and population substructure using a 48-insertion–deletion (INSEL) ancestry-informative marker (AIM) panel. Human Mutation, 31(2), 184–190.

    Article  CAS  PubMed  Google Scholar 

  • Sarginson, J. E., Killen, J. D., Lazzeroni, L. C., Fortmann, S. P., Ryan, H. S., Schatzberg, A. F., et al. (2011). Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5–A3–B4) predict severity of nicotine addiction and response to smoking cessation therapy. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 156B(3), 275–284.

    Article  Google Scholar 

  • Schlaepfer, I. R., Hoft, N. R., Collins, A. C., Corley, R. P., Hewitt, J. K., Hopfer, C. J., et al. (2008). The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults. Biological Psychiatry, 63(11), 1039–1046.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sherva, R., Kranzler, H. R., Yu, Y., Logue, M. W., Poling, J., Arias, A. J., et al. (2010). Variation in nicotinic acetylcholine receptor genes is associated with multiple substance dependence phenotypes. Neuropsychopharmacology, 35(9), 1921–1931.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sousa, N. O., Grevet, E. H., Salgado, C. A., Silva, K. L., Victor, M. M., Karam, R. G., et al. (2011). Smoking and ADHD: An evaluation of self medication and behavioral disinhibition models based on comorbidity and personality patterns. Journal of Psychiatric Research, 45(6), 829–834.

    Article  PubMed  Google Scholar 

  • Stevens, V. L., Bierut, L. J., Talbot, J. T., Wang, J. C., Sun, J., Hinrichs, A. L., et al. (2008). Nicotinic receptor gene variants influence susceptibility to heavy smoking. Cancer Epidemiol Biomarkers and Prevention, 17(12), 3517–3525.

    Article  CAS  Google Scholar 

  • Thorgeirsson, T. E., Geller, F., Sulem, P., Rafnar, T., Wiste, A., Magnusson, K. P., et al. (2008). A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature, 452(7187), 638–642.

    Article  CAS  PubMed  Google Scholar 

  • Thorgeirsson, T. E., Gudbjartsson, D. F., Surakka, I., Vink, J. M., Amin, N., Geller, F., et al. (2010). Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nature Genetics, 42(5), 448–453.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Van Voorhees, E., McClernon, F. J., Fuemmeler, B., English, J., Holdaway, A., Hallyburton, M., et al. (2012). An examination of differences in variables maintaining smoking behavior in adult smokers with and without attention-deficit/hyperactivity disorder. Addiction Research and Theory, 20(1), 72–81.

    Article  Google Scholar 

  • Volkow, N. D., Wang, G. J., Newcorn, J., Telang, F., Solanto, M. V., Fowler, J. S., et al. (2007). Depressed dopamine activity in caudate and preliminary evidence of limbic involvement in adults with attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 64(8), 932–940.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J. C., Grucza, R., Cruchaga, C., Hinrichs, A. L., Bertelsen, S., Budde, J. P., et al. (2009). Genetic variation in the CHRNA5 gene affects mRNA levels and is associated with risk for alcohol dependence. Molecular Psychiatry, 14(5), 501–510.

    Article  CAS  PubMed  Google Scholar 

  • Wang, G. J., Volkow, N. D., Wigal, T., Kollins, S. H., Newcorn, J. H., Telang, F., et al. (2013). Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder. PLoS One, 8(5), e63023.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weiss, R. B., Baker, T. B., Cannon, D. S., von Niederhausern, A., Dunn, D. M., Matsunami, N., et al. (2008). A candidate gene approach identifies the CHRNA5–A3–B4 region as a risk factor for age-dependent nicotine addiction. PLoS Genetics, 4(7), e1000125.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wellman, R. J., DiFranza, J. R., Savageau, J. A., & Dussault, G. F. (2004). Short term patterns of early smoking acquisition. Tobacco Control, 13(3), 251–257.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zembrzuski, V. M., Callegari-Jacques, S. M., & Hutz, M. H. (2006). Application of an African ancestry index as a genomic control approach in a Brazilian population. Annals of Human Genetics, 70(Pt 6), 822–828.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS-PRONEX), Hospital de Clínicas de Porto Alegre (FIPE-HCPA), PRONEX and FAPERGS/DECIT/SCTIE/MS/PPSUS.

Conflict of Interest

The author(s) declare the following potential conflict of interest with respect to the research, authorship and/or publication of this article: Dr. Rohde was on the speaker’s bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis and Shire for the last 3 years. He also received travel awards (air tickets and hotel accommodations) for participating in two child psychiatric meetings from Novartis and Janssen-Cilag. The ADHD and Juvenile Bipolar Disorder Outpatient Programs that were chaired by him received unrestricted educational and research support from the following pharmaceutical companies over the last 3 years: Abbott, Bristol-Myers Squibb, Eli-Lilly, Janssen-Cilag, Novartis and Shire. Dr. Belmonte-de-Abreu is on the speaker’s bureau or is a consultant for Janssen-Cilag and Bristol-Myers Squibb. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Caixa Postal 15053, CEP: 91501-970, Porto Alegre, RS, Brazil

    Evelise R. Polina, Diego L. Rovaris, Lucas A. de Azeredo, Nina R. Mota & Claiton H. D. Bau

  2. Adult ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Eduardo S. Vitola, Katiane L. Silva, Paula O. Guimarães-da-Silva, Felipe A. Picon, Paulo Belmonte-de-Abreu, Luis A. Rohde, Eugenio H. Grevet & Claiton H. D. Bau

  3. Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Paulo Belmonte-de-Abreu, Luis A. Rohde & Eugenio H. Grevet

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  1. Evelise R. Polina
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  2. Diego L. Rovaris
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  3. Lucas A. de Azeredo
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  4. Nina R. Mota
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  5. Eduardo S. Vitola
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  6. Katiane L. Silva
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  8. Felipe A. Picon
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  9. Paulo Belmonte-de-Abreu
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  10. Luis A. Rohde
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  11. Eugenio H. Grevet
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  12. Claiton H. D. Bau
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Correspondence to Claiton H. D. Bau.

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Polina, E.R., Rovaris, D.L., de Azeredo, L.A. et al. ADHD Diagnosis May Influence the Association between Polymorphisms in Nicotinic Acetylcholine Receptor Genes and Tobacco Smoking. Neuromol Med 16, 389–397 (2014). https://doi.org/10.1007/s12017-013-8286-2

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  • DOI: https://doi.org/10.1007/s12017-013-8286-2

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