Advertisement

Journal of Neural Transmission

, Volume 115, Issue 2, pp 341–345 | Cite as

Adrenergic α2A receptor gene and response to methylphenidate in attention-deficit/hyperactivity disorder-predominantly inattentive type

  • T. L. da Silva
  • T. G. Pianca
  • T. Roman
  • M. H. Hutz
  • S. V. Faraone
  • M. Schmitz
  • L. A. Rohde
Article

Summary

An association between ADRA2A −1291 C > G polymorphism and response to methylphenidate in inattentive symptoms was previously suggested in children with ADHD. No investigation specifically assessed this association in ADHD–inattentive type (ADHD-I). In this naturalistic pharmacogenetic study, 59 subjects with ADHD-I from a non-referred sample were treated with short-acting methylphenidate and genotyped for ADRA2A −1291 C > G polymorphism. The primary outcome measure was the inattentive subscale of the SNAP-IV applied by a child psychiatrist blinded to genotype at baseline and first month of treatment. Children and adolescents with the G allele showed significantly lower inattentive scores with MPH treatment at the first month of treatment than subjects without the G allele (n = 59; F = 6.14; p = 0.016). We extended to ADHD-I previous findings suggesting the influence of the G allele at the ADRA2A −1291 C > G polymorphism on the improvement of inattentive symptoms with methylphenidate in children with all ADHD subtypes.

Keywords: Attention-deficit/hyperactivity disorder; inattentive type; ADRA2A gene; methylphenidate; pharmacogenetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arnsten, AF, Dudley, AG 2005Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: relevance to therapeutic effects in Attention Deficit Hyperactivity DisorderBehav Brain Funct12PubMedCrossRefGoogle Scholar
  2. Arnsten, AF, Li, BM 2005Neurobiology of executive functions: catecholamine influences on prefrontal cortical functionsBiol Psychiatry5713771384PubMedCrossRefGoogle Scholar
  3. Arnsten, AF, Steere, JC, Hunt, RD 1996The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function: potential significance for attentiondeficit hyperactivity disorderArch Gen Psychiatry53448455PubMedGoogle Scholar
  4. Belfer, I, Buzas, B, Hipp, H, Phillips, G, Taubman, J, Lorincz, I, Evans, C, Lipsky, RH, Enoch, MA, Max, MB, Goldman, D 2005Haplotype-based analysis of _ 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each geneJ Hum Genet501220PubMedCrossRefGoogle Scholar
  5. Biederman, J, Spencer, T 1999Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorderBiol Psychiatry4612341342PubMedCrossRefGoogle Scholar
  6. Faraone, SV, Perlis, RH, Doyle, AE, Smoller, JW, Goralnick, JJ, Holmgren, MA, Sklar, P 2005Molecular genetics of attention-deficit/hyperactivity disorderBiol Psychiatry5713131323Jun 1PubMedCrossRefGoogle Scholar
  7. Friedel, S, Saar, K, Sauer, S, Dempfle, A, Walitza, S, Renner, T, Romanos, M, Freitag, C, Seitz, C, Palmason, H, Scherag, A, Windemuth-Kieselbach, C, Schimmelmann, BG, Wewetzer, C, Meyer, J, Warnke, A, Lesch, KP, Reinhardt, R, Herpertz-Dahlmann, B, Linder, M, Hinney, A, Remschmidt, H, Schafer, H, Konrad, K, Hubner, N, Hebebrand, J 2007Association and linkage of allelic variants of the dopamine transporter gene in ADHDMol Psychiatry1292333OctPubMedCrossRefGoogle Scholar
  8. Goldman, LS, Genel, M, Bezman, RJ, Slanetz, PJ 1998Council on Scientific Affairs, American Medical Association Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescentsJAMA27911001107PubMedCrossRefGoogle Scholar
  9. Hebebrand, J, Dempfle, A, Saar, K, Thiele, H, Herpertz-Dahlmann, B, Linder, M, Kiefl, H, Remschmidt, H, Hemminger, U, Warnke, A, Knolker, U, Heiser, P, Friedel, S, Hinney, A, Schafer, H, Nurnberg, P, Konrad, K 2006A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairsMol Psychiatry11196205FebPubMedCrossRefGoogle Scholar
  10. Khan, SA, Faraone, SV 2006The genetics of ADHD: a literature review of 2005Curr Psychiatry Rep8393397PubMedCrossRefGoogle Scholar
  11. Kurth, JH 2000Pharmacogenomics: a genetic tool for identifying patients at riskDrug Inform J34223227Google Scholar
  12. Lapiz, MD, Morilak, DA 2006Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capabilityNeurosci13710391049FebCrossRefGoogle Scholar
  13. Lario, S, Calls, J, Cases, A, Oriola, J, Torras, A, Rivera, F 1997MspI identifies a biallelic polymorphism in the promoter region of the alpha2A-adrenergic receptor geneClin Genet51129130PubMedCrossRefGoogle Scholar
  14. Markowitz, JS, Straughn, AB, Patrick, KS 2003Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder: focus on methylphenidate formulationsPharmacotherapy2312811299OctPubMedCrossRefGoogle Scholar
  15. McGough, JJ 2005Attention-deficitthyperactivity disorder pharmacogenomicsBiol Psychiatry5713671373PubMedCrossRefGoogle Scholar
  16. Park, L, Nigg, JT, Waldman, ID, Nummy, KA, Huang-Pollock, C, Rappley, M, Friderici, KH 2005Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHDMol Psychiatry10572580PubMedCrossRefGoogle Scholar
  17. Polanczyk, G, de Lima, MS, Horta, BL, Biederman, J, Rohde, LA 2007aThe worldwide prevalence of ADHD: a systematic review and metaregression analysisAm J Psychiatry164942948JunCrossRefGoogle Scholar
  18. Polanczyk, G, Zeni, C, Genro, J, Guimarães, AP, Roman, T, Hutz, MH, Rohde, LA 2007bAssociation of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorderArch Gen Psychiatry64218224CrossRefGoogle Scholar
  19. Polanczyk, G, Zeni, C, Genro, JP, Roman, T, Hutz, MH, Rohde, LA 2005Attention-deficit/hyperactivity disorder: advancing on pharmacogenomicsPharmacogenomics6225234PubMedCrossRefGoogle Scholar
  20. Roman, T, Polanczyk, G, Zeni, C, Genro, J, Rohde, LA, Hutz, M 2006Further evidence of the involvement of alpha-2A-adrenergic receptor gene (ADRA2A) in inattentive dimensional scores of ADHDMol Psychiatry11810PubMedCrossRefGoogle Scholar
  21. Roman, T, Schmitz, M, Polanczyk, GV, Eizirik, M, Rohde, LA, Hutz, MH 2003Is the alpha-2A adrenergic receptor gene (ADRA2A) associated with attention deficit/hyperactivity disorder?Am J Med Genet B Neuropsychiatr Genet120116120PubMedCrossRefGoogle Scholar
  22. Schmitz, M, Denardin, D, Silva, TL, Pianca, T, Roman, T, Hutz, M, Faraone, SV, Rohde, LA 2006aAssociation between alpha-2a-adrenergic receptor gene and ADHD inattentive typeBiol Psychiatry6010281033CrossRefGoogle Scholar
  23. Schmitz, M, Denardin, D, Silva, TL, Pianca, T, Hutz, M, Faraone, S, Rohde, LA 2006bSmoking during pregnancy and ADHD inattentive type: a case-control studyJ Am Acad Child Adolesc Psychiatry4513381345Google Scholar
  24. Spencer, T, Biederman, J, Wilens, T, Harding, M, O’Donnell, D, Griffin, S 1996Pharmacotherapy of attention deficit hyperactivity disorder across the lifespanJ Am Acad Child Adolesc Psychiatry35409428PubMedCrossRefGoogle Scholar
  25. Stevens, J, Quittner, AL, Abikoff, H 1998Factors influencing elementary school teachers’ rating ADHD and ODD behaviorsJ Clin Child Psychol27406414PubMedCrossRefGoogle Scholar
  26. Swanson, JM, Kraemer, HC, Hinshaw, SP, Arnold, LE, Conners, CK, Abikoff, HB, Clevenger, W, Davies, M, Elliott, GR, Greenhill, LL, Hechtman, L, Hoza, B, Jensen, PS, March, JS, Newcorn, JH, Owens, EB, Pelham, WE, Schiller, E, Severe, JB, Simpson, S, Vitiello, B, Wells, K, Wigal, T, Wu, M 2001Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatmentJ Am Acad Child Adolesc Psychiatry40168179PubMedCrossRefGoogle Scholar
  27. Waldman, ID, Nigg, JT, Gizer, IR, Park, L, Rappley, MD, Friderici, K 2006The adrenergic receptor alpha-2A gene (ADRA2A) and neuropsychological executive functions as putative endophenotypes for childhood ADHDCogn Affect Behav Neurosci61830PubMedCrossRefGoogle Scholar
  28. Wechsler D: WISC III/Manual (1991) The psychological corporation. New York, NYGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • T. L. da Silva
    • 1
  • T. G. Pianca
    • 1
  • T. Roman
    • 2
  • M. H. Hutz
    • 3
  • S. V. Faraone
    • 4
  • M. Schmitz
    • 1
  • L. A. Rohde
    • 1
  1. 1.From the ADHD Outpatient Clinic, Child and Adolescent Psychiatric DivisionHospital de Clínicas de Porto Alegre, Federal University of Rio Grande do SulRio Grande do SulBrazil
  2. 2.Department of Morphological SciencesFederal School of Medical Sciences of Porto AlegreRio Grande do SulBrazil
  3. 3.Department of GeneticsFederal University of Rio Grande do SulRio Grande do SulBrazil
  4. 4.Department of PsychiatryUpstate Medical UniversitySyracuseUSA

Personalised recommendations