Adrenergic α2A receptor gene and response to methylphenidate in attention-deficit/hyperactivity disorder-predominantly inattentive type
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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
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References
- 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
- Arnsten, AF, Li, BM 2005Neurobiology of executive functions: catecholamine influences on prefrontal cortical functionsBiol Psychiatry5713771384PubMedCrossRefGoogle Scholar
- 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
- 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
- Biederman, J, Spencer, T 1999Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorderBiol Psychiatry4612341342PubMedCrossRefGoogle Scholar
- Faraone, SV, Perlis, RH, Doyle, AE, Smoller, JW, Goralnick, JJ, Holmgren, MA, Sklar, P 2005Molecular genetics of attention-deficit/hyperactivity disorderBiol Psychiatry5713131323Jun 1PubMedCrossRefGoogle Scholar
- 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
- 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
- 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
- Khan, SA, Faraone, SV 2006The genetics of ADHD: a literature review of 2005Curr Psychiatry Rep8393397PubMedCrossRefGoogle Scholar
- Kurth, JH 2000Pharmacogenomics: a genetic tool for identifying patients at riskDrug Inform J34223227Google Scholar
- Lapiz, MD, Morilak, DA 2006Noradrenergic modulation of cognitive function in rat medial prefrontal cortex as measured by attentional set shifting capabilityNeurosci13710391049FebCrossRefGoogle Scholar
- 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
- Markowitz, JS, Straughn, AB, Patrick, KS 2003Advances in the pharmacotherapy of attention-deficit-hyperactivity disorder: focus on methylphenidate formulationsPharmacotherapy2312811299OctPubMedCrossRefGoogle Scholar
- McGough, JJ 2005Attention-deficitthyperactivity disorder pharmacogenomicsBiol Psychiatry5713671373PubMedCrossRefGoogle Scholar
- 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
- 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
- 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
- Polanczyk, G, Zeni, C, Genro, JP, Roman, T, Hutz, MH, Rohde, LA 2005Attention-deficit/hyperactivity disorder: advancing on pharmacogenomicsPharmacogenomics6225234PubMedCrossRefGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- Stevens, J, Quittner, AL, Abikoff, H 1998Factors influencing elementary school teachers’ rating ADHD and ODD behaviorsJ Clin Child Psychol27406414PubMedCrossRefGoogle Scholar
- 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
- 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
- Wechsler D: WISC III/Manual (1991) The psychological corporation. New York, NYGoogle Scholar
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