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Article
Possible Involvement of Alpha-2A Adrenergic Receptors in Attention Deficit Hyperactivity Disorder: Radioligand Binding and Polymorphism Studies
American Journal of Medical Genetics Part B. Neuropsychiatric Genetics (2006)
  • J. D. Deupree, University of Nebraska Medical Center
  • S. D. Smith, University of Nebraska Medical Center
  • C. J. Kratochvil, University of Nebraska Medical Center
  • D. Bohac, University of Nebraska Medical Center
  • C. R. Ellis, University of Nebraska Medical Center
  • Jodi Polaha, University of Nebraska Medical Center
  • D. B. Bylund, University of Nebraska Medical Center
Abstract
Neuropharmacological and genetic association studies have implicated norepinephrine and adrenergic receptors in the pathogenesis of ADHD. The purpose of this study was to compare genetic association studies of three polymorphisms of the alpha‐2A adrenergic receptor gene (ADRA2A) with radioligand binding studies of the alpha‐2A adrenergic receptor protein in platelets from a sample of children without or with ADHD. The pediatric subjects ranged from 6 to 18 years of age. A thorough clinical assessment of each child resulted in one of the following DSM‐IV ADHD diagnoses: inattentive, hyperactive/impulsive, combined, or no ADHD. No significant linkage was found between the ADRA2A polymorphisms (MspI, HhaI, and DraI) and any of the phenotypes tested. Association analysis, however, did detect significant linkage disequilibrium for the DraI polymorphism. Association was also evaluated considering the three ADRA2A single nucleotide polymorphisms as haplotypes. The HhaI‐DraI and the MspI‐HhaI‐DraI haplotypes were significantly associated with ADHD. The platelet alpha‐2 adrenergic receptor density did not differ between children without or with ADHD. The affinity of the receptor for the radioligand however, differed significantly between those without and with ADHD. In addition, there were some significant correlations between binding parameters and severity of ADHD in this well‐characterized clinical population, and significant association was found between these measures of receptor function and MspI and DraI polymorphisms. Thus, both the genetic and the binding studies indicate that the alpha‐2 adrenergic receptor may play a role in ADHD. 
Disciplines
Publication Date
2006
DOI
10.1002/ajmg.b.30371
Citation Information
J. D. Deupree, S. D. Smith, C. J. Kratochvil, D. Bohac, et al.. "Possible Involvement of Alpha-2A Adrenergic Receptors in Attention Deficit Hyperactivity Disorder: Radioligand Binding and Polymorphism Studies" American Journal of Medical Genetics Part B. Neuropsychiatric Genetics Vol. 141B Iss. 8 (2006) p. 877 - 884 ISSN: 1552-485X
Available at: http://works.bepress.com/jodi-polaha/7/