Association between homozygosity of a G allele of the alpha-2a-adrenergic receptor gene and methylphenidate response in Korean children and adolescents with attention-deficit/hyperactivity disorder

Biol Psychiatry. 2009 Apr 1;65(7):564-70. doi: 10.1016/j.biopsych.2008.12.003. Epub 2009 Jan 15.

Abstract

Background: Methylphenidate (MPH) blocks the norepinephrine transporter as well as the dopamine transporter. The alpha-2a-adrenergic receptor is a key component of the noradrenergic system. The aim of this study was to evaluate the association between the ADRA2A -1291 C>G polymorphism and the response to MPH treatment in Korean subjects with attention-deficit/hyperactivity disorder (ADHD).

Methods: This study enrolled 114 ADHD children (mean age = 9.08 +/- 1.94 years) from a child psychiatric clinic in South Korea. Subjects who had an improvement of >/= 50% compared with the baseline ADHD rating scale (ARS) score or who had a Clinical Global Impression-improvement score of 1 or 2 points after treatment were defined as the "good response". We examined the relationship of the ADRA2A to MPH response.

Results: We found that a good response to MPH treatment, measured by the ARS as assessed by the parents, was observed for 76.9% of the subjects carrying the G/G genotype but for only 46.0% and 41.7% of those with the C/G and C/C genotypes, respectively [chi(2)(2) = 11.929, p = .003]. We also found a significant difference in the change in total ARS scores between subjects with and without the G/G genotype [t(1) = 2.21, p = .029].

Conclusions: Our findings provide evidence of an association between the ADRA2A -1291 C>G genotype and response to MPH treatment in Korean subjects with ADHD. Nonetheless, the methodological limitation of not being a randomized placebo-controlled trial and primarily basing results on parent report to clinicians suggest that these results should be viewed as more preliminary.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Alleles
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Female
  • Homozygote*
  • Humans
  • Korea
  • Male
  • Methylphenidate / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Receptors, Adrenergic, alpha-2 / genetics*

Substances

  • ADRA2A protein, human
  • Central Nervous System Stimulants
  • Receptors, Adrenergic, alpha-2
  • Methylphenidate