Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val⁶⁶Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children

Int J Neuropsychopharmacol. 2011 Nov;14(10):1399-410. doi: 10.1017/S146114571100099X. Epub 2011 Jun 28.


Research on psychostimulants, analysis of animal models and genetic association studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be a good candidate for pharmacogenetic studies of attention deficit hyperactivity disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF in ADHD. A total of 102 drug-naive ADHD children (8.7±2.1 yr) were treated with osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds of response criteria were applied, based first, on a combined threshold of the ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale; third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of the aforementioned criteria. The Val⁶⁶Met polymorphism of BDNF and six single nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for association with each criterion. Relative to other genotypes, homozygosity for the Val allele of the BDNF Val⁶⁶Met polymorphism was associated with a greater relative frequency of good response under all four response criteria (after controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH at 12 wk, and level of academic functioning). This association was significant at the uncorrected level for the first and third response criteria (p=0.013 and p=0.018, respectively) and significant at a Bonferroni-corrected level for the second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our findings support an association between homozygosity for the Val allele of BDNF and better response to OROS-MPH in Korean ADHD children as assessed by four different response criteria.

Trial registration: NCT01012622.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Age Factors
  • Analysis of Variance
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Brain-Derived Neurotrophic Factor / genetics*
  • Central Nervous System Stimulants / administration & dosage*
  • Chi-Square Distribution
  • Child
  • Child Behavior / drug effects*
  • Delayed-Action Preparations
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Male
  • Methylphenidate / administration & dosage*
  • Pharmacogenetics
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Republic of Korea
  • Time Factors
  • Treatment Outcome
  • Valine


  • Brain-Derived Neurotrophic Factor
  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Methylphenidate
  • Valine

Associated data