Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val {66}Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children

Bung-Nyun Kim, Tarrant Cummins, Jae-Won Kim, Mark Andrew Bellgrove, Soon Beom Hong, Sook Hyung Song, Min Sup Shin, Soo-Churl Cho, J H Kim, Jung Woo Son, Yun Mi Shin, Un Sun Chung, Doug Hyun Han

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Abstract

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 (8.72.1 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 Val 66Met 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 Val 66Met 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.
Original languageEnglish
Pages (from-to)1399 - 1410
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume14
Issue number10
DOIs
Publication statusPublished - 2011
Externally publishedYes

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