title: Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val⁶⁶Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children.
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 (8.7±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.
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Korea.
authors: Bung-Nyun
authors: BN
authors: Kim
authors: Tarrant D R
authors: TD
authors: Cummins
authors: Jae-Won
authors: JW
authors: Kim
authors: Mark A
authors: MA
authors: Bellgrove
authors: Soon-Beom
authors: SB
authors: Hong
authors: Sook-Hyung
authors: SH
authors: Song
authors: Min-Sup
authors: MS
authors: Shin
authors: Soo-Churl
authors: SC
authors: Cho
authors: Ji-Hoon
authors: JH
authors: Kim
authors: Jung-Woo
authors: JW
authors: Son
authors: Yun-Mi
authors: YM
authors: Shin
authors: Un-Sun
authors: US
authors: Chung
authors: Doug-Hyun
authors: DH
authors: Han
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D003692:Delayed-Action Preparations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; D014633:Valine