Attention deficit hyperactivity disorder (
ADHD) is a prevalent neurodevelopmental childhood
psychiatric disorder. Brain-derived neurotropic factor (
BDNF) has been suggested to play a role in the pathogenesis of
ADHD and two family-based association studies demonstrated an association of
BDNF polymorphisms with
ADHD. The aim of the current study was to investigate the
BDNF gene for association with
ADHD in a large sample of families from Toronto. The transmission of three polymorphisms of the
BDNF gene (rs6265, rs11030104, and rs2049046) was examined in 266 nuclear families ascertained through a proband with
ADHD (315 affected children) using the transmission/disequilibrium test (TDT). In addition, we conducted quantitative analysis to assess the relationship between these marker alleles and the symptom dimensions of
ADHD (inattention and hyperactivity/impulsivity) and cognitive measures of working memory. None of the individual marker alleles showed significant evidence of association with
ADHD, dimensional symptom scores, or working memory ability in our sample of
ADHD families. There was no significant evidence for biased transmission of individual haplotypes with frequency >10% (global chi2 for these three haplotypes: chi2 = 6.349, df = 3, P = 0.096). One uncommon haplotype (A-G-G; frequency 2.2%) showed a significant association with
ADHD in the categorical (chi2 = 5.293, df = 1, P = 0.021) and quantitative analyses (parents' rated inattention: Z = -2.504, P = 0.012; and hyperactivity/impulsivity: Z = -2.651, P = 0.008). These results should be interpreted cautiously, however, because of the low haplotype frequency. In light of the evidence for an involvement of
BDNF in
ADHD, further analysis of the
BDNF gene in
ADHD is warranted.