Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder

Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder that often persists into adolescence and adulthood and is characterized by inappropriate levels of inattention, hyperactivity, and/or impulsivity. Genetic and environmental factors are believed to be involved in the continuity of the disorder as well as in changes in ADHD symptomatology throughout life. Neurotrophic factors (NTFs), which participate in neuronal survival and synaptic efficiency, are strong candidates to contribute to the neuroplasticity changes that take place in the human central nervous system during childhood, adolescence, and early adulthood and might be involved in the genetic predisposition to ADHD. Methods We performed a population-based association study in 546 ADHD patients (216 adults and 330 children) and 546 gender-matched unrelated control subjects with 183 single nucleotide polymorphisms covering 10 candidate genes that encode four neurotrophins (NGF, BDNF, NTF3, and NTF4/5), a member of the cytokine family of NTFs (CNTF), and their receptors (NTRK1, NTRK2, NTRK3, NGFR, and CNTFR). Results The single-marker and haplotype-based analyses provided evidence of association between CNTFR and both adulthood (p = .0077, odds ratio [OR] = 1.38) and childhood ADHD (p = 9.1e-04, OR = 1.40) and also suggested a childhood-specific contribution of NTF3 (p = 3.0e–04, OR = 1.48) and NTRK2 (p = .0084, OR = 1.52) to ADHD. Conclusions Our data suggest that variations in NTFs might be involved in the genetic susceptibility to ADHD, support the contribution of the CNTFR locus as a predisposition factor for the disorder, and suggest that NTF3 and NTRK2 might be involved in the molecular basis of the age-dependent changes in ADHD symptoms throughout life span.