No association between CHRNA7 microsatellite markers and attention-deficithyperactivity disorder

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, comm on psychiatric disorder of childhood that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system ma y be functionally significant in ADHD. First, nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, s mokers, and nonsmokers. Second, ADHD is a significant risk factor for early initiation of cigarette smoking in children and maternal cigarette smoking appears to be a risk factor for ADHD. Finally, animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems a nd locomotor activity. The nicotinic system has previously been studied in schizophrenia where the neuronal nicotinic acetylcholine receptor alpha7 su bunit gene (CHRNA7) has been implicated in decreased P50 inhibition and att entional disturbances in patients with schizophrenia and in many of their n onschizophrenic relatives. Three known microsatellite markers (D15S165, D15 S1043, and D15S1360) near the nicotinic acetylcholine alpha7 receptor gene, CHRNA7, were studied in 206 ADHD parent-proband trios of children aged 5-1 6 with ADHD according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded fr om the study. Markers D15S165 and D15S1360 were in linkage disequilibrium. The extended Transmission Disequilibrium Test analyses demonstrated no evid ence that variation at the microsatellite markers D15S1360, D15S1043, and D 15S165 influences susceptibility to ADHD. However, it remains possible that the CHRNA7 gene and other nicotinic system genes may be involved in confer ring susceptibility to ADHD. (C) 2001 Wiley-Liss, Inc.