Nicotinic acetylcholine receptor α4 subunit gene polymorphism and attention deficit hyperactivity disorder

Lindsey Kent, Fiona Middle, Ziarah Hawi, Michael Fitzgerald, Michael Gill, Cathy Feehan, Nick Craddock

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Attention deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder that presents in childhood and that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD: (a) nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers and non-smokers; (b) ADHD is a significant risk factor for early initiation of cigarette smoking in children; (c) maternal cigarette smoking appears to be a risk factor for ADHD; (d) animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity; and (e) a central nicotinic agonist, ABT-418, improves attention in both monkeys and ADHD adults. The current study examined the α4 receptor, one of the sites of action of ABT-418. A known Cfo1 polymorphism within the nicotinic acetylcholine α4 receptor gene, CHRNA4, was studied in 70 ADHD parent-proband trios from an ongoing sample collection of children aged 6-12 with ADHD, according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ <70) were excluded from the study. The Transmission Disequilibrium Test demonstrated no evidence that variation at the nicotinic acetylcholine α4 receptor Cfo1 polymorphism influences susceptibility to ADHD (P > 0.35). The continuing sample collection will enable further study of other potential nicotinic system polymorphisms in ADHD in more powerful samples.

Original languageEnglish
Pages (from-to)37-40
Number of pages4
JournalPsychiatric Genetics
Issue number1
Publication statusPublished - 2001
Externally publishedYes


  • Association study
  • Attention deficit hyperactivity disorder
  • CHRNA4
  • Genetics

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