An overview of the pharmacogenetics and molecular genetics of ADHD

Naomi Lowe, Edwina Barry, Michael Gill, Ziarih Hawi

Research output: Contribution to journalReview ArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, symptoms of which include inattentiveness, impulsiveness, distractibility and hyperactivity. Although the etiology of ADHD is not known, high heritability estimates (ranging from 60-90%) have been reported. The mode of inheritance is also unknown, however, it is widely believed that multiple susceptibility genes (each of small effect) are contributing to the liability of the disorder. Animal, pharmacological and molecular studies have implicated disruption in catecholamine neurotransmission (dopaminergic, serotonergic, and noradrenergic) in the etiology of ADHD. Recent genetic studies have identified ADHD susceptibility genes including DAT1, DRD4 and DRD5. In addition, there is evidence that DNA variation at the serotonin transporter (5-HTT), serotonin receptor 113 (5-HT1B) and the synaptosomal associated protein-25 (SNAP-25) genes contribute to susceptibility for ADHD. Genetic variants at these and other candidate genes have been examined for their potential to predict medication response in ADHD. Preliminary results are conflicting with no clear pattern emerging. However, the number of pharmacogenetic studies is limited and they are mainly focused on memylphenidate and variants etc. A more focused approach is required, examining genetic variation in genes involved kinetically and dynamically in medications used to treat ADHD. In this context, studies should be extended to include atomoxetine, a selective inhibitor of the noradrenergic transporter used in the treatment of ADHD. These studies might include a range a noradrenergic system genes.

Original languageEnglish
Pages (from-to)231-243
Number of pages13
JournalCurrent Pharmacogenomics
Volume4
Issue number3
DOIs
Publication statusPublished - Sep 2006
Externally publishedYes

Keywords

  • Attention deficit hyperactivity disorder (ADHD)
  • Dopaminergic
  • Genetic association
  • Methylphenidate
  • Pharmacogenetic
  • Serotonergic and noradrenergic systems

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