An Overview of the Pharmacogenetics and Molecular Genetics of ADHD

Author(s): Naomi Lowe, Edwina Barry, Michael Gill, Ziarih Hawi.

Journal Name: Current Pharmacogenomics

Volume 4 , Issue 3 , 2006

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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 1B (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 numbers of pharmacogenetic studies to date are limited and are mainly focused on methylphenidate and variants at the dopaminergic system genes. 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.

Keywords: Attention deficit hyperactivity disorder (ADHD), pharmacogenetic, methylphenidate, dopaminergic, serotonergic and noradrenergic systems, genetic association

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Article Details

VOLUME: 4
ISSUE: 3
Year: 2006
Page: [231 - 243]
Pages: 13
DOI: 10.2174/157016006778195106
Price: $58

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