Children with certain
dopamine system gene variants respond better to ADHD drug
Children with certain dopamine system gene
variants have an improved response to methylphenidate - the most
commonly prescribed medication for Attention Deficit Hyperactivity
Disorder - a finding that could help eliminate the guesswork from
prescribing effective medications for children with ADHD.
Researchers reporting their results in the Oct. 21 Journal of the
American Academy of Child and Adolescent Psychiatry tested 89 children
with ADHD between ages 7 and 11. They found that children with specific
variants of the dopamine transporter (DAT) and dopamine receptor
D4 (DRD4) genes showed greater improvement in hyperactivity and
impulsivity after taking methylphenidate compared to children with
alternative DAT and DRD4 versions.
"Physicians don't have a good way of predicting who will experience
great improvement in ADHD symptoms with a particular medication,
so currently we use a trial-and-error approach. Unfortunately, as
a result, finding an effective treatment can take a long time,"
explained Tanya Froehlich M.D., lead investigator on the study and
a physician in the division of Developmental and Behavioral Pediatrics
at Cincinnati Children's Hospital Medical Center.
"With more information about genes that may be involved in
ADHD medication response, we may be able to predict treatment course,
tailor our approach to each child, and improve symptom response
while decreasing health care costs," she added.
The study is the first-ever placebo-controlled pharmacogenetic
drug trial for ADHD in school age children to evaluate the effects
of dopamine system genes variants using teacher as well as parent
ratings of children's symptoms. Given the importance of academic
functioning for children with ADHD, Dr. Froehlich said it is crucial
to consider medication impact at school as well as at home. Children
in the study were not already taking stimulant medications for their
ADHD.
Participants were prescribed one week each of placebo and three
different doses of methylphenidate for their ADHD. Parents and teachers
assessed and scored the children's behavioral symptoms based on
the Vanderbilt ADHD Parent and Teacher Rating Scales.
The researchers analyzed DNA from saliva samples to see which ADHD-related
gene types the children carried. They looked initially at four genes
frequently implicated in ADHD - DRD4, DAT, COMT and ADRA2A. DRD4
and DAT, the most well studied genes for ADHD, showed the strongest
effects on methylphenidate dose-response in study participants,
according to the researchers.
The DRD4 gene encodes the dopamine receptor protein, which helps
control the synthesis and release of dopamine and the firing rate
of neurons. The DAT gene encodes the dopamine transporter protein,
which removes dopamine from the brain synapses.
Children who lack what is known as the DAT 10-repeat variant showed
greater improvement after taking methylphenidate compared to those
carrying the 10-repeat. Children without the DRD4 gene 4-repeat
variant showed less symptomatic improvement with methylphenidate
compared to 4-repeat carriers.
Dr. Froehlich and her colleagues indicate in their study that although
findings are promising, additional research is needed in larger
patient samples to confirm current study findings and their clinical
relevance.
Also collaborating on the study were researchers from the University
of Cincinnati College of Medicine, the University of Arkansas for
Medical Sciences, the University of Illinois (Chicago) and Duquesne
University. Funding support came from the National Institute of
Mental Health (NIH) and a Cincinnati Children's Hospital Medical
Center Education and Research Therapeutics Award.
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