Researchers tested 89 children with ADHD aged between 7 and 11 years and discovered that those with specific variants of the dopamine transporter (DAT) and dopamine receptor D4 (DRD4) genes demonstrated a bigger improvement in hyperactivity and impulsivity after taking methylphenidate compared with children who had alternative DAT and DRD4 versions.
Lead researcher Tanya Froehlich M.D., from Cincinnati Children's Hospital Medical Center explained:
"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. 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."
Froehlich's study is the first-ever placebo-controlled pharmacogenetic drug trial for ADHD that examines the effects of dopamine system genes variants in school-age children using teacher and parent ratings of children's symptoms. Considering that it is essential for ADHD children to function academically Dr. Froehlich stated that it is vital to consider the impact of medication at school as well as at home.
The researchers administered one week each of placebo and three different doses of methylphenidate to their ADHD participants. None of the participating children were taking stimulant medications for their ADHD at the start of the study. Parents and teachers both evaluated and scored the children's behavioral symptoms based on the Vanderbilt ADHD Parent and Teacher Rating Scales.
To establish which types of ADHD-related genes where found in the children, researchers analyzed the children's DNA from saliva samples. At first they focused on the four most frequent genes in ADHD, such as DRD4, DAT, COMT and ADRA2A.
They discovered that DRD4 and DAT, which are also the best-studied genes for ADHD, demonstrated the most powerful effect on methylphenidate dose-response in the participants.
Whilst the DRD4 gene encodes the dopamine receptor protein, that helps to control the synthesis and releases dopamine and the firing rate of neurons, the DAT gene encodes the dopamine transporter protein, which removes dopamine from the brain synapses.
Researchers observed a greater improvement after taking methylphenidate in children without what is known as the DAT 10-repeat variant compared to those who carried the 10-repeat. A "repeat" is a gene's repetition of a short nucleotide coding sequences. They also found that children without the DRD4 gene 4-repeat variant displayed less symptomatic improvement with methylphenidate compared to 4-repeat carriers.
Dr. Froehlich and team explained that while their findings are promising, further larger scale studies will be needed to replicate their results before confirming what they found.
Written by Petra Rattue