From Our 2011 Archives
ADHD: Genetic Mutation May Be Key
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Single-Letter Change in DNA Code May Spell ADHD
By Daniel J. DeNoon
Reviewed by Laura J. Martin, MD
April 18, 2011 – A single-letter change in the DNA code may spell ADHD, Korean researchers report.
ADHD -- attention deficit hyperactivity disorder -- makes it very hard for about 5% of school-aged children to learn. Kids with ADHD are impulsive and can't sit still. They can't focus their attention and have trouble learning and remembering.
It's not clear why some children get ADHD and others don't. Now Korean researchers report that children with ADHD tend to have a particular DNA misspelling -- a single-nucleotide polymorphism or SNP -- that affects an important brain function gene called GIT1.
Mice genetically engineered to carry this SNP are hyperactive and have poor learning and memory skills. But when given stimulant ADHD drugs, the mice become normal.
"Our study reveals a previously unidentified role of GIT1 in ADHD and establishes a new mouse model for ADHD," conclude Hyejung Won of the Korea Advanced Institute of Science and Technology and colleagues in the journal Nature Medicine.
Won and colleagues compared the genomes of 192 Korean children with ADHD to 196 age-matched children without ADHD. It was very rare for any child to inherit copies of gene mutation from both parents. But having just one copy of the mutation meant a 2.66-fold higher risk of ADHD.
Mice With ADHD Mutation Better With ADHD Treatment
Mice needed two copies of the mutant SNP to get ADHD, not just the single copy linked to ADHD in children. But these mice had nearly all the symptoms of human ADHD -- and just like children, their symptoms improved when they got stimulant ADHD drugs.
Just like some children with ADHD, mice with the ADHD genetic mutation tended to get over their ADHD when they grew up. At a mouse age of 7 months, equivalent to human age of 20 to 30 years, ADHD symptoms spontaneously went away.
What happens in the brains of children with ADHD? The mouse studies offer a clue.
Brain cells maintain a careful balance between excitation and inhibition. By affecting the function of the GIT1 gene, the ADHD-linked mutation makes brain cells more excitable.
SOURCE: Won, H. Nature Medicine, published online April 17, 2011.
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