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A genetic variation that boosts risk for Attention Deficit Hyperactivity Disorder (ADHD) paradoxically appears to predict who will grow out of the learning disability. Scientists found that brain development in ADHD-afflicted children with this variation was out of whack at age 8 but normalized by 16. ADHD symptoms in this group were also more likely to disappear with age. The study is the first to identify a genetically determined pattern of brain development linked to ADHD and indicates a real neurological basis for the disorder, which has been viewed by some as a contrivance of pharmaceutical marketers or the product of bad parenting.

“This is the first step in individualizing treatment for ADHD based on genetic make-up,” says Philip Shaw, a neuroscientist at the National Institute of Mental Health in Bethesda, MD, who led the study.

ADHD is one of the most common childhood disorders in the United States, affecting about three to five percent of school-aged kids. Scientists have already uncovered several genetic variations that raise risk for ADHD, which is likely caused by a complex combination of genetic and other factors. The biggest genetic culprit identified to date is a variation in a receptor for dopamine–one of the brain’s signaling molecules–which increases risk for the disorder by 20 to 30 percent.

To try to understand how this variation influences attention, Shaw and colleagues scanned the brains of 105 children with ADHD and 103 healthy controls between 8 and 16 years old, repeating the scans in a subset of children through their teen years. They also determined how many copies, if any, the children carried of the target variation.

Scientists found that ADHD-afflicted children with the high-risk genetic variation seemed to be worst off at younger ages–parts of the cortex crucial for attention were thinner in this group than in both their normal counterparts and in children with ADHD lacking that variation. However, the high-risk variant group also showed the best chance of recovery. In contrast to other children with ADHD, the cortices of these children naturally normalized by age 16. Like gangly teenagers growing into their too-long limbs, they were also most likely to have grown out of their ADHD symptoms. “People who have the risk gene have a distinctive pattern of brain growth that normalizes with age,” says Shaw. “That might be what’s driving the good clinical outcome they have.” The findings were published this week in the Archives of General Psychiatry.

Scientists don’t yet know exactly how this genetic marker contributes to differences in brain size or in behavior. But previous research has shown that receptors with the variation don’t respond to dopamine as effectively as other forms of the gene. “That biological action of the brain may help to explain why in this study, the cortical thickness was thinner in the people who carried this variant,” says James Kennedy, professor of psychiatry at the University of Toronto. “The reasoning would be that people with that allele would have a bit less nerve transmission activity in areas of their brain where this is located.” Kennedy likens grey matter in the brain to muscle, which gets bigger with exercise. “The more you use it, the more synapses are formed and the more volume is created.”

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Credit: Philip Shaw, M.D., NIMH Child Psychiatry Branch

Tagged: Biomedicine, neuroscience, genetics, ADHD

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