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New Gene Study of ADHD Points to Defects in Brain Signaling Pathways
Date:12/4/2011

ur genes with a significantly higher number of CNVs in children with ADHD. All the genes were members of the glutamate receptor gene family, with the strongest result in the gene GMR5. Glutamate is a neurotransmitter, a protein that transmits signals between neurons in the brain. "Members of  the GMR gene family, along with genes they interact with, affect nerve transmission, the formation of neurons, and interconnections in the brain, so the fact that children with ADHD are more likely to have alterations in these genes reinforces previous evidence that the GRM pathway is important in ADHD," said Hakonarson. "Our findings get to the cause of the ADHD symptoms in a subset of children with the disease."

"ADHD is a highly heterogeneous disorder, and separating out the different subgroups of genetic mutations that these children have is very important," said co-first author Josephine Elia, M.D., a child psychiatrist at Children's Hospital and an ADHD expert. She added that thousands of genes may contribute to the risk of ADHD, but that identifying a gene family responsible for 10 percent of cases is a robust finding in a common neuropsychiatric disorder such as ADHD. Overall, according to the CDC, 5.2 million U.S. children aged 3 to 17 have been diagnosed with ADHD.

Elia said the fact that their study identified gene variants involved in glutamate signaling is consistent with studies in animal models, pharmacology and brain imaging showing that these pathways are crucial in a subset of ADHD cases. She added, "This research will allow new therapies to be developed that are tailored to treating underlying causes of ADHD. This is another step toward individualizing treatment to a child's genetic profile."

Hakonarson expects this study will set the stage for further discoveries of ADHD-related genes along GMR signaling pathways. Moreover, the current research strongly suggests that selective GRM agonists could be
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SOURCE The Children's Hospital of Philadelphia
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