More Evidence Links Specific Genes to ADHD

Future treatments might target these genetic pathways, researchers say

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SUNDAY, Dec. 4 (HealthDay News) -- Variations in genes involved in brain signaling pathways appear to be linked to attention-deficit/hyperactivity disorder (ADHD), according to a new study.

The findings suggest that drugs that act on these pathways may offer a new treatment option for ADHD patients with the gene variants, the Children's Hospital of Philadelphia researchers said.

In the study, researchers conducted whole-genome analyses of 1,000 children with ADHD and 4,100 children without ADHD. They then evaluated the findings in light of other research involving nearly 12,000 subjects -- 2,500 with ADHD and 9,200 without.

The genomic analysis revealed at least 10 percent of the children with ADHD had so-called "copy number variations" -- deletions or duplications of DNA sequences -- in four genes that are all part of the glutamate receptor gene family. The strongest result was in gene GMR5.

Glutamate is a neurotransmitter, a protein that transmits signals between neurons in the brain, the study authors explained in a hospital news release.

"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 GMR pathway is important in ADHD," study leader Dr. Hakon Hakonarson, director of the Center for Applied Genomics at Children's Hospital, said in the news release.

"Our findings get to the cause of the ADHD symptoms in a subset of children with the disease," he added.

One expert said the finding could prove to be significant.

"This study is important not only in that it has identified gene variants that are associated with ADHD in approximately 10 percent of cases, but it identifies novel treatment strategies related to the neurotransmitter glutamate that researchers can now try to develop for individuals with the newly identified gene variants," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Steven & Alexandra Cohen Children's Medical Center of New York in New Hyde Park, N.Y.

"This study provides further evidence not only that ADHD has a genetic basis in a distinct subset of children with ADHD but that the neurotransmitter glutamate seems to play a big role in some cases," he added. "Hopefully, these findings will allow researchers to identify safe and effective treatment strategies for the subset of children with ADHD who have variations in their glutamate-related genes."

The study was published online Dec. 4 in the journal Nature Genetics.

ADHD affects as many as 7 percent of school-age children and a smaller percentage of adults. Symptoms include short attention span, impulsive behavior and excessive activity. The causes are not known, but ADHD tends to run in families and is believed to be influenced by many interacting genes.

Adesman also noted that the technique used in this study, comparative whole-genome analysis, "may in the future identify other treatment opportunities for sub-groups of children with ADHD and other conditions."

More information

The American Academy of Family Physicians has more about ADHD.

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