Navigation Links
New gene study of ADHD points to defects in brain signaling pathways
Date:12/4/2011

Pediatric researchers analyzing genetic influences in attention-deficit/hyperactivity disorder (ADHD) have found alterations in specific genes involved in important brain signaling pathways. The study raises the possibility that drugs acting on those pathways might offer a new treatment option for patients with ADHD who have those gene variantspotentially, half a million U.S. children.

"At least 10 percent of the ADHD patients in our sample have these particular genetic variants," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "The genes involved affect neurotransmitter systems in the brain that have been implicated in ADHD, and we now have a genetic explanation for this link that applies to a subset of children with the disorder."

The study appears online today in Nature Genetics.

ADHD is a common but complex neuropsychiatric disorder, estimated to occur in as many as 7 percent of school-age children and in a smaller percentage of adults. There are different subtypes of ADHD, with symptoms such as short attention span, impulsive behavior and excessive activity. Its causes are unknown, but it tends to run in families and is thought to be influenced by many interacting genes. Drug treatment is not always effective, particularly in severe cases.

The study team did whole-genome analyses of 1,000 children with ADHD recruited at The Children's Hospital of Philadelphia, compared to 4,100 children without ADHD. The researchers searched for copy number variations (CNVs), which are deletions or duplications of DNA sequences. They then evaluated these initial findings in multiple independent cohorts that included nearly 2,500 cases with ADHD and 9,200 control subjects. All the study subjects were children of European ancestry.

Among those cohorts, the research team identified four 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 tested in clinical trials as a potential therapy for ADHD in patients harboring particular CNVs. He added that further preclinical studies must first be done to evaluate candidate drugs.


'/>"/>
Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

Related medicine news :

1. Few Contact Lens Users Follow All Care Guidelines, Study Finds
2. Socioeconomic Status Main Predictor of Health Habits: Study
3. Police at No Greater PTSD Risk Than General Public: Study
4. Study shows many older Floridians have no backup plan after hanging up their keys
5. Circle of Friends Key to Adopting Healthy Habits: Study
6. Time of Surgery Doesnt Influence Results, Study Says
7. When babies awake: New study shows surprise regarding important hormone level
8. Many Ignore Symptoms of Lung Disease, Study Finds
9. More Exercise Could Make For Better Sleep: Study
10. Younger Americans Face Greater Health Disparities: Study
11. Study: Working moms multitask more and have worse time doing so than dads
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/26/2016)... ... May 26, 2016 , ... W.S. Badger Co. ... been honored with a 2016 When Work Works Award for its use of effective ... the national When Work Works project administered by the Families and Work Institute (FWI) ...
(Date:5/26/2016)... ... May 26, 2016 , ... Intalere, the healthcare ... suppliers for its inaugural Member Conference at the Paris Hotel in Las Vegas, ... operational health of America’s healthcare providers. , The conference was highlighted by the ...
(Date:5/26/2016)... , ... May 26, 2016 , ... Connor Sports, ... basketball as a partner for the Tamika Catchings Legacy Tour that will ... industry leader in hardwood basketball surfaces in all forms and levels of the game, ...
(Date:5/26/2016)... ... ... The Woodlands at John Knox Village , Florida’s first Life Plan ... and healing, celebrated its grand opening, today. The Woodlands at John Knox Village is ... Staff. , “This is an incredibly fulfilling time for John Knox Village as we ...
(Date:5/26/2016)... ... May 26, 2016 , ... There are nearly 14.5 million people living ... survivors worldwide. On Sunday, June 5, 2016, communities around the world will gather to ... , National Cancer Survivors Day® is an annual worldwide Celebration of Life that ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... PARIS , May 25,2016 ... with the near-infrared Cellvizio platform for urological and ... MKEA, OTCQX: MKEAY) inventor of Cellvizio®, the multidisciplinary ... important regulatory milestone in the US with the ... Food and Drug Administration (FDA). This new FDA ...
(Date:5/25/2016)... and GERMANTOWN, Maryland , May 25, 2016 ... ; Frankfurt Prime Standard: QIA) today announced that the company ... Diagnostics GmbH to develop and commercialize predictive assays in oncology. ... as a marker to predict effectiveness of anthracycline treatment in ... "We are pleased to partner with Therawis, which developed the ...
(Date:5/25/2016)... May 25, 2016 According to ... Development, Growth and Demand Forecast to 2022 - Industry ... and Others)" published by P&S Market Research, the global ... in 2015, and it is expected to grow at ... the insulin pump segment is expected to witness the ...
Breaking Medicine Technology: