New gene study of ADHD points to defects in brain signaling pathways
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 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.
Provided by Children's Hospital of Philadelphia
- ADHD genes found, known to play roles in neurodevelopment Jun 23, 2009 | not rated yet | 0
- Mutant gene linked to ADHD Apr 18, 2011 | not rated yet | 0
- New ADHD findings Nov 14, 2011 | not rated yet | 0
- Studies examine genetic determinants of ADHD Jan 07, 2009 | not rated yet | 0
- Study finds new ADHD genes, links susceptibility with autism and other neuropsychiatric conditions Aug 10, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Solvability of a circuit
2 hours ago Let's say I have a circuit consisting only of a finite number of batteries and resistors, all ideal. Given an arbitrary shape of this circuit, will I...
Question about perception of colors around light sources
6 hours ago When I look at a distant light source (like car headlights, or street lamp lights) I notice colors of the visible spectrum (as separated (as in after...
Does a charged particle rotate when traveling through a static Bf?
8 hours ago I have been looking at mass spectrometers, in particular the interactions between the Bf ind of a charged particle in motion in a static Bf of the...
Find a link between physics and assignment problems
9 hours ago Hi ! I've been working about assignments problems and how to solve them. I will have to do a presentation about it in few weeks. However, I'll...
Light as a source of electricity
9 hours ago Hello Dear Fellows! We all know that light is an electromagnetic wave and also we know that an antenna receives EM waves and...
A question about the energy stored in a capacitor.
9 hours ago If we imagine a simple circuit with a battery and a capacitor with negligible internal resistance, the capacitor is charged up to a point where the...
- More from Physics Forums - Classical Physics
More news stories
Researchers are interested in exploring how sunlight, sleep and screens (like those on computers and TVs) may affect those with attention-deficit/hyperactivity disorder (ADHD), says Dr. L. Eugene Arnold, a child psychiatrist ...
Attention deficit disorders May 17, 2013 | 5 / 5 (3) | 0
Long-term treatment of attention deficit/hyperactivity disorder (ADHD) with certain stimulant medications may alter the density of the dopamine transporter, according to research published May 15 in the open access journal ...
Attention deficit disorders May 15, 2013 | not rated yet | 0
Breastfeeding has a positive impact on the physical and mental development of infants. A new study suggests that breastfeeding may protect against the development of attention-deficit/hyperactivity disorder ...
Attention deficit disorders May 14, 2013 | not rated yet | 0
The stimulant drug methylphenidate "normalizes" activation of several brain areas in young patients with attention-deficit/hyperactivity disorder (ADHD), according to a review published in the May Harvard Review of Psychiatry. ...
Attention deficit disorders May 09, 2013 | 5 / 5 (2) | 0
90 percent of pediatric specialists not following clinical guidelines when treating preschoolers with ADHD
A recent study by pediatricians from the Cohen Children's Medical Center of New York examined to what extent pediatric physicians adhere to American Academy of Pediatrics (AAP) clinical guidelines regarding pharmacotherapy ...
Attention deficit disorders May 04, 2013 | 5 / 5 (1) | 0
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
8 hours ago | not rated yet | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
9 hours ago | 5 / 5 (2) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
9 hours ago | 5 / 5 (3) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
8 hours ago | 5 / 5 (1) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
13 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
8 hours ago | not rated yet | 0