ADHD - Four Genes Linked To The Disorder
Editor's ChoiceAcademic Journal
Main Category: ADHD
Also Included In: Neurology / Neuroscience; Genetics
Article Date: 06 Dec 2011 - 0:00 PST
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Four gene variants, all members of the glutamate receptor gene family, appear to be involved in vital brain signaling pathways in a sub-set of children with ADHD (attention deficit hyperactivity disorder), researchers from the Center for Applied Genomics at The Children's Hospital of Philadelphia reported in the journal Nature Genetics. The authors add that their findings could help create drugs that target those pathways, offering potential therapies for ADHD patients with those specific gene variants. There are an estimated half-a-million American children with ADHD and these gene variants.
Study leader Hakon Hakonarson, M.D., Ph.D., said:
"At least 10 percent of the ADHD patients in our sample have these particular genetic variants. 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."
ADHD is fairly common and tends to run in families
ADHD, which is thought to affect about 7% of kids of school age and a smaller percentage of adults, is a complex neuropsychiatric disorder. ADHD has several subtypes, with varying symptoms that may include short attention span, impulsivity, and overactivity.ADHD tends to run in families, nobody is sure what causes it - scientists and experts believe it is mainly caused by many genes which interact in certain ways. Although drugs are frequently prescribed for ADHD, they do not always work, especially if symptoms are severe.
The researchers carried out a study involving 1,000 kids with ADHD from a database at the Children's Hospital of Philadelphia; they were compared with 4,100 others of the same age who did not have ADHD (controls). They did whole-genome analyses of all of them.
Researchers looked for duplications or deletions of DNA sequences
The scientists were looking for CNVs (copy number variations) - duplications or deletions of DNA sequences. They then compared these preliminary findings with various cohorts, made up of 2,500 kids with and 9,200 without ADHD. All the children where Caucasian.They identified four genes with a considerably greater number of CNVs in the ADHD children. They were all glutamate receptor (GMR) genes. The one with the strongest result was gene GMR5.
Glutamate is an amino acid, one of the 20 AAa used to make all of the proteins in our body, it transmits signals between brain neurons - it is a neurotransmitter.
GRM pathway is important in ADHD
Hakonarson said:"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. Our findings get to the cause of the ADHD symptoms in a subset of children with the disease."
Co-first author Josephine Elia, M.D., said:
"ADHD is a highly heterogeneous disorder, and separating out the different subgroups of genetic mutations that these children have is very important."
Dr. Elia, an ADHD expert, explains that thousands of genes may be involved in ADHD risk. However, finding a gene family which might be a major contributory factor in 10% of ADHD cases is a major breakthrough. 5.2 million children in the United States have been diagnosed with ADHD (overall), says the CDC (Centers for Disease Control and Prevention).
Their findings are consistent with those done with animal models, brain imaging studies and other investigations, Elia wrote, showing that these pathways play a vital role in certain types of ADHD cases.
New ADHD therapies may be developed
Dr. Elia explained:"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 believes his team's findings will trigger further research and subsequent discoveries of ADHD-related genes along the GMR signaling pathways. According to current research, carefully selected GRM agonists could be used in human studies to determine whether they might have potential as therapies for ADHD patients with particular CNVs. Preclinical studies will need to be carried out first on candidate medications.
Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Josephine Elia, Hakon Hakonarson, Joseph T Glessner, Kai Wang, Nagahide Takahashi, Corina J Shtir, Dexter Hadley, Patrick M A Sleiman, Haitao Zhang, Cecilia E Kim, Reid Robison, Gholson J Lyon, James H Flory, Jonathan P Bradfield, Marcin Imielinski, Cuiping Hou, Edward C Frackelton, Rosetta M Chiavacci, Takeshi Sakurai, Cara Rabin, Frank A Middleton, Kelly A Thomas, Maria Garris, Frank Mentch, Christine M Freitag, Hans-Christoph Steinhausen, et al.
Nature Genetics (4th Dec, 2011) doi:10.1038/ng.1013
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23 Feb. 2012. <http://www.medicalnewstoday.com/articles/238664.php>
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Visitor Opinions In Chronological Order (12)
May, at least 10 percent, possibly, any more uncertainty?
posted by Marcus Stephens on 5 Dec 2011 at 2:18 pmThe one single element highlighting these studies is the lack of certainty. "appear", "at least 10 percent", it is believed etc... It just seems more like science fair than life saving discoveries.
Toxins?
posted by tina on 5 Dec 2011 at 3:00 pmCould problems with neurotransmitters be effected by toxins that attack neurotransmitters, such as those recently banned in the E.U.? I mean, is such genetic damage ONLY transmitted through inheritance?
Lefthandedness Disorder
posted by Steve on 5 Dec 2011 at 5:09 pmLefthandedness would be considered a disorder if all kids were forced to use their right hands.
The cause of "disorder" is not this particular variety of genetic diversity. It's our educational, medical and pharmaceutical institutions' self-serving insistence that all children should think, do and perform like each other.
Our society has created a tortuous environment for the kids who, years ago, would have simply grown up to be exactly what nature had in store for them, in their own fantastic or mundane ways.
People need to stop this madness of labeling differences as ailments to cure. Stop trying to make your kids what they hate. Find a way to support their own interests and watch how attentive they become.
If you can't see that your kids aren't actually broken, then you're part of their problem.
Flame on.
The truth that Giant Pharma won't allow
posted by Hugh Massengill on 6 Dec 2011 at 5:56 amSteve is terribly right. Of course certain "disorders" seem to have a genetic base, when you set out to define normal in an abnormal way, when you ignore their trauma and needs.
Want to understand someone's disorder? Simply draw out three lines, a lifeline with life trauma, a social services available line, and a third lifeline for the parents or caregivers. That explains so much.
Hugh
ADHD
posted by Dee on 8 Dec 2011 at 7:06 amI was born with ADHD. I did not mind the excess energy, I did mind that inner nervous tension within me. It was hard for me to learn and retain Info. and I would sometimes feel spaced out. As an adult I found this book called "A Touch of Life' by Robert Fulford. Robert Fulford was a Osteopathic doctor who healed children with ADD & ADHD. I found a Osteopath in NYC who healed my ADHD symptoms with Cranial Sacral theatment. I felt like a new person. Craniosacral therapy is the gentle manipulation of the bones of the skull to restore balance to the whole body.
After my healing I brought my daugther to him she was born with a math disability. Dyscalculia is a specific math learning disability involving innate difficulty in learning or comprehending simple arithmetic. Later on my Osteopath gave me an Osteoapth adjustment for my sudden onset of Hypoglycemia (low blood sugar). I was permanently healed. When the body is out of alignment it can cause all kinds of health problems.
Appears baloney
posted by Thomas on 9 Dec 2011 at 3:29 amWhether this is substantial in any way, beyond all the crappy formulations, is not possible to derive.
They appear to have burned a lot of resources and came up with the result:
"At least 10 percent of the ADHD patients in our sample have these particular genetic variants. ... We now have a genetic explanation ... that applies to a subset of children with the disorder."
Did they also check the subjects astrological profile? I would ques that about 10 percent would be born it the sign of the Capricorn.
Leave them alone
posted by Dial on 10 Dec 2011 at 2:43 pmI'm with you, Steve. The genes run in my family, but hey, where would we be without ADHD? We are all supposed to be different, an essential element of 'survival of the species'. If it ain't broke, don't fix it. Nobody thought about 'fixing' Einstein, Columbus, and all the other famous people with ADHD. In fact, after googling that list, I'm surprised they aren't trying to develop a drug that mimics ADHD.
Opinionated
posted by Tiffany on 12 Dec 2011 at 8:23 amThis article does have some bones to it - as with anything scientific you have to start with an idea.
What's difficult is reading the opinions of others who have no idea what it's like for my child to have ADHD. He made noises, didn't sit still and rambled on so badly that no one wanted to be friends with him. He had a label of "weird" and no friends - at all. Imagine that torment. His medicine has made him feel important, relaxed and smarter. He says he feels like he can think before he reacts now. He still does some of these things because we don't have him on the highest dosage - it's just enough to help him control the outbursts.
He's now a straight A student, with a healthy self esteem, a lot of friends and a great imagination.
I am not surprised this is a genetic disorder - my mother didn't graduate school. She couldn't make it past the ninth grade and has always believed she's just "stupid". Just think of her possibilities if in the 50's they could've helped her.
Opinions are great - but as this study is doing - do some research before you judge so absolutely.
Re-Opionionated
posted by Steve on 19 Dec 2011 at 8:43 am@Tiffany
I'm glad you've found a satisfactory way to treat your son, and I take your statement to heart. However, I believe that many ADHD diagnoses and prescriptions are not for kids with such a severe affliction that causes universal disorder.
I think that doctors, teachers and parents are failing to properly distinguish a growing population of kids who are labeled with "disorder", out of convenience or, skeptically, profit for drug companies. Too many "weird" or challenging kids are being labeled sick, and drugged for the sake of conformance, or lack of creative options.
My point is to suggest adults' greater acceptance and appreciation of kids' differences (yes, even more severe ones) and don't "judge so absolutely" that a child is broken and can only be fixed with drugs, or needs to be fixed at all. Often, it is still the situations we create that give rise to the disorder suffered.
I agree that research is valuable, but this article discussing "genes linked to disorder" is another example how the industry systematically discounts a natural view, and just as conveniently jumps to drugs as the uncontested answer.
Notice this statement from the first paragraph: "The authors add that their findings could help create drugs that target those pathways, offering potential therapies for ADHD patients with those specific gene variants."
Are these genes a recent mutation or a longstanding part of humanity's genetics? Before deciding to "target" anything, are they first going to research how long the genes have existed? If some humans have always been this way, are they simply assuming nature just got it WRONG and they are all diseased?
Well, something is very wrong. According to the CDC, 5.2 million U.S. children aged 3 to 17 have been diagnosed with ADHD. This is about 8% of our children. So, either:
A) Nature/Evolution/God got it wrong and we need to fix kids with drugs.
B) Nature/Evolution/God got it right and we need to fix parents, teachers and doctors with new attitudes.
C) Something new is mutating kids' genes and we need to fix THAT.
Not all or nothing
posted by Tara on 24 Dec 2011 at 8:43 amNo one should be diagnoised w/ ADD/ADHD without a nueropsychological evaluation. There may be way too many people diagnoised with this, but that does not mean it does not exsist. The all or nothing mentality is not scientific. I have SEVER ADD. Medication keeps me functional-however, I am not sure I would ever give a child medication unless absolutely nessisary. And I also agree that our society that expects everyone to be "fast and accurate" robots really makes the problem worse. Even on medication, I have trouble finding jobs I can do well. ADD often gets labled a learning disablity, and supposidly people grow out of it. It is actually considered a mental illness, and my guess is if you grow out of it you just grow up and learn how to sit still. To me, a person does not TRUELY have ADD/ADHD unless as an adult their ablity to work a job or function in everyday life impairs them. The reason the illness is not respected is because it is over diagnoised. Those who do not have ADD say "OMG like I am so ADD!" when they forget to do something. No one (I hope) goes around saying "I am like so scizophrenic" like it is some kind of joke! ADD is the worlds first and finest exceptable mental illness so people assume it is a minor problem that doctors make it up. This is what happens when dr. hand out pills in pez despensers-the people who actually need them are looked down upon as guilable and not taken serviously.
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