Ok, it is still too early to be popping the corks, but this does look to be the most promising lead to date in the hunt for the elusive genetic tie-in to ADHD…
Location of Major Gene in ADHD Found; Targeted Region Also Linked To Autism Research by UCLA Geneticists
http://www.eurekalert.org/pub_releases/2002-10/uoc—ugf102202.php
UCLA Neuropsychiatric Institute researchers have localized a region on chromosome 16 that is likely to contain a risk gene for Attention Deficit Hyperactivity Disorder, the most prevalent childhood-onset psychiatric disorder.
Their research, published in the October edition of the American Journal of Human Genetics, suggests that the suspected risk gene may contribute as much as 30 percent of the underlying genetic cause of ADHD and may also be involved in a separate childhood onset disorder, autism.
Pinpointing a gene with a major role in ADHD will help researchers and clinicians better understand the biology of this disorder and likely lead to the development of improved diagnosis, treatment and early intervention.
“We know there are about 35,000 genes in the human genome. By highlighting this region on chromosome 16, we have narrowed our search for a risk gene underlying ADHD to some 100 to 150 genes,” said Susan Smalley, principal investigator of the study and co-director of the Center for Neurobehavioral Genetics at the UCLA Neuropsychiatric Institute.
“Still, we must wait for independent replication of our results to confirm these findings,” said Smalley, also a professor of psychiatry and biobehavioral sciences at the David Geffen School of Medicine at UCLA. “Ultimately, we must identify the specific risk gene from among the 100 to150 genes in this region before we can move to the next level of using such findings to help individuals with ADHD.”
By studying families in which there are two or more ADHD siblings, the investigators were able to “scan” the entire human genome, containing some35,000 genes, to focus in on specific regions likely to contain a gene contributing to ADHD.
In their initial scan, several regions showed modest support for a risk gene; however, in a follow-up study of one region on chromosome 16,evidence of a risk gene was striking — with favorable odds of 10,000 to 1.Surprisingly, independent studies have implicated the same region as harboring a risk gene for autism, suggesting that ADHD and autism may have some common genetic underpinnings. Whether a common gene contributes to both remains to be determined.
ADHD and autism are very distinct clinical conditions. Although certain features are shared, the underlying biological mechanisms are thought to be distinct. If a common risk gene on chromosome 16 were found to underlie ADHD and autism, Smalley said, the finding would illustrate that genes affecting neurobiological mechanisms can cut across clinical boundaries, as most geneticists suspect.
“This study provides compelling evidence that ADHD and autism may have a lot more in common than we ever thought, with implications for both diagnosis and treatment,” Smalley said. “However, further investigation is required to determine the significance of this finding, as it is also quite feasible that distinct risk genes underlying each condition just happen to be in close proximity on chromosome 16.”
UCLA researchers spent five years collecting clinical, cognitive and genetic data from 203 families with multiple ADHD children. Their initial search for shared DNA markers suggested regions on chromosomes 16, 10 and12. Focusing their attention on chromosome 16, researchers found a series of molecular “markers” shared among sibling pairs at a rate higher than the 50 percent sharing expected due to their degree of relationship.
Based on the observed degree of DNA sharing among ADHD siblings, the researchers estimate that the risk gene — if replicated by other scientists studying ADHD — might account for as much as 30 percent of the genetic cause of ADHD. As with any initial finding, however, the investigators caution that replication is necessary and that significant work with more families will be needed to find a specific risk gene in that location.
Previous investigations into a genetic cause for ADHD have focused on specific candidate genes, such as those involved in regulation of dopamine, a chemical in the brain implicated in ADHD. Previous studies of dopamine receptor genes (whose products are important in releasing dopamine in the cells) and dopamine transporter genes (whose products are involved in movingdopamine between cells) suggest they may also be involved in ADHD. The riskfor ADHD in individuals carrying these genes, however, is very small, maybe1.2 to 1.5 times the risk of those without such genes.
ADHD is the most common childhood-onset behavioral disorder, affecting as many as one in 10 children and three times as many boys as girls. Symptoms of both inattention and hyperactivity, which can last into adulthood, can affect school and work performance as well as social skills. Researchers estimate that the cause of ADHD is 70 percent to 80 percent genetic, and the remainder largely environmental.
Autism is a neurological disorder that affects perhaps as many as one in 500 children and usually appears within the first three years of a child’s life. It affects the brain in the areas of social interaction and communication. Autism, like ADHD, is thought to be due to multiple genetic and environmental factors, although genetics seems to dominate, with more than 60 percent to 70 percent of the underlying cause of autism thought to be genetic.
The National Institute of Mental Health, a University of California BioStar grant and the Wellcome Trust, through the Wellcome Trust Centre for Human Genetics in Oxford, England, provided financial support for the research.
A team of investigators at UCLA and the Wellcome Trust Center for Human Genetics in Oxford conducted the research. The UCLA team includes Stanley F. Nelson and members of his lab, Vlad Kustanovich, Jennifer Stone and Matthew Ogdie of the UCLA Center for Neurobehavioral Genetics and Department of Human Genetics; James J. McGough and James T. McCracken of the UCLA Department of Psychiatry and Biobehavioral Sciences; Rita M. Cantor of the UCLA Department of Human Genetics; and Sonia L. Minassian of the UCLA Center for Neurobehavioral Genetics and Department of Biostatistics. The team from Wellcome Trust Centre for Human Genetics, led by Anthony P. Monaco, includes Simon E. Fisher, Laurence MacPhie and Clyde Francks.
The UCLA Neuropsychiatric Institute is an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders.
Research at the Institute’s Center for Neurobehavioral Genetics focuses on the discovery of the genetic basis of major neurobehavioral disorders, including autism, attention deficit hyperactivity disorder, dementias, depression, manic-depressive illness (bipolar disorder) and schizophrenia.
Re: Location of Major Gene in ADHD Found
It would seem to me that a logical outcome might be better ability to diagnose ADHD. Right now, ADHD is diagnosed as a residual disorder–problems consistent with the disorder that can not be explained any other way. This becomes very difficult with complex kids who have processing problems that may account for some of the symptoms. Some of these kids suffer from both processing problems and ADHD but very difficult to tease out, given current knowledge.
More definitive testing would also eliminate the bias that some have towards ADHD—those are kids that just need to be parented better.
Beth
This is one of the most important points
“It would seem to me that a logical outcome might be better ability to diagnose ADHD. …More definitive testing would also eliminate the bias that some have towards ADHD—those are kids that just need to be parented better.”
Accuracy in dx and elimination of false presumptions (ie ADHD does not exist) are two of the most important results that identification of a genetic marker would bring.
Another is a better understanding of the bio-mechanics of ADHD, which could lead to a safer and more effective method of treatment than current use of heavy stimulants (if we could treat the true source we may not have to treat the symptoms).
And finally, if we can identify the genetics, there is a strong possibility that we can identify the environmental triggers which cause the genes to express, thereby avoiding ADHD altogether.
This is one of the most important points
“It would seem to me that a logical outcome might be better ability to diagnose ADHD. …More definitive testing would also eliminate the bias that some have towards ADHD—those are kids that just need to be parented better.”
Accuracy in dx and elimination of false presumptions (ie ADHD does not exist) are two of the most important results that identification of a genetic marker would bring.
Another is a better understanding of the bio-mechanics of ADHD, which could lead to a safer and more effective method of treatment than current use of heavy stimulants (if we could treat the true source we may not have to treat the symptoms).
And finally, if we can identify the genetics, there is a strong possibility that we can identify the environmental triggers which cause the genes to express, thereby avoiding ADHD altogether.
Re: This is one of the most important points
Currently, ADD (without hyperactivity) is considered a subtype of ADHD. It is ADD-inattentive with which my son has been diagnosed. You don’t get the poor parenting attributions with ADD-inattentive but I think it is even more difficult to separate from other types of processing issues.
Beth
Re: This is one of the most important points
I have struggled with the idea that processing disorder leads to poor attention. I also wonder how much poor attention as the the primary cause would not affect processing.
It surely seems to vary child to child but I am stuck with the picture of the brain being an organ with many moving parts. All the pieces need to be functioning or else other parts become affected.
I really believe all of this can be dealt with in several ways. An improvement in any area will affect other parts.
I think that is why meds help some kids seem to process better. I will try biofeedback first. I still look at meds as the last ditch effort, but I don’t see why you shouldn’t go after attention directly in other ways if that it is an area the child has a problem with. (I know for other kids with different problems, meds are the answer. I hope no one sees this as a judgement call. We all have to do what is right for our child.)
Re: This is one of the most important points
It is hard to know. My son’s resource teacher wrote me a note yesterday that his auditory processing is so much improved over last year. I guess she gave him a writing assignment and he told her in detail all the steps of it.
I actually think this might be partly attention. Last year he would just zone out. One on one at home he was quite capable of telling you detailed information (after we did Fast Forward after first grade which dramatically improved his receptive language skills).
I think every one has to find their own place with the meds issue. I know I got to the place last year when my son was struggling so, despite tons of intervention on our part, that it seemed like meds were worth a try. I thought that if they could make learning easier for my son, who had to work so hard, it might be almost a miracle.
Beth
Re: This is one of the most important points
Beth,
I am seeing the same thing with my son. Since doing IM I have seen gains in what I can only think is attention. He has better attention which now helps me to see that it was never that he didn’t get it, but rather that he wasn’t paying attention. When he pays attention things come to him very quickly. Other times he will bring home work and say, “I didn’t do that, I know how to do that and wouldn’t have done it that way.” It’s weird, almost like he is two children. He also has difficulty paying attention to the easier work, he does better on work that is more challenging.
He has gotten so much better with his attention with IM that I am encouraged that he can go even further with other types of therapy and more IM. If he needs meds, he will get them, but not until I try a few more things first.
Linda
We are seeing improvements in attention too..
which could very well be from IM. Hard to say because its creeping up on us, not a sudden change. But its there. Unfortunately I would say attention is more a problem this year at school than last, which is a reflection of the fact that 3rd grade is more demanding, and there are more children in his class.
I also ponder how much anxiety affects attention (along with processing speed). I know it plays a part, so that’s another facet to address.
Re: We are seeing improvements in attention too..
This is all quite interesting because I’ve been wondering if my son may have ADD (without the hyperactivity) or if his problems are specifically SID/RAN deficit/word retrieval.
Is the problem due to attention or is there are processing “glitch” or maybe it’s both? Kind of like…what came first; the chicken or egg?
Without good reliable testing for ADD, I don’t know how I’d truly figure out the answer to this question. We did the Conner questionaire last year, but I don’t feel it’s a reliable test. It seemed much too subjective. For example, I know that the answers this year’s teacher would give, would be very different from those last year’s teacher indicated. Also, for those “symptoms” that resemble attention deficit, how do I know they are not caused by something else?
I’m glad to hear UCLA has made some progress in researching the genetic component in ADHD. Perhaps it may lead to an answer.
Re: We are seeing improvements in attention too..
I don’t think you can truly know. My son was diagnosed by a leading neurologist as add-inattentive this summer. The forms (not Conner’s but another) were very suggestive of ADD. But the clincher for me was when he told me that most all kids with severe LD (which is my son) are ADD-inattentive. And, get this, if medication did not work, then it is because his LD is too severe. So he gets to be right, no matter what!!!!
The therapist he has worked with for some time thinks it is processing not ADD. And I, the parent, well…… I have cancelled two doctor appt. to discuss medication. He is doing much better this fall post IM and the Neuronet therapist does not want to do Neuronet with him while we are doing a trial of medication. So, I have decided to continue to work on processing issues while keeping an eye on school.
Me—well my gut feeling is that he is ADD-inattentive but that there are processing issues as well.
I would love an objective test so we wouldn’t have to wring our hands over this stuff!!
Beth
Yes, inattentive but why?...
It seems like there are so many reasons why a kid might be inattentive, and who knows if its really ADD ,( as in we can now scan your brain or look at your chromosome and tell ) ….And a meds trial doesn’t prove anything either.
One thing I’ve noticed with my son is how much better focused he is at home in general, and specifically with certain tasks. Last night he completed his math homework, completely alone, perfectly, in 5 minutes. Had this been a writing assignment we’d still be working on it. So if he’s much more likely to go off-task when its hard and anxiety producing is that really ADD?
(Also, just an aside, my husband, who’s not LD or ADD, can’t ever remember anything he’s supposed to do, and never listens to me… )
Re: Yes, inattentive but why?...
On the Schwablearning.org site is a great lecture by Russell Barkley that describes ADHD as a problem of output, not input; the child pays attention, but can only exert partial mental control(executive function) over output, so it’s very inconsistent. That’s the hallmark of the AD/HD kid, the inconsistent response to situations, the inability to take external demands and events and exert mental control over their responses each time. I think Dr. Barkley and others see the slow, dreamy, ADD/inattentive kid in a different way; this is the kid who’s always a step off, not the one who’s in control sometimes and not in control other times.
Re: We are seeing improvements in attention too..
Beth,
It seems to me that even if he were ADD/inattentive with processing difficulties, by helping processing you have a good chance of helping attention. The two really do seem intertwined. When you think about it, if one’s having difficulty processing information, they can’t help but be at least moderately inattentive. It has to be extremely frustrating, especially for a child.
The fact that you have seen improvement in attentiveness is a good sign that what you are doing is having at least some impact.
Yes, it would be great to have an objective test! With all the interest and attention ADD and ADHD gets, I think there’s a good chance someone out there will develop one relatively soon.
P.s. I’m still thinking very seriously about IM. All of the research I’ve come across, and everyone’s experiences here suggest to me that it may be beneficial for my son. If there was a local provider I’d make an appointment to start right away, but with the location of services is so far from home, I have to seriously consider the “logistics.” We may need to wait until summer.
Re: Yes, inattentive but why?...
That is very interesting. I’ll have to go re-read that article … While my son is a dreamy inattentive child (we were sitting one on one doing homework last night and I lost him - he just went to another universe..) He also has some exec. function stuff. Its all mild, in many ways he just seems young for his age. Thanks for the reference.
Re: We are seeing improvements in attention too..
I would consider IM, and I’m saying that as the person on this board who has seen the least amount of benefit. I do see positive change in my son, but its subtle. Perhaps its still rolling out so to speak. My only “regrets” about doing IM is the cost, but also the time spent on it. I wonder if he would have been better off spending that time being remediated for example. But as we’ve said before, many of these therapies are complementary - you can’t get the gains in one without the time spent in another. I still think IM makes sense…
Re: We are seeing improvements in attention too..
Karen,
I have an idea about why IM didn’t work as well with your son. I think that one of the ways IM works is that it forces the child to stay in an attentive state. It helps the child use this state of attention to accomplish the tasks. I wonder if your son was sent into the anxiety-attentive, flight or fight state. Perhaps he just couldn’t find that calm attentive state that brings optimal performance.
One of the reason’s I say this is that I saw a little of this with my son. I had to stop the exercise a few time and rub his back and get him to calm down. He would be flicking his fingers or something else that was impeding him. When I felt his shoulders he was very tight. Remember he never made it down to the optimal level either and he also required extra sessions.
I came up with this theory while reading about attentive states. It is just a thought and as such should be taken with a major grain of salt.
I am hoping that biofeedback does a better job of training him to stay in the calm attentive state.
Re: Yes, inattentive but why?...
“So if he’s much more likely to go off-task when its hard and anxiety producing is that really ADD?”
Quite possibly, yes, quite possibly no. Dr. Barkley’s view of ADHD is that it is not so much a disorder of attention as it is of one of self-control. When any of us is doing something interesting and/or not difficult, it is easier to persist with the task. We’ve all also had the experience of finding it harder to stick with something that is boring, repetitive or difficult. But, those who do not have ADHD are normally able to muster up the effort to persevere, at least for a reasonable amount of time, even while doing hard or boring things. People with ADHD just don’t have the self-control necessary to sustain that effort. Sometimes parents (and teachers and even doctors who lack sufficient knowledge or experience) will say something like “It can’t be ADHD because the child can pay attention when he is playing video games, or building with legos, or playing soccer, etc. It is only when he is doing homework, or reading or writing that he can’t attend.” That a person can attend while doing things he likes, but can’t while doing things he doesn’t does not mean there is no ADHD. To the contrary, it may mean that the disorder IS present. The really hard part is to tease out whether it is anxiety, depression or a learning disability that is producing the lack of ability to sustain effort and attention. Anxiety and depression can often mimic ADHD, especially in children. It is an even closer call when LD is present, because research shows that the majority of children with LD, but certainly not all, will also have some form of ADHD. IMHO, the key to all of this is obtaining a really thorough evaluation that involves not merely educational testing but also specific consideration of possible psychological and neurological causes.
Andrea
I wonder how they will treat once they have determined the gene? I was never very good in science so maybe that is a dumb questions but I was just wondering. I watched a show today on the Discovery Channel that said they have showed that children with ADHD have different levels of dopamine in their system that non-ADHD children. I also remembering reading that there is research that shows that the brains of ADHD children are slightly smaller.
I am curious to know how scientists and Dr. will combine all this information!
K.