DNA chip for Attention Deficit Hyperactivity Disorder

[Date: 2013-02-07]

Is your child like this? ‘He does not sit still, he makes you crazy always tapping or moving his leg, he cannot do one thing at a time and he is unable to remain seated at the table during dinner. It’s like he’s got a motor in him; he doesn’t stop talking.’ In school you may hear teachers say things like ‘he does not listen, he does not pay attention, he loses everything, he is unable to do his own work and he makes so many mistakes’. This could be a case of Attention Deficit Hyperactivity Disorder (ADHD).

ADHD is the most common childhood neuropsychiatric disorder. It is a potentially serious problem; a European survey conducted in 2010 found that children with ADHD are statistically more likely to be afflicted with other impairments on their quality of life than children without ADHD. Yet, despite the warning signs, parents take on average 26.8 months to achieve a diagnosis for their child. One reason is that there is currently no tool to confirm an ADHD diagnosis. However, Spanish researcher Araitz Molano-Bilbao from the the UPV/EHU-University of the Basque Country has come up with an innovation that she believes could improve the rate of diagnosis of this disorder, and open the way to potential new therapeutic treatments.

The prevalence of ADHD is calculated to be between 8 % and 12 % among infant-adolescents worldwide, with 50 % continuing to exhibit symptoms in adult life. Children with ADHD have great difficulty in paying attention and completing assignments, and are frequently distracted. They may also display impulsive behaviour and act inappropriately at times. They may experience greater difficulty in controlling these impulses. ‘All these symptoms seriously affect their social, academic and working life of the individuals, and impact greatly upon their families and milieu close to them,’ says Molano.

Dr. Molano studied how genetic polymorphisms (variations in the DNA sequence between different individuals) are associated with ADHD. ‘We looked for all the associations that had been described previously in the literature worldwide, and did a clinical study to see whether these polymorphisms also occurred in the Spanish population; the reason is that genetic associations vary a lot between some populations and others.’

Around 400 saliva samples of patients with ADHD and a further 400 samples from healthy controls (people without a history of psychiatric diseases) were analysed. The analysis of over 250 polymorphisms led to the discovery that 32 polymorphisms could be associated not only with the diagnosis of ADHD, but also with the evolution of the disorder, the specific ADHD subtype, the severity and the presence of comorbidities (the presence of one or more disorders).

On the basis of these results, Dr. Molano has proposed that a DNA chip with these 32 polymorphisms could be used not only for diagnosing the disorder, but also for calculating genetic susceptibility to different variables, including how well the patient is responding to drugs or the normalisation of symptoms.

The study also confirmed the existence of three distinct ADHD subtypes: lack of attention, hyperactivity, and a combination of both. ‘It can be seen that on the basis of genetics, the children that belong to one subtype or another are different,’ explains Dr. Molano.

By contrast, no direct associations were found between the polymorphisms analysed and the response to pharmacological treatment (atomoxetine and methylphenidate). Dr. Molano believes that this could be due to the fact that ‘in many cases, the data on drugs we had available were not rigorous.’ Dr. Molano therefore intends to pursue her research in this field. ‘We want to concentrate on the drug response aspect, obtain more, better characterised samples, and monitor the variables in the taking of drugs very closely, whether they were actually being taken or not,’ she says.

Dr. Molano hopes that this tool will reach clinics and begin to help children with ADHD.

The project was funded by Progenika Biopharma and the pharmaceutical company JUSTE SAFQ. Already 10 collaborating clinics belonging to public and private centres in Spain are looking into this tool with the aim of marketing it.

For more information, please visit:

Elhuyar Fundazioa

http://www.elhuyar.org/EN

Category: Miscellaneous
Data Source Provider: Elhuyar Foundation
Document Reference: Based on information from Elhuyar Foundation
Subject Index: Medical biotechnology; Medicine, Health

ADHD’s Genetic Link

What causes attention-deficit hyperactivity disorder – ADHD? Research in the English medical journal, The Lancet, says it’s not too much sugar, bad diet, or poor parenting. Professor Anita Thapar, lead author of the study, says it’s likely genetic.

Thapar and her group of scientists at Cardiff University in Wales compared 366 children with ADHD to 1,047 kids without ADHD. In particular, the researchers examined differences in the children’s DNA. They found that kids with ADHD were more likely to have small segments of DNA that were duplicates or missing (copy number variants or CNVs — either a deletion or duplication of genetic material).

“We hope that these findings will help overcome the stigma associated with ADHD,” Professor Anita Thapar, the study’s lead author, said in a written statement. “Too often, people dismiss ADHD as being down to bad parenting or poor diet. As a clinician, it was clear to me that this was unlikely to be the case. Now we can say with confidence that ADHD is a genetic disease and that the brains of children with this condition develop differently to those of other children.”

While being media friendly, Thapar’s last statement is a stretch in relation to her research. People and the media love statements that provide seemingly conclusive answers.

Let’s go beyond the media hype that says this research concludes there is a definite genetic link. The researchers really only say there seems to be a possible “genetic link.”  However, their research did not conclude that it is purely or even primarily genetic. What they truly are saying is that this study is evidence that ADHD is not purely social.

The authors conclude:

“Our findings provide genetic evidence of an increased rate of large CNVs in individuals with ADHD and suggest that ADHD is not purely a social construct.”

This is logical because only 15% of the research subjects with ADHD demonstrated increased CNVs. So is it safe to conclude that genetic makeup may contribute, at least in some particular cases, to ADHD? Yes, but to be clear,  this research did not conclude that it is entirely genetically based and was only partially genetically based in a small segment of their study population. This is very similar to other genetic research.

Why is it, if ADHD is genetically based, at least in part, that 30% don’t have it as adults when diagnosed as a child? What happened? Where did it go? This is what is most  important to parents and professionals.

Epigenetic theory, now being widely embraced by the scientific community, maintains that human development  includes both genetic origins of behavior and the direct influence that environmental forces have on the expression of those genes (nature/nurture). Epigenetic theory regards human development as a dynamic interaction between these two influences.

Simply put, how our genes express themselves is greatly impacted by environment. This is likely why, over time, 30% of children don’t display symptoms as adults. The brain changes, rewires, or (a radical version of epigenetic theory) their genes change.

Do tools exist to do this? Yes. See www.playattention.com.

If I may quote Dr. Theodore Dalrymple, “What seems to have happened is that parents have lost the awareness that they had for decades – if not for centuries – that concentration and self-discipline do not come naturally to children, and have to be taught (as well, sometimes, as enforced).”

The ADHD link to social dynamics

If I told you that women who received only basic education were 130 % more likely to have a child on ADHD medication than women with university degrees, you’d see a link, wouldn’t you?

Well, that’s what a  study published this month in Acta Paediatrica found.  That implies that nearly half of the serious cases of ADHD  in children are closely tied to social factors. The study reveals that factors like single parenting and poor maternal education were directly tied to ADHD medication use.

While we know that a genetic propensity likely exists, the human brain develops based on a complex interplay between nature and nurture; between genetic endowment (nature) and environment/social factors (nurture). Epigenetic theory tries to explain this relationship.

Curiously, few large-scale studies have tried to determine the impact of social and family influences on ADHD. Researchers at the Karolinska Institute in Stockholm, Sweden assessed data on 1.16 million school children and examined the health histories of nearly 8,000 Swedish-born kids, aged six to 19, who had taken ADHD medication.

“We tracked their record through other registers … to determine a number of other factors,” said lead author Anders Hjern.

Here’s what the researchers found:

  • Living in a single parent family increased the chances of being on ADHD medication by more than 50 percent.
  • A family on welfare upped the odds of medication use by 135%.
  • Boys were three times more likely to be on medication than girls.
  • Social dynamics affected both sexes equally.

“Almost half of the cases could be explained by the socioeconomic factors included in our analysis, clearly demonstrating that these are potent predictors of ADHD-medication in Swedish school children,” Hjern said.

It’s clear that this study found a link between socioeconomic factors and ADHD medication use/diagnosis. Other US studies have found that minority children and children of low socioeconomic status were more likely to receive ADHD medication.

Factors like low income and diminished quality time are more common in single-parent families. These typically lead to stressors like family conflict and a lack of social support, Hjern said.

While more research must be done, one has to ask, is medication the answer to social stressors like lack of time and money? Sounds too silly to ask, but it seems that our answer, ridiculously, is a resounding, YES!

We are the masters of our lives. We can make significant personal changes, but we must have the tools to do so. That’s why I began Play Attention (www.playattention.com) years ago.

What Lurks Below the ADHD Iceberg?

Virtually anyone that knows, teaches, counsels, or works with an ADHD person is aware that ADHD is not a simple matter of attention deficit. That’s just the tip of a very large iceberg.

As a matter of fact, the term ‘attention deficit’ is actually a misnomer of sorts. ADHD people have diffused attention, not a deficit or lack of attention. Ask them. I often asked ADHD students what was happening in my classroom. They could tell me about the bird outside the window, the cobwebs in the corner of the room, a little about my lesson, a little about the whispering around them, and a little about when the air conditioner was turning on and off. That’s actually a great amount of attention. It’s just scattered or diffused over a wide area all day long.

A true hallmark of ADHD is the brain’s inability to direct attention for long periods without becoming distracted. So, it’s not a deficit at all; ADHD is an inability to direct attention. But there’s more.

ADHD is also a matter of difficulty in multiple domains of cognition. These domains are also labeled “Executive Functions.” Aside from diffused attention, ADHD also encompasses difficulty in organization of thought and tasks; sustaining effort while filtering out distractions; memory (both short-term and working memory); managing behavior/emotion; and visually directing attention and actions.

How does one cope with all these areas? It seems a monumental task. Of course, the primary medical intervention is medication. Does medication actually address all of these cognitive domains? No, it does not. Medication has limitations. That’s a fact. That’s why many parents do not see academic, behavioral, or social improvements [see the MTA study] over time. Another fact is that many of these cognitive domains can be strengthened by direct instruction.

Several small and large software companies have introduced themselves recently into the brain fitness category. Each company tends to address a specific domain like memory or focus. So, to satisfy the cognitive and behavioral needs of an ADHD person, one would need to purchase many of these games.

As the original pioneer and developer back in the late 1980s,  I saw that there was a vast gap in the needs of the ADHD person and what was being delivered. By 1994, I developed Play Attention to teach sustained attention, visual tracking with attention (like watching a teacher move about the classroom), organizing and finishing tasks, memory, filtering out distractions, and motor skills. I even included behavioral shaping. Later this year we’ll deliver social skills, more working memory & short-term memory modules, and more.  We’ve received 3 patents for this pioneering effort.

Play Attention is a careful collaboration between you, the Play Attention software, and the Play Attention professional support staff. It’s provided us with a 92% satisfaction rating.

Of course, to get results, you need to use it. Next week I’ll address how Play Attention transcends being useful to being compelling.

Is ADHD Simply a Developmental Delay?

Attention-deficit hyperactivity disorder (ADHD) is conservatively estimated to affect anywhere between 5-7% of the world’s school-children. Is it possible that ADHD is the result of a brain that just develops slower than the brain of a child that doesn’t have ADHD?

Research has shown that the ADHD brain may develop differently than one without ADHD. However, no conclusive pathology (diseased or damaged location in the brain) exists; we don’t know what causes it.

What we do know: As a child’s brain develops, his experiences and environment help shape the connections in the brain. This development is also connected to genetic endowment. Thus, the brain develops dependent upon a complex interplay between nature (genetic endowment) and nurture (experience/environment). These connections form networks which help us process language, calculate math, feel, see, smell, think, and all else the brain is responsible to perform.

The part of the brain that is crucial to a child’s development is the cerebral cortex, the brain’s outer layer. The brain’s most complex functions like attention, consciousness, memory, and language are believed to be regulated in the cerebral cortex. As a child develops, gains experiences, and is subjected to his/her environment, the connections between the neurons (nerve cells in the brain) increase causing the cortex to thicken. The brain acts much like a muscle during adolescence; it’s a use it or lose it proposition. Connections which are frequently used are strengthened while unused connections are pruned away.

Researchers Philip Shaw, Judith Rapaport and others from the National Institute of Mental Health have proposed that ADHD may be the result of  lagging brain development resulting in an average 3 year delay. This theory is supported by earlier studies which found that children with ADHD have similar brain activity to slightly younger children without the condition.

Shaw and Rapaport used MRI (magnetic resonance imaging) to measure the brains of 447 children of different ages. They frequently noticed that the volume of the brain in the prefrontal cortex was thinner in ADHD children than other children of the same age. The cortex developed correctly over time, but the ADHD brain’s  development lagged behind about 3 years before it reached maturity. Among other things, the prefrontal cortex has the responsibility of governing attention, short-term memory,  and controlling inappropriate thoughts and actions. The researchers theorized that ADHD is a lack of control over these tasks, so it was logical to suggest that ADHD is a matter of developmental delay.

Significantly, Shaw and Rapaport found that the primary motor cortex developed faster in ADHD children. As its name implies, the motor cortex helps to plan and control movements. Shaw theorized that this might explain the restlessness, fidgeting and uncontrolled hyperactivity found in ADHD children.

This research raises more questions than it answers. Currently, the cause of the delay is unknown.  If ADHD is just a developmental delay, why do approximately 70% to 80% of children carry their ADHD traits into adulthood? This fact does not rule out Shaw’s conclusions, just that developmental delay may only be present in a minority of children labeled ADHD. Other children, the 70% to 80% previously mentioned, do carry their brain differences into adulthood.

Other research points to a set of genes responsible for the ADHD trait. If either genes and/or developmental delay are the cause, then what is one to do? The brain is an incredibly flexible organ. It is shaped by a variety of factors which means that parents, teachers, and other professionals can influence outcomes. Finding a program that addresses the needs of an ADHD child, helps shape behavior, and optimizes their potential is still the best practice.

ADHD & Fetal Development

 

Obviously, being pregnant can be stressful in itself, but current research shows that stress can affect fetal development which may lead to long-term problems including ADHD.

Dr. Vivette Glover of Imperial College London, surveyed pregnant women at her hospital. Of these, nearly one quarter felt anxious and depressed due to stressors including work, money, arguing with spouse, and moving to accommodate a larger family. When compared to their non-stressed counterparts in this research, the babies of the stressed mother had lower birth weight, lower IQ, slower cognitive development, and more anxiety. Lower birth weight has been an indicator for coronary heart disease in later life.

In 2007, research in the Journal of the American Academy of Child and Adolescent Psychiatry indicated that being stressed during pregnancy is as detrimental for the baby’s development as smoking or being obese. Glover’s research reveals why and how this happens: stress produces the hormone cortisol. An abundance of stress can actually diminish the barrier enzyme that inhibits cortisol from reaching the fetus. Costisol impacts fetal brain development.

According to Glover, “People used to think that if something was congenital, apparent at birth, it had to be genetic. In fact it can be an in-vitro reaction of genes and environment.”

Glover also contends that her research shows stress greatly increases the likelihood of a child having ADHD (attention-deficit hyperactivity disorder), cognitive delay, autism , anxiety and depression. 

Glover’s research reinforces previous data from the UK where stress was shown to increase the risk for development of ADHD. In that research, the women who experienced the most stress doubled the chances of developing ADHD.

“The organs are forming during the first trimester of pregnancy, but the brain is developing all the way through,” Glover explains. “The organs are sensitive while they are forming and, once formed, they are harder to change.”

“In evolutionary terms, stress perhaps prepares the child for survival in a stressful environment. If a child is anxious and has attention deficiency, it will be very alert to danger. This may once have been adaptive, beneficial for the child, but it isn’t any more,” Glover says.

Significantly, Glover’s research implies that the changes may be on a genetic level so that it may be passed on generation to generation.

Therefore, it’s important to realize that taking care oshutterstock_3753070f ourselves during pregnancy is more important now than ever. Small efforts like seeking health services early, meditating, eating a balanced diet, taking pre-natal vitamins, and laughing are good practices.

Minimizing stress by maintaining a consistent schedule both at work and at home is a good idea.

 

ADHD and Genetic Research

Research over the past decade has been relatively inconclusive regarding the etiology of ADHD and its genetic links. The January 07, 2009 special issue of American Journal of Medical Genetics (AJMG): Part B: Neuropsychiatric Genetics presents a comprehensive overview of the latest genetic research of ADHD. In search of the ADHD holy grail, researchers have attempted to identify specific genes that underlie the disorder in the hopes that gene discovery will lead to better treatments for the disorder.

The studies cited in the AJMG indicate that one genetic marker may be associated with ADHD symptoms with the possibility that many genes are involved in ADHD. Each of these genes may play small roles in their overall presentation of ADHD symptoms. The currents studies then are inconclusive and suggest the need for larger studies a) to determine if there are genetic mechanisms underlying ADHD, b) to determine what these mechanisms do if they exist, and c) to determine whether these initial findings can be confirmed.

An important issue needs to be raised here: If one can find a genetic marker and the various genes involved in ADHD, is it therefore a disease like diabetes, cancer, or atherosclerosis? Or is it a genetic trait like red hair, crooked teeth, or freckles? Personally, it seems to me to be more of a trait than anything else. Even the noted ADHD expert, Dr. Ed Hallowell and his colleague, Dr. Peter Jensen, have indicated they perceive ADHD as a trait.

The second issue that needs to be raised here is: What is it that the researchers can do with the genetic information they are seeking? The answer to this question is medication. Most of the genetic studies have leaned toward a genomic search for genes that may someday be used to predict which children respond most favorably to the stimulant medications. The current studies indicate that, although there are likely to be genetic factors that are associated with stimulant efficacy in children with ADHD, there are no single genes with a very large impact on treatment response. This may be because ADHD is a conflation of diffused attention, poor organization, hyperactivity, etc. Are there genetic markers for each of these individual characteristics?

This presents us with the problem of antecedence (chicken or the egg). It appears that ADHD is a conflation of a variety of characteristics. This is precisely how it is diagnosed. These characteristics could be acquired in one of two methods: They could be genetic (heritable) or they could be learned. One can learn to be disorganized, hyperactive, or even have diffused attention. Most of us experience this now in our busy, noisy existence on this planet. Does this change our genetic makeup?

We know that when we learn something, certain genes are switched on which activate messenger RNA to build neural networks supporting long-term memory. Therefore, we are substantially changing our genetic makeup. The brain is incredibly malleable or labile. This is both significant and promising. We can and do shape it through our various daily activities. It would hold then, that we can change our diffused attention into focused attention, our disorganization into organization, and our hyperactivity into calm behavior. However, if we obdurately argue that ADHD is a disorder or disability, then hope for this change is diminished if not extinguished. Now is the time to realize that there is hope for persons with attention challenges; change is quite possible and achievable. Genetic research points us in this direction. It’s past time to follow

ADHD and Genetics

Research shows a gene link to ADHD

The head of child psychiatry at the Royal Children’s Hospital (University of Melbourne, Australia), Professor Alasdair Vance, thinks that children with ADHD have impaired brain function most likely linked to a genetic condition occurring during pregnancy.

Dr. Vance believes he has conclusive evidence that key areas of the brain do not develop as quickly in children with ADHD. These areas, he posits, are linked to a child’s understanding of time and space as well as the ability to use working memory.

“So their ability to read other people’s body language, to pick up on the nuances of what their peer group are up to, would clearly be affected by the sort of developmental delays in brain development that we’ve identified,” he said.

“The most exciting part of this research is the opportunity to understand in detail the brain dysfunction in this group of children so we can better understand how, by changing the child’s environment, facilitated by medication treatments, we can maximize their learning.”

Vance used fMRI on an unmedicated group of boys aged eight to 12 who were diagnosed with ADHD. The fMRI enabled Vance to examine their brains while performing mental tasks. This data was compared to a group of healthy children. Vance said the data demonstrated that ADHD was not just a behavioral issue.

“If it was, one would expect the child’s brain would be functioning normally and that at some level they are making choices to behave in this way. This suggests they are actually activating their brain differently when they are doing the same task as a healthy kid.”

In an interview with the Brisbane Times, Vance, “…believes the research strongly suggests ADHD is a genetic condition occurring most probably during the second trimester of a woman’s pregnancy, but which can be modified through medication and by adapting the child’s environment.”

“I’m not saying that because you have such brain changes the only treatment is medication. Environmental cueing can help those compensatory brain networks to develop.”

“Helping teachers and parents understand how to more frequently cue a child with ADHD through such means as positive reinforcement when the child exhibits desired behavior and through emotional connections that reward the child for better attitudes, are just some of the ways in which the condition can be helped, Professor Vance says.”

“The number and quality of empathic, confiding, nurturing, flexible and adaptive human relationships can build resilience, build compensation or, if absent, make ADHD symptoms worse,” he said.

Vance’s results are preliminary. Furthermore, one cannot forget that ADHD is diagnosed from subjective analysis; it is one of the few diagnoses that can be made over the telephone since it involves acknowledging a series of characteristics or behaviors performed over time. So, we have a problem of antecedence; Vance examined boys that were subjectively diagnosed with ADHD to compare them with boys that were not diagnosed. Does the subjective diagnosis present a problem in this research? I would think so. Could it also be possible that the brain changes in the fMRI could occur as a result of conditioning, environmental toxins, etc? Possibly. Is it equally possible that Vance’s data only accounts for one possible cause out of many? Likely. That’s why I would contend the results are preliminary. We’ll see if the future proves me wrong on this one.

On a positive note Vance does seem to understand neuroplasticity. He does see value in behavioral shaping, compensatory training, etc. While his research is NOT the Holy Grail of ADHD, there is light at the end of the tunnel if we are forging ahead in our understanding of neuroplasticity from research like this.

Genetics and ADHD ADD

Clearly, there is no current research (2005) that has determined that ADHD is genetic either partially or entirely. While empirical data suggest that a genetic link exists, research is still sparse as scientists primarily focus on childhood onset of the disorder with little research on adult AD/HD.

Andrea Chronis of the University of Maryland  has focused on AD/HD mothers and their performance as parents. In her study of 70 families with elementary-school-age children she found that:

  • Mothers of ADHD children are 24 times as likely as the average woman to have it
  • Fathers of ADHD children are 5 times higher than average to have it
  • The mothers often weren’t very involved with their children
  • The mothers had few skills to cope with their children
  • The mothers didn’t give praise or show affection regularly
  • Discipline was inconsistent
  • Most of their children also had ADHD

While Chronis’ research does not prove a genetic link, it offers strong support for the theory. And while poor parenting may exacerbate ADHD symptoms, it does not cause ADHD. Thus, the aforementioned poor parenting skills would likely contribute to worsening their childrens’ symptoms. This would lead one to think that parenting skills/counseling should be a primary consideration for families with ADHD.