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Taking a genetic view of ADHD

1 Oct, 2010
Blocks used to assess children in the ADHD tests

Blocks used to assess children in the ADHD tests

Attention deficit hyperactivity disorder (ADHD) is a common mental health problem that severely disrupts people’s lives. It is poorly understood and is often dismissed as bad behaviour or laziness. It has recently been discovered that children with ADHD are more likely to have pieces of their DNA duplicated or missing than other children. Penny Bailey spoke with Professor Anita Thapar, from the Cardiff University School of Medicine, about the importance of showing that there is a genetic basis to ADHD, and how this might help us understand its biological causes.

“We know very little about what causes ADHD and how it develops,” says Professor Anita Thapar, Clinical Academic Child and Adolescent Psychiatrist at Cardiff University School of Medicine. Indeed, children with ADHD are not always taken seriously, or given public sympathy. ADHD is often seen as an excuse for bad behaviour and laziness, or simply blamed on bad parenting, For many, it is not a ‘serious’ disorder, even though it affects one to two per cent of children, and is one of the most common reasons for children to use mental health services.

“One of the things I’m really struck by when I see families and children in the clinic is this issue about public perceptions of ADHD, and the media representations of ADHD,” says Professor Thapar. “My sincere hope is that, through these scientific findings, the general public and services will take ADHD seriously.”

Over the last 15 years, Professor Thapar and colleagues have been building evidence to show that ADHD has genetic links. Now, by looking across the genomes of children with ADHD, they have uncovered direct evidence of a genetic contribution to the disorder as well as intriguing links to autism and schizophrenia.

Genetic clues

ADHD’s hallmark symptoms are hyperactivity, inattention and impulsiveness: children are restless and fidget, can’t concentrate on schoolwork or TV, and are very impulsive, not waiting their turn, and doing things without thinking. Most children show at least some of these symptoms at times in their development, but for those with ADHD, the symptoms are not only extremely severe, but they are also inappropriate for the age of the child and are present in more than one setting.

The problems accompanying ADHD disrupt both learning at school and relationships with family and friends in childhood. Adults with ADHD are more likely to have difficulties getting or keeping employment, abuse drugs and alcohol, and end up in prison or with a criminal record.

So what do researchers currently understand about the genetic basis of the ADHD?

“We’ve known for many years that ADHD tends to run in families, so there is likely to be a genetic contribution,” says Professor Thapar. “Over a decade ago, we studied identical and non-identical pairs of twins, and showed that ADHD is indeed highly heritable, as people who have close relatives with ADHD are more likely to develop it themselves.”

A researcher investigating the genetics of ADHD.

A researcher investigating the genetics of ADHD.

Population studies

Another clue came from a study of ‘candidate genes’ between 2000 and 2003, funded by the Wellcome Trust. This study looked at a selection of genes affectingthe brain and behaviour in 300 children with ADHD from clinics in England and Wales. They found that a variant in a gene called COMT, which is involved in the breakdown of the brain transmitter dopamine, was linked to antisocial behaviour in those with ADHD.

Furthermore, the children with ADHD were more likely to have a variant that produced a more active version of the COMT enzyme that breaks down dopamine faster in the brain – a finding that has since been replicated by many other groups in different countries.

Searching across the genome

This was important progress, but complex disorders such as ADHD are likely to affect many different genes. In 2007, Professor Thapar and colleagues were awarded funding by the Wellcome Trust to investigate the genomes of children with ADHD, to find out which other regions might be involved in the disorder.

Findings in a paper published in the ‘Lancet’ in September 2010 confirmed that there are differences in certain parts of the genome between children with and without ADHD. These discrepancies were in copy number variants (CNVs) – pieces of the genome that are duplicated, sometimes many times, or deleted altogether. “These children had double the rate of rare, large CNVs than normal controls,” says Professor Thapar.

Another exciting finding was that the CNVs associated with ADHD occur in regions of the genome associated with both autism and schizophrenia. Although these are clinically separate conditions from ADHD – and the study specifically excluded people who might have them – there appears to be a genetic overlap.

“We’ve known that ADHD and autism share some clinical similarities,” says Professor Thapar, “but they’ve always been regarded as separate conditions. Now that we’ve found that there is an overlap between regions of the genome that harbour CNVs related to ADHD, and regions implicated in autism and schizophrenia, it brings these neurodevelopmental disorders together. That is important because some people believe ADHD is better viewed as a behavioural problem or social construct rather than a neurodevelopmental disorder that shares biological similarities with autism and schizophrenia.”

Also emerging from the study was the finding that the increased rate of CNVs in ADHD was not related to intellectual disability. “A proportion of people with ADHD do have intellectual or learning disabilities, so it could be that the CNVs we found are related to IQ, not to ADHD,” she explains. “But we’ve shown that these CNVs are not just found in people with learning disabilities.”

Towards better-tailored treatments

Professor Thapar hopes that this research will stimulate scientific interest in this area. “These aren’t the sort of findings that will lead to a test for ADHD,” she points out. “We already have that – the best method for diagnosis at present is to ask the right sorts of detailed, careful questions. But this type of research might help us to refine our diagnoses or define meaningful subgroups.”

A written child and adolescent psychiatric assessment.

A written child and adolescent psychiatric assessment.

“Most importantly, the results can help us understand the causes and biology of ADHD, which can suggest how it might be treated. At the moment, we only have a limited range of treatments available; but if we can understand what is happening in the brain during the development of ADHD, we might be able to develop more precisely tailored, more effective treatments.”

Equally important is the impact such findings can have for families, as parents are often blamed for their children’s ‘bad behaviour’. “The parents of children with ADHD that I meet in the clinic are heroes,” says Professor Thapar. “And they don’t get a break – they don’t get any sympathy, as there’s no visible problem with their child. The affected children struggle with school and rejection by their peers. Now we can show people that these children have a neurodevelopmental disorder with an observable genetic contribution.”

“We’ve come a long way in the last 20 years in our understanding of autism and schizophrenia, such that people hopefully don’t encounter the sorts of stigma that they might have in the past. I hope that this will help do the same for children and families with ADHD.”


Williams NM et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 2010 (In press).

Thapar A et al. Catechol- O-methyltransferase gene variant and birth weight predict early onset antisocial behavior in children with Attention Deficit Hyperactivity Disorder. Arch Gen Psychiatry 2005;62(11):1275-8.

Caspi A et al.A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2008; 65(2):203-10.

Thapar A et al. Does the definition of ADHD affect heritability? J A Acad Child Adolesc Psychiatry. 2000; 39:1528-36.

Thapar A et al.Childhood hyperactivity scores are highly heritable and show sibling competition effects: twin study evidence. Behav Genet 1995;25:537-44.


You can also watch a short film about the discovery.

Top image credit: Anita Thapar
2 Comments leave one →
  1. Lou permalink
    1 Oct, 2010 1:51 pm

    Thank you to Wellcome for supporting this research.
    Congratulations to Dr Nigel Williams and Prof Anita Thapar and their teams involved in this study.

    So many welcome this compelling evidence, that there’s a genuine underlying cause behind the problems many of us endure. We do not disclose the fact that we suffer this disorder and never use the label ADHD. We have not told our parents, siblings, friends, or even our son’s teacher. The stigmatisation is too great and the negative repercussions are too risky.

    When our precious son developed anxiety at 4 yrs of age (when he started preschool) and then depressive symptoms at 6 (during his 2nd year at school), our belief that it would be “safe” for us to have a child as long as we provided a nurturing yet stimulating environment was proved wrong. We believed our own problems had stemmed from our upbringing, pure laziness and poor choices. But the chronic working memory deficit and the faulty reward-motivation feedback slowly became evident in our son. Psychologists and doctors thought I was “unhinged” when I suggested that my son suffered ADHD and that I believed that this was the specific problem underlying the development of the psychological issues my son suffered.

    As it turns out, my son is very bright and was acutely aware that he was strangely unable to perform as he should and as people told him he could “if he tried hard enough”, and subsequently he became increasingly anxious. He eventually came to the conclusion that he was simply “bad” because he couldn’t do what everyone told him he could, then helplessness ensued. A placid, happy baby and outgoing, contented toddler gradually transformed into an almost unrecognisable, anxious and timid little boy. It was heartbreaking. So I gave up work to dedicate myself to resolving the mystery.

    Thankfully, I learned of a developmental paediatrician who was part of a team undertaking groundbreaking research using EEGs as a diagnostic tool. I suspected the inattentive type of ADHD but for 2 years I was repeatedly told that our son suffered chronic anxiety, not ADHD. Innately I knew that the anxiety was simply symptomatic of the ADHD.

    It seems that my son’s intelligence masked the ADHD. He was ahead of his peers in basic literacy skills and, when tested one-on-one, none of the DSM symptoms for diagnosis of ADHD were apparent. But I knew in group settings, such as in the classroom, it was very apparent. My own and my husband’s very negative experiences at school prevented us from involving the school in any way. When the dev.paed. finally provided a definitive diagnosis, thanks to the qEEG and the medication test, the relief was enormous.

    My 10yo son and I both take medication now and are reaping the benefits. My son’s anxiety is rarely an issue now and the depressive symptoms have vanished. He attends a selective school for bright children and has wonderful friends. The future looks brighter now thanks to the medication. Things are still challenging though, especially when the meds have worn off. But incomparably better than they were.

    At school I was noticed as being brighter than average, yet I struggled with motivation, slow processing and writing output issues. My performance was extremely erratic, which seemed to almost enrage the teachers. They couldn’t understand why such a bright girl would want to waste her ability. I suffered chronic depression as a result. I managed to graduate to university to study my love of languages, but the depression was crippling and I dropped out.

    Now I am back at university studying Science this time, and I’m enjoying it so much. I grieve for lost opportunities, but am thankful my son will have more of a chance to have an engaging career and avoid the mental illness that I struggled with and the addictive tendencies my husband has fought all his life.

    Thank you so much for funding this research, and deeming ADHD a worthy cause.

  2. Dr Robert Peers permalink
    9 Oct, 2010 11:24 am

    I am disappointed that Dr Thapar has not mentioned a major role for refined vegetable oils in causing ADHD prenatally. I have sent her full details several times, and she has never bothered to reply, which reflects on her scientific integrity. Genome-wide studies in ADHD have not previously shown any proof of a major gene for ADHD, while these copy number variations clearly do not cause ADHD on their own, as shown in the control children bearing such variations. These latest variations may have more to do with autistic tendencies than with typical ADHD, that is, the link may may be more with ADD without the “hyper”, which US expert Dr Russell Barkley believes is a separate disorder. In Australia and New Zealand, retired primary teachers I have met over the years do not recall any ADHD children until the 1960s, which was when refined vegetable seed oils first became common in those two countries. Such oils, which are now linked with Alzheimer’s disease as well, are partly vitamin E depleted during refining: they cause lipid peroxidation and memory deficits in rats. ADHD children in Scotland and Durham exhale ethane gas, a known marker of lipid peroxidation. In 1995, I noted a high frequency of ADHD kids in young families consuming refined seed oils, and I went on to discover that in 80 cases, 78 of the pregnancies involved regular seed oil consumption, compared with no such maternal exposure in 80 control pregnancies. I got very good results in these kids, by switching the families to olive oil, and by supplementing the affected child’s diet with fish oil. All of the mothers of ADHD kids had “Seed Oil Syndrome”–memory faults, glare sensitivity and night blindness–symptoms that Dr Thapar would be hard put to explain. Government action to correct low vitamin E levels in refined polyunsaturated seed oils will eliminate both ADHD and Alzheimer’s. Forget about these minor genetic influences–the age of Brain Nutrition is fast approaching!

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