Have gene findings taken the stigma from ADHD?
By Andy Coghlan For the first time, evidence has emerged of genetic mutations linked to attention-deficit hyperactivity disorder. But how strong is the link, and how far does the finding undermine claims that children with the condition are simply naughty kids, victims of bad parenting or driven to hyperactivity by dietary additives? What did the researchers do? A research team in the UK screened DNA across the entire genome from 366 children with ADHD and 1047 children without the condition for rare but massive regions of DNA that were either missing from where they should be or duplicated. They looked for these abnormalities, called copy-number variants or CNVs, because some had been linked previously with other psychiatric disorders, including schizophrenia and autism. And what was the result? They found that 16 per cent of the children with ADHD had abnormally high numbers of CNVs, double the 8 per cent of normal children who had them: the ADHD children had double the risk of carrying these genetic abnormalities. Is that a big deal? “We have the first scientific evidence of a direct genetic link,” said their leader, Anita Thapar of Cardiff University, at a press conference in London. Another researcher contacted by New Scientist agreed that the findings were important, groundbreaking and reliable. “It is a significant finding, and it’s by far the largest genetic effect seen so far,” says Philip Asherson, who studies the genetics of ADHD at the Institute of Psychiatry in London. Did they find anything else to strengthen the conclusions? Yes. Most strikingly, the rate of CNVs was six times as high as normal in ADHD children who had IQs lower than 70 and so had a more severe form of the disorder – there were 50 such children. “That’s huge,” says Asherson. Also, the ADHD children had CNVs in sites on chromosome 16 that overlapped with CNVs previously found in children with schizophrenia. The implication, says Asherson, is that these regions may be crucial to development of the brain in the womb or in infancy, and that disruption in this region may play a role in many psychiatric conditions. But the researchers found the CNVs in only 16 per cent of the ADHD kids. Might bad parenting or poor diet have caused the disorder in all the rest? Possibly. But the researchers say that when diet has been fingered as a culprit in ADHD and changed in an attempt to treat the condition, little good has come of it. And many children with ADHD have stable relationships with parents and are well behaved generally – their condition manifests itself only through an inability to concentrate and focus on specific tasks. “There’s not a great deal of evidence for what the environmental factors might be,” said Thapar’s colleague Kate Langley. Might other genes be involved? Thapar stressed that her findings are “only the start of unravelling the genetics”, pointing out that her team searched only for the biggest known CNVs, covering 500,000 base-pair units of DNA or more. Asherson agrees, saying that unpublished research shows links with smaller CNVs. Previous studies have found weak links with other genes, particularly those that make components of the brain’s “reward” circuitry, such as receptors for the neurotransmitter dopamine. One of the main hypotheses to explain ADHD is that the reward system in the brain is defective in some way, producing such transitory satisfaction that sufferers become bored quickly and constantly seek out new stimulation to “top up” the reward circuit. Another possibility is that ADHD children have an abnormal sense of time, so they perceive short spells as inordinately long and boring. So where does all this leave diagnosis and treatment? Thapar stressed that ADHD is treatable both with drugs such as Ritalin and through behavioural therapy, and that the ultimate cause of the condition in each case wouldn’t affect current treatments, because knowing genes could be to blame would probably not change which treatment a doctor recommends. Also, existing methods for diagnosing ADHD are fine, she says, although screening for certain CNVs could one day be helpful in some people who have intellectual disability. Does it mean that ADHD is inheritable? Too early to say, but when the researchers looked in more detail at 15 specific CNVs, they found that 11 came from the children’s parents, suggesting the possibility of inheritance. But equally significantly, the remaining four were not inherited and so must have emerged either in the womb or during childhood, suggesting that environmental factors may account for them. Asherson says previous studies have looked for links between ADHD and smoking during pregnancy, but the findings have been inconclusive. Finally, does it mean that we’re any closer to knowing the exact cause of ADHD and whether the condition is being overdiagnosed in children who are simply going through a naughty phase? ADHD is so complicated that all sorts of factors feed into it, but what these findings do prove once and for all is that there is indeed a genetic component to a condition that we already know tends to run in families. Now comes the tricky part – teasing apart the interaction between genes and the environment, and turning this into new ways to treat the condition. Journal reference: The Lancet, DOI: 10.1016/s0140-6736(10)61109-9 More on these topics: