/ 1 October 2010

ADHD’s roots are complex

Attention-deficit hyperactivity disorder is the bane of many parents, nurseries and schools. Children who suffer from the condition find it difficult to concentrate, and they can be disruptive and difficult at home and in the classroom.

The argument over what causes the disorder has been raging for decades. Many blame bad parenting, whereas others point the finger at disorders of brain chemistry or hormonal disturbances in the womb. But research that has just been published in the Lancet claims to have found the answer: it’s all down to genes.

The study, headed by Professor Anita Thapar from Cardiff University, examined 366 children with ADHD and 1 047 in a control group. They searched for mutations that occur when a chunk of DNA is either duplicated or deleted. The study found these in 14% of children with ADHD, but only 7% of the controls. The Lancet press release claimed that the study “is the first to find direct evidence that ADHD is a genetic disorder”. Thapar stated: “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.”

But is 14% compared to 7% sufficient evidence for claiming that ADHD is a genetic disease? It’s easy to turn the numbers around and show that seven out of eight children with ADHD had no detectable genetic abnormality. That sounds very different from the kind of disease, such as cystic fibrosis or muscular dystrophy, that we normally describe as “genetic”. The genetic lesions discovered in the Cardiff study occur in only a small minority of patients and half as frequently in perfectly healthy children. To put it in yet another way, of 100 children who inherit the kind of mutation identified by the Cardiff group, only four of them will develop ADHD.

Heritability
The study is clearly not strong evidence for ADHD being a genetic disease. However, to make their case, Thapar and other geneticists would cite heritability. This is a measure of how much conditions tend to run in families. Earlier studies report a rather high heritability for ADHD of about 76%.

So where are the missing genes? It is of course possible that more genes will turn up in further studies that might close the gap. But perhaps we need to look again at the evidence for these high levels of heritability.

And heritability itself is a funny thing that isn’t as heritable as people often imagine. For instance, lung cancer was mostly an inherited disease until people starting smoking, and then it became a disease that was caused mostly by cigarettes. Heritability only really works as a measure of the influence of genes if the environment of the individuals concerned is held constant. And that clearly is not the case for children with and without ADHD, as many studies have found plenty of evidence for environmental influences.

Of course Thapar knows this and, when questioned, is keen to stress that it’s not just genes but rather a complex mix of genes and environmental factors that cause ADHD. But that is very different from asserting that ADHD is a genetic disease.

Conditions such as tuberculosis show relatively high levels of heritability in some studies, despite having a well-known environmental cause: the tuberculosis bacterium, for example. Indeed, all diseases are caused by “a complex mix of genes and environmental factors”. Claiming that a particular disease is genetic when the evidence is, at best, suggestive is misleading and potentially dangerous. – guardian.co.uk