Study is First to Find Direct Evidence That ADHD is a Genetic Disorder

In a study published Online First (www.thelancet.com) and in an upcoming Lancet, researchers have provided the first direct evidence that attention-deficit/hyperactivity disorder (ADHD) is a genetic condition. ADHD is a brain development disorder, concludes the Article—written by a team of scientists at the MRC Centre in Neuropsychiatric Genetics and Genomics and Department of Psychological Medicine and Neurology, Cardiff University, UK, and colleagues. The study was funded mostly by the Wellcome Trust.*

ADHD affects around 1 in 50 children, and makes children restless, impulsive, and distractible. Children with ADHD exhibit significant problems at home and school. For many years, the disease has been attributed to bad parenting or high-sugar diets, despite a number of factors suggesting genetic factors are at play. For example, the child of a parent with ADHD is more likely to have the condition than a child of a parent without it. And if one of a set of identical twins has ADHD, the other twin has a 75% chance of having it. Currently there is no cure for the condition, but symptoms can be treated with a combination of medications and behavioural interventions.

The study involved genetic analysis of DNA from 366 children with ADHD and 1047 without the condition (controls). The researchers found that children with ADHD were more likely to have small DNA segments duplicated or missing than controls. This type of genetic variation is found to be more common in brain disorders. Thus this new study provides the first direct evidence that ADHD is a neurodevelopmental disorder.

Furthermore, they also found significant overlap between these segments—known as copy number variations or CNVs—and those linked to autism and schizophrenia. Whilst these disorders are currently thought to be entirely separate, there is some overlap between ADHD and autism in terms of symptoms and learning difficulties. This new research suggests there may be a shared biological basis to the two conditions. The most significant overlap was found at a particular region on chromosome 16 which has been previously implicated in schizophrenia and other major psychiatric disorders and spans a number of genes including one known to play a role in the development of the brain.

"We hope that these findings will help overcome the stigma associated with ADHD," says lead investigator Professor Anita Thapar. "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."

"Children with ADHD have a significantly higher rate of missing or duplicated DNA segments compared to other children and we have seen a clear genetic link between these segments and other brain disorders," says author Dr Nigel Williams. "These findings give us tantalising clues to the changes that can lead to ADHD."

"ADHD is not caused by a single genetic change, but is likely caused by a number of genetic changes, including CNVs, interacting with as yet unidentified environmental factors," explains a third author, Dr Kate Langley. "Screening children for the CNVs that we have identified will not help diagnose their condition. We already have very rigorous clinical assessments to do just that."

The research team says their findings should help clear up misunderstanding about ADHD, so that affected individuals and their families encounter less stigma. They say their results also show that ADHD is better considered as a neurodevelopmental disorder like autism rather than as a behavioural problem. "Genetics gives us a window into the biology of the brain. In the future these findings will help unravel the biological basis of ADHD which in turn will help develop new and more effective treatments," says Professor Thapar.

In a linked Comment, Dr Peter H Burbach, Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Netherlands, says: "The first gains beyond today's study might be initial insights into the pathogenesis and neurobiology of brain development as influenced by these genetic variants. This knowledge will eventually enter the clinic and might affect the way people think about and treat neurodevelopmental disorders by accounting for the biological consequence of the specific patient's genotype."

For full Article and Comment, see: press.thelancet.com/adhdchild.pdf