Diagnoses of Attention Deficit Hyperactivity Disorder (ADHD), like those of food allergies, have risen dramatically in children over the last few generations. And again like food allergies, the cause is unclear. However, a team of researchers in England recently identified a genetic link for the disorder . The study, published in The Lancet, found that children with ADHD were more likely to have small segments of their DNA duplicated or missing than other children that don’t have the disorder.
ADHD is one of the most common mental health disorders in childhood, affecting approximately 2% of children . It is characterized by intense motor restlessness, problems with concentration and radical impulsivity. While it’s known that ADHD is highly heritable, there hasn’t been an identification of specific susceptibility genes until this study. Researchers compared the genomes of children with ADHD to healthy controls and found chromosomal duplications and deletions in the ADHD group.
In theory, we each have two copies of every gene: one on the chromosome from our mother and the other on the chromosome from our father. In reality, however, this isn’t necessarily the case. The Human Genome Project revealed that Copy Number Variations (CNVs) — the presence of more or less than two copies of a region of DNA due to its duplication or deletion — is quite widespread in humans. CNVs have been shown to be associated with a number of human maladies, including cancer, susceptibility or resistance to HIV infection, and notably, neurodevelopmental disorders and intellectual disabilities.
The genomes of 366 white British children (316 boys and 50 girls) with ADHD between the ages of 5 and 17 were included in the study, which took place between 2001 and 2009. Children with neurological disorders like schizophrenia, Tourette’s syndrome, autistic spectrum disorders or epilepsy were excluded from the study. These disorders are known to have higher rates of CNVs and researchers did not want to bias the study; they wanted to be sure that any extra CNVs they saw were due solely to ADHD. Control genomes came from 1,047 British men and women born during one week in 1958. The study was then repeated with an Icelandic population — 825 patients with ADHD and 35, 243 controls — to independently confirm the results.
The scientists looked for large CNVs spanning at least 500 kilobases of DNA as these are the easiest to detect accurately and are known to be associated with neurodevelopmental disorders. Children with ADHD exhibited twice as many large CNVs as controls, both deletions and duplications. The excess was most apparent in, but not limited to, children who had intellectual disabilities (IQ lower than 70) along with ADHD. There were some CNVs in the ADHD children that overlapped with regions of the genome implicated in autism spectrum disorders. Six duplications observed in patients with ADHD span a region of the genome known to be involved in schizophrenia. No duplications of this region were found in controls; however, a deletion was observed in one control individual.
This region is located on the short arm of chromosome 16 and contains seven genes. One of them — nuclear distribution gene E homologue 1 (NDE1) — is particularly interesting because it plays a role in neurodevelopment and interacts with disrupted in schizophrenia 1 (DISC1), a gene implicated in schizophrenia and other major psychiatric disorders that encodes a protein also involved in neurodevelopment. Duplications in this region have also been detected in patients with autistic spectrum disorders and intellectual disabilities. Although ADHD is currently thought to be completely separate from schizophrenia and autism, there is some overlap in terms of clinical symptoms and cognitive deficits. These recent findings suggest there is a shared biological basis to these disorders.
The researchers note that they do not intend for children to be screened for these CNVs as a means of diagnosing ADHD -– there are rigorous clinical assessments for that. Rather, they set out to demonstrate that ADHD clearly is a genetic disease and that the brains of children with ADHD are different from those without it.
Dr. Anita Thapar, Professor of Child and Adolescent Psychiatry at Cardiff University School of Medicine who led the study, said :
We hope that these findings will help overcome the stigma associated with ADHD. 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.
- Williams et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet. 2010 Oct 23;376(9750):1401-8. Epub 2010 Sep 29.
- Franke et al. Genome-wide association studies in ADHD. Hum Genet. 2009 Jul;126(1):13-50. Epub 2009 Apr 22.
- ADHD’s genetic link. Cardiff University News Centre. 2010 Sep 30.