From Medscape Medical News
September 29, 2010 — New research provides the first direct evidence that attention-deficit/hyperactivity disorder (ADHD) is genetic.
In a study published online September 30 in The Lancet, investigators from the University of Cardiff in the United Kingdom say their findings, which show that ADHD has a genetic basis, suggest it should be classified as a neurodevelopmental and not a behavioral disorder.
"We've known for many years that ADHD may well be genetic because it tends to run in families in many instances. What is really exciting now is that we've found the first direct genetic link to ADHD," principal investigator Anita Thapar, MD, told reporters attending a press conference to unveil the study results.
In the genomewide analysis, 366 children 5 to 17 years of age who met diagnostic criteria for ADHD but not schizophrenia or autism and 1047 matched controls without the condition were included. Researchers found that compared with the control group without ADHD, children with the disorder were twice as likely — approximately 15% vs 7% — to have copy number variants (CNVs).
CNVs, explained study investigator Nigel M. Williams, PhD, are sections of the genome in which there are variations from the usual 2 copies of each chromosome, such that some individuals will carry just 1 (a deletion) and others will have 3 or more (duplications).
"If a gene is included in one of these copy number variants, it can have deleterious consequences," said Dr. Williams.
Shared Biological Link
The study authors note that the increased rate of CNVs was particularly high among children with a combination of ADHD and learning disabilities but "there was also a significant excess in cases with no such disability."
The researchers also found that CNVs overlap with chromosomal regions that have previously been linked to autism and schizophrenia. Although these disorders are thought to be completely separate, there is some overlap between ADHD and autism in terms of symptoms and learning difficulties.
We've looked at only 1 class of variation, but it's an important one because it has been linked to other brain disorders.
This finding suggests there may be a shared biological basis for the 2 conditions and, according to investigators, provides the first direct evidence that ADHD is a neurodevelopmental condition.
"We found that the most significant excess of these types of copy number variants was on a specific region of chromosome 16. This chromosomal region includes a number of genes, including one that affects brain development," said Dr. Thapar.
The team's research marks the start of the "unraveling of the genetics" of ADHD, according to Dr. Thapar.
"We've looked at only 1 class of variation, but it's an important one because it has been linked to other brain disorders," she said.
Implications for DSM-5?
Dr. Thapar added that the study results also have direct implications for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is currently under development by the American Psychiatric Association.
A "huge debate" about whether ADHD should be classified as a behavioral or neurodevelopmental disorder is ongoing. However, she said, these findings should help put this controversy to rest.
"Our results clearly show that ADHD should be considered a neurodevelopmental disorder," she said.
In fact, Dr. Thapar noted that the study findings have been submitted to one of the DSM-5 work groups for consideration in the development of the new manual.
The investigators note that despite epidemiologic evidence derived from twin studies showing high heritability and the fact that ADHD is often accompanied by learning disabilities, there is still a great deal of public misunderstanding about the disorder.
Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma.
"Some people say this is not a real disorder, that it is the result of bad parenting. Children and parents can encounter much stigma because of this. So this finding of a direct genetic link to ADHD should help clear this misunderstanding and help address the issue of stigma," said Dr. Thapar.
Although there are no immediate treatment implications, Dr. Thapar said she hopes the research will have an immediate impact in terms of shifting public perception about ADHD and fuel further research into the biological basis of the disorder with a view to developing better, more effective therapies for affected individuals.
In an accompanying editorial, Peter H. Burbach, PhD, from the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands, writes, "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."
The study authors and Dr. Burbach have disclosed no relevant financial relationships.
Lancet. Published online September 30, 2010.