Canadian researchers have uncovered some new genes that appear to contribute to ADHD in some children — and found an intriguing genetic overlap with other neuropsychiatric conditions, in particular autism.

Besides adding to growing evidence that ADHD has a strong genetic underpinning, the findings may help explain why those with the condition sometimes exhibit certain symptoms seen in other neurodevelopmental conditions, such as autism spectrum disorder, schizophrenia and bipolar disorder.


Sheree Fitzgerald is shown at her Macungie, Pa., home with her son, Eddie, who has ADHD. It which affects three to five per cent of school-aged children. (George Widman/Associated Press)

Attention-deficit hyperactivity disorder, which affects three to five per cent of school-aged children  and is more common in boys, causes poor attention, restlessness and impulsive behaviour that can affect social interaction and learning.

More than half of children with ADHD continue to have difficulties into their teens and adulthood, which can lead to substance abuse, underemployment and other psychosocial problems.

Autism spectrum disorder, which covers a number of related conditions and affects about one in 100 children, is characterized by impaired social understanding and communication, as well as repetitive behaviours. Symptoms typically begin before a child is three years old. Autism is believed to affect how the brain processes information by altering connections between neurons.

Most people with ADHD also have at least one other condition, such as anxiety, mood, conduct or language disorders. Up to 75 per cent of those with ASD also have attention deficits or hyperactivity.

Co-author Dr. Russell Schachar of Toronto's Hospital for Sick Children said he often sees children with ASD who also have the restlessness of ADHD, while kids with ADHD can display atypical social skills common in autism.

"What we're saying is the boundary lines of these conditions may be very blurred because the underlying genetic mechanism may be very blurred," said Schachar, a child psychiatrist and researcher at Sick Kids.

Schachar and co-principal investigator Stephen Scherer led a team that studied the DNA of 248 unrelated patients with ADHD and more than 2,000 healthy individuals to detect differences in their genomes.

Abnormal copies of DNA stretches

They were specifically searching for what are known as copy number variations, or CNVs, which are mutations that cause a cell to have an abnormal number of copies of one or more sections of DNA.

In three of 173 children for whom the DNA of both parents was available, they found spontaneous CNVs, meaning they had not been inherited from the parents and are new to the child. Rare CNVs inherited from parents, who sometimes showed ADHD symptoms of their own, were found in 19 of 248 patients.

"We found that a few of these copy number variants were repeated in ADHD kids. We were finding copy number variants affecting the same gene multiple times," said Schachar.

"So these are copy number variants that are really unique to ADHD — or so we thought."

In fact, what they discovered was that within the group of inherited CNVs were genes previously identified to play a role in other conditions, including autism spectrum disorder. So they decided to test a different group of patients to see if there was any genetic commonality between the two conditions. 

'What we're saying is the boundary lines of these conditions may be very blurred because the underlying genetic mechanism may be very blurred.' — Dr. Dr. Russell Schachar

After testing the genomes of 349 children who'd been diagnosed with autism, the researchers found that nine carried CNVs related to ADHD, while five of the 248 children with ADHD had identical CNVs to the kids with ASD, said Schachar. "So what we found was a small but significant overlap between these two disorders."

Scherer, director of the Centre for Applied Genomics at Sick Kids, said that led the team to ask the question: "Are these genes we're finding in the autism patients, are they ADHD genes or are they genes that are common to both ADHD and autism?"

In other words, could an alteration in one of these genes create different trajectories — leading primarily to ADHD in one patient, autism in another or schizophrenia or bipolar disorder in still others, depending on other genetic and environmental factors.

"We don't have the answer to that yet," said Scherer.

The study, published online Wednesday in the journal Science Translational Medicine, points out that some of the ADHD genes have been previously identified by other researchers in genetic analyses of people with schizophrenia or bipolar disorder.

A team led by Dr. Hakon Hakonarson, a researcher at the Children's Hospital of Philadelphia, identified an overlap in genetic mutations in some patients who had autism and others diagnosed with schizophrenia. An upcoming paper by his group will report on their own findings about ADHD.

"So this does not surprise me," said Hakonarson, director of the hospital's Center for Applied Genomics.

"They have highlighted several interesting genes. Some of them have been seen by us and others in autism and schizophrenia. It makes it more intriguing because we know how these neurodevelopmental disorders, they obviously relate to some sort of malfunction of the neuronal connections in the brain.

 "And when you see them overlap like this, it raises the bar that this is likely going to be important."

Schachar said the study results could be reassuring for doctors, who may see characteristics of different neuropsychiatric conditions in their patients but are concerned they are over-interpreting those traits.

Much more research is needed before complete genetic pictures of ADHD, autism and other neuropsychiatric disorders are constructed, added Scherer.

But if the conditions do share some similar genetic features, it may mean that finding drugs to overcome one disorder may offer potential treatments to help alleviate one or more of the others.

"I don't think one drug would knock everything out," Scherer said. "But if we can do one trait at a time and incrementally help individuals, that's really the approach."