The research team was led by Dr. Russell Schachar, Senior Scientist and Psychiatrist at SickKids and Professor of Psychiatry at the University of Toronto, and Dr. Stephen Scherer, Senior Scientist at SickKids, Director of The Centre for Applied Genomics at SickKids and the McLaughlin Centre at the University of Toronto.
The scientists used microarrays (gene-chip technology) to study the DNA of 248 unrelated patients with ADHD. They specifically searched for copy number variants (CNVs), which are insertions or deletions affecting the genes. In three of 173 children for whom the DNA of both parents was available, they found spontaneous CNVs, which occur when the parents are not affected and mutations are new to the child. Rare CNVs that were inherited from affected parents were found in 19 of 248 patients.
Within the group of inherited CNVs, the researchers found some of the genes that had previously been identified in other neuropsychiatric conditions including ASD. To explore this overlap, they tested a different group for CNVs. They found that nine of the 349 children in the study, all of whom had previously been diagnosed with ASD, carried CNVs that are related to ADHD and other disorders.
The findings suggest that some CNVs, which play a causal role in ADHD, demonstrate common susceptibility genes in ADHD, ASD and other neuropsychiatric disorders.
"For the first time, we've tested these genetic alterations in ADHD and have a pretty good handle on a couple of decent ADHD candidate genes," says Scherer, who is also Professor in the Department of Molecular Genetics at the University of Toronto and GlaxoSmithKline Chair in Genome Sciences at SickKids. "This is critical, as it gives us confidence in interpreting our results."
Like ASD, ADHD cases are largely unique, notes Schachar, who is also the TD Chair in Child and Adolescent Psychiatry at SickKids. People carrying the same CNVs can have different symptoms, he says. "It's not always the same risk. As we've seen in autism and other conditions, relatively few of these CNVs repeat in affected individuals."
Most individuals with ADHD also have at least one other condition, such as anxiety, mood, conduct or language disorders. Up to 75 per cent of people with ASD also have attention deficits or hyperactivity. "A lot of these associated problems probably arise from the fact that they are sharing genetic risk for different conditions," says Schachar.
The research results could be reassuring for clinicians who may see characteristics of different neuropsychiatric conditions in their patients – such as ASD-like social problems in a child with ADHD – but are concerned that they are over-interpreting these traits. "This research reinforces the notion that their gut observation is correct," Schachar says.
According to Scherer, the historical mindset in research has been to define the specific clinical syndrome and explore it. "Researchers don't tend to look across disorders very often. This method is perhaps one of the most exciting findings in neuropsychiatric genetics and it is really starting to redefine how we think about neuropsychiatric conditions," he says.
"These are probably genetic factors that increase the risk for various kinds of neuropsychiatric disorders and it poses a huge challenge to us to figure out what makes an ADHD case, what makes an ASD case. There are lots of different possibilities to explain why some common risks can manifest into different kinds of disorders," Schachar says, adding that while the new study observed this phenomenon, more research is needed to determine the cause.
ADHD is a common neuropsychiatric disorder that affects four per cent of school-age children worldwide. It is associated with inattention, hyperactivity and impulsiveness that often results in learning difficulties, social problems and underachievement.
ASDs are diagnosed in roughly one in 100 children in North America and cause deficits in communication, social understanding and behaviour.
The study was funded by The Centre for Applied Genomics, Genome Canada, The Ontario Genomics Institute, the Canadian Institutes of Health Research, the Canadian Institute for Advanced Research, the McLaughlin Centre, the Canada Foundation for Innovation, the Ministry of Research and Innovation, NeuroDevNet, Autism Speaks and SickKids Foundation.
About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world's foremost paediatric health-care institutions and is Canada's leading centre dedicated to advancing children's health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada's most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.
About SickKids Research & Learning Tower
SickKids Research & Learning Tower will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The Tower will physically connect SickKids science, discovery and learning activities to its clinical operations. Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Tower will create an architectural landmark as the eastern gateway to Toronto's Discovery District. SickKids Research & Learning Tower is funded by a grant from the Canada Foundation for Innovation and community support for the ongoing fundraising campaign. For more information, please visit www.buildsickkids.com.
About the University of Toronto
Established in 1827, the University of Toronto has assembled one of the strongest research and teaching faculties in North America, presenting top students at all levels with an intellectual environment unmatched in breadth and depth on any other Canadian campus. U of T faculty co-author more research articles than their colleagues at any university in the US or Canada other than Harvard. As a measure of impact, U of T consistently ranks alongside the top five U.S. universities whose discoveries are most often cited by other researchers around the world. The U of T faculty are also widely recognized for their teaching strengths and commitment to graduate supervision.
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