Environmental Factor, January 2011, National Institute of Environmental Health Sciences
Study finds mitochondrial dysfunction in autistic children
By Eddy Ball
"If we find some kind of blood marker that is consistent with and unique to children with autism, maybe we can change the way we diagnose this difficult-to-assess condition," Giulivi said as she looked forward to future research. (Photo courtesy of the University of California Regents)
"This important exploratory research addresses in a rigorous way an emerging hypothesis about potential mitochondrial dysfunction and autism," said Cindy Lawler, Ph.D., NIEHS program administrator who oversees grants in the area of autism research. (Photo courtesy of Steve McCaw)
A new exploratory study funded in part by NIEHS presents evidence that deficits in the ability to produce cellular energy are significantly more common in children with autism.
Published in JAMA, the findings from what may be the first study of its kind are the result of an interdisciplinary research effort by a team of scientists at the University of California, Davis (UCD). The team included NIEHS grantees Irva Hertz-Picciotto, Ph.D.(http://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=R01ES015359) (see related story (http://www.niehs.nih.gov/news/newsletter/2011/january/science-guest.cfm)), and Isaac Pessah, Ph.D.(http://tools.niehs.nih.gov/portfolio/index.cfm?action=portfolio.grantdetail&grant_number=P01ES011269), of the UCD Medical Investigation of Neurodevelopmental Disorders (MIND) Institute.
The study(http://www.ncbi.nlm.nih.gov/pubmed/21119085) looked at biomarkers of mitochondrial function in blood samples from 20 children - ten diagnosed with autism and ten typically developing controls of similar age and demographic. The team randomly selected the autistic children from Northern California subjects who were previously enrolled in the NIEHS-funded 1,600-participant Childhood Autism Risk from Genetics and the Environment (CHARGE) Study(http://beincharge.ucdavis.edu/) .
Although the differences between measures of mitochondrial function in subjects and controls were dramatic, the authors were understandably cautious about the interpretation of their findings. "More research is needed to understand the molecular causes of mitochondrial dysfunction and how this and other neurometabolic defects may contribute to autism or related phenotypes," wrote lead author Cecilia Giulivi, Ph.D.(http://biosci3.ucdavis.edu/FacultyAndResearch/FacultyProfile.aspx?FacultyID=14245) Giulivi is a professor in the Department of Molecular Biosciences in the School of Veterinary Medicine at UCD and a recipient of an Autism Speaks Pilot Award that provided partial funding for the study.
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A possible link between energy deficits and cognitive development
The researchers speculate that a lack of the ability to fuel the brain neurons, which consume high levels of energy second only to levels required by the heart, might trigger some of the cognitive deficits associated with autism. Mitochondria are the primary source of energy production in the cells, and mitochondrial dysfunction and resulting oxidative stress have been associated with a number of other neurological disorders.
The researchers found that mitochondria from children with autism consumed far less oxygen than mitochondria from the group of control children, a sign of lowered mitochondrial activity. Findings that hydrogen peroxide levels in autistic children were twice as high as in normal children support the concept that the cells of children with autism were exposed to higher oxidative stress.
According to Giulivi, mitochondrial diseases cause exercise intolerance, seizures, and cognitive decline, among other conditions. Some children will manifest disease symptoms and some will appear as sporadic cases. "Many of these characteristics are shared by children with autism," she is quoted as saying in a Nov. 30 press release(http://www.ucdmc.ucdavis.edu/newsroom/newsdetail.html?key=4765&svr=http://www.ucdmc.ucdavis.edu&table=published) from UCD.
"Only one child with autism in this study fulfilled the diagnostic criteria for a definite mitochondrial respiratory chain disorder," Giulivi said. "Collectively these results suggest that cumulative damage and oxidative stress over time may - through reduced capacity to generate functional mitochondria - influence the onset or severity of autism and its co-morbid symptoms."
Looking to the future
Echoing the study's call for further investigations, NIEHS Principal Investigator William Copeland, Ph.D., also expressed a need for more research. "This is a very preliminary study, and the high percentage of mitochondrial defects seen in this very small patient study is unprecedented and will need to be verified in a more expanded study," observed Copeland, who is head of the NIEHS Mitochondrial DNA Repair Group in the Laboratory of Molecular Genetics.
Such future studies may benefit from new NIEHS-funded efforts to determine the best or most widely accepted cellular or biological measures that signal mitochondrial dysfunction more accurately in non-invasive or minimally invasive sample collections (see related story (http://www.niehs.nih.gov/news/newsletter/2011/january/science-niehs.cfm)).