UC Davis Study Finds Children with Autism More Likely to have Mitochondrial Defects that Limit Cellular Energy Production

December 13, 2010

  http://www.autismspeaks.org/press/jama_mitochondria_autism.php

NEW YORK, N.Y. (November 30, 2010) - A new study published in the Journal of the American Medical Association (JAMA) and partially funded by Autism Speaks, found that children with autism have more trouble fueling the energy demands of their cells due to dysfunctional mitochondria. These new findings from UC Davis reveal several different types of mitochondrial dysfunction and suggest a novel way of screening for these deficits using blood samples.

Mitochondria, the "powerhouses" of cells, provide energy for cell functions through a cascade of enzyme complexes. Together, those enzyme complexes create energy through a process called oxidative phosphorylation. Previous studies have shown that mitochondrial dysfunction can lead to a host of disorders particularly affecting brain cells which are characterized by high energy demands. Although mitochondrial dysfunction has previously been suspected in some individuals with autism spectrum disorders, the evaluation was difficult, and typically required a sample from muscle cells.

For the study, blood samples were taken from ten children with autism and ten unrelated typically developing children, all aged 2-5 years. The researchers analyzed mitochondria in children's white blood cells. Mitochondria in the samples from children with autism were less efficient at creating energy through oxidative phosphorylation. In some, there was a genetic mutation that affected mitochondrial function. In others, the researchers observed that one or more enzyme complexes were dysfunctional. In most of the children with autism, there were many extra copies of mitochondria, which may partially compensate for each one not working optimally.

"It is remarkable that evidence of mitochondrial dysfunction and changes in mitochondrial DNA were detected in the blood of these young children with autism," said Geraldine Dawson, Ph.D., Autism Speaks chief science officer. "We look forward to seeing other groups replicate these findings. We need to understand why these differences exist. One of the challenges has been that it has been difficult to diagnose mitochondrial dysfunction because it usually requires a muscle biopsy. If we could screen for these metabolic problems with a blood test it would be a big step forward."

Cecilia Giulivi, the study's lead author, is a biochemist in the Department of Molecular Biosciences in the School of Veterinary Medicine at UC Davis and a recipient of an Autism Speaks Pilot Award. Isaac Pessah, director of the Center for Children's Environmental Health and Disease Prevention at UC Davis MIND Institute, a recipient of an Autism Speaks Environmental Innovator Award, is a co-author. Other study authors include Yi-Fan Zhang, Alicja Omanska-Klusek, Catherine Ross-Inta, Sarah Wong, Irva Hertz-Picciotto and Flora Tassone of UC Davis. (Read the abstract here).

"The real challenge now is to try and understand the role of mitochondrial dysfunction in children with autism," said Pessah. "For instance, many environmental stressors can cause mitochondrial damage. Depending on when a child was exposed, maternally or neonatally, and how severe that exposure was, it might explain the range of the symptoms of autism."

Funding for the study was provided by a UC Davis MIND Institute Pilot Research Grant, the National Institute of Environmental Health Sciences (NIEHS), the U.S. Environmental Protection Agency and Autism Speaks.