Autism in children is strongly associated with defects in the mitochondria, the cell’s energy producer, according to a UC Davis study. Researchers believe that built-up damage and oxidative stress in mitochondria may perpetuate the development of autism as well as the severity of the disorder.

Second only to the heart, the brain is the largest energy user in the body. Mitochondria have their own set of genetic instructions, called mitochondrial DNA (mtDNA), that perform aerobic respiration. Therefore, researchers suggest that when the brain’s neurons don’t receive enough fuel, the results may include the negative cognitive symptoms associated with autism.

Mitochondrial dysfunction is also linked to several other neurological conditions, such as Alzheimer’s disease, Parkinson’s disease, schizophrenia and bipolar disorder.

“Children with mitochondrial diseases may present exercise intolerance, seizures and cognitive decline, among other conditions. Some will manifest disease symptoms and some will appear as sporadic cases,” said Cecilia Giulivi, professor in the Department of Molecular Biosciences in the School of Veterinary Medicine at UC Davis and the study’s lead author.

“Many of these characteristics are shared by children with autism.”

While prior research has suggested possibilities of a connection between autism and mitochondrial dysfunction, the results are considered speculative or have included tissue that was not very representative of neural metabolism.

“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, chief science officer of Autism Speaks, which provided funding for the study.

“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.”

For the study, 10 autistic children (ages 2 to 5) were recruited to participate along with 10 age-matched regularly developing children from similar backgrounds. Blood samples were taken from each child so that researchers could analyze the mitochondrial metabolic pathways in immune cells, called lymphocytes. These lymphocytes strongly rely on the aerobic respiration conducted by mitochondria.

The study revealed that mitochondria in autistic children used much less oxygen (a sign of lowered mitochondrial activity) than in the control group. For example, the oxygen use of one vital mitochondrial enzyme complex, NADH oxidase, in autistic children was only a third of that found in the control group.

“A 66 percent decrease is significant,” Giulivi said. “When these levels are lower, you have less capability to produce ATP (adenosine triphosphate) to pay for cellular work. Even if this decrease is considered moderate, deficits in mitochondrial energy output do not have to be dismissed, for they could be exacerbated or evidenced during the perinatal period but appear subclinical in the adult years.”

Overall, the many abnormalities, deficiencies and levels of malfunction found in the mitochondria of autistic children suggest that oxidative stress in these organelles could be influencing autism’s onset.

“The various dysfunctions we measured are probably even more extreme in brain cells, which rely exclusively on mitochondria for energy,” said Isaac Pessah, Ph.D., director of the Center for Children’s Environmental Health and Disease Prevention, a UC Davis MIND Institute researcher and professor of molecular biosciences at the UC Davis School of Veterinary Medicine.

Giulivi notes, however, that these findings still do not establish a cause for autism.

“We took a snapshot of the mitochondrial dysfunction when the children were 2 to 5 years old. Whether this happened before they were born or after, this study can’t tell us,” she said.

“However, the research furthers the understanding of autism on several fronts and may, if replicated, be used to help physicians diagnose the problem earlier.”

“Pediatricians need to be aware of this issue so that they can ask the right questions to determine whether children with autism have vision or hearing problems or myopathies,” Giulivi said.

The study is published in the Journal of the American Medical Association (JAMA).

Source: University of California

Cell Energy Dysfunction Seen in Autism