Mitochondrial Dysfunction Evident in Some Patients With Autism Spectrum Disorder
NEW YORK (Reuters Health) - A significant proportion of patients with autism spectrum disorder (ASD) has evidence of mitochondrial dysfunction on magnetic resonance studies, in a study that one expert called "fascinating."
"We now have compelling evidence for the common presence of metabolic dysfunction in the brains of persons with ASD," Dr. Bradley S. Peterson from Columbia University Medical Center, New York told Reuters Health. "This provides vitally important information about the mechanisms of disease and clues for the development of new interventions in this very common, life-long, and highly debilitating illness."
Although mitochondrial disease is an established cause of syndromic autism, it remains unknown whether mitochondrial dysfunction is present in the brains of individuals with ASD and whether it plays a role in the core cognitive and behavioral symptoms of ASD.
Dr. Peterson and colleagues acquired proton magnetic resonance spectroscopic (MRS) imaging data to assess in vivo evidence of mitochondrial dysfunction in the brains of 75 adults and children with ASD and 96 typically developing controls matched by age and sex.
They used the presence of lactate doublets as an indication of mitochondrial dysfunction.
Lactate doublets were present in significantly more individuals with ASD (13%) than in typically developing controls (1%; p=0.001), they reported April 9th online in JAMA Psychiatry.
The presence of lactate doublets in the ASD group increased with age and was significantly more common in adults (20%) than in children (6%). Their location varied across individuals, but they seemed to aggregate preferentially within the cingulate gyrus.
Lactate doublets did not correlate with sex, ASD subtype, intellectual ability, Autism Diagnostic Observation Schedule total score or subscores, or the presence of comorbid neurological or psychiatric diagnoses.
"Regardless of its cause, our finding suggests that the inclusion of adults is important for understanding the complex role of mitochondrial dysfunction in ASD," the researchers say.
"Our strong evidence for the common presence of mitochondrial dysfunction in persons with ASD suggests that patients should undergo clinical evaluation for the presence of mitochondrial disease," Dr. Peterson said.
"Novel treatments for known mitochondrial diseases are under development and showing promise," Dr. Peterson said. "These might one day prove helpful in the treatment of mitochondrial dysfunction in persons who have ASD."
Dr. Richard E. Frye from the University of Arkansas for Medical Sciences in Little Rock recently reviewed mitochondrial dysfunction in ASD. He told Reuters Health, "It is not uncommon for children with autism to have mitochondrial disease, a disorder that has many potential treatments. Diagnosing mitochondrial disease in children with autism can lead to appropriate treatments that may substantially improve the child's life."
"This supports the notion that we should be screening children with autism for mitochondrial disease, especially if they have symptoms that are commonly reported in children with autism and mitochondrial disease, including seizures, gastrointestinal problems, gross motor delays, and regression," Dr. Frye said.
"More research is needed into this subgroup of children with autism so that we can provide appropriate treatment," Dr. Frye concluded.
Dr. Agustin Legido from Drexel University College of Medicine in Philadelphia recently reviewed mitochondrial dysfunction in autism. He told Reuters Health by email, "Every patient with autism should have an easy, nonaggressive evaluation of the mitochondrial respiratory chain."
"This should not be interpreted as the answer to autism," Dr. Legido cautioned. "It addresses another piece of the big and complex puzzle of the cause of autism."
Dr. Legido added, "The cause of autism is complicated. Mostly, the prenatal cases are due to genetic abnormalities involved in brain development. Acquired post-natal cases are due to damage of brain structures involved in brain functions of language, behavior and socialization (e.g. west syndrome or infantile spasms, tuberous sclerosis, etc.). The question is: what is the role of mitochondria and particularly of mitochondria genes and nuclear genes regulating mitochondria function? The fact of finding signs of abnormal mitochondria function is the tip of the iceberg."
Dr. Derrick Fraser MacFabe directs the Kilee Patchell-Evans Autism Research group at University of Western Ontario in London, Ontario, Canada. He told Reuters Health by email, "This initial study may lead to more careful studies/metabolic controls pointing to environmentally induced mitochondrial function from many environmental agents( PCPs, metals, organophosphates, inflammation-induced oxidative stress), but particularly (what we have proposed) from short chain fatty acids from an abnormal gut microbiome (i.e., history of early antibiotics/hospitalization/and/or altered host immune system)."
He continued, "This fascinating study points to autism as a systemic metabolic disease as opposed to a primary brain disorder, and to future metabolic biomarkers . . . or treatments (i.e., augmenters of mitochondrial function - e.g., carnitine, coenzyme Q10), and risk factors (gut dysbiosis, antibiotics, hospitalization) in at least a subset of patients."
JAMA Psychiatry 2014.
Cite this article: Mitochondrial Dysfunction Evident in Some Patients With Autism Spectrum Disorder. Medscape. Apr 14, 2014.