Mitochondrial Dysfunction in Autism Spectrum Disorder: Unique Abnormalities and Targeted Treatments

Several lines of evidence implicate mitochondria in the pathophysiology of autism spectrum disorder (ASD). In this review, we outline some of the evidence supporting this notion, as well as discuss novel abnormalities in mitochondrial function that appear to be related to ASD, and treatments that both target mitochondria and have evidence of usefulness in the treatment of ASD in clinical trials. A suspicion of the mitochondrion's involvement in ASD can be traced back to 1985 when lactic acidosis was noted in a subset of children with ASD. A large population-based study in 2007 confirmed this notion and found that a subset of children with ASD (∼4%) could be diagnosed with a definite mitochondrial disease. Further studies suggested that children with ASD and mitochondrial disease may have certain characteristics such as fatigability, gastrointestinal disorders, unusual types of neurodevelopmental regression, seizures/epilepsy, and motor delay. Further research examining biomarkers of mitochondrial dysfunction and electron transport chain activity suggest that abnormalities of mitochondrial function could affect a much higher number of children with ASD, perhaps up to 80%. Recent research has identified a type of dysfunction of mitochondria in which the activity of the electron transport chain is significantly increased. This novel type of mitochondrial dysfunction may be associated with environmental exposures and neurodevelopmental regression. Several treatments that target mitochondria appear to have evidence for use in children with ASD, including cofactors such as L-Carnitine and the ketogenic diet. Although the understanding of the involvement of mitochondria in ASD is evolving, the mitochondrion is clearly a novel molecular target which can be helpful in understanding the etiology of ASD and treatments that may improve function of children with ASD.