Adenosine and Autism: Physiological Symptoms and Metabolic Opportunities

Abstract

Autism is characterized by impairments in social interactions, deficits in communication, and repetitive behaviors or stereotyped interests. People with autism also have an increased incidence of seizures, gastrointestinal disorders, sleep disruption, and psychological disorders such as anxiety and depression. Purine abnormalities have been associated with autism, but evidence has not typically linked purines to either the neurochemistry or behavioral hallmarks of the disorder. Here we review emerging and converging lines of evidence suggesting that a metabolic increase in the influence of the purine nucleoside adenosine has the potential to play a key role in reducing multiple behavioral and physiological symptoms of autism. First, results from a questionnaire study of parents of children with autism indicated that stimuli and activities predicted to increase adenosine are observed to reduce symptoms of autism. Second, a ketogenic diet—a high-fat, low-carbohydrate regimen used to treat epilepsy—can reduce electrographic seizures in mice via actions at adenosine A1 receptors, and other research has shown that a ketogenic diet can improve symptoms of autism in children with autism and improve sleep in children with epilepsy. In animal studies, this established metabolic therapy has been shown to increase ATP levels and reduce levels of the intracellular adenosine-metabolizing enzyme adenosine kinase, suggesting possible mechanisms for increased extracellular adenosine. While the number of studies investigating each of these areas is limited to date, accumulating evidence suggests that metabolic strategies to increase adenosine could address some of the core and comorbid symptoms of autism. Further research is needed.