The relationship between the neuromodulator adenosine and behavioral symptoms of autism

Abstract

The neuromodulator adenosine is an endogenous sleep promoter, neuroprotector and anticonvulsant, and people with autism often suffer from sleep disruption and/or seizures. We hypothesized that increasing adenosine can decrease behavioral symptoms of autism, and, based on published research, specific physiological stimuli are expected to increase brain adenosine. To test the relationship between adenosine and autism, we developed a customized parent-based questionnaire to assess child participation in activities expected to influence adenosine and quantify behavioral changes following these experiences. Parents were naive to study hypotheses and all conditions were pre-assigned. Results demonstrate significantly better behavior associated with events pre-established as predicted to increase rather than decrease or have no influence on adenosine. Understanding the physiological relationship between adenosine and autism could open new therapeutic strategies - potentially preventing seizures, improving sleep, and reducing social and behavioral dysfunction.

Adenosine and Autism - Recent Research and a New Perspective

“…Still, these results are promising and provide preliminary data supporting a link between a ketogenic diet and autism, and potentially among autism, adenosine and a ketogenic diet. The biggest improvements were quantified in those patients who showed only mild autistic behavior, similar to our findings for a trend for the biggest benefit for adenosine-increasing activities in individuals with Asperger's (Masino et al, 2011a). In addition to a reduction of their seizures, children on the ketogenic diet can enjoy other benefits -including reduced drug intake and general improvements in cognition, alertness, development, attention and social life (Kinsman et al, 1992;Sirven et al, 1999;Pulsifer et al, 2001;, and -as we found in our retrospective study -fewer behavioral problems (Svedova et al, 2010).…”

“…Parents were naive to all study hypotheses. Results from this study revealed a significant relationship between engaging in stimuli preassigned as expected to increase adenosine and parental report of decreased severity of ASD symptoms (Masino et al, 2011a). We found a trend for persons diagnosed with Asperger's to show a stronger behavioral effect of adenosine-increasing activities, a finding which deserves additional exploration.…”

“…Based on animal research suggesting non-pathological stimuli that could increase adenosine, we explored the possibility of a beneficial relationship between autism and adenosine via a customized behavioral questionnaire focused on behaviors typical of ASD (Masino et al, 2011a). Subjects were recruited with the assistance of the Interactive Autism Network (IAN) Research Database at the Kennedy Krieger Institute and Johns Hopkins Medicine -Baltimore, sponsored by the Autism Speaks Foundation.…”

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

“…Indeed, caloric restriction alone has seizure-reducing effects in EL mice [64,65]. In parallel, evidence is building that limiting glucose is anticonvulsant through an adenosine-based mechanism [54,56,66] and we hypothesized that ASD core symptoms could be alleviated by this same mechanism [67]. Here, for ASD-like symptoms, there appears to be a dissociation among caloric restriction, KD, and blood glucose.…”

Adenosine and autism: A spectrum of opportunities

“…Regarding adenosine modulation and autism, several reports have suggested therapeutic potential with diverse postulated benefits (Freitag et al, 2010; Ghanizadeh, 2010; Masino et al, 2009, 2011a; Tanimura et al, 2010). However, at this time the direction of the relationship, the relevance for particular symptoms, and the receptor subtypes and brain regions involved remain speculative.…”