International Meeting for Autism Research: Exploring the Relationship Between the Neuromodulator Adenosine and Behavioral Symptoms of Autism

Exploring the Relationship Between the Neuromodulator Adenosine and Behavioral Symptoms of Autism

Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
S. A. Masino , Neuroscience and Psychology, Trinity College, Hartford, CT
M. Kawamura , Neuroscience and Psychology, Trinity College, Hartford, CT
J. Svedova , Neuroscience and Psychology, Trinity College, Hartford, CT
L. M. Plotkin , Neuroscience and Psychology, Trinity College, Hartford, CT
F. J. DiMario , Pediatric Neurology, Connecticut Children's Medical Center, Hartford, CT
I. M. Eigsti , Psychology, University of Connecticut, Storrs, CT
Background: The neuromodulator adenosine is an endogenous sleep promoter, neuroprotector and anticonvulsant, and people with autism often suffer from sleep disruption and/or seizures. Unfortunately, measuring plasma adenosine is not informative, measuring brain adenosine is not practical, and direct administration of adenosine or adenosine receptor agonists results in significant peripheral side effects. Recent efforts to regulate adenosine in the brain have yielded some success. To our knowledge, dysregulation of adenosine has neither been proposed nor tested with respect to the symptoms of autism. 

Objectives: Based on published research (primarily with animal models), specific physiological stimuli are expected to increase brain adenosine. We sought to determine if changing adenosine would influence specific behaviors. We hypothesized that in addition to established beneficial physiological effects of adenosine, such as reducing seizures, increasing adenosine would decrease behavioral symptoms of autism. In contrast, adenosine-neutral or adenosine-decreasing activities would not be expected to improve behavioral symptoms of autism.

Methods: To test this relationship between adenosine and autism, we developed a customized parent-based questionnaire to assess child participation in activities expected to influence adenosine, and the behavioral changes that follow these experiences. For each type of activity, we established both adenosine-increasing and adenosine-neutral or decreasing questions. Within a defined time window after each event, parents reported changes in nine domains (social and communicative skills, repetitive or perseverative activities, eye contact, social interest, sound sensitivity, sleep, anxiety, adapting to transitions and aggressive behavior) using a 5-point Likert scale (“lots of decline,” “some decline,” “no noticeable change,” “some improvement,” “lots of improvement”).

Results: The results of this questionnaire demonstrate significantly better behavior associated with events predicted to increase rather than decrease or have no influence on adenosine. There were no age-related effects, suggesting that the adenosine-related functional effect is independent of developmental level; there was also no effect of gender. Although this initial report relies on parental observation, parents were naive to any study hypotheses and all conditions were pre-assigned.

Conclusions: Pilot data from an internet-based parent survey customized to explore the relationship between autism and adenosine indicate a significant relationship between events predicted to increase adenosine and parental observations of behavioral symptoms of autism. Abnormalities in purine metabolism have been observed in autism, but have not been linked to core symptoms. Ultimately, understanding the relationship between adenosine and autism could help simultaneously to prevent seizures, improve sleep and reduce social and behavioral dysfunction. Importantly, a meaningful physiological relationship between adenosine and symptoms of autism opens new therapeutic strategies for Autism Spectrum Disorders.

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See more of: Clinical & Genetic Studies