Mitochondrial Dysfunction in Autism Spectrum Disorder

Objective: The main objective of this proposal is to develop a minimally-invasive biological assay that can be widely used to identify variations in mitochondrial function and dysfunction in children with autism spectrum disorder (ASD). This assay will allow the investigators to determine the true range of mitochondrial function and dysfunction across a population of children with ASD. The relationship between mitochondrial function and dysfunction in ASD, redox metabolism and core ASD symptomology will also be investigated. To understand the true variation in mitochondrial function and its relationship to cognitive development and autism symptoms, participants will be evaluated at two time points to understand the within subject variation of mitochondrial measurements. Specific Aims: 1) To develop a minimally-invasive assay that can accurately identify children with ASD/MD from the general ASD population. 2) To establish whether there is simply an ASD/MD subgroup or whether mitochondrial dysfunction occurs on a spectrum from mild to severe in ASD. 3) To determine the relationship between mitochondrial function and redox metabolism in children with ASD. 4) To evaluate the effect of mitochondrial dysfunction and glutathione redox status on language and social development and ASD symptoms. Study Design: Using the Seahorse Analyzer, investigators will develop profiles of mitochondrial function for individuals with ASD and known MD (ASD/MD) and individuals with ASD known not to have MD (ASD/NoMD). These two groups will serve as the two ends of the spectrum of mitochondrial function in children with ASD and will be compared to profiles from TD children. Investigators will then examine the profiles of mitochondrial function in a general population of individuals with ASD to determine how these individuals fall into this spectrum defined by the ASD/MD and ASD/NoMD groups, as well as DD and no ASD/MD. Glutathione redox metabolism will be measured in all participants. The relationship between mitochondrial function, redox metabolism and core ASD symptoms will be studied in the ASD groups with particular attention to whether ASD symptoms, language ability and adaptive behavior are directly related to mitochondrial function or indirectly related to mitochondrial function through its effect on redox metabolism. Study Population: Investigators will recruit several groups of children for this study: 50 children with ASD who have MD (ASD/MD); 50 children with ASD who do not have MD (ASD/NoMD); 50 no ASD/MD; 50 no ASD/no MD but DD; 100 TD controls; and a general population of 150 children with ASD. Children with ASD with and without MD will be identified in the autism multispecialty clinic (AMC), as well as the ATN and other medical clinics that evaluate children with ASD in outpatient clinics in Arkansas. When a child is identified, the study coordinator will contact the parents and describe the study. If the parents are interested, the coordinator will screen by asking inclusion/exclusion criteria questions. If the child qualifies, the coordinator will schedule the visit and mail consent forms to the parents for their review. During the visit they will undergo a blood draw for metabolic testing. The child will then be sent to breakfast since the blood tests require collection prior to breakfast. After breakfast the participant will undergo further language and behavioral assessment while the parent will be interviewed for the Vineland and other questionnaires. The parents will be provided questionnaires for the teacher to fill out and mail in an addressed, postage paid envelope. For the TD participants, these children will be recruited in several ways including using social media through Arkansas Children's Hospital, flyers posted in the community (i.e. primary pediatric clinics), as well as referrals from pediatricians. When a child is identified, the study coordinator will contact the parents and describe the study. If the parents are interested, the coordinator will screen by asking inclusion/exclusion criteria questions. If the child qualifies, the coordinator will schedule the visit and mail consent forms to the parents for their review. During the visit they will undergo a blood draw for metabolic testing.