Immune Functioning and Reward Processing in Autism

Project Summary This exploratory grant seeks to evaluate linkages between social reward processing in autism spectrum disorder (ASD) and systemic inflammation. The social motivation theory of autism posits that reduced motivation to interact with people and decreased pleasure derived from social interactions may derail typical social development and contribute to the emergence of social communication deficits in ASD. This framework highlights the centrality of impaired brain reward circuitry functioning to the etiology of ASD and suggests that when young children with ASD lack the motivation to participate in activities where social skills are typically forged, the resulting impoverished social environment contributes to the emergence of social communication impairments in the disorder. There is increasing evidence that inflammatory processes contribute to ASD risk and pathogenesis, and that neuroinflammation, in turn, interferes with social reward processing. However, no research to date has examined relations between immune function and neural responses to social rewards in ASD. The objective of this proposal is to investigate relations between (i) neural responses to social rewards, measured via electroencephalography (EEG), (ii) a blood-derived composite marker of systemic inflammation, and (iii) ASD symptoms and quality of life. Additionally, half of participants will be recruited from a companion study collecting positron emission tomography (PET) data using a translocator protein 18 kDa (TSPO) tracer to measure neuroinflammation centrally, and an exploratory goal of this proposal is to investigate relations between EEG-based responses to social rewards, PET-derived (i.e., central) measures of neuroinflammation, and a blood-derived (i.e., peripheral) measure of systemic inflammation from the portion of autistic participants who completed TSPO PET scans. This project will provide a deeper understanding of relations between neural responses to social rewards, immune functioning, and symptom expression in ASD. It also has the potential to contribute to the development of EEG-based measures that may be suitable endpoints in future mechanistic trials investigating novel ASD interventions targeting inflammatory processes.