Proof of Mechanism Study for the Treatment of Social Anhedonia in ASD

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PROJECT SUMMARY Understanding the biological underpinnings of variation in social “wanting”, or lack thereof, in individuals with ASD could open important areas for intervention. Despite solid evidence-based approaches for improving social functioning in ASD, the majority of high-functioning adults with ASD remain isolated, with outcome studies consistently noting little or no motivation to achieve relationships. Yet contrary to Kanner's original hypothesis that autism is a ubiquitous “deficit in affective contact”, contemporary studies find extraordinary variation in social behavior in ASD, with preservation of typical attachment behaviors, social cognition, and social knowledge in many. Social neuroscience has revealed the importance of central nervous system dopamine interactions with other systems such as neuropeptide signaling in normal social function, but dopamine's role has not been carefully probed in people with ASD. This project proposes a proof of mechanism study to test the hypothesis that individual differences in dopaminergic tone will help reveal differences in social motivation, and that modification of dopaminergic tone will impact social “wanting” and social reward responsivity. We plan to enroll a sample of high-functioning adolescents and young adults with ASD who will be receiving a 16-week social skills training program. We will examine differences in indices at multiple levels of social motivation and social reward, from: 1) neural reward circuit activation; 2) physiologic responses; 3) affective responses to social interaction; and 4) social interest and enjoyment, at pre-treatment, and during the placebo-controlled administration of a dopamine agonist. This project is synergistic with other Center components, obtaining common measures of reward responsivity in Project 3, applying shared Diagnostic and Phenotyping Core measures, and collecting biospecimens for combined genetic and other analyses, enabling broader investigations of heterogeneity across age and gender. Project results will yield a definitive “Yes” or “No” confirmation of dopamine as a possible treatment target for social dysfunction in ASD. !