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

This project will use the experimental medicine approach of a Phase IIa Proof of Mechanism 16-week, randomized, double-blind, controlled trial of L-DOPA versus placebo administration in combination with a 16 week social skills training group in order to: 1) identify differences in social reward processes in adolescent and young adult ASD participants versus healthy controls as measured by fMRI activation in reward circuitry; 2) provide evidence of dopaminergic moderating effects on social reward components in ASD with greater pre- to post-treatment changes expected in the subjects randomized to L-DOPA versus placebo; 3) examine the hypothesis that baseline readouts of putative dopamine signaling (wanting activation responses) will predict the extent of fMRI reward-related activation changes pre- to post-treatment; and, 4) examine the proposed relationship between pre- to post- L-DOPA fMRI reward changes and changes in individual self-report ratings of social wanting and ratings of videotaped positive affect in a structured interaction with an examiner. The study will enroll 56 participants with DSM-5 ASD between the ages of 13-30 years of age and 18 healthy control participants without histories of psychopathology for baseline comparisons.