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

Participants will comprise two groups: 1) 56 (male and female) adolescents and young adults likely to meet inclusion/exclusion confirmed by study assessment who will be outpatients, ages 13 to 30 years, inclusive; and 2) 18 (male and female) healthy adolescents and young adults without any history of significant psychiatric disorders or treatment, who will be ambulatory, and will reflect the racial, ethnic, and socio-economic composition of Los Angeles, and will be recruited without regard to gender, race, or ethnic background. Healthy control adolescents (and parents) and young adults who meet all inclusion and exclusion criteria, will undergo a one-day 4-5 hour research evaluation of current functioning and behavior, cognitive function, including intellectual testing, urine drug screen, completion of questionnaires about possible psychological symptoms, perform brief tests to measure reward response, and complete a research Magnetic Resonance Imaging scan. Healthy control will not receive any interventions or medication. All eligible ASD participants will be enrolled concurrently in a 16-week, structured, group-based, social skills training program (PEERS®). After screening evaluations, eligible subjects will undergo baseline MRI scanning and behavioral assessments (self- and parent-report measures, videotaped interaction) and then randomized in a blocked schedule to yield 1:1 L-DOPA: placebo assignment, before beginning weekly social skills training. Medication administration will begin simultaneously with social skills training, and subjects will be seen weekly for the 1st 8 weeks, then biweekly for the final 4 weeks for safety assessments, dose titration, and compliance checks. During the 16-week study period, primary behavioral assessments will be repeated at Week 8 and at end of study on Week 16. A second MRI scan will be obtained within + 4 days of last social skills session. A follow-up safety phone call to assess post-study condition will be performed 30 days after completion of double-blind. The rich set of behavioral observations obtained across the 16 weeks will allow the possible identification of early clinical efficacy changes associated with L-DOPA administration, which could add further support for investigating this mechanism in future studies. Results from the project should inform reseacher's understanding of determinants of social dysfunction in ASD and may support further investigation of treatments modulating central nervous system dopamine function as a therapeutic strategy to enhance social functioning in ASD.