This project describes an attempt to develop the first effective drug treatment for the core social impairments of autism spectrum disorders (ASDs). The project takes a significant step forward towards improving the quality of life of persons with ASDs through the development of more effective medicines. The primary objective of this project is to conduct a clinical trial of acamprosate in youth with ASDs. Based on preliminary data, acamprosate may be a safe and effective treatment for the social impairments associated with ASDs. A 10-week short-term acamprosate treatment study will be conducted in 36 youth with ASD aged 5 to 17 years followed by a 16 week study extension for participants who respond well to acamprosate in the short-term study. In addition to assessing whether acamprosate use is associated with reduced social impairments, this study will also closely assess how the youth taking acamprosate tolerate the drug. In addition, this project will measure proteins in the blood following acamprosate treatment, a study that may provide a better understanding of the brain biology associated with ASDs. Finally, a novel eye tracking test will be used to assess whether treatment with acamprosate is associated with any changes in how children with ASDs visually assess faces. Findings from this project will be essential to the design of a future, larger, more definitive study of acamprosate in youth with ASD. Developing effective medication options for the core social impairment of ASDs will fill a clear area of unmet medical need thus enhancing the quality of life of persons impacted by ASDs.