This Baltimore-Washington STAART Center will study the neurobiological origins of motor planning and communication impairments in autism. The goal is to identify fundamental biologic alterations of brain development that underlie the core manifestations of autism and to translate these insights into effective therapies through early identification and intervention. In order to accomplish this goal, we have assembled a group of 22 investigators representing 7 disciplines (psychiatry, neuropsychology, psychology, speech-language pathology, developmental pediatrics, neuroscience) in a consortium involving the Kennedy Krieger Institute (lead agency), Children's National Medical Center, Johns Hopkins University, Morgan State University, and Georgetown University. We propose 3 research projects (1 basic science and 2 clinical) and two cores (administration and clinical). We will also have the core support of two Mental Retardation and Developmental Disabilities Research Centers in molecular genetics, cellular neuroscience, functional neuroimaging, and biostatistics. The first project addresses the role of 5-HT afferents in the initiation and progression of synaptogenesis in the cortex during postnatal development in a neonatal 5-HT depleted animal model of autism. The second project will address origins of symptoms, early neurobiological mechanisms, and treatment of key deficits near the time of their emergence through studies of toddlers at high risk for autism. The third project will extend understanding of autism provided by the other projects to a point later in life: in school-aged children. It will focus on motor execution and its relationship to cognitive functioning. This project will use structural and functional MRI procedures to elucidate the neurobiological basis of attention, motor planning, and executive function in individuals with high functioning autism. Taken as a whole, the projects should add significantly to our knowledge of the ontogeny of autism and thereby lead to the development of novel treatment approaches.