Early Pharmacotherapy Guided by Biomarkers in Autism

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DESCRIPTION (provided by applicant): The investigators have previously shown a different time course in the developmental values of brain serotonin synthesis in children with autism using positron emission tomography (PET). These data are consistent with the notion that serotonin synthesis is abnormal during critical periods of brain development in autistic children. Specific to this project, the investigators demonstrated that serotonin synthesis capacity in children less than the age of six years showed significantly lower values than non- autistic children. Since serotonin is known to be an important factor involved in postnatal synaptogenesis, they hypothesized that one approach to the treatment of autism pharmacologically is the use of serotonin agonists in children less than the age of six years. The goal of this treatment is to provide a more normal serotonergic modulation of synaptic plasticity in autistic children during the early childhood years. For this study, they chose the 5HT1A serotonin agonist buspirone. The rationale for the choice of buspirone was based upon basic studies demonstrating a prominent role of the 5HT1A receptor in the regulation of postnatal synaptogenesis. The long-range goal is to utilize biochemical and genetic factors in autism that can be used in the rational design of treatment in groups or subgroups of children with autism. This study is to test further the safety and efficacy of buspirone in a large group of young autistic children. This trial is guided by pilot study results funded by NICHD through the Pediatric Pharmacology Research Unit (PPRU) network. In their pilot study, the investigators demonstrated improvement in social interaction, repetitive behavior, sensory dysfunction, and anxiety with three months of buspirone treatment. A subset of the children continued in a six-month open label study and showed further improvement by the end of the open label study. In addition, serotonin synthesis capacity measured with a-[11C]-methyl-L-tryptophan (AMT) PET was related to the response to buspirone in the pilot study, while plasma serotonin was not. Thus AMT PET will be tested as a biomarker for drug response.