The development of better treatments for autism would be facilitated greatly if we understood the specific abnormalities in the brain that are associated with autism. A very common feature of individuals with autism is difficulty with social interactions. Behaviors associated with normal social interactions are processed in several areas of the brain, but especially in a region called the anterior cingulate cortex. Interestingly, the anterior cingulate cortex is an area of the brain where brain imaging studies of living subjects with autism have shown several abnormalities. In particular, abnormalities in the white matter of the anterior cingulate cortex have been consistently observed in autism. A major function of white matter of the anterior cingulate cortex is to transmit information to and from neurons of the cortex where information related to social interaction behaviors is processed. There are two major types of cells in the white matter of the anterior cingulate cortex that support white matter function. Based on imaging and other research findings, it seems highly likely that these two cell types are dysfunctional in the white matter in autism. We believe that a detailed molecular examination of these two major cell types in the white matter of the anterior cingulate cortex will reveal information that is extremely important to our understanding of the biological basis of autism, particularly as it relates to disruption of social interactions. We will use state-of-the-art research methods that allow us to dissect with high accuracy the individual cell types of the white matter from postmortem brain tissue from highly characterized autistic subjects and matched control subjects. These tissues have been made available to us through national and foundation-based brain banks. We will use high-throughput microarray and gene expression methods to screen cells for signs of disruption of cell function. Elucidating molecular pathologies in these two cell types in autism will yield clues to the etiology of autism and has the potential to stimulate the development of diagnostic tools through identification of biomarkers. Most importantly, the proposed studies have the potential to identify unique molecular targets for drug development, which could have a major impact on autism therapy given the lack of adequate drug treatments for autism.