Autism may result from a complex interaction between genetic, metabolic, and environmental factors. In examining the genetic factors in autism, which genes are actually converted into protein (“expressed”) can matter as much as which genes have mutations. The importance of gene expression in autism was demonstrated recently by Dr. Hu's group in a study of the rare cases of identical twins in which only one twin has autism. Although genetically identical, many genes involved in neural development and function were expressed differently between the twins. Additional evidence suggests that metabolic pathways that produce steroid hormones and neuropeptides are altered in autism, and these products may also influence gene expression and neural development. This project will explore the mechanisms that regulate gene expression in cell lines derived from people with autism, and it will screen for steroid hormones and neuropeptides in these cell lines. Finally, experiments will study the interaction of genetic, metabolic (steroid hormones), and environmental (oxidative stress) factors in a neuronal cell model. Specifically, the effect of turning off certain genes alone, and in combination with exposure to steroid hormones or oxidative stress will be examined. What this means for people with autism: Understanding the complex interplay of genetic, metabolic, and environmental factors in a single cell will be a major step toward understanding how these factors may interact to cause autism.