Autism occurs four times more frequently in males compared to females, suggesting that a complex genetic predisposition, involving hormones, is involved. According to these researchers, since females have stronger emphasizing capability, while males have stronger systemizing capability, an "extreme male brain" (EMB) theory may explain the genetic basis of autism. This theory proposes that individuals along the autism spectrum are characterized by impairments in empathy alongside intact or even exceptional systematizing capacities. The researchers suggest that endogenous hormone levels of either or both the parent and the fetus during development are important. They hypothesize that inherited genetic variations in androgen metabolism modify the risk of autism, that there is a critical time when fetal exposure to androgens, specifically testosterone, is related to later development of autism spectrum disorder. They will test the EMB theory by undertaking genetic studies in 260 mother-child pairs in which the child has autism. First, the researchers will identify different forms of androgen-metabolizing genes that are biomarkers for integrated hormone levels. They then will assess this relationship between androgen metabolism and autism risk by analyzing forms of genes that favor the production and accumulation of testosterone. Thereafter, they will confirm whether the forms of genes identified occur in 300 healthy mother-child pairs, and whether maternal or fetal hormonal levels are key. Through this process, the researchers will derive direct evidence on whether or not the EMB theory is valid. Significance: If the EMB theory is validated, it would lead to further clinical efforts to assess genetic or individual susceptibility factors that increase the risk of autism, and to explore whether contributing hormonal, environmental or dietary exposures might be minimized.