Autism appears to be caused by a complex interplay of genetic and environmental factors. Over the past decade, scientists have established multiple animal models of autism using both genetic and environmental manipulations, demonstrating the presence of communication and social behavior deficits in these animals, as well as the presence of repetitive behaviors characteristic of individuals with autism. Randy Blakely and his colleagues at Vanderbilt University in Nashville, Tennessee, believe that the activation of a class of enzymes known as p38-alpha MAP kinases (p38-alpha MAPK) may underlie the ability of both genetic and environmental factors to produce autism.

Illness or infections during early pregnancy are associated with increased incidence of autism. In pregnant mice, exposure to viral or bacterial agents alters fetal brain development, and pups show behavioral changes that are analogous to features seen in autism.

Immune‐related genes and immune responses to environmental stimuli are receiving attention due to their potential involvement in several neurodevelopmental disorders, including autism. Immune‐related genes have been associated with autism and maternal infection has been found to be the most compelling environmental risk factor for the disorder. Additionally, immune molecules have been shown to play many roles throughout brain development, including the initial establishment of synaptic connections, as well as synaptic plasticity.

There is growing support for the idea that both genetic and environmental risk factors contribute to autism. One environmental risk is maternal infection, as validated by large epidemiological studies showing links between infection during pregnancy and autism in the child. Similar associations were found with elevated immune responses in maternal serum or amniotic fluid. Also consistent with an immune pathophysiology are findings of activated microglia — immune cells within the brain — in people with autism, as well as dysregulation of immune-related genes in the brain, cerebral spinal fluid and periphery.