Background: Genetics is a major etiological contributor to autism spectrum disorder (ASD). Environmental
factors, however, also appear to contribute. ASD pathophysiology due to gene x environment is also beginning
to be explored. One reason to focus on environmental factors is that they may allow opportunities for
intervention or prevention.
Methods and Results: Herein, we review two such factors that have been associated with a significant proportion
of ASD risk, prenatal stress exposure and maternal immune dysregulation. Maternal stress susceptibility appears
to interact with prenatal stress exposure to affect offspring neurodevelopment. We also explore how maternal
stress may interact with the microbiome in the neurodevelopmental setting. Additionally, understanding of the
impact of maternal immune dysfunction on ASD has recently been advanced by recognition of specific fetal brain
proteins targeted by maternal autoantibodies, and identification of unique mid-gestational maternal immune profiles.
This might also be interrelated with maternal stress exposure. Animal models have been developed to explore
pathophysiology targeting each of these factors.
Conclusion: We are beginning to understand the behavioral, pharmacopathological, and epigenetic effects related
to these interactions, and we are beginning to explore potential mitigating factors. Continued growth in understanding
of these mechanisms may ultimately allow for the identification of multiple potential targets for prevention
or intervention for this subset of environmental-associated ASD cases.