David Q. Beversdorf*, Hanna E. Stevens, Kara Gross Margolis and Judy Van de Water Pages 4331 - 4343 ( 13 )
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.Autism spectrum disorder, prenatal stress, immune dysregulation, maternal antibodies, microbiome, pathophysiology.
Departments of Radiology, Neurology, and Psychological Sciences, and The Thompson Center for Neurodevelopmental Disorders, William and Nancy Thompson Endowed Chair in Radiology, University of Missouri, Columbia, MO, Departments of Psychiatry and Pediatrics, Iowa Neuroscience Institute, University of Iowa, Iowa City, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Morgan Stanley Children’s Hospital, Columbia University Medical Center, New York, Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, And the MIND Institute, University of California, Davis, CA