Autism, ADHD ? Genetics, Epigenetic, Nutrition, Gestational Growth, and Environmental Factors

The size of an infant at birth, a measure of gestational growth, has been recognized for many years as a biomarker of future risk of morbidity. Both being born small for gestational age (SGA) and being born large for gestational age (LGA), are associated with increased rates of obesity and metabolic disorder, as well as a number of mental disorders including attention deficit/hyperactivitydisorder, autism, anxiety, and depression. The common risks raise the question of what neurobiological mechanisms are altered in SGA and LGA offspring. Here we review recent findings allowing for direct comparison of neurobiological outcomes of SGA and LGA in human and animal models. We also present new data highlighting similarities and differences in behavior and neurobiology in our mouse models of SGA and LGA. Overall, there is significant data to support aberrant epigenetic mechanisms, particularly related to DNA methylation, in the brains of SGA and LGA offspring, leading to disruptions in the cell cycle in development and gene expression in adulthood.

Autism spectrum disorders (ASD) have been increasing in prevalence over the last two decades, primarily because of increased awareness and diagnosis. However, autism is clearly a complex human genetic disorder that involves interactions between genes and environment. Epigenetic mechanisms, such as DNA methylation, act at the interface of genetic and environmental risk and protective factors. Advancements in genome-wide sequencing has broadened the view of the human methylome and revealed the organization of the human genome into large-scale methylation domains that footprint over neurologically important genes involved in embryonic development. Future integrative epigenomic analyses of genetic risk factors with environmental exposures and methylome analyses are expected to be important for understanding the complex etiology of ASD.

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