Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social function, abnormal communication and repetitive or unusual behavior. Estimated rates of autism in US surveillance populations have increased to one in sixty-eight children (1/68) in 2010.
Recent epidemiological studies have suggested a link between maternal folate status during pregnancy and risk of autism in children. The role of folate for the process of neurodevelopment is increasingly recognized by the scientific community. Folate is critical for the process of DNA methylation which in its turn affects expression of certain genes. When folate levels are insufficient DNA methylation is adversely affected causing a cascade of neurodevelopment consequences.
In the 1st month of gestation, the central nervous system begins to form with neurogenesis and cell migration occurring in the forebrain, midbrain and hindbrain. Neurogenesis in most cortical and subcortical structures occurs between 5 and 25 weeks of gestation. The development of functional neuron networks requires high concentrations of methyl donors, such as folate, for differentiation of cells. Early alterations in DNA methylation that cause developing brain cells not to develop and differentiate properly can result in irreversible reductions or expansions of neuron pools. As a result, brain connectivity may become adversely affected. Impaired connectivity between various brain regions is one of the most common fMRI findings in autism.
Besides its impact on DNA methylation, folate status can influence development in other ways. For example, mutations in the gene called FOLR1 coding for folate receptor α were linked to hypomyelination of the brain, a condition that also affects connectivity of brain structures. Another important implication of folate deficiency is that it affects production of important neurotransmitters in the brain, such as serotonin. Serotonin dysregulation is another common finding across autism spectrum.
Maternal folate status may very well be a plausible biological risk factor for autism, however more research will be needed to better understand this connection and the mechanisms by which exerts its influence on the developmental process.
In the US, CDC currently recommends 400 mcg (micrograms) of daily supplementation with folic acid for women of childbearing age.
Sources:
CDC Folic Acid Recommendations https://www.cdc.gov/ncbddd/folicacid/recommendations.html
DeVilbiss, E. A., Gardner, R. M., Newschaffer, C. J., & Lee, B. K. (2015). Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. British Journal of Nutrition, 114(5),
663-672.
Walsh, W. Epigenetics. Retrieved from https://www.walshinstitute.org/epigenetics.html
