In response to a 1996 government mandate, food producers in the U.S. began fortifying their grain-based products with folic acid to reduce serious birth defects affecting the brain, spinal cord, and spine. Now, a study reported July 3 in JAMA Psychiatry demonstrates that a mother’s exposure to folic acid during pregnancy continues to support their child’s brain development after birth and reduces the risk that they will experience psychosis.

Joshua L. Roffman, M.D., M.M.Sc., a 2014 Independent Investigator and 2007 Young Investigator at Massachusetts General Hospital, led the study, which used MRI scans to compare the brains of more than 1,200 children and adolescents born from a few years before through a few years after the folic acid mandate was first implemented. 2008 Distinguished Investigator, 1995 Independent Investigator and 1987 Young Investigator Ezra S. Susser, M.D., Ph.D. at Columbia University, 2010 Young Investigator Theodore D. Satterthwaite, M.D. and 2007 Distinguished Investigator Ruben Gur M.D., Ph.D., both at the University of Pennsylvania, were also on the research team.

It took about two years for folic acid to be incorporated into all grain-based products after the mandate first took effect. This gave the research team an opportunity to study children whose mothers had likely consumed low, medium, or high levels of folic acid-enriched grains during their pregnancies, depending on whether their pregnancy occurred before, around the time of, or well after the mandated folic acid fortification.

Brain scans were taken when study participants were between the ages of 8 and 18. Dr. Roffman’s team found that on average, the brain’s cortex was thinnest in children who were born prior to the mandate and thickest in those who were born after it had been widely implemented. Children born between 1996 and 1998, whose mothers are expected to have been exposed to intermediate levels of folic acid during their pregnancies, had brains whose cortical thickness was in between that of the other groups.

The team noted that thinning in parts of the cerebral cortex, a normal part of brain development that occurs during childhood, occurred later in life for those born after 1998. This delayed cortical thinning was associated with a lower risk of psychosis symptoms. Early and accelerated cortical thinning have previously been linked to autism and schizophrenia; the new findings suggest folic acid exposure during pregnancy might protect against this.

“Prospective studies are needed to validate these effects,” says Dr. Roffman, “but more broadly, this work may help establish one of the first prenatal protective interventions in psychiatry aimed at reducing risk of severe mental illness in the child.”

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