Prenatal exposure to folic acid linked to altered cerebral cortex development that protects against psychosis

New research provides evidence that prenatal exposure to folic acid fortification is associated with a reduced risk for symptoms of psychosis. The study, published in JAMA Psychiatry, found that increased in utero folic acid exposure was associated with changes in later brain development.

“Schizophrenia, autism, and other serious mental illness (SMI) that affect young people are chronic, debilitating, and difficult to treat. With converging evidence that risk for these disorders begin in the womb, it makes sense to focus on interventions during pregnancy that can enhance brain health and resilience,” said Joshua Roffman of Massachusetts General Hospital, the senior author of the study.

“Recent studies point to prenatal folic acid exposure as potentially important, with well-replicated public health studies showing a substantial reduction in autism risk following folic acid intake early in pregnancy. But mechanistic links between prenatal folic acid exposure and mental health outcomes are needed to help establish causality.”

A 1996 U.S. Food and Drug Administration regulation called for grain products such as enriched bread, flour, corn meal, rice and pasta to be fortified with folic acid by January 1, 1998.

“Using MRI scans we studied nearly 1,400 children who were born just before, during, or after the rollout of government-mandated folic acid fortification of grain products, a public health intervention that was introduced to reduce risk of spinal cord malformations and that doubled blood folic acid levels in women of childbearing age,” Roffman told PsyPost.

The researchers found that young people born after the implementation of folic acid fortification tended to have a different pattern of cortical maturation compared with participants born before the program began.

“We found that children and adolescents who were exposed to fortification during pregnancy showed changes in the development of their cerebral cortex that protected against psychotic symptoms,” Roffman explained. “This new evidence links exposure to a safe, inexpensive, and readily available intervention to reduced SMI risk through specific changes in cortical development.”

The study — like all research — has some limitation.

“Additional prospective cohort studies are needed to validate these results, and we still have much to learn about the basic neurobiology that underlies the long-term protective effects of prenatal folic acid exposure,” Roffman explained.

“That said, it’s important to point out that prenatal folic acid is already universally recommended to prevent spina bifida and other neural tube defects that occur in the first month of fetal life, before many pregnancies are recognized. The problem is that less than one third of women of childbearing age take folic acid supplements (pills), and less than half of the world’s population is exposed to folic acid fortification of grain products.”

“Were these numbers to improve, the impact on prevention of serious mental illness could potentially be dramatic,” Roffman added. “As such, our results have policy implications – with additional potential benefits on brain health that go above and beyond the known protective effects against neural tube defects, the case for increasing access to prenatal folic acid becomes that much stronger.”

The study, “Association of Prenatal Exposure to Population-Wide Folic Acid Fortification With Altered Cerebral Cortex Maturation in Youths“, was authored by Hamdi Eryilmaz, Kevin F. Dowling, Franklin C. Huntington, Anais Rodriguez-Thompson, Thomas W. Soare, Lauren M. Beard, Hang Lee, Jeffrey C. Blossom, Randy L. Gollub, Ezra Susser, Ruben C. Gur, Monica E. Calkins, Raquel E. Gur, Theodore D. Satterthwaite, and Joshua L. Roffman.