Food With Folic Acid May Decrease Risk of Schizophrenia

July 11, 2018

Prenatal exposure to grain products fortified with folic acid is linked with changes in brain development that, in turn, predict a decreased risk of psychosis, according to a study published online in JAMA Psychiatry.

The study compared brain images of school-age children born prior to, during, and after implementation of the 1996 mandate to fortify grain-based foods with folic acid in an attempt to reduce the risk of neural tube defects in babies.

Researchers reviewed 3 sets of magnetic resonance imaging (MRI) brain scans of children aged 8 to 18. The first set was taken at Massachusetts General Hospital, Boston, as part of the clinical care of 292 patients. The second set involved 861 participants from the Philadelphia Neurodevelopmental Cohort and included assessment of psychiatric symptoms. A third set was for 217 participants in a multisite National Institutes of Health study.

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Participants were grouped according to their probable prenatal exposure to folic acid: those born before July 1, 1996, when fortification began; those born in the next 2 years, during intermediate exposure; and those born after July 1, 1998, when implementation of folic acid fortification was complete.

Young people born after full implementation of folic acid fortification had different patterns of cortical maturation, compared with participants born before folic acid fortification, the study found. Specifically, children born after full implementation had significantly thicker brain tissue and delayed thinning of the cerebral cortex in regions linked with schizophrenia. Cortical thickness of children born during the rollout period was intermediate between the other groups.

While thinning of the cerebral cortex is a normal part of brain maturation, early and accelerated cortical thinning has been linked with autism and psychosis symptoms, researchers explained.

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Psychiatric symptom data from the Philadelphia cohort showed that the delayed cortical thinning seen in children fully exposed to folic acid fortification was associated with significantly reduced risk of psychosis symptoms. 

“While our results link prenatal exposure to folic acid fortification with changes in cortical development and with a reduced risk of psychotic spectrum symptoms, they cannot directly link folic acid exposure to reduced schizophrenia risk, since the typical age of onset for that disorder is in the early 20s,” said study senior author Joshua Roffman, MD, of Massachusetts General Hospital, Boston. “But since such symptoms in youth are on the same continuum as schizophrenia, the results hold some promise for schizophrenia prevention.”

“The oldest participants in our study are now approaching the age of greatest risk for several psychiatric disorders—also including bipolar disorder and depression—so it will be of great interest to see whether exposure does have an effect on the incidence of these disorders.”

—Jolynn Tumolo


Eryilmaz H, Dowling KF, Huntington FC, et al. Association of prenatal exposure to population-wide folic acid fortification with altered cerebral cortex maturation in youths. JAMA Psychiatry. 2018 July 3;[Epub ahead of print].

Prenatal exposure to folic acid fortification of foods may reduce mental illness risk [press release]. Boston, MA: Massachusetts General Hospital; July 3, 2018.