Joshua L. Roffman, MD Department of Psychiatry Mass General Hospital

Perinatal Folic Acid May Protect Against Serious Mental Illness in Young People Interview with:

Joshua L. Roffman, MD Department of Psychiatry Mass General Hospital

Dr. Roffman

Joshua L. Roffman, MD
Department of Psychiatry
Mass General Hospital What is the background for this study? What are the main findings?

Response: Autism, schizophrenia, and other serious mental illness affecting young people are chronic, debilitating, and incurable at present.  Recent public health studies have associated prenatal exposure to folic acid, a B-vitamin, with reduced subsequent risk of these illnesses.  However, until this point, biological evidence supporting a causal relationship between prenatal folic acid exposure and reduced psychiatric risk has remained elusive.

We leveraged the rollout of government-mandated folic acid fortification of grain products in the U.S. from 1996-98 as a “natural experiment” to determine whether increased prenatal folic acid exposure influenced subsequent brain development.  This intervention, implemented to reduce risk of spina bifida and other disabling neural tube defects in infants, rapidly doubled blood folate levels among women of childbearing age in surveillance studies.

Across two large, independent cohorts of youths age 8 to 18 who received MRI scans, we observed increased cortical thickness, and a delay in age-related cortical thinning, in brain regions associated with schizophrenia risk among individuals who were born during or after the fortification rollout, compared to those born just before it.  Further, delayed cortical thinning also predicted reduced risk of psychosis spectrum symptoms, a finding that suggests biological plausibility in light of previous work demonstrating early and accelerated cortical thinning among school-aged individuals with autism or psychosis. What should readers take away from your report? 

Response: Substantial evidence now suggests that vulnerability to severe mental illness begins in the womb.  Accordingly, it makes sense to target preventative efforts toward this critical period of brain development.  Our findings suggest that an inexpensive, safe, and readily available intervention, prenatal folic acid, influences postnatal brain development in ways that may protect against risk of serious mental illness in young people. What recommendations do you have for future research as a result of this work?

Response: Prospective clinical studies that link maternal folate levels directly to indices of brain development and risk of psychiatric illness early in life are warranted, as are basic studies that elaborate specific molecular mechanisms by which early folic acid exposure influences subsequent brain maturation.

This work could have important policy implications, as fortification is mandated in only 81 countries and reaches less than half of the world’s population.  With added potential benefits for brain health, as well as its known protective effects against spina bifida and other neural tube defects, folic acid fortification may hold greater appeal for governments that have not yet adopted it.

Author disclosures are listed at the end of the article.


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. Published online July 03, 2018. doi:10.1001/jamapsychiatry.2018.1381

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