July 05, 2018
2 min read

Fetal exposure to folic acid via fortified foods tied to lower psychosis risk

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Joshua L. Roffman

Increased gestational exposure to fortification of grain products with folic acid may protect against psychotic symptoms in offspring, according to findings published in JAMA Psychiatry.

“Schizophrenia, autism and other serious mental illnesses that occur in young people tend to be chronic, debilitating and incompletely responsive to medication and other treatments,” Joshua L. Roffman, MD, MMSc, of the department of psychiatry, Massachusetts General Hospital, told Healio Psychiatry. “Efforts to prevent these illnesses have also been elusive, but with mounting evidence suggesting that risk for severe mental illness begins in the womb, finding ways to target this critical developmental time point has become a priority.”

Researchers examined the connections between fetal folic acid exposure, cortical maturation and psychiatric risk in children in this retrospective, observational clinical cohort study. They measured the differences in cortical thickness among nonexposed, partially exposed and fully exposed youths as well as the underlying links between age and cortical thickness in all cohorts.

“Our work builds on recent, large public health studies that have linked maternal use of folic acid supplements with substantial decreases in autism risk for the child — work that although well replicated has lacked biological mechanisms to support a causal relationship between folic acid exposure and reduced risk of illness,” Roffman said.

Conducted at Massachusetts General Hospital, the investigators identified 292 children aged 8 to 18 years born between 1993 and end of 2001 with normal clinical MRI results and divided them into three age-matched groups based on birthdate and related level of prenatal folic acid fortification exposure. MRI took place between January 2005 and March 2015. They studied two independent, community-based cohorts — the Philadelphia Neurodevelopmental Cohort and NIH MRI Study of Normal Brain Development — which comprised 1,078 youths born throughout or before the rollout of the U.S.-mandated grain product fortification with folic acid in effect by mid-1997, for replication, clinical extension and specificity. In analysis of the Philadelphia cohort, they also examined the ties between age-cortical thickness slopes and the risk for psychotic symptoms.

Analysis revealed that 139 girls and 153 boys in the Massachusetts General Hospital cohort had exposure-related cortical thickness increases in their bilateral frontal and temporal regions (9.9% to 11.6%; P < .001 to P = .03) and emergence of quadratic (delayed) age-associated thinning in their temporal and parietal regions ( = –11.1 to –13.9; P = .002).

The Philadelphia cohort, composed of 417 girls and 444 boys, also demonstrated exposure-related delays of cortical thinning ( = –1.59 to –1.73; P < .001 to P = .02), observed in similar brain regions and with alike delay durations as those seen in the Massachusetts cohort, according to the results. The frontal, temporal and parietal brain regions that demonstrated flatter thinning profiles were tied to lower risk for psychosis spectrum symptoms in the Philadelphia cohort (OR = 0.37-0.59; P < .05).

In addition, researchers found that all identifiable brain regions showed earlier thinning in the nonexposed NIH cohort comprised of 118 girls and 99 boys.

“While more studies are needed to conclusively link prenatal folic acid exposure with subsequent brain health, it is also important to point out that prenatal folic acid is a safe, inexpensive, and readily accessible intervention that is already recommended in women of child-bearing age to prevent spina bifida and other neural tube defects,” Roffman told Healio Psychiatry. “The prospect that such an intervention could reduce risk for severe mental illness in youth — even if only a small number of children ultimately benefit — lends some hope that large-scale preventative interventions are possible in psychiatry, as they are in areas of medicine like infectious disease.” – by Savannah Demko

Disclosure: Roffman reports grant support and consulting income from Pamlab.