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Gestational folic acid exposure reduces risk of psychosis in children

Tristan Manalac
11 Jul 2018
The demands for folate increase during pregnancy due to its role in nucleic acid synthesis.

Gestational exposure to grain products fortified with folic acid appears to be linked to a lower risk of psychosis in offspring, according to a recent study.

The study included three cohorts: the Massachusetts General Hospital cohort (MGH; n=292), with youth born during the folic acid fortification rollout; the Philadelphia Neurodevelopmental Cohort (PNC; n=861), with youth born throughout the rollout; and the National Institutes of Health cohort (NIH; n=217), with youth born before the rollout.

In the MGH cohort, 99 participants were fully exposed to the folic acid-fortified grain products (mean age 12.9±2.0 years; 47.5 percent female), 96 were partially exposed (mean age 13.5±2.8 years; 44.8 percent female) and 97 were nonexposed (mean age 13.3±2.1 years; 50.5 percent female). [JAMA Psychiatry 2018;doi:10.1001/jamapsychiatry.2018.1381]

Imaging showed group differences in cortical thickness, such that those who were fully exposed to folic acid fortification during gestation had thicker bilateral frontal and inferior frontal temporal regions than those who were nonexposed. Intermediate effects were observed for participants who were only partially exposed.

To generalize the findings from the MGH cohort, researchers repeated the analysis in the PNC and NIH prospective cohorts. Researchers found delayed age-related thinning in participants fully exposed to folic acid fortification. This effect was observed in the following areas of the brain: left frontal, right inferior temporal, left inferior parietal and right inferior parietal.

“An analogous pattern was evident in the contemporaneous PNC cohort: individuals who were exposed to folic acid fortification exhibited delays of cortical thinning of similar duration, which occurred in similar frontal, temporal and parietal regions,” researchers explained.

These findings were further confirmed in the NIH cohort, which included participants who were all born before the folic acid fortification rollout. Unlike both the MGH and PNC cohorts, nonlinear cortical thinning in the NIH cohort was sparse.

Significant nonlinear thinning in the NIH cohort was only observed in the left frontal cortex, but even within this cluster, thinning occurred significantly earlier than in the PNC cohort (p<0.001).

To assess the risk of psychosis, researchers again drew from the PNC cohort, where detailed clinical characterization was available. In this group, 248 were typically developing, 199 had a diagnosis along the psychosis spectrum, 104 had attenuated symptoms and 309 had other psychopathologic conditions.

The risk of psychosis was significantly lower in those with flatter age-related cortical thinning profiles, with adjusted odds ratios ranging from 0.37–0.59 and p-values ranging from 0.02–0.15.

“Collectively, these data suggest an association of prenatal exposure to folic acid fortification with increased cortical thickness through early adolescence, accompanied by delayed onset of cortical thinning and reduced risk of psychosis,” said researchers.

“Beyond its known association with the prevention of neural tube defects, increased gestational exposure to folic acid through food fortification may protect against psychosis through altered postnatal cortical development,” they added.

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