From the Journals

Fetal exposure to folic acid may reduce youth psychosis risk

 

Key clinical point: Gestational exposure to grain products fortified with folic acid resulted in delayed thinning of the cerebral cortex, and thus may protect against later psychosis.

Major finding: Increases in cortical thickness were associated with folic acid exposure in the bilateral frontal and temporal regions of the brain (9.9%-11.6%; corrected P less than .001 to P = .03).

Study details: A retrospective, observational cohort study of 292 patients aged 8-18 years.

Disclosures: The study was funded by MQ: Transforming Mental Health, with support from grants from several additional sources, including the National Institutes of Health.

Source: Eryilmaz H et al. JAMA Psychiatry. 2018 Jul 3. doi: 10.1001/jamapsychiatry.2018.1381.

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Findings complement previous studies

The results of this study complement previous studies in the Netherlands “addressing similar questions using plasma levels of folate in maternal blood during pregnancy,” Tomáš Paus, MD, PhD, wrote in an editorial (JAMA Psychiatry. 2018 Jul 3. doi: 10.1001/jamapsychiatry.2018.1255) published with the study. However, he added, “it is unfortunate that the authors did not report values of cortical surface area in the different groups of individuals studied.”

Previous studies have shown that the children of mothers with high folic acid levels during pregnancy showed greater head growth and larger brain volumes at 6-8 years of age, Dr. Paus wrote, adding that future research should explore the possibility that exposure to folic acid induces effects such as DNA methylation, that may persist over time.

“This folate-methylation hypothesis needs to be tested empirically in large data sets, ideally in conjunction with relevant brain phenotypes, to replicate and expand the initial findings reported” in this study, he concluded.

Dr. Paus is affiliated with the department of psychology at the Rotman Research Institute, Toronto. He reported no conflicts of interest.


 

FROM JAMA PSYCHIATRY

Gestational exposure to grain products fortified with folic acid resulted in delayed thinning of the cerebral cortex, and thus may protect against later psychosis, according to results published in JAMA Psychiatry.

In a retrospective, observational cohort study of 292 patients aged 8-18 years, increases in cortical thickness were associated with folic acid exposure in the bilateral frontal and temporal regions of the brain (9.9%-11.6%; corrected P less than .001 to P = .03). Delayed, age-associated thinning in temporal and parietal regions was also observed (beta = –11.1 to –13.9; corrected P = .002), reported Hamdi Eryilmaz, PhD, of the department of psychiatry at Massachusetts General Hospital, Boston, and his coauthors.

The study authors first observed MRI scans in the Massachusetts General Hospital (MGH) cohort, which included the 292 patients aged 8-18 years, and then conducted subsequent analyses on two additional cohorts – the Philadelphia Neurodevelopmental Cohort (PNC) and the National Institutes of Health MRI Study of Normal Brain Development (NIH) cohort – to test the reliability and specificity of cortical development associations and the relevance of MRI changes to psychopathological characteristics, the authors wrote.

Using the U.S. implementation of folic acid fortification in grain foods in 1996 and 1997 to define exposure status, the investigators identified MRI scans of 97 prerollout (not exposed), 96 rollout (partly exposed), and 99 postrollout (fully exposed) unique individuals in the MGH group between January 2005 and March 2015, for patients born between January 1993 and December 2001. They also collected information on demographics; reason for MRI scan; and prior use of psychotropic medications, folic acid, or multivitamins.

The PNC cohort consisted of 861 patients, also aged 8-18 years, from community health settings in Philadelphia who had an MRI assessment and a clinical assessment of psychiatric symptoms. The NIH comparison cohort included 217 patients recruited from six health sites across the United States and born before the fortification rollout.

The MGH analysis contrasted mean cortical thickness and linear and quadratic models of age-associated change in cortical thickness within the fully exposed and nonexposed groups. PNC and NIH analyses evaluated quadratic associations of age with cortical thickness.

In the MGH cohort, increases in cortical thickness were associated with folic acid exposure in the bilateral frontal and temporal regions of the brain (9.9%-11.6%; corrected P less than .001 to P = .03), and delayed, age-associated thinning in the temporal and parietal regions was observed (corrected P = .002). Thickness was higher in the fully exposed group, compared with those in the nonexposed group. The effect was intermediate in the partly exposed group, Dr. Eryilmaz and his coauthors wrote.

In the PNC cohort, delayed, age-related thinning was observed in four clusters overlapping with the MGH analysis: left frontal, right inferior temporal, left inferior parietal, and right inferior parietal. In addition, onset of cortical thinning was found to be between 13.0 and 14.3 years of age in least-square regression analysis. In the comparison NIH cohort, though, only the left frontal cortex demonstrated significant quadratic thinning; the break point occurred at a significantly younger age, compared with those in the PNC group (P less than .001).

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