Folate and global health: part 5. syntheses on neuropsychiatric disorders.

Authors

Samantha Yoo, Azita Montazeri, Derrick Bennett, Yacong Bo, Peizhan Chen, Susan Duthie, Natalie Jensen, Atipatsa Kaminga, Jun-Shi Lai, Xue Li, Amanda J MacFarlane, Homero Martinez, Helene McNulty, Franco Momoli, Peter Mossey, Ron Munger, Rajendra Prasad Parajuli, Monique Potvin Kent, Michele Rubini, Marjanne Senekal, Lindsey Sikora, Alain Stintzi, Evropi Theodoratou, Hui Wang, Ann Yaktine, Julian Little

Published in

Journal of global health. Volume 16. Pages 04286. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

The global burden of neuropsychiatric disorders has been increasing rapidly. Folate has been studied in the context of these disorders due to its role in cellular methylation capacity, which is crucial for normal neuronal gene expression and neurotransmitter syntheses. Epidemiological evidence linking folate and neuropsychiatric disorders is growing, yet inconclusive.
We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects from inception to February 2024 for systematic reviews and meta-analyses investigating the associations between folate exposure and any neuropsychiatric disorders. Two independent reviewers screened the syntheses in two stages and extracted relevant data. Evidence was categorised into unique associations (unique exposure measure - unique outcome - unique setting). We identified evidence for each category of unique associations. We evaluated the risk of bias of all included syntheses using ROBIS and assessed the credibility of evidence using predefined criteria.
From a total of 76 syntheses, we identified 44 unique associations from meta-analyses and 18 unique associations from qualitative syntheses across 14 outcome categories. Most of the reviews consisted of case-control studies or cross-sectional studies, and most were at high risk of bias. We identified two associations at a suggestive level of credibility: folic acid supplementation during or before pregnancy was associated with a reduced risk of perinatal depression, while prenatal maternal folic acid use was associated with a reduced risk of autism spectrum disorder in offspring. Seven associations were downgraded to weak due to unavailable data. Other associations were at a weak level of credibility due to insufficient statistical power.
The available evidence on the relationship between folate status and neuropsychiatric disorders primarily comprised data from observational studies, limiting causal inference on folate exposure and the risk of onset or progression of neuropsychiatric disorders. Prospective studies and sex-stratified analyses could add to the evolving knowledge on this topic.
PROSPERO: CRD42021265041.

PMID:
42606922
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.