A US study links rare variants in the FOLR2 gene, which makes a folate receptor found on some immune cells, to neurodevelopmental diagnoses, mainly ADHD. It does not show that folic acid prevents or treats ADHD: that was not its question, and it did not measure supplement use. The Vanderbilt Health press release of 26 October 2026 is accurate, but it needs some context.
- The study: Frontiers in Immunology, 10 September 2026, 170,889 people from two US biobanks.
- The signal: an association, not a cause, with a group of diagnoses dominated by ADHD and with genitourinary infections during pregnancy.
- The limits: billing codes, estimated genotypes, no independent replication, nothing on diet or supplements.
- What does not change: folic acid before and in early pregnancy is still recommended to prevent neural tube defects. That recommendation is not about ADHD.
What the researchers did
The team led by Digna Velez Edwards (Vanderbilt University Medical Center) and David Aronoff (Indiana University) ran a phenome-wide association study (PheWAS): you start from one gene and compare it with every diagnosis in the medical records. The authors describe it as a hypothesis-generating approach.
- Population: 73,813 people from BioVU, Vanderbilt's biobank, and 97,076 from the eMERGE network, which brings together about a dozen US healthcare centres. Of these, 28,516 were of African ancestry and 142,373 of European ancestry; other ancestries were excluded because the numbers were too small.
- Genetics: rare FOLR2 variants, grouped into three models. The strictest keeps only variants that change the protein (5 to 20 depending on the group). Genotypes came from DNA chips completed by statistical imputation, not from sequencing.
- Diagnoses: billing codes grouped into categories; 1,267 were tested in the final combined analysis.
What they found, and a detail that matters
When both biobanks and both ancestries were combined, the variants that change the protein were associated with the category "pervasive developmental disorders". In the classification used, it groups ADHD, tics and autism: 6,111 cases, 4,546 of them coded as ADHD. Hence the "mainly ADHD" in the press release.
The detail that matters: on its own, the ADHD code does not reach the strict threshold the authors set to account for more than a thousand tests (p of about 0.0001, against a threshold of about 0.00004; Table 3). The significant signal is for the broad category, not for ADHD alone, even though ADHD makes up nearly three quarters of its cases.
Other associations reported: genitourinary infections during pregnancy (458 cases), tension headache and, in women with a pregnancy history, high blood pressure in pregnancy and problems with the amniotic membranes. Weaker leads, described as suggestive, concern pain during intercourse and eye inflammation.
Two words of caution. No association was significant in BioVU or eMERGE taken separately: the signals only appear once the data are combined. And the main text of the paper gives only p-values; odds ratios, placed in a supplementary table, are presented as a simple indication of the direction of the association. So we do not know how much the risk changes for carriers, who are by definition few.
Limits acknowledged by the authors
- Association, not cause: an exploratory study, with an unknown mechanism.
- Billing codes: they do not always reflect a careful diagnosis, and practices vary between hospitals, especially for neurodevelopment and pregnancy.
- Estimated rare variants: imputation is less reliable than sequencing.
- No replication in an independent population, and no reliable data on diet or supplements.
The study received no dedicated funding (the first author was supported by a US NIH career development programme) and the authors declare no conflict of interest.
FOLR2 is not FOLR1
- FOLR1 (receptor alpha): it moves folate from the blood into the fluid that surrounds the brain. Mutations in both copies cause cerebral folate transport deficiency, a very rare disease (fewer than 20 cases described, according to MedlinePlus): regression around age 2, seizures, movement problems. It is not ADHD.
- FOLR2 (receptor beta): it is found almost only on monocytes and macrophages, which are immune cells. The organ where it is most expressed is the placenta, because of its macrophages.
In mice, embryos lacking the equivalent of FOLR1 die in the womb, while those lacking the equivalent of FOLR2 develop normally. And in 2026, David Aronoff's team removed FOLR2 from macrophage-like cells: an inflammation pathway worked less well, and adding folate did not fix the defect. This is only work on cells in a dish, but if FOLR2 plays a role, the current lead points to immunity, not to a folate shortage that a pill could make up for.
Folic acid in pregnancy and ADHD: mixed results
The data are observational and of uneven quality.
- A modest association: a 2025 umbrella review found only one meta-analysis on ADHD (6 studies): about 14% lower odds (OR 0.86) when the mother had taken folic acid, with evidence rated low or very low quality. A 2019 review, by contrast, found the ADHD data inconclusive.
- Denmark: in the national birth cohort (about 35,000 children), folic acid alone was not associated with a hospital diagnosis of hyperkinetic disorder (1.1% of children) or with ADHD treatment (1.8%). Multivitamins were (about 30% lower risk for the diagnosis, 21% for treatment), which is still an association.
- Norway (MoBa cohort): among 14,539 mothers, those carrying more genetic variants linked to ADHD were slightly less likely to take folate (OR 0.92). So part of the apparent link could come from genes shared by mother and child, not from the vitamin.
- More is not better: a 2023 meta-analysis (39 studies) found no benefit from over-supplementation and flags a possible negative effect.
What about the "MTHFR mutation"?
Another shortcut is common online: an "MTHFR mutation" would stop you from using folic acid and would explain ADHD. The facts:
- The C677T variant is very common: in the United States, more people carry one or two copies than none (CDC).
- Carriers do use folic acid. At the same intake, people with the TT genotype have about 16% less folate in their blood, and according to the CDC these variants are not a reason to avoid folic acid.
- A 2022 meta-analysis found no link between C677T and ADHD. For the other variant, A1298C, the association is barely significant (p = 0.047), based on 5 small studies (434 cases).
- The American College of Medical Genetics and Genomics (ACMG) considers the clinical usefulness of MTHFR testing minimal in the work-up for blood clotting disorders.
What is established: folic acid and the neural tube
The benefit behind the recommendation concerns neural tube defects, such as spina bifida. The WHO recommends supplementation for all women, from the moment they begin trying to conceive until 12 weeks of pregnancy. In France, Santé publique France restates the 2009 recommendation of the HAS, the national health authority: a systematic prescription of folate, at least 4 weeks before conception and in early pregnancy. In 2021, only 27.2% of women in France reported taking it before pregnancy.
This recommendation has nothing to do with ADHD, and the FOLR2 study does not change it. If you are planning a pregnancy, talk to your doctor or midwife. Do not add supplements on your own to try to prevent ADHD.
What this means for you
In practice, nothing. A FOLR2 test is of no use for ADHD, which is diagnosed clinically. A large genetic study of ADHD published in 2023 (38,691 people with ADHD) found 27 regions of the genome associated with ADHD. FOLR2 is, at best, one more lead to check.
If attention or impulsivity raises questions for you or your child, our adult ADHD self-assessment questionnaire (ASRS) or our questionnaire for parents can help you organise what you notice before talking to a doctor. An online result is not a diagnosis.
Further reading: the viral "genetics of ADHD" wheel, fact-checked, the placenta and PlGF study and paracetamol and antidepressants in pregnancy.
Frequently asked questions
Can folic acid prevent or treat ADHD?
There is no basis to say so. Pregnancy studies are observational and mixed, and the FOLR2 study tested no supplement. For any question about treatment, talk to your doctor.
Should I get my FOLR2 or MTHFR genes tested?
For ADHD, it adds nothing today: none of these results can confirm or rule out a diagnosis, or tell you which supplement to take.
My child has ADHD and I did not take folic acid: is it my fault?
No. ADHD has a strong genetic component, and an association seen across a population cannot pin one child's ADHD on a choice made during pregnancy.
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