Screening for Methylenetetrahydrofolate Reductase (MTHFR) Mutation




Charolia, Samita


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Purpose: The C677T and A1298C allele codes for methylenetetrahydrofolate reductase enzyme in the liver that coverts folate to L-methylfolate (LMF). L-methlyfolate is the version of folate the brain can absorb. Once in the brain L-methyl folate is thought to help stimulate production of essential neurotransmitters. Mutations in this enzyme are strongly linked to depression, however it could also lead to other psychiatric conditions.1 Studies show that when L-methylfolate supplementation was used alongside antidepressants in 502 participants with depression, they reported improvement in depressive symptoms.2 With more people tested for this mutation we can identify people that need on proper L-methylfolate supplement and get them on it. Thus, improving their overall health.

Methods: We implemented a screening tool that comprised of multiple questions including a PHQ-9 and GAD-7. We gave it to all adult patients at the Hendrik Family Medicine Clinic in Abaline, Texas between August 2022 and October 2022. Positive screening results were based on the criteria of history of depression or a five or greater on the screening.

Results: We screened a total of 188 patients with 106 qualifying for the test. Fifty-three patients preformed the test, and the other half did not due to cost, loss to follow up, or other reasons. Forty-one, or 77%, of the patients screened tested positive for a mutation in one or both alleles. On average PHQ-9 scores were higher in patient who had a mutation in both alleles. 14 of the 41 positive mutation patients were on additional pain medication (Tylenol-3, Tramadol, or Both).

Conclusion: This study suggests that MTHFR gene mutations is prevalent in people who met criteria through the screening. Even though it was prevalent more research need to be done to know the impact of obtaining screenings and outcomes once starting supplementation. A future goal is to follow up with patients who have the mutation and test if there is any improvement in their symptoms after supplementation.

  1. Wan L, Li Y, Zhang Z, Sun Z, He Y, Li R. Methylenetetrahydrofolate reductase and psychiatric diseases. Translational psychiatry. Published November 5, 2018. Accessed October 5, 2022.

  2. Shelton RC, Sloan Manning J, Barrentine LW, Tipa EV. Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial. Prim Care Companion CNS Disord. 2013;15(4):PCC.13m01520. doi:10.4088/PCC.13m01520