MTHFR gene and depression

What is the MTHFR gene and what role does it play in depression?

The MTHFR gene is the gene that tells cells in the body how to make the methylenetetrahydrofoloate reductase (MTHFR) enzyme.  This enzyme plays an important role in the body in making amino acids (the protein building blocks) utilizable in the body.  In particular, this enzyme methylates the amino acids so that they are active (ready to be used).  Mutations in the MTHFR gene can affect enzyme function.  Folate (vitamin B9) is one molecule that has to be methylated to be active in the body.  When one has reduced activity of this enzyme it can lead to risk factors for cardiovascular disease, blood clots, and pregnancy complications as well as decreased production and regulation of neurotransmitters like serotonin, dopamine, and norepinephrine.

The common MTHFR gene variants C677T and A1298C can reduce the amount of the enzyme available to make these neurotransmitters and this can impact neurological and psychiatric conditions, including depression.  Folate is also necessary to make SAMe which is involved in the synthesis of neurotransmitters.  Adequate folate levels have been shown to lead to better responses in antidepressant treatments.  Some studies suggest that individuals with mutations in MTHFR gene may have less response to traditional antidepressant treatments.

One solution to this dilemma is to take a supplement in which the folate has already been methylated to methylfolate.  Usually this is also supplemented with methylcobalamine (methylated B12) since this is also important for neurotransmitter function.

Supplements are not FDA regulated therefore it is important to buy supplements backed by a reputable pharmaceutical company.  One that employs testing to ensure quality and content of their products.

While there is evidence suggesting a link between MTHFR variants and depression the study findings are mixed.  There are likely multiple factors influencing this relationship including genetic, environmental, and lifestyle factors.  Not all individuals with depression have this gene mutation and not all people with this mutation will experience depression.


(This information was obtained using ChatGPT and reviewed by Dr. George)