Understanding The MTHFR-Depression Connection

Reviewed by Wendy Boring-Bray, DBH, LPC

Published 07/14/2022

Did you know there’s anywhere from 20,000-25,000 genes inside the human body? That number is subject to change as we learn more about them, but there’s no arguing over how important they are to human life. In fact, genes are often referred to as the “blueprint of all life.”

Genes are tiny sections of DNA that make up anywhere from 200 DNA bases to 2,000,000+ DNA bases. We each have two copies of each gene, one coming from each parent, and are necessary for the human body's growth, development, and function.

More specifically, genes provide cells with instructions for making certain proteins or RNA. They help instruct the cells on what to do, when to do it, how long to do it, and, most importantly, how to do it -- hence the name “blueprint of all life.”

While there are 20,000 to 25,000 genes found inside the body, one specific gene has started to raise eyebrows with mental disorders, such as depression. That gene is called the MTHFR gene, and there’s a good chance you’ve heard about on social media.

So, what is the MTHFR gene?

It might be confusing to some, but the MTHFR gene provides instructions for making an MTHFR enzyme. It’s also referred to by its scientific name, methylenetetrahydrofolate reductase, but they’re both called MTHFR for short.

The enzyme is the prized possession here, but it can’t exist without the MTHFR gene. The enzyme plays a major role in converting homocysteine to methionine in the blood. It also converts folate -- which many of us know as Vitamin B9 -- into the body's active form (methyl folate).

Without the MTHFR gene, we experience a buildup of homocysteine in the blood, as well as a methionine deficiency. We also experience a deficiency of Vitamin B9, but keep in mind this is really a deficiency of methyl folate since you’re receiving the right amount of Vitamin B9 -- just not processing it properly.

You might be asking yourself why this is important for the body. First off, a buildup of homocysteine can cause blood clots and arterial damage, among other things.

Second, a methyl folate deficiency can lead to a wide range of issues, including blood clots, stroke, depression, anxiety, schizophrenia, bipolar disorder, and chronic fatigue. It also plays a role in dopamine, serotonin, and norepinephrine -- three mood-related neurotransmitters.

Finally, the body struggles with the methylation process necessary for gene expression, hormone regulation, building DNA and RNA, detoxification, and mood regulation. This is largely due to the deficiency of methyl folate required for the methylation process to function properly.

Where Do We Go Wrong With The MTHFR Gene?

As you can see, the MTHFR gene (and subsequent MTHFR enzyme) play an important role in the body. While we mentioned a wide range of things that can go wrong with the MTHFR gene, that’s only if you don’t have it -- so, what’s the problem?

The problem is that not all genes are created equal, and some don’t work properly. This lack of function is caused by a mutation of the gene, which is essentially a change in the genetic sequence. The mutation causes the gene to either underperform, overperform, or not perform at all.

Over time, researchers have revealed several different variants (mutations) to the MTHFR gene. Still, only two pose a risk to our body’s ability to convert homocysteine in the blood and convert Vitamin B9 -- the C677T variant and the A1298C variant.

Since we each have two copies of the MTHFR gene, we can have no variants (best-case scenario), one variant (either one), two of the same variants, or one of each variant. It will largely depend on the genes you receive from your parents.

For example, your parents each have two MTHFR genes. If one of your parents has one variant, there’s a 50% chance you get it, too. If one of your parents has two variants, then you’re 100% likely to get one.

The C677T variant is the most damaging, causing up to 30% loss of function in the gene with one variant and up to 70% loss of function with two variants. On the other hand, the A1298C variant results in a 40% loss of function with two variants, but not as much damage with one.

Is There An MTHFR-Depression Connection?

One of the biggest reasons the MTHFR gene mutation has raised so many eyebrows is because it’s estimated that nearly 40% of the population lives with at least one variant. That means nearly 40% of the population doesn’t process homocysteine or Vitamin B9 as well as they should.

That’s scary, considering how important Vitamin B9 is to the body, as well as the conversion of homocysteine to methionine. We discussed many of the dangers above, but none intrigue researchers more than the effect it has on depression.

Since a folate deficiency is one of the leading similarities in many depression patients, it’s no wonder we see the MTHFR-depression connection receive so much attention. In fact, many studies suggest Vitamin B9 plays a major role in the synthesis of dopamine, serotonin, and norepinephrine.

For those that don’t know, these are three neurotransmitters necessary for mood regulation. They’re also the three neurotransmitters that most antidepressants target.

While antidepressants make these neurotransmitters more available to receptors in the brain, they don’t always increase the neurotransmitters' production. Since an MTHFR gene mutation makes it difficult for the body to produce the neurotransmitters, the antidepressants often don’t work.

Not only that, but eating folate and supplementing with folic acid won’t do much either. It won’t matter how much you consume; the body won’t convert it. This means a limited supply of Vitamin B9 no matter what you do.

Symptoms Of An MTHFR Gene Mutation

To summarize what we’ve learned thus far, there is a wide range of studies linking a Vitamin B9 deficiency to depression. For the body to use Vitamin B9, it needs to be converted into methyl folate. This conversion is only possible with the help of the MTHFR enzyme.

Since the MTHFR enzyme is produced by the MTHFR gene, any issues with the gene would affect the enzyme. Unfortunately, nearly 40% of the population lives with at least one mutation of the MTHFR gene, rendering it less effective than normal.

What we’re left with is a Vitamin B9 (folate, methyl folate) deficiency that causes a wide range of issues with the body -- including depression. That’s why it’s becoming more important to understand the symptoms of an MTHFR gene mutation, that way, you can start to find the help you need.

Don’t worry. We’re going to discuss some of the most prominent symptoms of an MTHFR gene mutation below:

  • Having a hard time managing the daily stress we experience
  • Constant over-reactions and behavioral issues
  • Inability to focus or difficulty learning
  • Certain respiratory issues like asthma or shortness of breath
  • Anxiety, depression, mood swings, or ADHD
  • Allergies and other problems with your immune system
  • High levels of homocysteine in the blood or low levels of methionine
  • Low levels of folate (Vitamin B9) in the blood or low levels of cobalamin (Vitamin B12)

Since an MTHFR gene mutation can affect the body in many ways, detecting it early is often a struggle. If you’re experiencing any of the symptoms above, it’s best to have a doctor run a blood sample to check homocysteine, folate, and cobalamin levels. 

Any imbalance in the three could mean you’re experiencing an MTHFR gene mutation. This would explain mood disorders and behavioral issues and the inability of certain antidepressants to work in the body.

Finding The Help You Need

Depression is one of the worst experiences an individual can go through in life. It’s something no one should have to do alone and something that takes an extreme amount of effort to overcome. With the right help, however, this is possible for anyone.

Unfortunately, many people have difficulty admitting that they’re depressed. Others mistake their depression for something else, allowing it to go unnoticed and untreated. Of course, this only gives the depression more time to negatively affect your life -- without you even knowing it.

Whether you suspect you’re struggling with depression, wonder whether you’re experiencing depression, or are just ‘in a funk,’ or are simply curious to see how you would test against something like that, Mind Diagnostics is here to help!

We’ve created a comprehensive online depression test to help others understand the difference between depression and that ‘awkward’ feeling we all get sometimes. By taking the test, you not only learn more about yourself, but you also unlock more opportunities to enhance your mental health moving forward.

Feel free to contact us if you have any questions about our online depression test, or check out all our other online tests to see if you’re going through anything that could be negatively affecting your life. We can’t wait to help you find the quality of life we’ve all been searching for!