MTHFR and Depression: Why Did My Psychiatrist Order an MTHFR Gene Test?

A Psychiatrist’s Guide to Understanding the Link Between MTHFR, Depression, Folate & Mental Health

MTHFR and Depression: Why Did My Psychiatrist Order an MTHFR Gene Test?
Sheenie Ambardar, MD is a Los Angeles-based Integrative Psychiatrist with 16+ years of experience in Adult Psychiatry. Dr. Ambardar sees patients throughout California and New York via telehealth and specializes in the diagnosis and treatment of adult men and women with Depression, Anxiety, ADHD, OCD, Panic Disorder, Binge-Eating Disorder, and a host of other common mental health concerns.
Are you experiencing any of these conditions? Concierge Integrative Psychiatry may be the solution you need. At The Happiness Psychiatrist®, we address the root causes of these issues—and many more—as well as give you the resources to build a fuller, happier life.

~ Join us as we learn more about the fascinating world of MTHFR ~

As an integrative psychiatrist serving patients in California and New York, I'm always looking for ways to provide my patients with the most comprehensive mental health care possible. One powerful tool in our treatment arsenal is MTHFR gene testing.

But why would a psychiatrist be interested in this particular gene? And what does it have to do with Depression, Anxiety, Mental Health, and Mood?

Let’s dive in!

MTHFR and Depression:What is MTHFR?

MTHFR stands for MethyleneTetraHydroFolate Reductase 🧬

MTHFR = MethyleneTetraHydroFolate Reductase. It's a big name for a gene that provides instructions for making the MTHFR enzyme.

The MTHFR enzyme plays an important role in converting inactive folate (Vitamin B9) into its active, bioavailable form, L-Methylfolate, a.k.a. methylfolate or L-5-MTHF.

L-Methylfolate is essential for numerous cellular functions, including the production of neurotransmitters – those all-important chemical messengers in our brains that influence our moods and overall mental health.

When there's a variation (or mutation or polymorphism) in our MTHFR gene, it can affect how well our MTHFR enzyme works.

About 40% of people in the United States have mutations in their MTHFR gene that can reduce their MTHFR enzyme's efficiency.

Common names for these mutations include the C677T and A1298C polymorphisms.

MTHFR and Depression and Neurotransmitter Production

L-Methylfolate plays a crucial role in neurotransmitter synthesis

To understand the connection between the MTHFR enzyme and depression, we need to understand the role MTHFR plays in the production of neurotransmitters on a more granular level. Here's a simplified breakdown: ⬇️

1. As mentioned above, the MTHFR enzyme helps convert inactive folate to its active form, L- Methylfolate. ⤵

2. L-Methylfolate is crucial for a biochemical process called methylation, the act of adding a methyl group (CH3) to a molecule or protein. Methylation is involved in numerous essential functions, including:

  • DNA repair
  • Detoxification
  • Hormone regulation and
  • Neurotransmitter synthesis

3. Optimal methylation is vital for the production of brain neurotransmitters like serotonin, dopamine, and norepinephrine.

4. These brain neurotransmitters play crucial roles in regulating our moods, emotions, and cognitive functions 😶‍🌫️

5. When there's a polymorphism (mutation) in the MTHFR gene, it can lead to reduced MTHFR enzyme activity. This means less inactive folate (Vitamin B9) is converted to active L-Methylfolate, resulting in deficiencies in the methylation process and thus lower levels of brain neurotransmitters 📉

6. Lower levels of brain neurotransmitters can contribute to the development of Depression, Anxiety, ADHD, OCD, Autism, Bipolar Disorder, Schizophrenia, and other health conditions ⛑️

It's important to note that having an MTHFR variation or mutation doesn't necessarily mean you'll develop any of these mental health conditions. However, it may increase your susceptibility, especially when combined with other genetic and environmental factors.

MTHFR and Depression: A Complex Relationship

The two most common mutations in the MTHFR gene are C677T and A1298C

While it would be convenient to make broad generalizations about the relationship between MTHFR and Depression, as with anything in medicine (and life), there are many variables and factors at play that can influence outcomes. Here are some points to consider:

  • Folate (or its active, bioavailable form L-Methylfolate) is a mood-boosting fuel for our brains. Studies have shown that people experiencing depression often have lower folate levels. If your MTHFR gene isn't working at full capacity, it might lower your folate levels and, consequently, your mood.
  • If you've tried numerous antidepressants without much success, an MTHFR mutation could be a contributing factor. It's like having a lock that needs a slightly different key - understanding your MTHFR status could help us find that key.
  • Once again, it's important to note that while there is a link between MTHFR and depression, having an MTHFR variation or mutation doesn't mean that a person will develop depression. Many other epigenetic and environmental factors also play roles in the development of depression. The MTHFR-Depression link is part of a broader, more complex picture of mental health.
  • However, understanding the link between MTHFR and depression can open up new avenues for treatment and prevention. By addressing underlying genetic factors, we can develop more tailored and effective strategies for managing depression, anxiety, OCD, ADHD, and other mental health conditions.

MTHFR Gene Test: How Does It Work?

At The Happiness Psychiatrist®, we believe in empowering you with knowledge about your brain, body, and mind.
That's why we offer MTHFR gene testing as an optional tool to help you understand your unique genetic makeup. But what exactly does this test involve? Let's go through the process, step-by-step:

A Friendly MTHFR Consultation 🌼

First, we'll sit down for a warm, open conversation. We'll discuss your mental health history, how you've been feeling, and reasons why an MTHFR test might be beneficial.

This is your chance to ask questions and share your concerns. There’s no pressure and the test is completely optional  - we're here to listen and offer guidance.

Choosing Your MTHFR Lab 🧪

If you decide to proceed, we'll help you select a lab that's right for you. We work with several reputable companies like Genomind, Cell Science Systems, Genesight, Quest Diagnostics, DNA RX, Boston Heart Diagnostics, and others. These companies charge anywhere from $50-$500 for the test, depending upon if other genes and biomarkers are also being tested.

Your insurance may cover a portion of the fee, but it’s likely you’ll have to pay some of the cost out-of-pocket. We'll handle the electronic paperwork and place the lab order for you.

Your MTHFR DNA Collection Kit 🧬

The lab will send a DNA collection kit right to your home. No need for needles or blood draws! You'll simply swab the inside of your cheek - it's quick, painless, and can be done in the comfort of your own home.

MTHFR Lab analysis 🥼

You’ll mail your sample back to the laboratory for genetic analysis.

Understanding Your MTHFR Results 📘

In a few weeks, we'll have your results. We'll schedule a follow-up appointment to go over everything together.

Don't worry if you don't completely understand the science - that's what we're here for! We'll explain your results in simple, friendly terms:

MTHFR gene testing results can fall into one of three categories:

  • The typical version, which works normally
  • A version that works a bit slower
  • A version that works much slower

If you have one of the slower versions, your body might not produce as much active folate as others. But don't worry! We’ll explain everything when we get your results back and help you understand what it means for you.

Your MTHFR Personalized Plan 📝

Based on your results and our understanding of your overall health and symptoms, we'll work together to create a treatment plan that's uniquely yours.

This might include lifestyle changes, dietary adjustments, and pharmaceutical-grade supplements - all designed to support your mental health and help you feel better 🦋

And if you decide that MTHFR gene testing isn't for you right now, that's okay too. We have plenty of other ways to help you boost your mental health and find your path to happiness.

The most important thing is that you're taking steps to take care of yourself and we think that's pretty amazing! ✨

MTHFR and Depression: Treatment Options


If your test results show that you have an MTHFR variation or mutation, don't worry – 40% of people in the U.S. have some kind of polymorphism and there are several treatment options available.

Remember, the goal is to support your body's methylation processes and to ensure adequate levels of active L-Methylfolate. Here are some approaches we might consider:

L-Methylfolate supplementation: 💚

Since your body may have difficulty converting inactive folate to its active form (L-Methylfolate, also called methylfolate), supplementing directly with L-Methylfolate can bypass this issue. This is often the first-line treatment for individuals with MTHFR variations.

We recommend starting with low doses of a high-quality L-Methylfolate supplement and slowly and gradually increasing over time as needed.

B-Vitamin Complex: 🩵

Other B vitamins, particularly Vitamins B12 (methylcobalamin), B6, and B2, work synergistically with L-Methylfolate and are often recommended concomitantly to enhance overall methylation.

A high-quality B-Vitamin complex supplement can help optimize methylation as well as neurotransmitter production.

We recommended taking a B-Complex supplement in conjunction with L-Methylfolate.

Dietary Changes: 🥗

Incorporating folate-rich foods into your diet can be very beneficial. These include things like uncooked leafy greens (salad), as well as collard greens, mung beans, lentils, kidney beans, avocado, okra, and eggs.

It's important to consume natural dietary folate sources rather than synthetic folic acid, which some individuals with MTHFR variations may have difficulty processing.

Lifestyle Modifications: 💜

Regular exercise, stress management techniques, limiting alcohol and cannabis intake, and ensuring quality sleep can all support optimal methylation and mental health.

Avoiding Folic Acid: 🩷

For some individuals with MTHFR variations, the synthetic folic acid found in fortified foods and folic acid supplements may not be well-tolerated.

We recommend avoiding folic acid sources and focusing on L-Methylfolate instead.

Addressing Co-Existing Conditions: 💙

Optimizing gut health, managing inflammation, and addressing any other health issues are all part of a comprehensive treatment approach.

It's important to note that treatment should always be personalized and monitored by a physician. What works for one person may not be suitable for another, even with the same genetic variant.

MTHFR + Depression: Knowledge is Power


If you've been struggling with Depression, Anxiety, ADHD, OCD, Bipolar Disorder, Autism, or Schizophrenia, exploring your MTHFR status could provide valuable insights.

Remember, knowledge is power – and in the case of MTHFR, it might be the key to unlocking better mental health.

At The Happiness Psychiatrist®, we're committed to providing integrative functional psychiatry and psychotherapy that addresses the root causes of mental health issues.

We don't just treat symptoms - we work with you to optimize your overall well-being.

Dr. Ambardar welcomes you to schedule a consultation today to learn more about MTHFR testing and how it could potentially benefit you.

Together, we can explore your unique genetic profile and develop a customized treatment plan that supports your mental health and overall wellness.

Your journey to better mental health can be supported by understanding your body at the deepest level. Reach out today to learn more about MTHFR testing and take a step towards a healthier, happier you!

MTHFR and Depression FAQs:

Uncooked leafy greens like those found in salad, are great sources of dietary folate

Is MTHFR the only gene that impacts mental health?

Nope. While the MTHFR gene is important, it's just one piece of the complex puzzle that is mental health.

There are many other genes that can impact mental health, including COMT, BDNF, SLC6A4, DRD4, OXTR, and CACNA1C, to name just a few.

However, testing for MTHFR variants is a good place to start and opens up new avenues for understanding and treating mental health conditions.

It allows us to move beyond a one-size-fits-all approach and into the realm of personalized functional medicine, where treatments are tailored to each individual's unique genetic makeup.

Do MTHFR mutations affect other conditions besides Depression?

Yes, MTHFR mutations can impact many different health conditions. Folate metabolism plays an important role in many bodily functions.

Some studies have suggested links between MTHFR mutations and cardiovascular health, chronic fatigue, migraines, fibromyalgia, diabetes, pregnancy outcomes, and certain neurological and immune system conditions.

However, it's important to remember that these are complex relationships influenced by many factors. 

How does MTHFR testing fit into an overall treatment plan for Depression?

We view MTHFR testing as just one possible tool in our treatment arsenal. Testing is optional and if it reveals a variation, we might adjust your treatment plan to include tailored nutritional support such as L-Methylfolate and B-complex supplementation.

However, we always consider the whole picture - your symptoms, life experiences, other health conditions, and personal preferences all play a role in crafting your unique treatment plan.

MTHFR testing can provide valuable insights, but it's just one piece of the puzzle in our patient-centered approach to care.

What are the costs associated with MTHFR testing?

The cost of MTHFR testing can vary depending on several factors, including the specific test and lab company used and whether the test is covered by your insurance.

Generally, commercial labs charge anywhere from $50 to $500, depending upon if other genes and biomarkers are being tested as well. Some insurance plans may cover part of this cost.

We view MTHFR testing as an optional investment in your long-term health and well-being. 

Once you know your MTHFR status, the information is good for life, since genes don't change over our lifespan.

Why don't all health organizations recommend MTHFR testing?

Recommendations for MTHFR testing vary among health systems and medical associations.

Some organizations and health systems don't recommend routine MTHFR testing for several reasons including:

- MTHFR mutations are relatively common in the general population

- Cost considerations

- Having an MTHFR mutation doesn't necessarily mean you'll develop health issues

- Inadequate awareness/training and extra burden of work

- Ongoing debate about the extent of the MTHFR gene's impact on various health conditions

At The Happiness Psychiatrist®, we believe in personalized, functional medicine. While we don't necessarily recommend universal testing, we find that for some patients, especially those with treatment-resistant depression or a strong family history of mental health concerns, MTHFR testing can provide valuable insights that inform more effective treatment strategies.

We always weigh the potential benefits against the costs and consider each patient's unique circumstances before recommending testing.

It's important to have an open discussion about the pros and cons of testing in your specific situation.

We're here to provide you with current, evidence-based information to help you make the best decision for your health.

Is Folic Acid the same thing as L-Methylfolate and Dietary Folate?

Nope. Here is a simplified breakdown:

  • Folic Acid is a synthetic, man-made substance used to fortify foods.
  • Dietary Folate is found naturally in foods and is inactive Vitamin B9
  • L-Methylfolate is the active, bioavailable form of folate (Vitamin B9) and is used in high quality supplements such as Metafolin®, Deplin®, EnLyte®, and Cerefolin®.

Can you supplement with too much L-Methylfolate?

Yes! Too much L-Methylfolate can lead to side effects including agitation, anxiety, heart palpitations, insomnia, hypomania, and mania, particularly in those with Bipolar Disorder.

That’s why we recommend starting with a low dose of L-Methylfolate and slowly increasing your dose over time as needed.

How do I know if I have an MTHFR gene mutation?

Gene Testing is always optional

The only way to know for sure is through genetic testing. We recommend MTHFR gene testing as part of our comprehensive, integrative approach to mental health but the test is 100% optional.

It's also important to remember that having a mutation doesn't necessarily mean you'll experience health issues.

If I have an MTHFR mutation, does that mean I'll definitely get Depression?

Not at all! An MTHFR variation is just one factor among many that can influence your mental health. Many people with MTHFR variations never experience depression, while others without variations may develop depression due to other factors.

Can changing my diet help if I have an MTHFR mutation?

Absolutely. Eating a diet rich in naturally occurring folate can be beneficial. Foods high in folate include uncooked leafy greens, legumes, and fruits like oranges and strawberries.

However, it's always best to consult with a healthcare provider before making significant dietary changes.

Are there any medications that can interfere with folate metabolism?

Yes, certain medications can affect folate metabolism. These include some anti-epileptic drugs as well as metformin, estrogen, methotrexate, and certain antibiotics.

If you're taking any of these medications, it's important to discuss potential interactions with your psychiatrist.

Is L-Methylfolate safe to take during pregnancy?

Yes, L-Methylfolate is generally considered safe during pregnancy and is often recommended for women with MTHFR variations.

However, it's crucial to consult with your OB/Gyn before starting any new supplements during pregnancy.

MTHFR and Depression: Integrative Concierge Psychiatry Works 🌿


Traditional psychiatry often focuses solely on medication. While this can be very helpful, it may not address the underlying genetic factors contributing to depression, anxiety, and other mood disorders.

"An integrative, holistic approach combines the very best of conventional psychiatry with evidence-based functional psychiatry, providing a more robust understanding of your overall mental health." - Sheenie Ambardar, MD

Serving California and New York 🗺️

Wherever you're located in New York or California, our integrative psychiatry services are accessible to you.

We combine cutting-edge science with compassionate care and offer convenient telepsychiatry options to ensure you receive the support you need, wherever you may be.

Take the Next Step 🛼

Curious to learn more about how your genes might influence your mental health? Have questions about MTHFR or depression? We're here to listen, explain, and guide.

Your journey to understanding and improving your mental health starts with a conversation - and we're excited to have that conversation with you.

Understanding your genes is more than just abstract science – it's one part of unlocking your best mental health.

Schedule a consultation today and take the first step towards personalized, gene-informed mental health care!

MTHFR and Depression: Key Takeaways 🔑

  • MTHFR gene mutations affect up to 40% of individuals in the United States
  • These mutations may contribute to treatment-resistant depression
  • Genetic testing can reveal MTHFR variations or polymorphisms
  • L-Methylfolate and B-Complex supplementation can help individuals with depression and anxiety
  • MTHFR gene testing is a valuable tool used by integrative functional psychiatrists

You Deserve To Feel Happier

Ready to begin your own therapeutic journey towards happiness and better mental health? Contact The Happiness Psychiatrist® today and discover how award-winning concierge psychiatrist Dr. Sheenie Ambardar can help put you on the path to your best, happiest self.

Want to learn more about integrative concierge psychiatry? Read these pieces next from The Happiness Psychiatrist® blog:

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  2. The Advantages of Seeing an Online Psychiatrist
  3. What is Psychodynamic Therapy?
  4. Carl Jung’s Contribution to Psychology: Jung and Hinduism