Your MTHFR Gene and the Genetics of Depression

Depression can be influenced by your unique genetic code. Your MTHFR gene may be particularly implicated in negative health outcomes. Genetic testing can help you and your doctor get to the root causes of your depression, and lifestyle and dietary interventions can help you feel whole again. In this blog, you will learn: 

• The genetics of depression
• How genetic testing for depression works
• How the MTHFR gene is implicated in depression

The Genetics of Depression: Your MTHFR Gene

We treat depression as a monolith in our culture, with one single definition and a clear set of symptoms. In movies, commercials, and more, depression is conveyed on a greyscale, with forlorn, somewhat disheveled women or men portrayed as people who feel they can’t enjoy anything in life.  While some individuals may suffer in this caricatured way, many have far different symptoms—including less “obvious” symptoms that are harder to pin down. Just as there is no single set of “symptoms” for depression, there is no single cause. Instead, there are many different “depressions” with multiple genetic variants, like MTHFR—and multiple biological pathways that need to be influenced—to bring about a full recovery.

Just as there is no single, monolithic “depression”, there is no single, easy, or uniform treatment. Instead, treatment of this endlessly varied, complex disease must be met with an equally individualized approach—one informed by an individual’s unique genetic makeup. Genetic testing has only just begun to revolutionize the treatment of mental illnesses like depression. And with Carla’s story, I hope you see how bright the horizons are for those who are desperate for a “genetic second opinion” that leads to a full recovery.

Carla's Story: Treating depression with genetic testing

My patient Carla may well have been one of those “influencers” you’ve seen on social media, whose lives look starry and bright—at least from the outside. Indeed, to an outside observer it seemed that Carla had it all: She was a well-regarded TV personality, author, and journalist, was married to a successful attorney, and had three thriving children. She certainly didn’t map to the stereotypical portrayal of a depressed person with a sad demeanor and a continuously cloudy outlook on life—but she was hiding something on the inside that nobody on the outside would’ve ever guessed. Carla was depressed, anxious, and felt as though her life was about to fall apart at any moment.

As a fitness fanatic who worked out every day and ate a strict and healthy diet, Carla felt shocked and bewildered by the onset of her symptoms, which quickly became debilitating. In our first session, she openly wept. “Dr. Kehr, it feels like I’m this close to losing everything I’ve worked so hard for all these years. If I don’t get better soon, my viewers are going to start to notice something is wrong with me. My ratings will fall, the network will fire me, we’ll lose the house, my husband will divorce me… I’ve already seen two other doctors, but nothing’s worked. I’m so desperate. What can I do?”

One of Carla’s previous doctors put her on Paxil, which gave her nausea, and the other placed her on Lexapro, which barely helped and caused unacceptable sexual side effects. I could hear the pain in her voice and explained to her that she still had reason to hope: “Carla, what you’re experiencing is not all that uncommon. Sadly, only about a third of patients on antidepressants fully recover. Another third only partially recover—and the last third don’t feel any relief. The problem is, depression is often treated as a single disease. But there is no such thing as ‘depression’—instead, there is ‘YOUR depression’. And that specific, individualized depression is the disease we can—and will—treat together, through a comprehensive evaluation, followed by treatment recommendations that will be precisely tailored to your personal genome.”

We performed the Genecept Assay and learned that Carla had a SLC6A4 S/S variant that predicted a poor response to SSRIs like Paxil and Lexapro – high rates of side effects and poor effectiveness – and so I placed her on Pristiq, an SNRI. Four weeks later she was 70% better and began to feel hopeful for the first time in months. As my mission is to do “Whatever It Takes” to help my patients achieve 100% recovery, we couldn’t stop there. I knew we could strive harder to achieve a full recovery, and so we persisted until we could find the right solutions.

Carla’s MTHFR Genes

As it turned out, her two MTHFR gene variants predicted about a 55% reduction in this important enzyme, which converts folic acid to L-Methylfolate. This vital molecule not only helps produce important mood and anxiety regulating neurotransmitters (serotonin, dopamine and norepinephrine), it also helps manufacture nucleic acids (the building blocks of DNA) and break down amino acids that help regulate the expression of DNA. We placed Carla on supplemental L-Methylfolate 15 mg daily, and I asked to come back and see me four weeks later. On that fateful morning I greeted her in the waiting room and she had a huge smile on her face! She came into the office and excitedly told me that she felt fully recovered! “I feel back to my old self for the first time in almost a year! I feel so lucky and grateful for the genetic test and you!” This time around, she wept with tears of joy!

Related Information

• Learn about Genetic Testing
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