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MTHFR and Mood Disorders: is there a Connection?


MTHFR and Mood Disorders: is there a Connection? | Methyl-Life

MTHFR and Mood Disorders: is there a Connection?

MTHFR genetic mutations play a key role in several aspects of emotional health.


Since DNA methylation and folate are essential in mental health, the reduced MTHFR enzyme and/or folate deficiency have been associated with many psychiatric disorders, including schizophrenia, bipolar disorder, depression, autism, and ADHD.


The C677T polymorphism, in particular, is considered a predisposition to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression.


This article will explore the link between MTHFR and mood disorders and how this genetic mutation affects mental health. We will also discuss how supplementation with various nutrients may support mental health and reduce the risk of developing a mood disorder.


What are Mood Disorders?

Mood disorders are defined as marked disruptions to one’s emotional state, such as severe lows (depression) or highs (mania). They often lead to severe functional impairment and reduced quality of life.


The broad categories of mood disorders include bipolar disorders and depressive disorders.


Some common types of mood disorders include:

  • Major depression: Reduced interest in usual activities, feelings of sadness or hopelessness, decreased energy levels, concentration, appetite and other symptoms for at least two weeks.

  • Dysthymia: Chronic, low-grade, depressed, or irritable mood persisting over at least two years.

  • Bipolar disorder: Periods of depression alternating with periods of mania or elevated mood

  • Illness-related mood disorder: Serious injuries or chronic medical illnesses may trigger symptoms of depression.

What Do Studies Show About the MTHFR Gene and Mental Health?

What Do Studies Show About the MTHFR Gene and Mental Health

Defects in the MTHFR enzyme can impair methionine synthesis, resulting in reduced SAMe production and a decrease in methylation reactions. Increased homocysteine levels block the production of monoamine neurotransmitters, especially those required for healthy mood (such as serotonin, norepinephrine, glutamate, dopamine, and γ-aminobutyric acid).


Altered homocysteine metabolism has been linked to the pathogenesis of autism, ADHD, schizophrenia, depression, bipolar disorder, and anxiety. MTHFR mutations interfere with normal methylation of subcellular components, promote neuron excitotoxicity, and induce oxidative stress and inflammation.


A meta-analysis found that MTHFR C677T was associated with a higher risk of depression, especially in Asian individuals.


The link between elevated homocysteine and depression has been described as resulting from folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism. Folate deficiency was observed in up to one-third of patients with severe depression.


The MTHFR gene and a corresponding folate deficiency may also increase the likelihood of a child being born with ADHD. Impaired folate metabolism has been linked to the accumulation of toxins that have been found in ADHD.


Can Supplementation Help?

It has been noted that many studies on patients with neuropsychiatric disorders have linked folate deficiency with low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). One study also showed that supplementation with folate restored CSF 5-HIAA levels to normal.


It is for this reason that Deplin (a methylfolate-based medical food) is often used as an adjunctive treatment to antidepressant medication. Deplin is particularly effective for those with major depressive disorder, schizophrenia, or hyperhomocysteinemia related to folate deficiency.


One study involving 127 people with severe depression found that women receiving 500 mcg of folic acid alongside antidepressants experienced a significant improvement in their symptoms, while the men did not. The researchers suggested that either the dose was insufficient or that 5-MTHF would have been more suitable due to the overrepresentation of MTHFR C677T among patients with depression, which impedes folic acid bioavailability.


A real-world trial found that patients with depression taking L-methylfolate experienced significant improvements in their symptoms and overall functioning, with 67.9% of patients responding and 45.7% achieving remission over 12 weeks.


Vitamin B12 also plays a vital role in homocysteine metabolism and neurological function. Vitamin B12 supplementation alongside antidepressants was found to significantly improve depressive symptoms in a subgroup of patients with vitamin B12 deficiency.


Supplementation with Omega 3 fatty acids has also been found to be effective in reducing symptoms of depression, and this is thought to be due to their anti-inflammatory activity and maintenance of membrane integrity and fluidity. A meta-analysis of 26 studies showed an overall beneficial effect on depression symptoms.


Probiotics play a major role in the bidirectional communication between the gut and the brain, which suggests probiotic supplementation may be valuable to those with mood disorders. A meta-analysis found that probiotics significantly decreased depression scores in both the healthy population and patients with major depressive disorder.


Key Takeaways

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Can Supplementation Help

A healthy, normal mood depends on the production of various neurotransmitters, many of which are provided via the methylation process. Deficiencies in specific nutrients, especially folate, have been shown to contribute to psychiatric disorders, namely depression and ADHD.


For many people, supporting the body’s key methylation processes may require supplementation with folate, particularly in the case of an MTHFR deficiency.


Many health practitioners have recommended L-Methylfolate as a safe and effective means of supporting serum folate levels. L-Methylfolate is suitable for those with mood disorders and impaired folate metabolism as it can bypass the MTHFR deficiency. Methyl-Life® offers a range of supplements designed to support healthy mood and cognition, including high-dose L-methylfolate and a Mood Elevating bundle.


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    Written By,
    - Katie Stone


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