mthfr mutation and depression

Major depression has always been an enigma—science still has not identified the exact cause of this prevalent mental health disorder. For generations, attempts have been made to isolate the cause of so much suffering, but to date most therapies stop short of curing the debilitating disorder.

As genetic research continues to reveal more and more gene mutations that help explain why someone might inherit a propensity toward a particular medical condition, addiction, or mental health disorder, one such discovery has shone light on a genetic link to depression in the MTHRF gene mutation. The MTHFR mutation is not uncommon and can be detected through a DNA test. Learning more about the MTHFR mutation and depression can provide important guidance for individuals seeking to discover what might be causing their own depression.

About the MTHFR Mutation and Depression

The abbreviation, MTHFR, stands for a gene called methylenetetrahydrofolate reductase.  A mutation, or variant, on this gene can cause high levels of homosysteine in the blood, along with a deficiency in folate and other vitamins. In turn, a variety of health issues can result from the gene mutation, particularly when there are two mutations on the gene. These variants are inherited from parents, causing either a singular mutation from one parent, or two mutations if both parents have the mutation. This is called a homozygous mutation.

Along with cardiovascular diseases, stroke, blood clots, leukemia, colon cancer, and nerve pain, MTHFR mutations are also linked to mental health disorders. These include depression, anxiety, bipolar disorder, and schizophrenia. This blog will focus on the connection between the MTHFR mutation and depression. Essentially, depression can result from the folate deficiency caused by this particular gene mutation.

The Connection Between the MTHFR Gene Mutation, low BH4, and Depression

There is a complex relationship between MTHFR genes and depression. One of the primary problems is that a MTHFR mutation can cause folate deficiency, which can cause low BH4, a cofactor that produces enzymes vital to healthy functioning neurotransmitters. The low BH4 can lead to low serotonin and dopamine levels. BH4 is needed to support the conversion of tryptophan into serotonin, so when BH4 levels are decreased, the folate cycle is negatively impacted, which can cause depression due to the low serotonin and abnormal dopamine levels.

What is Methylation-Related Treatment for Depression?

When the brain is not producing adequate serotonin levels, symptoms of depression result. These symptoms, such as persistent low mood, fatigue, sleep disturbance, over eating or lack of appetite, can be mitigated by drug therapy, such as using SSRIs and/or use of certain supplements that aid the methylation cycle.

To aid this biochemical process in the body, and to overcome symptoms of depression, certain supplements and dietary changes can help significantly. Some of these interventions include:


  • Eat leafy greens, such as spinach, kale, Brussels sprouts, and asparagus
  • Fruits such as cantaloupe, banana, strawberries, raspberries, and grapefruit
  • Legumes, such as beans, peas, and lentils
  • Peanut butters and sunflower seeds, almonds, and walnuts
  • Pineapple juice, orange juice, tomato juice, and grapefruit juice


  • Omega-3 fish oil
  • Folates, B6, B12, and riboflavin
  • Magnesium and zinc
  • Selenium
  • Vitamin C, D, and E
  • Protein powder
  • Serosyn
  • Probiotics


  • Regular exercise, especially cardio
  • Stress-reducing activities, such as yoga, meditation, deep breathing, and mindfulness
  • Do not smoke
  • Reduce alcohol intake

Treatment Options for Depression

The above dietary interventions can significantly increase the effectiveness of traditional depression treatment therapies by assisting the body in improving the methylation process and increase folate levels. Traditional depression treatment involves a two-pronged approach that includes both antidepressant therapy and psychotherapy.


Antidepressant therapy is utilized for individuals battling depression because they help normalize serotonin levels. There are several types of antidepressants, including selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and monoamine Oxidase inhibitors (MOI). Generally, the mental health professional will select the type of medication he or she feels is best suited for the individual patient’s symptoms, mental health history, and general health status.

Antidepressants take 4-6 weeks to take effect, so the patient is encouraged to be patient during the trial period to give it time to work. However, there is a significant percentage of patients suffering from depression who do not respond well to these drugs. The drugs may not succeed in reducing symptoms of depression, or the side effects may have been intolerable. Side effects from antidepressants vary per drug, but generally include weight gain, dry mouth, fatigue, nausea, sexual dysfunction, and insomnia.


Talk therapy, or psychotherapy, is a mainstay in the treatment of depression. The purpose of psychotherapy is to assist the individual in examining potential underlying factors related to their depression. In the individual therapy sessions, patients feel safe to open up and explore difficult life events, past traumas or painful memories that may be triggering the symptoms of depression.

There are a variety of treatment modalities that can be accessed to treat patients with depression. Among the most popular are cognitive therapy, cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), psychodynamic therapy, interpersonal therapy, and attachment therapy. Sessions can be formatted in both individual or group therapy, and most psychotherapists recommend participation in each format for best results.

When considering the possible genetic link to one’s depression, it is helpful to be tested for the MTHFR mutation if blood tests reveal a high level of homocysteine, which may be an indicator of the mutation. Genetic testing can be ordered by the physician.

The Treatment Specialist Can Answer Questions About MTHFR Mutation and Depression

The Treatment Specialist is a renowned research for topics and treatment options pertaining to mental health and addiction disorders. Knowledge about the MTHFR mutation and depression can help guide the individual toward seeking out appropriate or specialized treatment. For more information about the MTHFR mutation and its possible connection to depression, please call (866) 644-7911.

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