MTHFR and Anxiety

Everyone experiences anxiety differently. Symptoms range from mild feelings of an upset stomach and fast heartbeat to feeling completely out of control, experiencing nightmares, panic attacks and dark thoughts. A general feeling of fear and worry, troubled sleep, poor concentration and restlessness are also common6.

Anxiety usually comes on gradually, and an anxiety attack typically occurs prior to a stressful situation, experience, or event. An anxiety attack can lead to feeling faint or dizzy, with shortness of breath, dry mouth, sweating and chills. Those affected will feel distressed, severely apprehensive, restless, fearful, and possibly experience numbness or tingling6.

These symptoms can result in avoidance of certain situations, as well as hyperventilation, becoming motionless, and/or difficulty speaking ³.

There are several types of anxiety disorders. The most common are:

Generalized anxiety disorder

People with generalized anxiety disorder feel anxious most of the time. They worry about several things at the same time, such as health, work, relationships, studies, etc.

Symptoms include: feeling restless or on the edge, fatigue, difficulty concentrating, irritability, muscle tension, sleep problems.

Panic disorder

People with panic disorder experience sudden periods of intense fear that come on quickly and reach their peak within minutes. Attacks can occur unexpectedly or can be brought on by a trigger, such as a feared object or situation. These folks may also worry about the next attack, making them avoid certain places and situations.

Symptoms include: heart palpitations, sweating, shaking, shortness of breath, and the feeling of being out of control.

Phobia-related disorder

Phobias are intense fears or aversions to specific objects or situations. This fear is often out of proportion to the actual danger.

Social anxiety

People with social anxiety may avoid certain social situations because they fear being judged, and are easily embarrassed.

Separation anxiety

A fear of being separated from people you are attached to.

Studies have confirmed that deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAMe). In the brain, SAMe donates methyl groups to catechol-O-methyltransferase (COMT), which is involved in neurotransmitter analysis. Increased levels of homocysteine have been linked to impaired monoamine synthesis (i.e., the making of serotonin) due to reduced levels of SAMe.

It’s also been found that elevated homocysteine results in stimulation of glutamate, the most abundant excitatory neurotransmitter in the nervous system. In cases of severe MTHFR deficiency, glutamate is increased in the amygdala and GABA is decreased in the thalamus ⁸.

Higher levels of glutamate have been detected in people affected by anxiety. Patients with social anxiety were found to have 13.2% higher glutamate levels than controls, which was correlated with their social anxiety symptoms ⁹.

Those with impaired methylation usually have excess levels of glutamate: an excitatory neurotransmitter that can promote increased feelings of stress and anxiety. As the MTHFR deficiency typically results in low levels of SAMe - and subsequently low levels of neurotransmitters - it may also result in low levels of GABA, an inhibitory neurotransmitter that balances the effects of glutamate and helps to reduce symptoms of anxiety. Excess glutamate in the brain is known to increase feelings of anxiety, fear, nervousness, restlessness and/or insomnia ¹⁰. Studies on MTHFR association with anxiety and depression have shown that MTHFR mutations and high homocysteine have been linked to depression without comorbid anxiety disorder.

People with MTHFR mutations and high homocysteine also appear to have lower vitamin D concentrations, which can affect mood as well ¹¹.

Adults and children may experience anxiety differently. While adults can explain their experiences and compare their symptoms to what might be considered anxiety-related, children don’t have the cognitive awareness to do so. Anxiety in children can also appear similar to normal developmental stages which cause insecurity and fear. However, high rates of ADHD and anxiety symptoms have been documented in autism, which has also been associated with MTHFR ¹².

Anxiety disorders are also common in adults who have ADHD, with some research showing that more than half of people with ADHD also have anxiety ¹³. Anxiety symptoms generally do not worsen on stimulant medication. A large meta-analysis found that treating ADHD individuals with psychostimulants significantly reduced their risk of developing anxiety ¹⁴.

However, it has also been found that those with ADHD are at risk for substance abuse, partly due to their symptoms and associated medication ¹⁵. Stimulants are therefore considered only as a second-line option for adolescents and adults with ADHD and substance use disorders. 

Poor MTHFR activity or folate deficiency have been associated with the onset of several psychiatric and cognitive conditions, including schizophrenia, bipolar disorder, depression, autism, dementia, and ADHD (Attention Deficit Hyperactivity Disorder).

A meta-analysis of seven studies found that people with TT homozygotes (double mutation) had the greatest risk of schizophrenia, compared to people with no mutation or a single mutation ¹⁶.

Another study reported that those with the homozygous TT genotype were also more likely to develop schizophrenia along with a higher risk of bipolar disorder ¹⁷. Interestingly, this association between homozygous 677TT genotypes and bipolar disorder appears to be even stronger in males than females ¹⁸.

Those suffering from anxiety are often at a loss as to why they feel the way they do. Their lives are significantly impacted by their disorder, and yet they often find no relief from medication.

The good news is that scientists now understand more about the MTHFR mutation and anxiety, particularly in terms of the impact that MTHFR has on biochemical processes within the body. The many requirements of folate are also better understood, particularly with regards to its role in creating chemicals involved in mood and brain function.

As you will have learned in this article, methylfolate is one of the most important nutrients for everyday function. It is necessary not only for healthy methylation but also reducing harmful homocysteine levels and the manufacturing of important neurotransmitters. The depletion of these nutrients has a detrimental effect on our ability to feel calm, positive, and motivated.

Anxiety can be managed with the right nutrients and lifestyle changes. This begins with taking a quality methylfolate supplement. Methylfolate bypasses the MTHFR mutation, providing your body with an active form of the folate it needs to carry out methylation and many other biochemical pathways. It’s the most effective way to optimize your body’s methylation processes and support a healthy mood.