MTHFR Gene Mutations and Mental Health: Understanding the Link
Mental health disorders have numerous contributing factors, from social and environmental to genetic. Recent research suggests that gene mutations may also play a part in the development and etiology of certain mental health conditions. Some examples of mental disorders that may be passed down through generations include depression, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder (ADHD).
So, is mental illness hereditary? Perhaps. This article will discuss the link between gene mutations and mental health, including current research into the causes of mental health problems and implications for diagnosis and treatment.
What Are Gene Mutations and How Do They Affect Mental Health?
A gene mutation is a change in an individual’s DNA sequence. This change can be inherited or it can occur due to errors in DNA replication during cell division, exposure to mutagens such as radioactive substances, ultraviolet radiation, and/or certain chemicals. Viral infections can also be a cause.
One mutation that has been linked to mental health is the MTHFR gene mutation. The MTHFR gene provides the body with instructions for making the enzyme methylenetetrahydrofolate reductase (MTHFR).
A mutated allele at either of two specific locations on the MTHFR gene can lead to 20-40% reduced activity of the MTHFR enzyme, impairing the body’s ability to convert folic acid into folate, or 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (methylfolate). Other reports suggest that people who are heterozygous for an MTHFR C677T mutation (a single mutation) have only 65% of normal MTHFR enzymatic function, while those who are homozygous for MTHFR C677T (a double mutation) have only 30% function. 
This level of function reflects how much methylfolate may or may not be available to convert homocysteine to methionine. Methionine is required for the production of several important compounds, including the neurotransmitters serotonin, dopamine, and norepinephrine.  These neurotransmitters contribute to healthy mood and normal cognitive function.
The MTHFR mutation on the MTHFR gene can increase the risk of health concerns such as cardiovascular disease and stroke, infertility, miscarriage, migraines, and certain cancers. More recently, studies have found that MTHFR is also associated with an increased risk of depression (including treatment-resistant depression), bipolar disorder, schizophrenia, and some behavioral disorders such as attention-deficit hyperactivity disorder (ADHD), or autism. While these are not technically genetic mental disorders, it does appear that genes are definitely involved.
The Genetics of Mental Health: What We Know So Far
Scientists have long sought to answer the question, is depression hereditary?
Mental health disorders such as depression, bipolar disorder, and schizophrenia are known to run in families, indicating that genetics may be involved. Recent studies have revealed shared genetic risk factors between these disorders and certain behavioral disorders.
MTHFR plays a critical role in one-carbon metabolism, which involves folate, homocysteine, vitamin B12, and the methylation of DNA. Mutations of this gene affect MTHFR enzyme activity, which in turn will affect the production of neurotransmitters implicated in psychiatric disorders. 
A 2022 meta-analysis of 81 published studies assessed the association between MTHFR mutations and susceptibility to psychiatric disorders.  The researchers found a significant link between both major depression and one of the most common MTHFR mutations, MTHFR C677T. This particular mutation was also linked to a higher risk of bipolar disorder. The other common MTHFR mutation, MTHFR A1298C, had only a minor link to major depression.
Another 2022 study investigated the genotypes of 30 adults with major depression. It found that 10 patients had the heterozygous C677T mutation, while none had the A1298C. Twenty-one patients had another MTHFR polymorphic marker, the T1565C mutation, while seven patients had compound mutations in both genes. 
Previous studies have also found genetic links to mental health. A 2016 study found that people with the genetic mutation DISC1 had changes in the structure of their brain linked with the severity of their symptoms of mental ill health. The researchers explained that similar genetic effects can increase the risk of major mental illnesses.
Implications for Diagnosis, Treatment, and Prevention:
So far, research into the link between MTHFR and mental health suggests that the C677T polymorphism increases the risk of both severe depression and schizophrenia in the general population. There also appears to be a higher risk of bipolar disorder in those with the C677T mutation.
Scientists have stated that more research is pending, but the current data implies that MTHFR may play a significant role in the development of mental illness, and that variations of the mutation may be involved in controlling the expression of genes associated with it.
More importantly, it has been suggested that genetic profiling may help with the early diagnosis and treatment of mental disorders. While detecting variations may not actually predict or diagnose specific conditions, the results of the above studies may help researchers move closer to making more accurate diagnoses. They may also help improve practitioners’ understanding of the factors that cause certain mental health disorders.
Future Directions into Genetics and Mental Health Research
The recent discoveries on MTHFR polymorphism and related DNA methylation in various psychiatric disorders has opened opportunities for further research into the genetics of mental health. These findings have also highlighted the importance of the relationship between MTHFR enzymatic activity and the role of folate in certain mental illnesses.
At present, most theories regarding the development of depression and schizophrenia are related to neurotransmitter imbalances. However, this new research into genetic links may help to pinpoint risk factors for specific psychiatric diseases, as well as new targets for specific treatment. This may also pave the way for answering questions such as, “is depression and anxiety hereditary?”
In the meantime, one option for those with MTHFR mutations is to supplement with a methylated form of folate.This is the form required for producing neurotransmitters that support good mood, and studies have shown that 7.5 mg or 15 mg methylfolate can improve depressive symptoms and overall quality of life. 
Gene mutations may provide valuable insights into the underlying causes and mechanisms of mental health disorders. In particular, it appears that MTHFR may contribute to the development of depression and other mental illnesses, and that detecting MTHFR variants in an individual may help researchers and health specialists in the early diagnosis and treatment of psychiatric disorders.
At present, however, more research is needed to fully understand the complex interaction between genes and mental health, and to address the ethical, social, and practical challenges of genetic testing and intervention in this context.
Updated On: March 31, 2023
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