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The Genetics of Inheriting Happiness:

MTHFR and Mental Health

We all know that people come in different shapes and sizes, with variations in aptitude and abilities. Some people can run fast, while others are math whizzes or have a way with words. 

We know people who are always bright and cheerful – and those who struggle to get through the day due to depression, which affects nearly 40 million adults in the United States. 

People feeling sad or depressed can point to their circumstances as the reason for their suffering. However, is it possible that some people genetically inherit a tendency to feel down and lack resilience? And if so, is there a way to change their outlook? 

How does MTHFR affect my brain?

While the intricacies of the brain are infinite, scientists have identified a common genetic variant that seems to play an important role in our ability to feel happy: methylenetetrahydrofolate reductase, or MTHFR. MTHFR is the gene that activates the folate (folic acid) in our diet into L-methylfolate, the form that our body can use, through a process called methylation. 

L-methylfolate functions in the brain as the building block for producing mood neurotransmitters like serotonin, norepinephrine, and dopamine. Most of the antidepressant medications on the market work by increasing one or more of these neurotransmitters in the brain. 

Where does the MTHFR gene come from?

Before we dive deeper, let’s get into some basic genetics. We all have two copies of every gene, one from each parent. These copies give us variation – you’re not a clone of one parent. You could inherit two functional genes or two non-functional genes, or one functional gene from one parent and one non-functional gene from the other parent. With this last combination, you could end up with a partially functioning gene.

With MTHFR there are two genes, so you have four chances to inherit different copies of the genes. Scientists use letters after the gene numbers to describe different variants of genes.  For MTHFR, the genes are called 677 and 1298. When you have decreased MTHFR function because of which gene variants you inherited, your body converts less dietary folate into active L-methylfolate. Ultimately, this means you have less of the raw material to make the mood neurotransmitters you need (serotonin, norepinephrine, and dopamine). 

How much less? Inheriting two malfunctioning copies of the 677 gene (which is called homozygous and is represented as 677 T/T) results in about 60 percent less MTHFR activity compared to someone who has the 677 C/C genotype. Having one malfunctioning gene, a 677 C/T genotype, results in 30 percent less MTHFR activity. The other MTHFR gene, 1298, has been less studied, but we know when you have 677 C/T variant and a 1298 A/C variant, you have a 60 percent decrease in MTHFR activity compared to someone who has the 677 C/C and 1298 A/A variants. 

For us regular people, less MTHFR activity means that less folate is properly used in the body, which could result in less mood-regulating brain text messages from our neurotransmitters – showing up as depression or another mood disorder.   

What can I do if I have a MTHFR variant?

While there are no established guidelines for the treatment of MTHFR gene variants, there is emerging evidence to suggest some mental health benefits of supplementing the body with pre-methylated folate – or folate that’s already prepared for your body to use. 

L-methylfolate is available in pill form and several studies suggest the benefit of L-methylfolate for depression, including as an add-on to prescription anti-depressant medications. One specific study found that patients with depression taking l-methylfolate reported significant improvements in depressive symptoms and functioning, with 67.9% of patients responding to supplementation and 45.7% achieving remission over 12 weeks.

We live in a time when information can empower us to make our own destiny rather than be limited by the genes we inherit. The knowledge of your MTHFR gene status may help you understand why you did not inherit happiness, and with the help of your healthcare provider, develop a solution to help unlock your potential to see a brighter, happier world. 

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