MTHFR: Another Piece of the ADHD-Genetics Puzzle

ADHD is a very complex disorder. The number of factors contributing to symptoms is vast — and growing. MTHFR is a genetic abnormality that’s somewhat common in individuals with ADHD, and its presence could explain a lot, and offer additional treatments. Here is what you need to know.

By Penny Williams Verified Updated on July 11, 2022

Genetic code for DNA that is linked to ADHD

If there’s one thing we know for sure about ADHD, it’s that no one knows for sure what causes it. Genetic inheritance and many environmental factors have been proven to increase a child’s risk of being born with ADHD. Yet, no one can say that any one thing in particular that causes it thus far. Indeed, ADHD is a complex disorder that isn’t likely caused by one certain genetic abnormality or environmental factor. Like autism, the disorder comprises a spectrum of symptoms varying in severity, and its causes are likely to mimic a similar pattern.

The genetic “instructions” for a child comprise a mash-up of instructions from each parent. The language of these instructions is our individual genetic code. Some genetic factors are passed along to offspring just as they appear in one parent — for instance, eye color or hair color. Other genetic traits are created by a new combination of different parent genes. Further still, abnormalities in the formation of genes can lead to differences and disorders; Down’s Syndrome is a well-known example of that. Certain genetic abnormalities also increase the risk for ADHD and autism.

We have learned all of this through the growing field of genetic science. And we’re learning more and more each day about neurological disorders, like ADHD and autism, through neurogenetics — the sub-field that brings together genetics and neuroscience to shed some welcome light on neurological disorders’ causes and, someday, treatments.

We know that parents with ADHD are more likely to have kids with ADHD, because it is inheritable. But what specific genes lead to an increased risk of ADHD or autism? One culprit is MTHFR. MTHFR genes control a biological process in the body that affects neurological function. MTHFR abnormalities have already been linked to more than 60 disorders, including autism and mood disorders. They’re seen in many individuals with ADHD as well.

What is MTHFR?

MTHFR is the name of both a gene and an enzyme in the human body — methylenetetrahydrofolate reductase to be specific. The gene tells the body how to make the enzyme. This enzyme is important to process folate or folic acid (B9) properly. In simplest terms, it turns folate into its bioavailable form, methylfolate, through a process called methylation. The methylfolate then converts amino acids for a variety of the body’s functions, including the manufacture of serotonin and dopamine.

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So, if the MTHFR gene is mutated, it cannot produce the enzyme correctly, which disrupts the processes on down the line — one of which is the production of serotonin and dopamine, key players in ADHD, autism, and mood disorders. The malformation of the MTHFR gene causes one’s body to change folate into methylfolate at a reduced capacity (as low as 10% for homozygous and 50% for heterozygous). An individual may have too much folate in his or her body, and not enough methylfolate, which, again, hinders the processes on down the line.

MTHFR also aids the process of detoxification in the body. When it’s not working properly, heavy metal and mineral levels can reach dangerous levels or imbalance, which can cause hyperactivity, mood disorders, and so much more.

How is MTHFR Treated?

If not treated, MTHFR mutations can cause a buildup of folic acid and make mood and behavioral disorders worse, and treatment of them more difficult (especially mood disorders). As such, this mutation often explains, at least in part, why some individuals have sensitivities or rare reactions to medications, and even supplements. It also explains why mood and behavior can worsen when your child takes an ordinary multivitamin, or even eats fortified cereals.

Treatment of MTHFR polymorphisms vary depending on the individual’s genetic makeup, or genome. Methylated versions of supplements like folate (methylfolate) and B-12 (Methylcobalamin, hydroxycobalamin, or adenocobalamin) are often recommended, as well as the biologically active form of B6 (pyridoxal-5-phosphate or P-5-P), and a quality antioxidant. Steering clear of extra folic acid is advised, too.

[Study: Gene That Helps Brain Regions Communicate May Be Linked to ADHD]

How Do You Test for MTHFR?

It’s best to work with a physician on testing for and treating MTHFR abnormalities. It’s a complex process that requires a delicate experimentation to get it just right. Most physicians don’t know anything about MTHFR, so you’ll want to look for an integrative medicine doctor.

Laura, a Connecticut mom of two kids, stumbled upon the potential need for MTHFR testing for her kids when searching for online support. Her kids had been diagnosed with PANS (or PANDAS) — an autoimmune disorder triggered by an infection and characterized by sudden onset of mental, emotional, and behavioral health symptoms, sharing many symptoms with ADHD.

If you cannot find a physician to work with you, you can still get the test. It’s available from different companies online and simply requires a saliva sample or cheek swab.

“We used 23andMe.com to obtain the raw genetic data, comparing how our genes compared to ‘typical’ genes for the general population,” explained Laura. “I then took that data and ran it through the app on www.geneticgenie.org, which parsed out roughly 30 genetic data points and told me whether our results were ‘typical’ or ‘atypical.’ These particular points indicate whether your body is able to efficiently process, or methylate, various vitamins, amino acids, minerals and nutrients, many of which help the body generate key neurotransmitters — primary drivers of mental and behavioral health. Our Genetic Genie report flagged any genes that weren’t working ‘as expected’ and had the potential of interfering with how the body made use of some of its neurotransmitters.”

“My daughter saw the largest benefit. I started by addressing her MTHFR ‘defect,’ which hinders her ability to convert folate (vitamin B9) into a form that can work with vitamin B12 to ultimately make energy and serotonin. In the first few months of supplementing and zeroing in on the right doses of a specific form of Vitamin B9 (methylfolate) and the form of B12 that works best for her (adenocobalamin), I saw a huge improvement in her drastic mood swings. She became much steadier mood-wise, much calmer.”

If your child’s treatment isn’t going well, or you feel like you’re doing everything right but still must be missing something, testing for MTHFR polymorphisms may be a logical next step.

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