The Warrior Gene: Understanding the Role of Monoamine Oxidase Enzymes (MAOA and MAOB)

Key takeaways:
~ Monoamine oxidase (MAO) enzymes break down neurotransmitters, helping to regulate neuron firing in the brain.
~ Higher or lower MAO enzyme levels can affect mood by altering neurotransmitter levels.
~ Genetic variants in MAOA and MAOB are linked to mood and aggression based on gender and environmental factors.
~ The low MAOA version was initially called the ‘warrior gene’ by researchers. This has somewhat been debunked.

What is the MAO enzyme?

MAO, or monoamine oxidase, is an enzyme that breaks down neurotransmitters. There are two slightly different forms of MAO, MAO A and MAO B.

Specifically, MAO enzymes break down monoamine neurotransmitters including serotonin, dopamine, and norepinephrine.[ref]

• MAO-A preferentially breaks down norepinephrine, serotonin, epinephrine (adrenaline), melatonin, dopamine, kynuramine, tyramine, and tryptamine.
• MAO-B breaks down dopamine, 3-Iodothyronamine, β– Phenylethylamine, kynuramine, and tyramine.

In addition to its role in neurotransmitter metabolism, MAO is also involved in the metabolism of certain drugs and biogenic amines. More on this below.

MAO is produced by cells in the brain, as well as in other parts of the body such as the liver. In the brain, MAO is primarily found in the mitochondria of neurons.[ref]

Neurotransmitter levels are tightly controlled in the brain. You want everything in balance, with neurons firing appropriately.

Other routes: I wanted to point out here that the MAO enzymes are just one way that serotonin, dopamine, epinephrine, and norepinephrine can be broken down. Other enzymes and pathways also influence the levels of monoamine neurotransmitters.

MAO and Mental Health:

The relationship between MAO levels and mental health is complex.

Imbalanced or rapidly changing neurotransmitter levels can lead to changes in mood and behavior.

Low levels of MAO have been linked to an increased risk for certain mental health conditions such as depression, aggression, and impulsive behavior. It is thought to be related to the role of MAOA in regulating neurotransmitter levels in the brain. When MAOA levels are low, neurotransmitters such as serotonin and dopamine may build up in the brain, which can lead to changes in mood and behavior.

On the other hand, high levels of MAOA may protect against certain mental health conditions. Studies have shown that individuals with high levels of MAOA may have a reduced risk for certain mental health conditions. It is possibly related to the role of MAOA in breaking down neurotransmitters, which helps to maintain balanced levels of these chemicals in the brain.[ref]

However, it isn’t as simple as more MAO is always good…

The MAO A variants can interact with environmental factors to influence mental health. For example, childhood trauma, stress, and exposure to toxins can affect the expression of the MAOA gene, leading to changes in MAO A levels.[ref]

During childhood and early adolescence, brain structures are rapidly developing. Researchers have found that traumatic events, such as physical or sexual abuse, during childhood can affect adult brain function in some people. The MAO-A genetic variants are linked to an increased risk of aggressive behavior in men exposed to childhood trauma.[ref]

One study (n=235) found that low MAO-A levels combined with childhood trauma, increased the risk of higher aggression scores in men.[ref]

Genetic Variants and MAO Levels:

Genetic variants in the MAOA and MAOB genes impact the levels of these enzymes. There are both MAOA variants (covered below in the genotype report) and also variable number tandem repeats, which are unavailable in your genotype data.

Importantly, genetic variants are not the only determinants of mental health. Studies show that the relationship between MAO A levels and mental health is complex, and can be influenced by various other genetic and environmental factors.

The Flip Side: Studies that show no link between a genetic variant and a trait are also important to consider. For example, a study of attention to task found that MAOA variants did not play a role.[ref]

The MAO A and MAO B genes are located on the X-chromosome, so men only have one copy of the gene. For women, only one X chromosome is active in a cell, but it can vary in different tissues as to which copy of the X chromosome is silenced.[ref]

The “Warrior Gene”? Not for everyone…

MAO-A has been nicknamed the Warrior or Criminal gene due to early research in mice and in men showing that lower MAO-A levels are linked to aggression and impulsiveness.

Newer and more in-depth research shows this isn’t true for most people. Instead, the research gives us a more nuanced picture of how MAOA variants impact personality.

Aggression studies in animals, such as those done in rats, clearly point to a role for MAOA in aggression. However, MAOA more strongly affects dopamine levels in rodents than in humans. For example, mice bred not to have the MAOA gene are much more aggressive.[ref]

Rare mutations that significantly decrease MAOA levels in humans cause Brunner syndrome, which includes impulsive and antisocial behavior. Brunner syndrome is really rare, and the research on it is all in one Dutch family.[ref]

Many studies have been done trying to tease out the differences between lower or higher MAOA levels.

It’s not as simple as “low MAO A causes aggression”. Instead, it seems that low MAO A increases the relative risk of aggression in males who were mistreated or neglected as children.

Warrior Gene Benefits:

With a positive childhood and good parenting, low MAO A levels are linked to a decreased risk of aggression in both men and women.[ref]

While parental acceptance and involvement benefit all teen boys, a study showed that teen boys with higher MAO A levels exhibited even higher sensitivity towards parental involvement.[ref]

Interestingly, women with the ‘warrior gene’ version of MAOA are at a lower risk of ADHD.[ref]

MAO and Tyramine:

In addition to the catecholamine neurotransmitters, MAO also breaks down tyramine, a naturally occuring biogenic amine. Tyramine is found in fermented foods, like aged cheese and cured meats, as well as chocolate, non-pasteurized beer, and some wines.

The MAO A enzyme is one of several enzymes that can break down tyramine.

MAO inhibitors (MAOIs) are psychiatric medications that block the MAO A enzyme, thus increasing serotonin and dopamine levels. MAOIs can interact with tyramine, causing tyramine levels to be higher than normal. People on MAOIs are cautioned not to eat foods containing high levels of tyramines. When tyramine levels are too high, a hypertensive crisis can occur – dangerously raising blood pressure and causing stroke-like symptoms.[ref]

Related article: Tyramine metabolism

MAO and Toxins:

While the monoamine oxidase enzymes mainly break down substances produced in the body (e.g. neurotransmitters), they also can interact with the way that a few drugs are broken down and some environmental toxicants.

Parkinson’s and MAO B:
One chemical that is metabolized by MAO B is 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP itself is non-toxic and can cross the blood-brain barrier. In the brain, MAO B converts it into a neurotoxin, MPP+, which can cause cell death in dopamine-producing neurons in the substantia nigra. The death of dopamine-producing neurons in the substantia nigra causes Parkinson’s disease.[ref]

MPTP was discovered as a contaminant in illegal drugs that caused immediate and irreversible Parkinson’s symptoms. Within a few years of its discovery, MAO B was identified as the enzyme that turned MPTP into the neurotoxic MPP+. Researchers now use it extensively to create animal models of Parkinson’s.[ref]

Oxidative Stress and Monoamine Oxidase:

When monoamine oxidase breaks down a monoamine (neurotransmitters, tyramine, etc.), the reaction produces hydrogen peroxide and possibly ammonia, which are reactive oxygen species (ROS). This production of ROS is normal, and cells produce anti-oxidants to balance out the ROS. In the brain, glutathione is the antioxidant that counteracts the hydrogen peroxide created by MAOs.[ref]

However, when cellular antioxidants are overwhelmed by too much ROS, a state of oxidative stress occurs in the cell. When MAO is upregulated, such as when exposed to lipopolysaccharides on bacteria, oxidative stress can occur.

In addition to changing neurotransmitter levels, MAO inhibitor drugs also can decrease inflammation. The research on this is pretty new, but it will be interesting to see whether part of the reason MAO inhibitors work for depression is due to decreasing neuroinflammation.[ref]

Related article: Inflammation as a cause of depression

COMT and MAOA:

The COMT enzyme also breaks down catecholamines (dopamine, norepinephrine, and epinephrine). It is mainly found in the cytosol of cells, while MAO is found in the mitochondria.[ref]

Recent studies on aggression and mood have looked at the interaction between slow COMT activity along with low MAOA activity.

In teen boys, having the low versions of both MAOA and COMT was protective against ‘non-suicidal self-injury’. The study was done on males who had been abused as children.[ref]

An interaction between COMT and MAOB has also been seen in research on the susceptibility to OCD (obsessive-compulsive disorder).[ref] This possible link seems to be specific to MAO B and not MAO A. Other research points to no interaction between COMT, MOA A, and OCD.[ref]

Related article: COMT and Neurotransmitters

Lifehacks:

If you are a low MAO producer, should you try to increase it? I don’t know that the answer to that question is clear. There may be long-term tradeoffs for higher MAO A or MAO B levels in terms of neurodegenerative diseases.[ref]

I definitely would suggest that if you are on any medication, you should talk with your doctor before taking any supplements that impact MAO.

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Cofactor for the MAO enzymes:

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