Are some people really “born to rage” and others destined to be the quiet and friendly “worrying” type? How significant is the science behind the “warrior” gene, which researchers know as MAOA, and can it impact our behavior? Read on as we dive deep into genetics research to separate facts from hype.
What is MAO-A?
Is Rage in Our Genes?
For a while, it seemed like the “warrior gene” was a hot topic everywhere – from National Geographic broadcasts to Dr. Phil’s talk show to “The Blacklist” (season 2 episode 4) to ABC News.
The trigger was a couple of scientific studies that found an association between certain variations of the MAOA gene and aggression. News outlets saw a great story in these discoveries, jumping to say that some people may carry “dangerous DNA.”
But science is not that simple.
Humans have about 25,000 genes that code for proteins – according to recent scientific estimates. These protein-coding genes are considered to be relevant, since they likely have a biological effect. The number of genes we carry is still an open question [1].
Still, scientists know that a genetic variation in a single gene doesn’t usually equate to complex traits like aggression and impulsivity.
Complex traits like aggression always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that interact and vary from one person to another.
If that weren’t the case, we’d probably degrade back to dangerous and fanatic ideologies – ones that could label some people as “criminals” based on the genes they were born with.
Nonetheless, MAOA opened pandora’s box. Many ethical questions started to arise…
For example, if a person is not responsible for the genes they carry, should they be held responsible for their actions (if their genes predispose them to violence)? Can a person who committed murder be found guilty because they carry the “warrior gene” [2]?
More Caveats
Let’s not forget that these “dangerous” variations are present in about 40% of the population (roughly speaking). They’re not rare nor are they particularly unique.
Plus, certain genetic variations in MAOA were only associated with aggression or mental health problems. That does not imply having them will make you more likely to be aggressive or suffer from a mood disorder. Data are lacking to make such claims since a cause-and-effect relationship hasn’t been established.
That doesn’t mean MAOA is completely insignificant. Let’s see what made the “warrior gene” discoveries equally interesting to scientists, media outlets, lawyers, and forensic experts.
MAOA Enzyme Basics
Monoamine oxidase A (MAO-A) is an enzyme that breaks down neurotransmitters such as norepinephrine, serotonin, and dopamine. In line with this, scientists have proposed that [3].
- High levels of this enzyme should translate to fewer neurotransmitters – as MAO breaks them down quicker.
- Low levels of this enzyme should imply more neurotransmitters – as there’s less MAO around to degrade them
Theoretically, MAO-A is not something we want to be too high or too low. Both situations have been associated with different negative effects [4].
According to one hypothesis, relatively high or low levels could have been advantageous in different environments in our evolutionary history. This might be precisely because “warrior” variations are relatively common in the population, so they likely served some purpose in our evolutionary past [5].
The MAO-A Gene
Versions
The MAOA gene is located on the X chromosome. For reference, women have two X chromosomes, while men have one X and one Y chromosome. The X and Y chromosomes determine a person’s sex at birth, which is why they’re also known as “sex chromosomes” [6].
This also means that men can only have one MAOA variant, while women have two [6].
There are a few main versions of the gene that produces MAO-A: 2R, 3R, 4R.
Limited studies have linked the 2R version with the lowest MAO-A production and more aggressive and impulsive reactions to stressful stimuli. 3R was associated with somewhat reduced MAO-A. That’s how these MAO versions became known as the “Warrior Gene” [6].
The 4R version was associated with the highest level of MAO-A [6].
Potential Effects of High or Low MAOA Activity
The basic interpretation is that people with 2R or 3R version may produce less MAO-A and have more circulating adrenaline, dopamine, and serotonin. This is still uncertain [6, 7].
Limited studies found associations between low-activity MAOA variants and a range of aggressive and antisocial behaviors, including adolescent antisocial behavior, reduced social cooperation, physical aggression, criminal violence, and recidivism in male violent offenders. But many of these associations were not properly confirmed [5]
Later studies suggested that low-activity MAOA may predispose people to antisocial behavior in life only if they suffered traumatic events in early life [7].
Other studies found opposite effects in women – they associated high-activity MAOA versions with increased risk of antisocial behavior and aggression. Some scientists have hypothesized that testosterone can modify the impact of MAOA on behavior to explain these findings [5].
One theory proposes that low-activity MAOA variants may be “sensitivity variants” that make carriers more responsive to both negative (trauma) and positive (resilience) factors [5].
In line with this theory, recent findings suggest that certain protective psychosocial factors like resilience may be able to shape a person’s genetic predispositions. That means a low-MAOA carrier might benefit more from a protective, enriched environment – but they may also suffer more from trauma. This has yet to be verified, though [5].
According to a study on Syrian refugees published in 2019, men with low-activity MAOA perceived less stress. The biggest reductions in perceived stress were seen in men with low-activity MAOA with low trauma exposure or high resilience levels [5].
More research is needed.
Mood
There’s a lot of contradictory information about the effects of high MAO.
Limited studies suggest that people with major depressive disorder may have higher brain MAO-A. This is hypothesized to lower monoamine neurotransmitters that help balance mood, potentially contributing to depressive episodes. A link between high MAO-A and suicide and sleep disturbances has also been proposed [8]
(Over)Reacting and Empathy
One recent small study suggested that people with high-activity MAO gene variations are less reactive and aggressive when provoked. The study participants were paid to punish those they believed had taken money from them by making them drink extra-spicy hot sauce [7].
The difference between high- and low-MAO carriers became somewhat evident only if most of their earnings were taken away from them: 75% of low-MAO carriers would harm their opponent, versus 62% of high-MAO carriers [7].
Although interesting, this study included only 8 people in total. Its sample was too small for us to draw any solid conclusions [7].
In another small study, high-activity MAO-A carriers (MAO-A R297R G or GG) weren’t as affected by the placebo effect, but this hasn’t yet been replicated. However, it is in line with the “sensitivity theory” [9].
Another open question is: Do people with high-MAO gene versions care more about others – or are they less sensitive and, thus, less likely to overreact? Only future research will tell.
Additional Research
Mice with low MAO-A are also more aggressive in general and are more likely to start turf wars [6]
In one study, men with low-activity alleles were found to be at greater risk of aggressive and impulsive reactions to stressful stimuli. On the other hand, women carrying the high-activity alleles seemed to be at an increased risk of aggression, but only if they were exposed to high early life adversity. Further work is needed [6].
Racial Differences
The Warrior Gene was found to be more or less prevalent in different ethnic groups [6].
The 3R version, which produces less MAO-A, was found in 59% of Black men, 56% of Maori men (an aboriginal New Zealand group), 54% of Chinese men and 34% of Caucasian men.
The 2R version, which produces the least MAO-A, is found in 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men.
How to Check Your Genes
No SNP directly translates to the 2-4R versions mentioned above, but some SNPs somewhat correlate with these versions. This depends on groups of SNPs that are looked at and a person’s gender.
You can check some SNPs in your DNA test results by looking for:
Rs909525
Rs909525 (MAOA Gene), considered to be the best proxy for the number of repeats of the MAOA warrior gene [10].
Limited studies suggest the following associations:
- T= “non-Warrior” version (“TT” or just “T” in men)
- C= “Warrior” version.
People with “T” are more likely to have the 4 or 5R non-Warrior version and people with “C” are more likely to have the 3R Warrior version.
On the other hand, only men with the T allele had higher rates of suicide compared to controls (70.5% vs 54%) in one study. This finding hasn’t been replicated [11].
Rs2064070
Males with rs909525 (C), rs6323 (G) and rs2064070 (A) had higher scores on the scale measuring the expression of anger outwards [11]. Females with TT allele reported higher “spontaneous aggression” [11].
Rs6323
Rs6323 (MAOA R297R Gene) – The G or GG allele was linked with higher levels of the enzyme, while the T allele indicated lower levels (T is the ‘risk’ allele). In females, the G allele was associated with higher outward anger (p = 0.002) and the G allele was also associated with aggression in males [11].
In one study, the T allele was linked with generalized anxiety disorder [11].
In another small study, women with TT reported higher levels of “angry temperament” and female suicide attempters with TT reported higher “self-aggression” [11].
Rs6609257
One SNP variation in rs6609257 was associated with low visuospatial working memory and was considered to be predictive of maladaptive behavior like aggression [12].
Specifically, the A allele of rs6609257 is associated with more MAO-A and higher levels of working memory and the G allele is associated with lower levels [12]:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309555/figure/fig3/
Rs3027399
The combination of the following indicate the 5R version, which is poorly understood: rs909525(T) AND rs6323(G) AND rs3027399(G) [13].
Factors that May Affect MAO-A Levels
When to See a Doctor
If your goal is to modify your MAO enzyme activity because you have a chronic or mental health problem, it’s important to talk to your doctor, especially your symptoms are significantly impacting your daily life.
Your doctor should diagnose and treat any underlying conditions causing your symptoms.
Precautions
Supplements have not been approved by the FDA for medical use and generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
Additionally, supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. That’s why it’s so important to consult your healthcare provider before supplementing and let them know about all drugs and supplements you are using or considering.
Dosage may also matter and different doses will have different effects. Safe supplement doses should not be exceeded.
Finally, have in mind that none of these strategies should replace what your doctor recommends or prescribes.
Research Limitations
Remember that the existing evidence did not verify that abnormal MAO-A causes any disorder.
The potential health effects of activating or blocking MAO-A in humans are still an area of research.
Remember changes in brain chemistry are not something that people can change on their own with the approaches listed below.
Thus, we’re providing a summary of the existing research, which should guide further investigational efforts.
The studies listed in this section were mostly done in animals and should not be interpreted as supportive of health benefits in humans.
Please read through them having these important limitations in mind.
May Increase or Support MAO-A
Supplements
- Ginkgo, reduced aggression to “normal| in mice without MAOA [14].
- Riboflavin is needed for MAOA [15].
Pathways and Hormones
The following hormones are highly experimental. Researchers are investigating them to better understand MAO-A-related biochemical pathways.
- Female sex hormones like progesterone and estrogen [16, 17, 18].
- 5HT2A blockers in mice without MAOA [14].
- BMAL1, a core circadian protein [19]. Circadian rhythm disruption may result in lower BMAL1 and lower MAOA. Learn how to keep to a circadian rhythm.
- SIRT1 is hypothesized to active (by deacetylation) MAO-A [20]. SIRT1 activation may, theoretically, increase MAOA.
- Valproic acid
Do not take any hormones or drugs without seeing a doctor.
Hormones (including progesterone, estrogen, and testosterone) and drugs (like valproic acid) are available only with a doctor’s prescription. Taking hormones or other prescription medication without medical supervision can be extremely dangerous.
May Reduce or Block MAO-A
Scientists are investigating whether the following substances can inhibit MAO in animals and cells:
- Resveratrol (but it activates SIRT1) [21]
- Curcumin [22]
- St John’s [23]
- Coptisine [24]
- Asparagus [25]
- Tinospora [26]
Human data are lacking.