behavioral genetics Archives

MAO-A Gene: An introduction

The MAO-A gene, popularly nicknamed the “warrior gene,” is responsible for the production of an enzyme monoamine oxidase A. (MAOA)

It breaks down monoamine neurotransmitters (dopamine, epinephrine, and serotonin) through oxidation.

Thus, mutations in the MAO-A gene can directly affect the levels of these neurotransmitters, which can potentially lead to various behavior-associated disorders.

Importance of MAOA

MAOA is an essential regulator of brain function and is highly expressed in the cells of the brain and heart. It mainly assists in the breakdown of neurotransmitters such as

Dopamine (also known as happy or feel-good hormones) is involved in mood, motivation and reward, arousal, memory, learning, focus, and movement control.
Serotonin, which is involved in impulse control, affects regulation, appetite, and sleep.
Epinephrine (also known as adrenaline) triggers the response to the body’s stress, including fight-or-flight response.

Because MAOA regulates the level of these “behavioral-hormones,” too little or too much of this enzyme plays a role in a number of psychiatric and neurological disorders like schizophrenia and ADHD. In fact, a class of drugs that inhibit this enzyme (MAOA inhibitors) is prescribed to treat depression.

The Types of MAO-A Gene

All of us have the MAO-A gene, but we have different versions (or types or variants) of them. There are two types of MAO-A genes: a high-activity (MAOA-H) and a low-activity (MAOA-L) type, based on the number of times the sequence of the gene is repeated. One of the most frequently studied variants is MAOA-4R, which has four repeats and is associated with a high-activity of the MAOA enzyme. Other alternate forms of the MAO-A variants, including the 2-repeat (2R) and 3-repeat (3R) versions.

Monoamine Oxidase Deficiency

The monoamine oxidase A deficiency follows an X-Linked inheritance pattern. Thus, this disorder is majorly seen affecting males.

Lower levels of this enzyme typically result in the buildup of neurotransmitters in the brain.

Various studies have linked this buildup with unusual behavioral patterns involving aggressive outbursts and abnormal sexual behavior. The deficiency of this enzyme has also been associated with abnormal brain development, which can directly lead to intellectual disabilities. There are also other variants of this gene that increase the enzyme levels.

Lower levels of the enzyme result in a slower breakdown of the neurotransmitters - (Worriers), and higher levels of the enzyme lead to a faster breakdown - (Warriors). Both decreased and increased levels of the enzyme have various implications.

Increased Risk For Depressive And Bipolar Disorders

A study on around 18,000 people with psychiatric issues identified an SNP rs1137070 associated with major depressive disorder and schizophrenia. People with the T allele had higher enzyme levels and, as a result, lower levels of the neurotransmitters.

Another study found that the G allele of rs6323 had the highest expression of the MAOA enzyme. “Subjects with major depressive disorder with the highest activity form of the enzyme (G or G/G)”

Increased Risk For ADHD

A study identified an SNP rs3027407 on the MAO gene associated with ADHD. This SNP affects dopamine-mediating action, which is related to the symptoms of ADHD in children. A allele was found in higher frequencies in people with ADHD.

Increased Risk For Aggression

T allele of rs909525 in the MAO gene is associated with less aggressive behavior due to the higher activity of MAOA - the warriors. The C allele is associated with more aggressive behavior.

Increased Expression for Anger

A variation in the MAOA gene was associated with higher levels of anger expressed outwards. The A allele of rs2064070 was associated with increased expression of anger.

The study also found two other variants, rs909525 - C allele, rs6323 - G allele, associated with increased anger.

Symptoms of MAOA Deficiency

Impulse control is seen in most boys with MAOA deficiency. They also exhibit aggressive or violent outbursts.
People with MAOA deficiency may also experience sleep problems like trouble falling asleep or night terrors.
Other symptoms include skin flushing, diarrhea, sweating, and headaches.

Diet and MAOA

A study found that a poor quality diet during adolescence can affect the verbal ability of individuals who have a low expression variant of the MAO-A gene. People who ate vegetables very rarely and included more junk food in their diet had verbal deficits in early adulthood.

The “psychopathic” personality traits were also observed more in subjects who frequently consumed fast foods during their adolescence - this was seen only in people with a low expression variant of the MAO-A gene.

Diet Recommendations for People on MAOA Inhibitors

MAOA inhibitors (MAOA-I) are a class of drugs that lower the enzyme MAOA levels. Higher MAOA levels have been linked to conditions like depression.

When on MAOA-I, it is important to limit high-tyramine foods. Tyramine is an amino acid that helps regulate blood pressure. MAOA enzyme is required to break down tyramine, the buildup of which is associated with migraine headaches and life-threatening blood pressure spikes.

So if you are on MAOA-I, it is important that you reduce your tyramine consumption.

Some foods high in tyramine are:

Aged cheese
Pickled fermented foods
Soybeans
Sauces
Dried or overripe fruits
Alcoholic beverages
Fava beans

Summary

MAO-A gene encodes an enzyme monoamine oxidase A (MAOA), which breaks down neurotransmitters like dopamine, serotonin, and epinephrine.
There are two types of MAO-A gene: MAOA-L and MAOA-H. MAOA-L results in lower levels of MAOA enzyme, and MAOA-H results in higher levels.
Lower MAOA results in the buildup of neurotransmitters, and higher levels of MAOA lead to a rapid breakdown of neurotransmitters - each comes with its own set of health risks.
The A allele of rs3027407, C allele of rs909525, and A allele of rs2064070 result in lower MAOA enzyme levels - these are associated with an increased risk of ADHD, aggression, and increased anger expression, respectively.
The T allele of rs1137070, the G allele of rs6323, and the C allele of rs2072743 result in higher MAOA levels - these are associated with an increased risk for depression.
A class of drugs that are inhibitors of MAOA enzymes (MAOA-I) are used to treat depression. MAOA-I interferes with the breakdown of tyramine (an amino acid that regulates blood pressure). So, when on MAOA-I, it is important to limit tyramine consumption. So tyramine-rich foods include aged cheese, alcoholic beverages, and overripe fruits.