Monoamine oxidase A (MAOA) is an enzyme in the brain that regulates chemical messengers called neurotransmitters. Its function is like a volume control system for these chemicals, which nerve cells use to communicate. By breaking down specific neurotransmitters after they are used, MAOA ensures that signals between nerve cells are properly managed, maintaining the brain’s chemical balance.
The Function of the MAOA Enzyme
The main role of the MAOA enzyme is the metabolic breakdown of neurotransmitters called monoamines. This process occurs on the outer membrane of mitochondria, the energy-producing structures within cells. By catalyzing a reaction known as oxidative deamination, MAOA deactivates neurotransmitters once their signaling job is complete, preventing their buildup between nerve cells.
Three of the main neurotransmitters MAOA metabolizes are serotonin, norepinephrine, and dopamine. Serotonin is associated with regulating mood, sleep, and appetite. Norepinephrine is involved in the body’s “fight-or-flight” stress response, and dopamine is part of the brain’s reward system and movement control.
The enzyme’s work ensures that neurotransmitter signals are terminated at the appropriate time, allowing the system to reset for the next transmission. This regulatory action helps to stabilize mood and cognitive processes by keeping these brain chemicals in balance.
Genetic Variations of MAOA
The instructions for building the MAOA enzyme are in the MAOA gene, located on the X chromosome. Because males (XY) have one X chromosome, they inherit a single copy of the MAOA gene. Females (XX) have two X chromosomes and inherit two copies, which has implications for how genetic variations affect them.
Scientists have identified different versions (alleles) of the MAOA gene that vary in efficiency. These differences are related to a genetic feature called a variable number of tandem repeats (VNTR). Versions with more repeats produce more of the enzyme and are known as high-activity (MAOA-H) alleles, while those with fewer repeats produce less enzyme and are called low-activity (MAOA-L) alleles.
The low-activity MAOA-L variant is known in popular media as the “warrior gene” due to research linking it to certain behavioral traits. Individuals with this allele produce less MAOA enzyme, leading to a less efficient breakdown of monoamine neurotransmitters. This can result in higher baseline levels of chemicals like serotonin and norepinephrine in the brain.
Gene-Environment Interaction and Behavior
Possessing a specific variant of the MAOA gene does not determine behavior. Instead, outcomes arise from a complex interplay between genetic predispositions and environmental factors. A person’s genetic makeup may create a susceptibility, but environmental experiences often act as a trigger.
Research has connected the low-activity MAOA-L variant to a higher likelihood of aggressive or antisocial behaviors, but only under a specific condition. This link is prominent in individuals who experienced maltreatment or significant stress during childhood. Studies found that males with the MAOA-L variant subjected to abuse were more prone to antisocial behaviors later in life.
Individuals with the same MAOA-L allele who did not experience childhood adversity showed no corresponding increase in aggression. This suggests a supportive environment can buffer the effects of a genetic vulnerability. The gene itself does not cause the behavior but appears to modify the body’s response to stressful life experiences.
The rare condition Brunner syndrome illustrates what occurs with a complete lack of MAOA enzyme function. This syndrome almost exclusively affects males and results from a mutation that makes the MAOA gene non-functional. It is characterized by intellectual disability and problematic impulsive behaviors, including aggression. This condition underscores the enzyme’s role in regulating brain chemistry and behavior.
Pharmacological Inhibition of MAOA
The MAOA enzyme is a target for medications known as Monoamine Oxidase Inhibitors (MAOIs). These drugs were among the first antidepressants developed and are prescribed for treatment-resistant depression and certain anxiety disorders. MAOIs work by blocking the action of the monoamine oxidase enzyme, including MAOA.
By blocking the enzyme, MAOIs prevent the breakdown of serotonin, norepinephrine, and dopamine. This leads to an increased concentration of these neurotransmitters in the brain, which can help alleviate the symptoms of depression and anxiety. By boosting monoamine levels, these drugs can improve mood and emotional regulation, and are often considered when other antidepressant treatments have not been effective.
Treatment with MAOIs involves specific dietary restrictions. Patients must avoid foods and beverages rich in tyramine, such as aged cheeses, cured meats, and certain alcoholic beverages. The MAOA enzyme also breaks down tyramine from food, so when the enzyme is inhibited by an MAOI, tyramine can build up and cause a dangerous spike in blood pressure known as a hypertensive crisis.