MAO-A vs. MAO-B: How These Enzymes Shape Mood, Behavior, and Neurological Health

By SWA

The behavioral differences between MAO-A (Monoamine Oxidase A) and MAO-B (Monoamine Oxidase B) are primarily rooted in the specific neurotransmitters they regulate and their influence on brain function. Each isoform of the monoamine oxidase (MAO) enzyme affects mood, behavior, and neurological health differently because they target different neurotransmitters and operate in distinct regions of the brain and body.

Overview of MAO-A and MAO-B

  1. MAO-A:

    • Primarily breaks down serotonin, norepinephrine, and dopamine (to a lesser extent).
    • Also metabolizes dietary tyramine and other biogenic amines.
    • Found in higher concentrations in areas of the brain associated with mood regulation, such as the limbic system, and in peripheral tissues like the gastrointestinal tract.
    • Dysfunction or altered activity of MAO-A is strongly associated with mood disorders, anxiety, and aggression.

  2. MAO-B:

    • Preferentially breaks down dopamine and phenylethylamine, with less effect on serotonin and norepinephrine.
    • Found in higher concentrations in regions of the brain associated with motor control, such as the basal ganglia.
    • Dysfunction or altered activity of MAO-B is strongly linked to neurodegenerative diseases like Parkinson’s disease, as well as to changes in motivation and cognitive function.

Behavioral Effects of MAO-A

  1. Mood Regulation:

    • Low MAO-A activity leads to higher levels of serotonin and norepinephrine, which can result in heightened emotional responses and impulsivity.
    • This is often associated with increased aggression, risk-taking behavior, and impulsivity, particularly in individuals with the so-called "warrior gene" (a variant of the MAO-A gene linked to aggressive behavior in some contexts).
    • High MAO-A activity can lead to excessive breakdown of serotonin and norepinephrine, contributing to depression, anxiety, and emotional numbness.

  2. Aggression and Impulsivity:

    • Studies suggest that individuals with low-functioning MAO-A genes may show greater tendencies toward aggression, antisocial behavior, or impulsivity, especially when exposed to environmental stressors like abuse or trauma during childhood.
    • MAO-A dysfunction has been implicated in mood instability and reactive aggression.

  3. Stress and Anxiety:

    • Altered MAO-A activity can influence the stress response by impacting norepinephrine levels, with high MAO-A activity associated with greater vulnerability to stress and anxiety disorders.

Behavioral Effects of MAO-B

  1. Motor Control and Motivation:

    • Low MAO-B activity can increase dopamine levels in areas associated with motor function, potentially improving motor control and reward sensitivity.
    • Conversely, high MAO-B activity is associated with excessive dopamine degradation in these areas, contributing to motor deficits and apathy, such as those seen in Parkinson's disease.

  2. Reward-Seeking and Addiction:

    • MAO-B breaks down phenylethylamine (PEA), a compound that promotes reward-seeking and euphoria. Low MAO-B activity can lead to increased PEA levels, which may heighten sensitivity to reward and increase tendencies toward addictive behaviors or novelty-seeking.

  3. Cognitive Function:

    • Excessive MAO-B activity may reduce dopamine availability in areas responsible for cognitive processes, such as decision-making and focus. This could contribute to cognitive decline or reduced motivation.
    • MAO-B inhibitors, like selegiline, are used to treat neurodegenerative diseases like Parkinson's and are believed to improve cognitive performance and mood by preserving dopamine levels.

  4. Age-Related Behavior Changes:

    • MAO-B activity naturally increases with age, which can lead to a decline in dopamine levels. This is thought to contribute to age-related reductions in motivation, mood, and motor function.

Key Behavioral Differences Between MAO-A and MAO-B

FeatureMAO-AMAO-B
Primary NeurotransmittersSerotonin, norepinephrine, dopamine (minor role)Dopamine, phenylethylamine
Location in BrainLimbic system (mood/emotion regulation)Basal ganglia (motor control and motivation)
Behavioral ImpactImpulsivity, aggression, depression, anxietyMotor control, reward-seeking, cognitive decline
Role in DisordersLinked to mood disorders (e.g., depression, anxiety), antisocial behaviorLinked to Parkinson’s disease, cognitive decline
Effect of Low ActivityIncreased serotonin/norepinephrine → impulsivity, aggressionIncreased dopamine/PEA → heightened reward sensitivity
Effect of High ActivityReduced serotonin/norepinephrine → depression, emotional numbnessReduced dopamine → motor deficits, apathy

Shared Behavioral Features

  1. Aggression and Impulsivity:

    • Both MAO-A and MAO-B can influence dopamine levels. Low activity in either enzyme may increase dopamine, which can contribute to heightened impulsivity or reward sensitivity.

  2. Mood Dysregulation:

    • Both isoforms influence mood, but MAO-A dysfunction is more closely linked to emotional instability (serotonin/norepinephrine), while MAO-B dysfunction is more related to apathy and lack of motivation (dopamine).

  3. Addiction and Reward Sensitivity:

    • Dysfunction in either enzyme can affect the brain’s reward pathways. Low MAO-A activity may increase susceptibility to thrill-seeking and risk-taking, while low MAO-B activity could heighten sensitivity to euphoria-inducing substances.

Conclusion

The behavioral differences between MAO-A and MAO-B stem from their distinct roles in neurotransmitter metabolism. MAO-A primarily influences mood regulation and emotional behavior, while MAO-B affects motor control, motivation, and cognitive function. Alterations in the activity of either enzyme—whether due to genetics, medication, or environmental factors—can profoundly affect behavior, contributing to mood disorders, aggression, impulsivity, or neurodegenerative diseases. Understanding these differences can help inform treatment strategies, such as the use of MAO inhibitors (MAOIs) for specific conditions, and provide insights into the biological basis of human behavior.

Reference:

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders https://pubmed.ncbi.nlm.nih.gov/23856854/

Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans https://pubmed.ncbi.nlm.nih.gov/19657584/

Modification of the association between early adversity and obsessive-compulsive disorder by polymorphisms in the MAOA, MAOB and COMT genes https://pubmed.ncbi.nlm.nih.gov/27821364/

See also: https://swaresearch.blogspot.com/2025/01/the-genetics-of-tryptophan-and-5-htp.html

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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