Genomics: Insight

Individuals with decreased levels of monoamine oxidase A (MAOA) activity display more aggressive tendencies; however, environmental stressors such as childhood abuse can magnify the effects of this genetic predisposition.

Background and Societal Implications

In February of 2021, the Supreme Court of New Mexico upheld the murder conviction against Anthony Blas Yepez, who killed a man in 2012, thereby jettisoning the defense's evidence that the so-called "warrior gene" predisposed him to violence and, therefore, attenuated his accountability to his crimes.¹ Located on the X chromosome, the warrior gene encodes monoamine oxidase A (MAOA), a mitochondrial enzyme that, along with monoamine oxidase B (MAOB), removes amine groups from certain neurotransmitters.² Although research has not conclusively established the mechanism through which MAOA deficiency promotes aggression, scientists suspect that the behavioral ramifications may stem from neurotransmitter imbalances.³ By asserting that "mere genetic susceptibility to a given mental condition is not relevant on the issue of deliberate intent," the court established a new precedent repudiating genomic evidence and roused controversy.¹ The affirmation followed in the wake of decades of contention regarding the warrior gene's applicability in the criminal justice system.⁴ In a previous case, a judge consigned the defendant to a remarkably lenient sentence, likely due to his appeal to the warrior gene, whereas another defendant in an analogous case received a draconian sentence after the prosecution asserted that the warrior gene converted the defendant into an inherent menace who required imprisonment.⁴ The controversy enveloping the warrior gene and MAOA reflects its epitomization of the perennial debate between nature and nurture: the presence of a single gene that fosters a propensity for violence erodes societal notions of individual autonomy, equality at birth, and the ability to improve oneself. Thus, this paper seeks to elucidate the merits of MAOA as a "warrior gene."

the presence of a single gene that fosters a propensity for violence erodes societal nations of individual autonomy, equality at birth, and the ability to improve oneself

The Discovery of MAOA

Han Brunner implicated low-activity or nonfunctional MAOA as a contributor to violent proclivities by conducting a study on a large Dutch kindred that sought genetic counseling due to the recurrent history of borderline mental retardation and problematic aggressive behavior.⁵ Located throughout the brain in the outer mitochondrial membrane, the two forms of monoamine oxidase, A and B, catalyze the removal of amino groups from monoamine neurotransmitters such as dopamine, norepinephrine, and 5-hydroxytryptamine in the brain and peripheral tissues.2, 6 In patients suffering from Norrie disease, an X-linked recessive disorder associated with blindness, hearing loss, and mental retardation, MAOA and MAOB are deleted.⁶ Through genomic analysis, Brunner linked the behavioral problems to the p11-p21 region of X chromosome in proximity with the regions coding for MAOA and MAOB, pinpointing a nonconservative point mutation at position 936 of the MAOA gene, with thymine replacing cytosine.⁵ The data suggested an association between deficient MAOA activity and abnormal aggressive behavior in males although obligate female carriers did not exhibit any abnormal tendencies, and the inactivation of X chromosomes hampered extrapolation of the findings to females.⁵

MAOA Knockout Mice

Through studies regarding MAOA knockout mice, researchers have deduced the consequences of MAOA deficiencies. According to controlled experiments conducted by Cases et al, MAOA knockout mice displayed serotonin levels up to nine times higher for pups and two times higher for adults, norepinephrine concentrations twice as high, and small increases in dopamine levels for pups.⁷ Moreover, the MAOA knockout mice manifested abnormal behavior, improper locomotion, stronger reactions to pinching, frenetic movements, spasms during sleep, predisposition to biting, altered postural traits, and enhanced aggression as illustrated by more common wounds and more prompt attacking of intruders.⁷

MAOA and Economics

Combining insights from biology and behavioral economics, researchers employed the hot-sauce paradigm on a sample of 139 males with high- or low-activity MAOA in order to determine the influence of MAOA activity on aggression as measured by the willingness to pay to punish opponents.⁸ In a four-round experiment, a purportedly anonymous but actually fictional person stripped away an experimentally-manipulated portion (20% or 80%) of a subject's earnings from a prior task.⁸ Following the ostensible thievery, the experimenters provided the subjects with the opportunity to forgo some of their remaining earnings to punish the person through forced administration of a hot sauce, with each dose administered commanding a certain price.⁸ While both the low- and high-MAOA activity groups demanded more severe punishment (i.e. paid for more doses of hot sauce) when confronted with the high-provocation (80% of earnings taken) scenario, low-activity MAOA subjects administered a statistically significantly greater quantity of hot sauce in the high-provocation circumstances.⁸ With willingness to pay for hot sauce as a behavioral measure of aggression, the study illustrated the influence of genetic differences mediated by environmental stimuli.

MAOA and Gene-Environment Interaction

Although the aforementioned study established the ramifications of low-activity MAOA for all individuals exhibiting the trait, an expanding literature has demonstrated that gene-environment interaction characterizes its effects, with MAOA moderating the consequences of maltreatment during adolescent development. According to a study conducted on a sample of 422 males observed from birth until adulthood, maltreated children with low levels of MAOA expression are more likely to develop antisocial problems: among males who experienced severe maltreatment, those with low MAOA exhibited higher frequencies of conduct disorder, violent offense convictions, disposition toward violence, and antisocial personality disorder symptoms.⁹ The same pattern arose for victims of probable maltreatment; however, for those who had not experienced maltreatment, low-activity MAOA individuals exhibited less problematic behavior than high-activity individuals rather than vice versa.⁹ An analogous study by Kim-Cohen et al posited a similar conclusion: through analysis of 975 boys in the Environmental Risk Longitudinal Twin Study, the researchers identified a more robust association between physical abuse and mental health or antisocial problems for children with low MAOA activity.¹⁰ Whereas high-activity MAOA subjects exposed to childhood maltreatment scored 0.63 on average on the composite mental health problem scale, their low-activity counterparts scored 1.24.¹⁰ Conversely, the inverse trend manifested for individuals not exposed to maltreatment: low-activity MAOA subjects scored -0.21 while high-activity MAOA subjects scored 0.02 on average.¹⁰ Despite the contentious debate enshrouding the warrior gene, the scientific community has largely converged upon the consensus that MAOA significantly moderates the behavioral results of childhood abuse. Indeed, Kim-Cohen et al conducted a meta-analysis of four studies, which corroborated their aforementioned experimental findings, and a later meta-analysis by Byrd and Manuck of 27 peer-reviewed, predominantly non-clinical studies established that early adversity augured antisocial outcomes more strongly for low-MAOA activity individuals to a highly significant extent.^{10, 11}

Despite the contentious debate enshrouding the warrior gene, the scientific community has largely converged upon the consensus that MAOA significantly moderates the behavioral results of childhood abuse.

Conclusion and the Path Forward

This paper recapitulated the scientific controversy and conclusions pertaining to the MAOA gene and its behavioral ramifications, determining that a preponderance of the evidence indicates that non functioning or low-activity MAOA predisposes individuals to violent propensities, particularly if they underwent childhood maltreatment. The notion that a single gene can exert appreciable influence on subtle behaviors when coupled with environmental factors, which conflicts with the general trend of polygenic inheritance dictating complex traits such as aggression, prompts a litany of philosophical and pragmatic issues that society must reconcile itself to. Notably, the possibility of inheriting a tendency to behave impulsively and commit acts of violence undermines the conception of human malleability and the paradigm of free will upon which our justice system hinges. Given the statistically and societally significant behavioral disparities that MAOA activity underlies, governmental institutions must contend with how they and private entities ought to engage with and punish such individuals.

References

1. Lee, M. (2021, February 25). High court rejects 'warrior gene' defense as unreliable. Associated Press. Retrieved January 16, 2022, from https://apnews.com/article/santa-fe-006071a1ae429c1a4d22ff4e002bdf14
2. Cesura, A. M. (2007). Monoamine oxidase A. ScienceDirect. Retrieved January 16, 2022, from https://www.sciencedirect.com/topics/neuroscience/monoamine-oxidase-a
3. Mentis, A.-F. A., Dardiotis, E., Katsouni, E., & Chrousos, G. P. (2021). From warrior genes to translational solutions: Novel insights into monoamine oxidases (MAOs) and aggression. Translational Psychiatry, 11(1). https://doi.org/10.1038/s41398-021-01257-2
4. Farahany, N., & Robinson, G. E. (2021, March 18). Criminal defendants still cite a 'gene for violence.' It doesn't exist. The Washington Post. Retrieved January 16, 2022, from https://www.washingtonpost.com/outlook/2021/03/18/genetics-criminal-defense-warrior-violence/
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6. Shih, J. C., Chen, K., & Ridd, M. J. (1999). Monoamine oxidase: From genes to behavior. Annual Review of Neuroscience, 22, 197-217. https://doi.org/10.1146/annurev.neuro.22.1.197 
7. O. Cases, Seif, I., Grimsby, J., Gaspar, P., Chen, K., Pournin, S., Müller, U., Aguet, M., Babinet, C., & Shih, J. C. (1995). Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science, 268(5218), 1763-1766. https://doi.org/10.1126/science.7792602
8. McDermott, R., Tingley, D., Cowden, J., Frazzetto, G., & Johnson, D. D. P. (2009). Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. Proceedings of the National Academy of Sciences, 106(7), 2118-2123. https://doi.org/10.1073/pnas.0808376106 
9. Caspi, A. T., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., Taylor, A., & Poulton, R. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297(5582), 851-854. https://doi.org/10.1126/science.1072290 
10. Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., & Moffitt, T. E. (2006). MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11(10), 903-913. https://doi.org/10.1038/sj.mp.4001851 
11. Byrd, A. L., & Manuck, S. B. (2014). MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene-environment interaction. Biological Psychiatry, 75(1), 9-17. https://doi.org/10.1016/j.biopsych.2013.05.004