This web page was produced as an assignment for Genetics 564, an undergraduate course at UW‐Madison.
What is Aggression?
Aggression is any behavior or disposition involving force, hostility or assault. Aggression can be displayed unprovoked or for retaliation, physical or conveyed through communication, with an intention to cause harm or to gain social dominance. The word aggression originates from the Latin word “aggressio”, which means "attack". [1]
The Warrior Gene: MAOA
There was little success in pinpointing specific genes responsible for aggressive traits until Brunner found an uncommon genetic mutation that was linked to antisocial behavior in a sizable Dutch lineage. [2] The discovery of Monoamine oxidase A (MAOA) is the first and most compelling candidate for a gene of susceptibility for human aggression. This gene has also been associated with a variety of other psychiatric disorders, such as Brunner Syndrome and Antisocial Personality Disorder.
- Where is the MAOA gene located?
Figure 1. Location of MAOA gene [Image adapted from Genetics Home Reference]
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Figure 2. The MAOA protein. [Image source: Wikipedia]
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- What does the MAOA gene do?
down important neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. Humans
have various forms of the MAOA gene, resulting in different levels of enzymatic activity. People with the low-
activity form (L-MAOA) produce less of the protein, whereas people with the high-activity form (H-MAOA)
produce more of the protein. [4]
How is MAOA gene linked to human aggression?
In 1993, it was discovered that complete MAOA deficiency caused by a point mutation that yields a premature stop codon in the eighth exon of the MAOA gene results in behavioral phenotype which includes mild mental retardation, tendency to aggressive outbursts and violent impulsive behavior. [2]
According to current imaging work, people with L-MAOA display greater reactivity in the amygdala and lower activity in the regulatory prefrontal areas during emotional arousal. This gives an insight of the emotional and cognitive channels that link L-MAOA to impulsive forms of aggression. [5, 6]
Polymorphism in the MAOA gene can facilitate the impact of traumatic premature life events on the tendency to participate in violence as an adult among humans. Particularly, children with L-MAOA who had been abused were much more likely to develop antisocial problems as adults. [7, 8] Further studies simulated the threat of L-MAOA in combination with traumatic premature life events increases both psychiatric patients and healthy adults’ tendencies toward physical aggression. [9]
According to current imaging work, people with L-MAOA display greater reactivity in the amygdala and lower activity in the regulatory prefrontal areas during emotional arousal. This gives an insight of the emotional and cognitive channels that link L-MAOA to impulsive forms of aggression. [5, 6]
Polymorphism in the MAOA gene can facilitate the impact of traumatic premature life events on the tendency to participate in violence as an adult among humans. Particularly, children with L-MAOA who had been abused were much more likely to develop antisocial problems as adults. [7, 8] Further studies simulated the threat of L-MAOA in combination with traumatic premature life events increases both psychiatric patients and healthy adults’ tendencies toward physical aggression. [9]
Figure 3. Rows 1 and 2 show that in individuals with a low-expressing MAOA allele, risk for adult violence is greater in those
who experience early-life abuse (row 1) compared to those who do not (row 2). Rows 3 and 4 demonstrate that risk for adult
aggressive behavior is low in individuals who possess a high-expressing MAOA allele, whether or not they experience an
abusive (row 3) or nonabusive (row 4) upbringing.
who experience early-life abuse (row 1) compared to those who do not (row 2). Rows 3 and 4 demonstrate that risk for adult
aggressive behavior is low in individuals who possess a high-expressing MAOA allele, whether or not they experience an
abusive (row 3) or nonabusive (row 4) upbringing.
Is there a need for medical intervention?
L-MAOA does not necessarily result in the phenotype of aggressive behavior. [8] Only when subjected to childhood maltreatment, an L-MAOA individual has a significantly increased chance of forming Anti-Social Personality Disorder (ASPD) over an H-MAOA individual. [10]
[Image source: Capsi et al., 2002.]
Figure 4. Capsi et al. (2002) genotyped this polymorphism in members of a sample without population stratification confounds.
This cohort of 1,037 children (52% male) has been assessed since age 3 until 21 and was virtually intact (96%) at age 26 years.
They discovered that while childhood maltreatment increased the likelihood of H-MAOA individuals manifesting ASPD as adults,
it more severely affected L-MAOA individuals. 85% of L-MAOA individuals who suffered abusive upbringing had ASPD as adults.
This group of individuals only comprised 12% of the entire cohort but committed 44% of the cohort’s crimes. [4]
This cohort of 1,037 children (52% male) has been assessed since age 3 until 21 and was virtually intact (96%) at age 26 years.
They discovered that while childhood maltreatment increased the likelihood of H-MAOA individuals manifesting ASPD as adults,
it more severely affected L-MAOA individuals. 85% of L-MAOA individuals who suffered abusive upbringing had ASPD as adults.
This group of individuals only comprised 12% of the entire cohort but committed 44% of the cohort’s crimes. [4]
Population level intervention cannot occur due to several ethical and practical problems. If we want to intervene effectively and ethically, there must be targeted intervention on individuals in order to take into account the difficulties of altering the social conditions of children. Targeted intervention on individuals who are beginning to manifest violent behavior at an early age would be helpful to prevent manifestation of ASPD when they become adults. The best candidates are those who suffer Conduct Disorder (CD)— the precursor to ASPD. CD symptoms are extremely similar to those of ASPD, but only youths under the age of 18 can be diagnosed with CD. Once an adolescent with CD turns 18 they cannot have CD; they either then have ASPD or are designated psychological problem free. [10]
Potential medical treatment
MAOA expression can be boosted by MAOA supplementation, but carries risks if the individual has an H-MAOA genotype along with symptoms of depression. Aggressive targets should thus be tested for their genotype before MAOA supplementation is prescribed. [10]
References:
- Aggression. Merriam-Webster Online. Retrieved Feb 2, 2014.
- Brunner, H.G., et al. (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science, 262(5133), 578-580.
- MAOA monoamine oxidase A [Homo sapiens (human)]. Genetics Home Reference. Retrieved Feb 20, 2014.
- Buckholtz, J. W. & Meyer-Lindenberg, A. (2008). Maoa and the neurogenetic architecture of human aggression. Trends in Neurosciences, 31(3), 120-129.
- Raine, A. (2008). From genes to brain to antisocial behavior. Current Directions in Psychological Science, 17(5), 323-328.
- Meyer-Lindenberg, A., et al. (2006). Neural mechanisms of geneticrisk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences of the United States of America, 103(16), 6269-6274.
- Caspi, A., et al. (2002) Role of genotype in the cycle of violence in maltreated children. Science, 297(5582), 851– 854.
- Caspi, A., & Moffitt, T. E. (2006). Gene–environment interactions in psychiatry: joining forces with neuroscience. Nature Reviews Neuroscience, 7(7), 583-590.
- Frazzetto, G., Di Lorenzo, G., Carola, V., Proietti, L., Sokolowska, E., et al. (2007) Early Trauma and Increased Risk for Physical Aggression during Adulthood: The Moderating Role of MAOA Genotype. PLoS ONE 2(5): e486.
- Tabery, J. (2009). From a Genetic Predisposition to an Interactive Predisposition: Rethinking the Ethical Implications of Screening for Gene-Environment Interactions. Journal Of Medicine & Philosophy, 34(1), 27-48.
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Author: Sin-Ruow Tey
Last updated: May 19, 2014
Last updated: May 19, 2014