Monoamine oxidase A (MAOA) and mental illness

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the catabolism of catecholamine neurotransmitters, including norepinephrine, serotonin, and dopamine

• MAOA gene is located on the X chromosome (Xp11.23)
  
  
• MAOA transcriptional efficiency is impacted by the variable number of tandem repeats (VNTR) domain of the gene, such that lower expression of MAOA is seen in carriers of 2, 3, and 5 repeats (L alleles; MAOA-L) and higher expression of MAOA is seen in carriers of 3.5 and 4 repeats (H alleles; MAOA-H (1)
  
  
  • MAOA-L carriage is associated with aggression, impulsive behavior, and antisocial personality disorders, especially in individuals who experienced childhood abuse
    • MAOA-L individuals showed higher levels of aggression than MAOA-H (high MAOA activity) subjects (2)
      • those with the MAOA-L genotype paired with maltreatment in childhood were correctly predicted to commit crime
      • imaging work in a large sample demonstrates that during emotional arousal, MAOA-L men show greater reactivity in the amygdala and lower activity in the regulatory prefrontal areas (3)
        • suggests the emotional and cognitive channels that link MAOA-L to impulsive forms of aggression
          
          
  • MAOA-H carriage
    • a study explored the relationship between MAOA and acute laboratory-induced psychosocial stress with functional magnetic resonance imaging (fMRI) (1)
      • MAOA-H allele carriers showed greater deactivation of the right anterior hippocampus and greater cortisol response after stress than did MAOH-L allele carriers
        • authors suggested that hippocampal deactivation may lead to disinhibition of the hypothalamic-pituitary-adrenal (HPA) axis and the initiation of stress hormone release under stress

Reference:

1. Sun X, Ming Q, Zhong X, Dong D, Li C, Xiong G, Cheng C, Cao W, He J, Wang X, Yi J, Yao S. The MAOA Gene Influences the Neural Response to Psychosocial Stress in the Human Brain. Front Behav Neurosci. 2020 May 15;14:65.
2. McDermott R et al. Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation. PNAS 2009;106 (7) 2118-2123
3. Sohrabi S. The criminal gene: the link between MAOA and aggression (REVIEW). BMC Proc. 2015 Jan 14;9(Suppl 1):A49.