Genetic determinants of aggression and impulsivity in humans

J Appl Genet. 2012 Feb;53(1):61-82. doi: 10.1007/s13353-011-0069-6. Epub 2011 Oct 13.

Abstract

Human aggression/impulsivity-related traits have a complex background that is greatly influenced by genetic and non-genetic factors. The relationship between aggression and anxiety is regulated by highly conserved brain regions including amygdala, which controls neural circuits triggering defensive, aggressive, or avoidant behavioral models. The dysfunction of neural circuits responsible for emotional control was shown to represent an etiological factor of violent behavior. In addition to the amygdala, these circuits also involve the anterior cingulated cortex and regions of the prefrontal cortex. Excessive reactivity in the amygdala coupled with inadequate prefrontal regulation serves to increase the likelihood of aggressive behavior. Developmental alterations in prefrontal-subcortical circuitry as well as neuromodulatory and hormonal abnormality appear to play a role. Imbalance in testosterone/serotonin and testosterone/cortisol ratios (e.g., increased testosterone levels and reduced cortisol levels) increases the propensity toward aggression because of reduced activation of the neural circuitry of impulse control and self-regulation. Serotonin facilitates prefrontal inhibition, and thus insufficient serotonergic activity can enhance aggression. Genetic predisposition to aggression appears to be deeply affected by the polymorphic genetic variants of the serotoninergic system that influences serotonin levels in the central and peripheral nervous system, biological effects of this hormone, and rate of serotonin production, synaptic release and degradation. Among these variants, functional polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) may be of particular importance due to the relationship between these polymorphic variants and anatomical changes in the limbic system of aggressive people. Furthermore, functional variants of MAOA and 5-HTT are capable of mediating the influence of environmental factors on aggression-related traits. In this review, we consider genetic determinants of human aggression, with special emphasis on genes involved in serotonin and dopamine metabolism and function.

Publication types

  • Review

MeSH terms

  • Aggression / physiology*
  • Dopamine / genetics
  • Dopamine / metabolism
  • Genetic Determinism*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Impulsive Behavior / genetics*
  • Impulsive Behavior / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Monoamine Oxidase / genetics
  • Monoamine Oxidase / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / physiology
  • Serotonin / genetics
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Sex Factors
  • Stress, Physiological
  • Testosterone / genetics
  • Testosterone / metabolism

Substances

  • Genetic Markers
  • Membrane Transport Proteins
  • Receptors, Estrogen
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Testosterone
  • Monoamine Oxidase
  • Dopamine