The neurobiological basis of human aggression: A review on genetic and epigenetic mechanisms

Abstract

Aggression is an evolutionary conserved behavior present in most species including humans. Inadequate aggression can lead to long-term detrimental personal and societal effects. Here, we differentiate between proactive and reactive forms of aggression and review the genetic determinants of it. Heritability estimates of aggression in general vary between studies due to differing assessment instruments for aggressive behavior (AB) as well as age and gender of study participants. In addition, especially non-shared environmental factors shape AB. Current hypotheses suggest that environmental effects such as early life stress or chronic psychosocial risk factors (e.g., maltreatment) and variation in genes related to neuroendocrine, dopaminergic as well as serotonergic systems increase the risk to develop AB. In this review, we summarize the current knowledge of the genetics of human aggression based on twin studies, genetic association studies, animal models, and epigenetic analyses with the aim to differentiate between mechanisms associated with proactive or reactive aggression. We hypothesize that from a genetic perspective, the aminergic systems are likely to regulate both reactive and proactive aggression, whereas the endocrine pathways seem to be more involved in regulation of reactive aggression through modulation of impulsivity. Epigenetic studies on aggression have associated non-genetic risk factors with modifications of the stress response and the immune system. Finally, we point to the urgent need for further genome-wide analyses and the integration of genetic and epigenetic information to understand individual differences in reactive and proactive AB.

A Prospective Cohort Study of Influences on Externalizing Behaviors Across Childhood: Results From a Nurse Home Visiting Randomized Controlled Trial

“…1,2 Studies have shown that externalizing behaviors are highly heritable (55–65%). 3–5 Variation in genes implicated in dopaminergic, serotonergic, and neuroendocrine systems appears to increase risk for development of externalizing behaviors. 3 …”

“…3–5 Variation in genes implicated in dopaminergic, serotonergic, and neuroendocrine systems appears to increase risk for development of externalizing behaviors. 3 …”

Comparative mRNA analysis of behavioral and genetic mouse models of aggression

“…Consequently, current research aims to identify genetic variants associated with aggressive behaviors, which may help to inform candidate gene selection and the identification of gene pathways to gain further understanding of the genetic substrate of this complex trait [Kudryavtseva et al, 2015;Waltes et al, 2015;Zhang-James and Faraone, 2015]. Gene selection has predominantly been driven by inspecting genes and neurobiological pathways with an established association with aggression, including the serotonin (5-HT) gene, levels of which were found to be low in more aggressive individuals.…”

Heterogeneity in the Development of Proactive and Reactive Aggression in Childhood: Common and Specific Genetic - Environmental Factors

“…Our study cannot directly address this question but hypotheses that temperamental characteristics such as anxiety, anger or psychopathic traits [26] could partly explain the common variation at the baseline level of PA and RA is supported by our results. Also, researchers have recently proposed that neurotransmitters from the aminergic system could be involved in the regulation of both PA and RA [44] through their role in response to stress and rewards. We found evidence of common genetic factors associated with developmental changes of PA and RA.…”