Key Points
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Dysregulated aggressive behaviour has important negative consequences for human societies. A complicating factor is that aggression that is exhibited in different social contexts can be regulated by different neurobiological mechanisms.
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Neurobiological studies have identified a subset of hypothalamic and limbic brain areas that tend to facilitate aggressive behaviour in rodents and primates. In contrast, neural activity in the frontal cortex generally acts to inhibit aggressive behaviour.
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Aggressive behaviours in animal models and humans are known to be regulated by serotonin neurotransmission. Behaviour can be modified at several levels, including regulation of serotonin release, reuptake and sensitivity (via serotonin receptors).
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Dopaminergic function appears to be necessary for aggressive behaviour, possibly by regulating arousal, learning and memory.
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Neuronal nitric oxide (nNOS) synthase signalling (via nitric oxide gas) exerts inhibitory effects on male aggression in rodents. Several studies suggest that nNOS assists in the processing of salient social stimuli.
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Mutations in the monoamine oxidase A (MAOA) enzyme are associated with increased aggressive behaviours in humans. MAOA knockout mice show increased aggression.
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Steroid hormones have long been a focus of aggression research, but the relationship among androgens, oestrogens and behaviour is complex. These hormones do not function in isolation and their actions are affected by the environmental context.
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Gene–environment interactions have important effects on aggressive behaviours. Mutations or hormones that increase aggression in one environment have no effect (or decrease aggression) in different environments.
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Novel pharmacological treatments must target specific subtypes of aggression to have improved effectiveness. An appreciation of the contribution of environmental stressors to aggressive phenotypes is necessary for further advancements in the successful management of maladaptive aggression.
Abstract
Unchecked aggression and violence exact a significant toll on human societies. Aggression is an umbrella term for behaviours that are intended to inflict harm. These behaviours evolved as adaptations to deal with competition, but when expressed out of context, they can have destructive consequences. Uncontrolled aggression has several components, such as impaired recognition of social cues and enhanced impulsivity. Molecular approaches to the study of aggression have revealed biological signals that mediate the components of aggressive behaviour. These signals may provide targets for therapeutic intervention for individuals with extreme aggressive outbursts. This Review summarizes the complex interactions between genes, biological signals, neural circuits and the environment that influence the development and expression of aggressive behaviour.
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Acknowledgements
The authors acknowledge support by grants from the US National Institutes of Health and the US National Science Foundation. We thank J. Gusfa, K. Navarra and three anonymous reviewers for helpful comments on the manuscript.
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FURTHER INFORMATION
Glossary
- Intermittent explosive disorder
-
A disorder characterized by repeated episodes of aggressive, violent behaviour that is grossly out of proportion to the situation; thought to affect as many as 7.3% of adults in the United States.
- Neuroleptic drug
-
An antipsychotic drug that is used to treat various psychiatric disorders, including schizophrenia. Although these drugs have stabilizing effects on mood, a major drawback is that they have potent sedative effects.
- Tardive dyskinesia
-
A disorder characterized by twitching of the face and tongue and involuntary motor movements of the trunk and limbs.
- Immediate early gene
-
A gene that is expressed rapidly and transiently in response to various cellular stimuli. Several of these genes (for example, Fos and Egr1) are used by neuroscientists as indirect markers of neuronal activity because they are expressed when neurons fire action potentials.
- Vasopressin
-
A neuropeptide that is present, among other regions, in the anterior hypothalamus and is known to affect aggression.
- Piloerection
-
The erection of hair on the skin, used as a threatening display by many animals.
- Lifetime History of Aggression (LHA) scale
-
An interview-based scale that is used by mental health workers to assess general aggressive tendencies in humans. Interviews can be supplemented with other sources such as clinical records.
- Selective serotonin-reuptake inhibitors
-
A class of antidepressants that inhibit the reuptake of serotonin (5-HT) by neural cells, thereby increasing the amount of 5-HT in the synapse.
- Borderline personality disorder
-
A disorder that is characterized by instability in moods, interpersonal relationships, self-image and behaviour; thought to affect approximately 2% of adults.
- Heteroreceptor
-
A receptor that modulates the synthesis and/or release of neurotransmitters other than its own ligand.
- Glutamic acid decarboxylase
-
An enzyme that produces GABA (γ-aminobutyric acid) from l-glutamic acid in an irreversible reaction.
- Gene chip
-
A method for analysing the expression of numerous genes simultaneously.
- Hormone response element
-
Sequences of DNA in promoter regions that are bound by hormone receptors. Binding of the receptor complex promotes transcription.
- Resident–intruder test
-
An aggression test in which an intruder is introduced into a resident's home cage. Residents are typically more aggressive because they are familiar with the environment and are defending their home territory.
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Nelson, R., Trainor, B. Neural mechanisms of aggression. Nat Rev Neurosci 8, 536–546 (2007). https://doi.org/10.1038/nrn2174
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DOI: https://doi.org/10.1038/nrn2174
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