The Modulatory Role of Serotonin on Human Impulsive Aggression

Biol Psychiatry. 2021 Oct 1;90(7):447-457. doi: 10.1016/j.biopsych.2021.05.016. Epub 2021 May 25.


The hypothesis of chronically low brain serotonin levels as pathophysiologically linked to impulsive aggression has been around for several decades. Whereas the theory was initially based on indirect methods to probe serotonin function, our understanding of the neural mechanisms involved in impulsive aggression has progressed with recent advances in neuroimaging. The review integrates evidence based on data from several neuroimaging domains in humans. In vivo molecular neuroimaging findings demonstrate associations between impulsive aggression and high serotonin 1B and serotonin 4 receptor binding, high serotonin transporter levels, and low monoamine oxidase A levels, suggesting that low interstitial serotonin levels are a neurobiological risk factor for impulsive aggressive behavior. Imaging genetics suggests that serotonergic-related genetic polymorphisms associate with antisocial behavior, and some evidence indicates that the low-expressing monoamine oxidase A genotype specifically predisposes to impulsive aggression, which may be mediated by effects on corticolimbic function. Interventions that (presumably) alter serotonin levels have effects on brain activity within brain regions involved in impulsive aggression, notably the amygdala, dorsal striatum, anterior cingulate, insula, and prefrontal cortex. Based on these findings, we propose a model for the modulatory role of serotonin in impulsive aggression. Future studies should ensure that clinical features unique for impulsive aggression are appropriately assessed, and we propose investigations of knowledge gaps that can help confirm, refute, or modify our proposed model of impulsive aggression.

Keywords: Amygdala; Anger; Functional magnetic resonance imaging (fMRI); Neuroimaging; Positron emission tomography (PET); Striatum.

Publication types

  • Review