Serotonergic Contributions to Human Brain Aggression Networks

Abstract

Aggressive behavior is associated with dysfunctional frontolimbic emotion regulation circuits. Recent findings suggest serotonin as a primary transmitter for prefrontal amygdala control. However, the association between serotonin levels, amygdala regulation, and aggression is still a matter of debate. Neurobehavioral models furthermore suggest a possible mediating influence of the monoamine oxidase A gene ( MAOA ) on this brain-behavior relationship, with carriers of low expressing allele varieties being a risk group for aggression. In the present study, we investigated the influence of brain serotonin modulation and MAOA genotype on functional amygdala connectivity during aggressive behavior. Modulation of serotonergic neurotransmission with acute tryptophan depletion (ATD) and placebo were administered in a double-blind, cross-over design in 38 healthy male participants. Aggressive behavior was modeled in a violent video game during simultaneous assessment of brain activation with functional magnetic resonance imaging (fMRI). Trait aggression was measured with the Buss-Perry Aggression Questionnaire (BP-AQ), and MAOA genotypes were assessed from blood samples. Voxel-wise functional connectivity with anatomically defined amygdala was calculated from the functional data. Tryptophan depletion with ATD reduced aggression-specific amygdala connectivity with bilateral supramarginal gyrus. Moreover, ATD impact was associated with trait aggression and MAOA genotype in prefrontal cortex regions. In summary, serotonergic corticolimbic projections contribute to aggressive behavior. Genotype-specific vulnerability of frontolimbic projections may underlie the elevated risk in low expressing allele carriers.

The Modulatory Role of Serotonin on Human Impulsive Aggression

“…Also, intervention with SSRI made healthy subjects more likely to judge harmful actions as forbidden in a set of moral dilemmas pitting utilitarian outcomes (e.g., saving five lives) against aversive harmful actions (e.g., killing an innocent person), but only in cases when harms were emotionally salient (96). Other effects of ATD include reduced connectivity between the amygdala and bilateral supramarginal gyrus in healthy males during violent versus non-violent actions in a video game (97). Some limitations to the use of SSRI and ATD should be mentioned.…”

Gut-Brain Axis: Probiotic,Bacillus subtilis, Prevents Aggression via the Modification of the Central Serotonergic System

“…In the CNS, 5-HT functions to inhibit aggression, thereby controlling domestic behaviors [161][162][163]. The 5-HT deficiency theory of aggression is driven from the negative correlation between the changes of the CNS 5-HT and aggressiveness in humans [164,165], non-human primates [166], rodents [25,167], and chickens [24,168]. Aggressive animals have low levels of 5-HT in the brain, including in the hypothalamus [169][170][171].…”

Disentangling the relationship between cholesterol, aggression, and impulsivity in severe mental disorders

“…Genome‐wide association studies implicate a role of cholesterol metabolism in SMDs (Andreassen et al., (2013)). Cholesterol has been shown to interact with serotonin (Kaplan et al., 1994; Vevera et al., 2016), which is central in the pathophysiology of mental disorders (Lucki, 1998) and aggression (Coccaro, Fanning, Phan, & Lee, 2015; Klasen et al., 2019). Despite the protective role of the blood–brain barrier against direct effects of circulating levels of cholesterol on the brain, indirect mechanisms mediated by cholesterol metabolites have been demonstrated (Olsson et al., 2017).…”

“…Genome-wide association studies implicate a role of cholesterol metabolism in SMDs (Andreassen et al, (2013)). Cholesterol has been shown to interact with serotonin (Kaplan et al, 1994;Vevera et al, 2016), which is central in the pathophysiology of mental disorders (Lucki, 1998) and aggression (Coccaro, Fanning, Phan, & Lee, 2015;Klasen et al, 2019).…”