Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders

Abstract

Impulsive aggression is characterized by an inability to regulate affect as well as aggressive impulses, and is highly comorbid with other mental disorders including depression, suicidal behavior, and substance abuse. In an effort to elucidate the neurobiological underpinnings of impulsive aggression and to help account for its connections with these other disorders, this paper reviews relevant biochemical, brain imaging, and genetic studies. The review suggests that dysfunctional interactions between serotonin and dopamine systems in the prefrontal cortex may be an important mechanism underlying the link between impulsive aggression and its comorbid disorders. Specifically, serotonin hypofunction may represent a biochemical trait that predisposes individuals to impulsive aggression, with dopamine hyperfunction contributing in an additive fashion to the serotonergic deficit. The current paper proposes a modified diathesis-stress model of impulsive aggression in which the underlying biological diathesis may be deficient serotonergic function in the ventral prefrontal cortex. This underlying disposition can be manifested behaviorally as impulsive aggression towards oneself and others, and as depression under precipitating life stressors. Substance abuse associated with impulsive aggression is understood in the context of dopamine dysregulation resulting from serotonergic deficiency. Also discussed are future research directions in the neurobiology of impulsive aggression and its comorbid disorders.

Dual regulating effect of Ningdong granule on extracellular dopamine content of two kinds of Tourette's syndrome rat models

“…Lots of evidence gave us a signal that dopamine is the final common neurobiological pathway for the expression of TS symptoms (25,26). It is transported across the pre-synaptic neuron membranes by DAT.…”

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

“…Increased ventral striatum reactivity in individuals with high levels of alcohol-induced reactive aggression suggests an involvement of dopamine, which has been discussed to facilitate aggression by increasing arousal and stress (Miczek et al, 2002;Ferrari et al, 2003;Nelson and Trainor, 2007). However, the interplay between neurotransmitters such as serotonin, dopamine, and GABA in alcoholinduced human aggression is not well understood (Miczek et al, 2002;Seo et al, 2008;Heinz et al, 2011). , and the number of voxels per cluster (k).…”

“…Using fMRI, alcohol-induced increased dopamine levels might be reflected by increased activation of the ventral striatum in humans (cf, Gilman et al, 2008). However, the interaction between alcohol intoxication and aggression is complex and likely involves other neurotransmitters than dopamine such as serotonin and gamma amino-butyric acid (GABA) (Miczek et al, 2002;Seo et al, 2008;Heinz et al, 2011).…”

Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs

“…Modulation of the dopaminergic reward system by serotonin is increasingly attracting attention in systems neuroscience (Seo et al, 2008;Kranz et al, 2010;Hayes and Greenshaw, 2011). A prevalent psychopharmacological example for such an interaction is the reward system's downregulation, which has been suggested to account for unsatisfactory effects of antidepressant serotonin reuptake inhibitors (SSRIs).…”