Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Comorbidity with other Clinical Disorders.

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.