Mechanisms differentiating normal from abnormal aggression: glucocorticoids and serotonin.

Psychopathology-associated human aggression types are induced by a variety of conditions, are behaviorally variable, and show a differential pharmacological responsiveness. Thus, there are several types of abnormal human aggression. This diversity was not reflected by conventional laboratory approaches that focused on the quantitative aspects of aggressive behavior. Recently, several laboratory models of abnormal aggression were proposed, which mainly model hyperarousal-driven aggressiveness (characteristic to intermittent explosive disorder, post-traumatic stress disorder, depression, chronic burnout, etc.) and hypoarousal-driven aggressiveness (characteristic mainly to antisocial personality disorder and its childhood antecedent conduct disorder). Findings obtained with these models suggest that hyperarousal-driven aggressiveness has at its roots an excessive acute glucocorticoid stress response (and probably an exaggerated response of other stress-related systems), whereas chronic hypoarousal-associated aggressiveness is due to glucocorticoid deficits that affect brain function on the long term. In hypoarousal-driven aggressiveness, serotonergic neurotransmission appears to lose its impact on aggression (which it has in normal aggression), certain prefrontal neurons are weakly activated, whereas the central amygdala (no, or weakly involved in the control of normal aggression) acquires important roles. We suggest that the specific study of abnormal aspects of aggressive behavior would lead to important developments in understanding the specific mechanisms underlying different forms of aggression, and may ultimately lead to the development of better treatment approaches.