The Role of Cortisol in the Cycle of Violence

Child abuse and neglect are universal risk factors for delinquency, violence and aggression; this phenomenon is known as the cycle of violence. Despite a wide body of research demonstrating this phenomenon, the processes which mediate this relationship remain largely unknown. One potentially relevant result of abuse and neglect may be disruptions in the development of the body’s stress response, specifically the function of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA-axis, and its end-product, cortisol, may play a role in regulating aggressive behavior, but this function may be disrupted following abuse and neglect. Another risk factor for aggression, psychopathy, may mediate the cycle of violence or independently contribute to aggressive behavior. This study examined the relationship between child abuse and neglect, HPA-axis function, psychopathy and aggression. History of abuse was measured using a self-report questionnaire, the Childhood Trauma Questionnaire. Using a within-subject, placebo-controlled, counter-balanced dosing design, 67 adults were given an acute dose of 20mg cortisol as a challenge to the HPA-axis. Following dosing, measures of cortisol response were obtained through saliva samples, and state-aggressive behavior was measured by a laboratory task, the Point-Subtraction Aggression Paradigm (PSAP). Basal measures of cortisol were obtained prior to dosing. Psychopathy and a trait-measure of aggression were assessed through self-report questionnaires. PSAP data and trait-aggression scores were normalized and summed for an overall aggression score. Linear regression analyses indicated that a history of abuse and neglect robustly predicted aggression, supporting the cycle of violence hypothesis. Further, abuse and neglect predicted a diminished HPA-axis response to the cortisol challenge. Although a diminished HPA-axis response significantly predicted increased aggression, mediation analysis revealed that HPA-axis reactivity did not mediate a significant portion of the effect of abuse and neglect on aggression. However, HPA-axis reactivity did mediate part of the effect, indicating that HPA-axis function may be a factor in the cycle of violence. Psychopathy robustly predicted increased aggression. Although the results indicate that cortisol, psychopathy and HPA-axis function are involved in the cycle of violence, further research is required to better understand the complex interaction of these factors.

Aggression, impulsivity and serotonin in drug dependence

Aggression, impulsivity, and central serotonergic function were evaluated in two groups of human volunteers; one group having a history of substance dependence (DRUG+) and another group with no drug use history (DRUG$-$). The hypothesis was that DRUG+ subjects would be more aggressive, more impulsive, and have attenuated serotonergic function. Results showed that DRUG+ subjects behaved more aggressively in a computer paradigm of aggression and also reported more aggression on questionnaires than DRUG$-$ subjects. In a computer paradigm of impulsivity, the DRUG+ group showed a lesser ability to delay gratification than the DRUG$-$ group in the last session of testing. The DRUG+ subjects also reported more venturesomeness and problems associated with low impulse control on questionnaires. Serotonergic function was measured through the neuroendocrine and hypothermic response to an orally administered serotonin (5-HT) agonist specific to the 5-HT$\rm\sb{1A}$ receptor subtype (ipsapirone). The neuroendocrine responses did not differ between DRUG$\pm$ groups, indicating no difference in the sensitivity of the presynaptic or postsynaptic 5-HT$\rm\sb{1A}$ receptors. An unexpected result was that the indicator hormone, cortisol, was at a lower baseline level in the DRUG+ group than the DRUG$-$ group. Lowered cortisol levels have been previously noted in children at high risk foul antisociality and future drug use. A principal components analysis including impulsivity, aggression, and serotonergic function measures produced three unique factors. The factors, Antisocial Tendency and Self-Control and Serotonergic Function combined to produce a significant regression equation explaining 36% of variability in the DRUG$\pm$ groups. These factors included measures of aggression, impulsivity, mood, and educational attainment. These results suggest that the current measures of aggression and impulsivity were predictive of a drug dependence disorder but that neuroendocrine function is not yet a useful indicator of drug dependence status. ^

Behavioral effects of plasma tryptophan depletion in aggressive and nonaggressive men

Serotonin (5-HT) neurotransmission deficits have been implicated in impulsive aggression. A Trp-free beverage of amino acids competitively inhibits Trp uptake into the brain for 5-HT synthesis and also lowers endogenous plasma Trp for several hours. This has worsened mood and/or increased aggressive behavior, especially in hostile persons or those with histories of depression. In 24 community-recruited men (12 each with and without significant aggression histories), aggressive and impulsive behavior in the laboratory was assessed before and after plasma Trp depletion and Trp loading. In the aggression model, subjects were provoked by periodic subtractions of participation earnings, and these subtractions were blamed on a ficitious other participant. Aggression was measured as the responses the subject made to subtract money from his antagonist. Impulsiveness was operationalized as: (1) the choice of smaller reward after a shorter delay over having to wait longer to receive a larger reward, and (2) “false alarm” commission errors in a modified Continuous Performance Task, which represent a failure to inhibit responding to stimuli similar (but not identical) to target stimuli. Finally, plasma cortisol and Trp were measured under each condition immediately following a aggression testing session when subjects were highly provoked. I hypothesized that 5-HT may tonically modulate (inhibit) the hypothalmnic-pituitary-adrenal stress response, such that Trp depletion may enhance the cortisol response to high provocation in aggressive men. ^ Trp depletion had no effect in the laboratory tasks purported to measure impulsive behavior, and failed to cause increases in aggressive behavior under low provocation conditions. Under higher provocation, however, aggressive responses we re elevated under Trp-depleted conditions relative to Trp-loaded conditions in aggressive men, whereas the reverse was true in nonaggressive men. Cortisol levels nonsignificantly paralled the group differences in aggression under Trp-depleted and Trp-loaded conditions. Aggressive men achieved lower plasma Trp levels after Trp loading than did nonaggressive men, possibly due to heavy alcohol use histories. The high post-loading plasma Trp levels in nonaggressive men tended also to correlate with their aggressive responding rates, due perhaps to increases in other psychoactive Trp metabolites. ^