Cortisol responses to ipsapirone challenge correlate with aggression, while basal cortisol levels correlate with impulsivity, in personality disorder and healthy volunteer subjects

Background: This study was performed to test the hypothesis that 5-HT-1a receptors, as assessed by the cortisol (post-synaptic) and temperature (pre-synaptic) responses to the 5-HT-1a agonist, Ipsapirone (IPSAP), play a role in the regulation of impulsive aggressive behavior in human subjects. Methods: Fifty-two healthy subjects (28 with Personality Disorder: PD; 24 Healthy Volunteers: HV) underwent acute challenge with the selective 5-HT-1a agonist, ipsaprione (IPSAP:.3 mg/kg po). Residual Peak Delta Cortisol (Delta CORT[IPSAP]-R; after removal of Basal CORT and IPSAP plasma levels) was used as the primary 5-HT-1a post-synaptic receptor variable. Residual Nadir Delta Temperature (Delta TEMP[IPSAP]-R; after removal of Basal TEMP) was used as the primary 5-HT-1a somatodendritic (pre-synaptic) receptor variable. Measures of trait aggression included the Aggression scales of the Buss-Durkee Hostility Inventory (BDHI) and the Life History of Aggression (LHA); trait impulsivity was assessed with the Impulsivity scale of the Eysenck Personality Questionnaire (EPQ-II). Results: Correlations between Delta CORT[IPSAP]-R responses and BDHI Aggression scores varied by group. Specifically, BDHI Aggression correlated inversely with Delta CORT[IPSAP]-R values in PD subjects but directly in HV subjects. While EPQ-II Impulsivity did not correlate with Delta CORT[IPSAP]-R responses, this measure of impulsivity correlated directly with Basal CORT levels in all subjects. Delta TEMP[IPSAP]-R responses did not correlate with measures of trait aggression or trait impulsivity. Conclusion: Physiologic responses of 5-HT-1a post-synaptic receptors may be reduced as a function of trait aggression, but not impulsivity, in PD subjects. In contrast, pre-synaptic 5-HT-la receptors may not play a role in the regulation of aggression or impulsivity in human subjects. (c) 2010 Elsevier Ltd. All rights reserved.