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

BackgroundThis 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.MethodsFifty-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 (ΔCORT[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 (ΔTEMP[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).ResultsCorrelations between ΔCORT[IPSAP]-R responses and BDHI Aggression scores varied by group. Specifically, BDHI Aggression correlated inversely with ΔCORT[IPSAP]-R values in PD subjects but directly in HV subjects. While EPQ-II Impulsivity did not correlate with ΔCORT[IPSAP]-R responses, this measure of impulsivity correlated directly with Basal CORT levels in all subjects. ΔTEMP[IPSAP]-R responses did not correlate with measures of trait aggression or trait impulsivity.ConclusionPhysiologic 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-1a receptors may not play a role in the regulation of aggression or impulsivity in human subjects.