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 (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).


RESULTS
Correlations 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.


CONCLUSIONS
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-1a receptors may not play a role in the regulation of aggression or impulsivity in human subjects.
Almeida
Marcela
M
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry and Behavioral Neuroscience, Division of Biological Sciences and Pritzker School of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Lee
Royce
R
Coccaro
Emil F
EF
D000328:Adult; D000374:Aggression / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001831:Body Temperature; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007175:Impulsive Behavior / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010554:Personality Disorders / Q000097:blood*; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D011795:Surveys and Questionnaires; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D011743:Pyrimidines; D058825:Serotonin 5-HT1 Receptor Agonists; C043077:ipsapirone; D006854:Hydrocortisone