Cortisol and Adrenocorticotropic Hormone Responses to Naloxone in Subjects With High and Low Neuroticism

Background: Neuroticism is a highly heritable personality trait that is a risk factor for certain affective and anxiety disorders. Studies link neuroticism with alterations in the Hypothalamic-Pituitary-Adrenal (HPA) stress response. We interrogated HPA axis dynamics as a function of neuroticism, employing the opioid receptor antagonist, naloxone. Methods: Subjects were assigned to either high or low neuroticism groups on the basis of Revised Neuroticism, Extraversion, Openness Personality Inventory (NEO-PI-R) scores and received naloxone hydrochloride (0, 125 μg/kg, and 375 ug/kg). Serum adrenocorticotropic hormone (ACTH) and cortisol levels were monitored. Results: Significant, dose-dependent differences in cortisol response were observed between neuroticism groups, whereas no differences were observed in ACTH. The low neuroticism group demonstrated a dose-dependent cortisol response with a plateau at the 125 μg/kg dose of naloxone. In contrast, the high neuroticism group demonstrated a graded cortisol response to all doses of naloxone. Conclusions: These findings show that neuroticism is associated with altered cortisol responses to opioid receptor blockade, suggesting that alterations in HPA axis function already exist in persons at increased risk for certain depressive and anxiety disorders.