High and low neuroticism predict different cortisol responses to the combined dexamethasone-CRH test

Background: Depression and posttraumatic stress disorder are both associated with altered function of the hypothalamic-pituitary-adrenal axis. Neuroticism is a strong predisposing factor for depression and probably also a risk factor for posttraumatic stress disorder. This study investigated whether young adults with high and low neuroticism scores show differences in hypothalamic-pituitary-adrenal axis regulation that might relate to their differential vulnerability to psychopathology. Methods: Neuroticism was measured with the Eysenck Personality Questionnaire in 258 students aged 18-25, Fourteen scoring in each of the upper and lower quartiles of the neuroticism distribution according to gender participated in a combined dexamethasone-corticotropin-releasing hormone test. Results: Low-neuroticism individuals showed a significantly greater cortisol response than high-neuroticism individuals. Conclusions: The mechanism of this effect remains to be elucidated. High-neuroticism subjects map have a down regulated hypothalamic-pituitary-adrenal axis to prevent harmful overactivation, This is the first demonstration of a difference in hypothalamic-pituitary-adrenal axis regulation associated with neuroticism. Biol Psychiatry 2001; 49:410-415 (C) 2001 Society of Biological Psychiatry.