Cortisol responses to daily events in major depressive disorder

Objective: Abnormal responses of the hypothalamic-pituitary-adrenal (HPA) axis to stress are thought to be involved in the pathophysiology of major depressive disorder (MDD). The aim of the present study was to determine whether cortisol responses to negative and positive daily events in depressed participants (N = 47) differed from such responses in healthy participants (N = 39). We also examined the influence of clinical characteristics and possible gender differences in cortisol responses to events. Finally, the role of mood changes in mediating cortisol responses was assessed. Methods: Experience sampling methodology (self-reports of mood and events, with simultaneous saliva samples, 10 times each day for 6 consecutive days) and multilevel regression analysis were used to examine the relationship between events in daily life and salivary cortisol levels. Results: In contrast to healthy participants, depressed participants showed no increase in cortisol following negative events. Responses were even more blunted in depressed participants with a family history of mood disorders. Although the effects of negative events on cortisol responses appeared to be mediated by changes in mood, negative affect tended to be less closely associated with cortisol levels in depressed participants. Depressed women showed larger cortisol responses to negative events than depressed men. Positive events had no effect on cortisol levels in either group. Conclusions: These results suggest that responses of the HPA axis to negative daily events and mood changes are blunted in MDD. Future studies will need to address whether these abnormalities disappear after clinical recovery.