An impressive number of data has been accumulated on dysfunctions of the hypothalamo-pituitary-adrenal (HPA) axis and cortisol hypersecretion in depression. To assess the dynamic HPA functioning, the cortisol awakening response (CAR) is an easily accessible and reliable approach. Some data suggest that elevated CAR in depressed patients has trait-like characteristics. Therefore we investigated whether patients in remission from a depressive episode have elevated CAR compared to control subjects. CAR of thirty-eight patients in remission from depression (11 men, 27 women, age range 24-66) and 52 control participants were analyzed (18 men, 34 women, age range 24-63). All patients had experienced ≥3 previous depressive episodes and were off psychotropic medication since at least 3 months. Saliva samples were collected only once, at home, either on weekend or weekday at 0, 15, 30, 45 and 60 min post-awakening. The area under the curve (AUC) above minimum cortisol concentration displayed large interindividual variability (6.4-fold in remitted patients and 8.1-fold in controls, based on 80% range). Investigation of possible variability factors showed that percent explained variance increased from 3.9% when group was considered alone to 8.8%, 12.3% and 19.2% after adjusting for significant effects of weekday vs. weekend, wake-up time and sleep duration, respectively. According to the latter model, AUC was estimated to be 51% higher in remitted patients than in controls (p = 0.007), while a 21% AUC decrease was associated with a 1-h longer sleep duration (p<0.001). In future studies, detection of between-group differences might benefit from adjusting for sleep duration and other possible confounders.
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