The Associations of Sleep Factors and Emotional Distress with Cortisol Awakening Response in Outpatients with Major Depressive Disorder

Objectives: The associations of time of awakening, total time slept, anxiety, and depressed levels with awakening cortisol levels and Cortisol Awakening Response (CAR) were compared between outpatients with Major Depressive Disorder (MDD) and healthy control patients. Methods: Self-reports of depressive and anxiety levels, time of awakening, total time slept, and healthy behaviors were completed by 125 outpatients with Major Depressive Disorder (MDD) and 107 healthy control patients. Saliva samples were collected for all patients to measure cortisol levels at awakening, 30-45 minutes after awakening, and at 12:00, 17:00, and 21:00 hours. Results: There was no significant difference in CAR (increased cortisol levels from waking to 30-45 minutes post-waking) between MDD outpatients and healthy control patients. However, factors associated with the magnitude of CAR were different between the two groups after controlling for potentially confounding factors such as gender, age, and smoking, alcohol, and coffee habits. Higher awakening cortisol levels were related to early time of awakening in healthy control patients but were correlated instead with higher anxiety levels in MDD outpatients. The larger magnitudes of CAR associated with later time of awakening in healthy subjects, on the other hand, were related to lower anxiety levels and history of mental illness in MDD outpatients. Conclusion: The time of awakening is likely a normal regulatory factor of morning cortisol responses in healthy people. Rather than this normal regulatory function, anxiety symptoms and family history of mental illness were the main regulatory factors for awakening cortisol levels and CAR magnitude in MDD outpatients. This might play an important role in underlying pathophysiological processes leading to HPA axis dysfunction in this patient group.