Lower cortisol levels predict recurrence in remitted patients with recurrent depression: a 5.5 year prospective study

Major Depressive Disorder (MDD) is a highly recurrent disease. Stress-responsive system dysfunction seems to persist after remission. In patients with more chronic and recurrent depressive episodes, state related HPA-axis dysregulation might be a risk factor for prospective recurrence. This study examines the predictive effect of cortisol on consecutive episodes in remitted recurrently depressed patients. Cortisol was assessed in saliva in remitted recurrently depressed patients (n=55) that were followed up prospectively for 5.5 years after remission. Recurrence was assessed using a well validated structured interview. Lower mean morning cortisol levels predicted earlier time to recurrence over 5.5 year after correction for residual symptoms (p=0.015). Residual symptoms and childhood trauma slightly confounded the association between cortisol and recurrence. Lower cortisol levels were associated with having experienced traumatic childhood life events (42.3% in patients with lower cortisol versus 19.2% in patients with higher cortisol). Our study provides further support for the predictive role over 5.5 year of HPA axis dysregulation, i.e. lower morning cortisol levels, of recurrence in recurrently depressed patients. Childhood trauma is associated to having lower cortisol levels. It might have long term consequences for dealing with stress and the HPA-axis.