Major Depressive Disorder (MDD) is a highly recurrent disease and stress-responsive system dysfunction seems to persist after remission. In patients with chronic and recurrent depressive episodes, state related hypothalamic-pituitary-adrenal (HPA)- axis dysregulation might be a risk factor for prospective recurrence. This study examined the predictive effect of cortisol on consecutive episodes in remitted recurrently depressed patients. Cortisol was assessed in the saliva of 55 remitted recurrently depressed patients who were followed prospectively for 5.5 years after remission. Lower mean morning cortisol levels predicted earlier time to recurrence over 5.5 years after correction for residual symptoms (P = 0.015); residual symptoms and childhood trauma slightly confounded this association. 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). The authors concluded that these data provide further support for the predictive role of HPA axis dysregulation (i.e. lower morning cortisol levels) on recurrence in recurrently depressed patients. They also suggested that childhood trauma is associated with having lower cortisol levels and that it might have long-term consequences for dealing with stress and the HPA-axis. Psychiatry Res. 2012 Apr 11. PMID: 22503382
