Mild hypercortisolemia is a biological marker found in a subset of patients with major depression. The cause is supposed to be a malfunction in the corticosteroid receptor. Long standing cortisol excess is toxic to nerve cells and especially the hippocampus seem vulnerable to hypercortisolemia. The well known memory and concentration difficulties found in stress and depressive illnesses are supposed to be partly caused by deterioration of the function of the hippocampus.

The cortisol awakening response(CAR)were measured in saliva by repeated saliva specimens (awakening, 20 min and 60 minutes after awakening) in patient participating in a double blind study using a fixed dosage of sertraline and randomised to either dim or bright light treatment. Cortisol measurements were made before medication and light treatment started. The hypothesis, stated in the protocol, was that saliva cortisol would have a predictive validity of the short term depression outcome.

A statistically significant increase in cortisol levels were found during the first hour after awakening. The area under the curve (AUC) from the CAR results was calculated and was found to have a statistically significant predictive validity for depression scores and remission at endpoint. Thus a statistically significant higher proportion of patient with low CAR values were in remission compared to patient with high CAR values. This effect was predominantly seen in the bright light treated group.

Patients with a high CAR were less likely to attain remission at endpoint. The high CAR seemed to block the effect of light treatment.