background Twenty years ago Carroll and coworkers published a classic paper on the value of the dexamethason suppression test in depression. That paper led to several additional investigations on the significance of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of depression.
aim To critically review the involvement of the hypothalamus-pituitary-adrenal (HPA) axis activity in the psychopathology of depression.
method A Medline literature search over the period 1981 to June 2001 using as keywords cortisone, hydrocortisone, depression, DST and combinations.
results High hydrocortisone concentrations (HPA-axis activity) are state dependent and are found in no more than 50% of the depressed patients. Such increases do not allow prediction of therapeutic response, but normalization is prognostic for lasting recovery. The significance of glucocorticoid receptor desensitization in depression is emphasized. Such desensitization is also found in chronic inflammation. Most anti-glucocorticoid treatments have slow antidepressant effects which are not necessarily related to low hydrocortisone, but hydrocortisone itself can have antidepressant effects within 48 hours.
conclusion In depression there may not always be an excess of cortisol, but a shortage instead. Cortisol may accelerate the therapeutic intervention of current antidepressant medication.