Diurnal Rhythm of Cortisol in Depression: What Is Normal and What Is Not

Abstract

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in depression have been reported in numerous studies. It has been suggested that patients with major depressive disorder—endogenous subtype (MDD-ED) have increased basal levels of cortisol (in plasma and urine) and nonsuppressibility of cortisol in response to dexamethasone, i.e., an abnormal dexamethasone suppression test (DST). A plethora of disturbances in the rhythm of cortisol secretion have been reported, mainly a “flattened curve” and a phase advance of cortisol, meaning that levels of plasma cortisol in MDD-ED patients peak earlier and they do not decrease in the early afternoon and evening, as is the case with the normal plasma cortisol curve. It has also been suggested that MDD-ED patients have a larger number of secretory episodes per 24 h, and that the amount of cortisol secreted during each episode is higher than normal.1–5 In most reports it has also been assumed than an abnormality of one of the functions of the HPA means that the entire system is abnormal; in particular, an abnormal DST is often reported as “abnormal HPA system” or “cortisol hypersecretion.”