Objective: Changes in the hypothalamic-pituitary-adrenocortical (HPA) system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GRs in depressed patients.
Methods: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR
IntroductionHormones play a critical role in the development and expression of a wide range of behaviours. One aspect of the influence of hormones on behaviour is their potential contribution to the pathophysiology of psychiatric disorders and the mechanism of action of psychotropic drugs, particularly in major depression. Of all endocrine axes, the hypothalamic-pituitary-adrenal (HPA) axis has been the most widely evaluated. 1,2 The HPA axis plays a fundamental role in the response to external and internal stimuli including psychological stressors. Abnormalities in the function of the HPA axis have been described in people experiencing psychiatric disorders. Moreover, is well known the fundamental role of stress in precipitating episodes of psychiatric disorders in predisposed individuals. 1 These abnormalities seem related to changes in the ability of circulating glucocorticoids to exert their negative feedback on the secretion of HPA hormones through binding to the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) in HPA tissues. 2,3,6 In fact, previous studies have described both an impaired HPA negative feedback, leading to hypercortisolemia, as in melancholic depression. 2,6 In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including anorexia nervosa with or without malnutrition, obsessive-compulsive disorder, panic anxiety, chronic active alcoholism, alcohol and narcotic withdrawal, excessive exercising, poorly controlled diabetes mellitus, childhood sexual abuse and hyperthyroidism. 7 Another group of states is characterized by hypoactivation of the stress system, rather than sustained activation, in which chronically reduced secretion of CRH may result in pathological hypoarousal and an enhanced HPA negative feedback. Patients with post-traumatic stress disorder, atypical, seasonal depression and the chronic fatigue syndrome fall in this category (see Table 1). Similarly, patients with fibromyalgia have decreased urinary free