TY - CHAP
T1 - Risk Factors for Development of Depression and Psychosis Glucocorticoid Receptors and Pituitary Implications for Treatment with Antidepressant and Glucocorticoids
AU - Pariante, Carmine M.
PY - 2009
Y1 - 2009
N2 - Increased levels of glucocorticoid hormones-the main product of the hypothalamic-pituitary-adrenal (HPA) axis-have been considered to be "depressogenic," but this notion has largely derived from studies in patients with endocrine conditions, such as Cushing's syndrome or exogenous treatment with synthetic glucocorticoids. In these conditions, it is likely that the full impact of the high glucocorticoid levels is felt on the brain, through over-stimulation of the glucocorticoid receptors (GRs); indeed, normalizing these high levels leads to an improvement of mood in these patients. However, a completely different mechanism may be operating in major depression, where the increased levels of glucocorticoid hormones are conceptualized as driven by an impairment in GR function (glucocorticoid resistance), and therefore as a "compensatory" mechanism. Moreover, clinical and experimental studies have shown that antidepressants increase GR function, thus leading to resolution of glucocorticoid resistance. Interestingly, a number of studies have also demonstrated that manipulating GR function with both agonists and antagonists has an antidepressant effect, and indeed that other drugs targeting the HPA axis and cortisol secretion-even drugs with opposite effects on the HPA axis-have antidepressant effects. These studies do not support the notion that "high levels of glucocorticoids" always have a depressogenic effect, nor that decreasing the effects of these hormones always has an antidepressant effects.
AB - Increased levels of glucocorticoid hormones-the main product of the hypothalamic-pituitary-adrenal (HPA) axis-have been considered to be "depressogenic," but this notion has largely derived from studies in patients with endocrine conditions, such as Cushing's syndrome or exogenous treatment with synthetic glucocorticoids. In these conditions, it is likely that the full impact of the high glucocorticoid levels is felt on the brain, through over-stimulation of the glucocorticoid receptors (GRs); indeed, normalizing these high levels leads to an improvement of mood in these patients. However, a completely different mechanism may be operating in major depression, where the increased levels of glucocorticoid hormones are conceptualized as driven by an impairment in GR function (glucocorticoid resistance), and therefore as a "compensatory" mechanism. Moreover, clinical and experimental studies have shown that antidepressants increase GR function, thus leading to resolution of glucocorticoid resistance. Interestingly, a number of studies have also demonstrated that manipulating GR function with both agonists and antagonists has an antidepressant effect, and indeed that other drugs targeting the HPA axis and cortisol secretion-even drugs with opposite effects on the HPA axis-have antidepressant effects. These studies do not support the notion that "high levels of glucocorticoids" always have a depressogenic effect, nor that decreasing the effects of these hormones always has an antidepressant effects.
UR - http://www.scopus.com/inward/record.url?scp=70449407836&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2009.04978.x
DO - 10.1111/j.1749-6632.2009.04978.x
M3 - Conference paper
SN - 978-1-57331-748-1
VL - 1179
T3 - GLUCOCORTICOIDS AND MOOD CLINICAL MANIFESTATIONS, RISK FACTORS, AND MOLECULAR MECHANISMS
SP - 144
EP - 152
BT - Unknown
PB - Blackwell Publishing
CY - OXFORD
T2 - Conference on Glucocorticoids and Mood - Clinical Manifestations, Risk Factors and Molecular Mechanisms
Y2 - 20 June 2008 through 21 June 2008
ER -