Activation of the hypothalamuspituitaryadrenal axis

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Depression is often accompanied by hypercortisolemia. Associated findings include attenuation of the corticotropin response to the administration of corticotrophin-releasing factor and nonsuppression of cortisol secretion after dexamethasone administration. Hypercortisolemia in association with blunted growth and sex hormones promotes central obesity and contributes to increased insulin resistance and diabetes among depressed subjects [31]. The presence of hypercortisolemia in insulin resistance has been documented in some, but not all, studies. A small case-control study has shown some evidence for increased cortisol production in the metabolic syndrome as well [32]. Notably, a contributory role for cortisol metabolism in the pathogenesis of the metabolic syndrome has been postulated. Deregulation of 11 betahydroxysteroiddehydrogenase, an enzyme that converts cortisol into cortison (which cannot activate the glucocorticoid receptor), may result in excess cortisol exposure at the tissue level and induce visceral adiposity [33].

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