Risk factors for development of depression and psychosis. Glucocorticoid receptors and pituitary implications for treatment with antidepressant and glucocorticoids.
Risk factors for development of depression and psychosis. Glucocorticoid receptors and pituitary implications for treatment with antidepressant and glucocorticoids.
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DOI：
10.1111/j.1749-6632.2009.04978.x
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发表时间：
2009-10
影响因子：
5.2
通讯作者：
Pariante CM
中科院分区：
文献类型：
--
作者：
Pariante CM
糖皮质激素水平升高——下丘脑-垂体-肾上腺（HPA）轴的主要产物——被认为具有“抑制作用”，但这一概念很大程度上源自对内分泌疾病患者的研究，例如库欣综合征或合成糖皮质激素的外源性治疗。在这些情况下，通过过度刺激糖皮质激素受体（GR），大脑可能会感受到高糖皮质激素水平的全面影响；事实上，使这些高水平正常化可以改善这些患者的情绪。然而，在重度抑郁症中可能存在一种完全不同的机制，其中糖皮质激素水平升高被概念化为由 GR 功能受损（糖皮质激素抵抗）驱动，因此被视为一种“补偿”机制。此外，临床和实验研究表明，抗抑郁药可增强 GR 功能，从而解决糖皮质激素耐药问题。有趣的是，许多研究还表明，用激动剂和拮抗剂操纵GR功能具有抗抑郁作用，事实上，其他针对HPA轴和皮质醇分泌的药物——甚至是对HPA轴具有相反作用的药物——也具有抗抑郁作用。这些研究并不支持“高水平的糖皮质激素”总是具有抑郁作用的观点，也不支持减少这些激素的作用总是具有抗抑郁作用的观点。
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.
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影响因子：
10.6
作者：
López, JF;Chalmers, DT;Watson, SJ
通讯作者：
Watson, SJ
影响因子：
3.4
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11.3
作者：
AXELSON, DA;DORAISWAMY, PM;KRISHNAN, KRR
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影响因子：
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作者：
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影响因子：
17.7
作者：
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通讯作者：
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