Pariante Carmine M
Sections of Perinatal Psychiatry & Stress, Psychiatry and Immunology, Division of Psychological Medicine and Psychiatry Institute of Psychiatry, King's College London, London, United Kingdom.
Ann N Y Acad Sci. 2009 Oct;1179:144-52. doi: 10.1111/j.1749-6632.2009.04978.x.
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.
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“致抑郁作用”，但这一观点很大程度上源于对患有内分泌疾病患者的研究，如库欣综合征或接受合成糖皮质激素的外源性治疗。在这些情况下，高糖皮质激素水平很可能通过对糖皮质激素受体（GRs）的过度刺激而对大脑产生全面影响；事实上，使这些高水平恢复正常会改善这些患者的情绪。然而，在重度抑郁症中可能存在完全不同的机制，其中糖皮质激素水平升高被认为是由GR功能受损（糖皮质激素抵抗）驱动的，因此是一种“代偿性”机制。此外，临床和实验研究表明，抗抑郁药可增强GR功能，从而导致糖皮质激素抵抗的缓解。有趣的是，许多研究还表明，使用激动剂和拮抗剂来调控GR功能均具有抗抑郁作用，而且实际上其他针对HPA轴和皮质醇分泌的药物——即使是对HPA轴有相反作用的药物——也具有抗抑郁作用。这些研究并不支持“高糖皮质激素水平”总是具有致抑郁作用这一观点，也不支持降低这些激素的作用总是具有抗抑郁作用这一观点。
