The role of mineralocorticoid receptor function in treatment-resistant depression
The role of mineralocorticoid receptor function in treatment-resistant depression
复制标题
DOI：
10.1177/0269881113499205
复制
发表时间：
2013-12-01
影响因子：
4.1
通讯作者：
Cleare, Anthony J.
中科院分区：
文献类型：
--
作者：
Juruena, Mario F.;Pariante, Carmine M.;Cleare, Anthony J.
背景资料：难治性抑郁症患者表现出糖皮质激素受体功能降低和下丘脑-垂体-肾上腺轴过度活跃。然而，很少有研究探讨盐皮质激素受体的作用。本研究旨在评估盐皮质激素受体系统在调节下丘脑-垂体-肾上腺轴的功能活动在明确的难治性depression patients.Material和方法：我们招募了24名受试者分为：（a）难治性抑郁症;（B）健康对照。我们评估了：（a）糖皮质激素受体/盐皮质激素受体联合刺激与泼尼松龙的作用;（B）泼尼松龙与盐皮质激素受体拮抗剂螺内酯的作用;和（c）单独螺内酯的作用。下丘脑-垂体-肾上腺轴的反应进行了测量，使用唾液皮质醇和药物的血浆水平也measured.Results：治疗抵抗性抑郁症患者有较高的皮质醇与对照组相比，所有的挑战。在对照组中，与安慰剂相比，螺内酯增加皮质醇。在对照组中，螺内酯与泼尼松龙的联合给药降低了泼尼松龙的抑制作用。相反，在难治性抑郁症中，与安慰剂相比，螺内酯没有增加皮质醇，螺内酯与泼尼松龙对泼尼松龙的抑制作用没有影响。难治性抑郁症患者的安体舒通转化为活性代谢物坎利酮的转化率降低。我们的数据证实，难治性抑郁症与皮质醇增多症有关，这些患者对盐皮质激素受体拮抗剂的给药不再显示下丘脑-垂体-肾上腺反应，这表明存在盐皮质激素受体功能障碍，例如下调，然而，这些受试者的药代动力学和药效学也可能对盐皮质激素受体反应的缺乏产生影响。
Background: Treatment-resistant depression patients show both reduced glucocorticoid receptor function and a hyperactive hypothalamic-pituitary-adrenal axis. However, few studies have examined the role of the mineralocorticoid receptor. This study aimed to evaluate the functional activity of the mineralocorticoid receptor system in regulating the hypothalamic-pituitary-adrenal axis in well-defined treatment-resistant depression patients.Material and method: We recruited 24 subjects divided into: (a) treatment-resistant depression; (b) healthy controls. We evaluated: (a) the effect of combined glucocorticoid receptor/mineralocorticoid receptor stimulation with prednisolone; (b) the effect of prednisolone with the mineralocorticoid receptor antagonist spironolactone; and (c) the effect of spironolactone alone. The response of the hypothalamic-pituitary-adrenal axis was measured using salivary cortisol and plasma levels of drugs were also measured.Results: Treatment-resistant depression patients had higher cortisol compared with controls after all challenges. In controls, spironolactone increased cortisol compared to placebo. The co-administration of spironolactone with prednisolone in controls decreases the suppressive effects of prednisolone. In contrast, in treatment-resistant depression, spironolactone did not increase cortisol compared to placebo and spironolactone with prednisolone had no effect on the suppressive effects of prednisolone. Patients with treatment-resistant depression had a reduction in the conversation of spironolactone to the active metabolite canrenone.Conclusion: Our data confirmed that treatment-resistant depression is associated with hypercortisolism and these patients no longer show an hypothalamic-pituitary-adrenal response to the administration of a mineralocorticoid receptor antagonist, suggesting that there is a mineralocorticoid receptor malfunctioning, such as a down regulation, however, pharmacokinetics and pharmacodynamics in these subjects could also have had an effect on the lack of mineralocorticoid receptor response.