Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression
Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression
复制标题
DOI：
10.1038/s41398-020-0789-7
复制
发表时间：
2020-04
影响因子：
6.8
通讯作者：
J. Nowacki;K. Wingenfeld;M. Kaczmarczyk;W. Chae;P. Salchow;I. Abu-Tir;D. Piber;J. Hellmann-Regen;C. Otte
中科院分区：
文献类型：
--
作者：
J. Nowacki;K. Wingenfeld;M. Kaczmarczyk;W. Chae;P. Salchow;I. Abu-Tir;D. Piber;J. Hellmann-Regen;C. Otte
重性抑郁症（MDD）与盐皮质激素受体（MR）和糖皮质激素受体功能改变以及多巴胺能信号转导紊乱有关。这两个系统紧密交织在一起，不仅可能导致MDD的病理生理学，而且可能导致MDD患者心血管风险增加。人们对其他类固醇激素（例如醛固酮和DHEA-S）以及它们如何影响谷氨酸能系统和MDD中的心血管疾病风险知之甚少。我们检测了116名未用药的抑郁症患者和116名年龄和性别匹配的健康对照者在刺激MR和NMDA受体后唾液皮质醇、醛固酮和DHEA-S的分泌。患者（平均年龄= 34.7岁，标准差= ±13.3; 78%为女性）和对照组被随机分配至四种条件：（a）对照条件（安慰剂），（B）MR刺激（0.4 mg氟氢可的松），（c）NMDA刺激（250 mg D-环丝氨酸（DCS）），和（d）MR/NMDA联合刺激（氟氢可的松+ DCS）。我们还确定了两组的心血管风险特征。DCS对类固醇激素分泌没有影响，而皮质醇分泌在两种氟氢可的松条件下均降低。与病情无关，与对照组相比，MDD患者显示（1）皮质醇增加，醛固酮增加，DHEA-S浓度降低，（2）葡萄糖水平升高，高密度脂蛋白胆固醇水平降低。抑郁症患者表现出与MDD病理生理学和心血管风险增加相关的几种类固醇激素系统的深刻改变。前瞻性研究应检查调节类固醇激素水平是否可能降低抑郁症患者的精神病理学和心血管风险。
Major depressive disorder (MDD) is associated with altered mineralocorticoid receptor (MR) and glucocorticoid receptor function, and disturbed glutamatergic signaling. Both systems are closely intertwined and likely contribute not only to the pathophysiology of MDD, but also to the increased cardiovascular risk in MDD patients. Less is known about other steroid hormones, such as aldosterone and DHEA-S, and how they affect the glutamatergic system and cardiovascular disease risk in MDD. We examined salivary cortisol, aldosterone, and DHEA-S secretion after stimulation of MR and glutamatergic NMDA receptors in 116 unmedicated depressed patients, and 116 age- and sex-matched healthy controls. Patients (mean age = 34.7 years, SD = ±13.3; 78% women) and controls were randomized to four conditions: (a) control condition (placebo), (b) MR stimulation (0.4 mg fludrocortisone), (c) NMDA stimulation (250 mg D-cycloserine (DCS)), and (d) combined MR/NMDA stimulation (fludrocortisone + DCS). We additionally determined the cardiovascular risk profile in both groups. DCS had no effect on steroid hormone secretion, while cortisol secretion decreased in both fludrocortisone conditions across groups. Independent of condition, MDD patients showed (1) increased cortisol, increased aldosterone, and decreased DHEA-S concentrations, and (2) increased glucose levels and decreased high-density lipoprotein cholesterol levels compared with controls. Depressed patients show profound alterations in several steroid hormone systems that are associated both with MDD pathophysiology and increased cardiovascular risk. Prospective studies should examine whether modulating steroid hormone levels might reduce psychopathology and cardiovascular risk in depressed patients.