Mineralocorticoid receptor function in depressed patients and healthy individuals
Mineralocorticoid receptor function in depressed patients and healthy individuals
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DOI：
10.1016/j.pnpbp.2016.08.003
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发表时间：
2016-11-03
影响因子：
5.6
通讯作者：
Otte, Christian
中科院分区：
文献类型：
--
作者：
Hinkelmann, Kim;Hellmann-Regen, Julian;Otte, Christian
背景：许多研究表明抑郁症患者存在糖皮质激素受体（GR）紊乱。相比之下，只有少数研究针对盐皮质激素受体（MR）的功能与不确定的结果。我们研究的影响，MR拮抗剂螺内酯对皮质醇分泌抑郁症患者和健康individuals.Methods：48未经药物治疗的抑郁症患者（平均年龄41.6岁）和45个年龄和性别匹配的健康参与者（40.7岁）接受了MR拮抗剂螺内酯（300毫克）或安慰剂与三天分开在一个随机的，双盲的，受试者内交叉设计。我们测量唾液皮质醇摄入前的研究药物（基线），以及+ 60分钟，+ 90分钟，+ 120分钟，+ 150分钟和180分钟后baseline.Results：重复测量方差分析的曲线下面积（AUC）皮质醇显示治疗效果与较高的皮质醇螺内酯和治疗组的相互作用。事后分析显示，在安慰剂条件下，抑郁症患者的皮质醇高于健康参与者。在螺内酯条件下，皮质醇水平没有显着different.Conclusions：潜在的，受损的MR或GR信号可能是负责较高的皮质醇水平在安慰剂条件下抑郁症患者。然而，在MR阻断后，增加皮质醇分泌，导致更高的GR占用，我们发现抑郁症患者和健康对照组之间没有差异。因此，我们的研究结果认为，抑郁症相关的改变MR信号，而不是干扰GR介导的反馈抑制。(C)2016 Elsevier Inc. All rights reserved.
Background: Many studies have shown disturbed glucocorticoid receptor (GR) in depressed patients. In contrast, only few studies targeted mineralocorticoid receptor (MR) function with inconclusive results. We examined the effects of the MR antagonist spironolactone on cortisol secretion in depressed patients and healthy individuals.Methods: Forty-eight unmedicated depressed patients (mean age 41.6 years) and 45 age-and sex-matched healthy participants (40.7 years) received the MR antagonist spironolactone (300 mg) or placebo with three days apart in a randomized, double-blind, within-subject cross-over design. We measured salivary cortisol before ingestion of study medication (baseline) as well as + 60 min, + 90 min, + 120 min, + 150 min and 180 min after baseline.Results: Repeated-measures ANOVA for area under the curve (AUCg) cortisol revealed a treatment effect with higher cortisol after spironolactone and a treatment by group interaction. Post-hoc analyses revealed higher cortisol in depressed patients compared to healthy participants in the placebo condition. In the spironolactone condition, the cortisol levels were not significantly different.Conclusions: Potentially, impaired MR or GR signaling could be responsible for higher cortisol levels in depressed patients in the placebo condition. However, after MR blockade that increased cortisol secretion across groups leading to higher GR occupation, we found no differences between depressed patients and healthy controls. Thus, our results argue for depression-associated alterations in MR signaling rather than disturbed GR-mediated feedback inhibition. (C) 2016 Elsevier Inc. All rights reserved.