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常规可及的盐皮质激素受体功能参数、抑郁亚型与反应预测:重度抑郁症早期药物调整试验的事后分析。

Routinely accessible parameters of mineralocorticoid receptor function, depression subtypes and response prediction: a post-hoc analysis from the early medication change trial in major depressive disorder.

机构信息

Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, Germany.

Translational Psychiatry, Department of Psychiatry and Psychotherapy & Focus Program Translational Neuroscience, University Medical Center, Mainz, Germany.

出版信息

World J Biol Psychiatry. 2022 Oct;23(8):631-642. doi: 10.1080/15622975.2021.2020334. Epub 2022 Jan 25.

Abstract

OBJECTIVES

Previous studies indicated a relationship between aldosterone, the mineralocorticoid receptor (MR), and antidepressant treatment outcome. Physiological indicators of MR function (blood pressure and electrolytes) are easily accessible and may therefore serve as useful predictors. Thus, our aim was to investigate the predictive value of peripheral MR-related markers for antidepressant treatment outcomes.

METHODS

826 MDD patients who had participated in the randomised-controlled Early Medication Change (EMC) trial were analysed. Depression severity and MR-related markers were assessed weekly. In 562 patients, genetic variation of five MR-related genes was determined.

RESULTS

Patients with blood pressure <120mmHg showed higher depression severity ( = 0.005) than patients with blood pressure ≥120mmHg. Patients with a melancholic subtype had significantly lower blood pressures ( = 0.004). Na/K ratio was positively and K-concentration was negatively correlated to depression severity and to relative changes in HAMD from baseline to day 14, and 56 respectively ( < 0.001). For none of the MR-related genes, genetic variation was associated with treatment outcomes.

CONCLUSIONS

We confirmed early observations of an altered peripheral MR sensitivity, reflected by lower blood pressure, low K or high Na/K ratio in patients with more severe depression. These routinely collected biomarkers may potentially be useful for risk stratification in an early stage of treatment. clinicaltrials.gov Identifier: NCT00974155; https://www.clinicaltrials.gov/ct2/results?term=NCT00974155.

摘要

目的

先前的研究表明,醛固酮、盐皮质激素受体(MR)与抗抑郁治疗效果之间存在关联。MR 功能的生理指标(血压和电解质)易于获取,因此可能作为有用的预测指标。因此,我们旨在研究外周 MR 相关标志物对抗抑郁治疗效果的预测价值。

方法

对参加随机对照早期药物调整(EMC)试验的 826 例 MDD 患者进行分析。每周评估抑郁严重程度和与 MR 相关的标志物。在 562 例患者中,确定了五个与 MR 相关基因的遗传变异。

结果

血压<120mmHg 的患者抑郁严重程度较高( = 0.005),而血压≥120mmHg 的患者则较低。具有忧郁型亚型的患者血压明显较低( = 0.004)。Na/K 比值与抑郁严重程度以及 HAMD 从基线到第 14 天和第 56 天的相对变化呈正相关( < 0.001),而 K 浓度则呈负相关。对于任何一个与 MR 相关的基因,遗传变异均与治疗效果无关。

结论

我们证实了早期观察到的外周 MR 敏感性改变,表现为更严重的抑郁患者血压较低、K 浓度较低或 Na/K 比值较高。这些常规收集的生物标志物可能在治疗早期具有风险分层的潜在作用。临床试验标识符:NCT00974155;https://www.clinicaltrials.gov/ct2/results?term=NCT00974155。

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