BACKGROUND A dysregulation in the hypothalamic-pituitary-adrenal (HPA)-axis function has been repeatedly observed in major depressive disorders (MDD). Normalization of this dysregulation, i.e. of cortisol suppression after glucocorticoid receptor (GR)-stimulation, may be mandatory for clinical remission in some patient subgroups. However, there are no biological measures applied in the clinical setting to identify patient subgroups with HPA axis alterations. OBJECTIVE We aimed to define a suppression index of cortisol concentrations before and after GR stimulation with dexamethasone to predict the variability in improvement of HPA axis activity during antidepressant treatment. METHODS A modified dexamethasone suppression test (mDST) was performed with blood withdrawal for cortisol and ACTH measurement before and 3 h after 1.5 mg dexamethasone intake at 18:00 in two cohorts of depressed patients treated in a naturalistic setting. The discovery sample consisted of 106 patients, the replication sample of 117 patients. The suppression index was defined as cCORTpreDEXcCORTpostDEX. RESULTS The baseline suppression index explained 27.4 % of the variance in changes of HPA axis activity before and after treatment with antidepressants. Age, cCORTpreDEXcACTHpreDEX at baseline and sex explained further variance up to 56.2 % (stepwise linear regression, p = 7.8e-8). A threshold of the suppression index at baseline was determined by ROC analysis and revealed, that only patients with a maximum index of 2.32 achieved a normalization of the HPA axis activity after antidepressant treatment. In the replication sample, the threshold was 2.86. However, the estimated suppression index was not associated with treatment response. CONCLUSION For the first time, by establishing a short-term suppression index of cortisol before and after GR-stimulation a threshold could be identified to predict improvement of HPA axis activity during antidepressant therapy. After replication in further studies this index may help to identify patients who benefit from a specific treatment that targets components of the HPA axis in the future.

中文翻译：

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基线皮质醇抑制程度可预测抗抑郁治疗期间 HPA 轴功能的改善

背景 在重度抑郁症 (MDD) 中反复观察到下丘脑-垂体-肾上腺 (HPA) 轴功能失调。这种失调的正常化，即糖皮质激素受体 (GR) 刺激后皮质醇抑制的正常化，对于某些患者亚组的临床缓解可能是强制性的。然而，在临床环境中没有应用生物学测量来识别具有 HPA 轴改变的患者亚组。目的 我们旨在定义地塞米松 GR 刺激前后皮质醇浓度的抑制指数，以预测抗抑郁治疗期间 HPA 轴活动改善的可变性。方法 进行改良的地塞米松抑制试验 (mDST)，并在 1 小时前和 3 小时后抽血进行皮质醇和 ACTH 测量。在自然环境中治疗的两组抑郁症患者中，18:00 时摄入 5 毫克地塞米松。发现样本由 106 名患者组成，复制样本由 117 名患者组成。抑制指数定义为 cCORTpreDEXcCORTpostDEX。结果 基线抑制指数解释了抗抑郁药治疗前后 HPA 轴活动变化的 27.4%。年龄、基线和性别的 cCORTpreDEXcACTHpreDEX 进一步解释了高达 56.2% 的差异（逐步线性回归，p = 7.8e-8）。通过 ROC 分析确定基线抑制指数的阈值，并显示只有最大指数为 2.32 的患者在抗抑郁治疗后才能实现 HPA 轴活动的正常化。在复制样本中，阈值为 2.86。然而，估计的抑制指数与治疗反应无​​关。结论首次通过在 GR 刺激前后建立皮质醇的短期抑制指数，可以确定一个阈值来预测抗抑郁治疗期间 HPA 轴活动的改善。在进一步研究中复制后，该指数可能有助于识别未来从针对 HPA 轴组成部分的特定治疗中受益的患者。