Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany; Interdisciplinary Center for Clinical Research, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Am Schwarzenberg 15, Würzburg, 97080, Germany.
Psychoneuroendocrinology. 2020 Apr;114:104590. doi: 10.1016/j.psyneuen.2020.104590. Epub 2020 Jan 26.
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.
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.
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.
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). 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.
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.
下丘脑-垂体-肾上腺（HPA）轴功能失调在重度抑郁症（MDD）中反复观察到。在某些患者亚组中，这种失调的正常化，即糖皮质激素受体（GR）刺激后皮质醇的抑制，可能是临床缓解的必要条件。然而，在临床环境中没有应用生物学措施来识别 HPA 轴改变的患者亚组。
我们旨在定义用地塞米松刺激 GR 前后皮质醇浓度的抑制指数，以预测抗抑郁治疗期间 HPA 轴活性改善的可变性。
在自然环境中接受治疗的两批抑郁患者中，在 18:00 时口服 1.5mg 地塞米松前后进行改良地塞米松抑制试验（mDST），以测量皮质醇和 ACTH 的采血。发现样本包括 106 例患者，复制样本包括 117 例患者。抑制指数定义为 cCORTpreDEXcCORTpostDEX。
基线抑制指数解释了抗抑郁治疗前后 HPA 轴活性变化的 27.4%的方差。年龄、基线时的 cCORTpreDEXcACTHpreDEX 和性别进一步解释了 56.2%的方差（逐步线性回归，p=7.8e）。通过 ROC 分析确定了基线抑制指数的阈值，结果表明只有抑制指数最大值为 2.32 的患者在抗抑郁治疗后 HPA 轴活性才能正常化。在复制样本中，该阈值为 2.86。然而，估计的抑制指数与治疗反应无关。
通过建立 GR 刺激前后皮质醇的短期抑制指数，首次可以确定一个阈值来预测抗抑郁治疗期间 HPA 轴活性的改善。在未来的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 轴特定成分的特定治疗中受益的患者。
