Agorastos Agorastos, Sommer Anne, Heinig Alexandra, Wiedemann Klaus, Demiralay Cüneyt
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Psychiatry, Division of Neurosciences, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Front Psychiatry. 2020 May 20;11:453. doi: 10.3389/fpsyt.2020.00453. eCollection 2020.
Major depressive disorder (MDD) constitutes the leading cause of disability worldwide. Although efficacious antidepressant pharmacotherapies exist for MDD, only about 40-60% of the patients respond to initial treatment. However, there is still a lack of robustly established and applicable biomarkers for antidepressant response in everyday clinical practice.
This study targets the assessment of the vasopressin (AVP) surrogate marker Copeptin (CoP), as a potential peripheral hypothalamic-level biomarker of antidepressant treatment response in MDD.
We measured baseline and dynamic levels of plasma CoP along with plasma ACTH and cortisol (CORT) in drug-naive outpatients with MDD before and after overnight manipulation of the hypothalamic-pituitary-adrenal (HPA) axis [i.e., stimulation (metyrapone) and suppression (dexamethasone)] on three consecutive days and their association with treatment response to 4 weeks of escitalopram treatment.
Our findings suggest significantly higher baseline and post-metyrapone plasma CoP levels in future non-responders, a statistically significant invert association between baseline CoP levels and probability of treatment response and a potential baseline plasma CoP cut-off level of above 2.9 pmol/L for future non-response screening. Baseline and dynamic plasma ACTH and CORT levels showed no association with treatment response.
This pilot study provide first evidence in humans that CoP may represent a novel, clinically easily applicable, endocrine biomarker of antidepressant response, based on a single-measurement, cut-off level. These findings, underline the role of the vasopressinergic system in the pathophysiology of MDD and may represent a significant new tool in the clinical and biological phenotyping of MDD enhancing individual-tailored therapies.
重度抑郁症（MDD）是全球致残的主要原因。尽管有有效的抗抑郁药物疗法可用于治疗MDD，但只有约40%-60%的患者对初始治疗有反应。然而，在日常临床实践中，仍缺乏强有力的、已确立且适用的抗抑郁反应生物标志物。
本研究旨在评估加压素（AVP）替代标志物 copeptin（CoP），作为MDD抗抑郁治疗反应的潜在外周下丘脑水平生物标志物。
我们在未接受过药物治疗的MDD门诊患者中，连续三天对下丘脑-垂体-肾上腺（HPA）轴进行过夜操作（即刺激[甲吡酮]和抑制[地塞米松]）前后，测量血浆CoP以及血浆促肾上腺皮质激素（ACTH）和皮质醇（CORT）的基线水平和动态水平，并将其与艾司西酞普兰治疗4周的治疗反应相关联。
我们的研究结果表明，未来无反应者的基线和甲吡酮治疗后的血浆CoP水平显著更高，基线CoP水平与治疗反应概率之间存在统计学上显著的负相关，并且对于未来无反应筛查，潜在的基线血浆CoP临界值水平高于2.9 pmol/L。基线和动态血浆ACTH及CORT水平与治疗反应无关联。
这项初步研究首次在人类中证明，基于单次测量的临界值水平，CoP可能代表一种新型的、临床易于应用的抗抑郁反应内分泌生物标志物。这些发现强调了加压素能系统在MDD病理生理学中的作用，并且可能代表MDD临床和生物学表型分析中的一个重要新工具，可增强个体化治疗。
