Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study

Agorastos Agorastos, Anne Sommer, Alexandra Heinig, Klaus Wiedemann, Cüneyt Demiralay, Agorastos Agorastos, Anne Sommer, Alexandra Heinig, Klaus Wiedemann, Cüneyt Demiralay

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: antidepressants; biomarker; copeptin; cortisol; depression; hypothalamus-pituitary-adrenal axis (HPA axis); treatment response; vasopressin (AVP).

Copyright © 2020 Agorastos, Sommer, Heinig, Wiedemann and Demiralay.

Figures

Figure 1
Figure 1
Effects of metyrapone (MET) and dexamethasone (DEX) on cortisol (CORT), ACTH, and CoP in responders and non-responders to ESC antidepressant treatment. Graphic presentation of Table 2. Pointwise values represent geometrical means adjusted for age, gender, BMI, history of previous depression and smoking. Group differences were assessed through a linear analysis of covariance (ANCOVA), controlling for age, gender, BMI, history of previous depression, and smoking. ACTH: Adrenocorticotropic hormone. Day 1: baseline; day 2: Post-MET: post-metyrapone; day 3: post-DEX: post-dexamethasone. A mixed between-within subject ANOVA indicated a highly significant effect of time (i.e. treatment condition) in all three measures with very large effect sizes, which confirmed the expected effects of each treatment condition (cf. Results section). Group (response vs. non-response) had a significant effect only for CoP, but not for CORT or ACTH, suggesting a statistically significant difference between responders and non-responders on CoP levels across days 1–3 (cf. Results section). *p < 0.05.

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