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

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 (p = 0.005) than patients with blood pressure ≥120mmHg. Patients with a melancholic subtype had significantly lower blood pressures (p = 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 (p < 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. Trial Registration: clinicaltrials.gov Identifier: NCT00974155; https://www.clinicaltrials.gov/ct2/results?term=NCT00974155

Keywords:

• Major depressive disorder
• biomarker
• mineralocorticoid receptor
• treatment outcome
• aldosterone

Acknowledgement

The authors are grateful to the members of the EMC Study Group, who were involved in the acquisition of data for this additional scientific investigation. These members are: Univ.-Prof. Dr. Klaus Lieb, Dr. André Tadić, Univ.-Prof. Christoph Hiemke, Dr. Nadine Dreimüller, Dr. Ömür Baskaya, Dr. Danuta Krannich, Dr. Sonja Lorenz, Annette Bernius, Dr. Tillmann Weichert, Dr. Markus Lorscheider, Dr. Martin Kloß, Dr. Dipl.-Psych. Isabella Helmreich, Dipl.-Psych. Karen Grüllich, Elnaz Ostad Haji, Yvonne Lober, Danuta Weichert, Dr. Konrad Schlicht, Dr. Christina Weigert, Dr. Jana Maurer (Department of Psychiatry and Psychotherapy, University Medical Centre Mainz); Prof. Dr. Dieter F. Braus, Dr. Julia Reiff, Dr. Christoph Kindler, Dr. Svenja Davis, Dr. Claudia Ginap, Dipl.-Psych. Julia Kraus, Dipl.-Psych. Sabine Kaaden, Dr. Dipl.-Psych. Jelena Janzen, Dipl.-Psych. Nina Löffler, Caterina Topaloglu, Elitza Klutscher (Clinic for Psychiatry and Psychotherapy, Wiesbaden).

Statement of interest

H. Murck is currently working at Aptinyx Inc, Evanston IL, USA. He is also the owner of the consulting company Murck-Neuroscience LLC, USA and has a patent for the use of glycyrrhizin in the area of depression treatment. A. Tadic is designated as inventor of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a mono-aminergic antidepressant’. He has received during the last five years consultancy fees from Janssen and Novartis. K. Lieb is designated as inventor of the European patent number 12171541.1–2404 ‘Method for predicting response or non-response to a mono-aminergic antidepressant’. D.F. Braus has received in the last 5 years fees for unrestricted educational lectures from Lilly, Janssen, Bayer, Lundbeck, Servier, Shire, TAD Pharma, MSD. None of the authors has relevant financial interests in this manuscript.

Additional information

Funding

The EMC trial was funded by the German Federal Ministry for Education and Research (BMBF grant n°: 01 KG 0906); the herein presented additional investigations are not part of the funding. The BMBF had no role in the conception of the study design, in the writing of the manuscript or the decision to submit the manuscript for publication.