Ex vivo glucocorticoid receptor-mediated IL-10 response predicts the course of depression severity.

Content Provider	Europe PMC
Author	von Zimmermann, Claudia Böhm, Lea Richter-Schmidinger, Tanja Kornhuber, Johannes Lenz, Bernd Mühle, Christiane
Abstract	Directly measuring hypothalamic pituitary adrenal (HPA) axis function, an important player in affective disorders, is intensive and invasive. A crucial component of this system, the activity of the glucocorticoid receptor (GR), can be assessed ex vivo instead. Here, we investigated GR sensitivity in patients with major depressive disorder (MDD) to determine its predictive potential. Psychometric data and blood samples were collected from patients experiencing a major depressive episode (MDE, n = 87), healthy control subjects (n = 49), and patients with remitted MDD (n = 31) at baseline and (for patients) after median 20 days of follow-up after treatment as usual. Blood cells were stimulated ex vivo with lipopolysaccharide and the effect was suppressed by increasing dexamethasone (DEX) concentrations. The resultant cytokine secretion profile (for IL-6, IL-10, and TNF-α) was considered indicative of GR activity. Higher baseline scores of the Montgomery–Åsberg Depression Rating Scale (MADRS) were associated with a stronger decrease of logIC IL-6 (indicating an increase of GR sensitivity). Higher baseline logEC IL-10 (indicating a lower GR sensitivity) and a stronger reduction of logEC IL-10 (indicating a stronger increase in GR sensitivity) were associated with a stronger decrease in the MADRS score. Patients with remitted MDD showed higher logIC TNF-α values (indicating lower GR sensitivity) in comparison to patients with a current MDD at baseline and follow-up. Initially low GR sensitivity measured ex vivo in peripheral blood cells that increases over the course of treatment could serve as a predictive marker for stronger improvement in depression severity.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7815576&blobtype=pdf
ISSN	03009564
Journal	Journal of Neural Transmission [J Neural Transm (Vienna)]
Volume Number	128
DOI	10.1007/s00702-020-02288-7
PubMed Central reference number	PMC7815576
Issue Number	1
PubMed reference number	33447872
e-ISSN	14351463
Language	English
Publisher	Springer Vienna
Publisher Date	2021-01-15
Publisher Place	Vienna
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021
Subject Keyword	Depression Glucocorticoid receptor Hypothalamic–pituitary–adrenal axis Cytokines
Content Type	Text
Resource Type	Article
Subject	Neurology Biological Psychiatry Neurology (clinical) Psychiatry and Mental Health