Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression

  • Circulating monocytes contribute to inflammatory processes. We here validate abnormal expression of inflammation-related genes in monocytes of a large and well-characterised group of MDD patients, and relate the outcomes to pertinent clinical characteristics. Thirty-two genes of a previously established inflammation-related gene signature were assessed in 197 patients with MDD, and 151 controls collected during the EU-MOODINFLAME project. Monocyte gene- expression data were related to age, sex, BMI, depression severity, childhood adversity (CA) and suicide risk (SR). Three distinct gene profiles were identified within the MDD group (downregulated, mixed upregulated and strongly upregulated genes). Patients in the merged upregulated groups had a significantly higher prevalence of CA and high SR. Using hierarchical clustering of the genes, we found a cluster of mainly cytokine (production)-related genes; patients with SR had a significantly higher expression of this cluster than patients without SR (particularly for IL-6, IL1A and IL1B). Such difference did not emerge for patients with and without CA. A downregulated gene profile was found for patients not exposed to CA and without SR (particularly for glucocorticoid-signalling genes NR3C1a and HSPA1/B). No inflammatory changes were observed for healthy controls exposed to CA. Our data show that inflammatory activation in MDD is not uniform, and that immunologically discernible phenotypes of depression can be linked to CA and high SR. The absence of monocyte inflammatory activation in healthy controls exposed to CA suggests an inflammatory involvement in MDD-prone individuals exposed to early stressors, but not healthy controls.
Author:Carmen SchiweckORCiD, Stephan ClaesORCiD, Lukas van OudenhoveORCiD, Ginette LafitORCiD, Thomas VaessenORCiDGND, Gommaar op de BeeckORCiD, Raf Berghmans, Annemarie Wijkhuijs, Norbert MüllerGND, Volker AroltORCiDGND, Hemmo DrexhageORCiD, Elske VriezeORCiD
Parent Title (English):Translational Psychiatry
Publisher:Nature Publishing Group
Place of publication:London
Document Type:Article
Date of Publication (online):2020/08/24
Date of first Publication:2020/08/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/01/12
Tag:Clinical genetics; Depression; Human behaviour
Issue:art. 296
Article Number:296
Page Number:12
First Page:1
Last Page:12
This study was funded by the EU MOODINFLAME (grant agreement number 222963) and H2020 EU MODDTSRATIFICATION (grant agreement number 754740) projects.
Open Access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:1 Philosophie und Psychologie / 15 Psychologie / 150 Psychologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0