Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression
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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.
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Childhood maltreatment induces lasting low-grade inflammation through persistent activation of microglia and peripheral immune cells, resulting in increased release of pro-inflammatory cytokines and nitric oxide, alongside reduced neurotrophic support.
“Childhood maltreatment induces lasting low-grade inflammation through persistent activation of microglia and peripheral immune cells, resulting in increased release of pro-inflammatory cytokines and nitric oxide, alongside reduced neurotrophic support (80).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [80]
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- Authors
- Schiweck, C., Claes, S., Van Oudenhove, L., Lafit, G., Vaessen, T., de Beeck, G. O., Berghmans, R., Wijkhuijs, A., Müller, N., Arolt, V., Drexhage, H., & Vrieze, E.
- Affiliations
- Goethe University Frankfurt (DE)
- KU Leuven (BE)
- Advanced Practical Diagnostics (Belgium) (BE)
- Erasmus MC (NL)
- Ludwig-Maximilians-Universität München (DE)
- University of Münster (DE)
- Corresponding author
- Schiweck, Carmen
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2020-08-24
- Volume
- 10
- Issue
- 1
- Pages
- 296-296
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC7445278
- OpenAlex
- W3080862223
- Cited by
- 59
- References
- 78
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 16 · 2023: 8 · 2022: 14 · 2021: 11 · 2020: 1
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Funders
- EC | EC Seventh Framework Programm | FP7 Health (222963)
- EC | Horizon 2020 Framework Programme (754740)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, childhood adversity, childhood trauma, suicide risk, monocyte gene expression, inflammation, cytokines, interleukin-6, interleukin-1, glucocorticoid signaling, NR3C1, HSPA1, early life stress
- MeSH terms
- Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Monocytes, Phenotype, Suicide, Gene Expression
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