ArticleBrain, behavior, and immunity2021
Depression and interleukin-6 signaling: A Mendelian Randomization study.
Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 3 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- A dual-database bibliometric analysis of post-COVID-19 condition and cognitive dysfunction (2021-2025).Frontiers in neurology · 2026Pooled it
- Circulating inflammatory proteins associated with risks of schizophrenia, bipolar disorder, and major depressive disorder: a mendelian randomization study.Translational psychiatry · 2025Pooled it
- Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.PLoS medicine · 2023Pooled it
- Does inflammation moderate the effect of vitamin D supplementation on depressive symptoms? Results of an interventional study in children and adolescents.European journal of nutrition · 2026Trial
- Effect of negative mood, serum inflammatory factors, miR-155, and brain-derived neurotrophic factor.World journal of psychiatry · 2025Trial
- Inflammation is associated with altered functional connectivity of the cingulate cortex in individuals with subthreshold depression.PLOS digital health · 2026Article
- Memory B Cells in Major Depressive Disorder: Toward Mechanistic and Clinical Refinement.Current medical science · 2026Article
- Targeting MAO-A With Ultrafast Kinetics: Affinity Probes for Precision Imaging of Brain Pathologies and Depression Biomarker Validation.Advanced healthcare materials · 2026Article
- Psychological Aspects of Rheumatic Diseases: Psychorheumatology in Clinical Practice.Rheumatology and therapy · 2026Review
- Nonlinear associations of plasma IL-9 with depression and anxiety symptoms in first-episode, drug-naïve major depressive disorder.European archives of psychiatry and clinical neuroscience · 2026Article
- Article
- Depressive symptoms mediate the associations between air pollution exposure and anemia risk: a nationwide longitudinal study in China.BMC public health · 2026Article
- Molecular mechanisms underlying psoriasis and depression: an integrated analysis using mendelian randomization, transcriptomics, and single-cell sequencing.Frontiers in molecular medicine · 2026Article
- Flow cytometry-based validation of soluble biomarker detection.Practical laboratory medicine · 2025Article
- Longitudinal trajectories of somatic and cognitive-affective depressive symptoms influence stroke risk across different populations: Three prospective cohort studies.World journal of psychiatry · 2025Article
- Mechanisms of oral ciprofloxacin-induced depressive-like behavior and the potential benefit of lactulose: A correlation analysis.Toxicology reports · 2025Article
- Molecular mechanisms and clinical value of the correlation between depression and cancer.Medical oncology (Northwood, London, England) · 2025Review
- Role of inflammation in depressive and anxiety disorders, affect, and cognition: genetic and non-genetic findings in the lifelines cohort study.Translational psychiatry · 2025Article
- The IL-6 autocrine loop promoting IFN-γ-induced fibroblast senescence is involved in psychological stress-mediated exacerbation of vitiligo.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Unusual Phospholipids fromJournal of the American Chemical Society · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundA large body of research has reported associations between depression and elevated interleukin-6 (IL-6), a cytokine with several roles including pro-inflammatory signaling. The nature and directionality of this relationship are not yet clear. In this study we use Mendelian Randomization to examine the possibility of a causal relationship between IL-6 and depressive symptoms, and to explore multiple signaling pathways that could serve as mechanisms for this relationship.
methodsThis study uses a two-sample Mendelian Randomization design. Data come from the UK Biobank (n = 89,119) and published summary statistics from six existing GWAS analyses. The primary analysis focuses on the soluble interleukin-6 receptor (sIL-6R), which is involved in multiple signaling pathways. Exploratory analyses use C-reactive protein (CRP) and soluble glycoprotein 130 (sgp130) to further examine potential underlying mechanisms.
resultsResults are consistent with a causal effect of sIL-6R on depression (PCA-IVW Odds Ratio: 1.023 (95% Confidence Interval: 1.006-1.039), p = 0.006). Exploratory analyses demonstrate that the relationship could be consistent with either decreased classical signaling or increased trans signaling as the underlying mechanism. DISCUSSION: These results strengthen the body evidence implicating IL-6 signaling in depression. When compared with existing observational and animal findings, the direction of these results suggests involvement of IL-6 trans signaling. Further study is needed to examine whether IL6R genetic variants might influence IL-6 trans signaling in the brain, as well as to explore other potential pathways linking depression and inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.