ArticleBrain and behavior2026
Elucidating Immune Cell Mediated Causal Pathways Linking Blood Metabolites to Major Depressive Disorder: A Mediation Mendelian Randomization Analysis.
Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundMetabolic and immune alterations have been reported in patients with major depressive disorder (MDD), yet the biological pathways linking these changes to MDD remain incompletely understood. This study aims to examine the association between blood metabolites and the risk of MDD, investigate the mediating role of immune cells, and explore their causal relationships.
methodsWe analyzed genome-wide association study (GWAS) summary statistics for 1400 circulating metabolites and 731 immune-cell traits, together with an MDD GWAS comprising 135,458 cases and 344,901 controls, all obtained from the GWAS Catalog and the Psychiatric Genomics Consortium. Causal effects of each metabolite on MDD were estimated with seven Mendelian randomization (MR) approaches: inverse variance weighted, MR-Egger, weighted median, debiased inverse variance weighted method (IVW), Bayesian weighted MR, Mendelian randomization robust adjusted profile score (MR-RAPS), and constrained maximum likelihood and model averaging. Horizontal pleiotropy was evaluated with Mendelian Randomization Pleiotropy RESidual Sum and Outlier method (MR-PRESSO), RadialMR, and the MR-Egger intercept, whereas Cochran's Q statistic and leave-one-out analyses assessed heterogeneity and sensitivity. Finally, MR-based mediation analysis quantified the extent to which immune-cell traits mediate the metabolite-MDD associations.
resultsMR analyses provided evidence consistent with potential causal effects of 10 metabolites, including 1-(1-enyl-stearoyl)-2-linoleoyl-GPE, 2-linoleoylglycerol, kynurenine, spermidine-to-histidine ratio, 1-linoleoylglycerol, 4-vinylguaiacol sulfate, dopamine 4-sulfate, N-acetyl-aspartyl-glutamate, sphingomyelin and taurine to glutamate ratio and MDD. Mediation analyses identified three immune-cell-mediated pathways: CD8dim T cells mediated 5% of the effect of 2-linoleoylglycerol on MDD risk; CD11b expression on basophils mediated 19% of the effect of dopamine 4-sulfate on MDD risk; and CD4 expression on resting regulatory CD4 T cells mediated 14% of the effect of the spermidine-to-histidine ratio on MDD risk.
conclusionOur findings suggest that specific metabolites may affect the risk of MDD via immune-related pathways.
Indexed as
Identifiers
What OpenQuestion holds
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.