Evidence map›Paper›PMID 26065825›Full record

SynthesisBrain, behavior, and immunity2015

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.

Rita Haapakoski, Julia Mathieu, Klaus P Ebmeier, Harri Alenius, Mika Kivimäki

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Brain, behavior, and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 562 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
562citing papers in PubMed, 10 pooled it
20.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

562 citing papers in PubMed, 10 syntheses or guidelines pooled it, 1,082 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. The Impact ofCurrent neuropharmacology · 2025
    Pooled it
  10. Pooled it
  11. Trial
  12. Trial
  13. Plasma proteomic profile of inflammatory depressive symptoms.Brain, behavior, & immunity - health · 2026
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

502 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

Rita HaapakoskiDepartment of Epidemiology and Public Health, University College London, London, UK; Finnish Institute of Occupational Health, Systems Toxicology Unit, Centre of Expertise for Health and Work Ability, Helsinki, Finland; Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. Electronic address: r.haapakoski@ucl.ac.uk.
Julia MathieuDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK; Université Pierre et Marie Curie, Paris, France.
Klaus P EbmeierDepartment of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Harri AleniusFinnish Institute of Occupational Health, Systems Toxicology Unit, Centre of Expertise for Health and Work Ability, Helsinki, Finland.
Mika KivimäkiDepartment of Epidemiology and Public Health, University College London, London, UK; Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Finnish Institute of Occupational Health · FIWarneford Hospital · GBUniversity of Helsinki · FI

Funding

Medical Research Council G1001354Medical Research Council K013351Medical Research Council MR/K013351/1
6 · The paper itself

Abstract

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=-0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.

Indexed as

AdultC-Reactive ProteinFemaleHumansInflammationInflammation MediatorsInterleukin-1betaInterleukin-6Major Depressive DisorderMaleTumor Necrosis Factor-alphaC-Reactive ProteinInflammation MediatorsInterleukin-1betaInterleukin-6Tumor Necrosis Factor-alphaC-reactive proteinCumulative meta-analysisInflammationInterleukin-1βInterleukin-6Major depressionTumour necrosis factor-α

Identifiers

PMID26065825
PMCPMC4566946
OpenAlexW581977681

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.