Evidence map›Paper›PMID 33410555›Full record

SynthesisGlia2021

A loss of mature microglial markers without immune activation in schizophrenia.

Gijsje J L J Snijders, Welmoed van Zuiden, Marjolein A M Sneeboer, Amber Berdenis van Berlekom, Astrid T van der Geest, Tatiana Schnieder, Donald J MacIntyre, Elly M Hol, René S Kahn, Lot D de Witte

Open access · hybridAbstract readMeta-Analysis
In one paragraph

Synthesis in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 3 pooled it
5.4field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 69 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Does a monoclonal antibody targeting immune cells affect glutamatergic level in schizophrenia? A multimodal PET/MRS brain imaging study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  12. Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
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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

10 authors at 7 institutions in 3 countries.

Gijsje J L J SnijdersDepartment of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), Utrecht, The Netherlands.ORCID 0000-0002-2694-1234
Welmoed van ZuidenDepartment of Psychiatry, Icahn School of Medicine, New York, New York, USA.
Marjolein A M SneeboerDepartment of Translational Neuroscience (BCRM-UMCU-UU), Utrecht, The Netherlands.
Amber Berdenis van BerlekomDepartment of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), Utrecht, The Netherlands.
Astrid T van der GeestDepartment of Translational Neuroscience (BCRM-UMCU-UU), Utrecht, The Netherlands.
Tatiana SchniederDepartment of Psychiatry, Columbia University, New York, New York, USA.
Donald J MacIntyreDivision of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Elly M HolDepartment of Translational Neuroscience (BCRM-UMCU-UU), Utrecht, The Netherlands.
René S KahnDepartment of Psychiatry, Icahn School of Medicine, New York, New York, USA.
Lot D de WitteDepartment of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University (BCRM-UMCU-UU), Utrecht, The Netherlands.
Utrecht University · NLCenter for Translational Molecular Medicine · NLColumbia University · USIcahn Enterprises (United States) · USJames J. Peters VA Medical Center · USNetherlands Institute for Neuroscience · NLUniversity of Edinburgh · GB

Funding

Medical Research Council MR/L016400/1
6 · The paper itself

Abstract

Microglia, the immune cells of the brain, are important for neurodevelopment and have been hypothesized to play a role in the pathogenesis of schizophrenia (SCZ). Although previous postmortem studies pointed toward presence of microglial activation, this view has been challenged by more recent hypothesis-driven and hypothesis-free analyses. The aim of the present study is to further understand the observed microglial changes in SCZ. We first performed a detailed meta-analysis on studies that analyzed microglial cell density, microglial morphology, and expression of microglial-specific markers. We then further explored findings from the temporal cortex by performing immunostainings and qPCRs on an additional dataset. A random effect meta-analysis showed that the density of microglial cells was unaltered in SCZ (ES: 0.144 95% CI: 0.102 to 0.390, p = .250), and clear changes in microglial morphology were also absent. The expression of several microglial specific genes, such as CX3CR1, CSF1R, IRF8, OLR1, and TMEM119 was decreased in SCZ (ES: -0.417 95% CI: -0.417 to -0.546, p < .0001), consistent with genome-wide transcriptome meta-analysis results. These results indicate a change in microglial phenotype rather than density, which was validated with the use of TMEM119/Iba1 immunostainings on temporal cortex of a separate cohort. Changes in microglial gene expression were overlapping between SCZ and other psychiatric disorders, but largely opposite from changes reported in Alzheimer's disease. This distinct microglial phenotype provides a crucial molecular hallmark for future research into the role of microglia in SCZ and other psychiatric disorders.

Indexed as

Alzheimer DiseaseSchizophreniaBiomarkersBrainGene Expression ProfilingHumansMicrogliaBiomarkersgene expressionimmunologymicrogliapostmortemschizophrenia

Identifiers

PMID33410555
PMCPMC7986895
OpenAlexW3118945957

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.