ArticleNature neuroscience2019
Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning.
Article in Nature neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 449 papers, 4 of them syntheses that pooled 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.
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
449 citing papers in PubMed, 4 syntheses or guidelines pooled it, 799 citations in OpenAlex.
- Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications.Molecular psychiatry · 2026Pooled it
- Convergent blood-brain barrier breakdown in schizophrenia and autism spectrum disorders: a systematic review of preclinical animal models.Fluids and barriers of the CNS · 2026Pooled it
- Inflammatory cytokine alterations in genetic and clinical high risk groups of psychosis: a systematic review and network meta-analysis.Psychological medicine · 2026Pooled it
- A systematic review and meta-analysis of neuroimaging studies examining synaptic density in individuals with psychotic spectrum disorders.BMC psychiatry · 2024Pooled it
- P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics.Brain : a journal of neurology · 2026Article
- miR-214-3p and NCKAP1: A microglial functional dimension of Alzheimer's progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Cerebrospinal fluid biomarkers reveal transdiagnostic synaptic dysfunction across major psychiatric disorders.Nature communications · 2026Article
- Genetically informed dissection of multimodal brain aging and ten major psychiatric disorders.Molecular psychiatry · 2026Article
- Integrative multi-omics reveals MHC class II-mediated neuroinflammation and systemic metabolic dysregulation as transdiagnostic drivers in major brain disorders.Translational psychiatry · 2026Article
- From Perinatal Stress to Schizophrenia: The Emerging Role of Glial Pathology.Annals of neurosciences · 2026Review
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Microglia-dependent regulation of fear memory extinction.Nature neuroscience · 2026Article
- Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Anti-Inflammatory Effects of Ginsenoside Rg1 and Low-Dose Ginseng Extract in an Astrocyte-Microglia Co-Culture Model of Inflammation.Pharmaceutics · 2026Article
389 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Synapse density is reduced in postmortem cortical tissue from schizophrenia patients, which is suggestive of increased synapse elimination. Using a reprogrammed in vitro model of microglia-mediated synapse engulfment, we demonstrate increased synapse elimination in patient-derived neural cultures and isolated synaptosomes. This excessive synaptic pruning reflects abnormalities in both microglia-like cells and synaptic structures. Further, we find that schizophrenia risk-associated variants within the human complement component 4 locus are associated with increased neuronal complement deposition and synapse uptake; however, they do not fully explain the observed increase in synapse uptake. Finally, we demonstrate that the antibiotic minocycline reduces microglia-mediated synapse uptake in vitro and its use is associated with a modest decrease in incident schizophrenia risk compared to other antibiotics in a cohort of young adults drawn from electronic health records. These findings point to excessive pruning as a potential target for delaying or preventing the onset of schizophrenia in high-risk individuals.
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.