ReviewTranslational psychiatry2021
Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia.
Review in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07759895 (Combination Therapy of Deferiprone and N-Acetylcysteine for Treating Negative Symptoms in Schizophrenia), which is not on this map. Cited by 56 papers, 5 of them syntheses that pooled it.
What it found
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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.
Combination Therapy of Deferiprone and N-Acetylcysteine for Treating Negative Symptoms in Schizophrenia
Who cites it
56 citing papers in PubMed, 5 syntheses or guidelines pooled it, 99 citations in OpenAlex.
- Mitochondrial Dysfunction and Cognitive Impairment in Schizophrenia: The Role of Inflammation.Schizophrenia bulletin · 2025Pooled it
- The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects.Frontiers in cellular neuroscience · 2024Pooled it
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.Molecular neurobiology · 2022Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- Co-expression-based models improve eQTL predictions for transcriptome-wide association studies and highlight new schizophrenia-associated genes.Nature genetics · 2026Article
- Neuroinflammation: an unfortunate term to describe schizophrenia.Molecular psychiatry · 2026Review
- The Hidden Architecture of Brain Structural Variability in 22q11.2 Deletion Syndrome: A Multi-site Study.medRxiv : the preprint server for health sciences · 2026Article
- Magnetic resonance texture alterations in the caudate nucleus following 18 weeks of clozapine treatment in patients with treatment-resistant schizophrenia.Translational psychiatry · 2026Article
- Why is schizophrenia a huge graveyard of molecules?Schizophrenia (Heidelberg, Germany) · 2025Article
- Oxidative Stress-Mediated Neuroinflammation in the Pathophysiology of Schizophrenia.International journal of molecular sciences · 2025Review
- Acute and Long-Term Consequences of Neonatal NMDA Blockade in the Cx3cr1 Knock-Out Mouse.Inflammation · 2025Article
- The Potential of Hair Matrix for Biomarker Analysis in Schizophrenia.International journal of molecular sciences · 2025Review
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- Cell-free DNA in extracellular vesicles: A candidate biomarker of schizophrenia.World journal of psychiatry · 2025Review
- Circadian clock genes and cell survival in bipolar disorder: Insights into lithium responsiveness and molecular mechanisms in patient-derived neural progenitor cells and mouse neurons.The FEBS journal · 2025Article
- Mitochondrial Oxidative Phosphorylation System Dysfunction in Schizophrenia.International journal of molecular sciences · 2025Review
- Transcriptional Regulators in the Cerebellum in Chronic Schizophrenia: Novel Possible Targets for Pharmacological Interventions.International journal of molecular sciences · 2025Article
- Ultrastructural disturbances in microglia-neuron interactions in the head of the caudate nucleus in schizophrenia.European archives of psychiatry and clinical neuroscience · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia disorder remains an unsolved puzzle. However, the integration of recent findings from genetics, molecular biology, neuroimaging, animal models and translational clinical research offers evidence that the synaptic overpruning hypothesis of schizophrenia needs to be reassessed. During a critical period of neurodevelopment and owing to an imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, a regionally-located glutamate storm might occur, triggering excessive dendritic pruning with the activation of local dendritic apoptosis machinery. The apoptotic loss of dendritic spines would be aggravated by microglia activation through a recently described signaling system from complement abnormalities and proteins of the MHC, thus implicating the immune system in schizophrenia. Overpruning of dendritic spines coupled with aberrant synaptic plasticity, an essential function for learning and memory, would lead to brain misconnections and synaptic inefficiency underlying the primary negative symptoms and cognitive deficits of schizophrenia. This driving hypothesis has relevant therapeutic implications, including the importance of pharmacological interventions during the prodromal phase or the transition to psychosis, targeting apoptosis, microglia cells or the glutamate storm. Future research on apoptosis and brain integrity should combine brain imaging, CSF biomarkers, animal models and cell biology.
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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.