SynthesisMolecular psychiatry2025
Cholinergic system in schizophrenia: A systematic review and meta-analysis.
Synthesis in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis.Schizophrenia bulletin · 2026Pooled it
- Molecular and topographic mapping of antipsychotic effects: a meta-analysis of postsynaptic density proteins in animal models with translational implications.Molecular psychiatry · 2026Pooled it
- Apical integration theory provides a neural basis for understanding disorganization and consciousness in the schizophrenias.Current research in neurobiology · 2026Article
- Toward a Pluralistic Model for the Schizophrenia Spectrum-Dopamine and Beyond.JAMA psychiatry · 2026Review
- Xanomeline and Trospium Chloride: Mechanism of Action, Clinical, and Translational Science.Clinical and translational science · 2026Review
- Photopharmacological Cholinergic Modulation of Cortical Activity in Human Brain Slices.Brain sciences · 2026Article
- Functional Expression of Nicotinic Receptors on iPSC-Derived Astrocytes and Signalling Disturbances by a Panel of Neonicotinoid Pesticides and Their Metabolites.International journal of molecular sciences · 2026Article
- A Meta-Analysis of the Converging Effects of Different Classes of Antipsychotics on the Frontal Cortex Transcriptome in Laboratory Rodents and Non-Human Primates.bioRxiv : the preprint server for biology · 2026Article
- Lower Muscarinic MBiological psychiatry · 2026Article
- Natural Molecules for Brain Health and Resilience.International journal of molecular sciences · 2026Review
- Molecular Diversity and Functional Implications of Mammalian Choline Acetyltransferases in Neuronal and Non-Neuronal Cells.International journal of molecular sciences · 2026Review
- Clozapine Mitigates Lipopolysaccharide-Induced Cognitive Dysfunction by Modulating Cholinergic Function, Oxidative Stress, and Apoptotic Signaling in Rats.Life (Basel, Switzerland) · 2026Article
- Moderating Role of Cigarette Smoking on the Efficacy of tDCS in the Treatment of Negative and Cognitive Symptoms of Schizophrenia: Results from a Randomized Clinical Trial.Brain sciences · 2026Article
- Beyond dopamine: KarXT and emerging mechanism-based therapies in schizophrenia.Frontiers in psychiatry · 2026Review
- From dopamine to muscarine: xanomeline-trospium (KarXT) as a novel direction in the psychopharmacotherapy of schizophrenia.Frontiers in pharmacology · 2026Review
- Genetic risk for neurodevelopmental disorders as a potential factor affecting antipsychotic responsiveness in schizophrenia: a postmortem brain study.Frontiers in psychiatry · 2026Article
- Mapping Neurochemical Signatures onto Brain Structure for Neurotransmitter-Informed Discrimination of Schizophrenia Patients from Healthy Controls.medRxiv : the preprint server for health sciences · 2025Article
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- From heart to brain: cognitive potential of propranolol and diltiazem through cholinergic enhancement via butyrylcholinesterase inhibition.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND/
objectivesStudies have shown widespread alterations in different components of the cholinergic system in schizophrenia, but to date the evidence has not been systematically reviewed and summarized. Here, we systematically review imaging and post-mortem studies on the central cholinergic system in schizophrenia/schizoaffective disorder. SUBJECTS/
methodsSearches were performed in Embase and Medline. Study designs included cross-sectional case control studies comparing individuals with schizophrenia/schizoaffective disorder to control population. Risk of bias was assessed with the NIH/NHLBI tool for Quality Assessment of Case-Control Studies. The current study followed the PRISMA 2020 guidelines (PROSPERO: CRD42023402126).
resultsA total of 3259 studies were screened and 61 met eligibility criteria for the systematic review, including 8 in vivo neuroimaging and 53 post-mortem studies. About 74% of these studies described significant alterations, most often reductions in either muscarinic or nicotinic receptor levels in schizophrenia. We also conducted 3 meta-analyses showing reductions in M1/M4 muscarinic receptors in the striatum (g = -0.809, k = 3, n = 108), hippocampus (g = -0.872, k = 3, n = 84), and fronto-cingulate cortex (g = -0.438, k = 4, n = 295). Six neuroimaging studies reported associations with clinical symptom severity measures, and four investigations with cognitive dysfunction.
conclusionsOur review demonstrates a widespread decrease in muscarinic and nicotinic receptor levels in schizophrenia, evident in both neuroimaging and post-mortem studies. Our meta-analyses show large to moderate effects for the reductions in M1/M4 muscarinic receptors in the striatum, hippocampus, and fronto-cingulate cortex. Limitations and future directions for the field are discussed.
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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.