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Record W4410537865 · doi:10.1038/s41380-025-03023-y

Cholinergic system in schizophrenia: A systematic review and meta-analysis

2025· review· en· W4410537865 on OpenAlexafffund
Zacharie Saint-Georges, Julia R. MacDonald, Roya Al-Khalili, Rami Hamati, Marco Solmi, Matcheri S. Keshavan, Lauri Tuominen, Synthia Guimond

Bibliographic record

VenueMolecular Psychiatry · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicReceptor Mechanisms and Signaling
Canadian institutionsCarleton UniversityOttawa HospitalRoyal Ottawa Mental Health CentreUniversité du Québec en OutaouaisUniversity of Ottawa
FundersCanadian Institutes of Health ResearchGovernment of Canada
KeywordsMeta-analysisSchizophrenia (object-oriented programming)CholinergicPsychologyNeuroscienceCholinergic systemPsychosisMEDLINEMedicinePsychiatryInternal medicineBiology

Abstract

fetched live from OpenAlex

BACKGROUND/OBJECTIVES: Studies 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/METHODS: Searches 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). RESULTS: A 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. CONCLUSIONS: Our 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.010
metaresearch head score (Gemma)0.023
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.016
Threshold uncertainty score0.054

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0100.023
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0160.028
Bibliometrics0.0090.009
Science and technology studies0.0010.001
Scholarly communication0.0030.002
Open science0.0020.002
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0050.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.299
Teacher spread0.282 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations14
Published2025
Admission routes2
Has abstractyes

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