ArticleMolecular psychiatry2009
Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia.
Article in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05105542 (Muscarinic M1 Receptor Availability and Cognition in Schizophrenia), which is not on this map. Cited by 66 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.
Muscarinic M1 Receptor Availability and Cognition in Schizophrenia
Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis.Schizophrenia bulletin · 2026Pooled it
- Cholinergic system in schizophrenia: A systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Trial
- Toward a Pluralistic Model for the Schizophrenia Spectrum-Dopamine and Beyond.JAMA psychiatry · 2026Review
- Global perspectives on central nervous system drug innovation: achievements, barriers, and priorities for the next decade.The international journal of neuropsychopharmacology · 2026Review
- Xanomeline-Trospium Validates Muscarinic Agonism as an Effective Non-Dopaminergic Treatment for Schizophrenia.International journal of molecular sciences · 2026Review
- Lower Muscarinic MBiological psychiatry · 2026Article
- Beyond dopamine blockade: mechanistic humility and the rise of muscarinic, TAAR1, and glutamatergic pathways in schizophrenia.Frontiers in psychiatry · 2026Article
- The mechanism of action and clinical efficacy of xanomeline-trospium in schizophrenia: A comprehensive review.Therapeutic advances in psychopharmacology · 2026Review
- Xanomeline-trospium: defining its place among the current antipsychotic landscape.Acta neuropsychiatrica · 2025Review
- From theory to therapy: unlocking the potential of muscarinic receptor activation in schizophrenia with the dual M1/M4 muscarinic receptor agonist xanomeline and trospium chloride and insights from clinical trials.The international journal of neuropsychopharmacology · 2025Review
- The Many Roles of Precision in Action.Entropy (Basel, Switzerland) · 2024Review
- Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies.International journal of molecular sciences · 2023Review
- Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment.Molecular psychiatry · 2023Review
- Domesticated HERV-W env contributes to the activation of the small conductance CaVirologica Sinica · 2023Article
- Editorial: Diagnostic and prognostic brain-based biomarkers in psychosis spectrum.Frontiers in psychiatry · 2023Article
- A growing understanding of the role of muscarinic receptors in the molecular pathology and treatment of schizophrenia.Frontiers in cellular neuroscience · 2023Review
- Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis.Translational psychiatry · 2022Article
- Statelets: Capturing recurrent transient variations in dynamic functional network connectivity.Human brain mapping · 2022Article
- Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.Biomedicines · 2022Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [(3)H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [(3)H]pirenzepine binding in BA9 divided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [(3)H]pirenzepine binding compared to controls. We suggest that these individuals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging.
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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.