STUDY PROTOCOL article
Front. Psychiatry
Sec. Schizophrenia
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1593211
Role of the Cholinergic System in the Psychopathology and Treatment of Schizophrenia: A Protocol for a Scoping Review
Provisionally accepted
- 1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Örebro, Sweden
- 2Clinical Trials Unit, Region Örebro County University Hospital, Örebro, Sweden
- 3Department of Psychiatry, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- 4Department of Clinical Neuroscience, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden
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The cholinergic system has broad implications for affective and cognitive processes, which makes it pertinent for the psychopathology and treatment of mental disorders. Questions concerning its role in schizophrenia, a chronic disorder characterized by psychosis, emotional blunting and cognitive deficits, have been made particularly relevant due to the recent Food and Drug Administration (FDA) approval of a muscarinic agonist as an antipsychotic agent. The present paper details the protocol for a scoping review that will map models, evidence and research gaps concerning the role of the cholinergic system in the positive, negative and cognitive domains implicated in the psychopathology of schizophrenia. The scoping review will be conducted according to JBI (formerly the Joanna Briggs institute) methodology, using articles from the following databases: PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials and PsycInfo. Two independent reviewers will screen the articles using title and abstract, after which full text-analysis will determine inclusion. Only published original peer-reviewed English-language studies from the last 20 years that pertain to the review objective will be included. Clinical studies will be assessed for methodological quality and risk of bias. The results, which the reviewers will extract independently of each other using a data extraction tool, will be presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocol Extension for Scoping Reviews (PRISMA-ScR). Clarifying the research gaps in the field can indicate where future pre-clinical and clinical studies and systematic reviews can be worthwhile, and the risk of bias assessment aids in this by stratifying the included clinical trials according to quality. However, the language and publication date restrictions risk excluding relevant studies, which can introduce bias.
Keywords: Acetylcholine, cholinergic, Cognition, emotion, Motivation, Schizophrenia, Scoping review
Received: 13 Mar 2025; Accepted: 07 May 2025.
Copyright: © 2025 Haczkiewicz, Hylén and Msghina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Michal Haczkiewicz, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, 701 82, Örebro, Sweden
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.