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Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis.
Jack B Fanshawe1,2, Cameron J Watson3,4,5, Valentina Mancini1,2,6
1Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Schizophrenia Bulletin
|May 11, 2026
Summary
This meta-analysis found elevated choline levels in the brain for individuals with psychosis, particularly in treatment-resistant cases. These findings suggest choline may help identify non-responders to dopamine antagonist treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Biomarkers
Background:
- Altered choline levels are implicated in psychosis based on animal, post-mortem, and pharmacological studies.
- Proton magnetic resonance spectroscopy (1H-MRS) offers a method for in vivo investigation of the brain's cholinergic system.
Purpose of the Study:
- To conduct a meta-analysis on the magnitude and variability of 1H-MRS choline levels across the psychosis spectrum.
- To investigate choline levels in individuals with psychosis, clinical high risk (CHR) states, and healthy controls.
Main Methods:
- A systematic search of MEDLINE, EMBASE, and PsycINFO was performed following a pre-registered protocol (CRD42023403879).
- Random-effects meta-analysis was used to pool standardized mean differences (SMDs) and log coefficient of variation ratios.
- Meta-regression was employed to examine associations with imaging and clinical parameters.
Main Results:
- 165 studies (5178 patients, 4269 controls) were included.
- Elevated choline levels were observed in the anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and dorsolateral prefrontal cortex (dlPFC) in individuals with psychosis.
- Significant elevations and increased variability were also noted in clinical high risk (CHR) states and treatment-resistant schizophrenia, with the largest effects in the ACC and dlPFC.
Conclusions:
- This meta-analysis represents the largest investigation of 1H-MRS choline in psychosis to date.
- Increased choline variability in psychosis and pronounced differences in treatment-resistant groups suggest choline may serve as a biomarker.
- Elevated choline levels could potentially identify a subgroup of patients unresponsive to dopamine antagonist therapy.
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