Variability and Magnitude of Choline Levels Across the Psychosis Spectrum: A Meta-analysis

Animal, post-mortem, and pharmacological studies suggest altered choline levels in psychosis. Proton magnetic resonance spectroscopy (1H-MRS) may allow in vivo investigation of the cholinergic system. This meta-analysis examined the magnitude and variability of 1H-MRS choline across the psychosis spectrum.

Following a pre-registered protocol (CRD42023403879), we searched MEDLINE, EMBASE, and PsycINFO for studies reporting 1H-MRS choline levels in individuals with psychosis, clinical high risk (CHR) states, and healthy controls. Standardized mean differences (SMDs) and log coefficient of variation ratios were pooled using random-effects meta-analysis, stratified by brain region and clinical subgroup. Meta-regression examined associations with imaging and clinical parameters.

We included 165 studies comprising 5178 patients and 4269 controls. Choline levels were elevated in people with psychosis in the anterior cingulate cortex (ACC: SMD = 0.23, CI 0.12-0.33), medial prefrontal cortex (mPFC: SMD = 0.12, CI 0.01-0.23), and dorsolateral prefrontal cortex (dlPFC: SMD = 0.15, CI 0.01-0.28). Elevations were also seen in CHR cohorts (ACC: SMD 0.19, CI 0.03-0.36; mPFC: SMD 0.36, CI 0.16-0.57), with the largest effects in treatment-resistant schizophrenia (ACC: SMD 0.65, CI 0.38-0.91; dlPFC: SMD 1.13, CI 0.65-1.60). Increased choline variability was observed in the dlPFC in psychosis cohorts and the mPFC and temporal lobe in CHR groups.

This is the largest meta-analysis of 1H-MRS choline in psychosis to date. Increased variability in psychosis and greater differences in treatment-resistant cohorts suggest increased choline levels might identify a subgroup who do not respond to dopamine antagonist treatment.