The Prevalence of Schizophrenia and Bipolar Disorder in Multiple Sclerosis: A Systematic Review and Meta-Analysis

Schizophrenia (SCZ) and bipolar disorder (BD) have been investigated in people with multiple sclerosis, with findings varying in prevalence. Our aim was to determine the global pervasiveness of SCZ and BD in people with MS.

Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Searches were performed in PubMed, Google Scholar, Europe PubMed Central, and Web of Science from their inception through April 2025. R statistical software was used for sensitivity analysis, subgroup analysis, and meta-regression, which was employed to address heterogeneity.

The pooled prevalence of SCZ in people with MS was 0.61% (95% CI, 0.25%-1.11%), and BD was 3.34% (95% CI, 2.04%-4.91%). Leave-one-out analyses showed minimal to mild variation in both estimates. The prevalence of BD was higher in people with early-stage MS or moderate disability and varied by sex ratio. For both SCZ and BD, significant geographic differences were identified, with higher prevalence reported in the Americas and Europe. The study period influenced both SCZ and BD prevalences, although study design affected BD estimates and diagnostic approach influenced SCZ. The meta-regression identified study period, sample size, sex ratio, and diagnostic method as sources of heterogeneity in BD, although SCZ heterogeneity was driven by diagnostic method and prevalence type.

SCZ and BD are clinically relevant comorbidities in people with MS, with significant heterogeneity across studies driven by various factors. BD appears to be more prevalent in people with early-stage MS and in those with moderate disability. These findings highlight the need for standardized assessments and further studies.