Prevalence of covert cerebrovascular changes in schizophrenia: A systematic review and meta-analysis

Covert cerebrovascular changes, particularly cerebral small vessel disease (CSVD) and silent brain infarction (SBI), may contribute to neurobiological vulnerability in schizophrenia but remain underrecognized. This meta-analysis aimed to estimate their prevalence and identify associated demographic and clinical factors.

Systematic searches of international and Chinese databases (through December 2024) were conducted to identify studies reporting CSVD and SBI prevalence in schizophrenia. Pooled prevalence estimates, sensitivity analyses, subgroup analyses, and meta-regressions were performed.

From 6371 records, 124 studies (11,611 patients) were included. Pooled prevalence was: white matter hyperintensities (WMH) 26.3% (95% CI: 16.8-38.8), perivascular spaces 45.7% (95% CI: 1.3-98.2), brain atrophy (BA) 34.8% (95% CI: 31.0-38.8), and SBI 12.8% (95% CI: 6.2-24.7). Lacune ranged from 2.5% to 12.5%, and one study reported cortical superficial siderosis at 4.4%. Subgroup analyses indicated that age, imaging modality, exclusion of stroke/diabetes, and study region may influence prevalence. Meta-regression showed associations of BA prevalence with older age, family history, and more recent publication year. BA prevalence was significantly higher in patients than controls (PR = 6.5), whereas differences for WMH (PR = 1.3) and SBI (PR = 2.0) were not statistically significant.

This meta-analysis synthesizes neuroimaging evidence on covert cerebrovascular changes in schizophrenia. WMH, SBI, and BA are frequently reported, although pooled estimates are highly heterogeneous. Case-control comparisons indicate a robust elevation in BA, whereas evidence for increased WMH or SBI relative to controls remains inconclusive. STRIVE-based definitions and systematic vascular risk assessment are needed to test schizophrenia-specific associations with covert vascular lesions.