Systematic review shows high prevalence of covert cerebrovascular changes in schizophrenia patients compared to controls

This systematic review and meta-analysis examined the prevalence of covert cerebrovascular changes in patients with schizophrenia. The study pooled data from international and Chinese databases involving a total sample size of 11,611 participants. The population included patients with schizophrenia and control subjects. The primary outcomes assessed included white matter hyperintensities, perivascular spaces, brain atrophy, silent brain infarction, lacunes, and cortical superficial siderosis. The review utilized STRIVE-based definitions to categorize these vascular markers.

The analysis reported specific prevalence rates for various covert cerebrovascular changes within the schizophrenia population. White matter hyperintensities were observed in 26.3% of patients, with a 95% confidence interval of 16.8% to 38.8%. Perivascular spaces were found in 45.7% of cases, showing a wide 95% confidence interval ranging from 1.3% to 98.2%. Brain atrophy prevalence was 34.8%, with a 95% confidence interval of 31.0% to 38.8%. Silent brain infarction was present in 12.8% of patients, with a 95% confidence interval of 6.2% to 24.7%. Lacunes were reported in a range of 2.5% to 12.5%. Cortical superficial siderosis was observed in 4.4% of the cohort.

When comparing prevalence rates between patients with schizophrenia and controls, brain atrophy showed a significantly higher prevalence in the patient group. The pooled ratio for brain atrophy was 6.5. In contrast, white matter hyperintensities showed a pooled ratio of 1.3, which was not statistically significant. Similarly, silent brain infarction prevalence was not statistically significant between groups, with a pooled ratio of 2.0. The review noted that associations of brain atrophy prevalence were linked to older age, family history, and more recent publication year.

Safety and tolerability findings were not reported in this meta-analysis. Adverse events, serious adverse events, discontinuations, and overall tolerability data were not available for review. The study did not report specific adverse event rates or discontinuation reasons. This lack of safety data is a notable gap in the current evidence base regarding covert cerebrovascular changes in this population.

The evidence for increased white matter hyperintensities or silent brain infarction relative to controls remains inconclusive. Pooled estimates are highly heterogeneous, which limits the ability to draw firm conclusions about specific vascular lesions. The associations of brain atrophy prevalence with older age and family history suggest that these factors may influence the observed rates. More recent publication years were also associated with higher prevalence estimates in the pooled data.

Practice relevance suggests that STRIVE-based definitions and systematic vascular risk assessment are needed to test schizophrenia-specific associations with covert vascular lesions. Current data cannot definitively establish causality or confirm a specific vascular burden unique to schizophrenia without further standardized investigation. Clinicians should interpret these prevalence rates with caution given the heterogeneity of the pooled estimates.

Several questions remain unanswered regarding the clinical implications of these findings. The lack of safety data and the inconclusive nature of comparisons with controls limit immediate practice changes. Future research must address the heterogeneity of pooled estimates and clarify the role of confounding factors like age and family history. Until then, these findings should inform research directions rather than alter standard clinical management protocols.