Enlarged brain perivascular spaces in chronic schizophrenia but not in first-episode psychosis: a cross-sectional study

Abstract Enlarged perivascular spaces (EPVS) are MRI-visible markers associated with glymphatic system function and brain waste clearance, and are thought to reflect neurovascular, neuroinflammatory, and age-related changes. While schizophrenia is associated with neuroinflammation and accelerated brain aging, little is known about metabolic brain waste clearance in the condition. Moreover, whether EPVS burden differs across stages of disease is unclear. This study aimed to compare EPVS in the centrum semiovale (CSO) and basal ganglia (BG) among individuals with schizophrenia, first-episode psychosis (FEP), and healthy controls, with a total of 174 subjects included. EPVS were quantified using high-resolution 3T MRI and a standardized rating scale, with assessments conducted by three independent raters. Ordinal logistic regression showed higher odds of being in a higher CSO-EPVS category in chronic schizophrenia versus healthy controls (OR 2.31, 95% CI 1.15–4.62, p = 0.02), as well as higher total EPVS burden (OR 2.02, 95% CI 1.04–3.93, p = 0.04), while no significant group differences were observed for BG-EPVS or between FEP and healthy controls. These findings suggest regional and group-specific differences in EPVS burden, with greater burden in chronic schizophrenia primarily reflected by CSO-EPVS rather than BG-EPVS. This study emphasizes the potential role of neurovascular and neuroinflammatory processes in schizophrenia, aligning with evidence of accelerated brain aging in the disorder.