Glymphatic system alterations in schizophrenia evaluated by the DTI-ALPS index: A systematic review and meta-analysis

The glymphatic system has been extensively implicated in neurodegenerative diseases as a key pathway responsible for cerebral metabolic waste clearance. However, its role in schizophrenia remains poorly understood. This study aimed to evaluate glymphatic system function in patients with schizophrenia through a systematic review and meta-analysis.

A systematic literature search was conducted to identify studies investigating glymphatic dysfunction in schizophrenia. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) was used as a surrogate marker of glymphatic system function. PubMed, Web of Science, Scopus, and Embase were systematically searched for eligible studies published up to April 10, 2026. A total of eight high-quality studies were included in the final analysis. A random-effects model was applied to calculate pooled standardized mean differences (SMD) and corresponding effect sizes.

Meta-analysis showed that the DTI-ALPS index in schizophrenia patients was significantly lower compared to healthy controls (SMD = -2.42, 95% CI: -4.06 to -0.79) suggesting potential glymphatic dysfunction. Sensitivity analysis confirmed the robustness of the findings, and no publication bias was detected. Subgroup analyses indicated that disease stage significantly influenced DTI-ALPS indices.

The present findings indicate significant alterations in the DTI-ALPS index in schizophrenia, with disease stage closely associated with these alterations. These results suggest that alterations in the cerebral glymphatic system, as indexed by DTI-ALPS, may represent a potential neurobiological correlate underlying the pathological disturbances observed in schizophrenia.