Glymphatic dysfunction is linked to brain aging in schizophrenia

In people with schizophrenia, impaired glymphatic clearance is tied to inflammation and accelerated aging, according to a preprint combining in vivo neuroimaging with post-mortem single-nucleus transcriptomics. Researchers analyzed distinct patient cohorts and identified reduced astrocytic expression of SNTA1 and DAG1, components needed for aquaporin-4 polarization. Markers of glymphatic dysfunction appeared only in an inflammatory subgroup marked by peripheral immune activation and pro-inflammatory glial transcription. In vivo imaging markers of glymphatic impairment were linked to cognitive dysfunction and polygenic risk scores enriched for immune- and oxidative stress-related aging pathways. At the cellular level, this impairment coincided with lost homeostatic microglia and astrocyte programs, elevated inflammatory signaling, and endothelial signatures of blood-brain barrier disruption. Across modalities, glymphatic dysfunction was associated with higher brain and epigenetic age.