Schizophr Res. 2026 Jan 20;289:79-88. doi: 10.1016/j.schres.2026.01.010. Online ahead of print.
ABSTRACT
BACKGROUND: The glymphatic system’s role in early schizophrenia remains unclear. This study investigated glymphatic function using the DTI-ALPS index in first-episode schizophrenia (FES), exploring its relationships with clinical features, antipsychotic treatment, and cognitive function.
METHODS: The study included 37 first-episode drug-naïve (FESDN) patients, 22 first-episode treated (FEST) patients, and 42 demographically matched healthy controls (HCs). ALPS indices were calculated, and clinical assessments included cognitive function (RBANS), psychiatric symptoms (PANSS), and peripheral biomarkers.
RESULTS: FES patients exhibited left-hemisphere predominant reductions in ALPS indices (p < 0.01). An interaction was observed between disease duration and treatment: the FEST group had lower DTI-ALPS than the FESDN group in patients with shorter illness durations, but this group difference diminished with longer disease duration (βinter = -0.8 × 10-2, p < 0.05). The ALPS-cognition association pattern differed between patients and HCs: left ALPS was positively correlated with RBANS in HCs (βHC > 0, p < 0.01) but negatively correlated in FES patients (βFESDN = -16.6, βFEST = -21.6, p < 0.1). Peripheral white blood cell count and total bilirubin were negatively associated with left ALPS in the FEST group (WBC: β = -0.63 × 10-2, p = 0.025; TBIL: β = -0.80 × 10-2, p = 0.039), with significant group interaction effects (p < 0.05).
CONCLUSION: FES patients demonstrate left-lateralized glymphatic dysfunction, the severity of which is dynamically modulated by treatment and disease duration. The observed negative ALPS‑cognition correlation raises the possibility of a compensatory mechanism in early schizophrenia. Associations noted between peripheral inflammatory/metabolic markers and ALPS offer tentative support for an interactive “periphery-brain” clearance system. DTI-ALPS may serve as a dynamic biomarker reflecting neuropathological mechanisms in early schizophrenia.
PMID:41564498 | DOI:10.1016/j.schres.2026.01.010
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