Assessing glymphatic function in schizophrenia and mood disorders: Insights from a diffusion tensor image along the perivascular space (DTI-ALPS) and neuroanatomical correlations.

Psychiatry and clinical neurosciences 2026

Zhu JD, Liao DL, Lin CP, Yang AC, Tsai HJ, Chang HI, Chang CC, Huang CY, Tsai SJ

Abstract

AIM: This study compared the diffusion tensor image along the perivascular space (DTI-ALPS) index among individuals with schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), and normal controls. We also examined associations between the ALPS index, gray matter volume (GMV), cognitive performance, and clinical symptom severity to evaluate its potential as a biomarker of neurobiological alterations in psychiatric disorders. METHODS: Participants were recruited from the Taiwan Aging and Mental Illness cohort. Group differences in ALPS indices were tested with analysis of covariance (ANCOVA) controlling for age and sex. General linear regression assessed correlations between ALPS indices and GMV. We performed partial correlations to evaluate the associations between ALPS indices and cognitive tests, as well as clinical symptoms. RESULTS: All psychiatric groups showed significantly lower ALPS indices compared with normal controls, with schizophrenia exhibiting the greatest reduction. Higher ALPS indices in schizophrenia were associated with larger GMV in the bilateral cerebellum and fusiform gyri and with better cognitive performance. In the BD group, the ALPS index was positively associated with left hippocampal volume and cognitive test and negatively associated with depression and anxiety severity. The MDD group showed a reduced ALPS index but did not exhibit significant associations with GMV or cognitive tests. CONCLUSION: The ALPS index may reflect glymphatic dysfunction across psychiatric disorders and relate to brain structure and clinical characteristics. These findings support its potential as an indirect biomarker of neurobiological alterations. Further research using direct glymphatic imaging is needed to clarify the mechanistic role of glymphatic function in psychiatric disorders.

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