Glymphatic system dysfunction in chronic schizophrenia: A comparison between risperidone combined with clozapine and...

Despite documented brain alterations in chronic schizophrenia patients on risperidone or clozapine, differences in their effects on glymphatic function remain unclear. This study compared glymphatic function between chronic schizophrenia patients receiving risperidone combined with clozapine (RCT-SZ) and risperidone monotherapy (RT-SZ), and explored its associations with clinical characteristics.

The study included 37 RCT-SZ, 30 RT-SZ, and 36 healthy controls (HC). All participants underwent diffusion tensor imaging (DTI), and the DTI-ALPS index was calculated. Using age, sex, education, smoking status, and BMI as covariates, analysis of covariance with post-hoc tests was employed to compare the ALPS index among the three groups. Interactions between group and clinical variables were examined using general linear models, and correlations between ALPS indices and clinical characteristics were analyzed.

Compared with the HC group, both the RCT-SZ and RT-SZ groups showed significantly decreased DTI-ALPS index. Compared with the RT-SZ group, the RCT-SZ group had significantly lower bilateral mean ALPS index and left hemisphere ALPS index. Correlation analyses revealed that the bilateral mean ALPS index and the left hemisphere ALPS index were negatively correlated with cognitive function.

Patients with schizophrenia treated with risperidone combined with clozapine exhibited a lower ALPS index than those receiving risperidone monotherapy, and the ALPS index was correlated with cognitive performance. This non-invasive imaging approach provides a potential basis for estimating glymphatic function in patients receiving different antipsychotic regimens.