Disruption of prefrontal and superior temporal gyrus white matter networks in antipsychotic-treated schizophrenia with comorbid metabolic syndrome.

Background: Metabolic syndrome (MS) is a frequent comorbidity in schizophrenia, yet the characteristics of white matter (WM) network alterations in this subgroup remain largely unknown. This study examined distinctive WM structural network disruptions in schizophrenia patients with comorbid MS and explored whether these alterations mediate the relationship between schizophrenia and metabolic abnormalities. Methods: Twenty-six schizophrenia patients with MS (SZ-MS), twenty-two without MS (SZ-nMS), and twenty-four age- and sex-matched healthy controls (HC) underwent diffusion tensor imaging. Individual WM structural networks were constructed, and group differences in connectivity and topological organization were analyzed using network-based statistics and graph theory, controlling for age and sex. Results: Both SZ-MS and SZ-nMS patients exhibited reduced FA-weighted connectivity in prefrontal, parietal, and temporal cortices, thalamus, and hippocampus compared to HC. Relative to SZ-nMS, the SZ-MS group exhibited significant reduction in prefrontal FA-weighted connectivity. Topological metrics revealed global and nodal disruptions in both patient groups, notably in prefrontal cortex, bilateral thalamus, supramarginal gyrus, left precuneus, and right superior temporal gyrus. The SZ-MS group demonstrated greater nodal efficiency impairments in prefrontal and right superior temporal gyrus regions. Further exploratory analyses revealed that WM network metrics correlated with triglycerides, BMI, waist circumference, hip circumference, and fasting glucose. Additionally, reduced nodal efficiency in the right superior temporal gyrus exhibited a potential mediating pathway between SZ-MS and elevated BMI. Conclusion: These findings indicate that SZ-MS patients display characteristic WM network disruptions, predominantly in prefrontal and right superior temporal areas. These alterations are associated with metabolic abnormalities, providing neuroimaging evidence that may clarify the neuropathological mechanisms connecting schizophrenia and metabolic dysfunction.