Man Xu ¹ Kangkang Xue ¹ Xueqin Song ² Yong Zhang ¹ Jingliang Cheng ^1* Junying Cheng ^1*

• ¹ Department of Magnetic Resonance Imaging, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ² Department of Psychiatry, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

Background and objective: Peak width of skeletonized mean diffusivity (PSMD) is a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage. However, its application in schizophrenic disease remains unexplored. This study aims to investigate PSMD along with other DTI markers in first-episode schizophrenia patients compared to healthy controls (HCs), and explore the correlations between these metrics and clinical characteristics. Methods: A total of 56 first-episode schizophrenia patients and 64 HCs were recruited for this study. Participants underwent structural imaging and DTI, followed by comprehensive clinical assessments, including the Positive and Negative Syndrome Scale (PANSS) for patients and cognitive function tests for all participants. We calculated PSMD, peak width of skeletonized fractional anisotropy (PSFA), axial diffusivity (PSAD), radial diffusivity (PSRD) values, skeletonized average MD/FA/AD/RD values and network global topological parameters, and examined between-group differences in these metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics. Results: Compared to HCs, patients exhibited significantly increased PSMD values (t = 2.467, p = 0.015), decreased global efficiency (Z = −2.188, p = 0.029), and increased normalized characteristic path length (lambda) (t = 2.270, p = 0.025). No significant differences were observed between groups in PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity or hierarchy (p > 0.05). Both PSMD and lambda values exhibited a significant negative correlation with reasoning and problem-solving scores (PSMD: r = −0.409, p = 0.038; lambda: r = −0.520, p = 0.006). No statistically significant correlations were observed between each PANSS score and the aforementioned metrics in patients (p > 0.05). Multivariate linear regression analysis revealed that increased PSMD (β = −0.426, t = −2.260, p = 0.034) and increased lambda (β = −0.490, t = −2.994, p = 0.007) were independently associated with decreased reasoning and problem-solving scores respectively (R2adj = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR>0.05). Conclusion: PSMD can be considered as a valuable neuroimaging biomarker that complements conventional diffusion measurements for investigating abnormalities in WM microstructural integrity and cognitive functions in schizophrenia.