Peak width of skeletonized mean diffusivity as a neuroimaging biomarker in first-episode schizophrenia

Peak width of skeletonized mean diffusivity (PSMD), a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage, has been shown to be associated with cognition in various WM pathologies. 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.

A total of 56 first-episode drug-naive 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 mean diffusivity (MD), average fractional anisotropy (FA), average axial diffusivity (AD), and average radial diffusivity (RD) values as well as structural network global topological parameters, and examined between-group differences in these WM metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics.

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 the groups in the remaining metrics, including PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity, or hierarchy (p > 0.05). After adjusting for relevant variables, 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 the patient group (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 ( $$ = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR > 0.05).

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.