Tractography-based classification in distinguishing patients with first-episode schizophrenia from healthy...

Schizophrenia has been characterized as a neurodevelopmental disorder of brain disconnectivity. However, whether disrupted integrity of white matter tracts in schizophrenia can potentially serve as individual discriminative biomarkers remains unclear.

A random forest algorithm was applied to tractography-based diffusion properties obtained from a cohort of 65 patients with first-episode schizophrenia (FES) and 60 healthy individuals to investigate the machine-learning discriminative power of white matter disconnectivity. Recursive feature elimination was used to select the ultimate white matter features in the classification. Relationships between algorithm-predicted probabilities and clinical characteristics were also examined in the FES group.

The classifier was trained by 80% of the sample. Patients were distinguished from healthy individuals with an overall accuracy of 71.0% (95% confident interval: 61.1%, 79.6%), a sensitivity of 67.3%, a specificity of 75.0%, and the area under receiver operating characteristic curve (AUC) was 79.3% (χ2 p < 0.001). In validation using the held-up 20% of the sample, patients were distinguished from healthy individuals with an overall accuracy of 76.0% (95% confident interval: 54.9%, 90.6%), a sensitivity of 76.9%, a specificity of 75.0%, and an AUC of 73.1% (χ2 p = 0.012). Diffusion properties of inter-hemispheric fibres, the cerebello-thalamo-cortical circuits and the long association fibres were identified to be the most discriminative in the classification. Higher predicted probability scores were found in younger patients.

Our findings suggest that the widespread connectivity disruption observed in FES patients, especially in younger patients, might be considered potential individual discriminating biomarkers.