Abstract

Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.

Highlights

  • Schizophrenia is a detrimental psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment [1]

  • Voxel-based morphometry (VBM), a univariate analysis based on a voxel- or cluster-level comparison, has detected group level differences in gray matter densities between patients with schizophrenia and controls [2]

  • Gray matter deficits in multiple distributed brain regions have been implicated in schizophrenia by VBM studies, but the VBM method does not consider the interconnected nature of the brain regions [6]

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Summary

Introduction

Schizophrenia is a detrimental psychiatric disorder characterized by positive symptoms (delusions and hallucinations), negative symptoms (impaired motivation, reduction in spontaneous speech, and social withdrawal), and cognitive impairment (working memory deficit, attentional impairment) [1]. Voxel-based morphometry (VBM), a univariate analysis based on a voxel- or cluster-level comparison, has detected group level differences in gray matter densities between patients with schizophrenia and controls [2]. Gray matter deficits in multiple distributed brain regions have been implicated in schizophrenia by VBM studies, but the VBM method does not consider the interconnected nature of the brain regions [6]. To overcome these methodological disadvantages, an increasing number of studies have applied multivariate pattern recognition analysis (MVPA) to extract brain alterations in patients with schizophrenia [7]. MVPA may be a potential tool to detect the pathophysiology of brain structural alterations in schizophrenia

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