Discriminating between bipolar disorder (BD) and major depressive disorder (MDD) is a major clinical challenge due to the absence of known biomarkers; hence a better understanding of their pathophysiology and brain alterations is urgently needed. Given the complexity, feature selection is especially important in neuroimaging applications, however, feature dimension and model understanding present serious challenges. In this study, a novel feature selection approach based on linear support vector machine with a forward-backward search strategy (SVM-FoBa) was developed and applied to structural and resting-state functional magnetic resonance imaging data collected from 21 BD, 25 MDD and 23 healthy controls. Discriminative features were drawn from both data modalities, with which the classification of BD and MDD achieved an accuracy of 92.1% (1,000 bootstrap resamples). Weight analysis of the selected features further revealed that the inferior frontal gyrus may characterize a central role in BD-MDD differentiation, in addition to the default mode network and the cerebellum. A modality-wise comparison also suggested that functional information outweighs anatomical by a large margin when classifying the two clinical disorders. This work validated the advantages of multimodal joint analysis and the effectiveness of SVM-FoBa, which has potential for use in identifying possible biomarkers for several mental disorders.

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