Classifying Schizophrenia Using Multimodal Multivariate Pattern Recognition Analysis: Evaluating the Impact of Individual Clinical Profiles on the Neurodiagnostic Performance

Abstract

Previous studies have shown that structural brain changes are among the best-studied candidate markers for schizophrenia (SZ) along with functional connectivity (FC) alterations of resting-state (RS) patterns. This study aimed to investigate effects of clinical and sociodemographic variables on the classification by applying multivariate pattern analysis (MVPA) to both gray matter (GM) volume and FC measures in patients with SZ and healthy controls (HC). RS and structural magnetic resonance imaging data (sMRI) from 74 HC and 71 SZ patients were obtained from a Mind Research Network COBRE dataset available via COINS (http://coins.mrn.org/dx). We used a MVPA framework using support-vector machines embedded in a repeated, nested cross-validation to generate a multi-modal diagnostic system and evaluate its generalizability. The dependence of neurodiagnostic performance on clinical and sociodemographic variables was evaluated. The RS classifier showed a slightly higher accuracy (70.5%) compared to the structural classifier (69.7%). The combination of sMRI and RS outperformed single MRI modalities classification by reaching 75% accuracy. The RS based moderator analysis revealed that the neurodiagnostic performance was driven by older SZ patients with an earlier illness onset and more pronounced negative symptoms. In contrast, there was no linear relationship between the clinical variables and neuroanatomically derived group membership measures. This study achieved higher accuracy distinguishing HC from SZ patients by fusing 2 imaging modalities. In addition the results of RS based moderator analysis showed that age of patients, as well as their age at the illness onset were the most important clinical features.

Keywords: brain imaging; clinical symptoms; multimodal; pattern recognition; schizophrenia.

Fig. 1.

Percentage difference in grey matter (GM) between healthy controls (HC) and schizophrenia (SZ) for the 95th percentile of reliable voxels. Reliability is defined as the mean value of the L2-LR weight divided by its standard error across all the generated models.

Fig. 2.

Percentage difference in connectivity between healthy controls (HC) and schizophrenia (SZ) for the 99th percentile of reliable connections. Reliability is defined as the mean value of the L2-LR weight divided by its standard error across all the generated models.