Structural neuroimaging differentiates between depressed bipolar disorder and major depressive disorder patients: a machine learning study

Abstract

Introduction Depression is the predominant mood alteration in bipolar disorder (BD), leading to overlapping symptomatology with major depressive disorder (MDD). Consequently, in clinical assessment, almost 60% of BD patients are misdiagnosed as affected by MDD. This calls for the creation of a framework for the differentiation of BD and MDD patients based on reliable biomarkers. Since machine learning (ML) enables to make predictions at the single-subject level, it appears to be particularly suitable for this task. Objectives We implemented a ML pipeline for the differentiation between depressed BD and MDD patients based on structural neuroimaging features. Methods Diffusion tensor imaging (DTI) and T1-weighted magnetic resonance imaging (MRI) data were acquired for 282 depressed BD (n=180) and MDD (n=102) patients. Axial (AD), radial (RD), mean (MD) diffusivity, and fractional anisotropy (FA) maps were extracted from DTI images, and voxel-based morphometry (VBM) measures were obtained from T1-weighted images. Each feature was entered separately into a 5-fold nested cross-validated ML pipeline differentiating between BD and MDD patients, comprising: confound regression for nuisance variables removal (i.e., age and sex), feature standardization, principal component analysis, and an elastic-net penalized regression. The models underwent 5000 random permutations as a test for significance, and the McNemar’s test was used to assess whether there was any significant difference between the models (significance threshold was set to p<0.05). Results The performance of the models and the results of the permutation tests are summarized in Table 1. McNemar’s test showed that the AD-, RD-, MD-, and FA-based models did not differ between each other and were significantly different from the VBM.Table 1. Models’ performance and p-value at 5000 permutation test. Feature Overall accuracy MDD specifictiy BD sensitivity p-value VBM 0.61 0.38 0.74 0.058 AD 0.78 0.65 0.86 <0.001 FA 0.79 0.61 0.89 <0.001 MD 0.79 0.63 0.88 <0.001 RD 0.79 0.63 0.88 <0.001 Conclusions In conclusion, our models differentiated between BD and MDD patients at the single-subject level with good accuracy using structural MRI data. Notably, the models based on white matter integrity measures relying on true information, rather than chance. Disclosure of Interest None Declared