Abstract

Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on “support vector machines” to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

Highlights

  • Major depressive disorder (MDD) is among the most common psychiatric disorders in the world, affecting more than 350 million individuals [1], and is associated with a large and increasing economic and personal burden [2]

  • Global abnormalities have not been reported in tractography-based graph metrics in major depressive disorder (MDD), so we used a machine learning approach based on “support vector machines” to differentiate depressed from healthy individuals based on multiple brain network properties

  • GLOBAL GRAPH METRICS Univariate analyses of global graph metrics Following previous structural graph analyses [11,12,13], we conducted univariate analyses on the global graph metrics examined in this study to assess the relations of specific global graph metrics to MDD

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Summary

Introduction

Major depressive disorder (MDD) is among the most common psychiatric disorders in the world, affecting more than 350 million individuals [1], and is associated with a large and increasing economic and personal burden [2]. While early work in this area documented anomalies in specific structures in MDD [3, 4], more recently investigators have begun to examine brain networks [5,6,7,8]. Initial evidence from this literature indicates that MDD is associated with abnormalities in both structural and functional networks [for reviews, see Ref. MDD is associated with abnormal resting-state functional connectivity in a cortico-limbic (prefrontal–amygdala– pallidostriatal–mediothalamic) mood-regulating circuit and in the default-mode network [DMN; [5]]. MDD is characterized by structural abnormalities in white matter regions that link prefrontal cognitive control areas with subcortical emotion processing regions [8]

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