Major depressive disorder (MDD) is frequently characterized as a disorder of the disconnection syndrome. Diffusion tensor imaging (DTI) has played a critical role in supporting this view, with much investigation providing a large amount of evidence of structural connectivity abnormalities in the disorder. Recent research on the human connectome combined neuroimaging techniques with graph theoretic methods to highlight the disrupted topological properties of large-scale structural brain networks under depression, involving global metrics (e.g., global and local efficiencies), and local nodal properties (e.g., degree and betweenness), as well as other related metrics, including a modular structure, assortativity, and (rich) hubs. Here, we review the studies of white matter networks in the case of MDD with the application of these techniques, focusing principally on the consistent findings and the clinical significance of DTI-based network research, while discussing the key methodological issues that frequently arise in the field. The already published literature shows that MDD is associated with a widespread structural connectivity deficit. Topological alteration of structural brain networks in the case of MDD points to decreased overall connectivity strength and reduced global efficiency as well as decreased small-worldness and network resilience. These structural connectivity disturbances entail potential functional consequences, although the relationship between the two is very sophisticated and requires further investigation. In summary, the present study comprehensively maps the structural connectomic disturbances in patients with MDD across the entire brain, which adds important weight to the view suggesting connectivity abnormalities of this disorder and highlights the potential of network properties as diagnostic biomarkers in the psychoradiology field. Several common methodological issues of the study of DTI-based networks are discussed, involving sample heterogeneity and fiber crossing problems and the tractography algorithms. Finally, suggestions for future perspectives, including imaging multimodality, a longitudinal study and computational connectomics, in the further study of white matter networks under depression are given. Surmounting these challenges and advancing the research methods will be required to surpass the simple mapping of connectivity changes to illuminate the underlying psychiatric pathological mechanism.
Keywords: Biomarker; Connectivity; Connectome; Diffusion tensor imaging; Graph theory; Major depressive disorder; Psychoradiology; White matter.