White-matter functional topology: a neuromarker for classification and prediction in unmedicated depression

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Abstract

Aberrant topological organization of brain connectomes underlies pathological mechanisms in major depressive disorder (MDD). However, accumulating evidence has only focused on functional organization in brain gray-matter, ignoring functional information in white-matter (WM) that has been confirmed to have reliable and stable topological organizations. The present study aimed to characterize the functional pattern disruptions of MDD from a new perspective—WM functional connectome topological organization. A case-control, cross-sectional resting-state functional magnetic resonance imaging study was conducted on both discovery [91 unmedicated MDD patients, and 225 healthy controls (HCs)], and replication samples (34 unmedicated MDD patients, and 25 HCs). The WM functional networks were constructed in 128 anatomical regions, and their global topological properties (e.g., small-worldness) were analyzed using graph theory-based approaches. At the system-level, ubiquitous small-worldness architecture and local information-processing capacity were detectable in unmedicated MDD patients but were less salient than in HCs, implying a shift toward randomization in MDD WM functional connectomes. Consistent results were replicated in an independent sample. For clinical applications, small-world topology of WM functional connectome showed a predictive effect on disease severity (Hamilton Depression Rating Scale) in discovery sample (r = 0.34, p = 0.001). Furthermore, the topologically-based classification model could be generalized to discriminate MDD patients from HCs in replication sample (accuracy, 76%; sensitivity, 74%; specificity, 80%). Our results highlight a reproducible topologically shifted WM functional connectome structure and provide possible clinical applications involving an optimal small-world topology as a potential neuromarker for the classification and prediction of MDD patients.

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Li, J., Chen, H., Fan, F., Qiu, J., Du, L., Xiao, J., … Liao, W. (2020). White-matter functional topology: a neuromarker for classification and prediction in unmedicated depression. Translational Psychiatry, 10(1). https://doi.org/10.1038/s41398-020-01053-4

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