Major depressive disorder (MDD) is a chronic and recurrent mental health condition that affects approximately 300 million people worldwide, causing a significant disease burden(Kandola, Lewis, Osborn, Stubbs, & Hayes, 2020). Among the primary symptoms of MDD, cognitive dysfunction emerges as a critical aspect, encompassing deficits in executive function, working memory, attention and speed of processing, etc. Recent studies have shed light on the profound impact of cognitive deficits in MDD, including hampered treatment response, increased risk of recurrent episodes, and persistent disabilities in occupational and social functioning(Dam et al., 2022; Knight & Baune, 2018). Recognizing the significance of these cognitive symptoms, there is a growing need to comprehend their neurobiological underpinnings in MDD.

White matter plays a crucial role in cognitive function and psychopathology(Fields, 2008). A review of neuroimaging studies reveals that white matter abnormalities are observed in processing speed deficits in MDD, and white matter hyperintensity resulting from small vessel disease is highlighted(Li et al., 2024). There is also evidence that alterations in the spatial localization of white matter microstructure correlate with cognitive performance(Ban et al., 2024). Compared to studies focusing on regional microstructural changes, brain network analysis is better at capturing the nuanced interactions between brain regions(Sporns, 2011). Studies with large samples have shown that the communication efficiency of the white matter network decreases in patients with MDD(Repple et al., 2023), but there is limited understanding of how the structure of these networks relates to cognition. A recent study has revealed that cognitive factors are linked to global connectivity strength, with particularly pronounced effects observed within identified subnetworks(Gruber et al., 2023). The study used exploratory factor analysis to derive cognitive factors from 14 cognitive test scores, which allowed them to abstract multiple cognitive tests into broader cognitive domains. While their findings establish important links between cognitive domains and white matter connectivity, their study did not specifically address the relationship between particular cognitive functions and white matter connectivity. Further investigation is required to fill this gap by providing a more detailed exploration of these associations.

We here examined the structural connectivity of 51 patients and 57 matched healthy controls based on graph theory, seeing how these altered topological properties in white matter networks may relate to specific cognitive deficits. We hypothesized that: 1) there existed compromised brain communication within the white matter network of individuals diagnosed with MDD, and that 2) the topological network abnormalities among MDD patients were correlated with distinct cognitive impairments, particularly in processing speed.