Difference in degree centrality of brain functional connectivity between patients with treatment-resistant depression and patients with non-treatment-resistant depression compared with healthy individuals

Background and objectives: Evidence suggests that treatment-resistant depression (TRD) is associated with more prominent and widespread brain alterations in areas related to mood and cognition compared with non-treatment-resistant depression (nTRD). However, direct comparisons of brain functioning between TRD and nTRD are scarce. Methods: We applied graph theory-based resting-state functional magnetic resonance imaging analysis to compare the degree centrality (DC) of brain functional connectivity among 31 patients with TRD, 28 patients with nTRD, and 30 healthy controls. Cognitive function was assessed using working memory and go/no-go tasks. Results: Compared with controls, patients with TRD exhibited reduced DC in the left cuneus, right frontal operculum cortex, cerebellum vermis I, II, and IX, and left cerebellum lobule X. The DC in the right cerebellum lobule III was lower in patients with TRD compared with those with nTRD. Among patients with TRD, we discovered positive associations between mean reaction time on the go/no-go task and DC in the left cuneus (r = 0.44, p = 0.015) and the right frontal operculum cortex (r = 0.41, p = 0.025). Conversely, the mean reaction time on the working memory task was inversely correlated with DC in the left cerebellar lobule X (r = −0.43, p = 0.019). Conclusion: Our findings highlight the important roles of the cerebellum (specifically, lobule X, and the right lobule III), frontal operculum, and cuneus in TRD. Dysfunction in these brain regions, which are integral to the salience and default mode networks, is likely associated with TRD-related cognitive dysfunction.