Eight-week antidepressant treatment effects on connectome gradient in first-episode drug-naïve patients with major depressive disorder

Given the limited understanding of the pathogenesis underlying depression and the specific targets of antidepressant medications, treatment of depression predominantly relies on empirical methodologies. Previous magnetic resonance imaging studies utilizing connectome gradient methods have revealed disruptions of the principal gradient in major depressive disorder (MDD) patients. However, the semiological meaning of the brain gradient and the effect of antidepressants are unknown. We recruited MDD patients and healthy controls to investigate baseline alterations in the principal connectome gradient. Changes in gradient scores were further analyzed within the responder group post-treatment, and repeated measures ANOVA was used to assess the gradient score changes across time (within-subject) and antidepressant types (between-subject). Compared to controls, MDD patients exhibited gradient score alterations in default and visual networks. After antidepressant treatment, the gradient scores for the left ventromedial prefrontal cortex (VMPFC) increased in patients who responded to therapy. The gradient scores for left VMPFC had an interaction effect between time and antidepressant types and correlated negatively with the core factor scores of HRSD17 at baseline. These results highlight the single-target antidepressants' effects on gradient scores for left VMPFC and provide evidence for future treatment targets and neurobiological underpinnings of antidepressant therapy.