Distinct Trajectories of Amygdala Connectivity Patterns Characterize Remission vs. Non‐Remission in Patients With Major Depressive Disorder

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Background: This study aimed to investigate the neural basis of individual differences in antidepressant efficacy using an 8-week longitudinal multitime point resting-state functional magnetic resonance imaging (fMRI) design. Methods: Forty-eight patients with major depressive disorder (MDD) completed two or three scans, and 44 healthy controls (HCs) underwent a baseline scan. Patients were categorized into remission (MDDr) and nonremission (MDDnr) groups based on treatment outcomes. Group differences in resting-state functional connectivity (rsFC) of the amygdala subregions at baseline were examined among MDDr, MDDnr, and HCs. Longitudinal changes in the identified rsFC were compared between the MDDr and MDDnr groups. Correlation analyses were conducted to explore the relationship between baseline rsFC or its longitudinal changes and depressive symptom severity or improvement. Results: At baseline, rsFC between the right basolateral (BL) amygdala and the right supplementary motor area (SMA) was lower in the MDDr group but higher in the MDDnr group compared with HCs, although this effect did not survive multiple comparisons correction across amygdala subregions. The trajectory of this rsFC differed between the two patient groups during treatment, with normalization observed at 2 and 8 weeks posttreatment. Correlation analyses indicated that baseline rsFC was associated with treatment response and that longitudinal changes in rsFC were aligned with symptom improvement, although some associations did not survive multiple comparisons correction. Conclusions: Our findings provide novel and valuable insights into the neural mechanisms underlying antidepressant response and highlight the role of amygdala subregional connectivity in explaining interindividual variability in treatment efficacy. Trial Registration: ClinicalTrials.gov identifier: ChiCTR2400093823.

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