BACKGROUND: The amygdala plays a crucial role in emotion processing and is a key target for understanding the mechanisms underlying major depressive disorder (MDD). This study aimed to investigate the magnetic susceptibility of the amygdala in MDD and examine its association with structural and cerebral blood flow (CBF) changes. METHODS: A total of 158 individuals were included in the study, comprising 86 patients with MDD and 72 healthy controls. Depression severity was assessed using Hamilton Depression Rating Scale. Quantitative susceptibility mapping (QSM), T1-weighted, and arterial spin labeling scans were conducted to measure amygdala magnetic susceptibility, volume, and CBF, respectively. Group differences were compared, and associations between susceptibility, volume, and CBF were examined. RESULTS: The median susceptibility of the amygdala was significantly higher in MDD patients than in controls (all p <
0.01). In the MDD group, increased QSM value in the right amygdala was associated with higher CBF (r = 0.28, p = 0.01), whereas no significant correlation was found between QSM value and volume (p = 0.76). Increased QSM value in the right amygdala was associated with worse depressed mood (r = 0.30, p <
0.01). LIMITATION: Retrospective cross-sectional study conducted at a single center. CONCLUSION: The magnetic susceptibility of the amygdala was higher in MDD patients with than in controls. QSM changes in the right amygdala correlated with increased CBF and worse depressed mood, indicating both microstructural and functional alterations. Our results encourage further use of the QSM technique in the elucidation of MDD pathophysiology.