Global and network-specific glymphatic-related alterations in major depressive disorder: evidence from multimodal imaging

Major depressive disorder (MDD) is associated with neuroinflammation, which may impair glymphatic system function. This study aimed to investigate alterations in glymphatic function at both global and network levels in patients with MDD and to explore their clinical relevance. MRI data were acquired from 32 patients with MDD and 35 healthy controls (HC) using a 5 Tesla system. Global glymphatic system function was assessed using three glymphatic-related imaging proxies, including choroid plexus volume (CPV), diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and global coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (gBOLD-CSF coupling). Network-specific BOLD-CSF coupling was evaluated by calculating BOLD-CSF coupling within seven functional networks. Depression severity of patients was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17). Compared with HC, patients with MDD showed weaker gBOLD-CSF coupling (Cohen’s d = 0.843, 95% CI: 0.179–1.339, p = 0.003) and network-specific BOLD-CSF coupling in the dorsal attention network (DAN) (Cohen’s d = 0.835, 95% CI: 0.208–1.334, p = 0.019, Bonferroni-corrected). No significant between-group differences were observed in either CPV or DTI-ALPS. Within the MDD group, gBOLD-CSF and network-specific BOLD-CSF coupling in the DAN was negatively correlated with suicide item of the HAMD-17 ( ρ = −0.475, 95% CI: −0.708-−0.111, p = 0.011, FDR-adjusted q = 0.028; ρ = −0.556, 95% CI: −0.769-−0.200, p = 0.002, FDR-adjusted q = 0.017). Additionally, network-specific BOLD-CSF coupling in the DAN was negatively associated with gray matter volume (GMV) ( r = − 0.504, 95% CI: −0.739-−0.162, p = 0.006, FDR-adjusted q = 0.025). These findings indicate altered glymphatic-related imaging measures reflected by BOLD-CSF coupling in MDD, particularly within the DAN. Besides, the alterations were associated with clinical symptoms and GMV of MDD patients.