Structural and functional glymphatic abnormalities in major depressive disorder and bipolar disorder: A multimodal MRI study of DTI-ALPS and gBOLD-CSF coupling.

BACKGROUND

The glymphatic system is essential for cerebral waste clearance. This study evaluated glymphatic function in major depressive disorder (MDD) and bipolar disorder (BD) by combining diffusion tensor imaging along the perivascular space (DTI-ALPS) and global blood‑oxygen-level-dependent (gBOLD)-cerebrospinal fluid (CSF) coupling, exploring associations with affective, sleep, and cognitive symptoms.

METHODS

We recruited 52 MDD patients, 31 BD patients, and 52 healthy controls (HCs) for multimodal magnetic resonance imaging (MRI). Glymphatic function was assessed via DTI-ALPS and gBOLD-CSF coupling. Standardized scales evaluated depression, anxiety, sleep disturbances, cognition, and anhedonia. Inter-group comparisons, correlation, regression, mediation, and receiver operating characteristic (ROC) curve analysis were performed.

RESULTS

MDD and BD patients exhibited significantly reduced DTI-ALPS indices and gBOLD-CSF coupling compared to HCs, with no significant differences between patient groups. Exploratory analyses indicated these indirect imaging markers were intercorrelated weakly but significantly. Additionally, modality-specific alterations correlated with cognitive decline and increased anhedonia in MDD, and poorer sleep in BD. ROC analysis showed the joint imaging model provided modest diagnostic performance for distinguishing patients from HCs, which improved when integrated with clinical variables. Furthermore, mediation analysis suggested gBOLD-CSF coupling statistically mediated the association between disease status and affective symptoms.

CONCLUSIONS

Glymphatic impairment is a shared feature of MDD and BD. DTI-ALPS and gBOLD-CSF coupling serve as complementary, indirect biomarkers linked to core clinical features. While causal relationships remain to be elucidated, targeting glymphatic function may offer a novel therapeutic avenue for mood disorders.