Glymphatic function assessment with diffusion tensor imaging along the perivascular space in patients with major depressive disorder and its relation to cerebral white-matter alteration.

Background: The link between glymphatic system function in the brain and alterations in white-matter microstructure among individuals with major depressive disorder (MDD) remains unclear. This study aimed to examine the assessment of glymphatic system function in patients with MDD using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and to evaluate its association with cerebral-white-matter abnormalities and neuropsychological scores.

Methods: From February 2023 to November 2023, this cross-sectional study recruited 35 patients with MDD from the Psychosomatic Diseases Department of the First Affiliated Hospital of Dalian Medical University. In this time period, 23 healthy controls (HCs) were enlisted from the community and matched with the MDD cohort in terms of years of education, gender, and age. All participants underwent magnetic resonance imaging, depression, anxiety, and cognitive assessments. The tract-based spatial statistics (TBSS) analyzed DTI parameters and identified significant clusters. Automated fiber quantification (AFQ) was used to automatically identify fiber bundles with statistical differences. Mann-Whitney tests or two-sample -tests were used for comparisons. Interobserver consistency of the DTI-ALPS measurements was evaluated using the interclass correlation coefficient (ICC). Partial correlation analyses and linear regression analyses were used to examine relationships. A comparison of the DTI-ALPS index was made between the two groups. Correlations among diffusion characteristics, neuropsychological scores, and the DTI-ALPS index were analyzed.

Results: Compared to HCs, patients with MDD exhibited a lower DTI-ALPS score (P=0.001). According to using linear regression analysis, the ALPS index was found to be an independent predictor of the Hamilton Depression Rating Scale [B=-25.32; P=0.001; 95% confidence interval (CI): -40.35 to -11.55], Hamilton Anxiety Rating Scale (B=-33.48; P=0.003; 95% CI: -55.38 to -11.24), and Montreal Cognitive Assessment total score (B=8.59; P=0.008; 95% CI: 2.38 to 14.79). According to the TBSS analysis, there were clusters of increased axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in patients with MDD as compared to HCs (all P values <0.05). A lower DTI-ALPS score was correlated with higher AD (r=-0.592; P<0.001), MD (cluster 1: r=-0.567, P=0.001; cluster 2: r=-0.581, P<0.001), and RD (r=-0.491; P=0.004) values. AFQ analysis identified the significantly different diffusion indicators in the left cingulum bundle (CB_L), left inferior longitudinal fasciculus (ILF_L), and left uncinate fasciculus (UF_L) between the two groups (all false discovery rate P values <0.05). DTI-ALPS score was negatively correlated with the AD value of CB_L (r=-0.304; P=0.024), ILF_L (r=-0.35; P=0.008), and UF_L (r=-0.354; P=0.008) in AFQ tract-level analysis. In point-wise analysis, the MD value of CB_L at nodes 33 to 36 was negatively correlated with DTI-ALPS score (r ranging from -0.504 to -0.535; P<0.01).

Conclusions: Our results indicated a decrease in DTI-ALPS index score in patients with MDD. DTI-ALPS score was associated with depression, anxiety, declined cognitive ability, and white-matter microstructural abnormalities and may thus be a promising biomarker for the partial evaluation of glymphatic system function in patients with MDD.