Assessment of glymphatic system function using DTI-ALPS in depressive disorders: a study of its correlation with clinical features and plasma GFAP levels.

Background: The function of the glymphatic system (GS) in patients with depressive disorders (DDs), as well as its relationship with clinical characteristics and plasma glial fibrillary acidic protein (GFAP) levels, remains poorly understood. In this study, the Diffusion Tensor Imaging-Analysis along the Perivascular Space (DTI-ALPS) method was applied to assess glymphatic function in individuals with DDs. Correlations between the DTI-ALPS index, clinical features of DDs, and plasma GFAP concentrations were analyzed to explore potential underlying mechanisms of DDs. Methods: Between August 2022 and March 2024, a total of 72 patients diagnosed with DD at the Department of Psychiatry and Psychology at the Affiliated Hospital of Guilin Medical University and 44 healthy controls (HCs) were enrolled in the study. Detailed information was collected and recorded for all participants, including demographic characteristics (sex, age, and education level), disease-related data (smoking and alcohol history, illness duration, and relevant clinical scales), neuroimaging parameters [brain magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) metrics], and fasting morning venous blood samples. GS function was assessed using the DTI-ALPS index, and plasma GFAP concentration was measured via enzyme-linked immunosorbent assay (ELISA). Chi-squared tests, non-parametric tests, and partial Spearman's rank correlation analyses were employed to examine the relationships between the DTI-ALPS index and clinical features of depression, as well as plasma GFAP levels. Results: The DTI-ALPS index was significantly lower in the persistent depressive disorder (PDD) group compared to both the HC (P<0.001) and non-persistent depressive disorder (NPDD) (P<0.001) groups. Conversely, plasma GFAP concentrations were significantly elevated in the PDD group relative to the HC (P<0.001) and NPDD (P<0.001) groups. No significant differences were observed between the HC and NPDD groups (P>0.05). Partial Spearman's rank correlation analyses were performed controlling for sex, age, and smoking. P values were adjusted for multiple comparisons using the Benjamini-Yekutieli false discovery rate (FDR) procedure, and are reported as q values. These analyses showed that the DTI-ALPS index across all the study participants was negatively correlated with the plasma GFAP levels (r=-0.290, q=0.009), indicating a significant correlation. No other variables showed statistically significant associations with the DTI-ALPS index (all q>0.05). Further, GFAP concentrations were positively correlated with illness duration, Hamilton Depression Rating Scale (HAMD-17), Patient Health Questionnaire-9 (PHQ-9), and Pittsburgh Sleep Quality Index (PSQI) scores (all q<0.05), and negatively correlated with Mini-Mental State Examination (MMSE) scores (r=-0.230, q=0.012). Conclusions: The DTI-ALPS index was found to be lower in the PDD group compared to both the HC and NPDD groups, and was correlated with plasma GFAP levels. These findings suggest that the covariation between glymphatic dysfunction and glial activation may represent a potential biological feature in the progression of DDs.