Lower DTI-ALPS index in patients with major depressive disorder: Correlation with fatigue

Background and purpose: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is an index that may provide insights into intracranial waste clearance processes. Glymphatic system dysfunction has been suggested to play a role in the development of major depressive disorder (MDD). Additionally, fatigue-a common precursor of MDD-is also closely connected to the waste clearance function of the central nervous system (CNS), further underscoring the significance of efficient waste removal in MDD. However, evidence linking altered DTI-ALPS index to MDD remains limited. This study aims to investigate the changes in the DTI-ALPS index in patients with MDD and explore the potential interplay between DTI-ALPS index alterations, fatigue, and the presence of MDD. Material and methods: A total of 46 patients with MDD and 55 healthy controls (HC) were included in the study. All participants underwent diffusion tensor imaging using the same 3-T MRI (3-Tesla Magnetic Resonance Imaging) scanner. The DTI-ALPS index was assessed, and the Chalder Fatigue Scale (CFS) was used to evaluate fatigue levels in both groups, and the 17-item Hamilton Depression Rating Scale (HAMD-17) was used to evaluate the severity of depression in the patients. We compared the DTI-ALPS index and clinical characteristics between the MDD and HC group, and explored the relationship among the DTI-ALPS index, CFS scores, and the presence of MDD through mediation analysis. Results: The DTI-ALPS index in the right hemisphere (DTI-ALPS-R) is significantly lower in patients with MDD (t = 2.41, P = 0.02). The MDD patients exhibited significantly higher scores on the CFS scales compared with HCs (t = 13.12, P <.001). Mediation analysis showed that the CFS score plays a significant mediating role between DTI-ALPS-R and the presence of MDD, acting as a full mediator (indirect effect beta = -0.230, 95 % CI: [-0.388, -0.059]). Conclusion: Our study found that patients with MDD have a reduced DTI-ALPS index. This reduction appears to contribute to the development of MDD by facilitating the accumulation of fatigue symptoms. These findings may provide a new perspective on the pathogenesis of MDD, suggest a potential new biomarker for MDD, and offer new insights for its treatment.