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Assessment of glymphatic function in treatment-resistant depression using DTI-ALPS index
Xin Zhang1, Shaoyong Ye2, Maoxin Zhang1
1Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai' an, 271000, China; School of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai' an, 271016, China.
Background:
Treatment-resistant depression (TRD) poses a significant burden on patients and society, yet its underlying pathophysiology remains poorly understood. Emerging evidence suggests that glymphatic system dysfunction may be involved in the pathogenesis of depression. However, the differences in glymphatic system alterations between TRD and non-treatment-resistant depression (nTRD), as well as their association with clinical symptoms, are still unclear.
Methods:
Participants comprised 65 patients with TRD, 110 patients with nTRD, and 84 healthy controls (HCs). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method was used to quantify glymphatic function for each participant. Partial correlation analyses were employed to examine the relationships between the DTI-ALPS index and clinical measures such as the Hamilton Depression Rating Scale (HAMD).
Results:
Patients with TRD exhibited elevated left-side and mean DTI-ALPS indices, accompanied by a reduction in the left diffusivity of projection fibers along the y-axis direction (Dyyproj) value compared to both nTRD and HCs. Within the TRD group, a higher DTI-ALPS index value was associated with more severe sleep disturbance, whereas lower Dyyproj values were correlated with lower levels of anxiety and cognitive impairment. Within the nTRD group, a lower DTI-ALPS index value was associated with more severe childhood trauma and milder anhedonia.
Conclusions:
In patients with TRD, the observed increase in the DTI-ALPS index, resulting from reduced Dyyproj, was correlated with clinical characteristics, suggesting that this elevation may not reflect enhanced lymphatic clearance capacity but rather be associated with perivascular space narrowing.
