Altered perivascular water diffusivity links childhood trauma and major depressive disorder: A multimodal integration...

Perivascular water diffusivity, as assessed by diffusion tensor imaging along the perivascular space (DTI-ALPS) index, serves as an indirect imaging marker potentially reflecting glymphatic function. This study investigated its associations with childhood trauma and major depressive disorder (MDD) and explored the related biological mechanisms.

We enrolled 86 patients with MDD and 74 matched healthy controls (HCs). Childhood trauma, cognitive performance, and peripheral blood transcriptomic profiles were evaluated. Regression and exploratory mediation analyses were performed.

MDD patients exhibited lower DTI-ALPS index (F = 15.716, p < 0.001), and poor attention, processing speed, visual memory and executive function performance (q < 0.05) than HCs. In the MDD group, the DTI-ALPS index was negatively correlated with CTQ score (r = -0.251, p = 0.02), spatial working memory strategy (SWM_Stra; r = -0.272, p = 0.013) and rapid visual information processing mean latency (RVP_ML; r = -0.232, p = 0.036). The yellow, turquoise, and blue transcriptomic modules were associated with MDD and enriched in immune-inflammatory, intracellular trafficking, and mitochondrial metabolic pathways, whereas the magenta module was associated with the DTI-ALPS index (r = -0.25, p = 0.022) and enriched in hemostasis, platelet activation, and vascular integrity pathway. Mediation analyses revealed that the DTI-ALPS index partially mediated the relationships between childhood trauma and the diagnosis of MDD (indirect effect: coefficient = 0.0001, p = 0.0372).

Altered DTI-ALPS may reflect links between childhood trauma, cognitive dysfunction, and vascular integrity, but as an indirect glymphatic marker, these findings require cautious interpretation.