Glycosylation state of vWF in circulating extracellular vesicles serves as a novel biomarker for predicting depression.

The clinical diagnosis of major depressive disorder (MDD), a heterogeneous disorder, still depends on subjective information in terms of various symptoms regarding mood. Detecting extracellular vesicles (EVs) in blood may result in finding a diagnostic biomarker that reflects the depressive stage of patients with MDD. Here, we report the results on the glycosylation pattern of enriched plasma EVs from patients with MDD and age-matched healthy subjects. In this cohort, the levels of Triticum vulgaris (wheat germ) agglutinin (WGA), N-acetyl glucosamine (GlcNAc) and N-acetylneuraminic acid (Neu5Ac, sialic acid) - binding lectin, were significantly decreased in patients with MDD in depressive state compared to healthy subjects (area under the curve (AUC): 0.87 (95% confidence interval (CI) 0.76 - 0.97)) and in remission state (AUC: 0.88 (95% CI 0.72 - 1.00)). Furthermore, proteome analysis revealed that the von Willebrand factor (vWF) was a significant factor recognized by WGA. WGA-binding vWF antigen differentiated patients with MDD versus healthy subjects (AUC: 0.92 (95% CI 0.82 - 1.00)) and the same patients with MDD in depressive versus remission state (AUC: 0.98 (95% CI 0.93 - 1.00)). In this study, the change patterns in the glycoproteins contained in plasma EVs support the usability of testing to identify patients who are at increased risk of depression during antidepressant treatment.