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 treatment 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 the depressive state compared in remission state (area under the curve (AUC): 0.88 (95% confidence interval (CI) 0.72 - 1.00)) and healthy subjects (AUC: 0.87 (95% CI 0.76 - 0.97)). Furthermore, proteome analysis revealed that von Willebrand factor (vWF) was a significant factor recognized by WGA. WGA-binding vWF differentiated patients with MDD in the depression state versus the remission state (AUC: 0.92 (95% CI 0.82 - 1.00)) and patients with MDD versus healthy subjects (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.

The authors have declared no competing interest.

This research was supported partly by Japan Agency for Medical Research and Development (grant number 22dk0307103h0002) and the the Strategic Research Program for Brain Sciences (Integrated Research on Neuropsychiatric Disorders). K.T. received support from SENSHIN Medical Research Foundation, Japan and The Finding-Out & Crystallization of Subliminals (FOCS) project by the Yamaguchi University of Medicine. This work was also the result of using program for supporting construction of core facilities in MEXT Project for promoting public utilization of advanced research infrastructure (grant number JPMXS0440400023).

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The Institutional Review Board of Yamaguchi University Hospital, Yamaguchi, Japan gave ethical approval for this work (H25-085-13, H23-153-19, H2022-203), and all subjects provided written informed consent for participation.

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