ArticleBMC psychiatry2026
Site-specific N-glycosylation alterations in serum proteins across subtypes of adolescent depressive disorder.
Article in BMC psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAdolescent depressive disorder is a clinically heterogeneous condition with poorly understood molecular mechanisms. Protein N-glycosylation, a key post-translational modification involved in immune regulation and neuronal communication, has not been systematically investigated across depressive subtypes in youth. Understanding glycosylation alterations may reveal novel biochemical pathways underlying disease heterogeneity and pathophysiology.
methodsWe applied a site-specific glycoproteomic approach integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS) and StrucGP to profile serum N-glycosylation in adolescents with major depressive disorder (MDD), MDD with non-suicidal self-injury (NSSI), and MDD with suicide attempts (SA), compared with healthy controls. Serum samples were pooled by group (10 individuals per pool), and glycan alterations were identified using predefined fold-change thresholds. This approach is classified as an exploratory research strategy, which does not support statistical inference.
resultsAll depressive subtypes displayed shared alterations, characterized by reduced bi-antennary glycans and LacNAc/Lewis structures, alongside elevated tetra-antennary sialylation, particularly N6H7S4. Candidate subtype-associated patterns were also observed: increased tri-antennary sialylation in NSSI, and selective upregulation of N6H7S4 on ORM2 in SA. Differentially glycosylated proteins, including SERPING1 and A2M, were enriched in immune, complement, and coagulation pathways. Notably, protein-level changes were minimal in label-free quantification, suggesting glycan-specific dysregulation.
conclusionsThis exploratory study identifies candidate subtype-dependent alterations in N-glycosylation in adolescent depression, which may implicate glycan-mediated immune and neuroinflammatory mechanisms in its molecular heterogeneity. This study provides a preliminary, pooled-sample based catalog of candidate site-specific N-glycosylation alterations for adolescent depression, warranting validation in larger, individual-level cohorts.
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