# Deciphering the Glycoproteomic Landscape of Mood Disorders: Unveiling Molecular Association Between CDG and Depression Resilience

## TL;DR

This study explores how changes in brain glycosylation relate to mood disorders and finds that impaired glycosylation may protect against depression.

## Contribution

The study reveals a novel link between glycosylation patterns and depression resilience, particularly in the context of CDG.

## Key findings

- MDD individuals showed increased protein glycosylation compared to controls and BD individuals.
- Depression prevalence was lower in CDG patients, suggesting impaired glycosylation may confer resilience.
- The findings highlight distinct biological mechanisms between unipolar and bipolar depression.

## Abstract

The lack of a molecular understanding of mood disorders has impeded progress in diagnosis and treatment. Glycosylation may provide insights into the complex mechanisms underlying these conditions. We conducted N-glycoproteomic analysis on dorsolateral prefrontal cortex samples from individuals with major depressive disorder (MDD) and bipolar disorder (BD), in depressive or manic states at death. Additionally, we examined depression prevalence in congenital disorders of glycosylation (CDG) through a literature review and assessment of 110 CDG patients. Glycoproteomic analysis revealed a significant increase in protein glycosylation in individuals with MDD relative to both controls and individuals with BD. Depression prevalence was lower in our pediatric and adult cohort of individuals with CDG. These results suggest brain glycosylation changes may play a role in mood disorder pathology and highlight the distinct biology of unipolar and bipolar depression. Our findings propose that impaired glycosylation may confer resilience to depression, offering potential therapeutic insights.