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Background: Although low-grade inflammation is associated with onset and persistence of depression, most biomarkers display modest predictive effects. GlycA (glycoprotein acetylation) is a unique metabolomic composite of pro-inflammatory acute-phase glycoproteins. We hypothesized that GlycA levels would predict depression incidence, remission and persistence, with higher accuracy than high-sensitivity c-reactive protein (hsCRP). We also explored the additive predictive value of GlycA above and beyond hsCRP.Methods: Cohort design using the sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)'s São Paulo site. Baseline GlycA and hsCRP levels were measured in blood plasma. Depression incidence, remission, and persistence were assessed using the Clinical Interview Scheduled Revised (CIS-R) at two time points separated by a mean of 3.8 years. Multivariable Poisson, logistic and linear regression models were used for prediction. Models were adjusted for sociodemographic and clinical confounders, including age, gender, ethnicity, education, cardiovascular assessments, antidepressant and anti-inflammatory drug use, anxiety disorders, alcohol use, and body mass index.Results: We included 4,364 participants (53.2% females, mean age 51.4 ± 8.9 years) with no autoimmune disorders. GlycA robustly predicted depression persistence (relative risk of 7.28, 95% confidence interval 1.33-45.57, p = 0.023 in the fully-adjusted model), but not depression onset. Although hsCRP also predicted depression persistence, its effects were fully explained by confounders and by GlycA levels. GlycA also predicted worsening of depressive symptoms in depressed patients and depression persistence vs. remission in fully-adjusted models.Limitations: Brief depressive episodes could not be measured by our assessments.Conclusions: GlycA might be a new inflammatory prognosis biomarker for depression. [ABSTRACT FROM AUTHOR]