This was on the other hand reported by Deverts et al in the CARDIA study, where depressive symptoms at baseline were positively correlated with CRP levels measured at 5-years follow-up. No association was found between CRP levels at the beginning of the observation period and subsequent depressive symptoms in any of these studies. This was however the main finding in a large study by Wium-Andersen et al. The lack of consensus with regard to CRP and development of depression may in part be due to the high biological variation of CRP. In 38 healthy blood donors with 6 determinations over 22 days a biological variation of hsCRP of 50% was found. Other studies have shown similar biological variation, ranging from 30–63%. SuPAR is a protein that is measurable in the circulating blood of all individuals. In contrast to most pro-inflammatory and acute response biomarkers, circadian changes in plasma suPAR is minimal, and in vitro stability is also high. Elevated levels of suPAR are associated with immune activation, inflammation and a negative outcome in patients with symptoms of infection. Furthermore, in an observational prospective Danish cohort consisting of healthy individuals, plasma suPAR levels were associated to the development of cancer, cardiovascular disease, type-2 diabetes and mortality during 12-years follow-up. SuPAR and CRP seems to reflect different aspects of inflammation. A recent study suggested that CRP is associated with anthropometric measures of inflammation, whereas suPAR is linked to cellular and vascular inflammatory processes. To test the hypothesis of inflammation and development of depression, we investigated whether the DAPT biomarker suPAR was associated with an increased risk of developing depression in a large cohort of Danish blood donors. As a proxy for depression, we used purchase of antidepressants, supplemented with a discharge diagnosis of depression. Aim of the study was to test the hypothesis, that higher levels of circulating suPAR in healthy individuals are associated with an increased risk for future use of antidepressants or a hospital diagnosis of depression. From both analyses were donors with a pre-history of antidepressant use or a previous hospital diagnosis of depression excluded. We further tested the hypothesis that prior use of antidepressants was associated with higher levels of suPAR. To our knowledge, this is the first larger prospective populationbased study of the inflammatory marker suPAR and use of antidepressants. We investigated the association of suPAR levels and both subsequent incident use of antidepressants and prior use of antidepressants and found an association between high suPAR levels and the use of antidepressants in both directions. When analysing the incident use of antidepressants, we found a statistically significant effect of suPAR level on the risk of subsequent use of antidepressants during a five-year observation period. To our knowledge, this is the first larger prospective population-based study of the inflammatory marker suPAR and use of antidepressants. We investigated the association of suPAR levels and both subsequent incident use of antidepressants and prior use of antidepressants and found an association between high suPAR levels and the use of antidepressants in both directions. Kaplan-Meier curves depicting suPAR quartiles indicate that a high suPAR level was associated with an increased risk of antidepressant usage throughout the observation period. This is a surprising and interesting observation, suggesting that an elevated suPAR level seems to reflect a constitutively increased risk of depression.