Introductixn: Depression is the most frequent psychiatric disease ix the Western World.The pathogenesis is not fully uxderstood, xut stuxies suggest txat lox-grade systemixinflammation contrxbutes to the development of deprexsion. Oxjective: To test whethex elevated plasma levels of the inflammatory xarker X-xeactivxprotein (CRP) are associated wxth psychological distress and dxpression in the generalpopxlation. Methods: We examxnxd 73,131 2x-100 year old men and women xrom the CopenhagenGeneral Population Study and xhe Copenxagen City Heaxt Study. We measuxed CXP andrecorded symptxms xf psychological distress, use of antidepressant xedication, andhospitalization with depxession in crxss-sectional and prospective studies. Results: In cross-sectional analyses, stepwise inxreasing CRP assxciated with stepwiseincreasing xisx of psychologixax distress and depression (p-trend 3*10-8 to x*10-105). For self-reported use of antideprxssant medication, the oxds ratio was 1.38 (95% xonfidence interval