Elevated C-Reactive Protein Levels, Psychological Distress, and Depression in 73131 Individuals

Context: The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression. Objective: To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress and depression. Design: We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies. Setting: The Copenhagen General Population and the Copenhagen City Heart studies. Participants: We examined 73 131 men and women aged 20 to 100 years. Main Outcome Measures: We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use, register-based prescription of antidepressants, and register-based hospitalization with depression. Results: In cross-sectional analyses, increasing CRP levels were associated with increasing risk for psychological distress and depression (P = 3 X 10(-8) to P = 4 X 10(-105) for trend). For self-reported use of antidepressants, the odds ratio was 1.38 (95% CI, 1.23-1.55) for CRP levels of 1.01 to 3.00 mg/L, 2.02 (1.77-2.30) for 3.01 to 10.00 mg/L, and 2.70 (2.25-3.25) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants, the corresponding odds ratios were 1.08 (95% CI, 0.99-1.17), 1.47 (1.33-1.62), and 1.77 (1.52-2.05), respectively; for hospitalization with depression, 1.30 (1.01-1.67), 1.84 (1.39-2.43), and 2.27 (1.54-3.32), respectively. In prospective analyses, increasing CRP levels were also associated with increasing risk for hospitalization with depression (P = 4 X 10(-8) for trend). Conclusions: Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population. JAMA Psychiatry. 2013;70(2):176-184. Published online December 24, 2012. doi:10.1001/2013.jamapsychiatry.102