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 × 10−8 to P = 4 × 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 × 10−8 for trend).
Conclusions
Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population.