Elevated C-Reactive Protein Levels, Psychological Distress, and Depression in 73 131 Individuals

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The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression.


To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress and depression.


We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies.


The Copenhagen General Population and the Copenhagen City Heart studies.


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.


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).


Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population.

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