The causal role of C-reactive protein and interleukin-6 on anxiety and depression symptoms and life satisfaction: Mendelian randomisation analyses in the HUNT study.

Abstract

Serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) have been associated with anxiety and depression in cross-sectional and Mendelian randomisation studies, but results regarding the effect size and direction have been mixed. A recent Mendelian Randomisation (MR) study suggested that CRP may decrease and IL-6 may increase anxiety and depression symptoms. Among 68 769 participants of the population-based Trøndelag Health Study (HUNT), we performed cross-sectional observational and one-sample MR analyses of serum CRP and two-sample MR analysis of serum IL-6. The main outcomes were symptoms of anxiety and depression assessed using the Hospital Anxiety and Depression Scale (HADS) and life satisfaction assessed using a seven-level ordinal questionnaire where higher scores indicate lower life satisfaction. In cross-sectional observational analyses, a doubling in serum CRP level was associated with 0.27% (95% CI -0.20 to 0.75) difference in HADS depression score (HADS-D), -0.77% (95% CI -1.24 to -0.29) difference in HADS anxiety score (HADS-A) and -0.10% (95% CI -0.41 to 0.21) difference in life satisfaction score. In one-sample MR analyses, a doubling in serum CRP was associated with 2.43% (95% CI -0.11 to 5.03) higher HADS-D, 1.94% (95% CI -0.58 to 4.52) higher HADS-A, and 2.00% (95% CI 0.45 to 3.59) higher life satisfaction score. For IL-6, causal point estimates were in the opposite direction, but imprecise and far from conventional criteria for statistical significance. Our results do not support a major causal role of serum CRP on anxiety and depression symptoms and life satisfaction, but provides weak evidence that serum CRP may modestly increase anxiety and depression symptoms and reduce life satisfaction. Our findings do not support the recent suggestion that serum CRP may lower anxiety and depression symptoms.