Key result
Genetically predicted CRP fails to show a major causal effect on depression symptoms.
Why the study?
Serum levels of CRP and IL-6 have been associated with anxiety and depression, but results regarding effect size and direction have been mixed.
Do genetically predicted serum CRP and IL-6 levels affect anxiety, depression symptoms, and life satisfaction in a population-based cohort?
Observational (n=68,769)
Do genetically predicted serum CRP and IL-6 levels affect anxiety, depression symptoms, and life satisfaction in a population-based cohort?
Effect estimate: 2.43% higher (95% CI -0.11 to 5.03)
p-value: p=0.061
The study provides weak evidence that genetically predicted higher serum CRP may modestly increase anxiety and depression symptoms and reduce life satisfaction, challenging previous suggestions that CRP lowers these symptoms.
Weak CRP-mood associations support no clinical action; leaves open causal effects on mental health.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Bekkevold et al. (2023) conducted an observational in Anxiety, depression symptoms, and life satisfaction (n=68,769). Genetically predicted serum C-reactive protein (CRP) and interleukin-6 (IL-6) vs. Lower genetically predicted serum levels was evaluated on Hospital Anxiety and Depression Scale depression score (HADS-D) (2.43% higher, 95% CI -0.11 to 5.03, p=0.061). Genetically predicted serum CRP levels did not show a major causal role on mental health, providing only weak evidence that a doubling in CRP modestly increases depression symptoms by 2.43%.
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