期刊
ECLINICALMEDICINE
卷 38, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.eclinm.2021.100992
关键词
Depression; Anxiety; Inflammation; CRP; Il-6; Mendelian randomisation
资金
- Wellcome Trust [201486/Z/16/Z]
- Data Science Award from the MQ: Transforming Mental Health [MQDS17/40]
- Medical Research Council UK [MC_PC_17213, MR/S037675/1]
- BMA Foundation
- International Max Planck Research School of Translational Psychiatry (IMPRS-TP)
- Medical Research Council [MC_UU_00011/1]
- Wellcome Trust [201486/Z/16/Z] Funding Source: Wellcome Trust
The study found that circulating CRP concentrations were associated with depressive and anxiety symptom scores and probable diagnoses in a dose-response manner. Genetically predicted higher IL-6 activity was linked to increased risk of depression, while higher CRP concentration was associated with decreased risks of depression and anxiety symptoms.
Background: Concentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse. Methods: Using population-based data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety. The study was conducted from June 2019 to February 2021. Findings: CRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms. Interpretation: Altered activity of the IL-6/IL-6R pathway could be a risk factor for depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety. (C) 2021 The Authors. Published by Elsevier Ltd.
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