K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Infectious Diseases, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Psychol Med. 2023 Dec;53(16):7561-7568. doi: 10.1017/S0033291723001290. Epub 2023 May 23.
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.
在横断面和孟德尔随机化研究中，血清 C 反应蛋白（CRP）和白细胞介素 6（IL-6）水平与焦虑和抑郁有关，但关于效应大小和方向的结果喜忧参半。最近的一项孟德尔随机化（MR）研究表明，CRP 可能降低，IL-6 可能增加焦虑和抑郁症状。
在基于人群的特隆赫姆健康研究（HUNT）的 68769 名参与者中，我们对血清 CRP 进行了横断面观察性和单样本 MR 分析，并对血清 IL-6 进行了两样本 MR 分析。主要结局是使用医院焦虑和抑郁量表（HADS）评估的焦虑和抑郁症状以及使用七级有序问卷评估的生活满意度，其中较高的分数表示较低的生活满意度。
在横断面观察性分析中，血清 CRP 水平加倍与 HADS 抑郁评分（HADS-D）差异 0.27%（95%CI -0.20 至 0.75）、HADS 焦虑评分（HADS-A）差异-0.77%（95%CI -1.24 至 -0.29）和生活满意度评分差异-0.10%（95%CI -0.41 至 0.21）相关。在单样本 MR 分析中，血清 CRP 加倍与 HADS-D 升高 2.43%（95%CI -0.11 至 5.03）、HADS-A 升高 1.94%（95%CI -0.58 至 4.52）和生活满意度评分升高 2.00%（95%CI 0.45 至 3.59）相关。对于 IL-6，因果点估计值方向相反，但不精确，远未达到统计学意义的常规标准。
我们的结果不支持血清 CRP 对焦虑和抑郁症状和生活满意度有主要的因果作用，但提供了微弱的证据表明，血清 CRP 可能适度增加焦虑和抑郁症状并降低生活满意度。我们的研究结果不支持最近关于血清 CRP 可能降低焦虑和抑郁症状的建议。
