Zhao Sizheng Steven, Holmes Michael V, Alam Uazman
Centre for Epidemiology Versus Arthritis, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Medical Research Council, Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Semin Arthritis Rheum. 2023 Jun;60:152188. doi: 10.1016/j.semarthrit.2023.152188. Epub 2023 Mar 11.
Depression and chronic widespread pain (CWP) frequently coexist, but whether depression is an independent causal risk factor for CWP, and/or vice versa, remains unclear. We investigated the bidirectional causal relationship between depression and CWP.
We performed a two-sample Mendelian randomisation (MR) study to estimate the causal relationship between genetically predicted depression (170,756 cases, 329,443 controls) and risk of CWP (6,914 cases, 242,929 controls), and the effect of CWP on depression susceptibility, using large population-level genetic data. We used a new MR method, Causal Analysis Using Summary Effect estimates (CAUSE), which allows for sample overlap, in addition to traditional MR and sensitivity analyses.
For each doubling in odds of genetic liability to depression, the risk of chronic widespread pain was increased (OR 1.004, 95% credible interval 1.003-1.005; p = 7.3 × 10 that the causal model is a better fit than non-causal model). There was bidirectional evidence of causality, with genetic liability to chronic widespread pain increasing depression susceptibility (OR 2.31; 95%CrI 1.57, 3.40; p = 0.0026 that the causal model is a better fit). Other MR methods produced concordant results.
This study provides evidence in support of a bidirectional causal relationship between depression and increased risk of chronic widespread pain, whilst overcoming the major limitations of previous epidemiological studies. Interventions for depression may be an effective strategy to prevent or reduce the burden of chronic widespread pain and vice versa.
抑郁症与慢性广泛性疼痛（CWP）常并存，但抑郁症是否为CWP的独立因果危险因素，和/或反之亦然，仍不明确。我们研究了抑郁症与CWP之间的双向因果关系。
我们进行了一项两样本孟德尔随机化（MR）研究，以使用大规模人群水平的遗传数据估计基因预测的抑郁症（170,756例病例，329,443例对照）与CWP风险（6,914例病例，242,929例对照）之间的因果关系，以及CWP对抑郁症易感性的影响。除了传统的MR和敏感性分析外，我们还使用了一种新的MR方法，即使用汇总效应估计值的因果分析（CAUSE），该方法允许样本重叠。
抑郁症遗传易感性的比值每增加一倍，慢性广泛性疼痛的风险就会增加（比值比1.004，95%可信区间1.003 - 1.005；p = 7.3×10，表明因果模型比非因果模型更适合）。存在双向因果关系的证据，慢性广泛性疼痛的遗传易感性增加了抑郁症易感性（比值比2.31；95%可信区间1.57, 3.40；p = 0.0026，表明因果模型更适合）。其他MR方法得出了一致的结果。
本研究提供了证据支持抑郁症与慢性广泛性疼痛风险增加之间的双向因果关系，同时克服了以往流行病学研究的主要局限性。抑郁症干预可能是预防或减轻慢性广泛性疼痛负担的有效策略，反之亦然。
