Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Neurology, University of Texas Southwestern, Dallas, TX, United States.
Mult Scler Relat Disord. 2024 Nov;91:105866. doi: 10.1016/j.msard.2024.105866. Epub 2024 Sep 6.
Depression is common and phenotypically heterogenous in multiple sclerosis (MS). MS may increase risk of some but not all affective symptoms or certain symptoms may predispose individuals to higher MS risk.
To assess the existence and direction of causality between distinct depressive symptoms and MS using two-sample Mendelian randomization (MR).
Using summary data from genome-wide association studies, we selected genetic instrument variables (IV) for MS (n = 115,776) and IVs for depressive symptoms (average n = 117,713): anhedonia, altered appetite, concentration, depressed mood, fatigue, inadequacy, psychomotor changes, sleeping problems and suicidality. We performed two-sample MR in either direction using inverse-variance models. Sensitivity analyses included weighted-median and MR-Egger regression. Obesity is a known risk factor for MS and depression; we adjusted for body mass index in multivariable-MR.
Genetic liability to MS was associated with anhedonia (IVW estimate per 10: 0.69; 95 % CI: 0.24-1.13; p = 0.002), concentration difficulty (0.66; 0.19-1.13; p = 0.006) and psychomotor changes (0.37; 0.08-0.65; p = 0.01). Results were similar in sensitivity analyses. In the opposite direction, we found no evidence of a causal relationship for any affective symptom on MS risk.
Genetic susceptibility to MS was associated with anhedonia, concentration, and psychomotor-related symptoms, suggesting a specific phenotype of depression in MS.
抑郁症在多发性硬化症（MS）中较为常见且表型异质。MS 可能会增加某些但不是所有情感症状的风险，或者某些症状可能使个体更容易患上 MS。
使用两样本 Mendelian 随机化（MR）评估不同抑郁症状与 MS 之间的存在和因果关系。
使用全基因组关联研究的汇总数据，我们选择了 MS 的遗传工具变量（IV）（n=115776）和抑郁症状的 IV（平均 n=117713）：快感缺失、食欲改变、注意力、情绪低落、疲劳、不足感、精神运动变化、睡眠问题和自杀意念。我们使用逆方差模型在两个方向上进行了两样本 MR。敏感性分析包括加权中位数和 MR-Egger 回归。肥胖是 MS 和抑郁症的已知危险因素；我们在多变量-MR 中调整了体重指数。
MS 的遗传易感性与快感缺失（每 10 个 IVW 估计值：0.69；95%CI：0.24-1.13；p=0.002）、注意力困难（0.66；0.19-1.13；p=0.006）和精神运动变化（0.37；0.08-0.65；p=0.01）相关。敏感性分析结果相似。在相反的方向，我们没有发现任何情感症状对 MS 风险有因果关系的证据。
MS 的遗传易感性与快感缺失、注意力和精神运动相关症状有关，提示 MS 中存在特定的抑郁表型。
