Zhou Xiang, Qiao Nidan
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Front Endocrinol (Lausanne). 2019 Aug 16;10:564. doi: 10.3389/fendo.2019.00564. eCollection 2019.
The conflicting evidence as to whether a real association exists between cortisol levels and depression lends support to adopting a Mendelian randomization approach to investigate whether cortisol levels have a causal effect with depression. Single nucleotide polymorphisms (SNPs) associated with serum morning plasma cortisol level and salivary cortisol level from CORNET consortium (12,597 participants) were proposed as instrumental variables. The primary outcome was depression, and the secondary outcomes were neuroticism and cognitive performance. Summary-level statistics were extracted from the Social Science Genetic Association Consortium including the United Kingdom Biobank cohort (105,739 subjects). Multiple analysis methods (inverse-variance weighted method, max likelihood method, weighted median estimator, model-based estimation, heterogeneity-penalized method, and MR-Egger regression) were applied to test the stability of the summary causal estimate. Weighted median analysis estimated that the effect of serum morning cortisol on depression score was 0.027 per standard deviation increase of cortisol (95% CI, 0.000-0.054; = 0.043). Other sensitivity analysis suggested similar results suggesting the result was robust. No evidence of pleiotropy (MR-Egger intercept, -0.002; = 0.739) was observed. The effect of serum cortisol on neuroticism was 0.030 (95% CI, 0.008-0.052; = 0.006) by weighted median estimator. None of the methods observed the effect of serum cortisol level on cognitive function. As for the effect of salivary cortisol level, no method obtained a -value lower than 0.05 in any of the outcomes. Mendelian randomization analysis provided evidence that a genetic predisposition to higher serum morning cortisol level was associated with increased depression score.
关于皮质醇水平与抑郁症之间是否存在真正关联的证据相互矛盾，这支持采用孟德尔随机化方法来研究皮质醇水平是否对抑郁症有因果影响。来自CORNET联盟（12597名参与者）的与血清早晨血浆皮质醇水平和唾液皮质醇水平相关的单核苷酸多态性（SNP）被提议作为工具变量。主要结局是抑郁症，次要结局是神经质和认知表现。汇总统计数据从社会科学遗传关联联盟提取，包括英国生物银行队列（105739名受试者）。应用多种分析方法（逆方差加权法、最大似然法、加权中位数估计法、基于模型的估计法、异质性惩罚法和MR-Egger回归）来检验汇总因果估计的稳定性。加权中位数分析估计，血清早晨皮质醇每增加一个标准差，对抑郁评分的影响为0.027（95%CI，0.000 - 0.054；P = 0.043）。其他敏感性分析表明结果相似，表明结果具有稳健性。未观察到多效性的证据（MR-Egger截距，-0.002；P = 0.739）。通过加权中位数估计法，血清皮质醇对神经质的影响为0.030（95%CI，0.008 - 0.052；P = 0.006）。没有一种方法观察到血清皮质醇水平对认知功能的影响。至于唾液皮质醇水平的影响，在任何结局中，没有一种方法获得的P值低于0.05。孟德尔随机化分析提供了证据，表明血清早晨皮质醇水平较高的遗传易感性与抑郁评分增加有关。
