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睡眠障碍与精神障碍:一项双向孟德尔随机化研究。

Sleep disturbance and psychiatric disorders: a bidirectional Mendelian randomisation study.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang Chinese Medical University, Hangzhou310053, China.

Department of Internal Medicine, University of Minnesota-Twin Cities Medical School, Minneapolis, MN, USA.

出版信息

Epidemiol Psychiatr Sci. 2022 Apr 25;31:e26. doi: 10.1017/S2045796021000810.

Abstract

AIMS

Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.

METHODS

To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).

RESULTS

The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22-1.45; p = 5.03 × 10-11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25-1.37; p = 6.88 × 10-31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23-1.40; p = 1.42 × 10-16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03-1.10, p = 7.85 × 10-4 for PTSD; OR = 1.37, 95% CI 1.14-1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.

CONCLUSIONS

Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.

摘要

目的

睡眠障碍是精神疾病病理生理学和进展的一个重要因素,但它是原因还是下游效应尚不清楚。

方法

为了研究三种与睡眠相关的特征与七种精神疾病之间的因果关系,我们使用与失眠、昼夜节律和睡眠时间相关的遗传变异,进行了两样本双向孟德尔随机化分析。精神疾病的汇总水平数据从精神疾病基因组学联盟中提取。使用逆方差加权(IVW)、加权-IVW、加权中位数法、MR-Egger 回归、MR 偏倚残差总和和异常值(MR-PRESSO)检验和稳健调整轮廓得分(RAPS)获得效应估计值。

结果

遗传确定的失眠症的因果比值比(OR)估计值为 1.33(95%置信区间(CI)1.22-1.45;p=5.03×10-11),与注意缺陷多动障碍(ADHD)相关,1.31(95%CI 1.25-1.37;p=6.88×10-31)与重度抑郁症(MDD)相关,1.32(95%CI 1.23-1.40;p=1.42×10-16)与创伤后应激障碍(PTSD)相关。晨型昼夜节律与 MDD 和精神分裂症(SCZ)的发病风险呈反向关联。遗传预测的睡眠时间也与双相障碍(BD)的发病风险呈正相关。相反,PTSD 和 MDD 与失眠风险增加相关(OR=1.06,95%CI 1.03-1.10,p=7.85×10-4,用于 PTSD;OR=1.37,95%CI 1.14-1.64;p=0.001,用于 MDD)。ADHD 和 MDD 与睡眠持续时间之间也观察到了提示性的反向关联。

结论

我们的研究结果提供了睡眠障碍与精神疾病之间潜在因果关系的证据。这表明异常的睡眠模式可能是精神疾病的标志物,并为精神疾病的预防和管理提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53bf/9069588/d41da707d159/S2045796021000810_fig1.jpg

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