Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China; Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an 710038, China.
Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China; Clinical Research Center for Reproductive Medicine and Gynecological Endocrine Diseases of Shaanxi Province, Xi'an 710038, China; Xi'an Medical University, Xi'an 710016, China.
J Affect Disord. 2024 Jun 1;354:258-266. doi: 10.1016/j.jad.2024.03.026. Epub 2024 Mar 13.
The direct causal relationships between common mental disorders (anxiety disorders, broad depression, major depressive disorder (MDD), bipolar disorder, and insomnia) and miscarriage or recurrent spontaneous abortion (RSA) are unclear. Therefore, this study aimed to explore these, using Mendelian randomization.
Genome-wide association studies (GWAS) meta-analyses with the largest sample size possible and selected independent single individuals of European ancestry were selected. Inverse variance weighted (IVW) was the main analysis method. The heterogeneity of the instrumental variables (IVs) was assessed using IVW and MR-Egger, and the horizontal pleiotropy of the IVs was assessed using MR-Egger and MR-PRESSO.
Based on IVW results, the four mental disorders were found to be causally associated with spontaneous abortion (anxiety disorder: OR (95%CI), 1.230 (1.063-1.420), P = 0.0050; major depressive disorder: 1.690 (1.239-2.307), P = 0.0009; bipolar disorder: 1.110 (1.052-1.170), P = 0.0001; insomnia: 1.292 (1.076-1.552), P = 0.0060). Furthermore, no causal relationship was observed between broad depression and spontaneous abortion. Five common mental disorders were not causally associated with the RSA.
(1) Our analysis was limited to the European population; (2) the duration of mental disorders was not analyzed, as no information was available; and (3) it was difficult to completely detect genetic pleiotropy.
Anxiety disorders, MDD, bipolar disorder, and insomnia may contribute to spontaneous abortion. Therefore, we should focus on the mental and sleep health of pregnant women. Future studies may be required on whether mental disorders directly lead to RSA, especially unexplained RSA.
常见精神障碍（焦虑障碍、广泛抑郁、重度抑郁症（MDD）、双相情感障碍和失眠）与流产或自然流产复发（RSA）之间的直接因果关系尚不清楚。因此，本研究旨在使用孟德尔随机化来探讨这些问题。
选择了具有最大样本量的全基因组关联研究（GWAS）荟萃分析和选定的独立欧洲血统个体。主要分析方法为逆方差加权（IVW）。使用 IVW 和 MR-Egger 评估工具变量（IVs）的异质性，并使用 MR-Egger 和 MR-PRESSO 评估 IVs 的水平偏倚。
基于 IVW 结果，发现四种精神障碍与自然流产存在因果关系（焦虑障碍：OR（95%CI），1.230（1.063-1.420），P=0.0050；重度抑郁症：1.690（1.239-2.307），P=0.0009；双相情感障碍：1.110（1.052-1.170），P=0.0001；失眠：1.292（1.076-1.552），P=0.0060）。此外，广泛抑郁与自然流产之间没有因果关系。五种常见精神障碍与 RSA 没有因果关系。
（1）我们的分析仅限于欧洲人群；（2）由于没有信息，我们没有分析精神障碍的持续时间；（3）很难完全检测遗传偏倚。
焦虑障碍、MDD、双相情感障碍和失眠可能导致自然流产。因此，我们应该关注孕妇的精神和睡眠健康。未来可能需要研究精神障碍是否直接导致 RSA，特别是不明原因的 RSA。
