Common mental disorders and risk of spontaneous abortion or recurrent spontaneous abortion: A two-sample Mendelian randomization study

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.