The relationship between COVID-19, depressive disorder, and anxiety: a bidirectional Mendelian randomization study

Liang Zihao; Song Jinyun; Gu Shuanglin; Chen Xiuzhen; Li Yonglin; Zhao Hongyu

doi:10.3389/fpsyt.2023.1257553

The relationship between COVID-19, depressive disorder, and anxiety: a bidirectional Mendelian randomization study

Front Psychiatry. 2023 Oct 19:14:1257553. doi: 10.3389/fpsyt.2023.1257553. eCollection 2023.

Authors

Liang Zihao^#¹, Song Jinyun^#¹, Gu Shuanglin¹, Chen Xiuzhen¹, Li Yonglin², Zhao Hongyu¹

Affiliations

¹ Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
² The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Previous clinical studies have found that negative mental states such as depression and anxiety are closely related to COVID-19 infection. We used Mendelian randomization (MR) to explore the relationship between depression, anxiety, and COVID-19 infection.

Methods: Our data were based on publicly available GWAS databases. The COVID-19 samples were obtained from the COVID-19 Host Genetics Initiative (HGI). The depression samples were obtained from the Psychiatric Genomics Consortium (PGC). The anxiety samples were derived from the Finngen database. We used inverse-variance weighting (IVW) as the primary analysis method, with weighted median, MR Egger, and multivariate MRI adjustment.

Results: There was no causal effect of different COVID-19 infection statuses on depression and anxiety as determined by MR analysis. In addition, in the reverse MR analysis, we found a significant causal effect of anxiety on severe symptoms after COVID-19 infection. The results of the MR Egger regression, weighted median, and weighted mode methods were consistent with the IVW method. Based on sensitivity analyses, horizontal pleiotropy was unlikely to influence the final results.

Conclusion: Our findings indicate that anxiety is a risk factor for severe symptoms following COVID-19 infection. However, the mechanism of interaction between the two needs further investigation.

Keywords: COVID-19; GWAS; Mendelian randomization; anxiety; depression.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Key Medical Science and Technology Development Project of Nanjing Health Science and Technology Development Fund (No. ZKX22039), Nature Foundation Project of Nanjing University of Chinese Medicine (No. XZR2020069), Obstetrics and Gynecology Disease Biobank, Jiangsu Biobank of Clinical Resources (BM2015004), and Jiangsu Province Major Disease Biological Resource Sample Library Open Project of Obstetrics and Gynecology Disease Subbank (Biological Sample Bank of Nanjing Gulou Hospital) (No. TC2021B021).