Causal associations between major depressive disorder and COVID-19

BACKGROUND: We aimed to evaluate whether major depressive disorder (MDD) could aggravate the outcomes of coronavirus disease 2019 (COVID-19) or whether the genetic liability to COVID-19 could trigger MDD. AIMS: We aimed to assess bidirectional causal associations between MDD and COVID-19. METHODS: We performed genetic correlation and Mendelian randomisation (MR) analyses to assess potential associations between MDD and three COVID-19 outcomes. Literature-based network analysis was conducted to construct molecular pathways connecting MDD and COVID-19. RESULTS: We found that MDD has positive genetic correlations with COVID-19 outcomes (r(g): 0.10–0.15). Our MR analysis indicated that genetic liability to MDD is associated with increased risks of COVID-19 infection (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.00 to 1.10, p=0.039). However, genetic liability to the three COVID-19 outcomes did not confer any causal effects on MDD. Pathway analysis identified a panel of immunity-related genes that may mediate the links between MDD and COVID-19. CONCLUSIONS: Our study suggests that MDD may increase the susceptibility to COVID-19. Our findings emphasise the need to increase social support and improve mental health intervention networks for people with mood disorders during the pandemic.