The effect of polygenic liability to mental disorders on COVID-19 outcomes in people with depression: the mediating role of anxiety

• Published in: Psychological medicine 2024-11, Vol.54 (15), p.1-10
• Main Authors: Monistrol-Mula, Anna, Felez-Nobrega, Mireia, Byrne, Enda M, Lind, Penelope A, Hickie, Ian B, Martin, Nicholas G, Medland, Sarah E, Colodro-Conde, Lucía, Mitchell, Brittany L
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291724001983

Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression. Data from three assessments of the Australian Genetics of Depression Study ( = 4405; 52.2 years ± 14.9; 76.2% females) were analyzed. Outcomes included COVID-19 clinical outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection and long COVID, noting the low incidence of COVID-19 cases in Australia at that time) and COVID-19 psychological outcomes (COVID-related stress and COVID-19 burnout). Predictors included PRS for depression, bipolar disorder, schizophrenia, and anxiety. The associations between these PRSs and the outcomes were assessed with adjusted linear/logistic/multinomial regressions. Mediation ( = 4338) and moderation ( = 3326) analyses were performed to explore the potential influence of anxiety symptoms and resilience on the identified associations between the PRSs and COVID-19 psychological outcomes. None of the selected PRS predicted SARS-CoV-2 infection or long COVID. In contrast, the depression PRS predicted higher levels of COVID-19 burnout. Anxiety symptoms fully mediated the association between the depression PRS and COVID-19 burnout. Resilience did not moderate this association. A higher genetic risk for depression predicted higher COVID-19 burnout and this association was fully mediated by anxiety symptoms. Interventions targeting anxiety symptoms may be effective in mitigating the psychological effects of a pandemic among people with depression.