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 (rg: 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.

[1]  A. Baranova,et al.  Causal associations and shared genetics between hypertension and COVID‐19 , 2023, Journal of medical virology.

[2]  A. Baranova,et al.  Shared genetics and bidirectional causal relationships between type 2 diabetes and attention-deficit/hyperactivity disorder , 2023, General Psychiatry.

[3]  A. Baranova,et al.  Shared genetics and causal associations between COVID‐19 and multiple sclerosis , 2022, Journal of medical virology.

[4]  A. Baranova,et al.  A phenome‐wide investigation of risk factors for severe COVID‐19 , 2022, Journal of medical virology.

[5]  A. Baranova,et al.  Causal Associations Between Basal Metabolic Rate and COVID-19. , 2022, Diabetes.

[6]  A. Baranova,et al.  Associations between pulse rate and COVID‐19 , 2022, Journal of Medical Virology.

[7]  L. Cai,et al.  Investigating genetic causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being , 2022, General Psychiatry.

[8]  N. Hoertel,et al.  Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19 , 2022, European Psychiatry.

[9]  Bin Zhang,et al.  Handgrip strength and the risk of major depressive disorder: a two-sample Mendelian randomisation study , 2022, General Psychiatry.

[10]  B. Mégarbane,et al.  Molecular Bases of Serotonin Reuptake Inhibitor Antidepressant-Attributed Effects in COVID-19: A New Insight on the Role of Bradykinins , 2022, Journal of personalized medicine.

[11]  A. Baranova,et al.  Causal effect of COVID‐19 on Alzheimer's disease: A Mendelian randomization study , 2022, Journal of medical virology.

[12]  A. Baranova,et al.  Bidirectional causal associations between type 2 diabetes and COVID‐19 , 2022, Journal of medical virology.

[13]  I. Mitchell,et al.  What are the long‐term holistic health consequences of COVID‐19 among survivors? An umbrella systematic review , 2022, Journal of medical virology.

[14]  Fuquan Zhang,et al.  Severe COVID-19 increases the risk of schizophrenia , 2022, Psychiatry Research.

[15]  M. D. Forti,et al.  TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms , 2022, General Psychiatry.

[16]  J. Seibel,et al.  The Acid Ceramidase Is a SARS-CoV-2 Host Factor , 2022, Cells.

[17]  A. Rodrigues,et al.  SARS-CoV-2 consequences for mental health: Neuroinflammatory pathways linking COVID-19 to anxiety and depression , 2022, World journal of psychiatry.

[18]  C. Pistarini,et al.  Psychiatric symptoms subsequent to COVID-19 and their association with clinical features: A retrospective investigation , 2022, Psychiatry Research.

[19]  Sara Bocci Benucci,et al.  Effects of the COVID-19 pandemic on psychological health in a sample of Italian adults: A three-wave longitudinal study , 2022, Psychiatry Research.

[20]  H. Fukuda,et al.  Acute and delayed psychiatric sequelae among patients hospitalised with COVID-19: a cohort study using LIFE study data , 2022, General Psychiatry.

[21]  K. Lloyd,et al.  COVID‐19‐related posttraumatic stress disorder in adults with lived experience of psychiatric disorder , 2022, Depression and anxiety.

[22]  Fuquan Zhang,et al.  Convergent lines of evidence supporting involvement of NFKB1 in schizophrenia , 2022, Psychiatry Research.

[23]  M. Bagatini,et al.  COVID-19, Oxidative Stress, and Neuroinflammation in the Depression Route , 2022, Journal of Molecular Neuroscience.

[24]  K. Hashimoto,et al.  Mechanisms of action of fluvoxamine for COVID-19: a historical review , 2022, Molecular Psychiatry.

[25]  Fuquan Zhang,et al.  Smoking quantitatively increases risk for COVID-19 , 2021, European Respiratory Journal.

[26]  A. Campo‐Arias,et al.  Relation of perceived discrimination with depression, insomnia and post-traumatic stress in COVID-19 survivors , 2021, Psychiatry Research.

[27]  A. Toubasi,et al.  Meta-analysis of prevalence: the psychological sequelae among COVID-19 survivors , 2021, International journal of psychiatry in clinical practice.

[28]  A. Akbari,et al.  Long COVID syndrome‐associated brain fog , 2021, Journal of medical virology.

[29]  R. McIntyre,et al.  Association Between Mood Disorders and Risk of COVID-19 Infection, Hospitalization, and Death: A Systematic Review and Meta-analysis. , 2021, JAMA psychiatry.

[30]  Jiu Chen,et al.  Genetic mechanisms of COVID-19 and its association with smoking and alcohol consumption , 2021, Briefings Bioinform..

[31]  Jiu Chen,et al.  Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder , 2021, The Journal of clinical investigation.

[32]  K. Hashimoto.  Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor , 2021, European Archives of Psychiatry and Clinical Neuroscience.

[33]  Camille Blais-Rochette,et al.  Prevalence of symptoms of depression, anxiety, insomnia, posttraumatic stress disorder, and psychological distress among populations affected by the COVID-19 pandemic: A systematic review and meta-analysis , 2020, Psychiatry Research.

[34]  OUP accepted manuscript , 2021, Human Molecular Genetics.

[35]  J. Miller,et al.  Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. , 2020, JAMA.

[36]  J. Flory,et al.  The COVID-19 Pandemic as a Traumatic Stressor: Mental Health Responses of Older Adults With Chronic PTSD , 2020, The American Journal of Geriatric Psychiatry.

[37]  N. Volkow,et al.  Increased risk of COVID‐19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States , 2020, World psychiatry : official journal of the World Psychiatric Association.

[38]  Z. Silver,et al.  The prevalence of depression, anxiety, and sleep disturbances in COVID‐19 patients: a meta‐analysis , 2020, Annals of the New York Academy of Sciences.

[39]  The COVID-19 Host Genetics Initiative.  The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic , 2020, European Journal of Human Genetics.

[40]  J. Kohn,et al.  Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms , 2020, Brain, Behavior, and Immunity.

[41]  Damian Szklarczyk,et al.  STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets , 2018, Nucleic Acids Res..

[42]  R. Marioni,et al.  Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions , 2018, Nature Neuroscience.

[43]  R. Marioni,et al.  Edinburgh Research Explorer Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways , 2022 .

[44]  Valeriia Haberland,et al.  The MR-Base platform supports systematic causal inference across the human phenome , 2018, eLife.

[45]  D. Posthuma,et al.  Functional mapping and annotation of genetic associations with FUMA , 2017, Nature Communications.

[46]  Toshio Tanaka,et al.  Immunotherapeutic implications of IL-6 blockade for cytokine storm. , 2016, Immunotherapy.

[47]  B. Penninx,et al.  Cytokine production capacity in depression and anxiety , 2016, Translational Psychiatry.

[48]  Yong-Ku Kim,et al.  The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression , 2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[49]  M. Daly,et al.  An Atlas of Genetic Correlations across Human Diseases and Traits , 2015, Nature Genetics.

[50]  G. Davey Smith,et al.  Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression , 2015, International journal of epidemiology.

[51]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

[52]  Sergei Egorov,et al.  Pathway studio - the analysis and navigation of molecular networks , 2003, Bioinform..