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The risk of social isolation and loneliness on progression from incident cardiovascular disease to subsequent depression

Nature Mental Health volume 3, pages 558–566 (2025)Cite this article

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Abstract

Loneliness and social isolation are crucial triggers in the development of cardiovascular disease (CVD) and depression. This study aimed to explore the associations of loneliness and social isolation with the transition from incident CVD to subsequent depression. Multistate models were constructed to investigate the effects of loneliness and social isolation on the transitions from a healthy state to incident CVD, further to subsequent depression and to death in the UK Biobank cohort (N = 265,794). Participants in the loneliness group had a greater risk for the transition from incident CVD to subsequent depression (hazard ratio = 2.008; 95% confidence interval 1.751–2.351). The hazard ratios of the transition from incident CVD to subsequent depression were 1.148 (1.036–1.274) in the moderately isolated group and 1.173 (1.020–1.348) in the most isolated group. These findings highlight the need for interventions targeting loneliness and social isolation to mitigate the risk of CVD and depression.

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Fig. 1: Flow chart for the selection of the study population.
Fig. 2: Multistate analysis in pattern A.
Fig. 3: Multistate analysis in pattern B.

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Data availability

This project corresponds to UK Biobank application ID 46478. The UKB data are available through the UK Biobank Access Management System (https://www.ukbiobank.ac.uk/). The variables utilized in this study are detailed in Supplementary Table 17.

Code availability

The code used for multistate analyses is available via the GitHub repository at https://github.com/xinqi0702/mstate.

References

  1. GBD 2021 Causes of Death Collaborators. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 403, 2100–2132 (2024).

    Article  Google Scholar 

  2. Piao, J. et al. Alarming changes in the global burden of mental disorders in children and adolescents from 1990 to 2019: a systematic analysis for the Global Burden of Disease study. Eur. Child Adolesc. Psychiatry 31, 1827–1845 (2022).

    Article  PubMed  Google Scholar 

  3. Djärv, T., Wikman, A. & Lagergren, P. Number and burden of cardiovascular diseases in relation to health-related quality of life in a cross-sectional population-based cohort study. BMJ Open 2, e001554 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yamabe, K., Liebert, R., Flores, N. & Pashos, C. L. Health-related quality of life outcomes, economic burden, and associated costs among diagnosed and undiagnosed depression patients in Japan. Clinicoeconon. Outcomes Res. 11, 233–243 (2019).

    Article  Google Scholar 

  5. Correll, C. U. et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry 16, 163–180 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kendler, K. S., Gardner, C. O., Fiske, A. & Gatz, M. Major depression and coronary artery disease in the Swedish twin registry: phenotypic, genetic, and environmental sources of comorbidity. Arch. Gen. Psychiatry 66, 857–863 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jha, M. K., Qamar, A., Vaduganathan, M., Charney, D. S. & Murrough, J. W. Screening and management of depression in patients with cardiovascular disease: JACC state-of-the-art review. J. Am. Coll. Cardiol. 73, 1827–1845 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Moradi, M., Doostkami, M., Behnamfar, N., Rafiemanesh, H. & Behzadmehr, R. Global prevalence of depression among heart failure patients: a systematic review and meta-analysis. Curr. Probl. Cardiol. 47, 100848 (2022).

    Article  PubMed  Google Scholar 

  9. Golaszewski, N. M. et al. Evaluation of social isolation, loneliness, and cardiovascular disease among older women in the US. JAMA Netw. Open 5, e2146461 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang, Y. et al. Loneliness, social isolation, depression and anxiety among the elderly in Shanghai: findings from a longitudinal study. Arch. Gerontol. Geriatr. 110, 104980 (2023).

    Article  PubMed  Google Scholar 

  11. Matthews, T. et al. Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis. Soc. Psychiatry Psychiatr. Epidemiol. 51, 339–348 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cacioppo, S., Grippo, A. J., London, S., Goossens, L. & Cacioppo, J. T. Loneliness: clinical import and interventions. Perspect. Psychol. Sci. 10, 238–249 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Escalante, E., Golden, R. L. & Mason, D. J. Social isolation and loneliness: imperatives for health care in a post-COVID world. JAMA 325, 520–521 (2021).

    Article  PubMed  Google Scholar 

  14. Freedman, A. & Nicolle, J. Social isolation and loneliness: the new geriatric giants: approach for primary care. Can. Fam. Physician 66, 176–182 (2020).

    PubMed  PubMed Central  Google Scholar 

  15. Weeks, M. S. & Asher, S. R. Loneliness in childhood: toward the next generation of assessment and research. Adv. Child Dev. Behav. 42, 1–39 (2012).

    Article  PubMed  Google Scholar 

  16. Paul, E., Bu, F. & Fancourt, D. Loneliness and risk for cardiovascular disease: mechanisms and future directions. Curr. Cardiol. Rep. 23, 68 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bowirrat, A. & Elman, I. Neurogenetics and epigenetics of loneliness. Psychol. Res. Behav. Manage. 16, 4839–4857 (2023).

    Article  Google Scholar 

  18. Valtorta, N. K., Kanaan, M., Gilbody, S., Ronzi, S. & Hanratty, B. Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies. Heart 102, 1009–1016 (2016).

    Article  PubMed  Google Scholar 

  19. Christiansen, J. et al. Loneliness, social isolation, and chronic disease outcomes. Ann. Behav. Med. 55, 203–215 (2021).

    Article  PubMed  Google Scholar 

  20. Bae, S. M. The association between adverse childhood and adulthood experiences, social isolation, loneliness, and depression among young adults in South Korea. Int. J. Environ. Res. Public Health 20, 6900 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Díaz-Mardomingo, M. D. C. et al. Sex-related differences in the associations between diurnal cortisol pattern and social and emotional loneliness in older adults. Front. Psychol. 14, 1199405 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Xia, N. & Li, H. Loneliness, social isolation, and cardiovascular health. Antioxid. Redox Signal. 28, 837–851 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Leistner, C. & Menke, A. Hypothalamic–pituitary–adrenal axis and stress. Handb. Clin. Neurol. 175, 55–64 (2020).

    Article  PubMed  Google Scholar 

  24. Kovaleva, M., Spangler, S., Clevenger, C. & Hepburn, K. Chronic stress, social isolation, and perceived loneliness in dementia caregivers. J. Psychosoc. Nurs. Ment. Health Serv. 56, 36–43 (2018).

    Article  PubMed  Google Scholar 

  25. Gulyaeva, N. V. Stress-associated molecular and cellular hippocampal mechanisms common for epilepsy and comorbid depressive disorders.Biochemistry 86, 641–656 (2021).

    PubMed  Google Scholar 

  26. Van Bogart, K. et al. The association between loneliness and inflammation: findings from an older adult sample. Front. Behav. Neurosci. 15, 801746 (2021).

    Article  PubMed  Google Scholar 

  27. Hackett, R. A., Hamer, M., Endrighi, R., Brydon, L. & Steptoe, A. Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women. Psychoneuroendocrinology 37, 1801–1809 (2012).

    Article  PubMed  Google Scholar 

  28. Akçay, E. et al. Loneliness, internalizing symptoms, and inflammatory markers in adolescent COVID-19 survivors. Child Care Health Dev. 48, 1112–1121 (2022).

    Article  PubMed  Google Scholar 

  29. Li, H. & Xia, N. The role of oxidative stress in cardiovascular disease caused by social isolation and loneliness. Redox Biol. 37, 101585 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Matthews, T. et al. Social isolation, loneliness, and inflammation: a multi-cohort investigation in early and mid-adulthood. Brain Behav. Immun. 115, 727–736 (2024).

    Article  PubMed  Google Scholar 

  31. Shankar, A., McMunn, A., Banks, J. & Steptoe, A. Loneliness, social isolation, and behavioral and biological health indicators in older adults. Health Psychol. 30, 377–385 (2011).

    Article  PubMed  Google Scholar 

  32. Colaianna, M. et al. Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress. Antioxid. Redox Signal. 18, 1385–1399 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chu, H. Y. & Chan, H. S. Loneliness and social support among the middle-aged and elderly people with visual impairment. Int. J. Environ. Res. Public Health 19, 14600 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kotwal, A. A. et al. A peer intervention reduces loneliness and improves social well-being in low-income older adults: a mixed-methods study. J. Am. Geriatr. Soc. 69, 3365–3376 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zaid, M. et al. Associations of high-density lipoprotein particle and high-density lipoprotein cholesterol with alcohol intake, smoking, and body mass index—the INTERLIPID Study. Circ. J. 82, 2557–2565 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Barua, R. S. & Ambrose, J. A. Mechanisms of coronary thrombosis in cigarette smoke exposure. Arterioscler. Thromb. Vasc. Biol. 33, 1460–1467 (2013).

    Article  PubMed  Google Scholar 

  37. Wang, X. et al. Joint association of loneliness and traditional risk factor control and incident cardiovascular disease in diabetes patients. Eur. Heart J. 44, 2583–2591 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hackett, R. A., Hudson, J. L. & Chilcot, J. Loneliness and type 2 diabetes incidence: findings from the English Longitudinal Study of Ageing. Diabetologia 63, 2329–2338 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sudlow, C. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Song, Y. et al. Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomization. EClinicalMedicine 64, 102236 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wang, X. et al. Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study. Thorax 78, 698–705 (2023).

    Article  PubMed  Google Scholar 

  42. Wang, X. et al. Ambient air pollution associated with incident asthma, subsequent cardiovascular disease and death: a trajectory analysis of a national cohort. J. Hazard. Mater. 460, 132372 (2023).

    Article  PubMed  Google Scholar 

  43. Bisquera, A. et al. Inequalities in developing multimorbidity over time: a population-based cohort study from an urban, multi-ethnic borough in the United Kingdom. Lancet Reg. Health. Eur. 12, 100247 (2022).

    Article  PubMed  Google Scholar 

  44. Han, Y., Hu, Y. & Yu, C. Lifestyle, cardiometabolic disease, and multimorbidity in a prospective Chinese study. Eur. Heart J. 42, 3374–3384 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Wang, X. et al. Population attributable fraction of lung cancer due to genetic variants, modifiable risk factors, and their interactions: a nationwide prospective cohort study. Chemosphere 301, 134773 (2022).

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank the UK Biobank participants and the UK Biobank team for their work in collecting, processing and disseminating these data for analysis. This study was supported by the Natural Science Basic Research Plan in Shaanxi Province of China (2021JCW-08 to F.Z.). The funding body played no role in study design, data collection and analysis, decision to publish or preparation of the paper.

Author information

Author notes

  1. These authors contributed equally: Xin Qi, Shiqiang Cheng.

Authors and Affiliations

  1. Department of Psychiatry, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P. R. China

    Xin Qi & Feng Zhang

  2. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, P. R. China

    Xin Qi, Shiqiang Cheng, Li Liu, Jingcan Hao, Wenming Wei, Chuyu Pan, Meijuan Kang, Yan Wen, Bolun Cheng & Feng Zhang

  3. Precision Medicine Center, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P. R. China

    Xin Qi & Jin Yang

  4. Department of Medical Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P. R. China

    Jin Yang

  5. The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P. R. China

    Jingcan Hao

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Contributions

F.Z. and X.Q. designed and conceptualized this study. F.Z., X.Q. and S.C. acquired the data. X.Q., W.W., C.P. and L.L. performed the data generation, processing and statistical analyses. J.Y., J.H., Y.W., M.K. and B.C. contributed to the interpretation of the significant results and scientific discussion. All of the authors wrote and revised the paper.

Corresponding author

Correspondence to Feng Zhang.

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Nature Mental Health thanks Elisabeth Lambert and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Tables 1–17.

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Qi, X., Cheng, S., Yang, J. et al. The risk of social isolation and loneliness on progression from incident cardiovascular disease to subsequent depression. Nat. Mental Health 3, 558–566 (2025). https://doi.org/10.1038/s44220-025-00418-2

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