Abstract
Social isolation and loneliness are increasingly recognized as detrimental risk factors for brain health. Here, utilizing data from 383,421 participants in the UK Biobank, we identify significant associations between social isolation, loneliness, and the incidence of 11 neurological and psychiatric disorders, including major depressive disorder (MDD), schizophrenia, bipolar disorder, anxiety disorders, sleep disorders, dementia, Alzheimer’s disease, Parkinson’s disease, stroke, multiple sclerosis, and epilepsy employing Cox regression models. Furthermore, using Mendelian randomization analysis we find evidence for putative relationships from social isolation and loneliness to MDD, schizophrenia, sleep disorders, and epilepsy. We also observe significant associations between social isolation, loneliness, and worse cognitive and emotional performance, as well as alterations in brain structures. Additionally, mediation analyses indicate that peripheral inflammatory and biochemical markers partially mediated the links from social isolation and loneliness to neurological and psychiatric disorders.
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Acknowledgements
This study was supported by grants from grants from the Science and Technology Innovation 2030 Major Projects (grant no. 2022ZD0211600 to J.-T.Y.), the National Natural Science Foundation of China (grant nos 82071201 and 91849126 to J.-T.Y.), Shanghai Municipal Science and Technology Major Project (grant no. No.2018SHZDZX01 to J.-F.F.) and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. We express our gratitude to all the participants and professionals who have contributed to the UK Biobank. We thank Figdraw (www.figdraw.com) to help us draw the study workflow.
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Zhao, YL., Zhang, DD., Gao, PY. et al. Associations of social isolation and loneliness with neurological disorders, psychiatric disorders, brain structures and behavioural phenotypes among UK Biobank participants. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72529-y
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DOI: https://doi.org/10.1038/s41467-026-72529-y
