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.