Social Isolation and Aging health in Schizophrenia spectrum disorders (SIAS): study protocol for a multinational longitudinal study

Individuals diagnosed with schizophrenia spectrum disorder (SSD) face an elevated risk of premature mortality, with life expectancy reduced by 10 to 20 years compared with the general population. This excess mortality is largely due to the early onset of medical conditions typically associated with older age, a process known as accelerated aging. While unhealthy lifestyle behaviors, such as smoking and poor diet, contribute to this risk, they do not fully account for the excess of physical comorbidities. Social isolation, which is associated with numerous health conditions in the general population and is a common, persistent characteristic among people with SSD, has not been comprehensively investigated as a contributing factor. The Social Isolation and Aging in Schizophrenia spectrum disorders (SIAS) study establishes a longitudinal database of 650 participants initially recruited to studies in the Netherlands, UK, Spain, and US, including 500 individuals with SSD and 150 unaffected first-degree relatives. An accelerated longitudinal design is employed, combining prior research data collected when participants were aged 20–55 with new follow-up assessments now that they are aged 40–70, allowing to study exposures and outcomes through the entire age-range of the sample (20–70). Clinical and digital phenotype data are being collected. The primary objective is to determine the association between social isolation and adverse health outcomes in SSD. Additionally, the study examines the directionality of this relationship, moderating factors, and the impact of the COVID-19 pandemic. This is the first large-scale follow-up study examining the long-term health impact of social isolation in individuals with SSD. Key strengths include the integration of data across a five-decade age span, the cross-national design, the inclusion of unaffected first-degree relatives to assess familial factors, and the integration of digital phenotypic and clinical assessments. Findings from SIAS will provide critical insights into prevention targets for reducing premature mortality and improving overall health in SSD. This study was registered at ClinicalTrials.gov with ID number NCT07419321.