The impact of social isolation on aging health in schizophrenia

PROJECT SUMMARY Individuals diagnosed with schizophrenia and related psychotic disorders (SZ) exhibit a markedly elevated risk of premature mortality, with a 10-20-year shorter lifespan relative to the general population. Increased mortality rates in SZ are largely attributable to the early manifestation of medical conditions that normally occur later in life, a process known as 'accelerated aging'. While unhealthy lifestyle behaviors, such as smoking and unhealthy diet, account, in part, for accelerated aging in SZ, the excess of physical comorbidities cannot be solely attributed to these factors. Remarkably, the direct adverse health effects of key clinical characteristics of SZ have rarely been considered. In the general population, the absence of social contact is known to pose enormous challenges for physical health, especially at older ages. Given that social isolation is a persistent and disabling feature of SZ, it is possible that this behavior may contribute to the premature manifestation of health conditions in SZ. Building on rich pilot data pointing to significant associations between social isolation and long-term perceived health in SZ, our overarching goal is to test whether and how social isolation contributes to the health challenges of individuals with SZ as they age. With participants from Europe (EU-GEI) and the US (Olin Neuropsychiatry Research Center), we will create a longitudinal database of 650 participants, including 500 individuals with SZ, and 150 of their unaffected siblings. We will apply an accelerated longitudinal design by re- assessing and by examining medical records of research participants who were first evaluated between the ages of 30-50 and are now 50-65 years of age, a period when many medical conditions and health problems tend to manifest. We will determine the age-related association between social isolation and adverse health outcomes in SZ, test for familiality, directionality, and factors moderating this association, and determine the extent to which the COVID-19 pandemic and the resulting imposed lockdowns impacted health in SZ. We will consider generalizability across countries, sexes, and race/ethnicities. The rationale for the proposed research is that in order to facilitate much-needed targeted therapies to prevent early mortality in SZ, we need to better understand factors that contribute to the excess of medical comorbidities in SZ. Our central hypothesis is that social isolation, a common and persistent characteristic of SZ, contributes to the excess of physical comorbidities in SZ. To meet our overall goal, we will pursue the following aims: (1) Determine the association between social isolation and adverse health outcomes in SZ; (2) Test for the directionality, and moderating factors, of the association between social isolation and health outcomes in SZ, and; (3) Examine whether the COVID-19 pandemic modified associations between social isolation and health outcome in SZ. This study will be the first to comprehensively examine the health impact of social isolation in SZ. The project may show that in SZ socialization in midlife can reduce the risk for poor health outcomes and ultimately facilitate much-needed preventive targeted therapies to reduce early-age mortality in SZ.