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Principal Investigator: ABRAHAM REICHENBERG
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2024
Award: $636,347
Funding agency: National Institute of Mental Health
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.
Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Acceleration><Active Follow-up><Age><Age Years><Aged 65 and Over><Aging><Antipsychotic Agents><Antipsychotic Drugs><Antipsychotics><BMI><BMI percentile><BMI z-score><Behavior><Biological Markers><Body mass index><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 exposure><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><CV-19><Characteristics><Clinical><Cognition><Coronavirus Infectious Disease 2019><Country><Data><Death Rate><Depressed mood><Diagnosis><Diet><Disabling><Disease><Disorder><Environment><Ethnic Group><Ethnic Origin><Ethnic People><Ethnic Population><Ethnic individual><Ethnicity><Ethnicity People><Ethnicity Population><Europe><Exhibits><General Population><General Public><Goals><Government><Health><Individual><Life><Loneliness><Major Tranquilizers><Major Tranquilizing Agents><Measures><Medical><Medical Records><Mental Depression><Natural experiment><Neuroleptic Agents><Neuroleptic Drugs><Neuroleptics><Outcome><Participant><Patients><Pattern><Physically Challenged><Physicians><Premature Mortality><Preventive><Process><Psychotic Disorders><Quetelet index><Race><Races><Racial Group><Research><Research Resources><Resources><Risk><Risk Factors><Risk Reduction><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2 exposure><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Schizophrenia><Schizophrenic Disorders><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 pandemic><Severity of illness><Siblings><Smoke><Smoking><Social Network><Social isolation><Socialization><Stress><Subgroup><Symptoms><Testing><Time><Unhealthy Diet><Vulnerable Populations><Work><above age 65><accelerated aging><accelerated biological age><accelerated biological aging><active followup><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age acceleration><age associated><age associated difference><age based difference><age correlated><age dependent><age dependent difference><age dependent variation><age difference><age linked><age of 65 years onward><age related><age related difference><age related variation><age specific><age specific difference><aged 65 and greater><aged 65+><aged ≥65><ages><bio-markers><biologic marker><biomarker><co-morbid><co-morbidity><cohort><comorbidity><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><dementia praecox><depressed><depression><design><designing><diets><differ by age><difference across age><difference in age><differences in health><digital phenotyping><disease severity><ethnic subgroup><ethnicity group><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><follow up><follow-up><followed up><followup><health data><health difference><human old age (65+)><lack of physical activity><life span><lifespan><lonely><longitudinal database><longitudinal design><medical examination><mid life><mid-life><middle age><middle aged><midlife><mortality><mortality rate><mortality ratio><neuropsychiatric><neuropsychiatry><old age><older adult><older adulthood><over 65 years><physical conditioning><physical health><physical inactivity><poor diet><poor health outcome><post-pandemic><premature><prematurity><prevent><preventing><psychotic illness><racial><racial background><racial origin><racial population><racial subgroup><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduced health outcome><reduces risk><reduces the risk><reducing risk><reducing the risk><risk-reducing><sadness><schizophrenic><secondary analysis><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><social contact><symptomatology><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><unhealthy lifestyle><variation by age><vulnerable group><vulnerable individual><vulnerable people><worse health outcome><≥65 years>