Social Isolation and Aging in Schizophrenia (SIAS)

The Impact of Social Isolation on Aging Health in Schizophrenia

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, the 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), the researchers will create a longitudinal database of 650 participants, including 500 individuals with SZ, and 150 of their unaffected siblings. The researchers will apply an accelerated longitudinal design by reassessing and by examining medical records of research participants who were first evaluated between the ages of 20-55 and are now 40-70 years of age, a period when many medical conditions and health problems tend to manifest. The researchers 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. The researchers 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, the researchers need to better understand factors that contribute to the excess of medical comorbidities in SZ. The central hypothesis is that social isolation, a common and persistent characteristic of SZ, contributes to the excess of physical comorbidities in SZ. To meet the overall goal, the following aims are: (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

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia and Related Disorders

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 650

Contacts and Locations

• Study Contact: Name: Eva Velthorst, PhD; Phone Number: +31618644345; Email: e.velthorst@ggz-nhn.nl

Study Locations

• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105AZ
      • Recruiting
      • AUMC, University Hospital
      • Contact: Lieuwe de Haan, PhD; Phone Number: +31 20 8913600; Email: l.dehaan@amsterdamumc.nl
• Spain
  • Madrid, Spain, 28030
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Celso Arango, PhD; Phone Number: +34 913283209; Email: carango@hggm.es
• United Kingdom
  • London, United Kingdom, Se58AF
    • Recruiting
    • King's College London
    • Contact: Craig Morgan, PhD; Phone Number: +44 2078480351; Email: craig.morgan@kcl.ac.uk
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Recruiting
      • Olin Neuropsychiatry Research Center, Hartfort
      • Contact: Michael Stevens, PhD; Phone Number: 860-545-7800; Email: michael.stevens@hhchealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

500 clinically stable schizophrenia participants, and 150 of their unaffected siblings from a list of eligible participants of large existing studies of schizophrenia: e.g. EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) and large scale research studies that took place at the Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT. All participants consented to be recruited for future studies.

Description

Inclusion and exclusion criteria for participants with SZ:

• DSM-IV or V diagnosis of a SZ related disorder (295.x, 297.1, 298.8, or 298.9; e.g., schizophrenia, schizoaffective disorder, schizophreniform disorder, but not psychotic disorder that is solely substance induced) based on clinical interview;
• Between 40 and 70 years of age at time of study recruitment;
• Participant was enrolled in a previous research study between the ages of 20-55, and this study took place at least 5 years ago;
• Able to understand the spoken language of the participating country sufficiently to comprehend testing procedures;
• No history of serious head injury (i.e., loss of consciousness longer than 1 hour, no neuropsychological sequelae, no cognitive rehabilitation treatment post head injury);
• No history of IQ < 70, or developmental disability based on chart review;
• Clinically stable (i.e., no inpatient hospitalizations for three months prior to enrollment, no changes in medication in the four weeks prior to enrollment;

The inclusion and exclusion criteria for sibling participants in this study will be:

• No history of any DSM IV/V Axis I or axis II diagnosis that is known to be associated with social functioning (e.g. severe mood disorder, schizoaffective personality disorder, autism spectrum disorder);
• Between 40 and 70 years of age at time of study recruitment;;
• Participant was enrolled in a previous research study between the ages of 20-55, and this study took place at least 5 years ago;
• Able to understand the spoken language of the participating country sufficiently to comprehend testing procedures;
• No history of serious head injury (i.e., loss of consciousness longer than 1 hour, no neuropsychological sequelae, no cognitive rehabilitation treatment post head injury);
• No history of IQ < 70, or developmental disability based on chart review;
• Clinically stable (i.e., no inpatient hospitalizations for three months prior to enrollment, no changes in medication in the four weeks prior to enrollment

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Individuals with SZ; Individuals with a schizophrenia-related diagnosis
Unaffected first-degree relatives; Unaffected first-degree relatives of individuals with a schizophrenia-related diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of newly diagnosed conditions	Physician diagnosed medical conditions - Medical records from hospitals and general practitioners will be reviewed to identify the occurrence and timing of any newly diagnosed conditions (e.g., cardiovascular disease, COPD, diabetes).	Day 1
Short Form Health Survey (SF-36),	The 36-Item Short Form Health Survey (SF-36), which includes five physical domains: physical functioning, role limitations due to physical problems, bodily pain, general health, and vitality. The individuals item scores (scored between 1-60, according to the manual) are summed to scale scores and transformed to a 100-point scale, with higher scores indicating a better health status.	Day 1
Number of Participants with High Cholesterol	High cholesterol (defined as low-density lipoprotein ≥160 mg/dL or total cholesterol ≥240 mg/dL)	Day 1
Number of participants with High Blood Pressure	High blood pressure (defined as systolic ≥130 mm Hg or diastolic ≥80 mm Hg).	Day 1
Schedule for Deficit Syndrome (SDS)	Social isolation is measured with the Schedule for Deficit Syndrome (SDS) - each item scored from 0 (normal) to 4 (severely impaired). there is also a global severity score (0 to 4). Full scale scored from 0 to 20, with higher score representing greater severity of symptoms.	Chart Review for the legacy data from when participants were first assessed between 2004 and 2015
The Birchwood social functioning scale (SFS)	Social isolation is measured with the Birchwood social functioning scale (SFS) - a 79 item instrument, and consists of seven subscales: (1) social engagement/withdrawal (amount of time to spend alone, the likelihood to initiate conversation); (2) interpersonal behaviour (number of friends, engagement in a romantic relationship); (3) prosocial activities (participation in social activities e.g. visit friends, play sports); (4) recreation (engagement in activities and hobbies); (5) independence-competence (ability to maintain independent living); (6) independence-performance (performance of the skills required for independent living); (7) employment/occupation (engagement in employment), The sum of each scale, and the full scale is standardized and normalized with a mean of 100 and standard deviation of 15. Higher scores represent better health outcomes.	Chart review for the legacy data from when participants were first assessed between 2004 and 2015; and Three times daily for 14 days
'Social Isolation' subscale of the Structured Interview for Schizotypy-Revised (SIS-R)	Social isolation is measured with the 'Social Isolation' subscale of the Structured Interview for Schizotypy-Revised (SIS-R). The subscale range from 0 (virtually no evidence of symptoms) to 6 (symptoms present and quite severe).	Chart review for the legacy data from when participants were first assessed between 2004 and 2015; and Three times daily for 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Revised UCLA Loneliness Scale (R-UCLA)	The Revised UCLA Loneliness Scale (R-UCLA) is a 20-item questionnaire. Every item is scored with a number that indicates how often each question is applicable (1 = Never, 2 = Rarely, 3 = Sometimes, and 4 = Always). To calculate the total score for each participant, all responses are summed to create a total score ranging from 20 to 80. Higher score indicates more loneliness. Total score <28 = no/low loneliness Total score 28-43 = moderate loneliness Total score >43 = a high degree of loneliness.	Day 1
Ecological Momentary Assessment (EMA)	Severity of psychotic symptoms and functional impairments related to SZ of the EMA questions using "EMA-wellness". Scored from 0-12, with higher score indicating poorer health outcomes	Chart review legacy data; and 3 times daily for 14 days
Barriers to Access to Care Evaluation scale (BACE)	The Barriers to Access to Care Evaluation scale (BACE) questionnaire will be used to establish any problems related to access to healthcare over the years. The BACE is designed to assess barriers to mental health care for people with mental health problems. It includes barriers related to, and unrelated to, stigma and discrimination. It has 30 items, and is scored by summing responses to these items, where each item uses a 0 (not at all) to 3 (a lot) scale, full scale scored from 0-90, with higher scores indicating greater perceived barriers.	Day 1

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: King's College London; National Institute of Mental Health (NIMH); Karolinska Institutet; Hospital General Universitario Gregorio Marañon; University of Miami; Yale University; Boston Children's Hospital; Hartford Hospital; GGZ Noord-Holland-Noord; Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
• Investigators: Principal Investigator: Abraham Reichenberg, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; psychosis; siblings; physical health; social isolation; longitudinal trajectory
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavior; Social Behavior; Schizophrenia; Psychotic Disorders; Social Isolation
• Other Study ID Numbers: STUDY-22-00730; 1R01MH128971-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this study available in publications is shared via the NIMH National Data Archives (NDA) and is available in NDA collection C4431.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No