Social Isolation and Aging in Schizophrenia

NCT07419321 | Recruiting

• 2 other identifiers: STUDY-22-007301R01MH128971-01A1
• Study Type: observational
• Target: 650
• Locations: 4 countries
• Sites: 4

Brief 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, 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

Conditions

Schizophrenia and Related Disorders

Keywords

schizophrenia; psychosis; social isolation; physical health; longitudinal trajectory; siblings

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (3)

• The Revised UCLA Loneliness Scale (R-UCLA)

  Day 1

• Ecological Momentary Assessment (EMA)

  Chart review legacy data; and 3 times daily for 14 days

• Barriers to Access to Care Evaluation scale (BACE)

  Day 1

Study Arms (2)

Individuals with SZ

Individuals with a schizophrenia-related diagnosis

Unaffected first-degree relatives

Unaffected first-degree relatives of individuals with a schizophrenia-related diagnosis

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

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

Study Sites (4)

Olin Neuropsychiatry Research Center, Hartfort

Hartford, Connecticut, 06106, United States

RECRUITING

AUMC, University Hospital

Amsterdam, North Holland, 1105AZ, Netherlands

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28030, Spain

RECRUITING

King's College London

London, Se58AF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Social Isolation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Social Behavior; Behavior

Study Officials

• Abraham Reichenberg

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva Velthorst, PhD

CONTACT

+31618644345; e.velthorst@ggz-nhn.nl

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 19, 2026
• Study Start: January 9, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

ES (1); NL (1); US (1); GB (1)