We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Neurobehavioral Mechanisms of Social Isolation and Loneliness in Serious Mental Illness

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04940663
Recruitment Status : Recruiting
First Posted : June 25, 2021
Last Update Posted : August 24, 2022
Boston University
Information provided by (Responsible Party):
Daphne Holt, Massachusetts General Hospital

Brief Summary:
The proposed research will test the hypothesis that objective social isolation and loneliness are linked to neurobehavioral mechanisms involved in social perception and motivation in individuals with and without serious mental illness. Moreover, it will investigate the specific dynamic interactions among these experiences in daily life and how they, and their neurobehavioral predictors, are linked to day-to-day functioning. The findings of this project could provide novel targets for therapeutics aimed at improving functioning and overall quality of life in individuals with serious mental illnesses, as well as quantitative phenotypes for use in early detection efforts.

Condition or disease Intervention/treatment Phase
Psychosis Schizophrenia Behavioral: EMA Not Applicable

Detailed Description:
Some of the most debilitating and harmful aspects of serious mental illnesses (SMI) are the 1) social isolation (low numbers of social contacts) and 2) the subjective experiences of social disconnection (loneliness) that frequently accompany these conditions. Social isolation and loneliness greatly impact day-to-day functioning and are associated with poor cardiometabolic health and early mortality in SMI, and currently there are no available treatments that can prevent or reverse these devastating consequences of having these illnesses. This may be in part because the neural and psychological mechanisms underlying social isolation and loneliness in SMI, and how they impact functioning and health outcomes, are poorly understood. However, recent clues from studies employing advanced neuroimaging and digital assessments have formed the basis of a novel approach to investigating such mechanisms, outlined in this proposal. Prior work has indicated that objective isolation and loneliness are correlated but also somewhat independent. Recent neuroimaging findings support this model, revealing that social isolation and loneliness have both shared and distinct neural correlates. However, it is also clear that these are not static phenomena; smartphone-based assessments have revealed transient, dynamic changes in social isolation and loneliness. Individual differences in the anticipation of rejection are associated with momentary experiences of loneliness, greater avoidance and subsequent increases in social isolation. Thus, in the current application, we propose to comprehensively measure both the relatively stable neural and behavioral predictors of social isolation and loneliness, as well as the moment-to-moment changes in these experiences, in 60 individuals with SMI and 60 control subjects. In Aim 1 of the proposed project, we will show that the higher levels of social isolation and loneliness in SMI are linked to shared and distinct neural responses to social stimuli, with deficient responses of social perception-related circuitry (medial temporal lobe regions) linked to social isolation, and deficient responses of reward-related circuitry (basal ganglia regions) linked to loneliness. In Aim 2, we will measure transient changes in social isolation and loneliness with smartphone assessments using a longitudinal "burst" design. Lastly, in Aim 3, we will determine how the quantitative markers of social isolation and loneliness identified in Aims 1 and 2 predict indices of real-world functioning, measuring the stability of these associations over time. Thus, in this project, we will show that fundamental neural and behavioral processes drive momentary variation in the experience of social isolation and loneliness, and directly impact functioning in SMI. In follow-up work, these findings can be used as objective targets in studies of novel interventions which aim to address these major causes of disability.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neurobehavioral Mechanisms of Social Isolation and Loneliness in Serious Mental Illness
Actual Study Start Date : July 13, 2022
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : June 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Ecological Momentary Assessment
EMA collected daily (4x/day) for two weeks
Behavioral: EMA
Participants will complete surveys about their feelings and social habits through a smartphone app (EMA)

Primary Outcome Measures :
  1. Trait level social isolation and loneliness [ Time Frame: 6 months ]
    UCLA Loneliness Scale(20 and 4 item), Social Network Index, Social Anhedonia Scale, Penn facial affect recognition Task, Social Disconnectedness Scale, Social Provisions Scale

  2. Characterize within-person, dynamic changes in objective isolation and loneliness [ Time Frame: 6 months ]
    EMA questions derived from the UCLA Loneliness Scales, perceived discrimination scale

  3. Psychosocial functioning [ Time Frame: 6 months ]
    Quality of Life Scale, Cornblatt Global Functioning - Social and Role Scales

  4. Physical health and cardiometabolic/immunological panel [ Time Frame: 6 months ]
    Height, weight, waist circumference, systolic and diastolic blood pressure, blood oxygen level, heart rate, interleukin-6, TNF-alpha, Complete metabolic panel, lipid panel, C-reactive protein, Cortisol, CBC, HbA1c

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. 18-55 years old
  2. Experienced a psychotic disorder or mood disorder

Exclusion Criteria:

  1. Any neurological disorder or current substance use disorder (during the past 6 months)
  2. Not proficient in English
  3. A recent change in medication, or an acute symptom presentation
  4. Standard exclusion criteria for participation in an MRI scan (e.g., presence of metal in the body, claustrophobia, a history of head trauma).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04940663

Layout table for location contacts
Contact: Daphne J Holt, MD, PhD 617-726-7618 dholt@partners.org

Layout table for location information
United States, Massachusetts
Massachusetts General Hospital Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Daphne J Holt, MD, PhD    617-726-7618    dholt@mgh.harvard.edu   
Contact: Nicole DeTore, PhD    617-726-2065    ndetore@mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
Boston University
Layout table for investigator information
Principal Investigator: Daphne J Holt, MD, PhD Massachusetts General Hospital
Layout table for additonal information
Responsible Party: Daphne Holt, Associate Professor of Psychiatry, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT04940663    
Other Study ID Numbers: 2021P001826
First Posted: June 25, 2021    Key Record Dates
Last Update Posted: August 24, 2022
Last Verified: August 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders