Neurobehavioral Mechanisms of Social Isolation and Loneliness in Serious Mental Illness

Schizophrenia Clinical Trial

Official title:

Neurobehavioral Mechanisms of Social Isolation and Loneliness in Serious Mental Illness

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04940663
• Other study ID #: 2021P001826
• Status: Recruiting
• Phase: N/A
• Start date: July 13, 2022
• Est. completion date: June 2026

Study information

• Verified date: October 2023
• Source: Massachusetts General Hospital
• Contact: Daphne J Holt, MD, PhD
• Phone: 617-726-7618
• Email: dholt[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Mental Disorders
• Psychosis
• Schizophrenia

Intervention

Behavioral:
• EMA
Participants will complete surveys about their feelings and social habits through a smartphone app (EMA)

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Charlestown	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Boston University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trait level social isolation and loneliness	UCLA Loneliness Scale(20 and 4 item), Social Network Index, Social Anhedonia Scale, Penn facial affect recognition Task, Social Disconnectedness Scale, Social Provisions Scale	6 months
Primary	Characterize within-person, dynamic changes in objective isolation and loneliness	EMA questions derived from the UCLA Loneliness Scales, perceived discrimination scale	6 months
Primary	Psychosocial functioning	Quality of Life Scale, Cornblatt Global Functioning - Social and Role Scales	6 months
Primary	Physical health and cardiometabolic/immunological panel	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	6 months