NIH – Research on Biopsychosocial Factors of Social Connectedness and Isolation on Health, Wellbeing, Illness, and Recovery (R01 Clinical Trial Required)

October 15, 2021 by


This funding opportunity announcement (FOA) invites research projects that seek to explain the underlying mechanisms, processes, and trajectories of social relationships and how these factors affect outcomes in human health, illness, recovery, and overall wellbeing. Types of projects submitted under this FOA include mechanistic studies that are classified as clinical trials. Mechanistic studies are defined as studies with the objective to understand the mechanism(s) of action of an intervention, a biological or behavioral process, or the pathophysiology of a disease/condition. See NOT-AT-20-001 and NOT-MH-19-006 for examples of clinical trials that are/are not considered mechanistic studies. Clinical trials that propose to influence a clinical outcome, test safety or feasibility of an intervention, demonstrate the clinical efficacy or effectiveness of an intervention, or analyze the effect size of an intervention on clinical outcomes are ineligible for this FOA. Types of studies that should submit under this FOA include clinical trials that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind. Researchers proposing basic science experimental studies involving human participants should consider this FOA’s companion for basic experimental studies with humans, PAR-21-349, “Research on Health, Wellbeing, Illness, and Recovery (R01 Basic Experimental Studies with Humans Required).” Applications proposing studies that include, but are not limited to, model animal research or observational studies involving humans should submit under the companion FOA, PAR-21-350, “Research on Biopsychosocial Factors of Social Connectedness and Isolation on Health, Wellbeing, Illness, and Recovery (R01 Clinical Trials Not Allowed).


It is well-established that social ties can facilitate overall wellbeing, recovery from acute illness, and self-management of chronic conditions. Less well understood are the processes by which connection and isolation lead to positive or negative impacts on health, wellbeing, illness, or recovery. A more comprehensive understanding of the mechanisms, processes, and trajectories involved in social connectedness and isolation may identify novel targets to inform future intervention developments and to strengthen individual and group functions.

For example, the prefrontal cortex can handle multiple, yet not infinite, concurrent processes. Changes in prefrontal processing may lead individuals to adaptively self-isolate as one way to reduce external social stimulation, to protect or avoid stress, or to focus on specific cognitive tasks. Yet extended isolation can lead to negative changes in neuronal size, activity patterns, and intracellular processes that can reduce cognitive and sensory capacities and subsequent behavior.

Social media usage, such as sharing photos and videos with family members and friends, can facilitate connections and have salutary effects. Social media also can be used to publicly bully or shame others, often youth. Targets of social media abuse consequently may engage in maladaptive behaviors including aggression, delinquency, substance use and misuse, self-harm, social withdrawal, or suicidal ideation. We currently lack an understanding of the biopsychosocial processes that facilitate wellbeing among some youth who use social media but not others.

This FOA solicits research to better understand the basic individual, social, and biobehavioral processes by which social connectedness and isolation have positive or negative impacts across the lifespan. It encourages projects that explore the relationships between various factors, including those that can be objectively measured (e.g., biomeasures or data from health records, occurrence, or length of relationship disruption) and those that require self-report.

The arena of social connectedness, connection, and isolation health research is relatively new, and therefore ripe for construct, theory, and measurement mapping and measurement harmonization efforts. Therefore, in addition to understanding the mechanistic relationships between aspects of social connection and isolation in health contexts, research projects in the areas such as knowledge representation and behavioral ontology development are welcomed. If appropriate, projects may use NIH-supported common data elements (CDEs), electronic health record data, and/or propose sophisticated statistical analyses of existing and/or synthesized datasets that lead to hypotheses for testing in humans or animals.

Research projects focused on either animal or human subjects are encouraged. Also encouraged are projects that strive to determine optimal measurement approaches across species, that validate and utilize measures across the lifespan, and that test measures in a range of clinical contexts.

This FOA solicits R01 applications that may range between 2-5 years. The R01 mechanism, common to all NIH ICOs participating in this FOA, was chosen expressly to empower investigators to propose innovative scopes of work with correspondingly appropriate budgets. Regardless of the number of project-years proposed, investigators should budget each year for travel to an annual meeting of grantees on or near the NIH Campus in Bethesda, MD, to share research methods and findings. Awardees will be encouraged to work together on some shared scientific opportunities at the annual meeting and across the award period.

Key Dates:

Open Date (Earliest Submission Date): May 21, 2022
Letter of Intent Due Date(s): Not Applicable
Earliest Application Due Date: June 21, 2022

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Filed Under: Funding Opportunities