Skip to content

Body and Social Behavior

Low-grade Inflammatory Challenge and Social Behavior

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05654441
Acronym
BSB
Enrollment
104
Registered
2022-12-16
Start date
2022-10-17
Completion date
2023-12-15
Last updated
2024-11-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Defeat, Social, Inflammation, Interaction, Social, Psychology, Social

Brief summary

This randomized, double-blind, placebo-controlled study of the influenza vaccine will shed important light on how the immune system responds to different positive and negative social experiences. Building on the nuanced animal literature showing that, while animals exposed to an inflammatory challenge show reductions in social exploration consistent with the sickness behavior of social withdrawal, they actually show increases in social engagement behavior during interactions with a cage mate or pair-bonded animal. The present study will examine if a mild inflammatory challenge (receipt of the influenza vaccine) leads to change in actual social behavior in interactions, specifically toward a stranger and separately, toward a close friend. This study will also build on foundational animal research showing that an inflammatory challenge leads to social defeat behaviors in animals.

Detailed description

Psychologists have long appreciated that the mind can impact the body, and that bodily changes can influence the mind. Social psychologists in particular have conducted pioneering work on connections between the mind and body, showing both that social experiences elicit changes in numerous physiological systems and that physiological changes influence social cognition and behavior. Until recently, however, little attention has been paid to the connections between social experiences and the immune system. This is a critical gap knowledge, as seminal animal work shows that there are profound relationships between social experiences and immune system functioning that have yet to be fully explored in humans. Further, there are strong theoretical reasons to suspect that the immune system matters for social psychological processes even beyond times of sickness, though many of these connections are yet to be uncovered empirically in humans. Thus, to develop a comprehensive understanding of the mind-body connections that drive social behavior, researchers must integrate the immune system. To address this critical gap in knowledge, the present study will examine the body-to-mind connection between the immune system and positive (i.e., interacting with a close other) and negative (i.e., social defeat) social experiences. Why does the immune system matter for social behavior? There are good theoretical reasons why the immune system would be tightly interconnected to even normative, everyday social experiences beyond times of sickness. First, despite the common belief that the immune system only comes online in response to pathogens or physical injury, the immune system is in fact always active and fluctuates considerably even in the absence of an acute infection. Indeed, the immune system is responsive to both real and imagined situations that may signal increased probability of injury or infection. This includes everyday social experiences and situations of greater interest to social psychologists, from falling in love to being socially ostracized. Second, the brain is constantly monitoring the physiological state of the body and integrating this interoceptive information with signals from the broader environment to anticipate current and future metabolic demands and guide adaptive behavior. Thus, even relatively minor fluctuations in immune system activation beyond times of sickness can feed back to the brain to guide social cognition and behavior. In sum, there are strong theoretical reasons why everyday, normative social experiences may affect and be affected by immune system activation. To date, social withdrawal is considered a hallmark sickness behavior, based on both animal and human work showing that experimentally-induced increases in inflammation lead to less social exploration and greater feelings of social disconnection. However, other animal work suggests that the effects of inflammation on social behavior may be more nuanced than uniform social withdrawal, as some research shows that animals spend more time huddling with familiar cagemates, and form pair bonds more quickly when exposed to an inflammatory challenge. Further, recent work in the field of psychoneuroimmunology with humans replicates this, showing that an inflammatory challenge causes heightened (not diminished) neural responses to reminders of social connection. Yet to date, no known human work has examined if an inflammatory challenge causes changes in actual social behavior in humans, a critical next step in this line of research. Techniques from experimental social psychology are ideally-suited to address this next step, as social psychology has been at the cutting-edge of developing tools for eliciting and quantifying social behavior, particularly in the context of dyadic interactions that are likely to be important during an inflammatory challenge. This study will bring this important perspective to bear to further understanding of how immune system activation may cause changes in social behavior. There is a storied history in psychoneuroimmunology (PNI) of using vaccines (e.g., influenza, typhoid) as a way to study immune system functioning. In vaccine trials, researchers typically examine how individual-differences in psychological processes (e.g., depressive symptoms, social connection) influence the effectiveness of the vaccine by examining the number of antibody titers produced following vaccination as a function of the individual-difference of interest. More recently, researchers have begun to use the influenza vaccine as a way to manipulate levels of inflammation, as the vaccine produces a small, but significant, increase in inflammatory markers (e.g., interleukin-6) in the 24-hours following vaccination administration. Prior work has examined the impact of vaccine-induced increases in inflammation on psychological processes such as mood and reward processing and shown that within-subject changes in inflammation in response to the influenza vaccine predict increases in daily negative affect and increases in reward responsivity. The present project will build on this prior work by adding a placebo-controlled (saline) condition, thus allowing researchers to determine if vaccine-induced changes in inflammation cause changes in social behavior. Using the influenza vaccine as an inflammatory challenge has numerous advantages over prior approaches: 1) It provides a public health service to the local community (i.e., given that vaccinations can prevent viral outbreaks) rather than making participants temporarily ill, as in the rhinovirus studies and endotoxin studies discussed previously; 2) The change in inflammation elicited by the vaccine is relatively small, thus mirroring more normative, day-to-day fluctuations in inflammation beyond times of sickness; and 3) Experimental procedures are less resource and cost-intensive, as almost every local pharmacy provides influenza vaccinations, and the cost is often covered by insurance and is relatively low (or free) for the uninsured. Given these advantages, the present study will use the influenza vaccine to examine if an experimental manipulation of inflammation causes changes in social behavior of interest to both social psychologists and psychoneuroimmunologists. In doing so, the study will advance a method that can be widely adopted by researchers to study how immune system activation feeds back to the brain to influence social experience.

Interventions

BIOLOGICALInfluenza vaccine

0.5 mL single-dose injection

BIOLOGICALPlacebo

0.5 mL single-dose injection with no therapeutic effect

Sponsors

U.S. National Science Foundation
CollaboratorFED
University of North Carolina, Chapel Hill
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes

Inclusion criteria

* 18-35 years old * Have a same-gender friend willing to participate in the second study session

Exclusion criteria

* Are not a student * Have already received the annual influenza vaccine or had the flu this season * Report current illness/sickness symptoms, including upper respiratory symptoms * Report any major medical conditions (e.g., diabetes, asthma) * Use mood or immune altering medications (e.g., anti-depressants) * Current regular nicotine/tobacco use (i.e., daily use of cigarettes or e-cigarettes) * Have an allergy to eggs * Have had COVID-19 in past two weeks * Current or history of depression or anxiety * Have had Guillain-Barre Syndrome * Are allergic to vaccine or ingredients present in vaccine * Have had an adverse reaction to a blood draw, including to needles or sight or blood * Weigh less than 110 pounds * Are unwilling to be video/audio recorded during the social interaction tasks * Are unwilling to be unmasked during the social interaction tasks

Design outcomes

Primary

MeasureTime frameDescription
IL-6 Levels 24 Hours After Vaccinewithin approximately 24 hours of treatmentThe investigators will examine levels of IL-6 measured in plasma 24-hours following the vaccine.
IL-10 Levels 24 Hours After Vaccinewithin approximately 24 hours of treatmentThe investigators will examine levels of IL-10 measured in plasma 24-hours following the vaccine.
TNF-alpha Levels 24 Hours After Vaccinewithin approximately 24 hours of treatmentThe investigators will examine levels of TNF-alpha measured in plasma 24-hours following the vaccine.
IFN-gamma Levels 24 Hours After Vaccinewithin approximately 24 hours of treatmentThe investigators will examine levels of IFN-gamma measured in plasma 24-hours following the vaccine.

Secondary

MeasureTime frameDescription
Low Arousal Positive Affect Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported low arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 5 low arousal positive emotions (i.e., attentive, calm, interested, grateful, relieved) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal positive affect.
Sickness Symptom Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported sickness symptoms, as measured by the Sickness Questionnaire, as a function of vaccine condition. The 10-item Sickness Questionnaire includes Likert-type questions using a 4- point scale, the total range is 0-30 with higher scores indicating greater sickness symptoms.
Social Disconnection Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported social disconnection, as measured by a subset of items utilized in prior research (Moieni et al., 2015), as a function of vaccine condition. The 10-item scale includes Likert-type questions using a 5- point scale ranging from 1 (Not at all) to 5 (Very much so) which are then averaged; the total range is 0-5 with higher scores indicating greater feelings of social disconnection.
Sleep Quality Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported sleep quality, as measured by five items adapted from the Brief Pittsburgh Sleep Quality Index, as a function of vaccine condition. The 5-item scale assess sleep duration, sleep quality, daytime dysfunction, sleep latency, and nighttime disturbances- each producing a score ranging from 0 to 3. These scores are then summed; the total range is 0-15 with higher scores indicating poorer sleep.
High Arousal Negative Affect Scoreswithin approximately 24 hours of treatmenthe investigators will examine if there are differences in self-reported high arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 11 high arousal negative emotions (i.e., angry, irritable, nervous, scared, upset, afraid, ashamed, distressed, frustrated, hostile, jittery) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal negative affect.
Low Arousal Negative Affect Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported low arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of four low arousal negative emotions (i.e., bored, guilty, sad, worn out) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal negative affect.
High Arousal Positive Affect Scoreswithin approximately 24 hours of treatmentThe investigators will examine if there are differences in self-reported high arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 10 high arousal positive emotions (i.e., amused, determined, enthusiastic, excited, happy, inspired, proud, strong, active, alert) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal positive affect.

Countries

United States

Participant flow

Participants by arm

ArmCount
Influenza Vaccine
Experimental group given influenza vaccine (Flulaval) Influenza vaccine: 0.5 mL single-dose injection
52
Sham Vaccine
The control group given a placebo (saline injection) Placebo: 0.5 mL single-dose injection with no therapeutic effect
50
Total102

Baseline characteristics

CharacteristicSham VaccineTotalInfluenza Vaccine
Age, Continuous20.62 years
STANDARD_DEVIATION 2.61
20.54 years
STANDARD_DEVIATION 2.18
20.46 years
STANDARD_DEVIATION 1.69
Ethnicity (NIH/OMB)
Hispanic or Latino
4 Participants9 Participants5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
46 Participants93 Participants47 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Asian
10 Participants16 Participants6 Participants
Race (NIH/OMB)
Black or African American
2 Participants7 Participants5 Participants
Race (NIH/OMB)
More than one race
7 Participants10 Participants3 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
4 Participants10 Participants6 Participants
Race (NIH/OMB)
White
27 Participants58 Participants31 Participants
Region of Enrollment
United States
50 Participants102 Participants52 Participants
Sex: Female, Male
Female
37 Participants77 Participants40 Participants
Sex: Female, Male
Male
13 Participants25 Participants12 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 520 / 52
other
Total, other adverse events
0 / 520 / 52
serious
Total, serious adverse events
0 / 520 / 52

Outcome results

Primary

IFN-gamma Levels 24 Hours After Vaccine

The investigators will examine levels of IFN-gamma measured in plasma 24-hours following the vaccine.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineIFN-gamma Levels 24 Hours After Vaccine0.44 log pg/mLStandard Deviation 0.38
Sham VaccineIFN-gamma Levels 24 Hours After Vaccine-0.14 log pg/mLStandard Deviation 0.21
p-value: <0.001ANOVA
Primary

IL-10 Levels 24 Hours After Vaccine

The investigators will examine levels of IL-10 measured in plasma 24-hours following the vaccine.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineIL-10 Levels 24 Hours After Vaccine0.50 log pg/mLStandard Deviation 0.14
Sham VaccineIL-10 Levels 24 Hours After Vaccine0.36 log pg/mLStandard Deviation 0.14
p-value: <0.001ANOVA
Primary

IL-6 Levels 24 Hours After Vaccine

The investigators will examine levels of IL-6 measured in plasma 24-hours following the vaccine.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineIL-6 Levels 24 Hours After Vaccine0.40 log pg/mLStandard Deviation 0.25
Sham VaccineIL-6 Levels 24 Hours After Vaccine0.23 log pg/mLStandard Deviation 0.23
p-value: <0.001ANOVA
Primary

TNF-alpha Levels 24 Hours After Vaccine

The investigators will examine levels of TNF-alpha measured in plasma 24-hours following the vaccine.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineTNF-alpha Levels 24 Hours After Vaccine0.93 log pg/mLStandard Deviation 0.1
Sham VaccineTNF-alpha Levels 24 Hours After Vaccine0.88 log pg/mLStandard Deviation 0.1
p-value: 0.007ANOVA
Secondary

High Arousal Negative Affect Scores

he investigators will examine if there are differences in self-reported high arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 11 high arousal negative emotions (i.e., angry, irritable, nervous, scared, upset, afraid, ashamed, distressed, frustrated, hostile, jittery) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal negative affect.

Time frame: within approximately 24 hours of treatment

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineHigh Arousal Negative Affect Scores8.67 score on a scaleStandard Deviation 11.94
Sham VaccineHigh Arousal Negative Affect Scores7.64 score on a scaleStandard Deviation 11.95
p-value: 0.666t-test, 2 sided
Secondary

High Arousal Positive Affect Scores

The investigators will examine if there are differences in self-reported high arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 10 high arousal positive emotions (i.e., amused, determined, enthusiastic, excited, happy, inspired, proud, strong, active, alert) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater high arousal positive affect.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineHigh Arousal Positive Affect Scores37.30 score on a scaleStandard Deviation 20.54
Sham VaccineHigh Arousal Positive Affect Scores33.99 score on a scaleStandard Deviation 22.12
p-value: 0.438t-test, 2 sided
Secondary

Low Arousal Negative Affect Scores

The investigators will examine if there are differences in self-reported low arousal negative affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of four low arousal negative emotions (i.e., bored, guilty, sad, worn out) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal negative affect.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineLow Arousal Negative Affect Scores20.35 score on a scaleStandard Deviation 16.02
Sham VaccineLow Arousal Negative Affect Scores18.19 score on a scaleStandard Deviation 16.02
p-value: 0.522t-test, 2 sided
Secondary

Low Arousal Positive Affect Scores

The investigators will examine if there are differences in self-reported low arousal positive affect, as measured by a subscale of the Positive Affect-Negative Affect Schedule-X, as a function of vaccine condition. Participants indicated the extent to which they felt each of 5 low arousal positive emotions (i.e., attentive, calm, interested, grateful, relieved) on a 0 (not at all) -100 (extremely) sliding scale. Responses were then averaged with higher scores indicating greater low arousal positive affect.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineLow Arousal Positive Affect Scores48.71 score on a scaleStandard Deviation 18.83
Sham VaccineLow Arousal Positive Affect Scores43.50 score on a scaleStandard Deviation 20.06
p-value: 0.181t-test, 2 sided
Secondary

Sickness Symptom Scores

The investigators will examine if there are differences in self-reported sickness symptoms, as measured by the Sickness Questionnaire, as a function of vaccine condition. The 10-item Sickness Questionnaire includes Likert-type questions using a 4- point scale, the total range is 0-30 with higher scores indicating greater sickness symptoms.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineSickness Symptom Scores7.00 score on a scaleStandard Deviation 4.39
Sham VaccineSickness Symptom Scores7.12 score on a scaleStandard Deviation 4.12
p-value: 0.886t-test, 2 sided
Secondary

Sleep Quality Scores

The investigators will examine if there are differences in self-reported sleep quality, as measured by five items adapted from the Brief Pittsburgh Sleep Quality Index, as a function of vaccine condition. The 5-item scale assess sleep duration, sleep quality, daytime dysfunction, sleep latency, and nighttime disturbances- each producing a score ranging from 0 to 3. These scores are then summed; the total range is 0-15 with higher scores indicating poorer sleep.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineSleep Quality Scores5.13 score on a scaleStandard Deviation 2.23
Sham VaccineSleep Quality Scores5.13 score on a scaleStandard Deviation 2.23
p-value: 0.833t-test, 2 sided
Secondary

Social Disconnection Scores

The investigators will examine if there are differences in self-reported social disconnection, as measured by a subset of items utilized in prior research (Moieni et al., 2015), as a function of vaccine condition. The 10-item scale includes Likert-type questions using a 5- point scale ranging from 1 (Not at all) to 5 (Very much so) which are then averaged; the total range is 0-5 with higher scores indicating greater feelings of social disconnection.

Time frame: within approximately 24 hours of treatment

Population: Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

ArmMeasureValue (MEAN)Dispersion
Influenza VaccineSocial Disconnection Scores2.34 score on a scaleStandard Deviation 0.44
Sham VaccineSocial Disconnection Scores2.42 score on a scaleStandard Deviation 0.65
p-value: 0.455t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026