- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05654441
Body and Social Behavior (BSB)
Low-grade Inflammatory Challenge and Social Behavior
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Tatum Jolink, MA
- Phone Number: 512-983-1538
- Email: tatum.jolink@unc.edu
Study Contact Backup
- Name: Keely Muscatell, PhD
- Phone Number: 919-843-9113
- Email: kmuscatell@unc.edu
Study Locations
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27514
- Active, not recruiting
- Clinical and Translation Research Center
-
Chapel Hill, North Carolina, United States, 27599
- Recruiting
- Howell Hall
-
Contact:
- Charlotte Boettiger, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Influenza Vaccine
Experimental group given influenza vaccine (Flulaval)
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0.5 mL single-dose injection
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Placebo Comparator: Sham Vaccine
The control group given a placebo (saline injection)
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0.5 mL single-dose injection with no therapeutic effect
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in unfair monetary offers accepted
Time Frame: within approximately 24 hours of treatment
|
Participants will play a decision-making game in which they will decide to accept or reject monetary offers (split from a $10 stake) from other (anonymous) participants, or "proposers".
If the participant accepts an offer, both they and the proposer will get the money.
If the participant rejects an offer, neither player will get any money.
During the 90 trials of the task, some of the monetary offers will be "fair", in that the stake offered to the participant will be high (e.g., 50% of total stake, or $5).
In some trials, the offers will be "unfair", in that the stake offered is low (e.g., 10% of total stake or $1).
The difference in the number of unfair (<30% of the stake) offers accepted (where higher numbers indicate larger proportion of unfair offers accepted) will be compared between participants in the experimental and control groups.
|
within approximately 24 hours of treatment
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Difference in self-reported social connection between two social targets
Time Frame: within approximately 24 hours of treatment
|
Participants will engage in a 15-minute social interaction with a close friend and separately, a stranger.
During these interactions, pairs will answer questions designed to generate closeness.
Participants will report social connection with each target after the interaction.
Social connection will be measured with ratings of enjoyment of the interaction (measured 1-did not enjoy at all to 7-very much enjoyed, higher scores mean greater enjoyment), interpersonal closeness (Inclusion of Other and the Self, measured with 7 images depicting increasing closeness, higher scores mean greater closeness), and perceived partner responsiveness (Perceived Partner Responsiveness, measured from 1-not at all true to 7-completely true, higher scores mean greater perceived responsiveness).
All ranges 1-7.
If internal reliability across measures is high, they will be combined for analyses.
Differences in social connection will be compared between targets and between experimental groups.
|
within approximately 24 hours of treatment
|
Difference in behaviorally coded social engagement between two social targets
Time Frame: within approximately 24 hours of treatment
|
Participants will engage in a 15-minute social interaction with a close friend and separately, a stranger.
During these interactions, they will ask and answer questions about each other (e.g., would you want to be famous?).
These questions are designed to generate closeness.
The interactions will be video recorded and coded for non-verbal behavior, specifically focusing on degree of engagement cues (e.g., head nods, eye contact, laughter) and disengagement cues (e.g., self-grooming, object manipulation).
After data collection concludes, videos will be watched and rated by multiple objective coders, who will be trained to form consensus/reliability among engagement codes, but will watch videos independently to rate/code.
Differences in behavioral engagement (as assessed by coding the behavior from the close friend interaction and the stranger interaction) will be compared between social targets (within-subjects) and between experimental groups (between-subjects).
|
within approximately 24 hours of treatment
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Keely Muscatell, PhD, University of North Carolina, Chapel Hill
Publications and helpful links
General Publications
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- Barrett LF. The theory of constructed emotion: an active inference account of interoception and categorization. Soc Cogn Affect Neurosci. 2017 Jan 1;12(1):1-23. doi: 10.1093/scan/nsw154. Erratum In: Soc Cogn Affect Neurosci. 2017 Nov 1;12(11):1833.
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- Eisenberger NI, Moieni M, Inagaki TK, Muscatell KA, Irwin MR. In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior. Neuropsychopharmacology. 2017 Jan;42(1):242-253. doi: 10.1038/npp.2016.141. Epub 2016 Aug 2.
- Gassen J, Hill SE. Why inflammation and the activities of the immune system matter for social and personality psychology (and not only for those who study health). Soc Personal Psychol Compass. May 2019:e12471. doi:10.1111/spc3.12471
- Kemeny ME. Psychobiological responses to social threat: evolution of a psychological model in psychoneuroimmunology. Brain Behav Immun. 2009 Jan;23(1):1-9. doi: 10.1016/j.bbi.2008.08.008. Epub 2008 Sep 10.
- Hennessy MB, Deak T, Schiml PA. Sociality and sickness: have cytokines evolved to serve social functions beyond times of pathogen exposure? Brain Behav Immun. 2014 Mar;37:15-20. doi: 10.1016/j.bbi.2013.10.021. Epub 2013 Oct 31.
- Dhabhar FS, Malarkey WB, Neri E, McEwen BS. Stress-induced redistribution of immune cells--from barracks to boulevards to battlefields: a tale of three hormones--Curt Richter Award winner. Psychoneuroendocrinology. 2012 Sep;37(9):1345-68. doi: 10.1016/j.psyneuen.2012.05.008. Epub 2012 Jun 22.
- Leschak CJ, Eisenberger NI. Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes. Psychosom Med. 2019 Oct;81(8):711-719. doi: 10.1097/PSY.0000000000000685.
- Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302. Epub 2014 Jan 13.
- Slavich GM, Cole SW. The Emerging Field of Human Social Genomics. Clin Psychol Sci. 2013 Jul;1(3):331-348. doi: 10.1177/2167702613478594.
- Murray DR, Haselton MG, Fales M, Cole SW. Falling in love is associated with immune system gene regulation. Psychoneuroendocrinology. 2019 Feb;100:120-126. doi: 10.1016/j.psyneuen.2018.09.043. Epub 2018 Oct 2.
- Muscatell KA, Dedovic K, Slavich GM, Jarcho MR, Breen EC, Bower JE, Irwin MR, Eisenberger NI. Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress. Brain Behav Immun. 2015 Jan;43:46-53. doi: 10.1016/j.bbi.2014.06.201. Epub 2014 Jul 9.
- Slavich GM, Way BM, Eisenberger NI, Taylor SE. Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14817-22. doi: 10.1073/pnas.1009164107. Epub 2010 Aug 2.
- Hart BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 1988 Summer;12(2):123-37. doi: 10.1016/s0149-7634(88)80004-6.
- Avitsur R, Cohen E, Yirmiya R. Effects of interleukin-1 on sexual attractivity in a model of sickness behavior. Physiol Behav. 1997 Dec 31;63(1):25-30. doi: 10.1016/s0031-9384(97)00381-8.
- Bluthe RM, Dantzer R, Kelley KW. Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat. Brain Res. 1992 Feb 28;573(2):318-20. doi: 10.1016/0006-8993(92)90779-9.
- Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun. 2010 May;24(4):558-63. doi: 10.1016/j.bbi.2009.12.009. Epub 2010 Jan 4.
- Moieni M, Irwin MR, Jevtic I, Olmstead R, Breen EC, Eisenberger NI. Sex differences in depressive and socioemotional responses to an inflammatory challenge: implications for sex differences in depression. Neuropsychopharmacology. 2015 Jun;40(7):1709-16. doi: 10.1038/npp.2015.17. Epub 2015 Jan 19.
- Willette AA, Lubach GR, Coe CL. Environmental context differentially affects behavioral, leukocyte, cortisol, and interleukin-6 responses to low doses of endotoxin in the rhesus monkey. Brain Behav Immun. 2007 Aug;21(6):807-15. doi: 10.1016/j.bbi.2007.01.007. Epub 2007 Mar 1.
- Yee JR, Prendergast BJ. Sex-specific social regulation of inflammatory responses and sickness behaviors. Brain Behav Immun. 2010 Aug;24(6):942-51. doi: 10.1016/j.bbi.2010.03.006. Epub 2010 Mar 17.
- Bilbo SD, Klein SL, DeVries AC, Nelson RJ. Lipopolysaccharide facilitates partner preference behaviors in female prairie voles. Physiol Behav. 1999 Dec 1-15;68(1-2):151-6. doi: 10.1016/s0031-9384(99)00154-7.
- Inagaki TK, Muscatell KA, Irwin MR, Moieni M, Dutcher JM, Jevtic I, Breen EC, Eisenberger NI. The role of the ventral striatum in inflammatory-induced approach toward support figures. Brain Behav Immun. 2015 Feb;44:247-52. doi: 10.1016/j.bbi.2014.10.006. Epub 2014 Oct 16.
- Muscatell KA, Moieni M, Inagaki TK, Dutcher JM, Jevtic I, Breen EC, Irwin MR, Eisenberger NI. Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun. 2016 Oct;57:21-29. doi: 10.1016/j.bbi.2016.03.022. Epub 2016 Mar 28.
- Aron A, Melinat E, Aron EN, Vallone RD, Bator RJ. The Experimental Generation of Interpersonal Closeness: A Procedure and Some Preliminary Findings. Pers Soc Psychol Bull. 1997;23(4):363-377. doi:10.1177/0146167297234003
- Berger J, Heinrichs M, von Dawans B, Way BM, Chen FS. Cortisol modulates men's affiliative responses to acute social stress. Psychoneuroendocrinology. 2016 Jan;63:1-9. doi: 10.1016/j.psyneuen.2015.09.004. Epub 2015 Sep 5.
- Glaser R, Robles TF, Sheridan J, Malarkey WB, Kiecolt-Glaser JK. Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults. Arch Gen Psychiatry. 2003 Oct;60(10):1009-14. doi: 10.1001/archpsyc.60.10.1009.
- Pressman SD, Cohen S, Miller GE, Barkin A, Rabin BS, Treanor JJ. Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. 2005 May;24(3):297-306. doi: 10.1037/0278-6133.24.3.297. Erratum In: Health Psychol. 2005 Jul;24(4):348.
- Christian LM, Iams JD, Porter K, Glaser R. Inflammatory responses to trivalent influenza virus vaccine among pregnant women. Vaccine. 2011 Nov 8;29(48):8982-7. doi: 10.1016/j.vaccine.2011.09.039. Epub 2011 Sep 22.
- Tsai MY, Hanson NQ, Straka RJ, Hoke TR, Ordovas JM, Peacock JM, Arends VL, Arnett DK. Effect of influenza vaccine on markers of inflammation and lipid profile. J Lab Clin Med. 2005 Jun;145(6):323-7. doi: 10.1016/j.lab.2005.03.009.
- Boyle CC, Kuhlman KR, Dooley LN, Haydon MD, Robles TF, Ang YS, Pizzagalli DA, Bower JE. Inflammation and dimensions of reward processing following exposure to the influenza vaccine. Psychoneuroendocrinology. 2019 Apr;102:16-23. doi: 10.1016/j.psyneuen.2018.11.024. Epub 2018 Nov 20.
- Kuhlman KR, Robles TF, Dooley LN, Boyle CC, Haydon MD, Bower JE. Within-subject associations between inflammation and features of depression: Using the flu vaccine as a mild inflammatory stimulus. Brain Behav Immun. 2018 Mar;69:540-547. doi: 10.1016/j.bbi.2018.02.001. Epub 2018 Feb 16.
- Kuhlman KR, Robles TF, Haydon MD, Dooley L, Boyle CC, Bower JE. Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation. Dev Psychobiol. 2020 Apr;62(3):400-408. doi: 10.1002/dev.21908. Epub 2019 Sep 6.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 22-1024
- 2047344 (Other Identifier: National Science Foundation)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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