Social Rejection – Inflammatory Responses
A study published in the Proceedings of the National Academy of Sciences of the USA (PNAS) indicates that a social stressor involving social-evaluative threat and rejection elicits significant increases in inflammatory activity, as indexed by both soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII) and interleukin (IL)-6.
Humans are social animals by nature. We feel stronger mentally and physically when we believe we belong and are accepted as part of a family, friendship network, tribe or larger cultural group. Thus, loneliness is one of the largest predictors of ill health and early mortality. One specific cause of loneliness is ostracism (‘social rejection’) and is particularly hurtful psychologically and emotionally.
Social rejection occurs when an individual is deliberately excluded from a social relationship or social interaction. The topic includes interpersonal rejection, romantic rejection and familial estrangement. A person can be rejected by individuals or an entire group of people. Furthermore, rejection can be either active, by bullying, teasing, or ridiculing, or passive, by ignoring a person, or giving the “silent treatment”.
As researchers have dug deeper into the roots of rejection, they’ve found surprising evidence that the pain of being excluded is not so different from the pain of physical injury. Rejection also has serious implications for an individual’s psychological state and for society in general. Social rejection can influence emotion, cognition and even physical health.
Interestingly, Roy Baumeister, a social scientist, in a series of experiments conducted with colleagues found that following social rejection people become significantly more aggressive, prone to cheating and risk-taking, and unwilling to help others.
There are many kinds of stressors that increase our risk for disease, but stressors that threaten our social standing, such as targeted rejection, seem to be particularly harmful. Targeted rejection activates the molecular signaling pathways that regulate inflammation. Thus, participants had elevated levels of mRNA for both NF-κB and I-κB, following visits when a recent targeted rejection life event had occurred. Interestingly, the effect was more pronounced in those who perceived their social status to be higher.
Recent evidence indicates that psychological stress may affect the onset or progression of several common human diseases at least in part by up-regulating acute or chronic inflammatory processes.
Among various stressors, it appears that social stress is a particularly strong trigger of inflammation, but the neurocognitive pathways that underlie this effect remain unknown. In particular, no studies to date have investigated the neural regions associated with differences in inflammatory responding to acute social stress. The brain plays a critical role in appraising social stressors, as well as in modulating the immune system’s response to stressors that involve social or physical threat.
Differences in inflammatory responses to social stress may thus be explained, at least in part, by individual differences in activity in neural regions that process social threat-related information.
Prior research has shown that an acute episode of social rejection is linked to activation of specific brain regions such as the dorsal anterior cingulate cortex (dACC) and the anterior insula.
In the PNAS study, George Slavich and colleagues from the University of California, Los Angeles report that a social stressor involving social-evaluative threat and rejection elicits significant increases in inflammatory activity, as indexed by both sTNFαRII and IL-6.
To examine the neurocognitive pathways that might underlie this effect, the authors focused on brain regions previously implicated in processing rejection-related distress and negative affect. Anatomical ROI analyses revealed that greater activity in the dACC and bilateral anterior insula during social exclusion (vs. inclusion) was associated with greater sTNFαRII responses to the laboratory-based social stressor; greater activity in the right anterior insula was marginally related to increases in IL-6. These associations were consistent with whole-brain analyses, which confirmed that greater activity in the dACC and left anterior insula was associated with greater increases in sTNFαRII.
According to the authors this indicates that neural responses to social rejection are associated with potentiated inflammatory responses to an episode of acute social stress. This is consistent with previous studies showing that greater social rejection-induced dACC activity during an fMRI session is associated with greater self-reported distress during daily social interactions.
The authors discuss that brain regions involved in processing social rejection-related information are most likely associated with a variety of biological responses to social and physical threat. Thus, these brain regions may have important implications for health and/or the individual’s susceptibility to inflammatory diseases.
SOURCE: Proc Natl Acad Sci USA 2010, 107:14817. Epub 2010 Aug 2
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A 2015 study by Keely Muscatell et al., published in Brain, Behavior, and Immunity explored how neural activity during a social stressor is linked with stressor-evoked inflammatory activity. The authors found that
greater neural activity in the left amygdala in response to negative social feedback was related to greater stressor-evoked changes in IL-6.
Also, the individuals who showed more tightly coupled activity of the amygdala and the dorsomedial prefrontal cortex (DMPFC) during negative feedback showed heightened inflammatory responses to the stressor.
Thus, according to the authors, their observations suggest that greater activity in a key threat-related neural region (i.e., amygdala), and stronger coupling between brain regions involved in sustaining or amplifying threat responses (i.e., DMPFC and amygdala), are associated with heightened inflammatory responses to stress.
A 2016 study by Keely Muscatell et al. published in Social Cognitive and Affective Neuroscience explored the neural mechanisms linking social status and inflammatory responses to social stress, in an effort to understand how social hierarchies may influence health and well-being.
The authors reported that
lower subjective social status was associated with greater increases in the pro-inflammatory cytokine IL-6 in response to a social stressor.
Furthermore, neuroimaging data revealed that status was related to neural responses in a key mentalizing-related brain region (DMPFC), with individuals lower in subjective social status showing greater activity in the DMPFC in response to receiving negative social feedback.
Lastly, the authors found that activity in the DMPFC in response to negative feedback mediated the relation between social status and inflammatory responses, suggesting a possible neurocognitive pathway by which lower subjective social status may lead to greater inflammation. The authors believe this is the first study to find mediational evidence
linking perceptions of social status, neural activation and stress-induced increases in inflammation.
A 2022 review by Keely Muscatell et al. published in Current Topics in Behavioral Neurosciences overviewed the research on the neural underpinnings of social stress processing. This includes
- the neural underpinnings of three types of social stressors commonly studied in the literature: social rejection, social evaluation, and racism-related stress. Within our discussion of each type of social stressor;
- and, the methods used to induce stress, the brain regions commonly activated among studies investigating that type of stress, and recommendations for future work.
This review identified activity in midline regions in both prefrontal and parietal cortices, as well as lateral prefrontal regions, as being associated with processing social rejection. Activity in the insula, thalamus, and inferior frontal gyrus is often found in studies using social evaluation tasks. In addition, the authors discussed, racism-related stress is associated with activity in the ventrolateral prefrontal cortex and rostral anterior cingulate cortex.
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