Sensitivity to Social Rejection and Inflammatory Responses to Stress

Oct 06 2010 Published by under Behavioral Neuro, Neuroscience

Sci thought this particular paper was of current relevance, due in part to the public attention that bullying and social rejection has been getting lately.  I think it's really important that this gets in the public eye and that something is done about it, and so Sci will contribute her sciencey best to talk about bullying and social rejection, and why these things are bad for your health in more ways than one.

You see, Sci was bullied as a kid.  I know that it wasn't a quarter of what other people experienced, but it was by no means a walk in the park.  At one point in middle school, it got bad enough that, at some point in 6th grade, I got bronchitis.  And I got bronchitis again.   AND AGAIN.  Pretty soon I was missing a lot of school. It wasn't the school itself, Sci's a geek and LOVED school. It would just have been a lot better if there weren't those particular people in it...

Did I HAVE bronchitis?  The first time or two, absolutely.  But after that, I figured out pretty quick that a good, chesty cough, repeated often enough, got you sent to the nurse's office and then home to lie on the couch and watch David the Gnome, and out of having the girls titter behind you making horrible remarks about how you were a slut because they thought you had a crush on the one guy in the grade who was taller than you (I didn't, I still think he might be tall, but all the air up there seeped into his brain). And each time, that cough turned into bronchitis.

Eventually I got better, and went back to school where a big part in the school play ensured I was magically not sick for the rest of the year.  But to this day I have wondered how I got bronchitis.  I really did think, at least some of the time, that I was faking.  But I DID end up with bronchitis.  And I wondered if being under stress at school made me sick.

Now, I am an n=1, and therefore not data.  But it turns out that other people HAVE data on whether your reactions to social stress influence the way your body responds.  And here it is. Slavich et al. "Neural sensitivity to social rejection is associated with inflammatory responses to social stress" PNAS, 2010.

It's been known that psychological stress (which is stress like being overworked or being chronically unhappy, as opposed to physical stress, which is things like being constantly cold or not getting enough food) can make you more susceptible to illness like colds, as well as being a strong indicator for some major diseases. Right now we think that stress causes negative impacts on your health by increasing inflammation, which is associated with all manner of illnesses ranging from asthma to heart disease to depression. Apparently SOCIAL stressors (like social rejection) are particularly good at increasing these inflammatory processes.

But the question is: why? How does this work? How does social stress impact the way the brain then controls inflammatory processes? What brain regions respond to both inflammation and social stress?

Well, let's break it down. We know two brain regions that respond particularly well (or, badly, really) to social stress and rejection. These areas are the anterior cingulate cortex, and the anterior insula.


Acute social rejection activates both of those areas when people are scanned in fMRI. But the question in, are these two areas associated with inflammation as well?

To test this, they took a bunch of people and subjected them to social rejection and stress. That sounds completely horrible, but it's not QUITE as bad as you'd think. The subjects had to prepare and give a five minute speech on how they'd be a great administrative assistant. They had to deliver this speech to a panel, who spent the whole time acting bored and looking like the subject was doing a REALLY bad job. They THEN had to do difficult mental arithmetic (which included things like counting backward by 7s from 2,935. Try it. Apparently both doing math in your head and giving public speeches are what many people consider the height of stressful), while the experimenter kept looking at them in an annoyed way, checking his watch, and saying "faster please", and generally acting all mean. During this, they took measures of their saliva and looked at their inflammation levels by measuring two proteins: TNF-alpha and interleukin-6 (I won't go into exactly what those are, but they indicate the start of inflammatory processes.

This was social stress, but not social REJECTION. So they took a subset of the subjects (who had already been through the regular stresses and had their inflammatory indicators looked at) and had them play a video game called "Cyberball" while lying in an MRI, in which they got kicked out of the game by two "opponents" who were apparently supposed to be in the next room.


You can see here the levels of the two inflammatory indicators both before and after testing. The levels of both increased significantly, showing that the subjects were feeling the stress, and that this stress was increasing their inflammatory processes.


But this, this is the super cool data. Here you can see a series of correlations in the subjects that got the social rejection (the "Cyberball" thing), with their inflammatory markers AND with their brain scans. And it shows that the MORE your brain responds to social rejection (the more the anterior cingulate and the anterior insula light up), the more your BODY responds with inflammatory indicators. The best correlation was in the anterior cingulate.

So social stressors increase inflammatory activity no matter what, but if areas of your brain are more sensitive to social rejection, you will have MORE inflammatory activity responses to stress. Not only that, but the regular stress (the math) and the social rejection took place several weeks apart in different tests, which suggests that these results are stable traits.

This has a lot of important implications. The research is early days yet, but other studies have shown that people with more social rejection induced activity in the anterior cingulate are more distressed by social rejection. This study suggests that this distress isn't just emotional, it may be physical as well.

But the question is now: WHY does higher activity in the brain in response to social stress correlate with increased inflammatory markers? And HOW do these brain regions control inflammatory production? The authors have a couple of hypotheses for the first question:

1) Social stress often leads to physical stress (or at least, it did in our evolutionary history), so the inflammatory response may be a preemptive strike against potential injury(though inflammation sounds like a bad word these days, it can actually help wound healing).

2) This could be part of the underlying overlap between the way the brain responds to physical and emotional pain. Emotional pain, due to overlap in our brains, HURTS. Hurts just like physical pain would. And since your body responds to PHYSICAL pain with inflammatory markers, why not to emotional pain as well?

Sci thinks both of these are probably pretty likely, and really it's probably a bit of both. For the second question, we really don't know yet. Both of the brain regions studied here, the anterior cingulate and the anterior insula, have connections to the hypothalamus, which can regulate some inflammatory processes, so it could be that. But it could be a number of other things as well.

As for the subjects in this study, no notes on whether or not they actually got SICK as a result of the study, but more research into this area could help us understand why some people are more susceptible to diseases that have a big inflammatory role.

But the big conclusion? Social rejection is NOT COOL. Your body and your brain feel the pain. Just another reason to stop bullying and social rejection wherever you can.

Slavich GM, Way BM, Eisenberger NI, & Taylor SE (2010). Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Proceedings of the National Academy of Sciences of the United States of America, 107 (33), 14817-22 PMID: 20679216

13 responses so far

  • becca says:

    Yes, but the real question is does chronic social rejection increase the odds of getting CANCER? And what are you going to do about it?? /k3rn3d

    Sticks and stones can break my bones but words... can just give me CANCER

    One thing that bugs me about this study was why they didn't also look at anti-inflammatory cytokines. Many stimuli induce both, and it's kind of the net balance that determines what will happen.

    • scicurious says:

      Oooh, good point about the anti-inflammatory cytokines. They also note that they didn't do a sickness followup. I would also be interested in a retrospective study of people who are high responders, suffered from social rejection, and their rates of illness (things like colds and flus and stuff, as well as chronic issues like asthma), as compared to those who have not been. That's gonna be a huge study though.

  • Remember those studies about acetaminophen "relieving the pain" of social rejection (actually it just reduced acc activation, but not reported negative feelings)? (neurocritic wrote them up here: .) This might be a mechanism through which that effect (if you're convinced it exists) works.

    Also, this study is by (some of) the same people.

    It may be that inflammation modulates affect in some way (in addition to/instead of the other way around,) so that the inflammation that social stress causes also results in reduced acc activity, which might have emotional/cognitive effects.

  • BeccaTheCyborg says:

    Very interesting. I just left my incredibly hostile (on the part of management) job because of, in addition to their questionable labour practices, I found myself fainting regularly and vomiting uncontrollably at work. I have a fainting disorder, but I hadn't passed out in months, and the throwing up was definitely a new one.

  • Adrian says:

    Those results are very interesting, and so are the speculations about mechanism. Correlations between psychological stress and chronic disease are pretty well-established, but I had only been aware of connections that take days to become significant (like the way emotional stress often interferes with deep sleep, and a person needs adequate sleep to fight off disease.) Inflammation happens in minutes, so it suggests all sorts of connections to acute disease.

  • Autistic Lurker says:

    Interesting (and I did suffer from many issues such as respiratory illness, allergies as well as cardiac problems recently and I haven't spoke about the psychiatric issues as well) but is there some studies on effective coping behavior for the significantly bullied before they land in the office of a psychiatrist and get prescribed a cocktail of meds?


  • neuraxon77 says:


    My excuse at school was a recurring upset stomach (anxiety) and later on migraines. I missed a quarter of my entire schooling because of socially induced stress. I was socially rejected at school just turning up one morning after being absent for the previous week. By recess the social rejection and resultant migraine (inflammation) had progressed to seeing flashes of light, and the point I had to lay down before going home. I became chronically depressed, suicidal and I never returned to school. 20 years later I'm acutely aware of the cost/reward relationship of interacting with others in general, and despite my ability to now, I find people rarely respond well to the real me, and so I rarely seek to socially interact with others and have become somewhat socially avoidant, or what I prefer to refer to as socially apathetic.


  • Hypothetical Woman says:

    Oh, god, I developed epilepsy while I was in high school. I still have it, although not as bad - i eventually ended up dropping out because of it. High school was a very stressful time for me.

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