For years, local scientists in Sacramento and Davis at the University of California, Davis have studied the brain's reaction to social rejection. For example, you can check out the UC Davis study published in Science back in 2003, "Does Rejection Hurt? An fMRI Study of Social - Carter Lab, UC Davis." In that research, a neuroimaging study examined the neural correlates of social exclusion and tested the hypothesis that the brain bases of social pain are similar to those of physical pain.
Participants were scanned while playing a virtual ball-tossing game in which they were ultimately excluded. Paralleling results from physical pain studies, the anterior cingulate cortex (ACC) was more active during exclusion than during inclusion and correlated positively with self-reported distress.
Right ventral prefrontal cortex (RVPFC) was active during exclusion and correlated negatively with self-reported distress. ACC changes mediated the RVPFC-distress correlation, suggesting that RVPFC regulates the distress of social exclusion by disrupting ACC activity. Now, a new study has been published by researchers at the University of Michigan Medical School team showing how chemicals in our brains make us feel better after finding out we've been rejected by someone, some organization, or some school, place of work, career, license, degree, friend, rank, date, family, community, religion, mate, or any other echelon to which we wanted to reach, feel accepted by, or achieve.
Knowledge that there are chemicals in our brains working to help us feel better after being rejected is comforting
Finding that the opioid system can act to ease social pain, not just physical pain, may aid understanding of depression and social anxiety. "Sticks and stones may break my bones, but words will never hurt me," goes the playground rhyme that's supposed to help children endure taunts from classmates.
Now a new study suggests that there's more going on inside our brains when someone snubs us – and that the brain may have its own way of easing social pain. You can check out the abstract of the original study, "Response of the μ-opioid system to social rejection and acceptance," published in the August 20, 2013 issue of the journal Molecular Psychiatry.
The findings by a University of Michigan Medical School team, show that the brain's natural painkiller system responds to social rejection – not just physical injury. What's more, people who score high on a personality trait called resilience – the ability to adjust to environmental change – had the highest amount of natural painkiller activation.
The team, based at University of Michigan (U-M)'s Molecular and Behavioral Neuroscience Institute, used an innovative approach to make its findings. They combined advanced brain scanning that can track chemical release in the brain with a model of social rejection based on online dating. The work was funded by the U-M Depression Center, the Michigan Institute for Clinical and Health Research, the Brain & Behavior Research Foundation, the Phil F Jenkins Foundation, and the National Institutes of Health.
They focused on the mu-opioid receptor system in the brain – the same system that the team has studied for years in relation to response to physical pain. Over more than a decade, University of Michigan (U-M) work has shown that when a person feels physical pain, their brains release chemicals called opioids into the space between neurons, dampening pain signals.
David T. Hsu, Ph.D., the lead author of the new paper, says the new research on social rejection grew out of recent studies by others, which suggests that the brain pathways that are activated during physical pain and social pain are similar. "This is the first study to peer into the human brain to show that the opioid system is activated during social rejection," says Hsu, in the October 10, 2013 news release, "Sticks and stones: Brain releases natural painkillers during social rejection, U-M study finds."
Hsu is a research assistant professor of psychiatry. "In general, opioids have been known to be released during social distress and isolation in animals, but where this occurs in the human brain has not been shown until now," Hsu explains in the news release. The study involved 18 adults who were asked to view photos and fictitious personal profiles of hundreds of other adults. Each selected some who they might be most interested in romantically – a setup similar to online dating.
Then, when the participants were lying in a brain imaging machine called a PET scanner, they were informed that the individuals they found attractive and interesting were not interested in them
Brain scans made during these moments showed opioid release, measured by looking at the availability of mu-opioid receptors on brain cells. The effect was largest in the brain regions called the ventral striatum, amygdala, midline thalamus, and periaqueductal gray – areas that are also known to be involved in physical pain.
The researchers had actually made sure the participants understood ahead of time that the "dating" profiles were not real, and neither was the "rejection." But nonetheless, the simulated social rejection was enough to cause both an emotional and opioid response.
Suffering slings and arrows differently
Hsu notes that the underlying personality of the participants appeared to play a role in how much of a response their opioid systems made. The amygdala is a region of the brain involved in emotional processing. "Individuals who scored high for the resiliency trait on a personality questionnaire tended to be capable of more opioid release during social rejection, especially in the amygdala," Hsu says in the October 10, 2013 news release, Sticks and stones: Brain releases natural painkillers during social rejection, U-M study finds. "This suggests that opioid release in this structure during social rejection may be protective or adaptive."
The more opioid release during social rejection in another brain area called the pregenual cingulate cortex, the less the participants reported being put in a bad mood by the news that they'd been snubbed
The researchers also examined what happens when the participants were told that someone they'd expressed interest in had expressed interest in them – social acceptance. In this case, some brain regions also had more opioid release. "The opioid system is known to play a role in both reducing pain and promoting pleasure, and our study shows that it also does this in the social environment," says Hsu.
The new research holds more importance than just pure discovery, note the authors, who also include senior author Jon-Kar Zubieta, M.D., Ph.D., a longtime opioid researcher. Specifically, they are pursuing further research on how those who are vulnerable to, or currently suffering from depression or social anxiety have an abnormal opioid response to social rejection and/or acceptance.
"It is possible that those with depression or social anxiety are less capable of releasing opioids during times of social distress, and therefore do not recover as quickly or fully from a negative social experience. Similarly, these individuals may also have less opioid release during positive social interactions, and therefore may not gain as much from social support," Hsu theorizes, according to the news release.
Hsu also notes that perhaps new opioid medications without addictive potential may be an effective treatment for depression and social anxiety. Although such medications are not yet available, he adds, "increasing evidence for the neural overlap of physical and social pain suggests a significant opportunity to bridge research in the treatment of chronic pain with the treatment of psychiatric disorders."
If nothing else, perhaps knowing that our response to a social snub isn't "all in our heads" can help some people understand their responses and cope better, Hsu says in the news release. "The knowledge that there are chemicals in our brains working to help us feel better after being rejected is comforting."
In the University of Michigan photo that illustrates this article, the photo represents in the study a situation similar to online dating, where the study participants chose profiles of people they are most attracted to. They viewed the profiles (left), and their own (right) while lying in a brain scanner that tracked their brain's opioid response when they were told the person they'd chosen did or did not like them (as in the last line of this image).
If you check out the other slideshow photo with this article, in that photo, you can see a brain image showing in orange/red one area of the brain where the natural painkiller (opioid) system was highly active in research volunteers who are experiencing social rejection. This region, called the amygdala, was one of several where the U-M team recorded the first images of this system responding to social pain, not just physical pain. Studying this response, and the variation between people, could aid understanding of depression and anxiety.
In addition to Hsu and Zubieta, the research team included BJ Sanford, KK Meyers, TM Love, KE Hazlett, H Wang, L Ni, SJ Walker, BJ Mickey, ST Korycinski, RA Koeppe, JK Crocker, and SA Langenecker. The research was funded by the National Institutes of Health (MH085035, MH074459, DA022520, DA027494), as well as by the Brain & Behavior Research Foundation, the Michigan Institute for Clinical and Health Research, a Rachel Upjohn Clinical Scholars Award, and the Phil F. Jenkins Foundation.