The pain of social rejection lasts longer for people with untreated depression, according to a new study.
That’s because the brain cells of depressed people release less of a natural pain and stress-reducing chemical called natural opioids, researchers report in the journal Molecular Psychiatry.
Conversely, when someone they’re interested in likes them back, depressed people do feel better — but only momentarily, the study found.
A team from the University of Michigan Medical School, Stony Brook University and the University of Illinois at Chicago worked together on the study, which used specialized brain-scanning technology and a simulated online dating scenario.
“Every day we experience positive and negative social interactions. Our findings suggest that a depressed person’s ability to regulate emotions during these interactions is compromised, potentially because of an altered opioid system. This may be one reason for depression’s tendency to linger or return, especially in a negative social environment,” said lead author David Hsu, Ph.D., formerly of the University of Michigan and now at Stony Brook.
“This builds on our growing understanding that the brain’s opioid system may help an individual feel better after negative social interactions, and sustain good feelings after positive social interactions.”
The researchers focused on the mu-opioid receptor system in the brain — the same system studied for years in relation to our response to physical pain. During physical pain, our brains release opioids to dampen pain signals.
The new research shows that this same system is associated with an individual’s ability to withstand social stress and to positively respond to positive social interactions, noted senior author Jon-Kar Zubieta, M.D., Ph.D., of the University of Michigan’s Molecular and Behavioral Neuroscience Institute, and a professor in the Department of Psychiatry.
“Social stressors are important factors that precipitate or worsen illnesses such as depression, anxiety and other neuropsychiatric conditions,” he said. “This study examined mechanisms that are involved in the suppression of those stress responses.
“The findings suggest novel potential targets for medication development that directly or indirectly target these circuits, and biological factors that affect variation between individuals in recovery from this otherwise chronic and disabling illness.”
The researchers recruited 17 individuals who met the criteria for major depressive disorder, but were not taking medication for the condition, as well as 18 similar but non-depressed individuals.
All participants viewed photos and profiles of hundreds of other adults in a simulated online dating scenario. Each person then selected profiles of the people they were most interested in romantically.
During a brain scan using an imaging technique called positron emission tomography (PET), the participants were informed that the individuals they found attractive and interesting were not interested in them. PET scans made during these moments of rejection showed both the amount and location of opioid release, measured by looking at the availability of mu-opioid receptors on brain cells.
The depressed individuals showed reduced opioid release in brain regions regulating stress, mood and motivation, according to the study’s findings.
When participants were informed that the people they chose liked them back, both the depressed and non-depressed individuals reported feeling happy and accepted. This surprised the researchers, according to Hsu, because depression’s symptoms often include a dulled response to positive events that should be enjoyable.
However, the positive feeling in depressed individuals disappeared quickly after the period of social acceptance had ended, and may be related to altered opioid responses, he noted.
Only the non-depressed people went on to report feeling motivated to connect socially with other people, according to the researchers. That feeling was accompanied by the release of opioids in a brain area called the nucleus accumbens, which is involved in reward and positive emotions.
The researchers note they actually informed participants ahead of time that the “dating” profiles were not real, and neither was the “rejection” or “acceptance.” Nonetheless, the simulated online dating scenario was enough to cause both an emotional and opioid response, the study found.
After the experiment, researchers gave the depressed participants information on treatment resources.
“We enrolled almost all of these subjects in a subsequent treatment study, which allows us to capture additional information about how these opioid changes to acceptance and rejection may relate to success or failure of our standard treatments,” said study co-investigator Scott Langenecker, formerly at U-M and now at the University of Illinois at Chicago.
“We expect work of this type to highlight different subtypes of depression, where distinct brain systems may be affected in different ways, requiring us to measure and target these networks by developing new and innovative treatments.”
The study’s findings have led the researchers to plan follow-up studies to test individuals who are more sensitive to social stress and vulnerable to disorders such as social anxiety and depression, and to test ways of boosting the opioid response.
“Of course, everyone responds differently to their social environment,” Hsu said. “To help us understand who is most affected by social stressors, we’re planning to investigate the influence of genes, personality and the environment on the brain’s ability to release opioids during rejection and acceptance.”