Teenage girls with depression show altered brain responses to repeated social rejection

A recent study published in the Journal of Affective Disorders suggests that teenage girls experiencing depression process anticipated social rejection differently in the brain compared to their peers. The researchers found that a specific brain region involved in threat detection fails to adapt to repeated social rejection in youth with depression. These findings highlight how the condition might change the way young brains navigate and learn from negative social interactions.

The teenage years are a sensitive period for socio-emotional development, a time when interactions with peers take on heightened importance. During adolescence, the brain heavily prioritizes social feedback, such as acceptance or rejection by friends and classmates. Developing depression during this formative window tends to negatively affect social functioning and alters how the brain interprets social environments.

A key brain structure involved in navigating these interactions is the amygdala. This small, almond-shaped cluster of neurons sits deep in the brain and helps process emotions and detect threats. The amygdala also attributes importance to social cues, flagging certain situations as needing immediate attention.

In a typical brain, the amygdala shows a biological pattern called habituation when exposed to a repeated emotional stimulus. Habituation means that as a person repeatedly encounters the exact same situation, their brain’s alarm response gradually decreases. If a specific social situation is stable and predictable, the brain conserves energy by reacting less intensely.

Previous research suggests that depression might alter how the brain responds to negative emotional information. “We know from prior work that youth experiencing depression show different neural responses to social cues from peers,” explained study author Michele Morningstar, an associate professor of psychology at Queen’s University in Ontario. “For instance, depression seems to be associated with a heightened neural response to being accepted or rejected by other teens, a pattern that might represent a ‘hypersensitivity’ to feedback from others.”

Less is known about how depression affects this specific process of neural habituation during complex social interactions. The scientists designed the current study to see if a failure to adapt to repeated social threats might explain some of the social difficulties experienced by teens with depression. “The current study wanted to explore how these patterns might emerge across interactions with peers,” Morningstar explained.

By understanding how the amygdala responds over time to the threat of rejection, the authors aimed to map out potential biological markers of the disorder. “Does the first rejection already elicit a hypersensitive response in a region like the amygdala, which is sensitive to salient social information?” Morningstar asked. “Or, does this pattern only emerge after repeated rejections from peers?”

The research team recruited 76 girls between the ages of 10 and 17. The sample included three distinct groups based on detailed clinical interviews. Twenty-two of the girls had a current diagnosis of major depressive disorder. Thirty girls had no personal history of depression but were considered at familial risk because at least one parent had a history of the disorder.

The remaining 24 girls formed a low-risk control group, meaning they had no personal or parental history of psychiatric conditions. To measure brain activity, the scientists used functional magnetic resonance imaging. This non-invasive scanning technology tracks blood flow in the brain to show which areas are active during specific cognitive tasks.

While resting inside the scanner, the girls participated in a computer-based social evaluation task called the Chatroom Interact. Before the scan, the participants viewed photographs of other youth and chose several peers they would theoretically like to talk to. During the actual brain scan, they were told they were interacting with two of these chosen peers in a virtual chatroom. In reality, the peers were computer programs designed with specific behaviors.

During the task, the girls repeatedly anticipated whether these virtual peers would choose to talk to them about a variety of topics or reject them. One virtual peer was programmed to be mean, rejecting the participant 67 percent of the time by placing a large X over the participant’s photo. The other peer was programmed to be nice, accepting the participant 67 percent of the time.

The task included a total of 60 trials, split between the mean peer and the nice peer. The researchers focused specifically on the anticipation period before the participant saw the peer’s final decision. This waiting period lasted an average of 4750 milliseconds.

The scientists looked at how the amygdala’s activation changed trial by trial as the girls implicitly learned which peer was most likely to reject them. The data showed that for the low-risk and at-risk groups, brain activity in both sides of the amygdala decreased steadily across the trials involving the mean peer. Their brains demonstrated typical habituation, adapting to the predictable threat of rejection.

“Over time, being repeatedly rejected by virtual peers elicited less and less amygdala response in youth without depression and youth at-risk for depression (but not currently experiencing depression themselves),” Morningstar told PsyPost. The girls with major depressive disorder displayed a different biological pattern. The right side of their amygdala showed a much flatter slope of activation over time.

“But, youth with depression continued to show high amygdala response to repeated rejection from peers across the entire task,” Morningstar noted. “In other words, their amygdala did not habituate to the repeated rejection.” This suggests that the brains of the girls with depression continued to react to the mean peer as if the threat of rejection was entirely new every single time.

“This finding suggests that the process of social learning about rejection cues might be disrupted in youth with depression,” Morningstar explained. “Unlike their non-depressed peers whose amygdala habituated to repeated rejection, youth with depression continued to show that ‘hyper-responsivity’ to a rejecting peer across multiple trials.”

The researchers noted that this lack of habituation was highly specific to the context of an expected social threat. When anticipating decisions from the nice peer, habituation did occur, and this biological adaptation did not differ across the three groups. The failure to learn and adapt at the neural level was uniquely tied to the anticipation of a negative social outcome.

The authors also looked at other brain regions to see if this pattern was widespread across the entire brain. They examined the anterior insula, a region involved in detecting important information, and the subgenual anterior cingulate cortex, which plays a role in emotional regulation. They found that the anterior insula showed normal habituation across all groups when facing the mean peer.

Additionally, the subgenual anterior cingulate cortex showed higher overall activation in the at-risk girls compared to the low-risk group when anticipating the mean peer’s decision. This provides evidence that genetic risk for depression might increase overall sensitivity in certain emotional regions. The specific failure to adapt over time to the mean peer remained uniquely localized to the right amygdala in the group experiencing depression.

It is important to note that the study measured brain activity rather than conscious awareness or explicit learning. The researchers did not assess whether the girls explicitly realized which peer was mean and which was nice, only that their brains stopped adapting to the behavioral pattern. A lack of neural habituation does not automatically mean a person is consciously obsessing over a social threat.

The study also cannot confirm whether altered brain habituation causes depression or if the experience of depression causes the brain to stop habituating to social threats. The relationship is likely complicated and goes in both directions. The sample size of 76 participants is relatively modest for this type of brain imaging research, which limited the researchers’ ability to explore how other individual differences might influence the learning process.

For example, the scientists could not easily measure how baseline anxiety or a general fear of social situations might alter a specific participant’s brain activity. The study was also restricted to adolescent girls assigned female at birth. The findings cannot be generalized to boys, adults, or individuals with other gender identities, as different demographic groups might process social information differently.

Future research will need to explore how different brain regions communicate with one another during these social tasks. Brain structures do not operate in isolation, and depression likely affects widespread networks that manage emotion and social behavior. Linking these neural patterns to actual social behaviors in everyday life will help clarify how altered social learning contributes to adolescent mental health.

The study, “Reduced amygdala habituation to anticipated social rejection in youth with major depressive disorder,” was authored by M. Morningstar, M.N.K. Gravelle, D.P. Dickstein, J.S. Silk, R.E. Dahl, E.E. Nelson, D. Yee, and L.R. Stroud.