Scholars know that early life stress exposures are associated with adverse health outcomes and heightened anxiety symptoms in adolescents. Wanting to explore this further, Aysenil Belger, PhD, a professor in UNC’s Department of Psychiatry and the director of the UNC Frank Porter Graham Child Development Institute (FPG), her graduate student Rachel Corr, and an interdisciplinary team of investigators from UNC and Children’s Hospital of Philadelphia examined the impact of exposure to multiple categories of victimization (polyvictimization) on brain circuits associated with acute stress responses and contributions to mental health. Findings were published in Social Cognitive Affective Neuroscience in December 2021, “Stress-related hippocampus activation mediates the association between polyvictimization and trait anxiety in adolescents.”  

Studying neurobiological mechanisms contributing to anxiety is critical, because nearly one-third of adolescents meet the criteria for an anxiety disorder, increasing their likelihood of developing psychiatric conditions in adulthood. The hippocampus and amygdala, which are stress-sensitive regions of the brain, are particularly impacted by early life adversities and are implicated in the development of anxiety disorders. Corr, Belger, and colleagues examined associations among polyvictimization and activation of the hippocampus and amygdala by studying 80 periadolescents (children and adolescents between ages nine to 16.)

Studying these associations in adolescence is particularly important because stress-sensitive brain regions undergo critical maturation during this period of development and the onset of severe mental health disorders, such as mood disorders and psychosis, are demonstrated to be accelerated by stress exposure. “Identifying neurobiological mechanisms connecting polyvictimization to anxiety in periadolescence is an important step for creating targeted preventative interventions to reduce the risk that polyvictimized youths will develop mental illness,” says Belger.

In this study, trained researchers used an abbreviated form of the Structured Clinical Interview for DSM-IV to assess psychopathology and State-Trait Anxiety Inventory for Children, a definitive instrument for measuring anxiety in children. Children also underwent a brain imaging protocol while performing the Montreal Imaging Stress Task (MIST), a well-validated psychosocial stress protocol, and subjective stress ratings assessments before, during, and after stress imaging.

During the experimental stress condition, subjects solved time-restricted math problems while their performance was recorded. A stressful tone with a rising pitch emphasized time pressure. Participants were told their performance was compared to that of other study subjects thereby creating a social evaluative context. Between each run, researchers informed subjects that their performance was below average and instructed them to try harder during the experimental condition, increasing evaluative psychosocial stress. During these tasks, the subjects’ brains were scanned with an fMRI at the Duke-UNC Brain Imaging and Analysis Center, to identify brain regions and circuits contributing to the acute stress experience.  After the MRI session, participants were debriefed about the task.

Results revealed that polyvictimization was associated with higher trait anxiety as well as greater stress-related activation in the right hippocampus, a region critical for learning and memory. This greater hippocampal activity predicted heightened trait anxiety. Using robust mediation analyses, the researchers discovered that stress-related right hippocampus activation partially mediated the relationship between polyvictimization and trait anxiety. These results expand upon the existing polyvictimization literature by suggesting a possible neurobiological pathway through which polyvictimization contributes to the etiology of mental illness.

“To our knowledge, this paper represents the first analysis connecting polyvictimization to neural activation,” says Belger. “Future longitudinal designs are necessary to determine the causal relationship between these variables and identify other factors impacting these pathways.”