Stress-related hippocampus activation mediates the association between polyvictimization and trait anxiety in adolescents

Abstract

Early life stress exposures are associated with adverse health outcomes and heightened anxiety symptoms in adolescents. Stress-sensitive brain regions like the hippocampus and amygdala are particularly impacted by early life adversities and are also implicated in the development of anxiety disorders. However, to date no studies have specifically examined the neural correlates of polyvictimization (exposure to multiple categories of victimization) or the contribution of stress-sensitive neural nodes to polyvictimization’s impact on mental health. To elucidate these relationships, the current study analyzed associations between polyvictimization, hippocampal and amygdalar activation during an acute stress task, and trait anxiety in a sample of 80 children and adolescents aged 9-16 years (33 female). Results showed that polyvictimization was associated with higher trait anxiety as well as greater stress-related right hippocampus activation, and this greater hippocampal activity predicted heightened trait anxiety. Robust mediation analyses revealed that stress-related right hippocampus activation partially mediated the relationship between polyvictimization and trait anxiety. Our results expand upon the existing polyvictimization literature by suggesting a possible neurobiological pathway through which polyvictimization is connected to the etiology of mental illness.

Resetting the Hippocampal Buffer: A Neurocognitive Account of Psychedelic Therapy for Anxiety-Related Psychopathology

“…Damage to the ventral hippocampus in animals (anterior hippocampus in humans) reduces several anxiety-like behaviors (Bannerman et al, 2004), with some work suggesting at least as much, if not more, dependence of these behaviors on the hippocampus than the amygdala (Bach et al, 2014;Korn et al, 2017;McHugh et al, 2004). Moreover, hyperexcitability of the hippocampus may be a feature of anxiety-related psychopathology that differentiates it from depression (Corr et al, 2022;Ghasemi et al, 2022;Hou et al, 2023), and SSRIs may normalize this hyperexcitability (Carey et al, 2004;Tural et al, 2018).…”

“…While the development of anxiety-related psychopathology is complex and differs across individuals as a function of environmental factors and biological predispositions, the focal point of our model is the hippocampus. As discussed above, anxiety-related psychopathology may be associated with a hyperexcitable hippocampus (Corr et al, 2022;Ghasemi et al, 2022;Hou et al, 2023), which may reflect a biased and imbalanced emphasis on encoding and storing anxietyrelated information. Such anxiety-related content then drives the amygdala and SN, which deploys the ECN to exert top-down control over emotional state and behavior (Hermans et al, 2014).…”