Publication date: Jul 01, 2025

Adolescence is a period of vulnerability wherein stress can become biologically embedded in ways that impact long-term trajectories of mental and physical health. In particular, stressors are transduced into physiological changes via the hypothalamic-pituitary-adrenal (HPA) axis in ways that can impact both physical and mental health. However, there continues to be uncertainty regarding how to best differentiate and understand well-regulated HPA axis reactivity to stress from dysregulated HPA axis reactivity. One promising approach involves examining multiple biomarkers; indeed, there is evidence that dysregulation of the HPA axis profoundly influences the regulation of the immune system. A cohort of adolescent youth was followed across two ubiquitous stressors-the transition to high school and the COVID-19 pandemic. Nuanced longitudinal associations between HPA axis activity (i. e., cortisol) and immune system activity (i. e., panel of inflammatory markers) were examined. Findings provide evidence of biological specificity wherein HPA axis hyperactivity during the COVID-19 pandemic was associated with elevated levels of an empirically derived inflammatory composite, which may be driven by elevations in tumor necrosis factor-alpha, interleukin-6, and c-reactive protein. The current work advances the literature on allostatic load and the glucocorticoid-resistance model in youth. By extending our current understanding of how stress influences adolescent well-being, it also has important implications for mental and physical health prevention and intervention efforts.

Semantics

Original Article