Cortisol Stress Reactivity and Cumulative Output Associations with Structural Neural Network Architecture in Adolescents

The hypothalamic-pituitary-adrenal (HPA) axis maintains homeostasis and responds to stressors in the environment, shaping responsivity and behavior at least partly through its effects on the brain. For example, increased cortisol levels are associated with increased neural connections and long-term potentiation, but persistently elevated cortisol levels are associated with deleterious effects on the brain. Recent work also links cortisol stress reactivity to individual differences in large-scale functional brain network organization. However, how the cortisol response to acute stress relates to white matter that facilitates signal transmission between gray matter structures is less clear. In 222 adolescents (53% girls, 75% African American/Black) from low-socioeconomic status families, we examined how different phases of the cortisol response to a laboratory stressor, as measured by saliva, and overall cumulative cortisol-cortisone output (a potentially stronger index of cumulative cortisol activity) in hair, were associated with white matter network organization. Greater cortisol stress reactivity and higher peak cortisol levels were associated with increased global efficiency (information transfer). Higher peak cortisol levels were also associated with greater small-world propensity (integration-segregation balance). Higher overall cumulative cortisol-to-cortisone output was associated with increased transitivity (robustness to information disruption). These findings suggest that greater stress reactivity is associated with more efficient information transfer, whereas higher overall cumulative stress activity is associated with more robust information transfer, potentially as a response to environmental stressors. Neither the cortisol response to acute stress nor overall cumulative cortisol-cortisone output was associated with network segregation, and cortisol stress recovery was not associated with network organization.