Related Experiment Video
Updated: Jul 5, 2025

Author Spotlight: Understanding Adolescent Social Adversity Effects on Neurodevelopment in Mice
Published on: March 15, 2024
Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain
Zoé Schilliger1,2, Yasser Alemán-Gómez3, Mariana Magnus Smith4
1Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Abstract:
Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13-15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.
Related Concept Videos
Stress and Mental Health
Individuals with depression often experience challenges in both their personal and professional...
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings....
Introduction to Stress and Lifestyle
Psychological Responses to Stress
Ethnic Identity within a Larger Culture
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...

