Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_CCCA37EE5321
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents.
Journal
Translational psychiatry
Author(s)
Schilliger Z., Alemán-Gómez Y., Magnus Smith M., Celen Z., Meuleman B., Binz P.A., Steullet P., Do K.Q., Conus P., Merglen A., Piguet C., Dwir D. (co-last), Klauser P.
ISSN
2158-3188 (Electronic)
ISSN-L
2158-3188
Publication state
Published
Issued date
17/01/2024
Peer-reviewed
Oui
Volume
14
Number
1
Pages
30
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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.
Keywords
Humans, Male, Adolescent, Female, Hydrocortisone, White Matter/diagnostic imaging, Cortodoxone, Brain/diagnostic imaging, Oxidation-Reduction, Hypothalamo-Hypophyseal System/physiology, Pituitary-Adrenal System/physiology, Antioxidants, Stress, Psychological
Pubmed
Web of science
Open Access
Yes
Create date
18/01/2024 16:29
Last modification date
09/08/2024 16:06
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