Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents
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 spe...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-01-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02728-4 |
| _version_ | 1797349638353715200 |
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| author | Zoé Schilliger Yasser Alemán-Gómez Mariana Magnus Smith Zeynep Celen Ben Meuleman Pierre-Alain Binz Pascal Steullet Kim Q. Do Philippe Conus Arnaud Merglen Camille Piguet Daniella Dwir Paul Klauser |
| author_facet | Zoé Schilliger Yasser Alemán-Gómez Mariana Magnus Smith Zeynep Celen Ben Meuleman Pierre-Alain Binz Pascal Steullet Kim Q. Do Philippe Conus Arnaud Merglen Camille Piguet Daniella Dwir Paul Klauser |
| author_sort | Zoé Schilliger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:34:16Z |
| format | Article |
| id | doaj.art-47e3353a1db945a29c03518ebe471a64 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-08T12:34:16Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-47e3353a1db945a29c03518ebe471a642024-01-21T12:36:38ZengNature Publishing GroupTranslational Psychiatry2158-31882024-01-0114111110.1038/s41398-023-02728-4Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescentsZoé Schilliger0Yasser Alemán-Gómez1Mariana Magnus Smith2Zeynep Celen3Ben Meuleman4Pierre-Alain Binz5Pascal Steullet6Kim Q. Do7Philippe Conus8Arnaud Merglen9Camille Piguet10Daniella Dwir11Paul Klauser12Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of LausanneConnectomics Lab, Department of Radiology, Lausanne University Hospital and University of LausanneDivision of General Pediatrics, Geneva University Hospitals and Faculty of Medicine, University of GenevaDepartment of Psychiatry, Faculty of Medicine, University of GenevaDepartment of Psychiatry, Faculty of Medicine, University of GenevaService of Clinical Chemistry, Lausanne University Hospital and University of LausanneCenter for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of LausanneCenter for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of LausanneService of General Psychiatry, Department of Psychiatry, Lausanne University Hospital and University of LausanneDivision of General Pediatrics, Geneva University Hospitals and Faculty of Medicine, University of GenevaDivision of General Pediatrics, Geneva University Hospitals and Faculty of Medicine, University of GenevaCenter for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of LausanneCenter for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of LausanneAbstract 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.https://doi.org/10.1038/s41398-023-02728-4 |
| spellingShingle | Zoé Schilliger Yasser Alemán-Gómez Mariana Magnus Smith Zeynep Celen Ben Meuleman Pierre-Alain Binz Pascal Steullet Kim Q. Do Philippe Conus Arnaud Merglen Camille Piguet Daniella Dwir Paul Klauser Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents Translational Psychiatry |
| title | Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| title_full | Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| title_fullStr | Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| title_full_unstemmed | Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| title_short | Sex-specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| title_sort | sex specific interactions between stress axis and redox balance are associated with internalizing symptoms and brain white matter microstructure in adolescents |
| url | https://doi.org/10.1038/s41398-023-02728-4 |
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