Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging
Abstract Recent evidence challenged the traditional, categorical approach to sex differences, indicating that each human brain comprises a mosaic of features, some of which are more common among males, others, among females, whereas the remaining are equally common between sexes. Thus, a focus on re...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60686-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238323200000000 |
|---|---|
| author | Raluca Petrican Alex Fornito Christopher Murgatroyd Emma Boyland Charlotte A. Hardman |
| author_facet | Raluca Petrican Alex Fornito Christopher Murgatroyd Emma Boyland Charlotte A. Hardman |
| author_sort | Raluca Petrican |
| collection | DOAJ |
| description | Abstract Recent evidence challenged the traditional, categorical approach to sex differences, indicating that each human brain comprises a mosaic of features, some of which are more common among males, others, among females, whereas the remaining are equally common between sexes. Thus, a focus on regional sexual differentiation of brain function, instead of holistic sex-based categorization, could be more useful for understanding psychiatric conditions, such as mood and behavioural disorders, to which males and females are differentially vulnerable. To probe this untested hypothesis, we estimate sexual differentiation within each brain in a longitudinal (N = 199) and cross-sectional (N = 277) sample of male and female adolescents. Greater feminization of association networks, involved in higher-order cognition, compared to sensory networks, at ages 9-10 correlates with earlier puberty and greater immune/metabolic dysregulation at ages 11-12, particularly among girls. Greater masculinization of association networks relates to later puberty and reduced immune/metabolic dysregulation, especially among boys. The brain and physiological profiles sequentially mediate the relationship between genetic risk and rising mood/behavioural symptoms. These links are replicated in the cross-sectional sample and shown to hold across sexes. Our study emphasizes the importance of integrating assessments of regional sexual differentiation and physiology in personalizing psychiatric intervention in adolescence. |
| format | Article |
| id | doaj-art-aaf75b20fe1f4eb587a5d564dc9ccbef |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-aaf75b20fe1f4eb587a5d564dc9ccbef2025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116112110.1038/s41467-025-60686-5Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological agingRaluca Petrican0Alex Fornito1Christopher Murgatroyd2Emma Boyland3Charlotte A. Hardman4Institute of Population Health, Department of Psychology, University of LiverpoolThe Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash UniversityDepartment of Life Sciences, Manchester Metropolitan UniversityInstitute of Population Health, Department of Psychology, University of LiverpoolInstitute of Population Health, Department of Psychology, University of LiverpoolAbstract Recent evidence challenged the traditional, categorical approach to sex differences, indicating that each human brain comprises a mosaic of features, some of which are more common among males, others, among females, whereas the remaining are equally common between sexes. Thus, a focus on regional sexual differentiation of brain function, instead of holistic sex-based categorization, could be more useful for understanding psychiatric conditions, such as mood and behavioural disorders, to which males and females are differentially vulnerable. To probe this untested hypothesis, we estimate sexual differentiation within each brain in a longitudinal (N = 199) and cross-sectional (N = 277) sample of male and female adolescents. Greater feminization of association networks, involved in higher-order cognition, compared to sensory networks, at ages 9-10 correlates with earlier puberty and greater immune/metabolic dysregulation at ages 11-12, particularly among girls. Greater masculinization of association networks relates to later puberty and reduced immune/metabolic dysregulation, especially among boys. The brain and physiological profiles sequentially mediate the relationship between genetic risk and rising mood/behavioural symptoms. These links are replicated in the cross-sectional sample and shown to hold across sexes. Our study emphasizes the importance of integrating assessments of regional sexual differentiation and physiology in personalizing psychiatric intervention in adolescence.https://doi.org/10.1038/s41467-025-60686-5 |
| spellingShingle | Raluca Petrican Alex Fornito Christopher Murgatroyd Emma Boyland Charlotte A. Hardman Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging Nature Communications |
| title | Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| title_full | Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| title_fullStr | Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| title_full_unstemmed | Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| title_short | Genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| title_sort | genetic risk predicts adolescent mood pathology via sexual differentiation of brain function and physiological aging |
| url | https://doi.org/10.1038/s41467-025-60686-5 |
| work_keys_str_mv | AT ralucapetrican geneticriskpredictsadolescentmoodpathologyviasexualdifferentiationofbrainfunctionandphysiologicalaging AT alexfornito geneticriskpredictsadolescentmoodpathologyviasexualdifferentiationofbrainfunctionandphysiologicalaging AT christophermurgatroyd geneticriskpredictsadolescentmoodpathologyviasexualdifferentiationofbrainfunctionandphysiologicalaging AT emmaboyland geneticriskpredictsadolescentmoodpathologyviasexualdifferentiationofbrainfunctionandphysiologicalaging AT charlotteahardman geneticriskpredictsadolescentmoodpathologyviasexualdifferentiationofbrainfunctionandphysiologicalaging |