Multilevel sex-influenced neurobiological signatures of early life adversity
Abstract
Stress exposure early in life is an established risk factor for adult psychiatric illness, yet these disorders—including anxiety disorders and depression—show significant sex differences in prevalence, symptomatology, and treatment response. The biology underlying these differences remains largely unexplored and may contribute to the clinical heterogeneity in anxiety and depression. Here, we characterize the lasting impact of developmental stress on adulthood neurobiology and behavior in mice by combining analyses of multiple levels of brain function, including whole-brain c-Fos mapping, manganese-enhanced MRI, and transcriptomics with advanced behavioral phenotyping. Across levels of investigation, we find distinct and often opposite effects of developmental stress based on sex. These results together showcase the strong influence of sex on how early life adversity affects the onset of stress-related disorders. This work emphasizes the necessity of considering sex when investigating developmental and neurobiological underpinnings of stress-related disorders and displays a vast range of lasting effects of developmental stress on the brain, which provides a valuable resource for future studies aiming to improve psychiatric treatments.
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BibTeX
@article{narayan2026multilevel,
title = {{Multilevel sex-influenced neurobiological signatures of early life adversity}},
author = {Sowmya Narayan and Christina Beer and Veronika Kovarova and Carlo Castoldi and Tibor Stark and Beatrice Dal Bianco and Simone Röh and Susann Sauer and Joeri Bordes and Stoyo Karamihalev and Shiladitya Mitra and Patricia Maidana Miguel and Bonnie Alberry and Darina Czamara and Patricia P Silveira and Michael Czisch and Bianca A Silva and Elisabeth B Binder and Patricia Maidana},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = aug,
doi = {10.1073/pnas.2603982123},
url = {https://hal.science/hal-05779285v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multilevel sex-influenced neurobiological signatures of early life adversity
AU - Sowmya Narayan
AU - Christina Beer
AU - Veronika Kovarova
AU - Carlo Castoldi
AU - Tibor Stark
AU - Beatrice Dal Bianco
AU - Simone Röh
AU - Susann Sauer
AU - Joeri Bordes
AU - Stoyo Karamihalev
AU - Shiladitya Mitra
AU - Patricia Maidana Miguel
AU - Bonnie Alberry
AU - Darina Czamara
AU - Patricia P Silveira
AU - Michael Czisch
AU - Bianca A Silva
AU - Elisabeth B Binder
AU - Patricia Maidana
PY - 2026
DA - 2026/08/27
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2603982123
UR - https://hal.science/hal-05779285v1
AB - Stress exposure early in life is an established risk factor for adult psychiatric illness, yet these disorders—including anxiety disorders and depression—show significant sex differences in prevalence, symptomatology, and treatment response. The biology underlying these differences remains largely unexplored and may contribute to the clinical heterogeneity in anxiety and depression. Here, we characterize the lasting impact of developmental stress on adulthood neurobiology and behavior in mice by combining analyses of multiple levels of brain function, including whole-brain c-Fos mapping, manganese-enhanced MRI, and transcriptomics with advanced behavioral phenotyping. Across levels of investigation, we find distinct and often opposite effects of developmental stress based on sex. These results together showcase the strong influence of sex on how early life adversity affects the onset of stress-related disorders. This work emphasizes the necessity of considering sex when investigating developmental and neurobiological underpinnings of stress-related disorders and displays a vast range of lasting effects of developmental stress on the brain, which provides a valuable resource for future studies aiming to improve psychiatric treatments.
SN - 0027-8424
SN - 1091-6490
ER -