- Developmental stress induces lasting, multilevel changes in adult brain function and behaviour, revealed by c-Fos mapping, manganese-enhanced MRI, and transcriptomics.
- Sex strongly modulates outcomes: developmental stress produces distinct, often opposing neurobiological and behavioural effects in males and females.
- Findings highlight necessity of incorporating sex in research to explain clinical heterogeneity in anxiety and depression and to guide improved, personalised treatments.
Proc Natl Acad Sci U S A. 2026 Sep;123(35):e2603982123. doi: 10.1073/pnas.2603982123. Epub 2026 Aug 27.
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.
PMID:42658766 | DOI:10.1073/pnas.2603982123
Share Evidence Blueprint
Save to Google Notes
Search Google Scholar
Save as PDF
⭐ My Revision List
