Aug 2026· Proceedings of the National Academy of Sciences of the United States of America· Vol 123· 0 citations· 57 references
Medicine
TL;DR
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.
Abstract
Significance Early life adversity is a risk factor for psychiatric disorders, yet the biological mechanisms driving these conditions-and their distinct prevalence in men and women-remain poorly understood. By integrating robust behavioral phenotyping, whole-brain mapping combining MRI and cFos, and transcriptomics in a translational mouse model, we demonstrate that developmental stress induces divergent neurobiological signatures in males and females. These findings reveal that sex plays a fundamental role in how early life stress interacts with the developing brain. This multilevel resource provides a framework for human comparison, especially through the use of cross-species modalities as MRI or deep behavioral phenotyping, and for developing hypotheses for future investigations into sex-specific biomarkers and mechanisms, promoting improved, targeted therapeutic interventions for stress-related mental illness.
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Recent advances in cell-type-specific epigenetic and transcriptional mechanisms underlying long-term stress susceptibility are discussed, which suggest peripheral epigenetic signatures associated with early life stress may provide accessible biomarkers of exposure and disease risk.
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Predictability, the degree to which environmental inputs are structured, patterned, and reliably signaled over time, has emerged as a central dimension of early experience with unique implications for brain development, stress physiology, and mental health. This review synthesizes convergent evidence from human and ani...
Mason Hardy, T. Baram· Annual Review of Development...· 0 citations
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Lea C. Michel, D. Rakesh, T. Banaschewski et al.· bioRxiv· 0 citations
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