Multilevel sex-influenced neurobiological signatures of early life adversity

• 成果类型: Article
• 署名作者: Narayan, Sowmya; Beer, Christina; Kovarova, Veronika; Castoldi, Carlo; Stark, Tibor; Bianco, Beatrice Dal; Roh, Simone; Sauer, Susann; Bordes, Joeri; Karamihalev, Stoyo; Mitra, Shiladitya; Miguel, Patricia Maidana; Alberry, Bonnie; Czamara, Darina; Silveira, Patricia P.; Czisch, Michael; Silva, Bianca; Binder, Elisabeth B.; Schmidt, Mathias V.
• 署名单位: Max Planck Society; Max Planck Society; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; CNRS - National Institute for Biology (INSB); Max Planck Society; Max Planck Society
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2603982123
• 发表日期: 2026-09-01
• 页码: e2603982123
• 关键词: early life stress; sex differences; resilience; transcriptomics; behavioral phenotyping; CHILDHOOD ADVERSITIES; ADULT PSYCHOPATHOLOGY; REWARD CIRCUITRY; DEPRESSION; stress; brain; mechanisms; disorders; ANXIETY; nucleus

摘要

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.