Sex-Specific Stress Outcomes Following Acute and Chronic Social Defeat Stress
- 1Division for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United States
Abstract
Stressful experiences are a major risk factor for the development of neuropsychiatric disorders in vulnerable individuals. Identifying features that can distinguish stress-susceptible from resilient individuals remains a central goal in stress neurobiology. Due to the routine exclusion of female subjects from stress research or the use of male-defined criteria in behavioral characterization of subjects post-stress, female stress responses and vulnerability profiles remain poorly understood. This work aimed to gain a better understanding of sex-specific stress responses to social defeat stress. Here, we used a novel paired male-female social defeat paradigm and tracked subjects longitudinally in a ''two-hit'' design to evaluate responses to both acute social defeat stress (ASDS) and chronic social defeat stress (CSDS), and to determine how prior stress exposure influences subsequent vulnerability. We found that both ASDS and CSDS induces changes in social avoidance/approach behavior in males but not females, as measured by a classic social interaction ratio. Prior ASDS exposure enhanced susceptibility to subsequent CSDS most clearly in males, with females displaying specific changes in corner zone occupancy. Furthermore, we observed divergent anxiety profiles between males and females in a post-stress behavioral battery. Finally, females exhibited specific stress-related locomotor responses following ASDS. Together, these findings suggest that females may adopt distinct behavioral strategies following social defeat stress.
Related
- Sex-dependent and region-specific morphological adaptations in astrocytes following early-life stress
- Chronic unpredictable stress induces negative cognitive bias in rats with sex-specific changes in neurogenesis and functional connectivity
- Longitudinal Functional and Safety Outcomes in Chronic Post-Ischemic Stroke Following a Multimodal Regenerative Medicine Protocol: A Case Report
- Preconception stress in mice alters maternal behavioral, neural, and endocrine outcomes, and produces sex-specific disruptions in offspring
- Chronic Social Isolation Reshapes the Metabolome in Drosophila
BibTeX
@misc{stewart2026sexspecific,
title = {{Sex-Specific Stress Outcomes Following Acute and Chronic Social Defeat Stress}},
author = {E. Stewart and A. Manganaro and K. Anderson and A. Lipshutz and S. Jagnarine and D. Fortuna and L. Bryan and L. Aziz and P. Rogu and V. Saltz and D. Dumitriu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754264},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754264v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Sex-Specific Stress Outcomes Following Acute and Chronic Social Defeat Stress
AU - E. Stewart
AU - A. Manganaro
AU - K. Anderson
AU - A. Lipshutz
AU - S. Jagnarine
AU - D. Fortuna
AU - L. Bryan
AU - L. Aziz
AU - P. Rogu
AU - V. Saltz
AU - D. Dumitriu
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754264
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754264v1
AB - Stressful experiences are a major risk factor for the development of neuropsychiatric disorders in vulnerable individuals. Identifying features that can distinguish stress-susceptible from resilient individuals remains a central goal in stress neurobiology. Due to the routine exclusion of female subjects from stress research or the use of male-defined criteria in behavioral characterization of subjects post-stress, female stress responses and vulnerability profiles remain poorly understood. This work aimed to gain a better understanding of sex-specific stress responses to social defeat stress. Here, we used a novel paired male-female social defeat paradigm and tracked subjects longitudinally in a ''two-hit'' design to evaluate responses to both acute social defeat stress (ASDS) and chronic social defeat stress (CSDS), and to determine how prior stress exposure influences subsequent vulnerability. We found that both ASDS and CSDS induces changes in social avoidance/approach behavior in males but not females, as measured by a classic social interaction ratio. Prior ASDS exposure enhanced susceptibility to subsequent CSDS most clearly in males, with females displaying specific changes in corner zone occupancy. Furthermore, we observed divergent anxiety profiles between males and females in a post-stress behavioral battery. Finally, females exhibited specific stress-related locomotor responses following ASDS. Together, these findings suggest that females may adopt distinct behavioral strategies following social defeat stress.
ER -