Individual Differences in Reactivity to Social Stress Predict Susceptibility and Resilience to a Depressive Phenotype: Role of Corticotropin-Releasing Factor
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Previous social stress exposure is a common risk factor for affective disorders. However, factors that determine vulnerability or resiliency to social stress-induced psychopathologies remain unclear. Using a rodent model of social stress, the present study was designed to identify putative neurobiological substrates that contribute to social stress-induced psychopathology and factors that influence or predict vulnerability. The resident-intruder model of defeat was used as a social stressor in adult male Sprague Dawley rats. The average latency to assume a subordinate posture (signaling defeat) over seven daily defeat exposures was calculated and examined with respect to endpoints of hypothalamic-pituitary-adrenal activity, components of the corticotropin-releasing factor (CRF) system, and behaviors that are relevant to human depression. In the present studies, a bimodal distribution emerged in an otherwise homogeneous population of Sprague Dawley rats such that 42% of rats exhibited short defeat latencies (<300 sec), whereas 58% of rats resisted defeat and exhibited longer latencies (>300 sec). These two phenotypes were associated with distinct endocrine and behavioral profiles as well as differences in components of the CRF system. Notably, the short-latency subpopulation exhibited hypothalamic-pituitary-adrenal dysregulation and behavior similar to that observed in melancholic depression. Examination of components of the CRF system suggested that proactive behavior in resisting defeat exhibited by long-latency rats was associated with decreased efficacy of CRF. Together, these data suggest that inherent differences in stress reactivity, perhaps as a result of differences in CRF regulation, may predict long-term consequences of social stress and vulnerability to depressive-like symptoms.
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During social defeat stress, animals that engage in less submissive posturing during attack show less social avoidance, suggesting this behavioral coping strategy may lessen stress effects.
“During social defeat stress, animals that engage in less submissive posturing during the attack show less social avoidance, suggesting that this behavioral coping strategy may affect the aggressive interaction and thereby lessen the effects of the stress55.”
From Neurobiology of resilience (2012) · cites this paper as [55]
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- Authors
- Wood, S. K., Walker, H. E., Valentino, R. J., & Bhatnagar, S.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Bhatnagar, Seema
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-04
- Volume
- 151
- Issue
- 4
- Pages
- 1795-1805
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2850230
- OpenAlex
- W2023866397
- Cited by
- 251
- References
- 56
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 19 · 2023: 5 · 2022: 18 · 2021: 14 · 2020: 16 · 2019: 20 · 2018: 27 · 2017: 9 · 2016: 18 · 2015: 20 · 2014: 28 · 2013: 20 · 2012: 7
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Children's Hospital of Philadelphia
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- social stress, stress reactivity, corticotropin-releasing factor, depression, resilience, hypothalamic-pituitary-adrenal axis, endogenous depression, individual differences, Sprague-Dawley rats
- MeSH terms
- Adrenocorticotropic Hormone, Analysis of Variance, Animals, Arginine Vasopressin, Behavior, Animal, Body Weight, Corticotropin-Releasing Hormone, Depression, Dominance-Subordination, Hypothalamo-Hypophyseal System, Individuality, Male, Paraventricular Hypothalamic Nucleus, Pituitary Gland, Pituitary-Adrenal System, Restraint, Physical, RNA, Messenger, Stress, Physiological, Stress, Psychological, Time Factors, Cluster Analysis, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, In Situ Hybridization, Rats, Long-Evans, Rats
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