Individual Differences in Reactivity to Social Stress Predict Susceptibility and Resilience to a Depressive Phenotype: Role of Corticotropin-Releasing Factor

• Published in: Endocrinology (Philadelphia) 2010-04, Vol.151 (4), p.1795-1805
• Main Authors: Wood, Susan K, Walker, Hayley E, Valentino, Rita J, Bhatnagar, Seema
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - blood; Affective disorders; Analysis of Variance; Animals; Arginine Vasopressin - genetics; Arginine Vasopressin - metabolism; Behavior, Animal - physiology; Biological and medical sciences; Body Weight - physiology; Cluster Analysis; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Depression - metabolism; Dominance-Subordination; Fundamental and applied biological sciences. Psychology; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - metabolism; Hypothalamus; In Situ Hybridization; Individuality; Latency; Male; Paraventricular Hypothalamic Nucleus - metabolism; Phenotypes; Pituitary; Pituitary Gland - metabolism; Pituitary-Adrenal System - metabolism; Population studies; Proto-Oncogene Proteins c-fos - metabolism; Psychopathology; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Resilience; Restraint, Physical - physiology; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Social interactions; Stress, Physiological - physiology; Stress, Psychological - metabolism; Time Factors; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2009-1026

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). 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. Individual differences in the coping strategy to repeated social defeat stress determine the profile of neuroendocrine and behavioral consequences.