1. Are Subordinates Always Stressed? A comparative analysis of rank differences in cortisol levels among primates Abbot et al., 2003 Kyle Nash May 12 th, 2009

2. Agenda 1.Stress and HPA axis review from Kloet, Joels & Holsboer, 2005 2.Abbott et al., 2003 Intro Method Results Conclusion 3.Discussion

3. What is Stress? Process: Stimulus  Response Stressor: – Stimulus that threatens animal’s physiological homeostasis (Kloets et al., 2005) – Physical vs. Psychological (Real vs. Predicted) Stress Response: – Active maintenance of physiological homeostasis – Sympathetic (Fight or Flight) & Hypothalamic- Pituitary-Adrenocortical (HPA) systems

4. Fight or Flight Response Stressor Sympathetic Nervous System/ Catecholamines ‘Fight or Flight’

5. http://www.biology.ucr.edu/people/faculty/ Garland/HPA_axis.jpg PVN Stressor Brain Stem (e.g. LC) ‘Limbic’ System

6. Corticosteroid Receptors Two types – Both respond to corticosteroids Minerocorticoid Receptor (MR): – Appraisal, initial stress response – Important in gene transcription activity – More sensitive corticosteroids (10x) Glucocorticoids Receptor (GR): – Terminates stress response for recovery (i.e. decrease CRH production) – Increased sensitivity to corticosteroids during stress – High density in PVN, aminergic & limbic pathways – Promotes stressor-related memory storage

9. MR x GR

10. Chronically Stressed Animal Prolonged and/or repeated exposure to stressor (i.e. prolonged increase in corticosteroids) can have maladaptive consequences – Hypertension, type-II diabetes, ulcers, etc. Chronic stress  Neuroendocrine change – hippocampal (CA3) atrophy, reduced proliferation (MR) – GRs and MRs downregulated – Diminished Denate Granule cell turnover rate – Reduced 5-HT receptor function – Reduced LTP/Facilitated LTD Produce a Stress-typology ‘Coping’ can disrupt maladaptive changes – offspring of ‘caring’ rat mothers, higher hippocampal GR gene expression and decreased anxiety-related behaviour Stress experience (stressors and coping) and genetic background cause long-term changes

11. Summary Stressors activate sympathetic and HPA systems Glucocorticoids regulate stress response through MR and GR interaction Prolonged stress  physiological problems and neuroendocrine funtioning Individual differences in genetics and experience important in stress response

12. Rank and Stress Stress levels may be higher in subordinates – Low access to resources, physical and social stressors, low ‘coping’ opportunities Certain subordinate primates – elevated glucocorticoids and catecholimines – higher blood pressure – Stress-related pathologies Not consistent for all primates

13. Abbot et al., 2005 Conflicting results on rank and stress Purpose – Survey researchers (quasi-meta-analysis) – Rank, Sex, Species  Stress – Looked at both physical/psychological factors

14. Method Questionnaire: 6 Domains, 17 questions I.What is it like to be a dominant individual in this society? II.What is it like to be a subordinate individual in this society? III.What are the typical routes by which ranks change? IV.What is the nature of revolutionary change in hierarchies? V.The role of kinship. VI.Non-agonistic factors relevant to the stress-response. 0 (Not at all) – 3 (Highly applicable)

15. Method: Sample 4 Old world (e.g. Rhesus)3 New World (e.g. Marmoset) Subordinates: indicated by expert of each sample Analyses: by species and sometimes sex 10 groups in total, large variance in group dynamics

16. Method DV: Relative Cortisol – Basal levels – Circulatory or urinary – Relative to dominant monkeys, controls for species differences i.e. 100% = equal cortisol levels

17. Analyses Two types of analysis 1.Multiple Regression with independent contrasts – Flips variables from dependent (i.e. similar species) to independent – After data collection, excluded questions based on missing values (5) High r’s with other questions or Low r’s with cortisol (4) 8 total questions 2.Data Tree - decision algorithm from response variability predicted – Different excluded values – Used 4 questions from 8 (above) in regression

18. Tree-Based Method – Single Branch (1) If Question 1A is >X, then this predicts relative cortisol levels = Y1% (branch 1). (2) If Question 1A is <X, then this predicts relative cortisol levels = Y2% (branch 2). Overall Tree = Minimum Branches for Maximum Predictive Power Q 1A Y2Y1

20. Final Q’s Multiple Regression 1A: How much of a role does aggression play in the attainment of dominance? 2A: How frequently are subordinates subject to stressors? 2B: How available is social support for subordinates? 2F: Overall, how much should subordinate status be thought of as an undesirable state actively imposed by more dominant animals? 3A: Do animals rise in the hierarchy through strenuous challenge of the status quo? 4A: How often do such “revolutions” occur? 5A: How important is kinship in understanding interactions among these animals? 6A: Are there circumstances in which one has to invoke a physiological adaptation to subordinate status, rather than a response to agonistic behavior, to make sense of the profile of a particular stress hormone? Two significant predictors, 2A and 2B

21. Results: 2A - Social Stressors

22. 2B - Social Support

23. Final Q’s for Tree-Based Analysis 2A: How frequently are subordinates subject to stressors? 2B: How available is social support for subordinates? 3A: Do animals rise in the hierarchy through strenuous challenge of the status quo? 5A: How important is kinship in understanding interactions among these animals?

25. Discussion Subordinates do not always express higher levels of cortisol Important factors: – Stressors frequency – Social support – Relevance of kinship Possible neuroendocrine mechanisms – Increased stressors  decreased GRs  diminished negative feedback in stress response  cortisol – Outlets (social support) diminishes cortisol levels – Kinship variable could predict both stressor frequency and social support quality

26. Problems Relative measure of cortisol consider the cortisol levels for dominant monkeys Questionnaire Exclusions were largely subjective Authors were respondents

27. Discussion Other important factors? – Other outlets or displacement behaviours? – Simple stressor disruption? – i.e., allowing rats access to a running wheel decreases the magnitude of the glucocorticoid response to shock Coping mechanisms: MRxGR? – Stops GR downregulation? Stressor controllability inhibits behavioural response Coping?Social Support?

28. References Unless otherwise noted, figures and tables from Abbot et al., 2003. Sapolsky, R.M., Krey, L., McEwen, B., (1984). Stress down-regulates corticosterone receptors in a site-specific manner in the brain. Endocrinology, 114, 287–292. Kloet, Joels, & Holsboer, (2005). Stress and the brain: From adaptation to disease. Nature Reviews: Neuroscience, 6, 463-475. http://www.biology.ucr.edu/people/faculty/Garla nd/HPA_axis.jpg