Neuro-endocrine responses to stress

1. Neuro-endocrine responses to stress Overview of systems involved

2. Overview of structures involved Nervous system Central nervous system (CNS) Peripheral nervoussystem (PNS) Brain Spinal cord Autonomic nervoussystem (ANS)(involuntary muscles) Somatic nervoussystem(voluntary muscles) Parasympathetic(conserves energy;undertakes ‘housekeeping’) Sympathetic(mobilizes & expends energy;prepares for fight or flight) (See nextslide)

3. Divisions of the autonomic nervous system

4. ANS structure: Adrenal Glands Adrenal glands • On top of the kidneys • Two parts: • Outer covering (cortex) • Inner part (the medulla) • Both parts secrete stress hormones • These perform complementary roles in up- and down-regulation.

5. Adrenals

6. Stress response Operates via two interrelated systems: • SAM (Sympathetic-adrenomedullary) • HPA (hypothalamic-pituitary-adrenocortical). • These balance each other • Both are triggered by the hypothalamus

7. SAM • Adrenal medulla (the inner part) releases hormones epinephrine (adrenaline) and norepinephrine • Stimulates rapid mobilization of metabolic resources: increased heart rate, BP, blood glucose • "Rapid response"

8. HPA • Adrenal cortex produces glucocorticoid (GC) & mineralocorticoid (MC) hormones. • These form a “back-up response"; slower effect • Cortisol is most important human glucocorticoid, involved in regulating metabolism, immune response, and general homeostasis. • Protein & fat are metabolized into glucose; this suppresses immune response; raises BP • Targets the brain • Receptors = GRs and MRs • Changes gene expression

9. GR and MR Receptors • The glucocorticoids from HPA bind to specific mineralocorticoid (MR) or glucocorticoid (GR) receptors on the target organs. • GRs mediate most of the stress response; MRs mediate basal responses such as regulating neurotransmitters, BP, circadian rhythm • GR effects therefore often oppose MR effects. This leads some to argue that vulnerability to stress is affected by the ratio of GR to MR receptors and their activation.

10. Hypothalamus • Secretes CRH, which • causes the pituitary to secrete ACTH, • which stimulates the adrenal medulla to release epinephrine, • and the adrenal cortex to release GC.

11. Function • Normal homeostasis (body temperature, etc) is maintained within relatively narrow limits. • By contrast, the stress response maintains homeostasis over a far wider range of adaptive circumstances, and in responding to challenges. • This is 'allostasis': achieving stability through change. • It occurs via the 'stress response'.

12. Reminder: structure & function of the overall ANS (See next slide)

13. The brain system for appraising threats • Limbic system: • Adds emotional dimensions to stress perception: fear, anger, anxiety • Especially centered in the hypothalamus

14. The Hypothalamus • Several parts of the limbic system in the centre of the brain (hypothalamus, amygdala, etc) are involved in the SAM and HPA responses. • The limbic system is closely connected to organs of perception (olfaction; memory) and plays a role in appraisal of the environment and hence in interpreting the stressfulness of a threat. It seems to be involved in processing the meaning of perceptions. • The limbic system adds emotional dimensions to stress perception: fear, anger, anxiety. • Hence the SAM & HPA stress response is not purely mechanical: it involves our feelings. The orchestration of the SAM and especially HPA responses involves a wide array of perceptual processes.

15. Resting responselevel Allostasis • Maintaining stress and adaptive responses over the long term implies high levels of activation of the homeostatic processes • This causes wear and tear, called 'allostatic load'. • See Selye's General Adaptation Syndrome diagram showing the level of endocrine response mounted:

16. Challenge high arousal engagement,flow apprehension,anxiety control worry relaxation apathy boredom low low high Confidence Notional model of emotions that arise fromthe balance between level of challenge and a person’s coping ability

17. + Peak performance Comfort zone Wearout Performance Rust out Burnout – – Stress (arousal) + Notional model of performance in a difficult task: Yerkes and Dodson curve (1908)

18. Early life experiences and the stress response Evidence from rodent models shows that infant rearing modifies activation of HPA response. • For example, when a mother rat grooms her offspring this stimulates the development of GR receptors, which therefore allows more efficient control of HPA system activation. • This epigenetic effect illustrates how neurobiology can be modified by social experience in critical periods of infant development. • Pups reared by nurturing mothers, yet which are given freedom to explore, become more stress resilient. The ratio of their GR : MR receptors is different from rat pups that experienced maternal separation. • Likewise, maternal neglect in non-human primates can permanently modify their stress response system (See Gunnar & Quevedo) • Humans in insecure relationships show elevated cortisol and heart rate in response to HPA activation: i.e., their stress reaction is prolonged. • Children who receive supportive care appear to have reduced stress responses "that may buffer or protect the developing brain and result in a more stress-resilient child." (Gunnar & Quevedo, p 156) • "Responsive caregiving allows children to elicit help by expressing negative emotions, without triggering the endocrine component of the stress response": plausibly a modified limbic system reaction.

19. Summary • "Stress reactivity is better understood as the result of intertwined biological and psychological processes that ultimately ensure an organism's survival." • "There is a cost to frequent physiological adjustments (allostatic load)" • “One of the most interesting findings emerging from the research ... is that in the absence of supportive care, stressors experienced during sensitive periods of development can ... leave permanent imprints in the neural substrate of emotional and cognitive processes. ... the nervous system of mammals carries their singular epigenetic history and expresses it in unique but predictable ways”. Reference: Gunnar M, Quevedo K. The neurobiology of stress and development. Annu Rev Psychol 2007; 58: 145-173.