Cortisol-Mediated Stress Response PDF

Stress Session objectives: Outline normal variation in the cortisol response. Describe influences of environment on the cortisol response, including cortisol dysregulation. First, a gentle introduction to stress: excerpts from Stress, Portrait of a Killer (2008) National Geographic....

Stress Session objectives: Outline normal variation in the cortisol response. Describe influences of environment on the cortisol response, including cortisol dysregulation. First, a gentle introduction to stress: excerpts from Stress, Portrait of a Killer (2008) National Geographic.  COPYRIGHT WARNING This material has been reproduced and communicated to you by or on behalf of Bond University in accordance with section 113P of the Copyright Act 1968 (Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice Stress is biological MENTAL = BIOLOGICAL o Contrary to current best practice, many practitioners and academics still think of the mind as separate from the body, and do not consider mental disorders as biological disorders affecting the brain. The hypothalamus is involved in a number of key stress responses, including the HPA axis which is the focus of this session. From: Edes AN, and Crews DE. Allostatic load and biological anthropology. Am. J. Phys. Anthropol. 2017;162:44–70. doi:10.1002/ajpa.23146. Cortisol can be measured using saliva or blood or hair. Salivary assays are the most commonly used method Hair gives the best measure of chronic stress  Normal diurnal variation in cortisol Cortisol is elevated 30 minutes post-awakening. Across the day there is a marked decline. One theory for the morning cortisol peak is that it stimulates the release of glucose to prepare for the shift from resting at night to daytime physical activity. An alternative theory is that cortisol also plays a role in regulating day and night time immunity (the circadian pattern of Th1 to Th2 shift). Source: Clow, A. (2004) Journal of Holistic Healthcare vol1. It’s not as simple as high versus low stress: Chronic stress can result in a blunted cortisol response to stressful situations, and/or a blunted awakening response. These results show evidence that children who have been bullied have a blunted response to a stressor (and lower stress levels in the lab before being given a stress-inducing test). (Source: Biol Psychiatry. 2011 December 1; 70(11):doi:10.1016/j.biopsych.20 11.06.017) The blunted response may be an adaptive way of coping with chronically stressful environments. Cortisol diurnal slopes for a sample of neglected children who have received a programme of nurturing intervention (ABC intervention) vs. controls. Those who received the intervention have a normal steep diurnal profile. Source: Intervention Effects on Diurnal Cortisol Rhythms of Child Protective Services–Referred Infants in Early Childhood Preschool Follow-up Results of a Randomized Clinical Trial. Bernard K, Hostinar C, Dozier M. JAMA Pediatrics 12/2014. What makes cortisol go up? an example: stress in children’s environment. Waynforth (2007) Developmental Psychobiology Vol 49, 640-8 The Trier stress test produces an increase in cortisol (here measured from saliva): physiology reflects what we feel. A five minute public speaking task (a mock job interview), followed by five minutes of mental arithmetic, out loud in front of a two-person panel. The calming effect of physical contact (a neck massage given by husband or long-term partner) resulted a reduced cortisol response. Ditzen et al. (2007) Psychoneuroendocrinology Vol. 32 565- Cortisol response to conflict in a single individual. Note that SIgA levels dropped post-conflict. The likely explanation is: chronic stressTh2 dominance/reduced T-cell mediated immunity illness Flinn (2006) Developmental Review Vol. 26: 138-174 Cortisol increases when children face social challenges, e.g., the transition from home to daycare: These data are from a study of German children going to daycare for the first time. Adaptation phase = when they attend with parents. Secure/insecure are attachment styles (don’t worry too much about these for this lecture). Ahnert et al. (2004) Child Development 75:639-650  Children at daycare also tend to have abnormal diurnal cortisol profiles: Dettling et al. (2000) Psychoneuroendocrinology 25: 819-836 found an increase from mid morning to mid afternoon in children in daycare in a US sample. Children at home showed the expected drop. Similar results have been found in other samples and other countries, e.g., Legendre (2003) Environment & Behavior 35: 523- Remember the normal diurnal pattern What should we measure? Peak cortisol in response to a stressor, or area under the curve, or the slope of the diurnal profile? New research uses hair to get a longer window on exposure to cortisol. Work-related stress and cortisol: In experimental studies, increased stress at work is associated with flattened diurnal cortisol profiles due to high PM levels (e.g., see work by Anna Dahlgren), and also very high post-awakening levels (see below) Lundberg & Hellstrom (2002) Work & Stress Taking overtime some days/weeks but not others may not allow the body to adapt by blunting the cort response. Cortisol and dysregulation of reproductive hormones Hormones necessary for successful ovulation, implantation and maintenance of early pregnancy are disrupted by stress. Results from a study of natural variation in stress and reproductive hormones. Pregnanediol- glucuronide (PdG) levels (a major metabolite of progesterone). Nepomnaschy et al. 2004 American Journal of Human Biology 16: 523- Cortisol and pregnancy loss in the first 3 weeks of pregnancy Note that here the researchers have used peaks in cortisol as their measure – similar to the assessment of growth hormone levels in children Nepomnaschy et al. 2006, www.pnas.orgcgidoi10.1073pnas.0511183103 Relationships between cortisol and BP (and other CV risk factors): This relationship is because cortisol stimulates gluconeogenesis  Some of the pathways between stress and health Social and physical environment: e.g., lack of control of life events, lack of predictability, SES, rank. Lifestyle response: Diet Exercise smoking Health outcomes HPA axis and other physiological mediators and mechanisms There’s a tendency to focus on addressing the downstream lifestyle variables, not upstream causes. In situations where the lifestyle response is an individual’s attempt at self-medication, focus on this variable could damage rather than improve patient health. Pharmacological stress management: Higher cortisol levels or cortisol dysregulation have been found in almost all types of anxiety disorder. o Anti-anxiety medications: benzodiazepines (e.g., Xanax, Ativan) inhibit the HPA axis (CRH inhibition -- see HPA axis diagram) * The difference between anxiety and stress is unclear: it could simply be linguistic rather than physiological Medications which unintentionally influence HPA axis activity: o Thousands of over-the-counter and prescription medications may directly or indirectly influence the HPA axis. Few have been systematically researched with regard to HPA axis activation. Some common medications which influence HPA activity: Steroids; corticosteroids Statins (may interfere with biosynthesis of cortisol) Antidepressants (change perception of environment) The pharmacodynamics of medications with regard to the influence on the HPA axis is complex. See: Granger, D. A., Hibel, L. C., Fortunato, C. K., & Kapelewski, C. H. (2009). Medication effects on salivary cortisol: Tactics and strategy to minimize impact in behavioral and developmental science. Psychoneuroendocrinology, 34(10), 1437–1448. doi:10.1016/j.psyneuen.2009.06.017 Should stress management be considered a public health priority, as obesity currently is? Or is it just an unavoidable part of modern life? Should people who feel stressed seek medical help?