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Reference topic 28: Stress and the Hijacked Alarm

Chronic stress: cortisol, and why the alarm stays on

ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.67 sources7 graded recommendationsTopic hub: Stress and the mind

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In 1978 Robert Sapolsky began watching a troop of olive baboons, Forest Troop, in Kenya's Masai Mara Reserve, and kept at it for decades.1 The troop slept near a tourist lodge. In the early 1980s the lodge greatly expanded its garbage pit, full of food no savanna could match: leftover drumsticks, half-eaten hamburgers, remnants of chocolate cake.2 A neighboring troop fed almost entirely from the pit, and soon some Forest Troop males were walking over at dawn for a share. The seven who went were no different in age or rank from the eight who stayed, only more aggressive.12

In 1983 the meat in the pit carried bovine tuberculosis. Within three years most of the dump-feeding troop was dead, and so was every Forest Troop male who had fed there: nearly half the troop's adult males. No other Forest Troop animal died.1 What remained had more than twice as many females per male, and only the mildest males. When researchers returned in 1993, none of those males was left, yet their manners had survived. In other troops, most dominance interactions pitted males more than two ranks apart, the strong leaning on the weak. In Forest Troop significantly fewer did, and males even groomed each other.12

Mismatch card

The system

The stress response: the fast sympathetic arm and the slower hypothalamic-pituitary-adrenal axis.

What it expects

Threats that arrive, get answered with the body, and end, among allies.

What it gets

Uncontrollable social evaluation without end, in steep hierarchies, carried into the night on short sleep and thin company.

What happens in the gap

Rhythms flatten, tissues stop hearing cortisol's stand-down order, inflammation runs on, wounds close slowly and primed arteries fail sooner.

The handrail

Move hard sometimes, keep people close, sleep, take back control of the schedule (●●○)

Strength of evidence

●●○ Mechanisms and gradients are well measured, but the effect of adult stress on disease is moderate and easily overstated.

What this topic covers

  • ·The Alarm and Its Inventors
  • ·What the Alarm Answers To
  • ·The Rank Gradient, Measured in Civil Servants
  • ·Catching Colds on Purpose
  • ·From the Amygdala to the Artery
  • ·The Price of Staying Ready

The practical version is in the book: Chapter 13, Stress and the Mind.

The handrail

Topics 40 to 42 hold the full programs; these are specific to the alarm.

Safety: chest pain, breathlessness or collapse during intense emotion is an emergency, not a stress-management problem. Persistent anxiety, low mood or burnout deserve professional attention, and effective treatments exist.

Each recommendation carries the strength of the evidence behind it. How the grades work.

  1. Move most days, and let some of it be hard

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.

    Evidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. for distress·Evidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials. for cortisol

    Across 97 reviews covering 1,039 trials and 128,119 people, physical activity produced medium reductions in depression, anxiety and distress, larger at higher intensity.64 In 10 trials it lowered cortisol modestly.65 Easy exercise does not raise cortisol; 30 minutes at 80% of maximum raised it 83% in 12 men, and that spike is the system working.66 Doses are in Topic 40. With heart disease or chest pain on exertion, get medical advice before training hard.

  2. Borrow calm from people before you need it

    ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.

    Bring a trusted person to the stressful thing, not just to the debrief.343536

  3. Protect the night

    EmergingEvidence grade: Emerging. Early, small, animal-only, or actively contested.

    One short night raised the next evening's cortisol by up to 45%.53 Topics 23 and 41 own sleep.

  4. Buy back control and predictability

    ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.

    Low control explained much of the Whitehall gradient,21 and long weeks track stroke risk.44 Fixed hours and a say in how work gets done are stress interventions even when the workload is not.

  5. Spend time outdoors

    EmergingEvidence grade: Emerging. Early, small, animal-only, or actively contested.

    A green space settles the alarm on its own timetable, not instantly (Topic 27 owns the evidence and the dose).

  6. For persistent anxiety or stress, consider an eight-week mindfulness course

    StrongEvidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism.

    Evidence grade: Strong. Multiple randomized controlled trials, or consistent large cohort studies with a well-understood mechanism. small-to-moderate benefit·Evidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials. head-to-head trial

    Meditation programs beat inactive controls modestly and no active treatment reliably.67 In one trial of 276 adults with anxiety disorders, an eight-week course of mindfulness-based stress reduction (MBSR) was non-inferior to (not meaningfully worse than) the anxiety drug escitalopram.68 It is an option alongside care, never a reason to stop or change medication; that decision is for you and your clinician (Topic 31).

  7. Slow the breath once the alarm is up

    ProbableEvidence grade: Probable. Good observational evidence with a plausible mechanism, or small or few trials.

    About five to six breaths a minute for 5 to 10 minutes. Pooled across 12 trials, breathwork produced small reductions in stress and anxiety (Topic 10).69 Avoid breath-holds and hyperventilation in water, while driving, and in pregnancy or epilepsy.

The skeptic's corner

The case against this topic, from the research itself.

"Cortisol is bad" is a cartoon. Part of the hormone's job is keeping the alarm from overshooting.7 In the cold studies, cortisol levels did not predict who got sick; receptor resistance did.30 In Whitehall, morning cortisol and the waking rise predicted nothing about death.51

Stress is a modest cause and a bigger trigger. Job strain accounts for about 3.4% of heart disease in the population, far less than smoking, and adult stress acts mainly on arteries already diseased.4345 Even the title of Sapolsky's Why Zebras Don't Get Ulcers has dated.9 The stomach bacterium Helicobacter pylori causes more than 90% of duodenal ulcers (in the upper small intestine) and up to 80% of stomach ulcers. It lives in about half of humanity, yet gives an ulcer to only 10% to 15% of those it infects.59 Stress survives as a cofactor. In a Danish study of thousands of adults over more than a decade, ulcers were more than twice as common in the most stressed third as in the least.60

Whitehall II workers who said stress had affected their health "a lot or extremely" had about twice the risk of coronary death or heart attack over nearly two decades. Beliefs may matter, or people may have been noticing early illness.61 The fashionable fix is oversold: training people to see stress as helpful reliably changes how it feels and reliably fails to change the physiology.62 Nasal-spray studies of oxytocin, a bonding hormone, are generally too small to trust,63 and the amygdala imaging work rests on people scanned for other reasons.40

Terms this topic defines

Related topics

Sources cited above

  1. 1.Sapolsky, R.M., and Share, L.J. (2004). "A pacific culture among wild baboons: its emergence and transmission." PLoS Biology, 2(4), e106. https://doi.org/10.1371/journal.pbio.0020106 (Masai Mara, Kenya; study from 1978, summers 1978-86 and continuously from 1993; 7 refuse-eating males vs 8 others, no difference in age or rank; physiology in 10 males, 1993-96) (refuse-eating males were raiding the dump by 1982; in comparison troops about 80% of dominance interactions were between males more than two ranks apart)
  2. 2.Sapolsky, R.M. (2007, 1 September). "Peace Among Primates." Greater Good Magazine, Greater Good Science Center, University of California, Berkeley. https://greatergood.berkeley.edu/article/item/peace_among_primates (dump contents; raids at the hour of communal grooming; adult males grooming each other afterward)
  3. 7.Sapolsky, R.M., Romero, L.M., and Munck, A.U. (2000). "How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions." Endocrine Reviews, 21(1), 55-89. https://doi.org/10.1210/edrv.21.1.0389
  4. 30.Cohen, S., Janicki-Deverts, D., Doyle, W.J., Miller, G.E., Frank, E., Rabin, B.S., and Turner, R.B. (2012). "Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk." PNAS, 109(16), 5995-5999. https://doi.org/10.1073/pnas.1118355109 (study 1: 276 adults, odds ratio 1.99 for a recent major stressful event, cortisol odds ratio 1.27 with confidence interval 0.20 to 7.94; study 2: about 80 adults) (in study 2, resistance predicted more inflammatory cytokines after infection)
  5. 51.Kumari, M., Shipley, M., Stafford, M., and Kivimaki, M. (2011). "Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study." Journal of Clinical Endocrinology and Metabolism, 96(5), 1478-1485. https://doi.org/10.1210/jc.2010-2137 (4,047 participants, mean age 61; 139 deaths, 32 cardiovascular, over a mean 6.1 years)
  6. 43.Kivimäki, M., Nyberg, S.T., Batty, G.D., Fransson, E.I., et al. (2012). "Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data." The Lancet, 380(9852), 1491-1497. https://doi.org/10.1016/S0140-6736(12)60994-5 (197,473 workers, 2,358 coronary events; population attributable risk 3.4%) (hazard ratio 1.23)
  7. 45.Kivimäki, M., and Steptoe, A. (2018). "Effects of stress on the development and progression of cardiovascular disease." Nature Reviews Cardiology, 15(4), 215-229. https://doi.org/10.1038/nrcardio.2017.189
  8. 9.Sapolsky, R.M. (2004). Why Zebras Don't Get Ulcers, 3rd ed. New York: Holt Paperbacks. (First published 1994.)
  9. 59.Nobel Assembly at Karolinska Institutet (2005). The Nobel Prize in Physiology or Medicine 2005: Barry J. Marshall and J. Robin Warren. https://www.nobelprize.org/prizes/medicine/2005/press-release/; primary: Marshall, B.J., and Warren, J.R. (1984). "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration." The Lancet, 1(8390), 1311-1315. https://doi.org/10.1016/S0140-6736(84)91816-6
  10. 60.Levenstein, S., Rosenstock, S., Jacobsen, R.K., and Jorgensen, T. (2015). "Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs." Clinical Gastroenterology and Hepatology, 13(3), 498-506.e1. https://doi.org/10.1016/j.cgh.2014.07.052 (3,379 Danish adults, 76 ulcers over 11-12 years; adjusted odds ratio 2.2, 95% confidence interval 1.2-3.9) (ulcer incidence 3.5% in the highest stress third against 1.6% in the lowest)
  11. 61.Nabi, H., Kivimäki, M., Batty, G.D., Shipley, M.J., et al. (2013). "Increased risk of coronary heart disease among individuals reporting adverse impact of stress on their health: the Whitehall II prospective cohort study." European Heart Journal, 34(34), 2697-2705. https://doi.org/10.1093/eurheartj/eht216 (7,268 participants, 352 events over 18 years; hazard ratio 2.12 after sociodemographic adjustment, 1.49 after full adjustment)
  12. 62.Liu, J.J.W., Ein, N., Gervasio, J., and Vickers, K. (2019). "The efficacy of stress reappraisal interventions on stress responsivity: a meta-analysis and systematic review of existing evidence." PLoS ONE, 14(2), e0212854. https://doi.org/10.1371/journal.pone.0212854 (subjective stress reduced, standardized difference 0.429; physiological stress unchanged, -0.084)
  13. 63.Walum, H., Waldman, I.D., and Young, L.J. (2016). "Statistical and methodological considerations for the interpretation of intranasal oxytocin studies." Biological Psychiatry, 79(3), 251-257. https://doi.org/10.1016/j.biopsych.2015.06.016
  14. 40.Tawakol, A., Ishai, A., Takx, R.A., Figueroa, A.L., et al. (2017). "Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study." The Lancet, 389(10071), 834-845. https://doi.org/10.1016/S0140-6736(16)31714-7 (293 people scanned in 2005-2008, median age 55; the perceived-stress correlations come from a separate subsample of 13) (median follow-up 3.7 years; 22 events; hazard ratio 1.59)
  15. 64.Singh, B., Olds, T., Curtis, R., Dumuid, D., et al. (2023). "Effectiveness of physical activity interventions for improving depression, anxiety and distress: an overview of systematic reviews." British Journal of Sports Medicine, 57(18), 1203-1209. https://doi.org/10.1136/bjsports-2022-106195 (median effects -0.43 depression, -0.42 anxiety, -0.60 distress; 77 of 97 reviews rated critically low quality)
  16. 65.De Nys, L., Anderson, K., Ofosu, E.F., Ryde, G.C., Connelly, J., and Whittaker, A.C. (2022). "The effects of physical activity on cortisol and sleep: a systematic review and meta-analysis." Psychoneuroendocrinology, 143, 105843. https://doi.org/10.1016/j.psyneuen.2022.105843 (cortisol standardized difference -0.37; trials mostly in women with breast cancer)
  17. 66.Hill, E.E., Zack, E., Battaglini, C., Viru, M., Viru, A., and Hackney, A.C. (2008). "Exercise and circulating cortisol levels: the intensity threshold effect." Journal of Endocrinological Investigation, 31(7), 587-591. https://doi.org/10.1007/BF03345606 (12 moderately trained men; cortisol +5.7%, +39.9% and +83.1% after 30 minutes at 40%, 60% and 80% of VO2max, measured immediately before and after)
  18. 34.Cohen, S., Janicki-Deverts, D., Turner, R.B., and Doyle, W.J. (2015). "Does hugging provide stress-buffering social support? A study of susceptibility to upper respiratory infection and illness." Psychological Science, 26(2), 135-147. https://doi.org/10.1177/0956797614559284 (hugging explained 32% of the buffering effect of perceived support; hugs were self-reported in nightly interviews, not assigned) (404 adults)
  19. 35.Heinrichs, M., Baumgartner, T., Kirschbaum, C., and Ehlert, U. (2003). "Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress." Biological Psychiatry, 54(12), 1389-1398. https://doi.org/10.1016/S0006-3223(03)00465-7 (37 healthy men, 24 IU intranasal oxytocin or placebo)
  20. 36.Hostinar, C.E., Sullivan, R.M., and Gunnar, M.R. (2014). "Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development." Psychological Bulletin, 140(1), 256-282. https://doi.org/10.1037/a0032671
  21. 53.Leproult, R., Copinschi, G., Buxton, O., and Van Cauter, E. (1997). "Sleep loss results in an elevation of cortisol levels the next evening." Sleep, 20(10), 865-870. https://pubmed.ncbi.nlm.nih.gov/9415946/ (small laboratory study in young men)
  22. 21.Marmot, M.G., Bosma, H., Hemingway, H., Brunner, E., and Stansfeld, S. (1997). "Contribution of job control and other risk factors to social variations in coronary heart disease incidence." The Lancet, 350(9073), 235-239. https://doi.org/10.1016/S0140-6736(97)04244-X (also the source for "about a quarter of this gradient could be attributed to coronary risk factors") (7,372 participants followed for a mean 5.3 years; lowest-grade men had 1.5 times the odds of new coronary disease)
  23. 44.Kivimäki, M., Jokela, M., Nyberg, S.T., Singh-Manoux, A., et al. (2015). "Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603,838 individuals." The Lancet, 386(10005), 1739-1746. https://doi.org/10.1016/S0140-6736(15)60295-1 (stroke relative risk 1.33, 95% confidence interval 1.11-1.61) (55 hours or more a week against 35 to 40, in a dose-response pattern)
  24. 67.Goyal, M., Singh, S., Sibinga, E.M., Gould, N.F., et al. (2014). "Meditation programs for psychological stress and well-being: a systematic review and meta-analysis." JAMA Internal Medicine, 174(3), 357-368. https://doi.org/10.1001/jamainternmed.2013.13018 (47 trials, 3,515 participants)
  25. 68.Hoge, E.A., Bui, E., Mete, M., Dutton, M.A., Baker, A.W., and Simon, N.M. (2023). "Mindfulness-based stress reduction vs escitalopram for the treatment of adults with anxiety disorders: a randomized clinical trial." JAMA Psychiatry, 80(1), 13-21. https://doi.org/10.1001/jamapsychiatry.2022.3679 (276 randomized, 208 completers; adverse events 15.4% with MBSR against 78.6% with escitalopram)
  26. 69.Fincham, G.W., Strauss, C., Montero-Marin, J., and Cavanagh, K. (2023). "Effect of breathwork on stress and mental health: a meta-analysis of randomised-controlled trials." Scientific Reports, 13, 432. https://doi.org/10.1038/s41598-022-27247-y (12 trials, 785 adults; stress effect -0.35, most studies at moderate risk of bias)

This topic carries 67 notes in the research manuscript; the 26 above are those behind the material on this page. Full source register.