Kurzgesagt – In a Nutshell

We thank the following experts for their critical reading, feedback and corrections:

– Prof. Ilia Karatsoreos

University of Massachusetts Amherst, USA

– Prof. Daryl O’Connor

University of Leeds, UK

– All living things strive for homeostasis, a state where their body is in balance. To maintain this balance they make adjustments like moving into the sunlight or eating nutrients. But the world is a cruel place with death lurking behind every corner and organisms need a way to react to extreme situations.

This is how stress evolved – As a physical response to a stressor – which is anything challenging or dangerous. Stress is a very fast, drastic change of the state of the body that prioritizes survival. An emergency program that lets the organism push way out of its comfort zone to survive.

#Taborsky B, Kuijper B, Fawcett TW, English S, et al. An evolutionary perspective on stress responses, damage and repair. Horm Behav. 2022

https://pubmed.ncbi.nlm.nih.gov/35569424/

Quote: “Variation in stress responses has been investigated in relation to environmental factors, species ecology, life history and fitness. Moreover, mechanistic studies have unravelled molecular mechanisms of how acute and chronic stress responses cause physiological impacts (‘damage’), and how this damage can be repaired. However, it is not yet understood how the fitness effects of damage and repair influence stress response evolution. Here we study the evolution of hormone levels as a function of stressor occurrence, damage and the efficiency of repair. We hypothesise that the evolution of stress responses depends on the fitness consequences of damage and the ability to repair that damage. To obtain some general insights, we model a simplified scenario in which an organism repeatedly encounters a stressor with a certain frequency and predictability (temporal autocorrelation). The organism can defend itself by mounting a stress response (elevated hormone level), but this causes damage that takes time to repair. We identify optimal strategies in this scenario and then investigate how those strategies respond to acute and chronic exposures to the stressor. We find that for higher repair rates, baseline and peak hormone levels are higher. This typically means that the organism experiences higher levels of damage, which it can afford because that damage is repaired more quickly, but for very high repair rates the damage does not build up. With increasing predictability of the stressor, stress responses are sustained for longer, because the animal expects the stressor to persist, and thus damage builds up. This can result in very high (and potentially fatal) levels of damage when organisms are exposed to chronic stressors to which they are not evolutionarily adapted. Overall, our results highlight that at least three factors need to be considered jointly to advance our understanding of how stress physiology has evolved: (i) temporal dynamics of stressor occurrence; (ii) relative mortality risk imposed by the stressor itself versus damage caused by the stress response; and (iii) the efficiency of repair mechanisms.”

#Goldstein, D. S., & Kopin, I. J. Evolution of concepts of stress. Stress. 2007

https://pubmed.ncbi.nlm.nih.gov/17514579/

Quote: “This essay describes the evolution of stress as a medical scientific idea. Claude Bernard, Walter B. Cannon and Hans Selye provided key founding concepts for the current view. Bernard introduced the idea of the internal environment bathing cells—the milieu intérieur—maintained by continual compensatory changes of bodily functions. Cannon coined the word, “homeostasis,” referring to a set of acceptable ranges of values for internal variables. Cannon taught that threats to homeostasis evoke activation of the sympathoadrenal system as a functional unit. Selye defined stress as a state characterized by a uniform response pattern, regardless of the particular stressor, that could lead to long-term pathologic changes. “Allostasis” was introduced as a concept in recognition that there is no single ideal set of steady-state conditions in life; instead, setpoints and other response criteria change continuously. Stress is now viewed neither as a perturbation nor a stereotyped response pattern but as a condition characterized by a perceived discrepancy between information about a monitored variable and criteria for eliciting patterned effector responses. Different stressors elicit different patterns of activation of the sympathetic nervous, adrenomedullary hormonal, hypothalamic-pituitary-adrenocortical and other effectors, closing negative feedback loops. This systems concept of stress yields predictions that observation or experimentation can test and that are applicable to normal physiology and to a variety of acute and chronic disorders.”

– His brain classifies the tiger as a critical stressor and unleashes the stress response. Adrenal glands pump out adrenaline that rushes through Urr’s body activating “fight or flight” mode.

#Chu B, Marwaha K, Sanvictores T, et al. Physiology, Stress Reaction. In: StatPearls [Internet]. 2024

https://www.ncbi.nlm.nih.gov/books/NBK541120/

Quote: “Any physical or psychological stimuli that disrupt homeostasis result in a stress response. The stimuli are called stressors, and physiological and behavioral changes in response to exposure to stressors constitute the stress response. A stress response is mediated through a complex interplay of nervous, endocrine, and immune mechanisms, activating the sympathetic-adreno-medullar (SAM) axis, the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system.[1] The stress response is adaptive to prepare the body to handle the challenges presented by an internal or external environmental challenge, such as stressors.”

#Dutt M, Wehrle CJ, Jialal I. Physiology, Adrenal Gland. In: StatPearls [Internet]. 2023

https://www.ncbi.nlm.nih.gov/books/NBK537260/

Quote: “The adrenal gland is made up of the cortex and medulla. The cortex produces steroid hormones including glucocorticoids, mineralocorticoids, and adrenal androgens, and the medulla produces the catecholamines, epinephrine, and norepinephrine.”

#Khalil B, Rosani A, Warrington SJ. Physiology, Catecholamines. In: StatPearls [Internet]. 2024

https://www.ncbi.nlm.nih.gov/books/NBK507716/

Quote: “Epinephrine and norepinephrine play a central role in the body’s “fight-or-flight” response. When the body perceives a threat, these hormones are rapidly released from the adrenal medulla and sympathetic nerve endings.”

– His heart starts beating faster and lungs accelerate, providing an emergency supply of nutrients and oxygen to all critical systems.

#Dalal R, Grujic D. Epinephrine. In: StatPearls [Internet]. 2025

https://www.ncbi.nlm.nih.gov/books/NBK482160/

Quote: “Through its action on α1-receptors, epinephrine induces increased vascular smooth muscle contraction, pupillary dilator muscle contraction, and intestinal sphincter muscle contraction.

Other significant effects of epinephrine include increased heart rate, myocardial contractility, and renin release via β1 receptors.”

#Drug Dictionary - Therapeutic epinephrine. National Cancer Institute. Retrieved June 2025.

https://www.cancer.gov/publications/dictionaries/cancer-drug/def/therapeutic-epinephrine

Quote: “Through its beta1 receptor-stimulating actions, epinephrine increases the force and rate of myocardial contraction and relaxes bronchial smooth muscle, resulting in bronchodilation.”

– Adrenaline dictates that his muscles have energy priority over his other organs and activates them for rapid action – their strength and speed are ramped up.

Adrenaline stimulates and enhances muscle activity by binding to specific receptors in the body, which increases both glucose release from the liver (glycogenolysis) and glucose breakdown within muscles (glycolysis). In muscle cells, glucose is then used to produce ATP, which fuels muscle contractions.

#Watt MJ, Howlett KF, Febbraio MA, et al. Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans. J Physiol. 2001

https://pmc.ncbi.nlm.nih.gov/articles/PMC2278696/

Quote: “The data demonstrate that elevated plasma adrenaline levels during moderate exercise in untrained men increase skeletal muscle glycogen breakdown and PDH activation, which results in greater carbohydrate oxidation. The greater muscle glycogenolysis appears to be due to increased glycogen phosphorylase transformation whilst the increased PDH activity cannot be readily explained.”

#Raz I, Katz A, Spencer MK. Epinephrine inhibits insulin-mediated glycogenesis but enhances glycolysis in human skeletal muscle. Am J Physiol. 1991

https://pubmed.ncbi.nlm.nih.gov/1900669/

Quote: “It is concluded that E inhibits insulin-mediated glycogenesis because of an inactivation of glycogen synthase and an activation of glycogenolysis. E also appears to inhibit insulin-mediated glucose utilization, at least partly, because of an increase in G-6-phosphate (which inhibits hexokinase) and enhances glycolysis by G-1,6-P2-, fructose 6-phosphate-, and F-1,6-P2-mediated activation of PFK.”

#Dalal R, Grujic D. Epinephrine. In: StatPearls [Internet]. 2025

https://www.ncbi.nlm.nih.gov/books/NBK482160/

Quote: “Through its action on α1-receptors, epinephrine induces increased vascular smooth muscle contraction, pupillary dilator muscle contraction, and intestinal sphincter muscle contraction.

Other significant effects of epinephrine include increased heart rate, myocardial contractility, and renin release via β1 receptors.”

– Pain and fatigue signals are muted, while his senses become super sharp and lock in on the threat. Urr perceives every detail with maximum clarity and realizes the tiger is getting ready to pounce!

Adrenaline can reduce pain perception. It can also reduce tiredness by increasing heart rate, breathing, and feelings of alertness and arousal. Furthermore, adrenaline is associated with heightened sensory perception through pupil dilation and increased oxygen supply to the brain.

#Pilozzi A, Carro C, Huang X. Roles of β-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism. Int J Mol Sci. 2020

https://pmc.ncbi.nlm.nih.gov/articles/PMC7796446/

Quote: “β-Endorphins are part of the system of opioid receptor agonists. The endorphin family includes β-endorphin, α-neoendorphin, enkephalins, and dynorphins [24]. β-Endorphins exert an analgesic effect that is more potent than morphine [1,2], and act primarily on the mu family of opioid receptors [25], which are, like the two other opioid receptors, delta and kappa, G-protein coupled receptors [24]. Naloxone, a typical antagonist of other opiates, has been found to reduce β-endorphin binding as well, and is commonly used in opioid-related studies [1]. β-Endorphins, along with other opioids, appear to attenuate cyclic adenosine monophosphate levels, and decrease calcium uptake [2]. The peptide is typically released to the periphery in response to a painful or stressful event, where they inhibit somatosensory fibers, with a focus on nociceptors [2].”

#Drug Dictionary - Therapeutic epinephrine. National Cancer Institute. Retrieved June 2025.

https://www.cancer.gov/publications/dictionaries/cancer-drug/def/therapeutic-epinephrine

Quote: “Through its beta1 receptor-stimulating actions, epinephrine increases the force and rate of myocardial contraction and relaxes bronchial smooth muscle, resulting in bronchodilation.”

#Dalal R, Grujic D. Epinephrine. In: StatPearls [Internet]. 2025

https://www.ncbi.nlm.nih.gov/books/NBK482160/

Quote: “Through its action on α1-receptors, epinephrine induces increased vascular smooth muscle contraction, pupillary dilator muscle contraction, and intestinal sphincter muscle contraction.

Other significant effects of epinephrine include increased heart rate, myocardial contractility, and renin release via β1 receptors.”

#Chu B, Marwaha K, Sanvictores T, et al. Physiology, Stress Reaction. In: StatPearls [Internet]. 2024

https://www.ncbi.nlm.nih.gov/books/NBK541120/

Quote: “When released, norepinephrine and epinephrine bind to specific membrane-bound G-protein receptors to initiate an intracellular cyclic adenosine monophosphate (cAMP) signaling pathway that rapidly activates cellular responses. The activation of these receptors results in the contraction of smooth and cardiac muscle cells, leading to vasoconstriction, increased blood pressure, heart rate, cardiac output, skeletal muscle blood flow, increased sodium retention, increased levels of glucose due to glycogenolysis and gluconeogenesis, lipolysis, increased oxygen consumption, and thermogenesis. [...] In addition, SAM [Sympathetic-Adreno-Medullar System] activation causes behavioral activation, such as enhanced arousal, alertness, vigilance, cognition, focused attention, and analgesia.”

#Larsen RS, Waters J. Neuromodulatory Correlates of Pupil Dilation. Front Neural Circuits. 2018

https://pmc.ncbi.nlm.nih.gov/articles/PMC5854659/

Quote: “Changes in pupil diameter are thought to coincide with the activity of neuromodulators, including noradrenaline and acetylcholine [...]”

#Chu B, Marwaha K, Sanvictores T, et al. Physiology, Stress Reaction. In: StatPearls [Internet]. 2024

https://www.ncbi.nlm.nih.gov/books/NBK541120/

Quote: “When released, norepinephrine and epinephrine bind to specific membrane-bound G-protein receptors to initiate an intracellular cyclic adenosine monophosphate (cAMP) signaling pathway that rapidly activates cellular responses. The activation of these receptors results in the contraction of smooth and cardiac muscle cells, leading to vasoconstriction, increased blood pressure, heart rate, cardiac output, skeletal muscle blood flow, increased sodium retention, increased levels of glucose due to glycogenolysis and gluconeogenesis, lipolysis, increased oxygen consumption, and thermogenesis. [...] In addition, SAM [Sympathetic-Adreno-Medullar System] activation causes behavioral activation, such as enhanced arousal, alertness, vigilance, cognition, focused attention, and analgesia.”

– Adrenaline forces Urr to make a quick, impulsive decision: Without thinking about it he chooses to fight and attacks with full force.

There is some evidence in animals, and preliminary evidence in humans, that adrenaline directly contributes to impulsive decision making. More generally, the acute stress response - of which adrenaline secretion is a big part of - is strongly associated with impulsiveness.

#Swann AC, Lijffijt M, Lane SD, Cox B, et al. Norepinephrine and impulsivity: effects of acute yohimbine. Psychopharmacology (Berl). 2013

https://pmc.ncbi.nlm.nih.gov/articles/PMC3742556/

Quote: ”For example, NE [norepinephrine] released in response to stress can impair inhibitory functions of the prefrontal cortex (Arnsten and Li 2005;Fitzgerald 2011). Accordingly, blockade of alpha-2 NE receptors, which increases NE release, has been shown to increase analogs of rapid-response impulsivity in rats (Arnsten and Li 2005;Sun et al. 2010), and in a preliminary study in humans (Swann et al. 2005a).”

#Maier SU, Makwana AB, Hare TA. Acute Stress Impairs Self-Control in Goal-Directed Choice by Altering Multiple Functional Connections within the Brain’s Decision Circuits. Neuron. 2015

https://pubmed.ncbi.nlm.nih.gov/26247866/

Quote: “Important decisions are often made under stressful circumstances that might compromise self-regulatory behavior. Yet the neural mechanisms by which stress influences self-control choices are unclear. We investigated these mechanisms in human participants who faced self-control dilemmas over food reward while undergoing fMRI following stress. We found that stress increased the influence of immediately rewarding taste attributes on choice and reduced self-control. This choice pattern was accompanied by increased functional connectivity between ventromedial prefrontal cortex (vmPFC) and amygdala and striatal regions encoding tastiness. Furthermore, stress was associated with reduced connectivity between the vmPFC and dorsolateral prefrontal cortex regions linked to self-control success. Notably, alterations in connectivity pathways could be dissociated by their differential relationships with cortisol and perceived stress. Our results indicate that stress may compromise self-control decisions by both enhancing the impact of immediately rewarding attributes and reducing the efficacy of regions promoting behaviors that are consistent with long-term goals.”

#Raio CM, Konova AB, Otto AR. Trait impulsivity and acute stress interact to influence choice and decision speed during multi-stage decision-making. Sci Rep. 2020

https://pmc.ncbi.nlm.nih.gov/articles/PMC7210896/

Quote: “For example, both acutely stressed participants and participants high in trait impulsivity exhibit increased response repetition after positive reinforcement, and faster response times (RTs) in simple RL tasks16,45–47. These effects on learning and decision-making are thought to occur either by stress ‘occupying’ or impairing cognitive resources that allow for more deliberative decision-making processes55,56 or by both factors imposing internally perceived time constraints that manifest in differential choice speeding25,57,58.”

– A new hormone joins the battle: cortisol. Cortisol is the slower, more strategic hormone that manages a longer stress response.

The graph showing adrenaline and cortisol dynamics during acute stress response is based on Fig. 1 of the below publication.

#Kuebler U, Wirtz PH, Sakai M, Stemmer A, Ehlert U. Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages. PLoS One. 2013

https://pmc.ncbi.nlm.nih.gov/articles/PMC3568075/

Figure 1. A to C. Course of norepinephrine, epinephrine, and cortisol over time in stress and stress-control group.

– It orders a total shift of all body systems. Ramping up the fuel supply while suppressing all non-essential functions like resting, disease defense or digestion.

Cortisol increases blood glucose levels to supply the body with energy. It does so via various means, including the stimulation of glucose production in the liver (gluconeogenesis), reducing glucose uptake and storage in the muscles, and limiting insulin production (insulin decreases blood glucose levels). Cortisol is also known to increase feelings of alertness in humans, which counteracts resting.

#Knezevic E, Nenic K, Milanovic V, Knezevic NN. The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells. 2023

https://pmc.ncbi.nlm.nih.gov/articles/PMC10706127/

Quote: “Cortisol helps regulate glucose metabolism by increasing gluconeogenesis and insulin resistance, ensuring an adequate energy supply during stress [17].”

#Kuo T, McQueen A, Chen TC, Wang JC. Regulation of Glucose Homeostasis by Glucocorticoids. Adv Exp Med Biol. 2015

https://pmc.ncbi.nlm.nih.gov/articles/PMC6185996/

Quote: “GC [Glucocorticoids] promote hepatic gluconeogenesis [1, 2] and reduce glucose uptake and utilization in skeletal muscle and white adipose tissue (WAT) [3, 4].”

#Chapotot F, Gronfier C, Jouny C, et al. Cortisol secretion is related to electroencephalographic alertness in human subjects during daytime wakefulness. J Clin Endocrinol Metab. 1998

https://pubmed.ncbi.nlm.nih.gov/9851761/

Quote: “the present study describes a temporal coupling between cortisol release and central alertness, as reflected in the waking EEGβ activity. These findings suggest the existence of connections between the mechanisms involved in the control of hypothalamo-pituitary-adrenal activity and the activation processes of the brain, which undergoes varying degrees of alertness throughout daytime wakefulness.”

#Hoyt LT, Zeiders KH, Ehrlich KB, Adam EK. Positive upshots of cortisol in everyday life. Emotion. 2016

https://pmc.ncbi.nlm.nih.gov/articles/PMC4868668/

Quote: “Specifically, an increase in individuals’ cortisol levels predicted increases in feelings of alertness in the next hour (b= .58, p = .03; 95% Confidence Interval (CI) = .07, 1.10), accounting for individuals’ average daily fluctuations in alertness, current level of alertness, and health variables.”

#Alotiby A. Immunology of Stress: A Review Article. J Clin Med. 2024

https://pmc.ncbi.nlm.nih.gov/articles/PMC11546738/

Quote: “Elevated levels of stress hormones, particularly cortisol, can suppress the activity of key immune cells and skew cytokine production, resulting in a weakened immune response [17]. This disruption can lead to decreased production of antibodies and impaired T cell function, ultimately compromising the body’s ability to fight infections and maintain overall health [2]. Furthermore, stress can induce changes in the distribution and behavior of immune cells, such as a reduction in circulating T cells and natural killer cells, which are vital for recognizing and eliminating infected or cancerous cells. This shift can diminish immune surveillance and increase susceptibility to both infectious diseases and chronic inflammatory conditions [18].”

#Baritaki S, de Bree E, Chatzaki E, Pothoulakis C. Chronic Stress, Inflammation, and Colon Cancer: A CRH System-Driven Molecular Crosstalk. J Clin Med. 2019

https://pmc.ncbi.nlm.nih.gov/articles/PMC6833069/

Quote: “Acute and chronic stressors have been reported to increase various inflammatory markers [47,48]. A potential interaction between chronic stress and inflammatory cytokine responses to acute stress has also been reported [49,50]. Excessive stress caused by chronic bad lifestyle habits, such as poor diet or dismal life events, may inflate cortisol levels, as a result of HPA activation. High cortisol levels in turn can cause BGA [brain-gut-axis] disturbance and subsequent immune system dysregulation in the GI tract. The consequences include compromised food digestion and absorption by the intestine, development of indigestion and an irritated and inflamed mucosal lining.”

– Their bodies shut down “fight or flight” and activate “rest and digest”.

#Tindle J, Tadi P. Neuroanatomy, Parasympathetic Nervous System. In: StatPearls [Internet]. 2025

https://www.ncbi.nlm.nih.gov/books/NBK553141/

Quote: “The parasympathetic nervous system (PNS) is 1 of the 2 functionally distinct and continuously active autonomic nervous system (ANS) divisions. It opposes the other, the sympathetic nervous system (SNS). The parasympathetic nervous system predominates in quiet “rest and digest” conditions. In contrast, the sympathetic nervous system drives the “fight or flight” response in stressful situations (see Diagram. Diagram of Efferent Sympathetic (red) and Parasympathetic (blue) Nervous System). The main purpose of the PNS is to conserve energy that can be used later and to regulate bodily functions like digestion and urination.[1]

[...]

In the heart, parasympathetic stimulation of M2 receptors causes decreased heart rate and conduction velocity through the AV node.

[...]

In the stomach and intestines, parasympathetic stimulation of M receptors leads to increased motility and relaxation of sphincters. Stimulation of M receptors also increases gastric secretions to aid in digestion.

[...]

In the pancreas, parasympathetic stimulation of M3 receptors leads to the release of digestive enzymes and insulin.

In the kidneys and bladder, parasympathetic stimulation of M3 receptors stimulates ureter peristalsis, contraction of the detrusor muscle, and relaxation of the internal urethral sphincter, aiding in the flow and excretion of urine.”

– Wounds begin to hurt and muscles cry in exhaustion.

Hormones secreted during periods of stress, such as adrenaline and cortisol, reduce pain perception. When the stress goes away, the concentration of these hormones in the body drops, resulting in an increase in perceived pain.

#Rice D, Nijs J, Kosek E, Wideman T, et al. Exercise-Induced Hypoalgesia in Pain-Free and Chronic Pain Populations: State of the Art and Future Directions. J Pain. 2019

https://pubmed.ncbi.nlm.nih.gov/30904519/

Quote: “[...] release of stress hormones like (nor)adrenaline and cortisol, which exert analgesic effects at the level of the brain (eg, noradrenaline is an important neurotransmitter for enabling descending nociceptive inhibition98) and spinal cord (eg, dorsal horn neurons contain glucocorticoid receptors, having nociceptive inhibitory capacity94).”

– But our brains are built to take fear very seriously, so if you experience even a short burst of anxiety over an email or because you scrolled through twitter, the helping hand of stress springs to action. You can have dozens of these micro stressors per day constantly activating your stress response, even if you barely notice anymore. While these micro-threats stack up we also have to deal with bigger stressors like unpaid overtime, angry clients, rising rents, inflation and healthcare or tariffs and chaos making our future more uncertain.

#Nicolas Rohleder. Chapter 9 - Chronic Stress and Disease. Insights to Neuroimmune Biology (Second Edition), Elsevier, 2016

https://doi.org/10.1016/B978-0-12-801770-8.00009-4

The quoted excerpt can be accessed here:https://www.sciencedirect.com/topics/immunology-and-microbiology/chronic-stress

Quote: “Many forms of chronic stress are further caused by truly chronic exposure to stressful life circumstances. A classic and well-studied example is familial caregiving. This type of chronic stress often affects older adults who care for a spouse with Alzheimer’s disease, to adults of any age who care for a family member with a chronic disease, such as cancer, or parents of children with disabilities.

In the workplace, chronic stress can result from high demands on someone’s time, time pressure, and responsibilities for other people’s lives, but also from hostile work environment and inhumane working conditions. Conversely, loss of employment can be equally chronically stressful due to the impact on feelings of subjective self-worth, but also constant pressure to apply for jobs, and escape unemployment. Living in impoverished conditions, as well as exposure to environmental threats can be a truly chronic stressor for families living in dangerous neighborhoods, and similar effects can be caused by racial or other forms of discrimination.

Finally, chronic stress can also be caused by repeated exposure to less-intense stressors, such as repeated daily hassles. The example of daily hassles further highlights that it is not only or necessarily the characteristics, severity, or frequency of events that determine the impact of an individual’s health. Instead, prospective studies have shown that differences in affective responses to these daily events determine their long-term health impacts, with stronger affective responses being predictors of mental and physical health.1,2”

– But the boost we get from stress can also be extremely helpful if you have to study for an exam, run a marathon or complete a big project.

Instances of stress that involve optimal levels of stimulation are also called “eustress”. They often result from challenging, but attainable, enjoyable and/or worthwhile tasks.

Kloidt, J., Barsalou, L.W. Establishing a Comprehensive Hierarchical construct of Eustress (CHE). Curr Psychol. 2024

https://pubmed.ncbi.nlm.nih.gov/39620106/

Quote: “[...] Comprehensive Hierarchical construct of Eustress (CHE). According to CHE, eustress emerges from three sources: (1) successful goal-directed action, (2) experiencing the moment in an enjoyable, fulfilling, or meaningful manner, and (3) positive stable qualities of the individual. [...] Rather than taking a single form, eustress manifests itself as diverse states during successful goal-directed action and fulfilling momentary experience. Regularly producing eustress in these manners likely establishes CHE’s trait-like qualities for generating eustress effectively on future occasions. Interestingly, these qualities overlap highly with well-established elements of wellbeing, suggesting that wellbeing contributes to eustress in challenging situations.”

– It is a proper superpower and can feel exhilarating, even addictive.

#Mandriota M. Are You Addicted to Stress? PsychCentral. 2022

https://psychcentral.com/stress/addicted-to-stress

Quote: “What is a stress addiction? It can be defined as a recurring pattern of seeking out situations or behaving in ways that increase stress, even when you’re distressed, aware of the potential consequences, and want to stop.

“Stress addiction isn‘t a clinical diagnosis,“ says Michael J. McGrath, MD, a psychiatrist who’s board certified in addiction and the medical director of The Ohana Addiction Treatment Center located on the Big Island of Hawaii. But it’s still possible to become addicted to stress or stressful situations.”

– The problem is that stress was only ever intended to be used in short spurts and critical situations. If it is activated over days, weeks and months with no release, it becomes chronic stress, one of the deadliest conditions for humans.

For the graph showing adrenaline and cortisol dynamics over time, we used Fig. 5 in the publication below as a reference. The other listed publications support the link between chronic stress and mortality.

#Agorastos A, Chrousos GP. The neuroendocrinology of stress: the stress-related continuum of chronic disease development. Mol Psychiatry. 2022

https://pubmed.ncbi.nlm.nih.gov/34290370/

#Russ T C, Stamatakis E, Hamer M, Starr J M, et al. Association between psychological distress and mortality: individual participant pooled analysis of 10 prospective cohort studies. BMJ. 2012

https://pubmed.ncbi.nlm.nih.gov/22849956/

Quote: “We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels.”

#Naja Rod Nielsen, Tage S. Kristensen, Peter Schnohr, Morten Grønbæk. Perceived Stress and Cause-specific Mortality among Men and Women: Results from a Prospective Cohort Study, American Journal of Epidemiology. 2008

https://pubmed.ncbi.nlm.nih.gov/18611955/

Quote: “The authors assessed the effect of psychological stress on total and cause-specific mortality among men and women. In 1981–1983, the 12,128 Danish participants in the Copenhagen City Heart Study were asked two questions on stress intensity and frequency and were followed in a nationwide registry until 2004, with <0.1% loss to follow-up. Sex differences were found in the relations between stress and mortality (p = 0.02). After adjustments, men with high stress versus low stress had higher all-cause mortality (hazard ratio (HR) = 1.32, 95% confidence interval (CI): 1.15, 1.52). This finding was most pronounced for deaths due to respiratory diseases (high vs. low stress: HR = 1.79, 95% CI: 1.10, 2.91), external causes (HR = 3.07, 95% CI: 1.65, 5.71), and suicide (HR = 5.91, 95% CI: 2.47, 14.16). High stress was related to a 2.59 (95% CI: 1.20, 5.61) higher risk of ischemic heart disease mortality for younger, but not older, men. In general, the effects of stress were most pronounced among younger and healthier men. No associations were found between stress and mortality among women, except among younger women with high stress, who experienced lower cancer mortality (HR = 0.51, 95% CI: 0.28, 0.92). Future preventive strategies may be targeted toward stress as a risk factor for premature death among middle-aged, presumably healthy men.”

#Aldwin CM, Jeong YJ, Igarashi H, et al. Do hassles mediate between life events and mortality in older men? Longitudinal findings from the VA Normative Aging Study. Exp Gerontol. 2014

https://pmc.ncbi.nlm.nih.gov/articles/PMC4253863/

Quote: “We investigated whether hassles mediated the effect of life events on mortality in a sample of 1,293 men (Mage = 65.58, SD = 7.01), participants in the VA Normative Aging Study. We utilized measures of stressful life event (SLE) and hassles from 1989 to 2004, and men were followed for mortality until 2010. For life events and hassles, previous research identified three and four patterns of change over time, respectively, generally indicating low, moderate, and high trajectories, with one moderate, non-linear pattern for hassles (shallow U curve). Controlling for demographics and health behaviors, we found that those with moderate SLE trajectories (38%) more likely to die than those with low SLE trajectories, HR = 1.42, 95% CI [1.16, 3.45]. Including the hassles classes showed that those with the moderate non-linear hassles trajectory were 63% more likely to die than those with low hassles trajectory, HR = 1.63, 95% CI [1.19, 2.23],, while those with consistently high hassles trajectory were over 3 times more likely to die, HR = 3.30, 95% CI [1.58, 6.89]. However, the HR for moderate SLE trajectory decreased only slightly to 1.38, 95% CI [1.13, 1.68], suggesting that the two types of stress have largely independent effects on mortality.”

#Aldwin CM, Molitor NT, Avron S 3rd, Levenson MR, et al. Do Stress Trajectories Predict Mortality in Older Men? Longitudinal Findings from the VA Normative Aging Study. J Aging Res. 2011

https://pmc.ncbi.nlm.nih.gov/articles/PMC3180855/

Quote: “We examined long-term patterns of stressful life events (SLE) and their impact on mortality contrasting two theoretical models: allostatic load (linear relationship) and hormesis (inverted U relationship) in 1443 NAS men (aged 41–87 in 1985; M = 60.30, SD = 7.3) with at least two reports of SLEs over 18 years (total observations = 7,634). Using a zero-inflated Poisson growth mixture model, we identified four patterns of SLE trajectories, three showing linear decreases over time with low, medium, and high intercepts, respectively, and one an inverted U, peaking at age 70. Repeating the analysis omitting two health-related SLEs yielded only the first three linear patterns. Compared to the low-stress group, both the moderate and the high-stress groups showed excess mortality, controlling for demographics and health behavior habits, HRs = 1.42 and 1.37, ps <.01 and <.05.”

#Alcántara C, Muntner P, Edmondson D, Safford MM, et al. Perfect storm: concurrent stress and depressive symptoms increase risk of myocardial infarction or death. Circ Cardiovasc Qual Outcomes. 2015

https://pubmed.ncbi.nlm.nih.gov/25759443/

Quote: “Participants included 4487 adults with coronary heart disease from the REasons for Geographic and Racial Differences in Stroke study, a prospective cohort study of 30,239 black and white adults. We conducted Cox proportional hazards regression with the composite outcome of myocardial infarction or death and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1% reported concurrent high stress and high depressive symptoms at baseline. During a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of follow-up, participants with concurrent high stress and high depressive symptoms had increased risk for myocardial infarction or death (adjusted hazard ratio, 1.48 [95% confidence interval, 1.08-2.02]) relative to those with low stress and low depressive symptoms. Those with low stress and high depressive symptoms (hazard ratio, 0.92 [95% confidence interval, 0.66-1.28]) or high stress and low depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57-1.29]) were not at increased risk. The association on myocardial infarction or death was not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95% confidence interval, 0.65-1.22]).”

– The price of chronic stress is nothing less than the slow destruction of every part of your body and brain. As the stress cascade is activated over and over, adrenaline and cortisol keep flooding your body. Your fight or flight systems are overactivated while your rest and digest functions are constantly suppressed.

Chronic stress affects numerous systems in our bodies in a way that is bad for our health in the long-term. The following are two reviews on the topic.

#Roberts BL, Karatsoreos IN. Brain-body responses to chronic stress: a brief review. Fac Rev. 2021

https://pmc.ncbi.nlm.nih.gov/articles/PMC8725649/

Quote: “In order to survive and thrive, organisms must adapt to constantly changing environmental pressures. When there are significant shifts in the environment, the brain and body engage a set of physiological and behavioral countermeasures collectively known as the “stress response”. These responses, which include changes at the cellular, systems, and organismal level, are geared toward protecting homeostasis and adapting physiological operating parameters so as to enable the organism to overcome short-term challenges. It is the shift of these well-organized acute responses to dysregulated chronic responses that leads to pathologies. In a sense, the protective measures become destructive, causing the myriad health problems that are associated with chronic stress. To further complicate the situation, these challenges need not be purely physical in nature. Indeed, psychosocial stressors such as ruminating about challenges at work, resource insecurity, and unstable social environments can engage the very same emergency threat systems and eventually lead to the same types of pathologies that sometimes are described as “burnout” in humans. This short review focuses on very recent empirical work exploring the effects of chronic stress on key brain circuits, metabolism and metabolic function, and immune function.”

#O’Connor DB, Thayer JF, Vedhara K. Stress and Health: A Review of Psychobiological Processes. Annu Rev Psychol. 2021

https://pubmed.ncbi.nlm.nih.gov/32886587/

Quote: “The cumulative science linking stress to negative health outcomes is vast. Stress can affect health directly, through autonomic and neuroendocrine responses, but also indirectly, through changes in health behaviors. In this review, we present a brief overview of (a) why we should be interested in stress in the context of health; (b) the stress response and allostatic load; (c) some of the key biological mechanisms through which stress impacts health, such as by influencing hypothalamic-pituitary-adrenal axis regulation and cortisol dynamics, the autonomic nervous system, and gene expression; and (d) evidence of the clinical relevance of stress, exemplified through the risk of infectious diseases. The studies reviewed in this article confirm that stress has an impact on multiple biological systems. Future work ought to consider further the importance of early-life adversity and continue to explore how different biological systems interact in the context of stress and health processes.”

– Your muscles tense up for a fight that never comes – instead your back, shoulders and neck scream under the tension and you get pounding headaches.

Tension headache, or tension-type headache, is the most common form of headache. The pain usually radiates from the lower back of the head and the neck and often affects both sides of the head. While many different factors can cause a headache, chronic stress has emerged as one of the most common triggers and represents a significant risk factor for headaches generally, including migraines.

#Cathcart S, Bhullar N, Immink M, et al. Pain sensitivity mediates the relationship between stress and headache intensity in chronic tension-type headache. Pain Res Manag. 2012

https://pmc.ncbi.nlm.nih.gov/articles/PMC3659009/

Quote: “Stress is known to be a contributing factor to chronic tension-type headache (CTH), with research indicating that mental stress is the most commonly reported trigger and aggravating factor of a CTH episode (1,2).”

#Maleki N, Becerra L, Borsook D. Migraine: maladaptive brain responses to stress. Headache. 2012

https://pmc.ncbi.nlm.nih.gov/articles/PMC3475609/

Quote: “Stress as a trigger for migraine attacks is present in nearly 70% of individuals 13. High levels of stress are reported in migraine patients, particularly in those suffering from chronic daily migraine 14. Both endogenous (e.g., hormone) and exogenous (e.g., physical stressors (e.g., light) or psychological stressors stressors add to the burden of the disease. Emotional or physical trauma (e.g., abuse, particularly in childhood), socioeconomic or social stress 15 are examples of psychological stressors.”

– Your digestive tract cramps and suffers under permanent duress. Either holding things in too long or rushing things out.

Chronic stress can negatively affect your digestive system in many different ways. For example, it can cause both constipation and diarrhea. The following is a review paper on how stress affects the gastrointestinal system.

#Leigh SJ, Uhlig F, Wilmes L, Sanchez-Diaz P, et al. The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota-gut-brain axis perspective. J Physiol. 2023

https://pubmed.ncbi.nlm.nih.gov/37756251/

Quote: “The physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic stress is associated with widespread maladaptive changes throughout the gut, although comparatively little is known about the effects of acute stress. Furthermore, these stress-induced changes in the gut may increase susceptibility to gastrointestinal disorders and infection, and impact critical features of the neural and behavioural consequences of the stress response by impairing gut–brain axis communication. Understanding the mechanisms behind changes in enteric nervous system circuitry, visceral sensitivity, gut barrier function, permeability, and the gut microbiota following stress is an important research objective with pathophysiological implications in both neurogastroenterology and psychiatry. Moreover, the gut microbiota has emerged as a key aspect of physiology sensitive to the effects of stress. In this review, we focus on different aspects of the gastrointestinal tract including gut barrier function as well as the immune, humoral and neuronal elements involved in gut–brain communication. Furthermore, we discuss the evidence for a role of stress in gastrointestinal disorders. Existing gaps in the current literature are highlighted, and possible avenues for future research with an integrated physiological perspective have been suggested. A more complete understanding of the spatial and temporal dynamics of the integrated host and microbial response to different kinds of stressors in the gastrointestinal tract will enable full exploitation of the diagnostic and therapeutic potential in the fast-evolving field of host–microbiome interactions.”

– Your fat metabolism is disrupted and starts slowing down fat breakdown, making weight loss harder – while increasing fat build up in your abdominal and belly area. Your cells become less responsive to insulin increasing your risk for metabolic diseases.

#Tomiyama AJ. Stress and Obesity. Annu Rev Psychol. 2019

https://pubmed.ncbi.nlm.nih.gov/29927688/

Quote: “Second, cortisol directly promotes fat deposition, particularly in the abdominal region. This is readily evident in Cushing’s disease, in which individuals have congenitally high levels of cortisol. A hallmark symptom of Cushing’s disease is abdominal obesity, which resolves when cortisol is medically reduced to normal levels (Björntorp 2001, Shibli-Rahhal et al. 2006). Diurnal salivary and 24-h urine cortisol levels predict higher BMI and abdominal obesity (Fraser et al. 1999, Rosmond et al. 1998). Indeed, the link between cortisol levels and abdominal obesity is so consistently observed that abdominal obesity has been suggested as a marker for long-term cortisol levels (Björntorp & Rosmond 2000). Abdominal obesity is a particularly toxic pattern of fat deposition and predicts poor metabolic and cardiovascular health in longitudinal studies (Despres et al. 2001).”

#Yaribeygi H, Maleki M, Butler AE, Jamialahmadi T, Sahebkar A. Molecular mechanisms linking stress and insulin resistance. EXCLI J. 2022

https://pmc.ncbi.nlm.nih.gov/articles/PMC8971350/

Quote: “The evidence indicates that stressful life events, traumatic experiences, general emotional stress, anger and hostility, distressed sleep and workplace stress may negatively modulate glucose homeostasis and induce insulin resistance (Lustman et al., 2000[76]; Lin et al., 2004[72]; Schneiderman et al., 2005[111]; Alexander et al., 2007[4]; Salleh, 2008[109]). Therefore, these stressors are now considered to be independent risk factors for DM [Diabetes mellitus] (Grigsby et al., 2002[40]; Lin et al., 2004[72]; Razzoli et al., 2017[103]; Yaribeygi et al., 2020[144]) and individuals with higher levels of chronic stress are more likely to develop DM when compared to their non-stressed counterparts (Razzoli et al., 2017[103]).”

#Xiao Y, Liu D, Cline MA, Gilbert ER. Chronic stress, epigenetics, and adipose tissue metabolism in the obese state. Nutr Metab. 2020

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