It’s 4:30 on Friday afternoon.  You are thinking about your plans for the upcoming long weekend when you get an email from your boss.  They need to see you right away about something, but they don’t say what.    What do they want to see you about this late in the day?  Is it about the rumored layoffs everyone’s been talking about?  Suddenly, your heart starts pounding, your palms become sweaty, your mouth feels dry, and your face feels hot.  Say hello to your fight-or-flight response.

 All mammals have a fight-or-flight response when under stress.  This makes sense from an evolutionary sense – animals that didn’t react to danger didn’t leave behind descendents.  As Stanford University neuro-endocrinologist Robert Sapolsky says, “If you’re a normal mammal, what stress is about is three minutes of screaming terror on the savannah, after which either its over with or you’re over with.” 

 Humans, on the other hand, are not normal mammals.  We are nearly unique in that the fight-or-flight response isn’t only a response to immediate danger.  We experience stress for many more reasons and much more often.  Essentially, our fight-or-flight response is on a permanent hair trigger.  The health consequences of this are stress-related diseases, many of which are rare or even unknown in other mammals.  In fact, Sapolsky has written a book aptly titled, “Why Zebras Don’t Get Ulcers.”

 Whether you are a luckless zebra fleeing on the savannah or a luckless pawn fighting in the corporate jungle, when you perceive danger the brain floods your system with stress hormones like epinephrine, norepinephrine and dopamine.  This is the familiar “adrenaline rush” that makes you ready for whatever action is necessary to respond to the danger.  Cortisol production is increased to modulate how our bodies use various fuel sources.  Any process that is not needed right now for this response is downgraded in favor of those that are.   Testosterone and DHEA levels go down.  If, for example, a leopard appears on a rock above you, your reproductive or digestive systems are put on hold so that blood is sent to the skeletal muscles to fuel escape.  While this is useful in the short term, you can’t sustain these reactions indefinitely and remain healthy.

 The reactions that the fight-or-flight response triggers affect nearly every part of your body. These reactions are started by the release of stress hormones.  These hormones prime the brain, making you more alert and aware of your environment.  They also make more neurotransmitters available in your peripheral nerve system so that nerve impulses to your muscles are faster.  Stress hormones enter the circulation, where they travel to the rest of the body.  The heart beats faster and stronger, breathing goes into overdrive, the digestive system slows down, blood is re-routed from internal organs and other areas to the skeletal muscles, production of saliva and tears stops, the pupils dilate, reflexes are accelerated, and more. 

 The modern human, however, doesn’t face many leopard attacks.  We face infuriating commutes, corporate reorganizations, tax returns, airport security, and a thousand other insults of life in the twenty-first century.  When we encounter one of these stressful situations, our body still reacts in the same way as if there was a leopard lurking above.  In this case, the fight-or-flight response turns from a helpful reaction that can possibly save your life into a negative reaction that can damage your health. 

 What’s more, that zebra on the savannah has to run from danger maybe once a day or even once a week or less.  We experience stress on a daily basis, and many times a day.  Our physiology is just not adapted to the constant demands we place on our bodies.   When we trigger production of stress hormones over a long period, we experience chronic stress. Both the fight-or-flight response and chronic stress are mediated by the same hormonal pathways.  In fact, another name for the fight-or-flight response is the acute stress response.  Although all animals have an acute stress reaction, only humans experience stress on an ongoing, purely psychological basis.   While animals do not normally harbor chronic stress like humans, when chronically exposed under experimental conditions, they get sick just like humans.

 When instead of immediate danger, the body experiences repeated or long-term physical or psychological stress, the hormones produced in the hypothalamus repeatedly or constantly trigger production of cortisol in the adrenal gland.  Chronically high cortisol levels affect a wide array of metabolic processes such as suppressing the immune system and increasing blood sugar.  High cortisol levels from chronic stress are linked to diabetes and obesity.  The combination of high cortisol and low testosterone leads to muscle wasting and can affect bone density.  Although recurrent stimulation of the fight-or-flight response can be one trigger for this type of stress response, it is not the only trigger.

 Acute stress from the fight-or-flight response causes a number of issues throughout the body differing from chronic stress associated with constantly high cortisol.  As Sapolsky says: “You need to turn off anything that’s not essential.  Growth, reproduction,…tissue repair,… do it later if there is a later.”  This is the compromise the fight-or-flight response imposes on your body. 

 Shunting resources from the digestive system, for example, slows down or stops digestion.  It’s not important to be properly digesting food if you’re about to become food, after all.  This can have some surprising effects.  By shutting down the intestines, however, we become more likely to suffer polyps, bowel cancer, diverticulitis, and more.  A bowel that moves is an all-around healthier bowel.  If we keep sending the signals that it should stop what it’s doing, then trouble can follow.

 Chronic stress also causes other conditions as the body attempts to adjust to the frequent stimulation of the fight-or-flight response.  Carnegie Mellon University psychologist Sheldon Cohen has found stress negatively contributes to the course of disease in conditions as diverse as depression, cardiovascular disease, and HIV/AIDS.

 Depression is perhaps the most clearly stress-linked disease.  Major clinical depression is the most common psychiatric disorder in the U.S, with between 32 and 35 million adults meeting the criteria for diagnosis at some point in their lifetime.  It also imposes a huge financial cost on society, with over 50% of cases requiring medical treatment and almost 60% resulting in severe or very severe impairment of ability to work or care for others.  In fact, depression causes more lost work days every year than substance abuse.

 Both the onset and the relapse of depression are associated with stress. Stress events, such as divorce and the death of a loved one, are among the biggest culprits in depression.  Depression also is common among people who have been diagnosed with a serious illness, because physical disease itself is a stressful event that can lead to depression.  In both such cases, the stress event or the diagnoses are treated as dangers and the fight-or-flight system is activated.  In one sense, this makes sense – the death of a loved one or being told you have an awful disease are definite threats to your emotional and physical health. 

 The problem is that you can’t run away from one of these events the way you can run away from our hypothetical leopard.  You still want to, and your body still tries, but there’s nowhere to run to.  So neither the stress nor the stress hormones dissipate and your brain metaphorically stews in a soup of stress hormones.  This interferes with normal neurotransmitter function and literally re-wires the brain.  In extreme cases, the constant psychological stress causes the brain to re-play the stressing event over and over, leading to post-traumatic stress disorder.  All this because your brain acts like a zebra’s.

 Cardiovascular disease is still the number one cause of death in the United States among adults.  Over a quarter of all deaths in the US every year is due to heart disease, and strokes account for another 5%.  The link between cardiovascular disease and stress is also well-established.  In one study, people who experience high levels of workplace stress had a 50% higher risk of cardiovascular disease.  In another, people that experienced physical, emotional, or sexual abuse as children also had higher risks of developing heart disease in later life. 

 The fight-or-flight response is related to these risks because psychological stress increases the physical stress on the heart.  In the fight-or-flight response, the heart rate and blood pressure both increase, and blood vessels constrict.  These reactions place a much higher burden on your entire cardiovascular system.  When these strains are continued for long periods, they can create dangerous changes in the heart, such as inflaming and weakening the heart muscle. 

 The fight-or-flight response also activates pathways that increase the inflammatory response and make coagulation happen faster.  In a true immediate life-or-death situation these prepare the body to deal with the damage that such a situation might inflict.  When these mechanisms are continually, chronically primed, they make blockages and clots in the arteries and veins more likely – possibly leading to strokes, heart attacks, or pulmonary emboli.

 HIV/AIDS is fundamentally different from depression and cardiovascular disease in that no amount of stress will cause AIDS.  If a person has not been exposed to the HIV virus, there is no chance of developing AIDS.  Stress will; however, worsen the course of the disease in a person who has HIV infection.  One study found that for every moderately to severely stressful event experienced while infected with HIV, the risk of progressing to full-blown AIDS increased by 50% and the risk of developing an AIDS-related condition increased by 2.5 times.

 How is the stress response able to change how a virus attacks the immune system?  First of all, stressful events may increase progression of AIDS by taxing an already weakened immune system.  Secondly, stress can reduce compliance with the often-complex antiviral regimens that have been successful in recent years in keeping the disease in check.  Lastly, the fight-or-flight response directly impairs the immune system’s ability to respond.

 The link between stress and cancer is less clear than for these diseases, but still suggestive.  Part of the issue is that cancer is not one disease but many, with different causes affecting different tissues.  Despite this confusing situation, however, it is clear that stress mechanisms negatively impact cancer through affecting antiviral defenses, DNA repair, and cellular aging.  During the fight-or-flight response, these physiological processes are, like digestion, not immediately necessary and therefore downgraded. 

 Stress can also cause us to age prematurely.  Most of us have seen the effects of stress on someone’s physical appearance.  Telomeres are part of our chromosomes that protect the genetic material as the cells divide.  Telomeres are longer when we are young and progressively shorten as we age, with each cell division.  At any given age, the length of our telomeres is the most accurate measure of our biological age.  A study reported in the National Academy of Sciences found that women with the highest levels of perceived stress had telomere shortening consistent with an additional decade of aging.  Whew!

 Triggering the fight-or-flight reaction, of course, requires us to perceive danger in some form.  Perception is a combination of what you know and the signals received from your senses.  Where one person perceives a harmless garter snake, another person may perceive a threatening serpent.  Most of us have some irrational fear.  So the conditions that provoke the fight-or-flight response are not universal, but instead are particular to each individual.  This also implies, of course, that perception can be changed to reduce our susceptibility to having the fight-or-flight reaction triggered. 

 Sapolsky’s studies in the Serengeti have found that production of stress hormones in animals is affected by many of the same things that experts recommend to humans.  For instance, male baboons that spend time with non-fertile females and infants have lower stress hormone levels, while males that cannot tell the difference between displays and threats are twice as stressed.  In other words, males that have multiple social connections and that don’t panic in the face of a threat are better off than their fellow apes.

 This is not very surprising.  Multiple studies have found that people with serious illness do better if they have a deep and dependable support system.  Cancer patients have been best studied in this respect.  In both quality of life and in severity and progression of disease, those patients that have support networks do better.  It does not seem to matter whether this network is family, church, support groups, friends, or other types of support, just that the patient feels able to depend on them.  The support reduces stress, improving health in both sorts of primates.

 Stress reduction is not merely making sure you have friends, of course.  Coping skills, meditation, good diet, exercise, etc. can all reduce your stress.  Self-medication with drugs or alcohol, a high-fat/high-sugar diet, inactivity, smoking, coffee, social isolation, etc. are all poor ways of coping with stress that can worsen the impact of stress on your health.

 Another way of managing stress is through learning more about it.  Learning that a garter snake is not a dangerous, poisonous reptile that demands a panicked response is one example.  It also applies on a more-general level.  The “four A’s” of learning about stress are:

  • Avoid the stressor. Learn your limits and stick to them. Learn the people and situations that cause you stress and find alternatives.  Learn what changes you can make to reduce the stress you inflict on yourself.
  • Alter the stressor. If you can’t avoid the stressor, learn how to alter it.  It may mean expressing your feelings instead of repressing them or learning to better compromise to the situation.  It may mean learning better time-management or organizing strategies.
  • Adapt to the stressor. If you can’t avoid or alter the stressor, you may need to adapt to it.  Learn to change yourself instead of the immovable situation.  Is the situation truly worth getting stressed about?  Are there positive aspects you haven’t focused on?
  • Accept the stressor. Finally, there are sources of stress you can’t avoid, you can’t change, and you can’t adapt to.  Learn not to try to control the uncontrollable.  Learn to forgive the slings and arrows of outrageous fortune. 

 Management of stress has no magic wands.  No pill or simple treatment eliminates stress.  If the stressor is there, your body is going to react to it just like a life-or-death situation.  The stress response cannot be shut off completely.  Management is a multi-pronged approach, involving sound nutrition, regular physical activity, psychological support and medical interventions to balance hormones and neurotransmitters. 

 Another reality of stress management is that it is a long-term project.  You will have set backs.  No single setback is going to cause a heart attack or a sudden tumor.  Don’t be discouraged when you feel stressed.  Even the experts have trouble.  Sapolsky himself says: “The reality is that I’m unbelievably stressed and Type-A and poorly-coping.  Why else would I study this stuff eighty hours a week?”


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Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105.

Leutwyler K. Stress Management Tips from the Serengeti. Scientific American. 2001 Feb 20. 284(2)

National Alliance on Mental Illness, Mental Health In the Workplace. The High Costs of Cutting Mental Health. 2010 (Jan).

National Geographic Television & Stanford University. Stress; Portrait of a Killer. Web resource at Accessed on 5/4/2010