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A Brief Primer on the Biology of Stress and How CBT Can Help
by Monica A. Frank, Ph.D.

"...instill hope by providing you with the knowledge that you have the resources within you to control the damaging effects of stress."
Almost six decades ago, Hans Selye first described his comprehensive theory of the General Adaptation Syndrome (GAS) based on research from the prior two decades showing the effect of stress on disease (Selye, 1955). Stress is such a ubiquitous term these days that most people think they know what it means. However, the common meaning may lead to a misunderstanding of the stress reaction.

The term stress has unfortunately become commonly associated with just psychological stress and many people don't realize that Selye's work was primarily based upon physical stress or what he called “noxious agents.” He showed that our bodies react fairly consistently to stress (both physical and psychological) in three progressive stages as described by his GAS theory (Selye, 1974):

1) Alarm reaction.
The initial stage of stress occurs when the individual is surprised by a new stress event (stressor). During this stage the body reacts by preparing itself to confront the stressor. The symptoms experienced can include increased heart rate, breathing and blood pressure, muscle tension, gastrointestinal distress (stomach upset), and visual changes as well as other physical reactions.

2) Resistance.
During the resistance stage of stress, the individual focuses on coping with the stressor. The exact nature of coping can vary from person to person. However, if the coping is effective, the body returns to its normal state. If the coping is ineffective, or if the stressor continues beyond the person's ability to cope, the individual may experience the final stage of exhaustion.

3) Exhaustion.
The exhaustion stage is when the body depletes all of its energy reserves and the body can no longer resist the effects of stress. During this stage the individual is likely to experience more severe symptoms including physical or psychological illness.

Background Concepts to Understand

1) Stressor.
A stressor is any event that is perceived as a threat to the body. Therefore, a stressor can be daily hassles or it can be a major trauma or tragedy. An occasional daily hassle such as unexpected car repair may not stress the system as much as the loss of a job. However, numerous daily hassles over a prolonged period of time can potentially trigger a stress reaction (DeLongis, 1982).

Even if a stressor is not a physical threat, it can still be thought of as an assault to the body. For instance, many people are surprised at the aftermath of surgery. After their surgeon has told them that they are healed, they wonder why they are still feeling fatigued, lethargic, even depressed. It is because their body has been assaulted by the surgery and it takes time to recover not just physically but from the exhaustion stage of the GAS. If there is other ongoing stress, the body may not have much opportunity to recover because it is continuing to react to the stressors.

Stressors can be psychological threats as well. If your boss places you on probationary status due to dissatisfaction with your work, you are likely to experience a psychological threat. This threat creates a stress reaction which may even have the effect of making it more difficult to address the work problems. However, psychological threats can be reduced by changing the perception of threat as discussed later in this article.

2) Optimal level.
Biological and psychological sciences have shown that in many instances an “optimal level” of brain chemistry exists. It is necessary to understand this concept to fully comprehend how the chemicals in your system interact in response to stress. Optimal level refers to the concept that too much or too little is likely to lead to deterioration or impairment. In other words, there is a balance that is necessary to maintain. Therefore, we can't say that a particular chemical in the body is good or bad because the true story involves maintaining the appropriate balance of the chemical for “optimal” or best functioning.

3) Homeostasis.
The internal process of balancing the body's chemistry is referred to as “homeostasis.” Think of it as similar to a thermostat to maintain a temperature of 72 degrees in a building. When the temperature measures below 72 degrees the air conditioning is activated and when it is above 72 the furnace is activated. Thus, the temperature is maintained in a balanced or homeostatic state. Many systems in the body also function in this way so the body tries to maintain a state of homeostasis.

4) Hypothalamic-pituitary-adrenal (HPA) axis disruption.
The primary structures of the brain that are involved in the stress response are the hypothalamus, the pituitary, and the adrenal gland. The adrenal gland may be somewhat familiar to many people because it is the source of adrenaline. The HPA axis is activated during the stress response through a complex interaction and release of various hormones and chemicals in the body. The purpose of the activation of the HPA axis is to maintain the body's homeostasis. A disruption to this process results in the experience of the physical and psychological symptoms of stress.

What Happens Biologically to the Body During the GAS Stages?

1) Biology of the alarm reaction.
When an individual encounters a stressful event, the body reacts by preparing to confront what it perceives as a physical threat. This preparation involves enhancing systems of the body that help in reacting to the stress and reducing focus on unnecessary systems of the body. For instance, systems that supply energy are important for coping with the stressor whereas systems that consume energy but are not needed immediately, such as digestion, are curtailed.

The glucose (sugar) in the bloodstream is used to provide the necessary energy to confront the threat. Endorphins, which are natural pain-relievers similar to morphine, are released to prepare for potential injury to the body. The release of these chemicals is triggered by a complex message process initiated by the hypothalamus sent through the pituitary to the adrenal gland.

Message Process sent Chemically to Maintain Homeostasis:*
Hypothalamus: “Hey, we're under attack! Something needs to be done!” Also, releases endorphins.
Pituitary: “Okay, I'll let the adrenal gland know. And I'll release some endorphins, too.”
Adrenal Gland: “Got it! Releasing epinephrine (adrenaline) and norepinephrine.”
Hypothalamus: “Great! That's enough. I'll let you know if we need more.”
Pituitary: “Stop the release for now.”
Adrenal Gland: “Okay.”

2) Biology of resistance.
During the stage of resistance, the primary focus is using the energy reserves to confront the stressful event because the glucose has been depleted. As short as a few hours, the energy stores (glucose created from glycogen) may also be depleted but the body still demands energy to confront the threat. In the body's search for additional energy, it stimulates the release of cortisol. The release of cortisol (often referred to as the “stress hormone”) is initiated by the hypothalamus sent through the pituitary causing the release of cortisol through the adrenal gland. Under normal conditions, the rise in cortisol sends a message back to the hypothalamus.

Message Process sent Chemically to Resist Stress:*
Hypothalamus: “We're still under attack! We need more energy!”
Pituitary: “Okay, I'll let the adrenal gland know. I'll release more endorphins.”
Adrenal Gland: “Got it! Releasing cortisol now.” Also, releases epinephrine (adrenaline) and norepinephrine.
Hypothalamus: “Great! That's enough. I'll let you know if we need more.”
Pituitary: “Stop the release of cortisol for now.”
Adrenal Gland: “Okay.”

The release of cortisol causes several reactions. Most importantly, it stimulates a process to create more energy. In addition, cortisol is an anti-inflammatory. Many people are familiar with the synthetic corticosteroids which are strong anti-inflammatory (steroidal) drugs prescribed for joint pain, skin conditions, allergies, asthma and many other medical problems. Think of cortisol as a natural anti-inflammatory steroid produced by the body to aid in healing (Sears, 2011).

3) Biology of exhaustion.
Eventually, however, the body uses all its alternative sources of energy. The “exhaustion” phase of the GAS refers to the body having exhausted all of its sources of energy. However, if the stress event is not resolved, the body may need to reduce its maintenance of the various systems of the body to conserve energy. This is why one of the primary effects of prolonged stress is extreme fatigue.

However, the body keeps requesting other energy sources. Unfortunately, just as steroid prescription medication (cortisone) can cause serious side effects if used too frequently for too long or in high doses, natural cortisol can also create problems if too much is released over a long period of time. In this case, a disruption to the homeostatic process occurs.

Message Process When Homeostasis is Disrupted:
Hypothalamus: “Can't stop! We are still under attack!”
Pituitary: “I'll let the adrenal gland know.”
Adrenal Gland: “Releasing more cortisol. But I got to warn you that this can cause other problems.”
Hypothalamus: “I don't care! We need to deal with the most immediate threat. Then we will deal with the others.”
Pituitary: “Release more cortisol.”
Adrenal Gland: “Releasing. I still don't think it is a good idea.”

*Please forgive the artistic license. Obviously, this is a very over-simplified explanation of a complex process.

The HPA axis can be disrupted whether too much cortisol or too little cortisol is released (Smith and Vale, 2006). Unfortunately, this can lead to a chronic cycle that can have devastating effects on the body including psychological illness (anxiety, depression, sleep disturbances/fatigue, addiction), metabolic diseases such as diabetes, cardiovascular disease/high blood pressure, and auto-immune diseases.

For a full description of this process, see Seeward (2006).

What is the Effect of this Process in the Short-Term and in the Long-Term?

In the short-term, the process initiated by the HPA axis is a positive one. It prepares the body to respond to a threat. To do this, it needs to activate certain systems of the body and it needs to curtail unnecessary systems so that most of the body's energy is focused on responding to the stressful event. The primary ways that it affects the body systems are as follows (Bowirrat et al., 2010; Buckingham, 2007; Saladin, 2011):

1) The body's defense system.
As explained above, the body has a natural anti-inflammatory response to threat. The purpose of this response is to prepare the body for possible physical injury. The body's “fight or flight” response to a threat is the same whether the threat is physical or psychological. Therefore, the body prepares for injury by releasing anti-inflammatory agents that fight pain, swelling, soreness, redness, and inability to function.

However, prolonged stress and release of the cortisol can have damaging effects on the immune system. In particular, the immune system can become suppressed which leads to less ability to fight off infections. Years of stress without treatment can lead to the development of auto-immune diseases such as lupus, fibromyalgia, rheumatoid arthritis, thyroid dysfunction, skin disorders, and multiple sclerosis among many others (NIH, 2012).

2) The metabolic system.
The initial response to a stress event is to draw on the body's stored energy. The body requires energy to respond to the threat by either fighting or running away both of which require a great deal of energy. Again, remember the body doesn't distinguish between a physical threat and a psychological one (unless you teach it—which we will discuss later).

Initially, the body uses glycogen which are the sugar (carbohydrate) stores. However, as soon as a few hours these stores may be depleted. This is the reason why some diabetics will have instability of blood sugars under stress. Under long-term stress this system can become deregulated and lead to metabolic disorders such as Type II diabetes and obesity which can contribute to a host of other problems.

3) The musculoskeletal system.
If the stress event continues once the available glucose and glycogen are depleted, the body turns to protein synthesis for additional energy. Initially, this increases energy and helps the body to respond to the threat.

However, normally this process of protein synthesis which occurs in the bone cells is meant to help with the building of muscle, not for prolonged response to stress. As a result, if the energy from protein synthesis is diverted over time to reacting to stress, it can have long-term consequences to the muscles and bone including osteoporosis as well as damage to the muscles and connective tissue (cartilage and tendons).

4) The central nervous system (CNS).
The initial release of the stress hormones has the effect of increasing the ability of the brain to function. Memory is enhanced and the ability to make quick decisions is increased. Again, this is for the purpose of preparing the body to react to the threat.

However, over time the prolonged release of the chemicals during the stress reaction and the depletion of the energy stores can have a devastating effect on the central nervous system. One of the primary symptoms that individuals complain about in the exhaustion stage of the GAS is the over-whelming fatigue. This symptom makes a great deal of sense when you understand that the body has depleted its energy stores and that it takes time to replenish those stores. However, some of the other symptoms experienced may interfere with the replenishment of those stores. For instance, the extreme fatigue may affect appetite so that someone is not ingesting enough calories to restore their energy.

Other effects of long-term stress to the CNS can be mood changes (depression and/or anxiety), impaired memory, confusion, and problems making decisions. Years of long-term impact to the CNS can even contribute to the development of brain disorders such as dementias (i.e. Alzheimers among others) and movement disorders such as Parkinson's disease.

5) The cardiovascular system.
When the body first responds to threat, it increases the retention of salt and water. Again, this is in preparation for a physical threat in which the body may have to respond with intense physical activity. The retention of salt and water is to prepare for the potential loss of fluids through sweating or bleeding.

However, the impact of salt and water retention can lead to increased salt craving and ingestion of more fluids. Prolonged retention of salt and water at high levels can lead to increased blood pressure and contribute to heart disease.

6) The reproductive system.
So as to manage the limited amount of energy available when confronting a stressful event, the body reduces the functioning of unnecessary systems. One of these systems is the reproductive system. Energy does not need to be expended on sexual activity or the production of the sex hormones while the body is under immediate threat. Therefore, the libido decreases and even the cessation of the menstrual cycle may occur so that the energy involved in these processes can be diverted to the threat.

However, prolonged threat can lead to a suppression of the sex hormones over a period of time. When this occurs, sexual dysfunction such as impotence and even infertility can result.

7) The gastrointestinal system.
Another system that is considered unnecessary is the digestive system. In particular, the production of bicarbonate and mucus which protects the lining of the stomach is reduced to conserve the body's energy. The immediate impact is the experience of stomach upset when confronted with a stressor.

However, the long-term impact of reducing the production of these contributors to the digestive process is much more serious. In particular, the individual may experience increased susceptibility to stomach problems such as ulcers, colitis, gastroesophageal reflux disease (GERD), and irritable bowel syndrome.

8) Systemic deterioration.
Perhaps, however, the most serious consequence of a prolonged stress reaction is the disruption to all these systems leading to failure of the body to respond adequately to future stress. Even if the individual is no longer experiencing a direct threat, the body perceives the impact to all these systems as a threat.

In other words, the reaction to stress itself becomes a stressor that triggers the GAS. Even if no further external stress is impacting the individual, without some sort of intervention to re-balance the system, the body continues in this cycle with ongoing systemic deterioration.

What Can Be Done to Stop This Damaging Reaction to Stress?

The above information is not meant to discourage you. Instead, it is meant to help you understand the complexities of not only the stress reaction but the different methods that can be used to manage the reaction. In fact, it is my intention to instill hope by providing you with the knowledge that you have the resources within you to control the damaging effects of stress. By using these more natural methods, over time you can develop a much more balanced approach to stress that can be more effective than medication without the unwanted side effects.

1) Reduce perceived threat.
As you may have gathered from the above description of the GAS, for the stress reaction to occur the body must perceive the event as a threat. The good news is that you have a great deal of control over this process. However, it may take some effort to change your body's perception and reaction.

The “fight or flight” response was developed when our bodies needed to react to very real external physical threats. For instance, in distant human history, when a cave man was confronted by a saber tooth tiger, he needed to respond quickly by either fighting the tiger or fleeing. However, in today's technological age, many of our stressors are not of the external physical type. Many of our stressors are due to psychological threat which involves the perception of an event.

For instance, if you have the all-too-common unfortunate event of having to deal with the customer service department of a major corporation, you may experience frustration and stress during this process. However, such stress stems from your perception of the event. If you view the interaction with customer service as deliberately annoying (making you talk to a computer, putting you on hold, friendliness but not helpfulness) and calculated to cause you to give up you are more likely to perceive the situation as a threat. In particular, the threat you perceive is someone barring your way to something you need.

Changing the way you perceive the situation can change the amount of stress you experience. For example, when I was recently confronted with this type of situation regarding refused warranty repair of my granddaughter's computer, I used it as a teaching opportunity for my granddaughter. I explained to her the process we would take to obtain the repair under warranty including how we would file a claim in small claims court. Instead of being upset about the computer, my granddaughter was very excited about learning how small claims court worked. In this way, the corporate hurdles of customer service were not seen as a threat but as steps we documented to provide in our claim. For myself, I was able to view the time as productive because I was teaching my granddaughter an important life lesson.

However, even more serious psychological threats such as being placed on probationary job status with a demand that your work improve or you will be terminated can be managed with changing the perception of threat. In fact, with such an event it is very important to change this perception or you are less likely to change the work situation. To change your perception of such a threat, you could determine if it is possible to comply with the expectations of your boss. If you determine that it is possible, then the threat diminishes because you have a way to solve the problem. However, if you determine that it is not possible then you could look for other solutions such as looking for another job. The belief that you can find another job also changes your perception of the threat.

The process of cognitive therapy aids in changing perception of threat. By identifying the type of thinking involved in your response, you can develop other ways to think about the situation which will change the perception. Sometimes, if you have certain automatic ways of thinking, you may need input from others to give you ideas of how you can think differently about a situation. If you work at changing your automatic perceptions you will develop a different initial response to many common events. In this case, the stress reaction described by the GAS doesn't even get activated.

Certainly, this may not be possible if actual physical threat occurs because your body will respond automatically. For instance, if you are physically assaulted on the street or if you have surgery or illness, your body will automatically respond with the GAS reaction. In this case, changing perception may not be possible or may only help to a limited degree.

However, with enough training and practice, even physical assault to the body can be perceived differently. For example, in my karate training, a very important part of self-defense was psychological preparation so that we could respond to an attack more effectively. This meant reducing our perception of threat. Yet, it did not mean eliminating the perception of threat because when under physical attack we need the activation of the autonomic nervous system that occurs during the GAS because it prepares our body to respond. However, we don't want to use up our energy stores too soon, so by reducing the perception of threat we are able to think more clearly and react more quickly.

2) Proper nutrition.
During prolonged stress we need to replenish our energy reserves. The best way to do this is through proper nutrition. Too often when people are stressed they either experience decreased appetite due to the curtailing the digestive system or they experience sugar, salt, and fat cravings as quick, simple ways to provide the body with energy. Both of these scenarios are problematic because they do not adequately address the nutritional needs to help re-build the energy stores.

To re-build the glycogen stores, it is necessary to consume adequate amounts of complex carbohydrates (whole grains, beans, vegetables). To re-build the stores required for protein synthesis it is necessary to consume proteins (meat, cheese, milk, nuts, beans). By paying attention to your body's nutritional needs during stress, you are less likely to experience the adverse consequences of long-term stress.

3) Using mindfulness and relaxation techniques.
Once the stress reaction has occurred and on-going stress is experienced, methods to reduce the excessive release of cortisol are necessary. By reducing the release of cortisol, the system can become balanced again and react more normally. This is the goal of anti-depressants. However, it is possible to achieve this goal more efficiently and without side effects with the more natural methods of relaxation and mindfulness.

Herbert Benson (who coined the term “relaxation response”) and colleagues have been researching the biology of relaxation. Although not as much is understood about the biology of the relaxation response as is known about the stress reaction, they are showing that a chemical process occurs in the body to reverse the effects of stress and produce relaxation (Bhasin, et al., 2013).

Research has shown that as little as eight weeks of training with the mindfulness and relaxation methods can reduce the secretion of cortisol (Jensen et al., 2012). Methods such as Qi Gong, Tai Chi, and yoga have been found to reduce the inflammation of stress and reduce cortisol which was not shown to occur with aerobic exercise (Lavretsky, 2013). For more information, read: Why Are Meditative Relaxation and Mindfulness Important?

Although an immediate course of mindfulness or relaxation training can assist with reducing cortisol and balancing the system, it is best to practice these tools consistently. Similar to exercise, these methods help most by being a lifestyle practice—not just something to use when stressed. The more you make it a part of your lifestyle, the more skilled you will be with the methods, and the more effective the methods will be.

For more assistance, read: Too Stressed to Relax?


Bhasin, M.K., Dusek, J.A, Chang, B., Joseph, M.G., Denninger, J.W., Fricchione, G.L., Benson, H. and Libermann, T.A. (2013). Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways, PLOS ONE, 8, www.plosone.org, e62817

Bowirrat, A., Chen, T.J.H., Blum, K., Madigan, M., Bailey, J.A., Chen, A.L.C., Downs, B.W., Braverman, E.R., Radi, S., Waite, R.L., Kerner, M., Giordano, J., Morse, S., Oscar-Berman, M. and Gold, M. (2010). Neuro-psychopharmacogenetics and Neurological Antecedents of Posttraumatic Stress Disorder: Unlocking the Mysteries of Resilience and Vulnerability. Current Neuropharmacology, 8, 335-358.

Buckingham, J.C. (2007). Glucocorticoids, Role in Stress. In Stress Science: Neuroendocrinology edited by Fink, G. Elsevier, San Diego, CA.

DeLongis, A., Coyne, J. C., Dakof, G., Folkman, S., & Lazarus,R. S. (1982). Relationship of daily hassles, uplifts, andmajor life events to health status. Health Psychology, 1, 119–136. doi: 10.1037/0278-6133.1.2.119

Jensen, C.G., Vangkilde, S., Frokjaer, V. and Hasselbalch, S.G. (2012). Mindfulness Training Affects Attention—Or Is It Attentional Effort? Journal of Experimental Psychology: General, 141, 106-123. DOI: 10.1037/a0024931.

Lavretsky, H. (2013). Mindful Exercises and Meditation: Neurobiological Effects. Psychiatric News,

NIH (2012). Understanding Autoimmune Diseases. National Institute of Arthritis, Musculoskeletal and Skin Diseases.

Sears, B. (2011) The differences between cortisol and cortisone?

Seaward, B.L. (2006). Physiology of Stress (Chapter 2). In Managing Stress: Principles and Strategies for Health and Wellbeing. Jones and Bartlett Publishers, Canada.

Saladin, K.S. (2011). Anatomy and Physiology, 6th Ed. McGraw-Hill, New York.

Selye, H. (1955). Stress and disease. Science, 122, 625-631.

Selye, H. (1974). Stress without distress. Signet, New York.

Smith, S.M. and Vale, W.W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in Clinical Neuroscience, 8, 383-395. HPA axis is activated in response to positive and negative states of energy balance.


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Dr. Monica Frank

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