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What Is Stress?

Your Body's Response to a Situation That Requires Attention or Action

Elizabeth Scott, PhD is an author, workshop leader, educator, and award-winning blogger on stress management, positive psychology, relationships, and emotional wellbeing.

• Identifying
• Next in How Stress Impacts Your Health Guide How to Recognize Burnout Symptoms

Stress can be defined as any type of change that causes physical , emotional, or psychological strain. Stress is your body's response to anything that requires attention or action. 

Everyone experiences stress to some degree. The way you respond to stress, however, makes a big difference to your overall well-being.

Verywell / Brianna Gilmartin

Sometimes, the best way to manage your stress involves changing your situation. At other times, the best strategy involves changing the way you respond to the situation.

Developing a clear understanding of how stress impacts your physical and mental health is important. It's also important to recognize how your mental and physical health affects your stress level.

Watch Now: 5 Ways Stress Can Cause Weight Gain

Signs of stress.

Stress can be short-term or long-term. Both can lead to a variety of symptoms, but chronic stress can take a serious toll on the body over time and have long-lasting health effects.

Some common signs of stress include:

• Changes in mood
• Clammy or sweaty palms
• Decreased sex drive
• Difficulty sleeping
• Digestive problems
• Feeling anxious
• Frequent sickness
• Grinding teeth
• Muscle tension, especially in the neck and shoulders
• Physical aches and pains
• Racing heartbeat

Identifying Stress

What does stress feel like? What does stress feel like? It often contributes to irritability, fear, overwork, and frustration. You may feel physically exhausted, worn out, and unable to cope.

Stress is not always easy to recognize, but there are some ways to identify some signs that you might be experiencing too much pressure. Sometimes stress can come from an obvious source, but sometimes even small daily stresses from work, school, family, and friends can take a toll on your mind and body.

If you think stress might be affecting you, there are a few things you can watch for:

• Psychological signs such as difficulty concentrating, worrying, anxiety, and trouble remembering
• Emotional signs such as being angry, irritated, moody, or frustrated
• Physical signs such as high blood pressure, changes in weight, frequent colds or infections, and changes in the menstrual cycle and libido
• Behavioral signs such as poor self-care, not having time for the things you enjoy, or relying on drugs and alcohol to cope

Stress vs. Anxiety

Stress can sometimes be mistaken for anxiety, and experiencing a great deal of stress can contribute to feelings of anxiety. Experiencing anxiety can make it more difficult to cope with stress and may contribute to other health issues, including increased depression, susceptibility to illness, and digestive problems.

Stress and anxiety contribute to nervousness, poor sleep, high blood pressure , muscle tension, and excess worry. In most cases, stress is caused by external events, while anxiety is caused by your internal reaction to stress. Stress may go away once the threat or the situation resolves, whereas anxiety may persist even after the original stressor is gone.

Causes of Stress

There are many different things in life that can cause stress. Some of the main sources of stress include work, finances, relationships, parenting, and day-to-day inconveniences.

Stress can trigger the body’s response to a perceived threat or danger, known as the fight-or-flight response .   During this reaction, certain hormones like adrenaline and cortisol are released. This speeds the heart rate, slows digestion, shunts blood flow to major muscle groups, and changes various other autonomic nervous functions, giving the body a burst of energy and strength.

Originally named for its ability to enable us to physically fight or run away when faced with danger, the fight-or-flight response is now activated in situations where neither response is appropriate—like in traffic or during a stressful day at work.

When the perceived threat is gone, systems are designed to return to normal function via the relaxation response .   But in cases of chronic stress, the relaxation response doesn't occur often enough, and being in a near-constant state of fight-or-flight can cause damage to the body.

Stress can also lead to some unhealthy habits that have a negative impact on your health. For example, many people cope with stress by eating too much or by smoking. These unhealthy habits damage the body and create bigger problems in the long-term.  

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Types of Stress

Not all types of stress are harmful or even negative. Some of the different types of stress that you might experience include:

• Acute stress : Acute stress is a very short-term type of stress that can either be positive or more distressing; this is the type of stress we most often encounter in day-to-day life.
• Chronic stress : Chronic stress is stress that seems never-ending and inescapable, like the stress of a bad marriage or an extremely taxing job; chronic stress can also stem from traumatic experiences and childhood trauma.
• Episodic acute stress : Episodic acute stress is acute stress that seems to run rampant and be a way of life, creating a life of ongoing distress.
• Eustress : Eustress is fun and exciting. It's known as a positive type of stress that can keep you energized. It's associated with surges of adrenaline, such as when you are skiing or racing to meet a deadline. 

4 Main Types of Stress:

The main harmful types of stress are acute stress, chronic stress, and episodic acute stress. Acute stress is usually brief, chronic stress is prolonged, and episodic acute stress is short-term but frequent. Positive stress, known as eustress, can be fun and exciting, but it can also take a toll.

Impact of Stress

Stress can have several effects on your health and well-being. It can make it more challenging to deal with life's daily hassles, affect your interpersonal relationships, and have detrimental effects on your health. The connection between your mind and body is apparent when you examine stress's impact on your life.

Feeling stressed over a relationship, money, or living situation can create physical health issues. The inverse is also true. Health problems, whether you're dealing with high blood pressure or diabetes , will also affect your stress level and mental health. When your brain experiences high degrees of stress , your body reacts accordingly.

Serious acute stress, like being involved in a natural disaster or getting into a verbal altercation, can trigger heart attacks, arrhythmias, and even sudden death. However, this happens mostly in individuals who already have heart disease.

Stress also takes an emotional toll. While some stress may produce feelings of mild anxiety or frustration, prolonged stress can also lead to burnout , anxiety disorders , and depression.

Chronic stress can have a serious impact on your health as well. If you experience chronic stress, your autonomic nervous system will be overactive, which is likely to damage your body.

Stress-Influenced Conditions

• Heart disease
• Hyperthyroidism
• Sexual dysfunction
• Tooth and gum disease

Treatments for Stress

Stress is not a distinct medical diagnosis and there is no single, specific treatment for it. Treatment for stress focuses on changing the situation, developing stress coping skills , implementing relaxation techniques, and treating symptoms or conditions that may have been caused by chronic stress.

Some interventions that may be helpful include therapy, medication, and complementary and alternative medicine (CAM).

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Psychotherapy

Some forms of therapy that may be particularly helpful in addressing symptoms of stress including cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) . CBT focuses on helping people identify and change negative thinking patterns, while MBSR utilizes meditation and mindfulness to help reduce stress levels.

Medication may sometimes be prescribed to address some specific symptoms that are related to stress. Such medications may include sleep aids, antacids, antidepressants, and anti-anxiety medications.

Complementary and Alternative Medicine

Some complementary approaches that may also be helpful for reducing stress include acupuncture, aromatherapy, massage, yoga, and meditation .

Coping With Stress

Although stress is inevitable, it can be manageable. When you understand the toll it takes on you and the steps to combat stress, you can take charge of your health and reduce the impact stress has on your life.

• Learn to recognize the signs of burnout. High levels of stress may place you at a high risk of burnout. Burnout can leave you feeling exhausted and apathetic about your job.   When you start to feel symptoms of emotional exhaustion, it's a sign that you need to find a way to get a handle on your stress.
• Try to get regular exercise. Physical activity has a big impact on your brain and your body . Whether you enjoy Tai Chi or you want to begin jogging, exercise reduces stress and improves many symptoms associated with mental illness.  
• Take care of yourself. Incorporating regular self-care activities into your daily life is essential to stress management. Learn how to take care of your mind, body, and spirit and discover how to equip yourself to live your best life.  
• Practice mindfulness in your life. Mindfulness isn't just something you practice for 10 minutes each day. It can also be a way of life. Discover how to live more mindfully throughout your day so you can become more awake and conscious throughout your life.  

If you or a loved one are struggling with stress, contact the  Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline  at 1-800-662-4357 for information on support and treatment facilities in your area.

For more mental health resources, see our  National Helpline Database .

Cleveland Clinic. Stress .

National institute of Mental Health. I'm so stressed out! Fact sheet .

Goldstein DS. Adrenal responses to stress .  Cell Mol Neurobiol . 2010;30(8):1433–1440. doi:10.1007/s10571-010-9606-9

Stahl JE, Dossett ML, LaJoie AS, et al. Relaxation response and resiliency training and its effect on healthcare resource utilization [published correction appears in PLoS One . 2017 Feb 21;12 (2):e0172874].  PLoS One . 2015;10(10):e0140212. doi:10.1371/journal.pone.0140212

American Heart Association. Stress and Heart Health.

Chi JS, Kloner RA. Stress and myocardial infarction .  Heart . 2003;89(5):475–476. doi:10.1136/heart.89.5.475

Salvagioni DAJ, Melanda FN, Mesas AE, González AD, Gabani FL, Andrade SM. Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies .  PLoS One . 2017;12(10):e0185781. Published 2017 Oct 4. doi:10.1371/journal.pone.0185781

Bitonte RA, DeSanto DJ 2nd. Mandatory physical exercise for the prevention of mental illness in medical students .  Ment Illn . 2014;6(2):5549. doi:10.4081/mi.2014.5549

Ayala EE, Winseman JS, Johnsen RD, Mason HRC. U.S. medical students who engage in self-care report less stress and higher quality of life .  BMC Med Educ . 2018;18(1):189. doi:10.1186/s12909-018-1296-x

Richards KC, Campenni CE, Muse-Burke JL. Self-care and well-being in mental health professionals: The mediating effects of self-awareness and mindfulness .  J Ment Health Couns . 2010;32(3):247. doi:10.17744/mehc.32.3.0n31v88304423806.

American Psychological Association. 2015 Stress in America .

Krantz DS, Whittaker KS, Sheps DS.  Psychosocial risk factors for coronary heart disease: Pathophysiologic mechanisms .  In R. Allan & J. Fisher,  Heart and mind: The practice of cardiac psychology. American Psychological Association; 2011:91-113. doi:10.1037/13086-004

By Elizabeth Scott, PhD Elizabeth Scott, PhD is an author, workshop leader, educator, and award-winning blogger on stress management, positive psychology, relationships, and emotional wellbeing.

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• Stress management

Stress symptoms: Effects on your body and behavior

Stress symptoms may be affecting your health, even though you might not know it. You may blame sickness for that annoying headache, your sleeping troubles, feeling unwell or your lack of focus at work. But stress may really be the cause.

Common effects of stress

Stress symptoms can affect your body, your thoughts and feelings, and your behavior. Knowing common stress symptoms can help you manage them. Stress that's not dealt with can lead to many health problems, such as high blood pressure, heart disease, stroke, obesity and diabetes.

Act to manage stress

If you have stress symptoms, taking steps to manage your stress can have many health benefits. Check out many possible stress management tips. For example:

• Get regular physical activity on most days of the week.
• Practice relaxation techniques. Try deep breathing, meditation, yoga, tai chi or massage.
• Keep a sense of humor.
• Spend time with family and friends.
• Set aside time for hobbies. Read a book, listen to music or go for a walk. Schedule time for your passions.
• Write in a journal.
• Get enough sleep.
• Eat a healthy, balanced diet.
• Stay away from tobacco and alcohol use, and use of illegal substances.

Aim to find active ways to manage your stress. Idle ways to manage stress that don't get you moving may seem relaxing. But they may make your stress go up over time. Examples are watching television, going on the internet or playing video games.

When to ask for help

If you're not sure if stress is the cause, or if you've taken steps to control your stress but you keep having symptoms, see your health care provider. Your health care provider may want to check for other potential causes. Or think about seeing a counselor or therapist, who can help you find the sources of your stress and learn new coping tools. And if you are concerned about harming yourself, call 911 or a suicide hotline.

Also, get emergency help right away if you have chest pain, especially if you also have shortness of breath; jaw, back, shoulder or arm pain; sweating; dizziness; or nausea. These may be warning signs of a heart attack and not simply stress symptoms.

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• How stress affects your health. American Psychological Association. https://www.apa.org/helpcenter/stress. Accessed Jan. 25, 2023.
• Stress and your health. U.S. Department of Health and Human Services. https://www.womenshealth.gov/mental-health/good-mental-health/stress-and-your-health. Accessed Jan. 24, 2023.
• Manage stress. Healthfinder.gov. http://healthfinder.gov/healthtopics/population/men/mental-health-and-relationships/manage-stress. Accessed Jan. 25, 2023.
• Warning signs of a heart attack. American Heart Association. https://www.heart.org/en/health-topics/heart-attack/warning-signs-of-a-heart-attack#.VsZCDtj2bIU. Accessed Jan. 25, 2023.
• Seaward BL. Essentials of Managing Stress. 5th ed. Jones & Bartlett Learning; 2021.
• Creagan ET (expert opinion). Mayo Clinic. Feb. 14, 2023.

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Effects of Stress on Human Health

Introduction, stress and health.

Stress has an adverse effect on human health; it leads to numerous health complications if not effectively managed. When stressed, people risk suffering from stress-related complications. According to Ciccarelli & White, 2012, health can broadly be divided as physical health (free of diseases) and psychological health (being able to make sound decisions).

When under stress, an individual’s decision making capacity is hampered making the person psychologically unhealthy (Ciccarelli & White, 2012). This paper discusses the relationship between stress and human health.

There are numerous theories and researches on stress and health, they all agree that stress has an adverse effect on human health; the statement goes “a stressed man is an unhealthy man”. Although human life cannot be free of stress, it becomes unmanaged stress which causes havoc to human body and mind . According to psychologists, human body is “wired’’ to communicate with the state of the mind; the communication is meant to protect threats against predators and other aggressors.

The statements predators and other aggressors used to mean life threatening activities or actions which include meeting deadlines, fighting back, reacting to a certain situation, or making life challenging decisions. The challenge facing human kind is failing to understand the right way to manage stress; in most cases the activities they engage in lead to more stress (Ciccarelli & White, 2012).

When someone is stressed for a long period, he or she exposes his body to uncontrolled brain cortisol and other stress managing hormones, which in turn can result in health complications like eczema, obesity, depression, digestive problems, sleeping challenges, and heart diseases.

Human state of mind determines the kind of life decisions they make; in the event that someone is stressed, his or her mind will be hampered from making sound and reliable decision as their mind, soul, and body are not at peace with each other. Some day-to-day health feelings like fatigue, headaches, and boredom can be attributed to the state of the mind; state of the mind is unhealthy with stress.

Stress affects human body, thoughts and feelings, when the above have been affected, then the behaviors and to some extent the personality of an affected person change. When unchecked, stress results in health complications like high blood pressure, heart disease, obesity and diabetes (Ciccarelli & White, 2012).

According to Ciccarelli & White, 2012, the human body responds differently to stress; some people are likely to show fast heath deterioration when stressed while others are likely to have slowed health complications. What remain constant is that prolonged stress without proper management will have a negative effect on human health.

Stressed people need to enroll in stress management classes/lessons where they can be trained on basic methods of preventing and managing stress. In the event that an individual is suffering from a certain ailment, and then happens to be stressed, the recovery rate of such an individual is low. There is much connection between the rate of recovery from health complication and stress that the patient has (Ciccarelli & White, 2012).

Stress is a common occurrence in human beings; well-managed stress is of benefit to human beings as it assists when making decisions. However when stress is not managed effectively, it has an adverse effect on human health. Some complications related with ineffective stress management include depression, heart diseases, and diabetes.

Ciccarelli, S. K., & White, J. N. (2012). Psychology. New Jersey: Pearson Prentice Hall.

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Psychology Discussion

Essay on stress: it’s meaning, effects and coping with stress.

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Essay on Stress: It’s Meaning, Effects and Coping with Stress!

Stress is a very common problem being faced today. Every individual will experience stress in one or the other time.

The term stress has many definitions, Lazarus and Folkman (1984) have defined stress as “an internal state which can be caused by physical demands of body or by environmental and social situations, which are evaluated as potentially harmful, uncontrollable, or exceeding our resources for coping”.

According to David Fontana “stress is a demand made upon the adaptive capacities of the mind and body”.

These definitions indicate that stress represents those conditions under which individuals have demand made upon them, that they cannot physically or psychologically meet, leading to breakdown at one or other of these levels.

Stress is usually thought of in negative terms. But ii can manifest itself in both positive and negative way. It is said to be positive when the situation offers an opportunity for one, to gain something.

Eustress (the Greek word ‘eu’ means good) is the term used to describe positive stress. It is often viewed as motivator, since in its absence the individual lacks the spirit necessary for peak performance. Distress is the term used to indicate negative stress.

Almost any change in the environment- even a pleasant change such as a joyful trip- demands some coping, and a little stress is useful in helping us to adapt. But beyond some point, stress becomes a ‘distress’.

What acts to produce distress varies from person to person, but some events seem to be stressors for every person.

Examples of stressors are:

1. Injury or infections of the body, dangers in environment, major changes or transitions in life which force us to cope in new ways.

2. Physical stressors like noise, pollutions, climatic changes, etc.

3. Hustles of everyday life centering on work, family, social activities, health and finances.

4. Frustrations and conflicts.

The physical, environmental and social causes of the stress state are termed stressors. Once induced by stressors the internal stress state can then lead to various responses. On the other hand, psychological responses such as anxiety, hopelessness, depression, irritability, and a general feeling of not being able to cope with the world, can result from the stress state.

Stress cycles:

Stress has a number of immediate effects. If the stressors are maintained, long-term behavioural, physiological, emotional and cognitive effects occur. If these effects hinder adaptation to the environment or create discomfort and distress, they themselves become stressors and, tend to perpetuate a ‘cycle’ of distress.

Example, a patient spends more money on treatment, may experience continued stress even after the cure of the disease, because repayment of debt cause stress for long time in him or a patient whose leg is amputated after accident may continue to worry about it.

On the other hand, many people have developed ways of coping with stressors, so that they are able to respond adaptively. This is the ‘wellness cycle’. Teaching people adaptive ways of handling stress, so as to promote the wellness cycle is an important part of the newly emerging field of behavioural medicine.

Effects of stress:

Stress is not always harmful. In fact, it is recognised that low levels of stress can even helps for better performance. For example, a student can prepare well for forthcoming examination only if he has some stress. However, excess level of stress is undoubtedly harmful.

The effects of stress are divided into three categories:

a. Physiological effects:

Commonly appearing stress related bodily disorders are-peptic ulcers, hypertension, chronic fatigue, hormonal changes, increased heart rate, difficulty in breathing, numbness of limbs, heart disease and reduction in immunity, etc.

b. Psychological effects:

Anxiety, depression, hopelessness, helplessness, anger, nervousness, irritability, tension and boredom may be experienced.

c. Behavioural changes:

Decreasing efficiency, making mistakes, inability to take decisions, under eating or overeating, sleeplessness, increased smoking, develop addiction to alcohol and drugs, forgetfulness, hypersensitivity or passiveness, accident proneness and interpersonal difficulties are seen.

Stress is linked to disorders such as cancer and heart disorders. There are several mediating variables that determine whether stress becomes dangerous or not. For example, good coping mechanisms which can help to reduce stress, having good social support, often help in reducing stress.

Perception of stress or how a person views stress is also very important. For example, a person may not perceive a situation as stressful whereas the same situation may be perceived as highly stressful by some other person.

People with personality type ‘A’ are more prone to be affected by stress related disorders like cardiovascular diseases. Personality character like hardiness or emotional stability helps to withstand effects of stress.

Hans Selye, a renowned biological scientist defines stress as the nonspecific response of the body to any demand upon it. He termed the body’s response to stressors the “General Adaptation Syndrome” (GAS).

The GAS consists of 3 stages:

1. Alarm reaction:

It is an emergency response of the body. In this stage prompt responses of the body, many of them mediated by the sympathetic nervous system, prepare us to cope with the stressor here and now.

2. Stage of resistance:

If the stressor continues to be present, the stage of resistance begins, wherein the body resists the effects of the continuous stressor. During this stage certain hormonal responses of the body are an important line of defence in resisting the effects of stressors (For example, release of ACTH).

3. Stage of exhaustion:

In this stage, the body’s capacity to respond to both continuous and new stressors has been seriously compromised. The person will no longer be able to face stressor and he will finally succumb to it. The person may develop psychosomatic illness.

The stress leads to many psychosomatic diseases. Treatment for such diseases involves medical help for the physical problems and, at the same time, attention to the psychological factors producing the stress.

Coping with Stress :

There are different ways of coping with stress such as: confronting (facing), distancing (remoteness), self-control, seeking social support, accepting responsibility, escape or avoid (from the stressor), plan a problem solving strategy and positive reappraisal.

Usually two broad type of coping types are seen- Instrumental coping and Emotional coping.

In instrumental coping, a person focuses on the problem and tries to solve it. In emotional coping, the focus is more on the feelings generated by the problem.

Today, self- help remedies, Do to yourself approaches, weight loss clinics and diets, health foods and physical exercise are being given much attention in mass media. People are actually taking more responsibility to maintain good health.

However, some specific techniques to eliminate or to manage more effectively the inevitable, prolonged stress are as follows:

Good physical exercise like walking, jogging, swimming, riding bicycle, playing soft ball, tennis are necessary to cope with stress.

Relaxation:

Whether a person simply takes it easy once in a while or uses specific relaxation techniques such as bio-feedback, or meditation, the intent is to eliminate the immediately stressful situation or manage a prolonged stressful situation more effectively.

Taking it easy may mean curling up with a good book on an easy chair or watching some light programme on television or listening to a light music. Meditation is scientifically proved to be very useful, both physically and mentally to cope with stress.

Behavioural self-control:

By deliberately managing the antecedents and the consequence of their own behaviour, people can achieve self-control. Besides managing their own behaviour to reduce stress, people can also become more aware of their limits and of ‘red flags’ that signal trouble ahead. They can avoid people or situations that they know will put them under stress.

Maladaptive strategies, rigid strategies or relying on one type of coping method lead to increase in the stress. Social support helps reduce the effect of stress. People may provide help, advice, material support or moral support that helps to reduce stress.

In addition to the above, psychotherapy (Beck’s cognitive therapy, Ellis’s rational emotive therapy and Meichenbaum’s stress- inoculation training), skill training, environmental changes, Bio-feedback (control of physical signs such as Blood pressure, headache, etc), family therapy, group therapy, hypnosis, yoga, are found to be very useful. Finally, uses of drugs are some of the other strategies adopted in coping with stress.

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Why Stress Is Both Good and Bad

Five facts that might surprise you—plus advice on how to cope..

Posted January 20, 2016 | Reviewed by Jessica Schrader

• What Is Stress?
• Find a therapist to overcome stress

Stress. We use that word quite a bit. And for good reason.

The American Psychological Association’s Stress in America survey discovered that recent stress levels in the U.S. population are 4.9 on a 10-point scale, with 10 being the highest level of stress. The most common stress sources are money, work, the economy, family responsibilities, and health concerns.

But what exactly is stress? Why do we experience it?

Here are five interesting facts about stress that might surprise you.

1. Stress is good

Stress is actually useful. Without stress, we would not be here to talk about stress. If our hunter-gatherer ancestors did not experience some stress when that lion was roaming around their sleeping quarters, or when those red berries looked good but also emitted a strange odor, they would have been eaten or poisoned. Hence, our ancestors experienced stress and used it to their advantage so that they could procreate, allowing us to have this discussion today.

Even in modern society, stress is useful. If college students didn't experience any stress over tests, they probably wouldn't study or show up for class. If workers didn't experience stress about project deadlines, they might end up getting fired.

So, stress keeps us accountable for our actions. It motivates us and inspires us to be better citizens.

2. Stress is bad

Unfortunately, there are equally as many reasons why stress is bad. Whereas mild stressors—such as what to get your spouse for his or her birthday—are motivating, major stressors can be debilitating. For instance, caring for a loved one who has a chronic illness is a serious stressor. Chronic or major stressors are extremely taxing on the brain and the body, possibly leading to depression and other mental health consequences, as well as physical health issues.

3. Stress is contagious

Stress is intimately tied to our social world. Social stress, such as feelings of loneliness or isolation, takes a toll on the brain and body. These forms of stress can lead to depression, anxiety , and heart disease.

But stress does not have to affect us directly to change our brains. Stress can also be contagious. Many of the sources of stress in our daily lives may not be ours directly, but rather those of our loved ones, such as health problems affecting a loved one, family responsibilities, and relationship issues. These stressors also have mental and physical health consequences—for our loved ones and for us.

4. We can learn about stress from animals

Animals can teach us quite a bit about stress. For example, prairie voles are social rodents. Scientists use them to study how the social environment influences health, and how we can cope with stress. Like people, prairie voles live in family groups, raise offspring cooperatively (both parents together), and display many negative effects from changes in their social environment.

We have learned from these rodents that social stress can influence the way that the brain communicates with the body and lead to poor functioning of the heart, increasing the risk for heart disease. We also have learned that exercise can be a useful strategy for reducing the effects of social stress. In fact, my laboratory is currently using these rodents to understand how the brain changes in response to contagious stress (stay tuned for results in a future blog).

5. Stress is about perception

So this brings us back to the original question. What exactly is stress?

Stress is a perceived disconnect between a situation and our resources to deal with the situation. In other words, stress is a (real or imagined) threat that taxes our resources. The operative word here is perceived. Stress does not always arise from an actual threat; but if we perceive it to be a threat, then it's a threat.

Consider a ride on a roller coaster, for example. For one person, this is a fun and fantastic thrill. For another person, it’s a scary and stress-inducing event.

If we perceive something as stressful , our brains release hormones into the blood. These hormones change our behavior, mental experience, and physical functioning. If the threat is real, such as a lion that is about to eat us, these hormones will help save our lives, for instance by helping to deliver necessary oxygen to our legs so we can run.

If the threat is imagined, such as thinking about a potential traffic jam each morning that will make us late for work, these same hormones flow through our bloodstreams. Over time, these hormones use critical energy, causing a detriment to our body and leading to psychological and physical problems.

So what can we do to combat bad stress?

The fact that stress is a perception also means that we can do something about it. We can train ourselves (or we can be trained by a professional, if necessary) to change our perspective.

Remember that stress is a perceived disconnect between the situation and our resources to handle the situation. Therefore, there are two possible ways we can change our perspective about stress.

First, we might be able to change the situation. If traffic is a chronic source of stress, can we take the train to work?

Second, in situations that cannot be changed directly, we can possibly change the way we view the situation. If we have no other option but to drive to work, can we use that time to our advantage instead of dwelling on how slowly the traffic is moving?

Perhaps we can use the time to mentally plan the day, so that when we arrive to work we are ready to get started. Perhaps we can use the time to relax and listen to some music or an audiobook. Perhaps we can engage in some mild relaxation exercises before we leave the house, so that when we get in the car we are equipped to cope with the traffic.

Some stress might be inevitable. But its negative effects on the brain and body do not have to be inevitable.

By altering the way we interpret the world around us, we can gain control over stress. By changing our perception about a situation, we can even gain the power to see its benefits.

Angela Grippo is an associate professor of psychology at Northern Illinois University .

American Psychological Association (2014). Stress in America. http://www.apa.org/news/press/releases/stress/ .

Cacioppo S, Grippo AJ, London S, Goossens L, Cacioppo JT (2015). Loneliness: clinical import and interventions. Perspectives on Psychological Science 10: 238-249.

Grippo AJ (2011). The utility of animal models in understanding links between psychosocial processes and cardiovascular health. Social and Personality Psychology Compass 5/4: 164-179.

Sgoifo A, Carnevali L, Grippo AJ (2014). The socially stressed heart: insights from studies in rodents. Neuroscience and Biobehavioral Reviews 39C: 50-60.

Wardwell J, McNeal N, Scotti ML, Colburn W, Dotson A, Ihm E, Woodbury M, Grippo AJ (2015). Combined vicarious stress and social buffering in the prairie vole. Society for Neuroscience (Chicago, IL).

Sapolsky RM (2004). Why zebras don’t get ulcers. Henry Holt and Company, New York, NY.

Angela Grippo, Ph.D. , is an Associate Professor of Psychology at Northern Illinois University.

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Home — Essay Samples — Nursing & Health — Stress Management — Coping With Stress Essay

Coping with Stress Essay

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Can scientists ‘solve’ stress? They’re trying.

From cardiovascular disease and obesity to a weakened immune system, the side effects of stress can be life-altering. But there may be a way to prevent those outcomes.

As modern-day stress ratchets up to what feels like unbearable levels, researchers are striving to learn more about the precise mechanisms through which it affects our body and mind. The hope is that by unlocking more about how stress works physiologically, we can find ways to prevent it from permanently harming people.

Over the last five decades, scientists have established beyond doubt that persistent stress really can poison our overall health. In addition to increasing the risk of cardiovascular disease , stress plays a role in obesity and diabetes and can weaken the immune system , leaving us more vulnerable to infectious diseases. You can recover swiftly from an episode of acute stress—for example, the alarm one might feel when caught unprepared for a presentation. Chronic stress, on the other hand, is more toxic as it is an unrelenting circumstance that offers little chance for a return to normalcy. Financial strain, having a bully for a boss, and social isolation are all examples.

Today chronic stress seems to be increasing worldwide, as people grapple with rapid socioeconomic and environmental change.   A 2023 national survey by the American Psychological Association found that stress has taken a serious toll since the start of the pandemic , with the incidence of chronic illnesses and mental health problems going up significantly, especially among those ages 35 to 44.

( Do you have chronic stress? Look for these signs. )

So far, one of the major realizations among scientists is that stress harms all of us in different and powerful ways. But is there any way to avoid it—or at least recover more quickly? Some promising avenues of research offer hope for the future.

Preventing chronic stress from harming you in the first place

Groundbreaking studies in orphans showed how stress in early life can leave an indelible mark on the brain.

For Hungry Minds

“Chronic stress in early life has more serious and lasting effects, because that’s when a lot of connections are being laid down in the brain,” says Aniko Korosi, a researcher at the University of Amsterdam who has been conducting experiments on mice to elucidate that link between early-life stress and brain development.

Korosi may have found a surprising link between stress and the resulting nutrient composition in the brain . She and her colleagues noticed that mouse pups that had been exposed to stress in the first week of their lives—having been moved from their mother’s care to a cage—had lower levels of certain fatty acids and amino acids in their brains compared with pups being raised in a stress-free environment.

She wondered if it was possible to normalize a stressed pup’s development by feeding it a diet rich in the specific nutrients its brain would be lacking. To find out, the researchers first fed a supplemented diet to the mothers so it would pass through their milk, then continued to provide it in the pups’ feed for two weeks after they were weaned. A few months later, the researchers tested the now adult mice in learning and memory. Unlike stressed mice that had never received an enriched diet, these mice did not display cognitive impairments.

( How wild animals cope with stress—from overeating to sleepless nights. )

“I was surprised that changing the nutrition could have such a powerful effect, because it’s such an easy intervention,” Korosi says.

If further studies provide more evidence of the nutritional pathway, she says, there would be a strong basis for supplementing the diets of infants born to mothers living in stressful conditions.

Developing an early warning system for stress

Katie McLaughlin, a psychologist at the University of Oregon, is investigating how mental health problems arise in adolescents as they’re going through a particularly vulnerable time in their lives, transitioning to adulthood.

She and her colleagues are still collecting data , but a smaller, precursor study tracking 30 teenagers offers clues about what the researchers might learn—and how it might help them identify stress before it goes too far.  

In that study, McLaughlin found that the extent of stress experienced by a subject in the month before their lab visit changed how their brain responded to emotionally impactful information such as when they were shown a picture of a threatening face. The brain’s prefrontal cortex, which helps regulate emotions, showed less activation when the subject had experienced higher levels of stress.

McLaughlin is optimistic that data from the ongoing study will help pinpoint changes in behavior as well as brain activity that predict the emergence of mental health problems like anxiety and depression. This could enable the development of targeted interventions delivered to teenagers at just the right time, she says. If the identified marker of stress were a sudden decrease in sleep duration or a sharp decline in social interactions, for example, it would be possible to push the intervention out to the individual on their smartphone.

“Like, here’s a reminder about good sleep hygiene, or this might be a good time to check in with your counselor at school about what’s been going on in your life,” McLaughlin explains.

( ‘Hysterical strength’? Fight or flight? This is how your body reacts to extreme stress. )

Learn more about stress and how to manage it

Preventing inflammation caused by chronic stress.

Gaining a deeper understanding of how stress affects the immune system may also help find a way to reverse those effects.

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In the 1980s, psychologist Janice Kiecolt-Glaser and her virologist husband, Ronald Glaser, began exploring the physiological impact of stress on two notably stressed segments of society: medical students and older caregivers. The researchers found the students’ immune systems were less robust when they were taking exams than during non-exam times—and that stress altered the body’s response to vaccines.

Researchers then administered the flu and pneumonia vaccines to individuals responsible for a spouse with dementia. Unlike medical students taking exams, who were likely stressed only in the short term, these people were experiencing unrelenting stress. When tested at set periods after inoculation, they had fewer antibodies compared with a control group —they couldn’t maintain their protective response. “That gave us good evidence that the changes brought on by stress were biologically meaningful,” says Kiecolt-Glaser, now an emeritus professor at the Ohio State University.

Around the same time, researchers led by Sheldon Cohen, now emeritus professor of psychology at Carnegie Mellon University, delivered cold-causing viruses into the nostrils of about 400 adult volunteers in the U.K. “The more stress they reported prior to our exposing them to a virus, the higher the risk was for them to develop a cold,” says Cohen. The duration and type of stress mattered: Chronic economic or interpersonal stress were what really put people at high risk—and the longer it went on, the greater the susceptibility to falling sick.

Cohen and his colleagues also learned that when exposed to viruses, chronically stressed people tended to produce an excess of cytokines—proteins that serve as messengers of the immune system, traveling to sites of infection and injury and activating inflammation and other cellular processes to protect the body. Too many cytokines cause an excess of inflammation.

Researchers still don’t know enough about how stress alters the immune system’s ability to regulate cytokines to devise an intervention to reduce the inflammation, but in one way, these findings signal some hope: There are clear targets for more work to be done.  

Understanding stress on a cellular level

The future of understanding and combating stress may lie in our DNA.

In 2023, Ursula Beattie, then a doctoral student at Tufts University, and her colleagues found possible evidence that stress can overwhelm DNA’s repair mechanisms . In their study, researchers repeatedly tapped on sparrow cages with pens, played the radio loudly, and other actions designed to cause distress but no physical harm. Blood and tissue samples from the sparrows after three weeks of this unpleasant treatment revealed damage to the DNA. “It’s like if you had two pieces of string coiled up, just like DNA, and you took a pair of scissors and cut them,” Beattie says.

While these kinds of double-strand breaks in DNA occur all the time in sparrows and other species, including humans, the damage is typically reversed through self-repair mechanisms. In a chronic-stress setting, “those repair mechanisms get overwhelmed, which is how we see a buildup of DNA damage,” Beattie explains. The damage in the birds appears to be the most severe in cells of the liver, she adds, suggesting that for humans, too, the extent and type of damage inflicted by stress might be different for different tissues of the body.

Separately, Kiecolt-Glaser and psychologist Lisa Christian at OSU are conducting a longitudinal study to determine whether chronic stress ages you more quickly. If results support a smaller, earlier study, it appears that chronically stressed caregivers not only are more likely to get sick and heal more slowly but they also show signs of accelerated aging.

We’re still learning how deep stress goes into our bodies. But these exploratory findings mean we’re getting closer to solving the puzzle that is stress, which promises a future where we can better meet the ongoing demand for change.

( 20 stress-relief gifts for the frazzled friend in your life. )

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• About Adverse Childhood Experiences
• Risk and Protective Factors
• Program: Essentials for Childhood: Preventing Adverse Childhood Experiences through Data to Action
• Adverse childhood experiences can have long-term impacts on health, opportunity and well-being.
• Adverse childhood experiences are common and some groups experience them more than others.

What are adverse childhood experiences?

Adverse childhood experiences, or ACEs, are potentially traumatic events that occur in childhood (0-17 years). Examples include: 1

• Experiencing violence, abuse, or neglect.
• Witnessing violence in the home or community.
• Having a family member attempt or die by suicide.

Also included are aspects of the child’s environment that can undermine their sense of safety, stability, and bonding. Examples can include growing up in a household with: 1

• Substance use problems.
• Mental health problems.
• Instability due to parental separation.
• Instability due to household members being in jail or prison.

The examples above are not a complete list of adverse experiences. Many other traumatic experiences could impact health and well-being. This can include not having enough food to eat, experiencing homelessness or unstable housing, or experiencing discrimination. 2 3 4 5 6

Quick facts and stats

ACEs are common. About 64% of adults in the United States reported they had experienced at least one type of ACE before age 18. Nearly one in six (17.3%) adults reported they had experienced four or more types of ACEs. 7

Preventing ACEs could potentially reduce many health conditions. Estimates show up to 1.9 million heart disease cases and 21 million depression cases potentially could have been avoided by preventing ACEs. 1

Some people are at greater risk of experiencing one or more ACEs than others. While all children are at risk of ACEs, numerous studies show inequities in such experiences. These inequalities are linked to the historical, social, and economic environments in which some families live. 5 6 ACEs were highest among females, non-Hispanic American Indian or Alaska Native adults, and adults who are unemployed or unable to work. 7

ACEs are costly. ACEs-related health consequences cost an estimated economic burden of $748 billion annually in Bermuda, Canada, and the United States. 8

ACEs can have lasting effects on health and well-being in childhood and life opportunities well into adulthood. 9 Life opportunities include things like education and job potential. These experiences can increase the risks of injury, sexually transmitted infections, and involvement in sex trafficking. They can also increase risks for maternal and child health problems including teen pregnancy, pregnancy complications, and fetal death. Also included are a range of chronic diseases and leading causes of death, such as cancer, diabetes, heart disease, and suicide. 1 10 11 12 13 14 15 16 17

ACEs and associated social determinants of health, such as living in under-resourced or racially segregated neighborhoods, can cause toxic stress. Toxic stress, or extended or prolonged stress, from ACEs can negatively affect children’s brain development, immune systems, and stress-response systems. These changes can affect children’s attention, decision-making, and learning. 18

Children growing up with toxic stress may have difficulty forming healthy and stable relationships. They may also have unstable work histories as adults and struggle with finances, jobs, and depression throughout life. 18 These effects can also be passed on to their own children. 19 20 21 Some children may face further exposure to toxic stress from historical and ongoing traumas. These historical and ongoing traumas refer to experiences of racial discrimination or the impacts of poverty resulting from limited educational and economic opportunities. 1 6

Adverse childhood experiences can be prevented. Certain factors may increase or decrease the risk of experiencing adverse childhood experiences.

Preventing adverse childhood experiences requires understanding and addressing the factors that put people at risk for or protect them from violence.

Creating safe, stable, nurturing relationships and environments for all children can prevent ACEs and help all children reach their full potential. We all have a role to play.

• Merrick MT, Ford DC, Ports KA, et al. Vital Signs: Estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention — 25 States, 2015–2017. MMWR Morb Mortal Wkly Rep 2019;68:999-1005. DOI: http://dx.doi.org/10.15585/mmwr.mm6844e1 .
• Cain KS, Meyer SC, Cummer E, Patel KK, Casacchia NJ, Montez K, Palakshappa D, Brown CL. Association of Food Insecurity with Mental Health Outcomes in Parents and Children. Science Direct. 2022; 22:7; 1105-1114. DOI: https://doi.org/10.1016/j.acap.2022.04.010 .
• Smith-Grant J, Kilmer G, Brener N, Robin L, Underwood M. Risk Behaviors and Experiences Among Youth Experiencing Homelessness—Youth Risk Behavior Survey, 23 U.S. States and 11 Local School Districts. Journal of Community Health. 2022; 47: 324-333.
• Experiencing discrimination: Early Childhood Adversity, Toxic Stress, and the Impacts of Racism on the Foundations of Health | Annual Review of Public Health https://doi.org/10.1146/annurev-publhealth-090419-101940 .
• Sedlak A, Mettenburg J, Basena M, et al. Fourth national incidence study of child abuse and neglect (NIS-4): Report to Congress. Executive Summary. Washington, DC: U.S. Department of Health an Human Services, Administration for Children and Families.; 2010.
• Font S, Maguire-Jack K. Pathways from childhood abuse and other adversities to adult health risks: The role of adult socioeconomic conditions. Child Abuse Negl. 2016;51:390-399.
• Swedo EA, Aslam MV, Dahlberg LL, et al. Prevalence of Adverse Childhood Experiences Among U.S. Adults — Behavioral Risk Factor Surveillance System, 2011–2020. MMWR Morb Mortal Wkly Rep 2023;72:707–715. DOI: http://dx.doi.org/10.15585/mmwr.mm7226a2 .
• Bellis, MA, et al. Life Course Health Consequences and Associated Annual Costs of Adverse Childhood Experiences Across Europe and North America: A Systematic Review and Meta-Analysis. Lancet Public Health 2019.
• Adverse Childhood Experiences During the COVID-19 Pandemic and Associations with Poor Mental Health and Suicidal Behaviors Among High School Students — Adolescent Behaviors and Experiences Survey, United States, January–June 2021 | MMWR
• Hillis SD, Anda RF, Dube SR, Felitti VJ, Marchbanks PA, Marks JS. The association between adverse childhood experiences and adolescent pregnancy, long-term psychosocial consequences, and fetal death. Pediatrics. 2004 Feb;113(2):320-7.
• Miller ES, Fleming O, Ekpe EE, Grobman WA, Heard-Garris N. Association Between Adverse Childhood Experiences and Adverse Pregnancy Outcomes. Obstetrics & Gynecology . 2021;138(5):770-776. https://doi.org/10.1097/AOG.0000000000004570 .
• Sulaiman S, Premji SS, Tavangar F, et al. Total Adverse Childhood Experiences and Preterm Birth: A Systematic Review. Matern Child Health J . 2021;25(10):1581-1594. https://doi.org/10.1007/s10995-021-03176-6 .
• Ciciolla L, Shreffler KM, Tiemeyer S. Maternal Childhood Adversity as a Risk for Perinatal Complications and NICU Hospitalization. Journal of Pediatric Psychology . 2021;46(7):801-813. https://doi.org/10.1093/jpepsy/jsab027 .
• Mersky JP, Lee CP. Adverse childhood experiences and poor birth outcomes in a diverse, low-income sample. BMC pregnancy and childbirth. 2019;19(1). https://doi.org/10.1186/s12884-019-2560-8 .
• Reid JA, Baglivio MT, Piquero AR, Greenwald MA, Epps N. No youth left behind to human trafficking: Exploring profiles of risk. American journal of orthopsychiatry. 2019;89(6):704.
• Diamond-Welch B, Kosloski AE. Adverse childhood experiences and propensity to participate in the commercialized sex market. Child Abuse & Neglect. 2020 Jun 1;104:104468.
• Shonkoff, J. P., Garner, A. S., Committee on Psychosocial Aspects of Child and Family Health, Committee on Early Childhood, Adoption, and Dependent Care, & Section on Developmental and Behavioral Pediatrics (2012). The lifelong effects of early childhood adversity and toxic stress. Pediatrics, 129(1), e232–e246. https://doi.org/10.1542/peds.2011-2663
• Narayan AJ, Kalstabakken AW, Labella MH, Nerenberg LS, Monn AR, Masten AS. Intergenerational continuity of adverse childhood experiences in homeless families: unpacking exposure to maltreatment versus family dysfunction. Am J Orthopsych. 2017;87(1):3. https://doi.org/10.1037/ort0000133 .
• Schofield TJ, Donnellan MB, Merrick MT, Ports KA, Klevens J, Leeb R. Intergenerational continuity in adverse childhood experiences and rural community environments. Am J Public Health. 2018;108(9):1148-1152. https://doi.org/10.2105/AJPH.2018.304598 .
• Schofield TJ, Lee RD, Merrick MT. Safe, stable, nurturing relationships as a moderator of intergenerational continuity of child maltreatment: a meta-analysis. J Adolesc Health. 2013;53(4 Suppl):S32-38. https://doi.org/10.1016/j.jadohealth.2013.05.004 .

Adverse Childhood Experiences (ACEs)

ACEs can have a tremendous impact on lifelong health and opportunity. CDC works to understand ACEs and prevent them.

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• v.1(3); 2015 Nov

The effects of chronic stress on health: new insights into the molecular mechanisms of brain–body communication

Agnese mariotti.

1 Science Writer in Lausanne, Switzerland

Today's life rhythms and demands are often challenging and require intense physical and psychological efforts in order to be sustained. An individual reacts to physical and mental strain that is potentially health threatening by activating interconnected neuroendocrine circuits. This response allows the body to face and deal with the challenge and re-establish homeostatic equilibrium. If the individual perceives a noxious stimulus as too intense, or its duration as too long, he may fail coping with it, and incur maladaptation. In this case, the stress response does not resolve into a state of balance (either similar or new, i.e., adapted, compared with the state before stress hits), neuroendocrine parameters remain altered, and illness may ensue.

It is clear that stress has both a physical (objective) and a psychological (subjective) component: the latter, as described by Koolhaas and colleagues, depends on the individual perception of its predictability and controllability [ 1 ]. The way a person can anticipate a certain stressor and then control it, largely defines the resulting stress response, how promptly and efficiently it is activated promoting adaptation, and how fast it is turned off once equilibrium has been recovered.

The time course of the stress response, characterized by measurable neuroendocrine and behavioral indexes, thus reveals whether a destabilizing stimulus is manageable, or conversely, cannot be handled and consequently becomes harmful.

This implies that not all stimuli that elicit strong neuroendocrine responses are real stressors, but only those that exceed the individual's ability to change and adapt.

Cortical centers in the brain sense a disturbing stimulus and respond by activating pathways that through the limbic system stimulate peripheral networks, including the sympathetic–adrenal–medullary axis and the renin-angiotensin system, and later the hypothalamic–pituitary–adrenal (HPA) axis [ 2 ]. A cascade of events follows that results in the orchestration of a complex response. Adrenaline and other hormones, and neuropeptides are produced and regulate cardiovascular and metabolic functions (inducing, for instance, increases in heart rate, breath frequency, glucose release) for a prompt response concerted to overcome the challenge.

If the distressing stimulus persists, the HPA axis kicks in to sustain the immediate reaction mediated by the centrally activated peripheral systems. The HPA response starts with the hypothalamus delivering corticotropin-releasing hormone to the pituitary and culminates with the stimulation of the adrenal cortex by the pituitary-derived adrenocorticotropic hormone to produce glucocorticoids (GCs). Most organs and tissues, including sympathetic nerves, immune cells and several brain regions express GC receptors and are responsive to GCs induced by stress. Consequently, these hormones participate in the regulation of disparate stress-associated processes, from the modulation of cardiovascular effects and the immune function, to the eventual dampening of the stress response through inhibition of the HPA axis when adaptation is attained.

In situations in which the stressor is overwhelming and cannot be resolved, stress becomes chronic. In this case, the GC-dependent negative feedback mechanism that controls the stress response does not work, GC receptor resistance develops, and the systemic levels of the molecular mediators of stress remain high, compromising the immune system and damaging in the long-term multiple organs and tissues [ 3 ].

What is the actual impact of chronic stress on health?

When considering the numerous cellular targets of the chemical mediators of stress, one would expect that protracted, stress-dependent neuroendocrine dysregulation may damage directly or through functional circuits practically all organs and tissues. To clarify this assumption and identify the biochemical pathways significantly impaired by chronic stress to the extent of producing illness, researchers have on one hand searched for putative morphological tissue alterations associated with stress, and on the other analyzed the molecular mechanisms of action of the main stress hormones.

Effects of chronic stress on brain structure

It has been shown that chronic stress is linked to macroscopic changes in certain brain areas, consisting of volume variations and physical modifications of neuronal networks. For example, several studies in animals have described stress-related effects in the prefrontal cortex (PFC) and limbic system, characterized by volume reductions of some structures, and changes in neuronal plasticity due to dendritic atrophy and decreased spine density [ 4 ]. These morphological alterations are similar to those found in the brains of depressed patients examined postmortem, suggesting that they could also be at the basis of the depressive disorders that are often associated with chronic stress in humans. This hypothesis is supported by imaging studies that evidenced structural changes in the brain of individuals suffering from various types of stress-related disorders, such as those linked to severe traumas, major negative life events or chronic psychosocial strain. In particular, Blix and colleagues observed atrophy of the basal ganglia and significantly reduced gray matter in certain areas of the PFC in subjects afflicted with long-term occupational stress [ 5 ]. In general, the consequences of these alterations in a brain region can expand to other functionally connected areas, and potentially cause those cognitive, emotional and behavioral dysfunctions that are commonly associated with chronic stress, and that may increase vulnerability to psychiatric disorders.

Interlink between the brain & the immune system

The understanding of the molecular circuits that underlie brain architectural changes and medical conditions linked to chronic stress is just at the beginning. Research in this area has centered primarily on the signaling functions of those molecules that are directly induced by stress through the activation of the sympathetic-adrenal-medullary and HPA networks, focusing on their possible cellular targets. Since receptors for stress neuropeptides and hormones are broadly expressed in immune cells [ 6 ], most studies have concentrated on the effects of stress on the immune system (IS). In fact, psychological stress can induce the acute phase response commonly associated with infections and tissue damage, and increase the levels of circulating cytokines and of various biomarkers of inflammation [ 2 ]. As suggested by Maier and Watkins, the interlink between the stress response and inflammation elicited by the IS can be explained from the evolutionary perspective by considering that the stress response is an adaptive process developed by co-opting the IS mechanisms of defense [ 7 ]. In this frame, a psychological stressor, perceived by the brain as ‘danger’, that is, potentially harming, sets in motion a neuroimmune circuit that stimulates the IS to mount a protective reaction intended to prevent damage, repair it and restore homeostasis.

This neuroimmune communication is bidirectional because the cytokines produced by stress-stimulated immune cells also convey a feedback to the nervous system, further modulating the release of stress hormones in the brain, as well as brain activity that regulates behavior and cognitive functions. In a situation of chronic stress, the neuroimmune axis can be overstimulated and breaks down, thus causing neuroendocrine/immune imbalances that establish a state of chronic low-grade inflammation, a possible prelude to various illnesses [ 8 ].

Diseases whose development has been linked to both stress and inflammation include cardiovascular dysfunctions, diabetes, cancer, autoimmune syndromes and mental illnesses such as depression and anxiety disorders.

Persistent, abnormal levels of cytokines and stress chemical mediators in the brain may also damage the parenchyma and cause neuronal death, thus contributing to the brain structural changes associated with chronic stress that are described above [ 9 ].

Despite the large number of studies that have addressed the biological effects of chronic stress and their impact on human health, the emerging picture still merely outlines the biochemical and functional responses of the nervous and immune systems to long-term stress, highlighting some nodes of information exchange between the two networks, but still lacking essential elements concerning additional cellular players, and functional and molecular mechanisms.

Some recent studies have, however, significantly improved our knowledge of how chronic stress promotes two of the diseases that have long been associated with it: atherosclerosis and depression.

Effects of chronic stress on hematopoietic stem cells in cardiovascular diseases

Heidt and colleagues demonstrated how stress increases the levels of circulating inflammatory leukocytes by direct stimulation of hematopoietic stem cell proliferation [ 10 ]. In this new pathway, stress induces the release of noradrenaline by sympathetic nerve fibers targeting blood vessels in the bone marrow of mice. The catecholamine then acts on mesenchymal stem cells located in the hematopoietic niche, which express high levels of the β3 adrenergic receptors. One of the consequences of this interaction is the downregulation of the chemokine CXCL12, a known target of noradrenaline, which is normally produced by several types of niche cells, including mesenchymal stem cells. This releases the inhibition typically exerted by CXCL12 on the proliferation of hematopoietic stem and progenitor cells and on leukocyte migration, thus promoting cell division and leukocyte mobilization into the bloodstream.

Predictably, the inflammatory response induced by the activation of this neuroimmune pathway may have adverse health effects, in particular by exacerbating pre-existing medical conditions. Specifically, the study demonstrated that this mechanism became activated when atherosclerosis-prone mice ApoE -/- were subjected to long-term stress, leading to enhanced recruitment of inflammatory cells in atherosclerotic plaques, higher levels of proteases and increased plaque fragility. Most interestingly, β3-adrenergic receptor blockers opposed leukocyte production and mobilization, thus counteracting plaque inflammation.

When shifting their attention to human subjects, the scientists determined that individuals under considerable occupational stress had significantly more circulating leukocytes compared with when they were not working, suggesting that the neuroimmune mechanism they discovered might be set off by chronic stress and sustain an inflammatory reaction also in humans. If demonstrated, this would open the way to conceptually new therapeutic possibilities not only for atherosclerosis and its related complications, but also for other stress-related diseases that are aggravated by chronic inflammation.

Mechanisms of chronic stress-associated depression & brain–skeletal muscle communication

The mechanisms by which stress chemicals may induce depression are mostly undetermined. Research in this field is starting to define how multiple, independent, though often interconnected biochemical pathways affected by chronic stress concur to promote this disease.

Ota and colleagues have identified a molecular mechanism triggered by chronic stress that contributes to neuronal atrophy in specific brain areas, an anomaly that is typically observed in depressed patients, independent of the cause of depression [ 11 ]. In their study, they observed that persistent high levels of GCs, resulting from stress-induced hyperactivation of the HPA axis, stimulate the production of the molecule REDD1 in the PFC of rodents subjected to prolonged stress. REDD1 is generally induced by a variety of stressors – from energy stress, to hypoxia, to DNA damage – in most tissues and inhibits the kinase mTORC1, thus altering the phosphorylation state and function of its targets. In the brain, the interference of REDD1 with mTORC1 signaling ultimately impinges on neuronal protein synthesis, spine formation and synaptic plasticity. The inhibition of mTORC is pivotal for synaptic impairment and appears to be a central endpoint of molecular pathways turned on by chronic stress. In fact, also the decrease of brain-derived neurotrophic factor levels in response to chronic stress disrupts mTORC1 function.

Proinflammatory cytokines induced by stress are also involved in the development of chronic stress-associated depression [ 12 ]. The acute phase response generally triggered by a harmful factor implies the so-called sickness behavior that includes symptoms similar to those typical of depressive disorders, like social withdrawal, decreased physical activity, fatigue, somnolence, mood and cognitive alterations. This adaptive response is orchestrated by cytokines, and is meant to divert an individual from normal activities in order to save energy, thus facilitating a reaction against the challenge, and subsequent recovery. In the case of chronic inflammation that may set in with prolonged stress, persisting cytokine signaling in the brain prevents the resolution of sickness behavior that consequently can degenerate into depression. The biochemical mechanisms underlying cytokine-induced depression are not well defined, but they may involve alterations of serotonin and glutamatergic transmission, and induction of GC resistance [ 12 ].

One of the pathways that are implicated drives the oxidation of tryptophan (a precursor of serotonin) to Kynurenin (Kyn) and results in the brain production of several neuroactive molecules ( Figure 1 ) [ 12 ]. The enzymes tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase trigger the Kyn pathway in the liver and extrahepatically respectively, and can both be activated by chronic stress: tryptophan 2,3-dioxygenase in fact responds to GCs, while indoleamine 2,3-dioxygenase is induced by proinflammatory cytokines. The Kyn pathway not only affects the brain levels of serotonin and thus serotonergic transmission and its mood and behavioral effects, but it is also responsible for the production of tryptophan metabolites that have neuroinflammatory properties or can affect glutamatergic neurotransmission in the brain either positively or negatively. It follows that a shift in the pathway that favors the production of 3-hydroxykynurenine – an inducer of reactive oxygen species and inflammation – and quinolinic acid – an N- methyl- d -aspartate receptor agonist – over the antioxidant and N- methyl- d -aspartate receptor inhibitor kynurenic acid, may promote depression [ 12 ].

There is evidence that physical exercise can sustain brain health by regulating the production of neurotrophic factors, neurotransmitters, as well as inflammatory molecules. This can translate in a general enhancement of cognitive abilities, a reduced risk of neurodegenerative diseases and a mitigation of depression [ 13 ].

An interesting study has recently demonstrated that a key mechanism by which physical exercise counteracts chronic stress-dependent depression is the modulation of the Kyn pathway of tryptophan degradation [ 14 ]. In this work, Agudelo and colleagues demonstrated that skeletal muscle contraction during protracted training induces locally the interaction of the transcriptional coactivator PGC-1α1 with the transcription factors PPARα/δ, thus increasing in the muscles the expression and activity of a set of kynurenin aminotransferases (KAT). KATs catalyze the peripheral transformation of tryptophan-derived Kyn into kynurenic acid, causing a drop in the levels of circulating Kyn. Since Kyn can cross the blood–brain barrier, its peripheral catabolism has the effect to reduce also its brain concentration and so the production of neurotoxic molecules along the 3-hydroxykynurenine and quinolinic acid branch of the degradation pathway. In mice, under conditions that mimic chronic stress, the overexpression in skeletal muscles of PGC-1α1 prevents neuroinflammation, synapses impairment and depression-like behaviors that are instead observed in control animals. Similarly, the scientists found that exercise training stimulates the PGC-1α1-KAT pathway also in humans, and through this mechanism, potentially regulates those Kyn-dependent toxic effects in the brain that contribute to chronic stress-associated depression.

By identifying new signaling cascades implicated in the regulation of depression caused by chronic stress, Ota's and Agudelo's studies suggest novel areas of investigation for therapy development. Drugs that inhibit REDD1 effects on mTORC1, or that modulate brain levels of Kyn by enhancing its peripheral metabolism could improve the treatment of depression maybe also when it is not stress related. Since depressed individuals are usually reluctant to carry out regular physical exercise, drugs that mimic exercise training and reduce the plasma concentration of Kyn by acting peripherally would be of particular interest.

Biological & social implications of the latest findings in chronic stress research

These studies significantly improve our understanding of the interactions between the nervous systems and peripheral tissues and organs, and how their alterations can cause illness ( Figure 2 ). An important discovery is that if on one hand chronic stress can cause immune dysfunctions, that is, impair a peripheral function, on the other hand proper stimulation of a peripheral tissue like skeletal muscles can relieve stress symptoms and protect the brain, possibly favoring recovery. This suggests that programs of physical exercise should be formally proposed as a preventive measure to people known to be exposed to intense stress (eg., work-related stress), and could be prescribed as a form of therapy in combination with other treatments to ease mood and cognitive deficits caused by chronic stress.

In addition, Heidt's study suggests another intriguing possibility: if chronic stress can stimulate hematopoietic stem and progenitor cells through the activation of the peripheral nervous system, it is plausible that it can activate also other types of stem cells in other tissues by a similar mechanism. Bidirectional communication could in principle exist between the nervous system and every organ and tissue, and represents a general mechanism of nervous control of tissue homeostasis. A few recent studies have provided evidence that supports this hypothesis [ 15–16 ]. One of the resulting and provoking implications is that chronic stress could promote cancer development also by direct induction of uncontrolled cell proliferation.

The recognition that chronic stress can cause serious diseases has intensified research to determine the biochemical perturbations that compromise homeostasis to a degree that prevents spontaneous recovery. The picture is very complex because chronic stress appears to affect organ and system functions at multiple levels. Yet, it is by pinpointing specific biochemical processes affected by chronic stress that it will be possible to envisage solutions to stimulate resilience and control stress-dependent diseases.

It is clear that in the case of illnesses caused by heightened occupational stress, priority should be given to preventive interventions with the purpose of creating and maintaining work conditions respectful of human physiological, emotional and social needs: in other words, the work environment should stimulate growth and productivity while supporting each individual in their challenges. If certain measures could be implemented through official regulations that assure, for example, fair contracts, training, and sensible work schedules in relation to the type and load of responsibilities and the levels of physical and mental engagement implied by the job, others are less manageable because they strictly depend on human factors. Elements like discordant interactions with coworkers and superiors’ demands beyond formal agreements, that are quite common in very competitive work environments, can sharpen tensions and exaggerate the psychosocial strain to the point of causing illness, yet they usually remain overlooked and uncontrolled [ 17 ].

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Open Access

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