Fall of 2015 was a stressful season for me. There is a lot I have forgotten since then, but I do remember my doctor asking how much of myself I should be willing to sacrifice to get a PhD. By that time I had already experienced several difficult PhD years full of long hours, failed experiments and lack of publishable results. The looming deadline (a PhD in Norway is 3 years) filled me with panic and I had finally come to some sort of stop. You probably know what I’m going to tell you next: I was burnt out.

Everyone experiences stress at some point in life. You’ve most likely experienced stress yourself. But what you might not know is that not all stress is bad. Short-term and moderate stress, like finishing projects at work or preparing for an exam, may in fact be beneficial. That “rush” to perform, the feeling that your brain is working on high gear and the feeling when everything just works are some of the enjoyable aspects of moderate stress. I enjoy it a lot! Your physical and mental performance can actually increase during stress as your body assembles its resources to survive any perceived danger, even if that danger is merely a deadline or an exam.

Some people thrive under the stress of temporary pressure and competition. Credit: nicolamargaret

Acute stress, such as taking an exam, giving a presentation or even physical exercise, is limited in time. Acute stress usually lasts from minutes to a few hours. Chronic stress, on the other hand, lasts for weeks or months. Difficult work environments, caring for a family member with chronic disease, experiencing bullying or living under low socioeconomic status are common examples of situations that lead to chronic stress.

Chronic stress is not good. If you have gone through weeks or months of stress you know why: a reduced ability to think clearly, fatigue, lack of sleep or lost ability to rest, irritability and so on. If the stress continues for years, the symptoms gradually become more severe and are often accompanied by neck, back or stomach pain. My short-term memory stopped working completely at some point during my PhD. I could be sitting in the office, look around and have no idea what I’d done during the previous hour, not to mention the previous day. Unchecked stress that continues for years can eventually cause severe fatigue, anxiety, depression and burnout.

But what IS stress? What does it look like on the inside of our bodies?

This is your body on stress

Stress can be defined as when “events or environmental demands exceed an individual’s perceived ability to cope” (Glaser and Kiecolt-Glaser 2005, “Stress-Induced Immune Dysfunction: Implications for Health”). It is clear from this definition that stress is personal and will manifest differently in different people. One of my friends has a “talking back”, whenever she needs to rest, her back will let her know in very unfriendly terms. In my case, I get a very specific stomach pain when I’ve been stressed for too long.

When you experience a stressful situation, stress hormones (prolactin, growth hormone, glucocorticoid hormones, noradrenaline and adrenaline) are released into the bloodstream and transported to various parts of your body. All cells have receptors on their surfaces and most cells have receptors for one or more stress hormones (Dhabhar 2014, “Effects of Stress on Immune Function: The Good, the Bad, and the Beautiful”). Receptors are proteins that can bind signaling molecules and convey the signals into the cells to set off a response. The response varies by cell type but often involves turning on or off specific genes.

Model of a receptor on the surface of a cell. The receptor binds signaling molecules and conveys signals to the inside of the cell. Credit: 7activestudio.

Immune cells, the cells in your body that fight off infections and cancerous cells, have receptors for stress hormones. They are directly affected by stress and stressful events you experience in your life.

Short-term bouts of stress, such as the fight-or-flight response to a stressful situation or event, have been shown to alter the distribution of immune cells throughout the body. A consequence of this is that white blood cells move into the blood vessels and tissues, ready to respond in case of tissue damage. White blood cells are involved in tissue repair and clear infected wounds. The altered distribution of these cells could therefore be beneficial, since damage to the skin is a typical consequence of aggressive encounters, such as fighting other humans or encountering predators. On the other hand, short-term stress also reduces proliferation of lymphocytes and increases production of inflammatory signaling molecules called cytokines. The production and release of cytokines need to be carefully regulated because excessive release has a range of negative effects on the body and can cause chronic inflammation.

When stress continues over long periods of time, the cellular responses to stress change. The cells that belong to the innate immune system remain active, while the cells of the adaptive immune system become less active and have reduced responses to stimuli over time. This has two main consequences:

  • Cells of the innate immune system create a state of chronic inflammation.
  • Cells of the adaptive immune system produce reduced defense responses against viruses.
A macrophage (red) producing the inflammatory cytokine TNFa (green) after phagocytosing a pathogenic bacteria (box). Scale bar represents 10 µm. Credit: Dr. Alexandre Gidon.
A macrophage (red) producing the inflammatory cytokine TNFa (green) after phagocytosing a pathogenic bacteria (box). Scale bar represents 10 µm. Credit: Dr. Alexandre Gidon.

How chronic inflammation can make you sick.

Chronic inflammation is a bit of a mystery. It is a long-term process where immune cells infiltrate tissue and produce inflammatory cytokines and other factors that contribute to tissue damage. There are many reasons why immune cells become overactive, such as exposure to irritants or cellular stressors (tobacco smoke for example), recurrent acute inflammation or an autoinflammatory disorder.

As you now know, stress increases the risk of developing chronic inflammation, but so does age, smoking, obesity, sleep disorders and possibly certain diets. It’s important to note that chronic inflammation is not a disease but a state, or a process, that is involved in many serious chronic diseases. It is a component in heart disease, diabetes, chronic obstructive pulmonary disease and cancer (Acabchuk et al. 2017, “Stress and Chronic Illness: The Inflammatory Pathway”). Scientists are now working out the details of how chronic inflammation contributes to, or even worsens, these diverse diseases.

Your adaptive immune system is not only required for viral defense but is also critical to mounting a proper response to vaccination. In one study, women and men living under the chronic stress brought on by caring for a spouse with dementia had reduced response to an influenza-vaccine when compared to people who were not caretakers (Vedhara et al. 1999, “Chronic Stress in Elderly Carers of Dementia Patients and Antibody Response to Influenza Vaccination”). In another study where volunteers were subjected to one of five different cold viruses, severe and chronic (lasting more than a month) stress increased the likelihood of developing a cold (Cohen et al. 1998, “Types of Stressors That Increase Susceptibility to the Common Cold in Healthy Adults”).

Surviving and then thriving again?

Coping with chronic stress is incredibly difficult. Many that live with chronic stress will need professional help at some point. With burnout, anxiety and depression lurking around the corner, it is important to take it seriously if your everyday life seems insurmountable. Recovering from burnout can take years, but thankfully burnout also takes a long time to develop. This leaves a lot of time for prevention, and prevention is the best cure. Getting proper nutrition, enough sleep and exercise can help to reduce stress levels, and is something we will explore in future blog posts. Getting enough rest is equally important in preventing stress-related disorders. Stressful periods should be followed by calmer “down-periods”, days or weeks with significantly less pressure. This is also the time to invest in stress reducing activities such as meditation, exercise, spending time in nature (“forest bathing”) with a book or with loved ones.

My daughter started daycare in the last year of my PhD. In the midst of experimental work, data analysis and endless writing, she brought home a new virus almost every month. I got them all. It is difficult, if not impossible, to judge whether one person’s stress is involved in an infection. What is clear is that severe and chronic stress can increase the risk of infection.

In my own case, I relied a lot on meditation to get through the most stressful periods of my PhD. I have used the Headspace meditation app for several years, but it was the series on anxiety that helped me the most. The idea is to note what you are thinking, not judge it, and then let it go. I would sit in the lab, feel the panic building up and then say to myself “oh, now I’m thinking about that problem”, draw a deep breath and picture the thought fly out the window. It might sound silly, but eventually the thoughts really do fly out the window and the anxiety and stress gradually become less severe. For me, meditation was a great help but not a cure. It wasn’t until maternity leave gave me a long break from work that I could recuperate and this is the key. Because fatigue might linger on after stress-induced anxiety or depression has disappeared it is important to give your body and mind enough rest. I believe this break has helped me cope with the workload, sleep deprivation and chronic colds that plagued my PhD life leading up to thesis submission. In future blog posts, we will take a closer look at how stress reduction, and especially meditation, can be beneficial for the immune system.

Relaxation. Credit: Ryan Adams, homedust.com, via Flickr.com.
Credit: Ryan Adams, homedust.com, via Flickr.com.

My recommendations for no-stress reading:

The Sheperd’s Life: Modern Dispatches from an Ancient Landscape

Factfulness: Ten Reasons We’re Wrong About The World – And Why Things Are Better Than You Think

LIFE Tips on Reducing Stress, from the Editors

Spend time in nature! There is both correlational and experimental evidence for a range of health benefits associated with exposure to nature, including longer healthspan and reduced somatic stress.

Seek social support from others. “The strength and size of your social network are actually some of the strongest predictors of human lifespan and health in older age (in animals, too),” says Christine Lattin, stress researcher at Louisiana State University.

Eat anti-inflammatory vegetables and fruits, and practice time-restricted feeding to reduce inflammation and keep your circadian rhythm and sleep patterns in check. We tend to seek out sweet or fatty foods when we are stressed, which can lead to weight gain as well as elevated levels of inflammation in the body that can lead to health issues.

Practice mindfulness! More on that soon from Signe here on Immune System for LIFE!