Take a Deep Breath

Take a Deep Breath

Stress can throw your body into overdrive. Your breath can help slow things down.

By Lauren Arcuri

It’s no surprise that most of us experienced increased stress in 2020. In the initial stages of the pandemic, many of us went through acute stressors: changes in work, school and caregiving responsibilities and disruption to our daily routines as we sheltered at home. Then, a steady stream of COVID-19 updates and worries, protests against systemic racism and police violence, and ongoing political unrest contributed to a state of more chronic stress.

With so many of us suffering from acute and chronic stress in the past year, what is happening in and to our bodies? The Physiologist Magazine asked several researchers to explain what triggers stress in our bodies, what problems it causes and how we might all calm ourselves down during these challenging times. 

Gary Sieck, PhD, FAPS, researches inflammation in the lung and the impact that has on the resilience of the cell. Sieck is professor at the Mayo Clinic in Rochester, Minnesota, and editor-in-chief of the APS journal Physiology.

When a virus like SARS-CoV-2 invades the lungs, the immune response includes production of chemicals called cytokines, some of which promote inflammation. This is a natural, resilient response to an invader, but if the response is exaggerated, what results is the phenomenon known as a “cytokine storm,” which can be harmful.

Sieck’s team is looking at the response of airway cells to a specific cytokine called tumor necrosis factor alpha, or TNFα. TNFα triggers the production of reactive oxygen species, which occur naturally in the body and also assist in the repair process—but in excess they can cause further injury. “So, you can see a cascade of problems. If you have a diminished stress response, your cell might continue to be injured and not be able to restore itself—its resilience has decreased,” Sieck says.

If the reactive oxygen species cause damage to proteins within the cells, either by causing the unfolding of proteins or damaging their structure directly, another homeostatic response kicks in within the endoplasmic reticulum (ER), known as the ER stress response. “It’s been known for a number of years, but we’re very interested in how it might feedback just like a thermostat, how it might trigger a response,” Sieck says. The damaged proteins need to be refolded correctly, a process that happens when chaperone proteins rush to the scene. If the proteins are too damaged to repair, the cell marks them to be carried away, broken down and recycled—a process called autophagy. 

Reactive oxygen species are produced in the mitochondria, so Sieck and his colleagues have turned their attention to these energy powerhouses of the cell. “If we reduce mitochondrial activity, we can reduce the amount of reactive oxygen species they produce,” Sieck explains. “We’re very interested in mitochondria as a signal of stress within the body.”

Mitochondria can be the source of stress, but they also respond to the stress. For example, if you put your body under stress by doing physical exercise, the damage to the muscle fibers will trigger the cells to make more mitochondria so that you have more energy to power your muscles.

In looking at acute versus chronic stress, Sieck says it is important to remember the role of resilience. “Getting a cold virus is an acute stress,” he says. “I have an immune response, I get over it and recover. That’s resilience. But if I don’t quite recover, and it persists at a low level, or if it’s layered on top of another issue like aging, then I can have longer-term stress.”

Chronic stress causes the level of circulating cytokines to increase. Sieck hypothesizes that chronically elevated cytokines may diminish our ability to respond fully to an acute stressor—our resilience may be decreased. Circulating cytokine levels increase with age as well. “This may explain why older people are more susceptible to coronavirus infection—not necessarily to becoming infected, but how they fare with it,” he says.

Chronic Stress and the Sympathetic Nervous System

Jeanie Park, MD, a nephrologist and clinical specialist in hypertension, studies the physiology of post-traumatic stress disorder (PTSD), a chronic condition that develops after an individual experiences or witnesses a very traumatic event. People with PTSD often experience nightmares, flashbacks and other symptoms related to the trauma that cause disruption and disability in their lives. Park is an associate professor of medicine and physiology at the Emory University School of Medicine in Atlanta and staff physician at Atlanta VA Healthcare System.

Part of our normal physiological reaction to stress is an increase in the activation of the sympathetic nervous system, our so-called “fight-or-flight” response. This activation includes increased blood pressure, increased heart rate and other physiological changes. But what happens with PTSD or a chronic stress situation, Park says, is that the individual is in a long-term state of fight-or-flight. Their sympathetic nervous system is chronically overactivated. “We believe that can cause deleterious effects to your body over time,” she says. “In particular, we believe that it contributes to increased risk of developing hypertension, cardiovascular disease and metabolic disease long-term.” 

“I think we need to do epidemiologic studies to see what is happening at a population level to people who are living through this pandemic. Also, those that are not coping as well, or have more stress during this time—what are their clinical outcomes going to be? What is their physiology? Are we seeing heightened sympathetic activation, inflammation or decreased parasympathetic activation?”

Jeanie Park, MD

While the epidemiologic connection between PTSD and developing these diseases is known, what is not yet understood is the mechanisms that connect the two. Park’s lab uses a method called microneurography to measure sympathetic activation. This method involves placing electrodes into the peroneal nerve, which is below the knee on the outside of the fibula, to measure sympathetic impulses in real time in humans. 

When Park used microneurography to study patients with PTSD, she found something a little surprising at first. The patients didn’t show higher baseline sympathetic nerve activity. But what their systems did show is higher sympathetic reactivity when under mental stress, whether that stress was related to their PTSD symptoms or not.

“So, what we think is that if you have these repeated episodes of mental stress, and repeated episodes of heightened blood pressure and sympathetic responses, over time that could lead to an increased risk of hypertension and cardiovascular disease,” she says. This is the beginning of unraveling the mechanisms that link chronic stress to developing cardiovascular disease.

Why should exposure to a stressor not related to their PTSD symptoms still cause an overreactivity of the sympathetic nervous system? Park and her colleagues discovered that patients with PTSD have an impairment in their baroreceptor activity. Normally, when your blood pressure rises, the baroreflex acts to dampen sympathetic activity. “But in people with PTSD, that mechanism is impaired, so the baroreflex that should be bringing down sympathetic activity is not working,” she says. “We’re not sure why, but we think that inflammation may have something to do with it because we also found that these patients have higher inflammation. And the more severe your PTSD symptoms are, the more inflammation you have.”

Park is still trying to figure out the mechanisms that connect inflammation and PTSD, but her work has already yielded some hints. “It’s unclear what happens first—if you have higher sympathetic nerve activity, there is greater release of norepinephrine, which has a pro-inflammatory effect. So, if you have higher sympathetic tone, that can increase inflammation. But inflammation itself can increase sympathetic activity directly through central effects, but also by impairing the baroreceptor nerve endings that detect changes in blood pressure and modulate sympathetic activity,” she explains. “Our hypothesis is that this increase in inflammation could be impairing the baroreceptors that then prevents a dampening of sympathetic activity during stress.” 

While Park’s research focuses on people with PTSD, she says there is also evidence that chronic stress is associated with an increased risk of hypertension, cardiovascular disease and likely abnormalities of the sympathetic nervous system regulation. “I think we need to do epidemiologic studies to see what is happening at a population level to people who are living through this pandemic,” she says. “Also, those that are not coping as well, or have more stress during this time—what are their clinical outcomes going to be? What is their physiology? Are we seeing heightened sympathetic activation, inflammation or decreased parasympathetic activation?”

Slow Breathing and Stress

Understanding the effect of chronic stress on our physiology is important so that we can find out ways to help mitigate those negative effects. One approach being studied by researchers is breathing manipulation. Conscious control and manipulation of the breath is part of many different existing therapies and centuries-old healing practices, such as the yogic breathing practice called pranayama, as well as mindfulness meditation and cognitive behavioral therapy, which are currently used to treat PTSD.

Park and her colleagues have been studying something called device-guided slow breathing to see if and how it may help improve autonomic nervous system function in patients with PTSD. The biofeedback device Park employs measures the user’s breathing rate and guides them to breathe more slowly. 

When breathing slowly, several things happen in the body. When you slow your breathing rate, you increase your tidal volume—or the amount of air you take into your lungs—so that your body maintains the same amount of air exchange. When you do that, the pulmonary baroreceptors are activated, and that leads to decreased sympathetic activity.

Park says another mechanism that may be at play is that controlling your breathing increases your interoception, or the awareness of your breathing. “If you can increase the awareness of your breathing, that also seems to have the effect of decreasing your sympathetic activity.”

Researchers saw a rapid reduction in both blood pressure and sympathetic activity in patients who practiced device-guided slow breathing. Park conducted a clinical trial comparing the intervention to a sham device without guided breathing, measuring sympathetic activity over eight weeks. “What we found was there was no difference in resting sympathetic activity between the groups,” she says. “But there was amelioration in the exaggerated sympathetic response to mental stress.”

Park and colleagues are also studying mindfulness-based stress reduction, which has been shown to reduce blood pressure in healthy individuals and in other patient populations, such as those with hypertension. They found that the practice of mindfulness itself leads to a natural reduction in breathing rate, even if participants are not instructed to specifically slow their breathing. Their study showed a reduction in sympathetic activity during mindfulness compared to sham intervention in patients with chronic kidney disease. But when patients were simply instructed to breathe at 12 breaths per minute without the mindfulness component that increases interoception or awareness of breathing it did not have any beneficial effect on nervous system activity. “What that suggests is that increased interoception of breathing was necessary to reduce sympathetic activity in that mindfulness study,” Park says. “But if you slow down to five breaths per minute, that is enough to reduce overactivity even without the mindfulness component. So, I think an intervention, which we haven’t tested yet, that combines slow breathing to subphysiologic rates of five breaths per minute, with a mindful component to increase interoception of breathing, may have a more beneficial effect.”

Slow Breathing and the Brain

Other researchers are also studying breathing and how it relates to physiological and emotional stress via the brain. Our breathing happens in a rhythmic way, without our conscious control most of the time. This breathing rhythm is a type of wave or oscillation. In the brain, there are a whole range of other oscillations—gamma waves, delta waves, theta waves and so on—that help the brain synchronize activity.

“Over the past decade or so, it’s become apparent that rhythms at the frequency of breathing are present throughout the brain,” says Jack Feldman, PhD, distinguished professor in neurobiology at the University of California, Los Angeles. “And these rhythms are not about breathing for oxygen and carbon dioxide regulation; they are found in regions involved in emotional function and cognitive function. These rhythms seem to be playing a role in this kind of signal processing.” 

However, breathing is a slower rhythm than most brain rhythms, which occur anywhere from a few per second to approximately 100 per second, while breathing in humans happens about once every five seconds.

Slow breathing can be done anywhere and is noninvasive. “That’s the wonderful thing about it. There are no side effects. It’s cheap. And everyone has had the experience of taking a single deep breath—you take one, and you feel it; it’s relaxing. Imagine doing that for 30 minutes and on a regular basis.”

Jack Feldman, PhD

A region in the brainstem of mammals, discovered by Feldman and colleagues in 1991 and dubbed the pre-Bötzinger Complex, contains neurons that fire rhythmically, driving each breath. These neurons are basically our breathing pacemaker. But unlike the cardiac pacemaker, the pre-Bötzinger Complex can produce a variety of patterns, such as a yawn, a gasp or a sigh.

Feldman and co-authors conducted an experiment in which they eliminated a subgroup of the pre-Bötzinger Complex neurons in mice. They discovered that while the primary breathing patterns of mice were unchanged, they behaved in a much calmer way. Upon further investigation, they discovered these neurons project to another area of the brain, the locus coeruleus, implicated in arousal, attention and panic. Thus, they have found a direct link between our breathing control center and higher-order brain functions, including our response to stress.

While there is much more to be learned about the mechanism by which slow breathing positively affects the brain, Feldman’s hypothesis is that by disrupting the one set of oscillations in the brain we can control—our breathing—we’re affecting the signal processing in the brain in areas that are important in emotion and cognition.

Feldman explains that a complex state such as depression can be thought of as a kind of “locked-in” circuit in the brain, a loop that fires repeatedly, forming something akin to a rut worn into the ground from walking in the same circle over and over. As it deepens, eventually it becomes nearly impossible to break out of the rut. But “heroic” measures (such as electroconvulsive shock therapy and deep brain stimulation) that disrupt all the activity in the brain transiently, including the locked-in loop, can “reset” the connections, making them weaker and allowing new connections to form. “Disrupting these circuits is a little bit like filling in the rut,” Feldman says. “And if you fill it in bit by bit, eventually it gets to the point where it’s at surface level and it’s not an issue anymore.”

It seems that deep, slow breathing—the specific kind doesn’t matter so much, Feldman says—helps disrupt these circuits and get the brain out of well-worn but maladaptive ruts. But compared to deep brain stimulation, slow breathing can be done anywhere and is noninvasive. “That’s the wonderful thing about it. There are no side effects. It’s cheap. And everyone has had the experience of taking a single deep breath—you take one, and you feel it; it’s relaxing. Imagine doing that for 30 minutes and on a regular basis.”

While exactly why and how it helps so much is still a matter of speculation, deep, slow breathing seems to be a powerful way we can mitigate the effects of the chronic stress that many of us are living through right now and increase our resilience.