McEwen, PhD, the Alfred E. Mirsky Professor and neuroscience lab leader at Rockefeller University in New York City and one of the world’s leading experts on the subject, then spends the rest of the lecture trying to convince the crowd that what we think of as stress — an unpleasant, cortisol-fueled reaction that we generally wish would go away — represents only a very slim slice of what researchers now understand about the human stress response. In reality, Dr. McEwen says, stressors come in many forms and operate at different levels of intensity for varying lengths of time. And the system hardwired into our bodies to respond to them is multitiered, complicated, and — if we get in its way, especially by overloading it — can teeter toward the dysfunctional and unhealthy. The key to living happily and with an appropriately stress-responsive brain and body? Get out of our own way and let the body and brain do what they know how to do, McEwen says. Everyday Health sat down with McEwen so that he could explain stress (because all our hands would have gone up, too), what researchers know and are still discovering about it, and how to harness this new wisdom to improve our lives. Everyday Health: What does the average person think stress is? Bruce McEwen: The average person’s definition of stress is a feeling of tension, an experience of a lack of control. Most people think it’s a factor of cortisol levels going up, and that cortisol is bad. But cortisol is only one of a series of chemical mediators that affect the brain and body when stressed. And cortisol goes up and down all the time, and is important for regulating many basic functions in the body. Many things can make cortisol go up. There’s a monkey study in which the monkeys on one side of the room got treats, and the ones on the other side didn’t, and the cortisol levels of the ones who did not get treats went way up. There was nothing threatening them. The highest level of cortisol observed in a male rat was when the rat was mating. RELATED: The United States of Stress: You’ll Never Think About Stress the Same Way Again What is also important to know about cortisol is that the body has a natural day-night rhythm called the “circadian rhythm,” in which cortisol’s level normally goes down during the night as we sleep and then rises early in the morning as a wake-up signal. A flat circadian rhythm impairs the ability of the body to mount an adaptive stress response — that is, turning it on when needed and turning it off again when the stressor is over. Moreover, the circadian production of cortisol is pulsating, and those pulses of cortisol promote turnover of synapses between nerve cells in the brain — getting rid of some and forming new connections — that allow the brain to efficiently learn new skills. So cortisol does a lot besides its role in adapting to stressors. EH: The truth — according to your book, The End of Stress as We Know It — is that there are a variety of types of stress, correct? BMc: We have what I’ll call good normal stress, tolerable stress, and toxic stress. Good normal stress is when you take a risk and meet a challenge, like a job interview, and are successful. It also refers to how cortisol helps us adapt to daily challenges, like getting up in the morning, getting stuck in traffic or running to catch a train, and being surprised for your birthday. Tolerable stress is when something bad happens, like the end of a relationship or the loss of a job, but you have good support by friends and family and good internal resources and can weather the storm and recover. Toxic stress happens when you don’t have those supports and also lack the internal balance because of adverse events early in life that impair the ability of the brain to be resilient. EH: You’re famous for coining the term “allostatic load” with regard to stress. Can you explain how that fits in with normal, tolerable, and toxic stress? BMc: First let’s discuss allostasis. Allostasis is a better term for the body’s normal stress response. It’s the active process of adapting to what happens to us throughout the day using the chemicals produced by the body and the brain. When something happens to us, whether it’s getting out of bed in the morning, which some people find stressful, or having a conversation, or almost anything we do, especially if it’s unexpected, the body amps up and produces a harmonious orchestra of chemical mediators, including cortisol and adrenalin, as well as neurotransmitters, metabolic hormones such as leptin and insulin, and cytokines from the immune system. They make the heart rate go up, trigger the release of glucose, increase the amount of oxygen that reaches the brain. It’s all designed to keep us alert to meet the challenge. But the key is that the body turns on this response when you need it and turns it off again when the challenge is over. Examples of daily stress and allostasis at work would be the things I’ve mentioned: the challenge of that morning wake-up call from the brain, running for a train or dealing with traffic, the exhilaration from a challenge with a satisfying outcome, like giving a successful talk. EH: How does tolerable stress fit into the picture? BMc: Tolerable stress, what I call allostatic load, can be an acute life event — the death of a loved one, the loss of a job, an accident, things that make a person feel a loss of a sense of control. The events may be severe, but if you have a good sense of internal support, good self-esteem, and external social and emotional support, you can weather the storm. The allostatic system may stay on for a bit too long — the orchestra of chemical mediators keeps playing an encore — and you may get some negative effects from it, like putting on some weight, but it can be transient and ameliorated so that you get back to normal. EH: And now we’ve arrived at toxic stress, which you refer to as allostatic overload. BMc: Toxic stress means that you don’t have enough control over your life. The triggers could be similar to tolerable stress, but if you don’t have good social or emotional support, or your brain architecture has been compromised because of early life struggles, you may not be as resilient bouncing back. As a result, your system has risen to the challenge to meet a stressor and that orchestra of chemical mediators has kicked in, but for various reasons, including the unremitting nature of the stressor, your system hasn’t shut off and the orchestra keeps playing. You are stuck, physiologically, in stress-response mode. And the chronic influx of hormones and cytokines and neurotransmitters has a negative effect on you. You start to see an elevated inflammatory response, which can cause coronary artery plaques to build up and metabolic dysregulation and increased abdominal fat. Prediabetes can occur and lead to type 2 diabetes. Bone minerals can erode. The chronic inflammation can also lead to other conditions, such as arthritis and inflammatory bowel diseases, among others. EH: You have mentioned something called the stress paradox, as well, which seems to contribute to the problem. Can you explain it? BMc: People sometimes tend to self-medicate under stress by smoking; eating sugary, fatty comfort foods; not getting enough sleep or physical activity, and sitting too much. And these behaviors activate the same mediators of allostasis that help us adapt to stressors but at the same time can contribute to allostatic load and overload. Behaviors such as exercise and getting enough sleep, conversely, can reduce allostatic load and overload. EH: How much of the population do you think is generally in a state of allostatic load or overload at any given time? BMc: Given the increasing incidence of obesity, diabetes, depression, and dementia, among other disorders, the percentage has dramatically and progressively increased in the last five or more decades, particularly in some areas of the country. EH: We’ve all heard a lot about fight-or-flight. Now there are newer concepts: tend and befriend and freeze or faint. How do they fit into the allostasis–tolerable stress–toxic stress picture? Do some of us tend to revert to some of these reactions more than others? BMc: Living in a dangerous or chaotic environment promotes a state of vigilance and can lead to chronic anxiety that increases the likelihood of a “freeze or faint” or “freeze and then flee” response to an unexpected event that may or may not be dangerous. There are, however, differences in how individuals react, often — but not always — differing by gender, with women (but not all) more likely to show a protective “tend and befriend” response that recognizes the importance of social networks to survival, while men (but not all) are more likely to get ready to fight or flee. EH: And there are genetic factors at play as well? You mention in your book, for instance, that some people are predisposed to having a difficult time shutting off the stress response even in response to the normal cyclical stressors of the day. BMc: There may be differences depending on genetics and disposition. Maybe allostatic load affects you more in the heart or more in the bone, for example. There will be differences in what people perceive as stressors — a hot or a cold environment, for example. And social stressors differ by temperament. Some people don’t like social interactions; their stress may be high in that situation. A person threatened by a social situation is going to have a different physical response in these scenarios than others. With regard to genes, we now know that even in a pair of identical twins, if one becomes depressed or develops cardiovascular disease, there’s a higher frequency of the same illness in the other twin than in unrelated siblings. But its not one hundred percent. Environment plays a role. And some of it goes back to the choices you make in your health-promoting or health-damaging behaviors, your lifestyle, and your social and physical environment. That’s what’s under our control to some extent. EH: You’ve mentioned the brain’s resilience being harmed in childhood by circumstances not under our control. How do those early life experiences play into our ability to regulate our stress response? BMc: If brain development has been altered by early life abuse, neglect, and poverty — which are commonly referred to as adverse childhood experiences, or ACEs — you might not have developed an adequate ability to regulate your impulses and behavior or enough self-confidence and a locus of control with which to cope with potentially stressful life experiences. In fact, we know that early life abuse, neglect, and poverty are a source of increased vulnerability to toxic stress and, as a result, both mental and physical disease over the lifespan, reducing what is now called your “healthspan”; that is, the time when you are able to function without disability. Diabetes and resistance to insulin is an example of a disorder that affects the brain — causing depression and cognitive impairment — as well as the body. Brain circuits are altered as an adaptation to early life adversity and this can include the adverse effect of diabetes. The question becomes, if we can’t prevent ACEs, how can we change these circuits later in life? EH: The amazing thing — given how scary all of this sounds — is that it’s not set in stone. There’s something you can do, right? BMc: Yes, in spite of its vulnerability, the brain has the capacity for adaptive plasticity — changing for the better. The challenge is to find ways of facilitating this plasticity to get the brain ”unstuck” and promote adaptation to a new, more positive environment. Physical activity is probably the best example of an intervention that benefits the brain and body and causes new neurons to form in the hippocampus, a part of the brain involved with consolidating short- and long-term memory and spatial memory, as well as mood. Physical activity can cause the hippocampus to become larger even when you’re in your sixties and seventies just by walking an hour a day. Enhancing hippocampal structure and function counteracts depression and insulin resistance. EH: And you said the brain is quite flexible like this, throughout life, but especially during times of transition? BMc: Exactly. The brain is more plastic during times of transition. That suggests that there are windows of opportunity, such as the transition to college and young adulthood, where one can promote even more brain plasticity. Pregnancy for a woman and the father opens a window for changing lifestyle and learning positive parenting skills. Menopause and retirement are also windows for positive change. These are all windows where good and bad things can happen depending on how we handle it. People are more likely to make changes during periods of transition, and the brain is more likely to show adaptive plasticity.
