Radio National with Norman Swan

Good Stress and Bad Stress
Monday 13 April 1998

Summary: A look at the protective and damaging effects of stress, including how certain hormones help us cope. Without these hormones we wouldn't survive but, if they are not turned off when the body doesn't need them, problems can occur.

Norman Swan: Welcome to a Health Report which has some surprises in it, because among other things, you'll find out that stress can be good for you; it can perk up your immune system for example.

Hello from me, Norman Swan on this Easter Monday, I hope you're having a good holiday, getting rid of the bad sort of stress which you'll also find out about in a moment and which can cause disease.

According to a leading researcher who has developed a new way of thinking about stress, it's possible to measure it very directly and its effects on our wellbeing.

The researcher is Dr Bruce McEwen, who's in the Laboratory of Neuroendocrinology at the prestigious Rockefeller University in New York. He calls his concept allostasis, which while it sounds very biological, has implications for us all, including governments in terms of their ability to have social policies which by increasing our resilience, allow us to resist disease.

I visited Bruce McEwen recently in his office.

Bruce McEwen: The word is really derived from Greek and 'allo' means 'variable' and 'stasis' means 'stability' and it literally means 'achieving stability through change' and what it really refers to is the fact that when the body is challenged we put out hormones, stress hormones, cortisol and adrenalin, and these help us cope with the situation, survive the immediate challenge. This active response in the body is actually helping the body re-establish homeostasis.

Norman Swan: So you would define stress as change.

Bruce McEwen: As a challenge to the systems of the body.

Norman Swan: And it's how well the body brings you back to --

Bruce McEwen: Back into the homeostatic balance that we all accept as the basis for life, and it does so actively and what people who invoke just homeostasis as a concept, are forgetting the fact that we are often challenged and perturbed from it, and the body's response, active response, is what we call allostasis and it's what brings us back to normal.

Norman Swan: And you believe this concept is a useful way of looking at that stress overall?

Bruce McEwen: Right, because the title of this recent article in the New England Journal of Medicine is called 'The protective and damaging effects of stress mediators'. So we've talked about the protective effect would not survive very well if you didn't have your adrenal glands to put out catecholamines and put out cortisol.

Norman Swan: By catecholamines you mean the adrenalin.

Bruce McEwen: The adrenalin, exactly. So we need these hormones to survive, they protect us. But at the same time we need to manage their secretion so that when we don't need them we turn them off, and hopefully when we do need them we turn them on in adequate amounts to help protect us. The concept of allostatic load refers to really the inefficient operation of these allostatic systems, the fact that the body often turns on these hormones and doesn't turn them off, or they become active like when we're sitting at home after a day's work and we still feel stressed out and our stress hormones are still elevated, that's when they can begin to cause problems. As long as this over secretion of these hormones goes on day after day for a long period of time.

Norman Swan: And when you say 'allostatic load', are you talking about the load from the outside environment, or the load -- ?

Bruce McEwen: The load from the stress mediators. So that that's the protective and damaging effects of stress mediators are related to the load, the fact that when they are produced in excess amounts either because a person is stressed a lot or because they're not turned off in time after the stress has gone, then they begin to work on tissues and organs of the body to cause damage.

Norman Swan: And of course we're talking about two forms of stress here: one is the acute stress like I threaten you with a gun, or you look as if you're about to crash into a barrier driving down the road; or the chronic stress which we've all experienced to some extent which is the work related type stress where people are telling you what to do, you can't control how you do it or when you do it and that puts an enormous load on you.

Bruce McEwen: Right, or a bad family or living situation, a living environment with continual interpersonal conflicts and dangerous neighbourhoods which produce a state of sort of constant vigilance and anxiety even, these are the kinds of things that lead to the over-production of these stress hormones and that lead to allostatic load.

Norman Swan: And you've talked about the chronic stresses, the accumulation of minor day-to-day events.

Bruce McEwen: Right, and in fact what the allostatic load concept emphasises is the fact that the things which really affect most people's health over long periods of time are not dramatic life events, but are really the day-to-day problems, the wear and tear that we all experience in one degree or another, and that these effects may accumulate over months and years to cause problems.

Norman Swan: I want to go through this fairly systematically, but just to leap ahead for a moment: some people believe it's something like post-traumatic stress disorder is when the cup brimmeth over, that you have this high load and then something happens to you, and it's usually something that you perceive as life-threatening - a car accident or something like that, and it just flips you over into uncontrollable responses to stress.

Bruce McEwen: And in fact people who have post-dramatic stress disorder probably experience some form of allostatic load because of their over-reactivity to things that don't bother normal people. And indeed that's one way of producing a sensitised body that over-reacts to situations.

Norman Swan: You talk about the effects of chronic stress being affected by things in the environment, like diet and exercise and so on. What evidence is there for that?

Bruce McEwen: One of the effects that we all recognise as being stressed out is that often we reach for potato chips or some other kinds of junk food, and although it provides maybe a short-term source of energy or satisfaction, the calories then can be processed by the body especially if there are elevated levels of cortisol and elevated levels of insulin, they can be processed into fat and lead to that position - increased body weight especially increased fat around the middle. So that's one way that the bad choice of diet or simply over-eating, can synergise with all the other things that are happening to make the body change.

In the other sense, of course choosing a more prudent diet can have a counterbalancing effect on some of these same situations, and choosing moderate exercise is a way of counteracting the elevated levels of stress hormones, especially the combination of elevated cortisol and elevated insulin, break the vicious cycle that can lead to the conversion of a lot of energy into fat.

Norman Swan: It's a common observation that the same level of stress in one person does not produce the response that you see in another, so people react to it differently. To what extent are genetic factors involved here?

Bruce McEwen: They are certainly important. For example people who have a familial history of hypertension -

Norman Swan: High blood pressure.

Bruce McEwen: High blood pressure, are seen in situations, work stress or other situations, to have elevated blood pressure which doesn't come back to normal as quickly as in a normal subject. So a genetic load of that kind can influence how much allostatic load a person has. Another example would be people who are prone to show one form of diabetes, especially the type 2 diabetes, which is the insulin resistant diabetes and who are also prone to put on extra body fat. These people are then more sensitive to the effects of stress and allostatic load and probably would show a more rapid build-up of body fat and progression towards coronary heart disease.

Norman Swan: Before we look at other factors which affect allostatic load, just describe to me again how you know somebody who's under high allostatic load. What's the diagnosis of it ?

Bruce McEwen: Well certainly body type is one indication, although it's not a certain indication. The pot belly is a sign of the accumulation of abdominal fat which is very sensitive to elevations of cortisol. Now again, people differ genetically in the degree to which that will occur.

Norman Swan: So a person with a pot belly you think is more likely to be under high allostatic load?

Bruce McEwen: Probably. And there are in fact studies in Sweden looking at the prevalence of what's called waist-hip ratio measurement of the pot belly syndrome as a function of people at different levels of their both education and income, and people who are generally poorer and living in poor environments and having less resources in terms of their daily life, tend to have a larger middle, a larger belly, than people who are at the other end of the scale on the average. And this has also come out in the Whitehall studies of Michael Marmot.

Norman Swan: And what you're saying is if you measure then the stress hormones, the stress hormones are also high?

Bruce McEwen: They tend to follow suit.

Norman Swan: Cause and effect, or just association?

Bruce McEwen: Well we know from the more mechanistic studies of how stress hormones affect body fat, especially abdominal fat, that it's very likely that if you have elevated cortisol you're going to accumulate abdominal fat. The problem is in developing measures overall and, for example, waist-hip ratio is a way of assessing the accumulation of one form of allostatic load. Another way of assessing this is to look at parameters of the heart, for example, the mass of the left ventricle is a sign of work related or chronic stress. Another measure would be basic blood pressure measures or the production overnight of cortisol and adrenalin, which is not a cumulative measure but sort of an indication of what every day the body is putting out. What we have done in a paper that was published before this article in the New England Journal is to study elderly people who are successfully ageing, who are basically quite healthy. And it turns out that as you accumulate the sort of life demands of allostatic load, you begin in elderly people to see the onset of actual disease. And so in this particular study, we took a series of measurements of things like waist-hip ratio, cortisol, adrenalin, etc., blood pressure and a number of other measures: cholesterol in the blood, and we scored people as to where they were in the distribution of these measures, in the extreme upper or lower end of this profile and those people who were in the extreme quartile, the upper quarter, in any one or more of these measures of allostatic load, this predicted an increased incidence of cardiovascular disease over three years. In other words, the measure at year one predicted the disease at year three. That was more or less to be expected from the fact that these were measures that are often related to cardiovascular disease, but what we also did was we looked at cortisol in particular and it turned out that increase in cortisol levels over three years predicted cognitive decline in women, but not in men, which was a surprise to us.

Norman Swan: You've got animal experiments as well where you've increased the levels of this allostatic load.

Bruce McEwen: And we know from animal studies; in fact the reason we did the cortisol measurements and related it to cognitive function, we know in animal experiments that increasing levels of cortisol as animals age lead to impaired function of the brain, especially the brain area called the hippocampus which is implicated in certain aspects of learning and remembering how we keep track of the daily events in our lives. And so we knew that in these animal experiments that progressively elevated cortisol in some individual animals predicts greater decline of their hippocampus.

Norman Swan: Not only that, the decline of their brain cells.

Bruce McEwen: And actually loss of brain cells and so on.

Norman Swan: Irreversibly?

Bruce McEwen: In the extreme apparently irreversibly, although we know that in our own laboratory experiments that a certain amount of stress initially produces an atrophy or shrinkage of cells which is reversible. So up to a certain point the atrophy of brain cells is probably a reversible process, but at some point something happens that causes cells to die.

Norman Swan: Did you interview these elderly people to find out where their source of stress came from?

Bruce McEwen: No, and in fact that's one of the interesting questions for a future research. There is a study that --

Norman Swan: So all you had was a measure of stress but you didn't know whether or not they perceived themselves to be stressed or indeed they had stressful --

Bruce McEwen: Or what would I think have been more relevant in this case is to look at their individual life histories and figure out not whether at the time we interviewed them they thought they were stressed, but whether during their life they had experienced an unusual number of, for example, hardships, the kind of work that they did, the kind of family life that they had and so on. And the reason I say that is that actually there was a paper a week before ours in The New England Journal by a group that had studied economic hardship as a measure of sort of lifelong stress, and had shown that people who had a lifelong history of economic hardship showed very distinct signs of decline in physical and mental functioning. So having a tough life is in fact producing a lot of allostatic load that is causing the body and brain to age more quickly.

Norman Swan: We've heard a lot about what causes stress, what it can do to us, and this concept of allostasis, the stress load we're under to bring ourselves back to normal. The issue here is what allows us to adapt to stress better?

Bruce McEwen.

Bruce McEwen: That's a very important question because when you asked the question earlier about genetics, I said that indeed there are genetic risk factors, no doubt. But animal experiments have taught us another thing, that early events in an animal's life can determine lifelong patterns of reactivity to stressful situations. For example, prenatal stress, unpredictable prenatal stress in rats -

Norman Swan: Such as?

Bruce McEwen: Such as in a pregnant rat, restraining the rat which of course is something the mother doesn't particularly like, it's not painful, or setting off a loud sound unpredictably while the mother is pregnant, will result in these rats at their adult life in their being more emotionally reactive and producing more cortisol when they're challenged and therefore producing a greater allostatic load throughout their lifetime. These animals' brains age more quickly, they lose cognitive function earlier.

Norman Swan: And after they're born? Because in some recent papers in Nature and Science I think on cuddling and grooming activity.

Bruce McEwen: Then I'm going to come to the other side, in fact the work that was done in Canada by Michael Meaney and was published not so long ago in Science, has followed up the opposite, which is if you take a newborn animal and you gently manipulate it, it's called handling, in a way that actually calms it down, it can even counteract some of the effects of prenatal stress and also it calms the animal down so it produces less cortisol when challenged, it's less emotionally reactive and therefore it experiences through its life a lower allostatic load, and its brain ages more slowly. So that very simple animal model suggests that in humans things that happen early in life that can influence how our stress adaptation, can either increase of decrease the amount of allostatic load we'll experience because we're going to react a certain way either more active or more calmly to situations of all sorts that occur to us.

Norman Swan: Well let's take a typical situation in humans to illustrate this problem of perception of stress, public speaking for example.

Bruce McEwen: Right. In fact that's a beautiful example because a group in Germany has developed a public speaking challenge test in which they also can measure cortisol, and what they find if you put a person up in front of a strange and perhaps slightly hostile audience, is that most of us will produce stress hormones, when we get up in front of the audience the first time. But most people, if they have to do it again, say four days in a row, will habituate and the next time will not produce as much cortisol, and the next time even less and by the fourth time they may produce no elevation of cortisol at all. That's sort of normal. But in this particular German study, there's a small percentage maybe 10% of the people who continue to produce cortisol each time they're challenged. And when you look at their personalities not surprisingly they tend to be less self-assured, have lower self-esteem, perhaps more emotionally reactive. So there are individual differences in how we handle these kinds of stresses and people who can't habituate or get used to things are more likely to have a greater allostatic load.

Norman Swan: And you also describe in children this extraordinary situation where you believe that there's evidence to suggest that children who have high allostatic load are at higher incidence of insulin dependent diabetes.

Bruce McEwen: Yes. There's a Swedish study that shows that actually family conflict which would result in considerable stress to a child, increases the incidence of insulin dependent diabetes and in fact there are animal studies that show that animal models of insulin dependent diabetes that stress can actually accelerate or increase the number of animals that will develop the disease, perhaps because the stress is enhancing some of the immune mechanisms that are thought to be responsible for destroying the pancreas.

Norman Swan: We all seem to be living in this world where, to use your phrase, the allostatic load is high and we feel it as a burden, and yet to talk about acute stress, people seem to be hooked on it. Fun parks around the world compete with each other for the scarier ride, and you see these queues that can take you half an hour to get on to these things which are designed to terrify you. What's going on there?

Bruce McEwen: Well people talk about good stress and bad stress and I think the notion that an acute stress is something that our bodies protect against, and actually it can make us feel very good, it can increase our arousal or tension, our sense of wellbeing.

Norman Swan: And research here in your own lab, your immunity as well.

Bruce McEwen: And enhance your immunity, absolutely. And so that's sort of the paradox of the stress hormones. It's when you don't turn them off again, when they're being produced after that experience is over and when you're worrying about something and expressing it as elevated levels of stress hormone, that's when it creates this allostatic load which is we could call the bad stress side effects.

Norman Swan: And of course you don't want to get rid of stress, because it is adapted even in a chronic situation. If you didn't have any stress at all, in other words you would have no allostasis.

Bruce McEwen: In fact probably the biggest source of allostatic load is sheer boredom. Having a very boring life, a very boring and perhaps time demanding job, like working on a production line in an automobile plant in the old sense, is probably one of the most stressful in the sense of allostatic load, jobs that one can have. So the excitement of having a challenge is not there for these people. The boredom of the sort of daily routine is there, and that's probably one of the greatest sources of allostatic load.

Norman Swan: Now you describe four situations which are associated with that high allostatic load. Do you want to just quickly go through them?

Bruce McEwen: Sure. Well the first is simply having lots of hardships like these people who had a lot of economic hardships in their life and whose brains and bodies wear out more quickly. The second is not being able to habituate; it's like the people who couldn't habituate in the public speaking challenge, or not being able to shut off the response, like the people with hypertension, a family history of hypertension who couldn't turn off their blood pressure response. So that's a situation in which your body is inefficiently managing your allostatis, your stress response. The final example is perhaps a little bit surprising, given the emphasis on over-production of hormones, but is not being able to produce a response when you need it, and if you can't produce enough cortisol for example, we know there are animal models, something called the Lewis Rat, which doesn't produce enough cortisol. And it suffers from auto-immune and inflammatory disease, because one of the things that the cortisol does, why we sometimes put it on our skin, is to work against, is to calm down an inflammation. It's often given for graft rejection in terms of kidney transplants and things because it's suppressing some of the bad aspects of the immune response.

Norman Swan: So you feel there might be an equivalent in humans?

Bruce McEwen: So undoubtedly there must be an equivalent in humans, people who suffer from auto-immunity, who suffer from arthritis, are people who are perhaps not producing enough cortisol to meet the demands of their inflammatory cytokines the things that cause inflammations. And so this is a situation --

Norman Swan: They might not be able to cope as a sideline, they may not be able to cope with stress that well either.

Bruce McEwen: That's right. And this is a situation then in which these people's inability to produce enough cortisol has led to another allostatic system, namely the cytokines that are involved in making the immune system work, they over-respond and they cause some of the damaging effects which they can produce. So the allostatic load is really in the cytokine, the excess cytokine and the processes that lead to inflammation or auto-immunity.

Norman Swan: I just get a sense that there's a danger in this theory which is that it becomes all encompassing and the whole world could be explained by it.

Bruce McEwen: You're right in a general sense, the theory can perhaps become an empty thing, but I think looked at in terms of specific disease processes, I think it can become very useful.

Norman Swan: And is there any experimental evidence which informs the relationship between one's psychological state and one's allostatic load? In other words, if one's depressed and more and more psychiatrists are defining depression as anxiety as well as depression, so if you're anxious, how does that feed into the situation?

Bruce McEwen: Well depression, one of the best examples of allostatic load is the loss of bone minerals that's been demonstrated in people with depression. It's presumably related to the slightly higher level of cortisol and slightly lower levels of some of the mediators that help with the bone metabolism. And we also know that in depression, in chronic depression there is often a loss of muscle mass and an increased deposition of fat, especially abdominal fat. So it's actually a classic example of allostatic load in which the person's mental state and their inability to cope with their environment, creates a situation in which the physiology then reflects that and leads to these gradual changes in the body.

Norman Swan: And the immune system?

Bruce McEwen: The immune system turns out to be much more interesting than we'd ever imagined because everybody agrees with the idea that stress suppresses immunity, and cortisol suppresses immune function. But it actually turns out that acute stress actually enhances immune function. It improves the ability of the body to respond to a pathogen or to take an immunisation, and that in a sense makes sense with the protective aspects of the stress mediators that I've been talking about. At the same time, if you chronically stress an animal, after actually many weeks of chronic stress, then you actually produce the opposite effect, namely to suppress the same immune responses. We still have to find out what the mechanisms are that account for that switch, and I think the jury is still very much out.

Norman Swan: With the cancer story. Can you intervene and make any difference to people who have what you'd call high allostatic load?

Bruce McEwen: Well I think at this point we still have a long way to go to develop a greater number of strategies, but I'll indicate three: one is this thing we've mentioned before about exercise. At the sort of more social level, we know that isolation is bad, because it increases allostatic load, and social support reduces allostatic load and getting one's emotions out in the open is apparently, even if it's painful while one's doing it, it apparently does also not only increase survivorship but probably changes the patterns of the stress hormones.

At the sort of societal level there is a very important study that occurred in Sweden in the Volvo plant. People who produced cars in the old-fashioned way in which they had to turn a bolt and do something repetitively, with a very definite time pressure of having another car coming down the line, experienced not surprisingly, a lot of dissatisfaction with the job and a lot of absenteeism, their blood pressure was elevated, they were just terribly unhappy. When Volvo reorganised the work schedule so that people formed teams in which they had more flexible work roles and could substitute for each other, job satisfaction increased, blood pressure decreased and they seemed to be heading towards a greater sense of wellbeing. I think there are things we can do as society that will improve the life of the newborn children that will make them more able to handle a lot of things that go on. Certainly having a better education gives one a command over one's life that you don't have if you don't learn to read, and if you can't command an option of jobs and if you don't know how to take care of yourself.

Norman Swan: How much scepticism do you still perceive out there for this sort of theory?

Bruce McEwen: I think it's very new. I think that it's also in some respects very subtle, and because there are so many aspects to this as your questions have sort of implied, I think it's going to take a while before it sinks in.

Norman Swan: Challenging stuff, the ability to achieve stability through change. Dr Bruce McEwen is Professor and Head of the Laboratory of Neuroendocrinology at Rockefeller University in New York.

Next week, we investigate the agenda behind the national review of medical research in Australia. What does this high-powered committee hope to achieve, especially when there already was another review on at the same time?

Reference:

McEwen B.S. Protective and damaging effects of stress mediators. New England Journal of Medicine 1998;338:171-179

Guests:

Dr. Bruce McEwen
Laboratory of Neuroendocrinology
Rockefeller University
New York