2015年7月1日

Robert Sapolsky discusses physiological effects of stress


'We’ve evolved to be smart enough to make ourselves sick'
Why do humans and their primate cousins get more stress-related diseases than any other member of the animal kingdom? The answer, says Stanford neuroscientist Robert Sapolsky, is that people, apes and monkeys are highly intelligent, social creatures with far too much spare time on their hands.
"Primates are super smart and organized just enough to devote their free time to being miserable to each other and stressing each other out," he said. "But if you get chronically, psychosocially stressed, you're going to compromise your health. So, essentially, we've evolved to be smart enough to make ourselves sick."
A professor of biological sciences and of neurology and neurological sciences, Sapolsky has spent more than three decades studying the physiological effects of stress on health. His pioneering work includes ongoing studies of laboratory rats and wild baboons in the African wilderness.
Sapolsky discussed the biological and sociological implications of stress at a Feb. 17 lecture at the annual meeting of the American Association for the Advancement of Science in San Francisco and in a recent interview with Stanford Report.
Stress response All vertebrates respond to stressful situations by releasing hormones, such as adrenalin and glucocorticoids, which instantaneously increase the animal's heart rate and energy level. "The stress response is incredibly ancient evolutionarily," Sapolsky said. "Fish, birds and reptiles secrete the same stress hormones we do, yet their metabolism doesn't get messed up the way it does in people and other primates."
To understand why, he said, "just look at the dichotomy between what your body does during real stress—for example, something is intent on eating you and you're running for your life—versus what your body does when you're turning on the same stress response for months on end for purely psychosocial reasons."
In the short term, he explained, stress hormones are "brilliantly adapted" to help you survive an unexpected threat. "You mobilize energy in your thigh muscles, you increase your blood pressure and you turn off everything that's not essential to surviving, such as digestion, growth and reproduction," he said. "You think more clearly, and certain aspects of learning and memory are enhanced. All of that is spectacularly adapted if you're dealing with an acute physical stressor—a real one."
But non-life-threatening stressors, such as constantly worrying about money or pleasing your boss, also trigger the release of adrenalin and other stress hormones, which, over time, can have devastating consequences to your health, he said: "If you turn on the stress response chronically for purely psychological reasons, you increase your risk of adult onset diabetes and high blood pressure. If you're chronically shutting down the digestive system, there's a bunch of gastrointestinal disorders you're more at risk for as well."
In children, the continual release of glucocorticoids can suppress the secretion of normal growth hormones. "There's actually a syndrome called stress dwarfism in kids who are so psychologically stressed that growth is markedly impaired," Sapolsky said.
Studies show that long-term stress also suppresses the immune system, making you more susceptible to infectious diseases, and can even shut down reproduction by causing erectile dysfunction and disrupting menstrual cycles.
"Furthermore, if you're chronically stressed, all sorts of aspects of brain function are impaired, including, at an extreme, making it harder for some neurons to survive neurological insults," Sapolsky added. "Also, neurons in the parts of the brain relating to learning, memory and judgment don't function as well under stress. That particular piece is what my lab has spent the last 20 years on."
The bottom line, according to Sapolsky: "If you plan to get stressed like a normal mammal, you had better turn on the stress response or else you're dead. But if you get chronically, psychosocially stressed, like a Westernized human, then you are more at risk for heart disease and some of the other leading causes of death in Westernized life."
Baboon studies In addition to numerous scientific papers about stress, Sapolsky has written four popular books on the subject—Why Zebras Don't Get Ulcers, The Trouble with Testosterone, A Primate's Memoir and Monkeyluv. Many of his insights are based on his 30-year field study of wild African baboons, highly social primates that are close relatives of Homo sapiens. Each year, he and his assistants follow troops of baboons in Kenya to gather behavioral and physiological data on individual members, including blood samples, tissue biopsies and electrocardiograms.
"We've found that baboons have diseases that other social mammals generally don't have," Sapolsky said. "If you're a gazelle, you don't have a very complex emotional life, despite being a social species. But primates are just smart enough that they can think their bodies into working differently. It's not until you get to primates that you get things that look like depression."
The same may be true for elephants, whales and other highly intelligent mammals that have complex emotional lives, he added.
"The reason baboons are such good models is, like us, they don't have real stressors," he said. "If you live in a baboon troop in the Serengeti, you only have to work three hours a day for your calories, and predators don't mess with you much. What that means is you've got nine hours of free time every day to devote to generating psychological stress toward other animals in your troop. So the baboon is a wonderful model for living well enough and long enough to pay the price for all the social-stressor nonsense that they create for each other. They're just like us: They're not getting done in by predators and famines, they're getting done in by each other."
It turns out that unhealthy baboons, like unhealthy people, often have elevated resting levels of stress hormones. "Their reproductive system doesn't work as well, their wounds heal more slowly, they have elevated blood pressure and the anti-anxiety chemicals in their brain, which have a structural similarity to Valium, work differently," Sapolsky said. "So they're not in great shape."
Among the most susceptible to stress are low-ranking baboons and type A individuals. "Type A baboons are the ones who see stressors that other animals don't," Sapolsky said. "For example, having your worst rival taking a nap 100 yards away gets you agitated."
But when it comes to stress-related diseases, social isolation may play an even more significant role than social rank or personality. "Up until 15 years ago, the most striking thing we found was that, if you're a baboon, you don't want to be low ranking, because your health is going to be lousy," he explained. "But what has become far clearer, and probably took a decade's worth of data, is the recognition that protection from stress-related disease is most powerfully grounded in social connectedness, and that's far more important than rank."
Coping with stress What can baboons teach humans about coping with all the stress-inducing psychosocial nonsense we encounter in our daily lives?
"Ideally, we have a lot more behavioral flexibility than the baboon," Sapolsky said, adding that, unlike baboons, humans can overcome their low social status and isolation by belonging to multiple hierarchies.
"We are capable of social supports that no other primate can even dream of," he said. "For example, I might say, 'This job, where I'm a lowly mailroom clerk, really doesn't matter. What really matters is that I'm the captain of my softball team or deacon of my church'—that sort of thing. It's not just somebody sitting here, grooming you with their own hands. We can actually feel comfort from the discovery that somebody on the other side of the planet is going through the same experience we are and feel, I'm not alone. We can even take comfort reading about a fictional character, and there's no primate out there that can feel better in life just by listening to Beethoven. So the range of supports that we're capable of is extraordinary."
But many of the qualities that make us human also can induce stress, he noted. "We can be pained or empathetic about somebody in Darfur," he said. "We can be pained by some movie character that something terrible happens to that doesn't even exist. We could be made to feel inadequate by seeing Bill Gates on the news at night, and we've never even been in the same village as him or seen our goats next to his. So the realm of space and time that we can extend our emotions means that there are a whole lot more abstract things that can make us feel stressed."
Pursuit of happiness The Founding Fathers probably weren't thinking about health when they declared the pursuit of happiness to be an inalienable right, but when it comes to understanding the importance of a stress-free life, they may have been ahead of their time.
"When you get to Westernized humans, it's only in the last century or two that our health problems have become ones of chronic lifestyle issues," Sapolsky said. "It's only 10,000 years or so that most humans have been living in high-density settlements—a world of strangers jostling and psychologically stressing each other. But being able to live long enough to get heart disease, that's a fairly new world."
According to Sapolsky, happiness and self-esteem are important factors in reducing stress. Yet the definition of "happiness" has less to do with material comfort than Westerners might assume, he noted: "An extraordinary finding that's been replicated over and over is that once you get past the 25 percent or so poorest countries on Earth, where the only question is survival and subsistence, there is no relationship between gross national product, per capita income, any of those things, and levels of happiness."
Surveys show that in Greece, for example, one of Western Europe's poorest countries, people are much happier than in the United States, the world's richest nation. And while Greece is ranked number 30 in life expectancy, the United States—with the biggest per capita expenditure on medical care—is only slighter higher, coming in at 29.
"The United States has the biggest discrepancy in health and longevity between our wealthiest and our poorest of any country on Earth," Sapolsky noted. "We're also ranked way up in stress-related diseases."
Japan is number one in life expectancy, largely because of its extremely supportive social network, according to Sapolsky. He cited similar findings in the United States. "Two of the healthiest states are Vermont and Utah, while two of the unhealthiest are Nevada and New Hampshire," he noted. "Vermont is a much more left-leaning state in terms of its social support systems, while its neighbor New Hampshire prides itself on no income tax and go it alone. In Utah, the Mormon church provides extended social support, explanations for why things are and structure. You can't ask for more than that. And next door is Nevada, where people are keeling over dead from all of their excesses. It's very interesting."
Typically, observant Mormons and other religious people are less likely to smoke and drink, he noted. "But once you control for that, religiosity in and of itself is good for your health in some ways, although less than some of its advocates would have you believe," Sapolsky said. "It infuriates me, because I'm an atheist, so it makes me absolutely crazy, but it makes perfect sense. If you have come up with a system that not only tells you why things are but is capped off with certain knowledge that some thing or things respond preferentially to you, you're filling a whole lot of pieces there—gaining some predictability, attribution, social support and control over the scariest realms of our lives."
New research From a neuroscience perspective, Sapolsky pointed to several exciting new areas of research. "It's becoming clear that in the hippocampus, the part of the brain most susceptible to stress hormones, you see atrophy in people with post-traumatic stress disorder and major depression," he said. "There's a ton of very exciting, very contentious work as to whether stress is causing that part of the brain to atrophy, and if so, is it reversible. Or does having a small hippocampus make you more vulnerable to stress-related traumas? There's evidence for both sides."
He also cited new studies suggesting that chronic stress causes DNA to age faster. "Over time, the ends of your chromosomes fray, and as they fray your DNA stops working as well, and eventually that could wind up doing in the cell," he said. "There are now studies showing that chromosomal DNA aging accelerates in young, healthy humans who experience something incredibly psychologically stressful. That's a huge finding."
According to Sapolsky, the most important new area of neuroscience research may be the effort to understand differences in the way individuals respond to stress. "This gets you into the realm of why do some people see stressors that other people don't, and why, in the face of something that is undeniably a stressor to everybody, do some people do so much worse than others?" he said. "Genes, no doubt, have something to do with it, but not all that much. However, there is evidence about development beginning with fetal life—prenatal stress, stress hormones from the mom getting through fetal circulation—having all sorts of long-term effects.
"We're now about 70 years into thinking that sustained stress can do bad things to your health. The biggest challenge for the next 70 years is figuring out why some of us are so much more vulnerable than others."
In the meantime, Sapolsky suggested that people do whatever they can to reduce stress in their daily lives. "Try stress management, change your priorities or go into therapy," he said. "It takes work. Some people clearly never can overcome it. But the same things that make us smart enough to generate the kind of psychological stress that's unheard of in other primates can be the same things that can protect us. We are malleable."

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