October 2007 13:03 A new commentary in the Oct. 10 edition of the Journal of the American Medical Association explores whether psychological stress leads to disease and concludes that the link is likely. The authors, who say consistent results across different kinds of studies suggest that stress plays a causal role in disease, looked at four diseases. “The evidence from studies of depression and heart disease is most convincing. The HIV/AIDS data are a little weaker. The evidence for stress playing a role in cancer isn't all that good, even though there is supporting evidence from studies of animals,” said lead author Sheldon Cohen. Cohen and colleagues want more time, thought and dollars invested to explore whether interventions designed to reduce stress influence health.
“The existing evidence linking stress to health is impressive,” said Cohen, a psychology professor at Carnegie Mellon University. “What we need now is to find out what actually works to reduce stress,” he added. “After that we'd like to see randomized controlled trials to determine if these stress-reducing strategies translate to less disease.” The commentators are all psychologists who study the interplay of biology and behavior on the body. Cohen says it would be unethical to expose someone to ongoing stress that might cause them permanent harm, so gold-standard evidence from randomized experimental studies is not available. Still, there is convincing confirmation from prospective cohort studies, natural experiments, animal studies and brief laboratory tests on humans. Cohen says the evidence adds up. In studies of people exposed to brief, acute stress, researchers have documented changes in the way the body functions. “That approach looks for the effect of stress on body systems related to disease — things like heart rate, blood pressure or changes in immune function — but we don't necessarily know that such changes would lead to disease,” Cohen said. Researchers have also noted associations between stress and disease in prospective studies. In those investigations, the stress levels of participants are measured; then investigators follow them to see if the participant groups who experienced the most stress are also the people with develop the highest rates of death and disease. “The problem with that approach is there could be environmental or personality characteristics that influence both why a person is stressed and why they developed a disease,” Cohen said. In natural experiments, investigators track the health and death rates of people who experience stressors that are beyond their control (such as death in the family or a natural disaster). Since the subjects do not cause the stressful event, these studies are not subject to the alternative explanations that plague prospective studies. Repeated, sustained stress could throw off everything from metabolism to resting heart rate to the body's response to infection and inflammatory insults, Cohen and colleagues write. Stress might also increase the risk of disease because, “stressed people smoke more and sleep less; they don't have healthy diets; they exercise less,” Cohen said. Michael Irwin is a physician who studies the interaction of the brain, behavior and immunity. He echoes the call for more research on stress and diseases. “This suggestion is critical as most of the data are correlations. Intervention studies are needed to show that stress amelioration impacts psychological and physical health outcomes. Randomized controlled trials are the ‘backbone' of evidenced-based medicine and are needed to change how doctors counsel their patients,” said Irwin, a professor at the University of California, Los Angeles. Both Cohen and Irwin have observed changing attitudes about the influence of stress on health. “My experience with doctors is that they do believe in the association between stress and disease, and they tell their patients to try and reduce their stress,” Cohen said.
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by National Institute of Health (NIH), 06/28/03
For thousands of years, people believed that stress made you sick. Up until the nineteenth century, the idea that the passions and emotions were intimately linked to disease held sway, and people were told by their doctors to go to spas or seaside resorts when they were ill. Gradually these ideas lost favor as more concrete causes and cures were found for illness after illness. But in the last decade, scientists like Dr. Esther Sternberg, director of the Integrative Neural Immune Program at NIH's National Institute of Mental Health (NIMH), have been rediscovering the links between the brain and the immune system.
The Immune System and the Brain
When you have an infection or anything that causes inflammation such as a burn or injury, many different kinds of cells from the immune system stream to the site. Dr. Sternberg likens them to soldiers moving into battle, each kind with its own specialized function. Some are like garbage collectors, ingesting invaders. Some make antibodies, the "bullets" to fight the infectious agents; others kill invaders directly. All these types of immune cells must coordinate their actions, and the way they do that is by sending each other signals in the form of molecules that they make in factories inside the cell.
"It turns out that these molecules have many more effects than just being the walkie-talkie communicators between different kinds of immune cells," Dr. Sternberg says. "They can also go through the bloodstream to signal the brain or activate nerves nearby that signal the brain."
These immune molecules, Dr. Sternberg explains, cause the brain to change its functions. "They can induce a whole set of behaviors that we call sickness behavior… You lose the desire or the ability to move, you lose your appetite, you lose interest in sex." Scientists can only speculate about the purpose of these sickness behaviors, but Dr. Sternberg suggests that they might help us conserve energy when we're sick so we can better use our energy to fight disease.
These signaling molecules from the immune system can also activate the part of the brain that controls the stress response, the hypothalamus. Through a cascade of hormones released from the pituitary and adrenal glands, the hypothalamus causes blood levels of the hormone cortisol to rise. Cortisol is the major steroid hormone produced by our bodies to help us get through stressful situations. The related compound known as cortisone is widely used as an anti-inflammatory drug in creams to treat rashes and in nasal sprays to treat sinusitis and asthma. But it wasn't until very recently that scientists realized the brain also uses cortisol to suppress the immune system and tone down inflammation within the body.
Stress and the Immune System
This complete communications cycle from the immune system to the brain and back again allows the immune system to talk to the brain, and the brain to then talk back and shut down the immune response when it's no longer needed.
"When you think about this cross-talk, this two-way street," Dr. Sternberg explains, "you can begin to understand the kinds of illnesses that might result if there is either too much or too little communication in either direction."
According to Dr. Sternberg, if you're chronically stressed, the part of the brain that controls the stress response is going to be constantly pumping out a lot of stress hormones. The immune cells are being bathed in molecules which are essentially telling them to stop fighting. And so in situations of chronic stress your immune cells are less able to respond to an invader like a bacteria or a virus.
This theory holds up in studies looking at high-levels of shorter term stress or chronic stress: in caregivers like those taking care of relatives with Alzheimer's, medical students undergoing exam stress, Army Rangers undergoing extremely grueling physical stress, and couples with marital stress. People in these situations, Dr. Sternberg says, show a prolonged healing time, a decreased ability of their immune systems to respond to vaccination, and an increased susceptibility to viral infections like the common cold.
Some Stress is Good
People tend to talk about stress as if it's all bad. It's not. "Some stress is good for you," Dr. Sternberg says. "I have to get my stress response to a certain optimal level so I can perform in front of an audience when I give a talk." Otherwise, she may come across as lethargic and listless.
But while some stress is good, too much is not good. "If you're too stressed, your performance falls off," Dr. Sternberg says. "The objective should be not to get rid of stress completely because you can't get rid of stress - stress is life, life is stress. Rather, you need to be able to use your stress response optimally."
The key is to learn to move yourself to that optimal peak point so that you're not underperforming but you're also not so stressed that you're unable to perform. How much we're able to do that is the challenge, Dr. Sternberg admits. This may not be possible in all situations, or for all people, because just as with the animals Dr. Sternberg studies, some people may have a more sensitive stress response than others.
"But your goal should be to try to learn to control your stress to make it work for you," Dr. Sternberg says. "Don't just think of getting rid of your stress; think of turning it to your advantage."
Controlling the Immune Response
Problems between the brain and the immune system can go the other way, too. If for some reason you're unable to make enough of these brain stress hormones, you won't be able to turn off the immune cells once they're no longer needed.
"There has to be an exit strategy for these battles that are being fought by the immune system and the brain provides the exit strategy through stress hormones," Dr. Sternberg says. "If your brain can't make enough of these hormones to turn the immune system off when it doesn't have to be active anymore, then it could go on unchecked and result in autoimmune diseases like rheumatoid arthritis, lupus, or other autoimmune diseases that people recognize as inflammation."
Dr. Sternberg says that there are several factors involved in these autoimmune conditions. There are many different effects that the brain and its nervous system can have on the immune system, depending on the kinds of nerve chemicals that are being made, where they're being made, what kind of nerves they come from, and whether they're in the bloodstream or not. Still, at least part of the problem in these diseases seems to involve the brain's hormonal stress response.
"So if you have too much stress hormone shutting down the immune response, you can't fight off infection and you're more susceptible to infection," Dr. Sternberg concludes. "Too little stress hormones and the immune response goes on unchecked and you could get an inflammatory disease."
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