Imagine yourself running from a hungry tiger. Your blood pounds and adrenaline flows as you flee.
Now imagine yourself stuck in a traffic jam for two hours on a hot summer day. Once again, your blood pounds and the adrenaline flows. Even more infuriating, a woman in a sport-utility vehicle, distracted by her cell phone, has cut you off from the exit ramp.
Which would you prefer, the lady or the tiger? Both situations cause similar reactions in the body, but you may be better off with the tiger, says Bruce McEwen, endocrinologist at Rockefeller University in New York.
The reason? Running from a tiger inspires a very short stress response, the kind the body is designed to handle. But long-term, chronic stress might damage your brain.
“The wear and tear of daily life, the different kinds of everyday stress, it all has an impact,'' says McEwen, echoing an argument he made in a review article earlier this year in the New England Journal of Medicine.
Stressful events, whether physical or psychological, set off an avalanche of chemical reactions in the body. As soon as a person perceives that something stressful is happening, the brain tells nerves to release adrenaline and related chemicals, sending quick energy to the muscles.
More important, a small part of the brain, the hypothalamus, sends a signal to the pituitary gland to start shipping a hormone called corticotrophin into the bloodstream. In turn, corticotrophin tells your adrenal glands, located atop the kidneys, to release more stress hormones, called glucocorticoids.
Glucocorticoids act like the Jekyll and Hyde of stress biology, McEwen says. These stress hormones tell the body to dump sugar into the bloodstream, providing quick energy for a sprint away from danger. During an emergency, glucocorticoids also suspend bodily processes not needed for immediate survival.
Stress hormones seem to particularly electrify a part of the brain called the hippocampus, which sits in right and left halves just above the hypothalamus. Researchers have determined that it plays a large role in forming memories.
This makes sense, because if you survive a stressful encounter, you'll want to remember it in order to avoid it next time, says Robert Sapolsky of Stanford University, author of a stress guidebook titled Why Zebras Don't Get Ulcers. Therefore, memory sharpens during a shocking moment -- one explanation for why people can still recall where they were when they learned of President Kennedy's assassination.
Once glucocorticoids have flooded the bloodstream, the hippocampus starts signaling the hypothalamus to stop making stress hormones, completing a feedback loop that keeps the body from burning itself out.
Repeated stress
The dark side of the helpful stress hormones emerges when someone repeatedly experiences stress, McEwen says. In those situations, glucocorticoids pound the brain like storm waves battering the shore. Over time, the beneficial effects of stress hormones are reversed: Memory worsens, energy levels droop and other health problems emerge.
For the past two decades, Sapolsky, McEwen and other researchers have shed light on how this brain battery occurs. Even a few days' exposure to high levels of stress hormones can weaken hippocampal brain cells, or neurons, leaving them more likely to die if their oxygen supply is interrupted, which happens during a stroke or heart attack.
And weeks of exposure to high levels of glucocorticoids can wither the fragile connections between neurons in that part of the brain.
Studies of rats placed under stress indicate that hippocampal brain cells die after years of elevated stress levels. But if the high levels of stress stop, the shriveled connections between neurons grow back. And the hippocampus retains a unique ability to grow replacement brain cells.
''The adult brain is more versatile than we ever imagined,'' McEwen says.
Very cautiously, researchers such as J. Douglas Bremner of Yale University School of Medicine have raised the idea that ''recovered memories'' experienced by some survivors of sexual abuse may result from this regrowth, liberating memories locked away in isolated brain cells.
Brain shrinkage
Bremner and his colleagues have led a pioneering effort to gather pictures of the effects of stress on the brain. He describes his research team's findings in a recent article in the journal Biological Psychiatry.
In their earliest study in 1993, the researchers examined the memorizing abilities of 26 Vietnam combat veterans suffering post-traumatic stress disorder (PTSD), a psychological ailment characterized by flashbacks, amnesia and psychic distress. Events threatening to your life, or the life of someone close to you, can trigger the disorder, according to the American Psychiatric Association in Washington, D.C.
''Traumatic stress is bad for the brain,'' Bremner says.
He and his colleagues discovered that the PTSD-afflicted veterans suffered deficits in recalling words and paragraphs on tests, compared with healthy individuals with similar backgrounds and intelligence. A follow-up 1995 study published in the American Journal of Psychiatry used magnetic resonance imaging (MRI) to look at the combat veterans' brains. The traumatized individuals averaged 8% smaller hippocampi on the right side of their brains.
Childhood sexual abuse also can set off the same type of brain damage. In a 1997 study, Bremner's group compared 18 male and female PTSD-afflicted victims of sexual abuse with 17 healthy peers. Again, they found shortfalls in recalling words among the traumatic stress patients -- deficits that increased with the severity of abuse.
An MRI study of the survivors revealed an average 12% reduction in hippocampal size on the left side of the brains, compared with healthy study participants.
Bremner suspects that people's ages at the time they suffer severe trauma influences which side of the brain is damaged. ''It's a developmental effect,'' he says.
Not every neuroscientist accepts the premise that traumatic stress shrinks the brain. Tamara Gurvits of the VA Medical Center in Manchester, N.H., also found smaller hippocampal size in a 1996 Biological Psy- chiatry study of PTSD-afflicted combat veterans. She keeps open the possibility that smaller hippocampal size may leave some people more susceptible to the ailment.
The 'common cold'
However, depression, a condition not commonly associated with traumatic stress, also appears to cause brain damage. Known as the ''common cold'' of mental illness, depression afflicts almost 10 million adults nationwide every year, according to the American Psychiatry Association. One in four women and one in 10 men can expect to develop this ailment, which causes stress-filled feelings of sadness and hopelessness, during their lifetime.
Bremner says MRIs of patients with depression, to be published in the American Journal of Psychiatry, found large reductions in hippocampal size, an average 19% shrinkage compared with healthy people.
McEwen goes beyond other researchers in describing the brain-damaging effects of everyday stress. He and some others suggest that stress over a lifetime wears out the hippocampus and hinders its ability to tell the hypothalamus to stop calling for more stress hormones. As a result, more glucocorticoids flood the bloodstream, causing additional degradation of the hippocampus and wrecking the stress mechanism. Thus, people who experience more stress may have brains more aged than their relaxed peers.
''In a broad sense, life experience may affect longevity,'' McEwen says. For evidence, he points to research conducted at McGill University in Montreal, where scientists followed a group of elderly women over four years. They found that women whose stress hormone levels increased over time suffered from hippocampi 14% smaller than their peers who were not as stressed.
McEwen speculates that kind of loss may dispose people to mild cognitive impairment, a condition of severely reduced memory found in the elderly that substantially raises the risk of developing Alzheimer's disease. People suffering this disorder typically suffer from a shrunken hippocampus, at least 10% smaller on average, similar to the reductions seen in victims of traumatic stress and depression.
Some researchers don't believe that everyday traffic jams and office politics can cause the types of brain damage seen in studies of the hippocampus. But even if normal stress doesn't cause brain damage, traumatic stress and depression still affect a significant number of people, Bremner says. ''There's enough traumatic stress to go around.''
In surveys conducted by the Centers for Disease Control and Prevention, for example, more than one in five women reported suffering some form of sexual abuse.
''We're just beginning to understand the individual things that stress can do to the brain,'' McEwen says.
He hopes researchers may someday capitalize on the ability of the hippocampus to grow new neurons to reverse stress-related brain damage. ''Very long, severe periods of stress may permanently damage the brain, but it's not a sure thing,'' he says.
And use of the epilepsy drug Dilantin appears to block stress-related brain cell death in the hippocampi of lab animals, according to a 1997 study led by McEwen and published in the Annals of the New York Academy of Science. Pharmaceutical researchers have increasingly honed their ability to deliver drugs to the brain, raising the possibility of anti-stress drugs. ''Someday, we might take something related to an antidepressant for aging,'' McEwen says.
Thought patterns hurt hearts
Cardiologists have long wondered why people with heart disease seem particularly vulnerable to stress. One researcher, basing his theory on pictures of brains in action, suggests these people think differently than healthy people, putting them at special risk.
''We use all the different parts of the brain to handle stress,'' says Robert Soufer of the VA Positron Imaging Center in West Haven, Conn., who led a study that peered into the brains of people with heart disease while they endured mental stress testing. His research team subjected 10 male heart patients and six healthy men to a series of math questions while a positron emission tomography device took pictures of their brains.
During testing, the men were asked to steadily subtract seven from a starting number. The questioners urged the men to speed up their responses until they made a mistake, then ''errors were corrected in a harsh tone, thereby providing an element of harassment,'' says the report published in the Proceedings of the National Academy of Sciences.
''Heart disease patients, compared to normal patients, use less of the right side of their brain,'' Soufer says.
The 10 heart patients displayed hyperactivity in left-side parts of the brain associated with mental calculation, according to the study. Three of them suffered decreased delivery of oxygen-rich blood to the heart during the testing, a condition called mental ischemia. Blood flow decreased to portions of the brain associated with pain perception.
''There's no warning system to these people of heart damage,'' Soufer says. ''It's diabolical.''
Between 3 million and 4 million Americans suffer these ''silent'' ischemic episodes, according to the American Heart Association.
From previous research, Soufer suspects that behavior, particularly a tendency toward anger and hostility, predisposes some people to mental ischemia.
''Certain people confront stress immediately,'' he says, which might trigger silent heart damage.
