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NIH Record

Stress — It Might Be Even Worse Than You Think

By Alison Davis

On the Front Page...

The dashboard clock reads 7:55 a.m. and you're trapped in traffic, miles from your office. Despite leaving earlier than usual, there is absolutely no chance you'll arrive on time for that important 8 a.m. meeting. In addition to coping with such routine annoyances of our busy lives, 9 out of 10 of us will experience a much more serious stress or — a life-threatening event such as a car accident or an act of personal violence such as a rape or mugging. Fifty percent of us will encounter two such events.


In all these instances, our brain snaps to attention, preparing the rest of the body for the potential consequences of the insult at hand. Blood pressure climbs. The heart pumps more blood, chock full of surging levels of stress hormones. The so-called "fight-or-flight" response has commenced.

And while such compensatory mechanisms help us (or any organism) cope with an immediate crisis, scientists are discovering that longer-term perturbations also occur — in the brain and elsewhere throughout the body — following a stressful and/or traumatic event. What's more, individuals may be significantly and inherently different in the ways they deal with stress, and may even be differentially vulnerable to its effects.

"We don't walk into trauma the same way...and we don't walk out of trauma the same way," said Dr. Rachel Yehuda, a research psychologist at Mt. Sinai School of Medicine in New York City, at a recent NIH symposium on the biology of stress. Furthermore, she emphasized, not all stress is the same.

Yehuda was one of a dozen leading scientists studying the biological effects of stress on the body who presented talks at the all-day meeting held Feb. 4 and cosponsored by the National Institute of General Medical Sciences and NIH's Office of Behavioral and Social Sciences Research. A prominent theme that emerged from the day's presentations was that reactions to stress vary widely, and that — as appears to be the case for much of biology — both behavioral and physiological outcomes of stressful events arise from a complex interplay between genes and the environment. Selected highlights follow:

Hostility, Mental Stress May Aggravate Heart Disease

Hostility and anger may have far-reaching effects on cardiovascular health, just one of the body's systems known to be affected by stress. Nearly a quarter-century ago, Dr. Redford Williams of Duke University began studying the now-infamous "type-A" behavior as a risk for coronary disease. Williams and his colleagues tested 19-year-old men considered to have a "high hostility" personality profile. When evaluated years later, at age 42, the same individuals were more likely to consume more caffeine, alcohol and tobacco; to weigh more; and to have higher cholesterol levels than their "low-hostility" peers. Williams and others have pinpointed hostility in particular as being the most "toxic component" of type-A behavior; although not all type-A personalities are necessarily hostile. Nevertheless, according to Williams, hostility, especially in combination with other risk factors such as depression, job strain, and low socioeconomic status, can precipitate heart disease, cancer and even death.

Social instability, improper diet, mental stress. A wealth of studies suggest that, in people with pre-existing heart disease, all of these can also provoke an already unhealthy cardiovascular system to fail. Dr. David Krantz of the Uniformed Services University of the Health Sciences presented data suggesting that ordinary activities — as innocuous as talking on the phone or as strenuous as climbing the stairs — can trigger episodes of impaired blood flow (called ischemia) in certain vulnerable people. Krantz discussed evidence for how everyday stressful events can "push" susceptible people over a certain threshold for developing heart disease, thus precipitating a heart attack.

Krantz and colleagues performed a study in which they asked patients wearing heart rhythm monitors to record "what they're doing and feeling" every day, and then looked for ischemia in blood vessels that feed the heart. They discovered that many incidents of ischemia are silent — that is, producing no outright symptoms. Most events also occur in the morning, he found, and there was a detectable association between ischemia and mental and emotional activities. Importantly, Krantz noted that many such silent ischemia events go unnoticed via standard hospital tests. Yet by knowing about the events, he said, patients might be better able to predict their risk for trouble. Better yet, Krantz suggested, they might actually do something about it, such as try to keep a lid on the stress in their lives. To that end, he cited a recent study conducted at Duke showing that practicing stress management techniques can lessen the occurrence of heart problems in cardiac patients with inadequate blood flow to the heart.

A Mother's Special Touch

Against the backdrop of a slide of a nursing mother, Dr. Saul Schanberg of Duke told the audience about the profound effects a mother's touch has on her developing child. His talk mostly focused on his research with rat pups, but Schanberg — a pediatrician — also supported the rodent data with results of human studies on the effect of physical contact on premature infants in neonatal wards. Separation from the mother, he said in jest, "is what some people consider a stress." So much so, Schanberg said in referring to the rat pup data, that when the pup realizes that "mother is not there," the animal enters into a survivalist state, conserving energy by shifting to a nongrowing metabolic state. Through careful observation, he and his group narrowed down the particulars of the rat mothers' influence to licking their pups during a critical developmental window: the first 20 days of life. Interestingly, day 22 is when a mother usually leaves her rat pups to fend for themselves.

Schanberg also presented data with human babies, in which the gentle massage of "preemies" in neonatal hospital wards led to a 46 percent increase in growth rate, as well as a perceived decrease in stress-correlated behaviors (such as clenched fists and grimacing).

Later in the day, Dr. Michael Meaney of McGill University presented more data on the remarkable influence of a mother on the general health and well-being of rat pups as they age. His studies show that rat pups handled during the first 3 weeks of life, which also correlates with the sculpting of the dentate gyrus (a brain region important for processing memory information), have a permanent increase in the number of glucocorticoid (a key stress hormone) receptors in the hippocampus, a neighboring brain region also important for memory. Meaney's group has begun to analyze the molecular determinants of the "handling effect" (mothers extensively lick and groom their young pups), and so far has pinpointed the neurotransmitter serotonin as at least one key molecule in the process.

Perhaps most remarkable is the long-lasting nature of such handling effects. Meaney's results suggest that the primary means for cementing the handling effect is through the mothers themselves. His data show that mothers behave differently toward handled pups than they do toward their non-handled counterparts. In this way, the behavior is passed on to the next generation, Meaney said. What's more, he added, pups that received more licking and grooming during those critical early days were much more able to deal effectively with stress later in life.

Post-Traumatic Stress Disorder: Impact of Severe Stress

Behavioral researchers often employ mathematics tasks as a means to inflict (and thereby investigate the consequences of) short-term, minor stress on study subjects. One such common exercise, counting backwards by 13, may qualify as a stressful activity for many, but such mental gymnastics are merely an annoyance when compared to what researchers call "extreme" stress or trauma: being raped or assaulted, subjected to childhood sexual abuse, or involved in a motor vehicle crash. As a consequence of such a harrowing experience, one in four people will develop post-traumatic stress disorder (PTSD), according to Dr. Rachel Yehuda. Typified by the occurrence of flashbacks, nightmares and other sleep problems, emotional outbursts or numbness, and memory and concentration difficulties, PTSD is indeed a disabling condition. The problem with PTSD, described Yehuda, is that "the stress doesn't go away."

Her research has shown that blood levels of certain stress hormones, especially one called cortisol, are markedly low in people with PTSD. And, she found, they are lowest in those people witnessing (or participating in) the most severely stressful events such as being in combat during the Vietnam War. A potentially utilitarian outcome of Yehuda's research is her observation that measuring a person's immediate (up to 1 hour after the traumatic event) response level can be predictive of how likely that person is to develop PTSD.

Time Heals Wounds

Dr. Janice Kiecolt-Glaser of Ohio State University reported on her studies, done in collaboration with Dr. Ronald Glaser of OSU, of the impact of stress on wound healing. Employing second-year medical and dental students as research subjects, Kiecolt-Glaser and her colleagues inflicted minor ("not very painful") wounds before and after periods of stress. What signifies stress to a student? Exams, of course. Kiecolt-Glaser reported that exam stress negatively impacted various immune-related processes, ranging from a delay in the ability to produce antibodies to a flu shot, to a lengthening of the time it took to heal a minor mouth or arm wound.

Since wound healing is a primary factor determining hospital stay in post-surgery patients, Kiecolt-Glaser also mentioned studies conducted by others suggesting that a very moderate level of behavioral intervention aimed at reducing stress ("reading a pamphlet or watching a video about the procedure the night before surgery") has been shown to have a substantial impact on the outcome of surgery, leading in some cases to a shorter recovery period in the hospital.

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