GOOD STRESS, BAD STRESS; RESEARCHERS EXPLORING NEW CAUSES, EFFECTS, TREATMENT.

Byline: Sue Goetinck Dallas Morning News

It's the stock market crashing. A lion lunging for your jugular. An impending blind date. Your boss imposing yet another deadline. Finding that perfect gift in time for the holiday exchange.

It's stress - outside forces that are part of life, usually whether you want them or not.

Scientists have known for decades that stress from the outside causes changes on the inside of the body - making it easier to run from the lion but harder to fight a cold if you're fretting about Wall Street.

Now, new research is probing the chemical changes that take place in the body in response to stress. Scientists are learning more about the links between stress and the immune system, body weight and diseases like depression and anxiety. Some researchers even are trying to come up with a drug that would blunt the body's response to stress, in hope that such a medication would relieve conditions such as depression.

In addition to studying how the body responds, researchers also are trying to figure out what influences how strongly someone reacts to stress - the hectic pace of the stock market may be easy for one experienced trader to handle, disastrous for another, and in any case probably would give a newcomer some serious jitters.

``Stress itself is a very individual proposition,'' said Dr. Bruce McEwen, a neuroscientist at Rockefeller University in New York.

Since what's stressful to one person may not bother the next in the least, researchers have to define stress using the more neutral language of science.

``It's something in the outside environment that pushes the organism to respond in a lifesaving, adaptive way,'' said Dr. Esther Sternberg, an endocrinologist at the National Institute of Mental Health in Rockville, Md.

Stress and response could take the form of jumping out of the way of a speeding car - clearly a good thing. But responding to stress also can be a bad thing, because hormones released during stress can, for example, suppress the immune system.

``The stock market falls, everyone gets nervous and your colleague coughs in your face,'' Sternberg said. Clearly, that can be a recipe for illness.

In other words, she said, ``these things are bad for you when they start being bad for you. They're good when they help you adapt to a situation.''

It begins in the brain

The body's response to stress starts in the brain. The speeding car approaches, and the brain sends a message to body muscles to run. A separate nervous system response causes less blood to go to the internal organs and more to the muscles. Hormones kick in.

Adrenalin, also known as epinephrine, puts the body into an aroused state so it can cope with the challenge at hand. But the brain also activates a biochemical process that - unless it gets slowed down - can put the body in long-term distress.

A major part of the process happens along what's known as the hypothalamic-pituitary-adrenal axis. The hypothalamus (as well as other regions of the brain) secretes a hormone known as CRH, for corticotropin-releasing hormone. CRH travels through the bloodstream to the pituitary gland, nestled under the lower portion of the brain.

The pituitary gland releases another hormone, called ACTH, for adrenocorticotropin hormone. Like CRH, ACTH travels through the bloodstream. ACTH triggers the adrenals, glands that sit on top of the kidneys. In response, the adrenal glands produce cortisol, the best-known stress hormone.

Cortisol is good over the short term. In fact, the hormone also is known as a glucocorticoid, because it causes cellular fuel - glucose - to move to the muscles. But over the long term, high levels of cortisol can be bad news. It suppresses the immune system and strains brain cells. Too much cortisol also can increase appetite and cause weight gain.

Normally, the body has a safety net to guard against a cortisol onslaught. Cortisol dampens the original sources of CRH, ensuring that the stress response doesn't spiral upward.

Sometimes, however, the spiral takes off anyway. In some forms of depression, for example, cortisol levels are higher overall, but the brain still produces a lot of CRH. Scientists suspect that either the cortisol somehow can't overcome the high CRH production, or that the brain becomes less sensitive to the cortisol.

A pill that interfered with CRH itself might be a new way to treat depression, said Dr. Mark Smith, a neuroscientist and psychiatrist at DuPont Merck Pharmaceutical Co. in Wilmington, Del. Such a pill might be an alternative to the current selection of antidepressants.

``It may be faster; it may be better,'' he said.

Nurturing is key

Scientists have found that the amount of nurturing an animal receives early in life directly relates to the strength of its stress response later. For example, separating baby rats from their mothers causes them to react to stress more strongly when they are adults. The licking that the mother rats do naturally is thought to be key, studies have suggested.

Experiments by Sternberg and her colleagues on two genetic strains of rats - which were known to have different stress responses - suggest that the early nurturing directly affects the immune system.

``There's probably some early influence - it may not all be genetic,'' she said.

At the neuroscience meeting, Sternberg and her colleagues described studies of the two strains of rats, known as Fischer and Lewis. Fischer rats are known to have a more intense stress response than Lewis rats. The Fischer rats also are less susceptible to arthritis than the Lewis variety. That fits with what's known about the stress response, because arthritis is a form of inflammation - a byproduct of an overactive immune response - whereas an increased stress response would suppress the immune system.

Sternberg said scientists always had assumed that the difference between the Fischer and Lewis rats was purely genetic. But experiments presented at the meeting suggest that how the rats are raised may play a role.

At least in the lab, Lewis rat mothers seem to be more attentive to their pups. When separated from the babies, the Lewis mothers round them up quicker than the Fischer mothers do. The Lewis rats also carry their pups; the Fischer mothers push them. And Lewis mothers are more likely to stay crouched over their litter.

Sternberg speculated that the difference in nurturing may contribute to the strength of the stress response that appears later in life, and, in turn, the behavior of the immune system.

Studies in the works now should help scientists determine whether that is true, she said.

The biology of stress responses doesn't vary much from rats to people, Smith said. But it's hard to know how to apply the results to situations people face every day. Long-term neglect of children's emotional needs elevates their stress response, as studies of Romanian orphans have suggested. Sporadic lapses, on the other hand, are not likely to have lasting effects, Smith said.

``Watching MTV for a couple of hours ain't gonna kill you,'' he said.

However, he said, children do need emotional nourishment as well as actual food.

``Kids need attention from a good caregiver, and you don't want to dilute that attention too much,'' he said.

Having a low overall stress response may be good for the waistline, too, other studies presented at the meeting suggested.

Continual, high levels of cortisol - as occur in some forms of depression, or during chronic psychological stress - can increase appetite and lead to weight gain. Studies by Mary Dallman and colleagues at the University of California, San Francisco, showed that rats given high doses of cortisol for long periods increased their appetite and their stores of abdominal fat. And, the researchers found, the rats chowed down when they would normally have been inactive - a little like having a midnight snack.

That may be significant, Dallman noted, because abdominal obesity is linked to adult-onset diabetes, heart disease and stroke - conditions associated with stress.

Many of the suggestions scientists might make for people based on animal studies of stress may seem like common sense, researchers acknowledge. A little stress keeps you on your toes, but too much is bad and everybody probably could do with less. But unraveling the biochemical changes that occur in response to stress gives scientists a more complete understanding of how the body works, and is necessary to begin any medical interventions, Dallman said.

``Before you can intervene,'' she said, ``you've got to know whether what you think is happening is really happening.''

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Photo: (1--Cover--Color) IT MAKES YOU WANT TO SNAP

... But scientists are working on a cure for stress

Michael Owen Baker/Daily News

(2) no caption (Stress - Stock Market)