Stress; depression, cortisol, and the body's delicate endocrine interplay

Scientists are only now beginning to understand what happens when stress disrupts the delicate interplay between the brain, the endocrine system—the glands and organs that make and release hormones — and the immune system, stimulating the release of compounds that cause inflammation. To be sure, the pressures of daily life—jobs, relationships, money, raising children and now, war and terrorism—have become such constant companions that many of us operate with ever-present feelings of pressure, anxiety or burnout. Although we try to ignore its presence, it doesn't go away, it just goes to work inside the body. Stress can become so unflagging that many people have accepted it as a standard part of life. Prolonged stress contributes to many physical and psychological ills. It overrides natural defenses against viruses that cause AIDS, chickenpox and the common cold; encourages the production of inflammatory hormones that drive heart disease, obesity and diabetes; sparks flare-ups of rheumatoid arthritis and digestive disorders; creates depression and ages the brain. "Numerous studies show that psychological stress can lead to illness, or even death," said Dr. Michael Irwin, director of the Norman Cousins Center for Psychoneuroimmunology at UCLA's Neuropsychiatric Institute. "How we cope with stress and whether or not we get depressed is crucial for our health."

Unchecked stress sends out complex signals that unleash a cascade of activity throughout the body. When someone is confronted with stress—whether physical or psychological—the brain is the first part of the body to respond, reacting in two distinct ways. In one of the reactions, a regulatory part of the brain called the hypothalamus sends signals through sympathetic nerves near the spinal cord to the adrenal glands, commanding them to release the stress hormones epinephrine and norepinephrine (also called adrenaline and noradrenaline). These hormones gird the body for action. They boost heart rate, blood pressure, breathing and blood flow to the muscles and brain, providing an extra surge of energy in times of physical danger. They can also keep athletes, entertainers and others on their toes, keeping them alert and productive when performance counts.

But chronic stress opens the floodgates to epinephrine and norepinephrine, regardless of whether there's a threat, allowing bacteria, viruses or tumors to flourish and making blood more prone to clotting. The brain's other reaction comes through the pituitary gland, which sends signals through the bloodstream instructing the adrenal glands to release the stress hormone cortisol and other steroids. In the right amounts, cortisol helps the body recharge, enhances disease resistance, fights inflammation and improves memory. In excess, however, cortisol promotes the accumulation of abdominal fat, suppresses immunity, shrinks brain cells and impairs memory. Over time, cells become less sensitive to the protective effects of cortisol, and inflammation goes unchecked.

Body's delicate interplay

Scientists are only now beginning to understand what happens when stress disrupts the delicate interplay between the brain, the endocrine system — the glands and organs that make and release hormones — and the immune system, stimulating the release of compounds that cause inflammation. They're also beginning to identify ways to stop this inflammation and other stress-related biological effects. "New treatments that teach us ways to relax and cope with daily stress offer great promise in decreasing the risk for many preventable illnesses," Irwin said. Recent research has identified some of the following ways in which stress influences the course of illnesses linked to viruses, aging or the body's misguided attack on its own tissues.

Cardiovascular disease

Physical or mental stress can take an enormous and sometimes deadly toll on the heart. It increases blood pressure, narrows blood vessels and causes blood to become stickier and more likely to clot, increasing the likelihood of a heart attack or stroke. In February, Irwin published a study in the American Journal of Psychiatry showing that stress and depression in heart attack patients increase amounts of chemicals that make certain immune cells sticky and help them travel to artery linings, where they produce inflammation and promote coronary artery disease. A study published last week in the journal Circulation found that mental stress also triggers irregular heartbeats, which can be deadly.

Digestive disease

Stress can certainly give you butterflies or a stomachache, but chronic stress can trigger flare-ups of irritable bowel syndrome, an intestinal condition that includes cramping, gas, diarrhea and constipation. Women with the condition (who vastly outnumber men) not only have elevated levels of cortisol, but also have exaggerated differences between the higher morning and lower evening levels found in healthy people, Italian researchers reported in 2001. Although stress is no longer believed to cause ulcers (they're sparked by an infection of the bacterium H. pylori), it can worsen symptoms.

AIDS

HIV-infected gay men who keep their sexual orientation secret get sicker and have shorter life spans than gay men who are more open about their sexuality, a 1996 study found. Closeted gay men tend to be shyer and their nervous systems overreact to stress; as a result, their bodies pump out more stress hormones, which encourage the virus to multiply. Steve Cole, an assistant professor of medicine at UCLA who conducted the 1996 study as part of his research into how disease-causing organisms respond to stress, further reported in the December 2003 issue of Biological Psychiatry that these more stress-sensitive men had higher levels of the AIDS virus in their blood and didn't respond as well to AIDS drugs. Cole and his colleagues found that an excess of stress hormones makes it easier for HIV to get into cells and reproduce more quickly, while suppressing production of chemicals that would protect cells from the invasion.

Rheumatoid arthritis

People who suffer from this autoimmune disease of the joints already have high levels of hormones called inflammatory cytokines, which cause swelling, pain and inflammation. Stress and depression, which can intensify pain and create more physical limitations, further increase those levels, according to a study in the March issue of the Journal of Rheumatology.

As their understanding of the biochemistry of stress increases, scientists around the country are developing and testing ways to protect the body from its ravages, using yoga and meditation, psychotherapy and medications, and even experimental devices. Among the simpler interventions that hold the most promise is tai chi, a centuries-old Chinese exercise often described as "meditation through movement." In a study of adults older than 60, UCLA researchers found last year that one type of tai chi improves immunity to shingles, a painful nerve disease caused by the reemergence of the chickenpox virus.

 

Medications may also prove effective at blocking the destructive effects of stress hormones. For example, Cole and his colleagues have just started a study in which they're giving beta blockers, which are typically prescribed for hypertension and heart disease, to HIV patients. The drugs should block the ability of stress hormones to make HIV multiply, the researchers say, thus lowering viral loads. Other medications, such as antidepressants and anti-anxiety drugs, alter the brain biochemistry that makes some people overreact to stress.

As a high-level executive for a large computer manufacturer, Dan Bishop was a self-described workaholic who thought he was ably juggling daily demands and corporate pressures. Then he woke up one night with tightness in his chest, barely able to breathe. At first he suspected a heart attack. The tightness quickly passed, but he was frightened enough to see his doctor. The doctor diagnosed an anxiety attack — caused by stress — and told him to "stop being so driven."

"I didn't know what stress was; I didn't think I had stress," said Bishop, now 52, referring to the 1990 diagnosis. Bishop first tried psychotherapy and the anti-anxiety medication BuSpar to reduce the stress that triggered his first panic attack. He even tried changing jobs, becoming a consultant. But the stress followed him; as his workload grew, he started getting shortness of breath again. Finally, he took a friend's advice and tried biofeedback, a mind-body approach that harnesses people's ability to improve their health using signals from their own bodies. With special biofeedback software and a fingertip sensor, Bishop learned to monitor his heart rhythms on a computer screen while using an emotional refocusing technique. The stress-neutralizing technique involves focusing attention on the heart, breathing consciously and invoking a positive feeling while watching heart-rhythm patterns on the computer screen. "If I'm worrying about stuff, I can see jagged lines; when I'm back at ease and calm, the lines smooth out," he said. When Bishop was diagnosed five years ago with multiple sclerosis, a degenerative neurological disorder that gets worse in stressful times, he began using the biofeedback technique more often. Today, the San Jose resident says, by turning to his laptop computer screen several times a day, "I can actually manage the level of exacerbation."

 

Another, more natural, approach to managing elevated cortisol levels is to supply the endocrine system the raw materials that it requires to function more optimally. "You can't tie your shoe when your running," says naturopath Dr. Michael Borkin. The same goes for the endocrine system. When the endocrine (hormonal) system, the shock absorber of the body, doesn't get what it needs to deal with stressful situations, (Of which depression is very much included) it literally cannibalizes the rest of the body to get what it wants, stealing nutrients from the other endocrine glands. The end result is that the immune, digestive, reproductive, limbic--emotional, systems are being compromised, usually resulting in underperformance. To that effect naruropaths have had great success with liposomally-based transdermal creams that, when applied to pressure points actually supplies the body system with everything it needs, helping to bring the chorus of endocrine glands into greater balance.  

 

Dr. Kevin J. Tracey, head of the Center for Patient-Oriented Research at the North Shore-Long Island Jewish Research Institute in Manhasset, N.Y., has been using vagus nerve stimulation to decrease inflammation in disorders aggravated by stress, including rheumatoid arthritis. The vagus nerve controls involuntary functions such as heart rate, respiration, digestion and bladder function. Stimulating the vagus nerve to slow the heart rate, in this case with a pacemaker-like device, is also the basis of biofeedback and meditation. Researchers at several institutions are experimenting with rapid transcranial magnetic stimulation, which delivers electromagnetic waves through a device placed against the roof of the mouth, to treat anxiety attacks and other manifestations of chronic stress. But, cautioned Dr. Paul J. Rosch, president of the American Institute of Stress in Yonkers, N.Y.: "Just as stress is different for each of us, there is no stress-reduction strategy that's a panacea."