Over the years since then, Ader's modest discovery has forced a new look at the links between the immune system and the central nervous system. The field that studies this, psychoneuroimmunology, or PNI, is now a leading-edge medical science. Its very name acknowledges the links: psycho, or "mind"; neuro, for the neuroendocrine system (which subsumes the nervous system and hormone systems); and immunology, for the immune system.
A network of researchers is finding that the chemical messengers that operate most extensively in both brain and immune system are those that are most dense in neural areas that regulate emotion.2 Some of the strongest evidence for a direct physical pathway allowing emotions to impact the immune system has come from David Felten, a colleague of Ader's. Felten began by noting that emotions have a powerful effect on the autonomic nervous system, which regulates everything from how much insulin is secreted to blood-pressure levels. Felten, working with his wife, Suzanne, and other colleagues, then detected a meeting point where the autonomic nervous system directly talks to lymphocytes and macrophages, cells of the immune system.3
In electron-microscope studies, they found synapse like contacts where the nerve terminals of the autonomic system have endings that directly abut these immune cells. This physical contact point allows the nerve cells to release neurotransmitters to regulate the immune cells; indeed, they signal back and forth. The finding is revolutionary. No one had suspected that immune cells could be targets of messages from the nerves.
To test how important these nerve endings were in the workings of the immune system, Felten went a step further. In experiments with animals he removed some nerves from lymph nodes and spleen—where immune cells are stored or made—and then used viruses to challenge the immune system. The result: a huge drop in immune response to the virus. His conclusion is that without those nerve endings the immune system simply does not respond as it should to the challenge of an invading virus or bacterium. In short, the nervous system not only connects to the immune system, but is essential for proper immune function.
Another key pathway linking emotions and the immune system is via the influence of the hormones released under stress. The catecholamines (epinephrine and norepinephrine—otherwise known as adrenaline and nor-adrenaline), cortisol and prolactin, and the natural opiates beta-endorphin and enkephalin are all released during stress arousal. Each has a strong impact on immune cells. While the relationships are complex, the main influence is that while these hormones surge through the body, the immune cells are hampered in their function: stress suppresses immune resistance, at least temporarily, presumably in a conservation of energy that puts a priority on the more immediate emergency, which is more pressing for survival. But if stress is constant and intense, that suppression may become long-lasting.4
Microbiologists and other scientists are finding more and more such connections between the brain and the cardiovascular and immune systems—having first had to accept the once-radical notion that they exist at all.5
TOXIC EMOTIONS: THE CLINICAL DATA
Despite such evidence, many or most physicians are still skeptical that emotions matter clinically. One reason is that while many studies have found stress and negative emotions to weaken the effectiveness of various immune cells, it is not always clear that the range of these changes is great enough to make a medical difference.
Even so, an increasing number of physicians acknowledge the place of emotions in medicine. For instance, Dr. Camran Nezhat, an eminent gynecological laparoscopic surgeon at Stanford University, says, "If someone scheduled for surgery tells me she's panicked that day and does not want to go through with it, I cancel the surgery." Nezhat explains, "Every surgeon knows that people who are extremely scared do terribly in surgery. They bleed too much, they have more infections and complications. They have a harder time recovering. It's much better if they are calm."
The reason is straightforward: panic and anxiety hike blood pressure, and veins distended by pressure bleed more profusely when cut by the surgeon's knife. Excess bleeding is one of the most troublesome surgical complications, one that can sometimes lead to death.
Beyond such medical anecdotes, evidence for the clinical importance of emotions has been mounting steadily. Perhaps the most compelling data on the medical significance of emotion come from a mass analysis combining results from 101 smaller studies into a single larger one of several thousand men and women. The study confirms that perturbing emotions are bad for health—to a degree.6 People who experienced chronic anxiety, long periods of sadness and pessimism, unremitting tension or incessant hostility, relentless cynicism or suspiciousness, were found to have double the risk of disease—including asthma, arthritis, headaches, peptic ulcers, and heart disease (each representative of major, broad categories of disease). This order of magnitude makes distressing emotions as toxic a risk factor as, say, smoking or high cholesterol are for heart disease—in other words, a major threat to health.
To be sure, this is a broad statistical link, and by no means indicates that everyone who has such chronic feelings will thus more easily fall prey to a disease. But the evidence for a potent role for emotion in disease is far more extensive than this one study of studies indicates. Taking a more detailed look at the data for specific emotions, especially the big three—anger, anxiety, and depression—makes clearer some specific ways that feelings have medical significance, even if the biological mechanisms by which such emotions have their effect are yet to be fully understood.7
When Anger Is Suicidal
A while back, the man said, a bump on the side of his car led to a fruitless and frustrating journey. After endless insurance company red tape and auto body shops that did more damage, he still owed $800. And it wasn't even his fault. He was so fed up that whenever he got into the car he was overcome with disgust. He finally sold the car in frustration. Years later the memories still made the man livid with outrage.
This bitter memory was brought to mind purposely, as part of a study of anger in heart patients at Stanford University Medical School. All the patients in the study had, like this embittered man, suffered a first heart attack, and the question was whether anger might have a significant impact of some kind on their heart function. The effect was striking: while the patients recounted incidents that made them mad, the pumping efficiency of their hearts dropped by five percentage points.8 Some of the patients showed a drop in pumping efficiency of 7 percent or greater—a range that cardiologists regard as a sign of a myocardial ischemia, a dangerous drop in blood flow to the heart itself.
The drop in pumping efficiency was not seen with other distressing feelings, such as anxiety, nor during physical exertion; anger seems to be the one emotion that does most harm to the heart. While recalling the upsetting incident, the patients said they were only about half as mad as they had been while it was happening, suggesting that their hearts would have been even more greatly hampered during an actual angry encounter.
This finding is part of a larger network of evidence emerging from dozens of studies pointing to the power of anger to damage the heart.9 The old idea has not held up that a hurried, high-pressure Type-A personality is at great risk from heart disease, but from that failed theory has emerged a new finding: it is hostility that puts people at risk.