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Article on Depression |
BY- MARIANNE SZEGEDY-MASZAK
An elderly man came into the clinic at Duke University Medical Center looking extremely depressed. Not surprising given what he had gone through during the previous year. His wife had died, he had suffered a heart attack, and he was taking a complicated cocktail of medications. But did his depression follow the heart attack, or did an earlier but undiagnosed dark melancholy trigger his cardiac problems?
Increasingly, it appears that what we call depression is not strictly psychological but is, instead, a condition that occupies the whole body. "Depression is really the only systemic disease that affects--and complicates--almost all other diseases," says Philip Gold, the chief of clinical neuroendocrinology at the National Institute of Mental Health. In fact, depression not only affects and complicates existing disorders like diabetes, heart disease, cancer, even osteoporosis; it might also trigger them.
That makes depression, already a huge public- health problem, even more serious. It affects more than 18 million Americans; nearly 25 percent of all women and 10 percent of all men will be clinically depressed at some point in their lives. The World Health Organization predicts that by 2020 depression will be second only to heart disease as the leading cause of disability worldwide.
The heart. The link to heart disease has been studied most extensively. Since a 1993 landmark study, doctors have known that when patients are depressed and have a heart attack or congestive heart failure, their outcomes tend to be poor compared with people who are not depressed. "Depression appears to be an independent risk factor for the development of heart disease," says Charles Nemeroff, chair of psychiatry at Emory University School of Medicine.
Of course, someone who is depressed is less likely to exercise, eat right, and take the correct medicines. But the connection goes much deeper, to the human stress response gone awry. Under stress, the blood-clotting system, especially sticky cells called platelets, goes on high alert to slow down bleeding should there be a wound. However, both heart attacks and strokes are caused by the formation of clots in arteries. One study found that depressed patients exhibited increased platelet activation in comparison with normal subjects. Stress also activates cytokines, chemical messengers from the immune system. Additionally, research has pointed to elevated cytokine levels triggering inflammation in the heart.
Other researchers have examined the way that both depressed patients and cardiac patients lose flexibility in their heart muscles. A normal heart moves easily between its resting and beating states. But patients with severe coronary artery disease or with depression have more rigid hearts, less able to respond to the changing demands of the body for blood and oxygen.
All of this leaves researchers with a conundrum, put simply by Nancy Frasure-Smith, a professor of psychiatry at McGill University who has studied depression in cardiac patients for nearly 20 years: "Does depression cause cardiac disease? Does cardiac disease cause depression? Or are they linked by a common factor, but there is no causality? And the fact is, it can be all three."
Diabetes. In 1674, Thomas Willis wrote, "Diabetes is caused by melancholy." Now, 328 years later, it turns out he may have been on to something. There is a close tie between depression and diabetes, says Sanford Garfield, the senior adviser for biometry and behavioral research at the National Institute of Diabetes and Digestive and Kidney Diseases. "Studies have shown that if you are depressed you have twice the likelihood of being diabetic, and if you are diabetic you have twice the likelihood of being depressed." And diabetes is more likely to rage uncontrolled when it's accompanied by depression.
While there may be a number of reasons for this interrelatedness--and lifestyle cannot be underestimated--one study has pointed to excess cortisol production. When cortisol, also known as the "stress hormone," is secreted, it leads to the release of amino acids. These acids are then turned into glucose for energy for the brain. A depressed brain sends out signals that it needs more energy, which can trigger cortisol production, thereby raising blood sugar. And that's a great problem for diabetics. Another study examined a brain region called the hippocampus and its role in the regulation of glucose, as well as its need for glucose. Researchers concluded that patients with Type I diabetes have a hippocampus that is damaged, even atrophied, in a way that is true also for those with depression. One possible explanation is that the brain-structure changes caused by diabetes can also trigger depression. Another is that the brain-structure changes caused by depression can exacerbate diabetes.
Osteoporosis. Depression has also been studied in people with osteoporosis, a disease in which bone mass disintegrates. Several studies have demonstrated that an earlier history of depression was associated with marked osteoporosis. And another found a significant association between reduced bone mineral density and depression. One study, published last year in Trends in Endocrinology & Metabolism, concluded that depression is a risk factor for osteoporosis as serious as smoking or a family history of the disease.
Why? One hypothesis focuses on the interplay between cortisol, the stress hormone, and interleukin 6, which is a cytokine and part of the immune system, in those who are depressed and have osteoporosis. Frequently, depressed patients have high levels of both, which may play a crucial role in bone loss.
Cancer. Who wouldn't be depressed with a cancer diagnosis? Too often depression is seen as a "normal reaction," which means, says Nemeroff, "that it doesn't require any special treatment." The prevalence of depression among cancer patients ranges from 23 percent to 60 percent. Obviously, the life-changing nature of a cancer diagnosis has a great deal to do with this, but so do cytokines.
Cytokines--like interleukin 6--are secreted by the immune system to fight anything that can harm the body, like cancer or infections. Depression alters the immune system for reasons that are not completely understood, but studies have shown that many depressed patients have unusually high levels of cytokines. High levels can provoke a syndrome called "sickness behavior"--a depressed mood, sleeplessness, poor concentration. Once more, a chicken and egg conundrum complicates the matter: Do cytokines released as cancer fighters trigger depression, or do the cytokines triggered by the depression compromise the immune response to the cancer?
These links between a troubled mind and an ill body are only beginning to be understood. The big question that remains, says Nemeroff, is "whether the treatment of depression fundamentally changes the outcome of medical disorders. We just don't know the answer to that. But we are getting there."
