Hearts and Minds

It seems absurd that in the third millennium intelligent human beings should still be surprised to "discover" that the mind and the body are linked in myriad ways. Nevertheless, it has fallen to modern science to make the case convincingly airtight and to describe the intricacies of how.

One of the most intriguing links turns out to be between the brain and the heart. Of course, poets have told us from time immemorial that hearts and minds work together-and often unravel together. But it's taken all this time for medicine to furnish the proof and describe the ways.

Some of the strongest evidence concerns depression and heart disease. Over the past decade, doctors have found that these two disorders are not just common companions. Each, it turns out, can lead to the other.

At Columbia University, where he is a professor of psychiatry, Alexander Glassman, M.D., had been studying the cardiac effects of antidepressant drugs when reports began to trickle in confirming what he had long suspected-that depression makes heart disease particularly deadly. But it wasn't clear just how much of a role cigarette smoking played; the depressed are especially apt to smoke, and by itself smoking is a potent contributor to heart disease.

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So Glassman teamed up with epidemiologists who had data on thousands of people who had been followed for over a decade. In 1993 the group reported that, even after they controlled for smoking, depression has catastrophic effects on hearts that are already weakened by disease. It essentially multiplies the lethality of heart disease, substantially increasing the risk of sudden death within the next year. And sudden death, observes Glassman, is almost always due to cardiac arrhythmia.

The report dropped an even bigger bombshell; it showed that depression may actually lead to the development of coronary artery disease. Healthy people who are struck by depression are more likely than their counterparts without the mental ailment to develop heart disease about 10 years down the road-just because they once got depressed. A subsequent study of 1551 people in Baltimore who were free of heart disease showed that those with a history of depression were four times more likely than the non-depressed to suffer a heart attack in the next 14 years.

"There are two things we can say without any hesitancy," commented Glassman. "If you're 45, in perfect health, and depressed, you're somewhere between 50% and 100% more likely to have a heart attack than if you weren't depressed. That's big. And if you have a heart attack and then get depressed, whether you simply get some symptoms of depression or the full diagnosis, over the next 18 months you are three and a half times more likely to die. That's even bigger." Later studies have confirmed that the risk of dying is two to four times higher among heart patients who are depressed compared to those who aren't.

The numbers add up. There are roughly 500,000 heart attacks a year in the U.S. And 20% of heart attack victims develop depression. "Fifty percent of the population of the U.S. still dies of heart disease," says Glassman. "It is clearly aggravated dramatically by depression."

The year 1994 presented another landmark reading on the seismograph charting body-mind connections. A day after the formidable Northridge earthquake in California, heart attacks jumped from an average of 4.6 to an off-the-charts 24. The psychic stress of disaster registered powerfully on the body.

Depression, it turns out, is not just a disease of mood. "That is a limited perception of what goes on in depression," Glassman told a recent conference on the disorder.

"Depression is a medical illness with psychiatric manifestations," Columbia University psychiatrist Philip R. Muskin, M.D., said at the same conference. "Lots of it is physical." Psychological distress, for example, multiplies the risk of stroke by 1.5 times. And it triples the likelihood of having a fatal stroke. "The sorrow which has no vent in tears may make other organs weep," said Muskin, quoting Victorian psychiatrist Henry Maudsley.

In the first six months after a heart attack, depression increases by a factor of 4.3 the risk of dying. Depression is the single biggest predictor of survival after a heart attack-although it is seldom recognized as such. Among emotional states, "anxiety doesn't change one's chances of dying after a heart attack. Nor does anger," Glassman observed. "Only depression has a dramatic effect on survival after a heart attack."

Exactly what puts the head and the heart on a collision course is a matter of intense speculation and considerable research. There are number of possible pathways connecting the two. Glassman and others think that depression affects the working of the body in a variety of ways, so that there are multiple channels by which depression and heart disease are linked.

* Sticky platelets. Blood platelets play a key role in the propensity of blood to form clots and the blood platelets of the depressed can become dangerously hyperactive. Platelets turn out to be stickier in those who are depressed. And blood platelets are loaded with receptors for serotonin.

At Emory University in Atlanta, researcher Dominique L. Musselman, M.D., has shown that the platelets of depressed people are hair-trigger responsive to activation signals, clumping when they should be flowing. Activated platelets are drawn to those spots in artery walls that have accumulated cholesterol-laden plaque, where they adhere and rope in even more platelets. Under the right circumstances, clotting can occur quickly, choking off blood flow to the heart, creating conditions for the most common type of heart attack.

It may be that treatment of the mood disorder with SSRI antidepressants has a favorable impact on heart disease. In preliminary test-tube studies, researchers elsewhere have found that the drug sertraline keeps blood platelets from clumping. The antidepressant was found to be as strong as super aspirin in preventing blood clotting.

Not all antidepressants are created equal with regard to heart disease. The tricyclic antidepressants, for example, are thought to be somewhat cardiotoxic, stimulating cardiac arrhythmias or setting the stage for them via release of adrenaline.

* Neglect. It may be that some links between depression and heart disease are a matter of psychologically driven behavior. Those with depression are apt to take poor care of themselves and may neglect signs of disease that could be treated, making it more deadly. They may smoke, eat poorly or exercise little, behaviors that promote heart disease. If the depressed are being treated for heart disease, they may not take cardiac medications reliably.

* Limited heart rate variability. The normal heart responds to challenges and to quiet by varying the rate at which it beats and pumps out blood. Depression may take a toll on the autonomic nervous system that orchestrates such responsiveness. Studies show that depressed people have less heart rate variability than non-depressed persons. The lack of heart rate variability may make those with existing heart disease especially susceptible to catastrophic incidents.

* Blood pressure abnormalities. In impairing autonomic control of the heart, depression subjects the body to oscillations of blood pressure that abet the thickening of blood vessel walls and build-up of cholesterol-laden deposits. Blood flow to the heart is reduced.

* Low-grade inflammation. Depression affects a number of elements of the immune system to produce an enhanced inflammatory response. Researchers now believe that inflammation is a major source of coronary artery disease and also exacerbates blood clotting.

* Stress hormones. Depression is associated with chronically elevated stress hormones, such as cortisol and adrenaline. These hormones have myriad actions on the brain and body organs. They may directly put a burden on heart muscle and result in cardiac distress. They also raise levels of blood sugar, insulin and cholesterol, promoting atherosclerosis in coronary arteries. What's more, stress hormones put the body in attack mode, preparing it for "fight or flight," diverting metabolism away from the needed repair of damaged heart tissue.

* Genes. There's growing evidence that some depressed people have variations in two genes that increase the risk of a heart attack. The genes also have an impact on many aspects of brain function. The co-existence of these two common gene mutations could predispose some people to both depression and heart disease.

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