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Human history is replete with dramatic stories of the connection between stress and disease. John Hunter (1728–1793), a surgeon and medical educator at St. George’s Hospital in London, reportedly stated publicly, “My life is at the mercy of any rogue who chooses to provoke me,” and soon afterward died following a contentious meeting with hospital administrators.

A review of coroners’ records in Los Angeles in 1994 revealed a marked increase in deaths, including sudden death, related to atherosclerotic cardiovascular disease on the day of the 1994 Northridge earthquake. In 1999 during a 7.3 magnitude earthquake in Taiwan, patients on Holter monitors showed heart rate variability derangement due to withdrawal of parasympathetic activity and increase in sympathetic arousal. In the quarterfinal of the 1996 European football championships between the French and Dutch teams, a draw at the end of overtime resulted in a sudden death penalty shootout, which was won by the French. An analysis of mortality in the total population of Dutch men and women aged 45 years or more revealed a relative risk of death from acute myocardial infarction (MI) or stroke of 1.51 among the men on the day of the match, compared with the 5 days on either side. There was no such effect on French men. This gave new meaning to the term “sudden death penalty.”

The psychological sequelae of exposure to life-threatening stressors are also problematic and disruptive to people’s lives. The terrorist attacks on the World Trade Center and the Pentagon on September 11, 2001, were witnessed directly by an estimated 100,000 people and vicariously by millions of Americans and others worldwide. In the period of time between October 16 and November 15, 2001, it is estimated that 7.5% of Manhattan residents south of 110th street were suffering from posttraumatic stress disorder (PTSD) and 9.7% were suffering from depression. In a representative sample of the American population surveyed 3–5 days following the attacks, 44% reported one or more symptoms consistent with acute stress disorder (ASD). Refugees and prisoners of war who have been exposed to torture are also likely to develop symptoms of PTSD, anxiety, and depression.

Less dramatically, research since the late 1960s has demonstrated correlations between significant changes in individuals’ lives and the subsequent onset of various types of physical and psychological illness. A consistent relationship has even been found between daily hassles and the onset of illness.

The interrelationship between mental stress and physical disease is complex and multifactorial. As a result, the study of stress and disease embraces a wide range of behavioral, emotional, cognitive, physiologic, hormonal, biochemical, cellular, environmental, and even spiritual interconnections, not easily understood or encapsulated in the controlled clinical trial.

It has been estimated that up to 70% of primary care visits are for problems related to stress and lifestyle. Most clinicians, however, have not been trained to extend their diagnostic workup ...

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