It seems obvious to most people that the brain and the rest of the body interact. Stress seems to worsen most general medical conditions, mortality is higher among widowers than married men, and almost everyone becomes moody when he or she has a viral infection. However, these are mostly anecdotal observations. The precise ways in which mind and body relate in health and disease is more elusive and, at times, controversial.

Perhaps the hardest evidence we have for a mind-body connection comes from studies showing that depression is an independent—and, surprisingly, quite a robust—risk factor for cardiovascular disease. Following acute coronary syndrome depression significantly worsens outcome, including increasing all-cause mortality rates.

Another well-documented finding, going in the opposite direction, is the high rate of depression experienced by those receiving α-interferon for the treatment of hepatitis C or malignant melanoma. Less secure is whether depression increases risk or worsens prognosis for cancer; why patients with schizophrenia are at greater risk for heart disease and cancer than the general population; if it is true that stress plays a role in exacerbations of multiple sclerosis; and what is the relationship between depression and the risk for Alzheimer's disease. In each there are conflicting epidemiological data and difficulties understanding the neural mechanisms that would broker the relationship between brain and targeted peripheral organ.