Comorbidity of Depression with Other Medical Diseases in the Elderly K. Ranga R. Krishnan, Mahlon Delong, Helena Kraemer, Robert Carney, David Spiegel, Christopher Gordon, William McDonald, Mary Amanda Dew, George Alexopoulos, Kathleen Buckwalter, Perry D. Cohen, Dwight Evans, Peter G. Kaufmann, Jason Olin, Emeline Otey, and Cynthia Wainscott A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Par- kinson’s disease, Alzheimer’s disease, stroke, and arthri- tis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate med- ical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions. Biol Psy- chiatry 2002;52:559 –588 © 2002 Society of Biological Psychiatry Key Words: Age, depression, medical, cardiac, cancer, HIV Introduction W hen discussing depression in the elderly a major consideration is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders such as cancer, heart disease, Parkinson’s disease, Alzheimer’s disease, stroke, and ar- thritis. In this article we focus on bringing clarity to the definition of comorbidity and then discuss a number of medical disorders for which there is emerging evidence in support of the various types of comorbidity. Most of the disorders that we have focused on occur in the elderly except for HIV infection. This review focuses exclusively on unipolar depressive disorder. There are a number of reasons for this: (1) the higher prevalence of depression versus bipolar disorder in the elderly; (2) the greater volume of research on depression with a wide range of other diseases which are highly prevalent in the elderly, and (3) the limits of time and resources of the work group. It should be noted that some work has been done on medical comorbidity and bipolar disorder. The existing literature focuses primarily on bipolar illness in the con- text of stroke, Cushing’s disease, multiple sclerosis and migraine. Hopefully in the near future a similar extensive literature review will be able to be done on comorbidity and bipolar disorder. Methodological Issues Challenges in the Definition of “Comorbidity” The term comorbidity refers to the co-occurrence of two disorders or syndromes (not symptoms) in the same patient. Defined as broadly as that, every pair of disorders or syndromes for which the diagnosis of one does not categorically exclude the diagnosis of the other are “co- morbid.” Thus, one might state that, for example, the risk of corns and colds are comorbid.” From this perspective, most comorbidity is of trivial clinical or practical signifi- cance, certainly not worth any investment of time or money for research purposes, nor is it important to clinical decision making. Corns and colds may seem an extreme example, but it is at least obvious in its potential limitations. Errors of this kind in the research literature on depression and comor- From the Duke University Medical Center (RRK), Durham, North Carolina; Emory University School of Medicine (MD, WM), Atlanta, Georgia; Stanford Uni- versity School of Medicine (HK, DS), Stanford, California; Washington University School of Medicine (RC), St. Louis, Missouri; National Institute of Mental Health (CG, JO, EO), Bethesda, Maryland; Western Psychiatric Institute and Clinic (MAD), University of Pittsburgh, Pittsburgh, Pennsylvania; Cornell University (GA), Ithaca, New York; University of Iowa (KB), Iowa City, Iowa; Parkinson’s Disease Foundation (PDC), New York, New York; University of Pennsylvania (DE), Philadelphia, Pennsylvania; National Heart, Lung and Blood Institute (PGK), Bethesda, Maryland; and National Mental Health Association of Georgia (CW), Atlanta, Georgia. Address reprint requests to K. Ranga R. Krishnan, M.D., Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3950, Durham NC 27710. Received September 27, 2001; revised April 12, 2002; revised May 13, 2002; accepted June 6, 2002. © 2002 Society of Biological Psychiatry 0006-3223/02/$22.00 PII S0006-3223(02)01472-5