The diagnosis of major depression represents a clinical syndrome with a number of biological, behavioral, affective, and cognitive components. Recent evidence suggests that depression places people at increased risk for physical morbidity and mortality. Increased risk among depressed persons is thought to be attributable to intense affect triggering biological changes that make people more susceptible to physical diseases. Because the immune system is known to respond to changes in affect, research has focused on immune alteration as a plausible pathway through which depression could influence physical health. There is substantial evidence that clinically depressed persons are immunologically different than nondepressed persons, although why these differences occur is not known. The primary focus of this investigation is to address the important question of why immune differences exist in clinical depression. To do this, four specific questions are asked: (1) Are the immune changes associated with clinical depression related to the start of depression or are they characteristic of those who have ever been clinically depressed? (2) Are associations between depression and immunity attributable to the affective component of the depressive state? (3) Do cortisol and/or the catecholamines mediate the immune alterations in subjects with clinical depression? and (4) Do health practices such as sleep, diet, caffeine and alcohol intake, cigarette use, and exercise account for the associations of depression with immunity? The scope of immune outcomes of interest in this study is broad and includes both enumerative measures (i.e., the numbers of circulating eosinophils, basophils, monocytes, neutrophils, and lymphocytes, as well as specific lymphocyte subsets including N-K, B, T, helper T, suppressor T, and cytotoxic T cells) and functional measures (i.e., IL-1 production by monocytes, IL-2 production by lymphocytes, lymphocyte proliferative response to PHA, Con A, and PWM, and NK cell cytotoxic activity). The design to be used will increase the reliability of data collected. Because immune system functions and enumerations are influenced by a variety of factors, obtaining a reliable characterization of an individual's immune status requires more than one assessment. Therefore, the reliability of measurement of the neuroendocrine and immune parameters will be improved by assessing subjects twice separated by 24 hours. Subjects for the study will be physically healthy, age- and race-matched women, between 25 and 50 years of age. No depressed patients will be hospitalized and all subjects will be free of medication.
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