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Psychosomatic Medicine 61:850-860 (1999)
© 1999 American Psychosomatic Society


ORIGINAL ARTICLE

Pathways Linking Major Depression and Immunity in Ambulatory Female Patients

Gregory E. Miller, PhD, Sheldon Cohen, PhD and Tracy B. Herbert, PhD

From the Department of Psychology (G.E.M., S.C., T.B.H.), Carnegie Mellon University, and Western Psychiatric Institute and Clinic (G.E.M.), University of Pittsburgh School of Medicine, Pittsburgh, PA.

Address reprint requests to: Gregory Miller, PhD, Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213. Email: gmiller{at}andrew.cmu.edu

OBJECTIVES: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship.

METHODS: We studied 32 women who met Diagnostic and Statistical Manual of Mental Disorder, fourth edition, criteria for major depressive disorder and 32 healthy female control subjects. The groups were matched for age and ethnicity. None were taking medication, and all were free of disease involving the immune system.

RESULTS: Depressed subjects had reduced proliferative responses to the mitogens concanavalin A and phytohemagglutinin compared with control subjects. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation.

CONCLUSIONS: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.

Key Words: psychoneuroimmunology • depression • immunity • physical activity

Abbreviations: ACTH = adrenocorticotropin; ANOVA = analysis of variance; BDI = Beck Depression Inventory; ConA = concanavalin A; CV = coefficient of variation; DSM-IV = Diagnostic andStatistical Manual of Mental Disorders, fourth edition; ELISA = enzyme-linked immunosorbent assay; GCRC = GeneralClinical Research Center; HAM-D = Hamilton Rating Scale forDepression; HPA = hypothalamic-pituitary-adrenal; IL-1ß =interleukin 1-ß; NKCC = natural killer cell cytotoxicity; PHA = phytohemagglutinin; POMS = Profile of Mood States; SADS-L = Schedule for Affective Disorders–Lifetime Version; SCID-P = Structured Clinical Interview for DSM-IV–PatientVersion; THC-tetrahydrocannabinol.




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