Abstract
A heightened risk of mood disorders, such as major depression, and acute depressive symptoms has been observed among HIV-seropositive individuals since the start of the AIDS epidemic, and an accumulating body of data now shows that depression may have an impact on morbidity and mortality among individuals with HIV disease. Although the specific physiologic mechanisms involved in this process have not been delineated, there is some evidence to suggest that certain components of innate immunity, including killer lymphocytes such as CD8+ T lymphocytes and natural killer cells, may represent key pathways through which depression affects HIV disease progression. This paper reviews some of the main studies examining the effects of depression on immunity and HIV disease progression and discusses the potential role of killer lymphocytes as an underlying mechanism by which depression may impact morbidity and mortality.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Spiegel D, Kraemer HC, Bloom JR, Gottheil E: Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989, 2:888–891.
Frasure-Smith N, Lesperance F, Talajic M: Depression following myocardial infarction: impact on 6-month survival. JAMA 1993, 270:1819–1825.
Frasure-Smith N, Lesperance F, Talajic M: Depression and 18-month prognosis after myocardial infarction. Circulation 1995, 91:999–1005.
Fawzy FI, Fawzy NW, Hyun CS, et al.: Malignant melanoma: effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psych 1993, 50:681–689.
Musselman DL, Evans DL, Nemeroff CB: The relationship of depression to cardiovascular disease: epidemiology, biology and treatment. Arch Gen Psych 1998, 55:580–592.
Faller H, Bulzebruck H, Drings P, Lang H: Coping, distress, and survival among patients with lung cancer. Arch Gen Psych 1999, 55:756–762.
Cruess DG, Leserman J, Petitto JM, et al.: Psychosocial-immune relationships in HIV disease. Semin Clin Neuropsychiatry 2001, 6:241–252.
Schleifer SJ, Keller SE, Bond RN, et al.: Major depressive disorder and immunity. Arch Gen Psych 1989, 46:81–87.
Evans DL, Leserman J, Pedersen CA, et al.: Immune correlates of stress and depression. Psychopharm Bull 1989, 25:319–324.
Stein M, Miller AH, Trestman RL: Depression, the immune system and health and illness. Arch Gen Psych 1991, 48:171–177.
Reichlin S: Mechanisms of disease: neuroendocrine-immune interactions. N Eng J Med 1993, 329:1246–1253.
Phillips MI, Evans DL: Neuroimmunology: Methods in Neurosciences, vol 24. San Diego: Academic Press Harcourt Brace Jovanovich; 1995.
Glaser R, Rabin B, Chesney M, et al.: Stress-induced immunomodulation. JAMA 1999, 281:2268–2270.
Kiecolt-Glaser JK, Glaser R: Depression and immune function: central pathways to morbidity and mortality. J Psychosom Res 2002, 53:873–876.
Ickovics JR, Hamburger ME, Vlahov D, et al.: Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women. JAMA 2001, 285:1466–1474. This large epidemiologic study documented elevated rates of psychologic symptoms among HIV+ women and also reported that greater depressive symptoms are associated with HIV disease progression among women.
Leserman J, Petitto JM, Gu H, et al.: Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors. Psychol Med 2002, 32:1059–1073. This empiric study presents data from a 9-year study of HIV+ men and suggests that stressful life events, dysphoric mood, and limited social support are associated with more rapid clinical HIV disease progression among men.
Evans DL, Mason K, Bauer R, et al.: Neuropsychiatric manifestations of HIV-1 infection and AIDS. In Psychopharmacology: The Fifth Generation of Progress. Edited by Charney D, Coyle J, Davis K, Nemeroff C. New York: Raven Press; 2002:1281–1299. This is a comprehensive review of the neuropsychiatric symptoms and conditions experienced by HIV+ individuals.
Dickey WC, Dew MA, Becker JT, Kingsley L: Combined effects of HIV-infection status and psychosocial vulnerability on mental health in homosexual men. Soc Psychiatry Psychiatric Epidemiol 1999, 34:4–11.
Griffin KW, Rabkin JG, Remien RH, Williams JB: Disease severity, physical limitations and depression in HIV-infected men. J Psychosom Res 1998, 44:219–227.
Lyketsos CG, Hoover DR, Guccione M, et al.: Changes in depressive symptoms as AIDS develops: the Multicenter AIDS Cohort Study. Am J Psychiatry 1996, 153:1430–1437.
Perkins DO, Stern RA, Golden RN, et al.: Mood disorders in HIV infection: prevalence and risk factors in a non-epicenter of the AIDS epidemic. Am J Psychiatry 1994, 151:233–236.
Rabkin JG, Goetz RR, Remien RH, et al.: Stability of mood despite HIV illness progression in a group of homosexual men. Am J Psychiatry 1997, 154:231–238.
Atkinson J, Grant I, Kennedy C, et al.: Prevalence of psychiatric disorders among men infected with human immunodeficiency virus: a controlled study. Arch Gen Psychiatry 1988, 45:859–964.
Williams JBW, Rabkin JG, Remien RH, et al.: Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection: standardized clinical assessment of current and lifetime psychopathology. Arch Gen Psychiatry 1991, 48:124–130.
Goggin K, Engelson ES, Rabkin JG, Kotler DP: The relationship of mood, endocrine, and sexual disorders in human immunodeficiency virus positive (HIV+) women: an exploratory study. Psychosom Med 1998, 60:11–16.
Moore J, Schuman P, Schoenbaum E, et al.: Severe adverse life events and depressive symptoms among women with, or at risk for, HIV infection in four cities in the United States of America. AIDS 1999, 13:2459–2468.
Morrison M, Petitto J, Ten Have T, et al.: Depressive and anxiety disorders in women with HIV infection. Am J Psychiatry 2002, 159:789–796.
Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960, 23:56–62.
Evans DL, Folds JD, Pettito J, et al.: Circulating natural killer cell phenotypes in males and females with major depression: relation to cytotoxic activity and severity of depression. Arch Gen Psych 1992, 49:388–395.
Herbert TB, Cohen S: Depression and immunity: a metaanalytic review. Psychol Bull 1993, 113:472–486.
Maes M: Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 1995, 19:11–38.
Page-Shafer K, Delorenze GN, Satariano W, Winkelstein W, Jr.: Comorbidity and survival in HIV-infected men in the San Francisco Men’s Health Survey. Ann Epidemiol 1996, 6:420–430.
Burack JH, Barrett DC, Stall RD, et al.: Depressive symptoms and CD4 lymphocyte decline among HIV-infected men. JAMA 1993, 270:2568–2573.
Mayne TJ, Vittinghoff E, Chesney MA, et al.: Depressive affect and survival among gay and bisexual men infected with HIV. Arch Int Med 1996, 156:2233–2238.
Patterson TL, Shaw WS, Semple SJ, et al.: Relationship of psychosocial factors to HIV disease progression. Ann Behav Med 1996, 18:30–39.
Ironson G, Friedman A, Klimas N, et al.: Distress, denial, and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus. Int J Behav Med 1994, 1:90–105.
Kemeny ME, Dean L: Effects of AIDS-related bereavement on HIV progression among New York City gay men. AIDS Educ Prev 1995, 7:36–47.
Kimerling R, Calhoun KS, Forehand R, et al.: Traumatic stress in HIV-infected women. AIDS Educ Prev 1999, 11:321–330.
Lyketsos CG, Hoover DR, Guccione M, et al.: Depressive symptoms as predictors of medical outcomes in HIV infection. JAMA 1993, 270:2563–2567.
Perry S, Fishman B, Jacobsberg L, Frances A: Relationships over 1 year between lymphocyte subsets and psychosocial variables among adults with infection by human immunodeficiency virus. Arch Gen Psych 1992, 49:396–401.
Rabkin JG, Williams JB, Remien RH, et al.: Depression, distress, lymphocyte subsets, and human immunodeficiency virus symptoms on two occasions in HIV-positive homosexual men. Arch Gen Psych 1991, 48:111–119.
Zorrilla EP, McKay JR, Luborsky L, Schmidt K: Relation of stressors and depressive symptoms to clinical progression of viral illness. Am J Psych 1996, 153:626–635.
Evans DL, Leserman J, Perkins DO, et al.: Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection. Am J Psychiatry 1995, 152:543–550.
Evans DL, Leserman J, Perkins DO, et al.: Severe life stress as a predictor of early disease progression in HIV infection. Am J Psychiatry 1997, 154:630–634.
Leserman J, Petitto JM, Perkins DO, et al.: Severe stress, depressive symptoms, and changes in lymphocyte subsets in human immunodeficiency virus-infected men. Arch Gen Psych 1997, 54:279–285.
Leserman J, Jackson ED, Petitto JM, et al.: Progression to AIDS: the effects of stress, depressive symptoms, and social support. Psychosom Med 1999, 61:397–406.
Leserman J, Petitto JM, Golden RN, et al.: Impact of stressful life events, depression, social support, coping and cortisol on progression to AIDS. Am J Psychiatry 2000, 157:1221–1228.
Evans DL, Ten Have T, Douglas SD, et al.: Association of depression with viral load, CD8 T lymphocytes, and natural killer cells in women with HIV infection. Am J Psychiatry 2002, 159:1752–1759. This is a recent empiric paper documenting an association between depression and killer lymphocyte number and function among HIV+ women.
Petitto JM, Folds JD, Ozer H, et al.: Altered diurnal variation in natural killer cell phenotypes and cytotoxic activity in major depression. Am J Psychiatry 1992, 148:694–696.
Chehimi J, Starr SE, Frank I, et al.: Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both health donors and human immunodeficiency virus-infected patients. J Exp Med 1992, 175:789–796.
Whiteside TL, Herberman RB: Role of human natural killer cells in health and disease. Clin Diagn Lab Immunol 1994, 1:125–133.
Levy JA: HIV and the Pathogenesis of AIDS. Washington, DC: American Society for Microbiology Press; 1998.
Oliva A, Kinter AL, Vaccarezza M, et al.: Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. J Clin Invest 1998, 102:223–231.
Jassoy C, Harrer T, Rosenthal T, et al.: Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha, and TNF-beta when they encounter their target antigens. J Virol 1993, 67:2844–2852.
Ho HN, Hultin LE, Mitsuyasu RT, et al.: Circulating HIVspecific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. J Immunol 1993, 150:3070–3079.
Fauci AS, Pantaleo G, Stanley S, Weissman D: Immunopathogenic mechanisms of HIV infection. Ann Int Med 1996, 124:654–663.
Ferbas J: Perspectives on the role of CD8+ cell suppressor factors and cytotoxic T lymphocytes during HIV infection. AIDS Res Hum Retroviruses 1998, 14:S153-S160.
Greenberg P, Riddell S: Deficient cellular immunity: finding and fixing the defects. Science 1999, 285:546–551.
Famularo G, Moretti S, Marcellini S, et al.: CD8 lymphocytes in HIV infection: helpful and harmful. J Clin Lab Immunol 1997, 49:15–32.
Perrit D, Sesok-Pizzini DA, Schretzenmair R, et al.: C1.7 antigen expression on CD8+ T cells is activation dependent: increased proportion of C1.7+ CD8+ T cells in HIV-1 infected patients with progressing disease. J Immunol 1999, 162:7563–7568.
Gea-Banacloche JC, Migueles SA, Martino L, et al.: Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term non-progressors. J Immunol 2000, 165:1082–1092.
Gamberg JC, Bowmer MI, Trahey JC, et al.: Functional and genetic integrity of the CD8 T-cell repertoire in advanced HIV infection. AIDS 1999, 13:2043–2053.
Levy JA: The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol 2001, 22:312–316.
Ironson G, Balbin E, Solomon G, et al.: Relative preservation of natural killer cytotoxicity and number in healthy AIDS patients with low CD4 cell counts. AIDS 2001, 15:2065–2073. This is a recent empiric paper documenting the preservation of NK cell number and function among healthy individuals with AIDS with low CD4+ cell counts.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cruess, D.G., Douglas, S.D., Petitto, J.M. et al. Association of depression, CD8+ T lymphocytes, and natural killer cell activity: Implications for morbidity and mortality in human immunodeficiency virus disease. Curr Psychiatry Rep 5, 445–450 (2003). https://doi.org/10.1007/s11920-003-0083-4
Issue Date:
DOI: https://doi.org/10.1007/s11920-003-0083-4