Hostname: page-component-77c89778f8-swr86 Total loading time: 0 Render date: 2024-07-19T22:15:43.037Z Has data issue: false hasContentIssue false

How does stress affect you? An overview of stress, immunity, depression and disease

Published online by Cambridge University Press:  11 October 2011

Clementine Maddock
Maudsley Hospital, London SE5 8AZ, UK
Carmine M. Pariante*
Section of Clinical Neuropharmacology, Institute of Psychiatry, King's CollegeLondon, London SE5 8AF, UK
Indirizzo per la corrispondenza: Dr. CM. Pariante, Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, 1 Windsor Walk, Denmark Hill, London SE5 8AF, UK. Fax: +44-(0)-20-7848.0051 E-mail:


Objective. Stress is a term that has become synonymous with modern life. This review aims to appraise the evidence linking stress with disease with particular reference to the major causes of morbidity and mortality in the Western World, cardiovascular disease, cancer, and depression. Changes in immune parameters in stressful situations were reviewed as a possible pathophysiological mechanism for such effects. Method – A Medline search was carried out for the period 1996-2000 to identify recent findings in this field using the terms “stress”, “disease”, “immune system”. Relevant references that were found in all identified publications were also followed up. Results – There is evidence to link stress with the onset of major depression and with a poorer prognosis in cardiovascular disease and cancer. Few small studies suggest that stress management strategies may help to improve survival. Chronic stress appears to result in suppression of the immune response, whereas immune activation and suppression have been associated with acute stress. Inflammatory cytokines, soluble mediators of the immune response, can result in symptoms of depression. Conclusion – Further prospective epidemiologically based studies are needed to clarify the role of stress on disease onset, course, and prognosis. Stress management strategies, aimed at prolonging survival in patients with cardiovascular disease, cancer, and possibly other chronic illnesses, are an exciting area of further research. Immune system changes may account for the relationship between stress and disease. We propose the “stress, cytokine, depression” model as a biological pathway to explain the link between stressful life events and depression.


Scopo – Il termine “stress” viene spesso usato come sinonimo di “vita moderna”. In questa revisione della letteratura abbiamo valutato la relazione tra lo stress e l'insorgenza o il decorso della depressione maggiore, dei disturbi cardiovascolari e delle malattie tumorali, le maggiori cause di morbidità e di mortalita nel mondo occidentale. Abbiamo anche discusso come i cambiamenti nei parametri del sistema immunitario indotti dallo stress possano essere considerati, almeno in parte, responsabili di questa relazione tra stress e malattia. Metodo – Abbiamo condotto una ricerca su Medline per il periodo 1996-2000, utilizzando i termine stress, disease (malattia) e immune system (sistema immunitario), allo scopo di identificare i più recenti sviluppi della ricerca in questo campo. Abbiamo anche rintracciato le più importanti pubblicazioni citate in questi articoli. Risultati – Gli studi in letteratura confermano il legame tra lo stress e l'insorgenza della depressione. Lo stress sembra anche avere un effetto negativo sulla prognosi dei disturbi cardiovascolari e delle malattie tumorali, ed evidenze preliminari suggeriscono che interventi di gestione dello stress possono migliorare la sopravvivenza in questi pazienti. Situazioni di stress cronico sono associate ad una soppressione della funzionalità del sistema immunitario, mentre stress acuti hanno un effetto sia attivante, sia inibitorio. La liberazione di citochine infiammatorie, mediatori solubili della risposta immunitaria, può indurre la comparsa di sintomi depressivi. Conclusioni – Studi epidemiologici prospettici sono necessari per chiarire il ruolo dello stress nell'insorgenza, decorso e prognosi delle malattie. L'utilizzo di terapie di gestione dello stress allo scopo di migliorare la prognosi dei pazienti con disturbi cardiovascolari, malattie tumorali ed altre malattie croniche, è un'area di ricerca particolarmente interessante. Gli effetti dello stress sul sistema immunitario sono importanti per capire il legame tra stress e malattia. In particolare, l'aumentata produzione di citochine infiammatorie durante situazioni di stress costituisce un possibile meccanismo biologico per spiegare il legame tra stress e depressione.

Invited Paper
Copyright © Cambridge University Press 2001

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



Ackerman, K.D., Martino, M., Heyman, R., Moyna, N.M. & Rabin, B.S. (1998). Stressor-induced alteration of cytokine production in mul-tiple sclerosis patients and controls. Psychosomatic Medicine 60, 60484.CrossRefGoogle Scholar
Andersen, B.L., Farrar, W.B., Golden-Kreutz, D., Kutz, L.A., MacCal-lum, R., Courtney, M.E. & Glaser, R. (1998). Stress and immune responses after surgical treatment for regional breast cancer. Journal of the National Cancer Institute 90, 90–30.CrossRefGoogle ScholarPubMed
Anisman, H., Ravindran, A.V., Griffiths, J. & Merali, Z. (1999). En-docrine and cytokine correlates of major depression and dysthymia with typical or atypical features. Molecular Psychiatry 4, 4182.CrossRefGoogle ScholarPubMed
Bartrop, R.W., Lazarus, L., Luckherst, E. & Kiloh, L.H. (1977). Depressed lymphocyte function after bereavement. Lancet 1, 1834.Google ScholarPubMed
Beem, E.E., Hooijkaas, H., Cleiren, M.H.P.D., Schut, H.A.W., Garssen, B., Croon, M.A., Jabaaij, L., Goodkin, K., Wind, H. & de Vries, M.J. (1999). The immunological and psychological effects of bereave-ment: does grief counselling really make a difference? A pilot study. Psychiatry Research 85, 85–81.CrossRefGoogle ScholarPubMed
Besedovsky, H.O. & Del Rey, A. (1996). Immune-neuro-endocrine in- teraction: facts and hypotheses. Endocrine Review 17, 1764.CrossRefGoogle Scholar
Blumenthal, J.A., Jiang, W., Babyak, M.A., Krantz, D.S., Frid, D.J., Cole-man, R.E., Waugh, R., Hanson, M., Appelbaum, M., O'Connor, C. & Morris, J.J. (1997). Stress management and exercise training in car-diac patients with myocardial ischaemia. Effects on prognosis and evaluation of mechanisms. Archives of Internal Medicine 157, 1572213.CrossRefGoogle Scholar
Brown, G.W. & Harris, T.O. (1978). Social Origins of Depression: a Study of Psychiatric Disorder in Women. Tavistock Publications': London.Google Scholar
Brown, G.W., Andrews, B., Harris, T., Adler, Z. & Bridge, L. (1986). So-cial support, self-esteem and depression. Psychological Medicine 16, 16813.CrossRefGoogle Scholar
Carpiniello, B., Orru, M.G., Baita, A., Pariante, C.M. & Farci, M.G. (1998). Mania induced by alpha-interferon withdrawal. Archives of General Psychiatry 55, 5588.CrossRefGoogle Scholar
Checkley, S. (1996). The neuroendocrinology of depression and chronic stress. British Medical Bulletin 52, 52597.CrossRefGoogle ScholarPubMed
Chrousos, G.P. & Gold, P.W. (1992). The Concepts of stress and stress system disorders. Journal of the American Medical Association 267, 2671244.Google ScholarPubMed
Cohen, S., Tyrrell, D.A.J. & Smith, A.P. (1991). Psychological stress and susceptibility to the common cold. New England Journal of Medicine 325, 325606.CrossRefGoogle ScholarPubMed
Cohen, S., Frank, E., Doyle, W.J., Skoner, D.P., Rabin, B.S. & Gwaltney, J.M. Jr (1998). Types of stressors that increase sus- ceptibility to the common cold in healthy adults. Health Psychology 17, 17214.CrossRefGoogle Scholar
Cohen, S., Doyle, W.J. & Skoner, D.P. (1999). Psychological stress, cy-tokine production, and severity of upper respiratory illness. Psy-chosomatic Medicine 61, 61175.Google Scholar
Dobbin, J.P., Harth, M., McCain, G.A., Martin, R.A. & Cousin, K. (1991). Cytokine production and lymphocyte transformation during stress. Brain, Behaviour, and Immunity 5, 5339.CrossRefGoogle ScholarPubMed
Fawzy, F.I., Cousins, N., Fawzy, N.W., Kemeny, M.E., Elashoff, R. & Morton, D. (1990a). A structured psychiatric intervention for can- cer patients. I. Changes over time in methods of coping and affective disturbance. Archives of General Psychiatry 47, 720725.CrossRefGoogle Scholar
Fawzy, F.I., Kemeny, M.E., Fawzy, N.W., Elashoff, R., Morton, D., Cousins, N. & Fahey, J.L. (1990b). A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures. Archives of General Psychiatry 47, 47729.Google ScholarPubMed
Fawzy, F.I., Fawzy, N.W., Hyun, C.S., Elashoff, R., Guthrie, D., Fahey, J.L. & Morton, D.L. (1993). Malignant melanoma: effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Archives of General Psychiatry 50, 50681.CrossRefGoogle ScholarPubMed
Friedman, M. & Rosenman, R.H. (1959). Association of specific overt behaviour pattern with blood and cardiovascular findings: blood cholesterol level, blood clotting time, incidence of arcus senilis and clinical coronary artery disease. Journal of the American Medical Association 169, 1691286.CrossRefGoogle Scholar
Gennaro, S., Fehder, W., Nuamah, I.F., Campbell, D.E. & Douglas, S.D. (1997). Caregiving to very low birthweight infants: a model of stress and immune response. Brain, Behaviour, and Immunity 11, 11201.CrossRefGoogle Scholar
Glaser, R., Kiecolt-Glaser, J.K., Bonneau, R.H., Malarkey, W., Kennedy, S. & Hughes, J. (1992). Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosomatic Medicine 54, 54–22.CrossRefGoogle ScholarPubMed
Glaser, R., Kiecolt-Glaser, J.K., Marucha, P.T., MacCallum, R.C., Laskowski, B.F. & Malarkey, W.B. (1999). Stress related changes in pro-inflammatory cytokine production in wounds. Archives of General Psychiatry 56, 56450.CrossRefGoogle Scholar
Haack, M., Hinze-Selch, D., Fenzel, T., Kraus, T., Kuhn, M., Schuld, A. & Pollmacher, T. (1999). Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. Journal of Psychiatric Research 33, 33407.CrossRefGoogle ScholarPubMed
Herberman, R.B. & Ortaldo, J.R. (1981). Natural Killer cells: their role in defences against disease. Science 214, 214–24.CrossRefGoogle ScholarPubMed
Herbert, T.B. & Cohen, S. (1993). Stress and immunity in humans: a meta-analytic review. Psychosomatic Medicine 55, 55364.CrossRefGoogle ScholarPubMed
Hollis, J.F., Connett, J.E., Stevens, V.J. & Greenlick, M.R. (1990). Stressful life events, type A behaviour, and the prediction of cardiovascular and total mortality over six years. Journal of Behavioural Medicine 13, 13263.CrossRefGoogle ScholarPubMed
Kent, S., Bluthe, R., Kelley, K.W. & Dantzer, R (1992). Sickness behaviour as a new target for drug development. Trends in Pharmacological Sciences 13, 1324.CrossRefGoogle Scholar
Kiecolt-Glaser, J.K., Glaser, R., Shuttleworth, E.C., Dyer, C.S., Ogrocki, P. & Speicher, C.E. (1987). Chronic stress and immunity in family caregivers of Alzheimer's disease victims. Psychoso-matic Medicine 49, 49523.Google ScholarPubMed
Kiecolt-Glaser, J.K. & Glaser, R. (1991a). Stress and immune func- tion in humans. In Psychoneuroimmunology, 2nd ed. (ed. Ad-er, R., Felter, D.L. and Cohen, N.), pp. 849867. Academic Press: New York.CrossRefGoogle Scholar
Kiecolt-Glaser, J.K., Dura, J.R., Speicher, C.E., Trask, O.J. & Glaser, R. (1991b). Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosomatic Medicine 53, 53345.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J.K., Marucha, P.T., Malarkey, W.B., Mercado, A.M. & Glaser, R. (1995). Slowing of wound healing by psychological stress. Lancet 346, 3461194.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, J.K., Glaser, R., Gravenstein, S., Malarkey, W.B. & Sheri-dan, J. (1996). Chronic stress alters the immune response to influenza virus vaccine in older adults. In Proceedings of the National USA 93, pp. 30433047.Google Scholar
Lanquillon, S., Krieg, J.C., Bening-Abu-Shach, U. & Vedder, H. (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopliarmacology 22, 22370.Google ScholarPubMed
Lazarus, R.S. & Folkman, S. (1984). Stress Appraisal, and Coping. Springer: New York.Google Scholar
Le May, L.G., Vander, A.J. & Kluger, M.J. (1990). The effects of psy- chological stress on plasma interleukin-6 activity in rats. Physiology and Behaviour 47, 47957.Google Scholar
Maes, M., Bosmans, E., Meltzer, H.Y., Scharpe, S. & Suy, E. (1991). In-terleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression? American Journal of Psychiatry 150, 1501189.Google Scholar
Maes, M., Song, G, Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., Bosmans, E., De Meester, I., Benoy, I., Neels, H., Demedts, P., Janca, A., Scharpe, S. & Smith, R.S. (1998). The effects of psychological stress on hu- mans: increased production of pro-inflammatory cytokines and a Thl- like response in stress-induced anxiety. Cytokine 10, 10313.CrossRefGoogle Scholar
Maes, M., Van Bockstaele, D.R., Van Gastel, A., Song, C., Schotte, C., Neels, H., DeMeester, I., Scharpe, S. & Janca, A. (1999). The effects of psychological stress on leukocyte subset distribution in humans: evidence of immune activation. Neuropsychobiology 39, 39–1.CrossRefGoogle ScholarPubMed
McGee, R., Williams, S. & Elwood, M. (1996). Are life events related to the onset of breast cancer? Psychological Medicine 26, 26441.CrossRefGoogle Scholar
Miller, A.H., C.M., & Pearce, B.P. (1999). Effects of cytokines on glu-cocorticoid receptor expression and function. Glucocorticoid re-sistance and relevance to depression. Advances in Experimental Medicine and Biology 461, 461–107.Google Scholar
Miller, A.H., Pearce, B.P. & Pariante, C.M. (2000). Immune system and central nervous system interactions. In Comprehensive Textbook of Psychiatry, 7th ed. (ed. Kaplan, H.I. and Sadock, B.J.), pp. 113133. Lippincott: Phildelphia.Google Scholar
Mohr, D.C., Goodkin, D.E., Bacchetti, P., Boudewyn, A.C., Huang, L., Marrietta, P., Cheuk, W. & Dee, B. (2000). Psychological stress and the subsequent appearance of new brain MRI lesions in MS. Neurology 55, 55–55.CrossRefGoogle ScholarPubMed
O'Connor, C.M., Gurbel, P.A. & Serebruany, V.L. (2000). Depression and ischaemic heart disease. American Heart Journal 140, S6369.CrossRefGoogle Scholar
Pariante, C.M. & Miller, A.H. (1995). Natural killer cell activity in ma-jor depression: a prospective study of the in-vivo effects of desmethylimipramine treatment. European Neuropsychopliarma-cology, Suppl. 5, 583.Google Scholar
Pariante, C.M., Carpiniello, B., Orru, M.G., Sitzia, R., Piras, A., Farci, A.M.G., Del Giacco, G.S., Piludu, G. & Miller, A.H. (1997a). Chronic caregiving stress alters peripheral blood immune parame-ters: the role of age and severity of stress. Psychotherapy and Psy-chosomatics 66, 66199.Google Scholar
Pariante, C.M., Pearce, B.D., Pisell, T.L., Owens, M.J. & Miller, A.H. (1997b). Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine. Molecular Pliannacology 52, 52571.Google ScholarPubMed
Pariante, C.M., Orru, M.G., Baita, A., Farci, M.G. & Carpiniello, B. (1999a). Treatment with interferon-alpha in patients with chronic hepatitis and mood or anxiety disorders. Lancet, 354, 354–131.CrossRefGoogle ScholarPubMed
Pariante, C.M., Pearce, B.D., Pisell, T.L., Sanchez, C.I., Po, C., Su, C. & Miller, A.H. (1999b). The pro-inflammatory cytokine, interleukin-1-alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 140, 1404359.CrossRefGoogle Scholar
Pariante, C.M. & Miller, A.H. (2001) Glucocorticoid receptors in ma- jor depression: relevance to pathophisyology and treatment. Bio-logical Psychiatry, 49, 49391.Google Scholar
Pariante, C.M., Makoff, A., Lovestone, S., Feroli, S., Heyden, A., Miller, A.H. & Kerwin, R.W. (2001). Antidepressant enhance glucocor-ticoid receptor function in vitro by modulating the membrane steroid transporter. British Journal of Pharmacology, in press.CrossRefGoogle Scholar
Petticrew, M., Fraser, J.M. & Regan, M.F. (1999). Adverse life-events and risk of breast cancer: a meta-analysis. British Journal of Health Psychology 4, 4–1.CrossRefGoogle Scholar
Rosengren, A., Orth-Gomer, K., Wedel, H. & Wilhelmsen, L. (1993). Stressful life events, social support, and mortality in men born in 1933. British Medical Journal 307, 11021105.CrossRefGoogle ScholarPubMed
Rosenman, R.H., Brand, R.J., Jenkins, C.D., Friedman, M., Straus, R. & Wurm, M. (1975). Coronary heart disease in the Western collabo-rative group study. Journal of the American Medical Association 233, 233872.Google ScholarPubMed
Schleifer, S.J., Keller, S.E., Camerino, M., Thornton, J.C. & Stein, M. (1983). Suppression of lymphocyte stimulation following be-reavement. Journal of the American Medical Association 250, 250374.Google Scholar
Spiegel, D., Bloom, J.R., Kraemer, H.C & Gottheil, E. (1989). Effects of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2, 888891.CrossRefGoogle ScholarPubMed
Tennant, C.C., Palmer, K.J., Langeluddecke, P.M., Jones, M.P. & Nel-son, G. (1994). Life event stress and myocardial reinfarction: a prospective study. European Heart Journal 15, 15472.CrossRefGoogle ScholarPubMed
Walker, J.G., Littlejohn, G.O., McMurray, N.E. & Cutolo, M. (1999). Stress system response and rheumatoid arthritis: a multilevel approach. Rheumatology 38, 381050.CrossRefGoogle ScholarPubMed
Weizman, R., Laor, N., Podliszewski, E., Notti, I., Djaldetti, M. & Bessler, H. (1994). Cytokine production in major depressed patients before and after clomipramine treatment. Biological Psychiatry 35, 3542.CrossRefGoogle ScholarPubMed
Whitehouse, W.G., Dinges, D.F., Carota, Orne E., Keller, S.E., Bates, B.L., Bauer, N.K., Morahan, P., Haupt, B.A., Carlin, M.M., Bloom, P.B., Zaugg, L. & Orne, M.T. (1996). Psychosocial and immune effects of self-hypnosis training for stress management through-out the first semester of medical school. Psychosomatic Medi-cine 58, 58249.Google Scholar
Whiteside, T.L. & Herberman, R.B. (1990). Characteristics of natural killer cells and lymphocyte-activated killer cells. Immunology and Allergy Clinics of North America 10, 10663.Google Scholar
Wright, R.J., Rodriguez, M. & Cohen, S. (1998). Review of psychoso-cial stress and asthma: an integrated biopsychosocial approach. Tliorax 53, 531066.Google Scholar
Zhou, D., Kusnecov, A.W., Shurin, M.R., DePaoli, M. & Rabin, B.S. (1993). Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pitu-itary-adrenal axis. Endocrinology 133, 1332523.CrossRefGoogle Scholar
Zhu, Z., Tang, W., Ray, A., Wu, Y., Einarsson, P.O., Landry, M., Gwalt-ney, J. & Elias, J.A. (1996). Rhinovirus stimulation of interleukin-6 in-vivo and in-vitro: evidence for nuclear factor kB-dependent transcriptional activation. Journal of Clinical Investigation 97, 421430CrossRefGoogle Scholar