Chronic stress can cause physiological changes that lead to long-lasting adaptations. Because one of its primary roles is to serve as a sensor for physiological stress, the immune system may be particularly useful in studying stress-induced changes throughout all stages of human development. Direct immune system manipulation or interventions secondary to stress-monitoring may enable us to intervene and prevent unwanted outcomes later in life. Studies of immune system altered responses during sleep disturbances and in patients with mood disorders have elucidated mechanisms of how physiologic stressors impact the immune system and how chronic disruptions of the normal rhythms of the immune system can contribute to disease states. However, caution should be taken when interpreting measures of immune system factors in studies of psychosocial stress because of the complex bidirectional interplay of the immune system with the neuroendocrine system. This chapter will describe how these two systems influence each other under normal circumstances and how disruptions at different points during development can lead to human disease or maladaptation.
- Immune system
- Mood disorder
- Human development
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Ader, R., & Cohen, N. (1975). Behaviorally conditioned immunosuppression. Psychosomatic Medicine, 37, 333–340.
Bauer, M. E. (2013). The role of stress and adrenal hormones in immunosenescence. In J. A. Bosch, A. C. Phillips, & J. M. Lord (Eds.), Immunosenescence, psychosocial and behavioral determinants (pp. 221–239). New York, NY: Springer. https://doi.org/10.1007/978-1-4614-4776-4_13
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012). Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proceedings of the National Academy of Sciences United States of America, 109, 5995–5999. https://doi.org/10.1073/pnas.1118355109
Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9, 46–56. https://doi.org/10.1038/nrn2297
Dhabhar, F. S. (2009a). A hassle a day may keep the pathogens away: The fight-or-flight stress response and the augmentation of immune function. Integrative and Comparative Biology, 49, 215–236. https://doi.org/10.1093/icb/icp045
Dhabhar, F. S. (2009b). Enhancing versus suppressive effects of stress on immune function: Implications for immunoprotection and immunopathology. Neuroimmunomodulation, 16, 300–317. https://doi.org/10.1159/000216188
Dhabhar, F. S. (2014). Effects of stress on immune function: The good, the bad, and the beautiful. Immunologic Research, 58, 193–210. https://doi.org/10.1007/s12026-014-8517-0
Freier, E., Weber, C. S., Nowottne, U., Horn, C., Bartels, K., Meyer, S., Hildebrandt,Y., Luetkens, T., Cao, Y., Pabst, C., Muzzulini, J., Schnee, B., Brunner-Weinzierl, M. C., Marangolo, M., Bokemeyer, C., Deter, H. -C., Atanackovic, D., (2010). Decrease of CD4+FOXP3+ T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor. Psychoneuroendocrinology 35(5):663–673
Glaser, R., & Kiecolt-Glaser, J. K. (2005). Stress-induced immune dysfunction: Implications for health. Nature Reviews Immunology, 5, 243–251.
Goligorsky, M. S. (2001). The concept of cellular “fight-or-flight” reaction to stress. American Journal Physiology Renal Physiology, 280, F551–F561.
Graham, J. E., Christian, L. M., & Kiecolt-Glaser, J. K. (2006). Stress, age, and immune function: Toward a lifespan approach. Journal of Behavioral Medicine, 29, 389–400. https://doi.org/10.1007/s10865-006-9057-4
Haahtela, T., Holgate, S., Pawankar, R., Akdis, C. A., Benjaponpitak, S., Caraballo, L., … Change World Allergy Organization Special Committee on Climate Change and Biodiversity. (2013). The biodiversity hypothesis and allergic disease, World Allergy Organization position statement. World Allergy Organization Journal, 6, 3.
Hidaka, B. H. (2012). Depression as a disease of modernity, explanations for increasing prevalence. Journal of Affective Disorders, 140, 205–214. https://doi.org/10.1016/j.jad.2011.12.036
Kessler, R. C., Merikangas, K. R., & Wang, P. S. (2007). Prevalence, comorbidity, and service utilization for mood disorders in the United States at the beginning of the twenty-first century. Annual Review of Clinical Psychology, 3, 137–158. https://doi.org/10.1146/annurev.clinpsy.3.022806.091444
Klengel, T., & Binder, E. B. (2015). FKBP5 allele-specific epigenetic modification in gene by environment interaction. Neuropsychopharmacology, 40, 244–246. https://doi.org/10.1038/npp.2014.208
Kozlowska, K., Walker, P., McLean, L., & Carrive, P. (2015). Fear and the defense cascade: Clinical implications and management. Harvard Review of Psychiatry, 23, 263–287. https://doi.org/10.1097/HRP.0000000000000065
Krishnan, H. R., Sakharkar, A. J., Teppen, T. L., Berkel, T. D., & Pandey, S. C. (2014). The epigenetic landscape of alcoholism. International Review of Neurobiology, 115, 75–116. https://doi.org/10.1016/B978-0-12-801311-3.00003-2
Maes, M. (1995). Evidence for an immune response in major depression: A review and hypothesis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 19, 11–38. https://doi.org/10.1016/0278-5846(94)00101-M
Maes, M., Smith, R., & Scharpe, S. (1995). The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology, 20, 111–116. https://doi.org/10.1016/0306-4530(94)00066-J
Maes, M., Yirmyia, R., Noraberg, J., Brene, S., Hibbeln, J., Perini, G., … Maj, M. (2009). The inflammatory & neurodegenerative (I&ND) hypothesis of depression: Leads for future research and new drug developments in depression. Metabolic Brain Disease, 24, 27–53. https://doi.org/10.1007/s11011-008-9118-1
Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65, 732–741.
Miller, A. H., & Raison, C. L. (2016). The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nature Reviews Immunology, 16, 22–34. https://doi.org/10.1016/j.biopsych.2008.11.029
Miller, D. B., & O’Callaghan, J. P. (2002). Neuroendocrine aspects of the response to stress. Metabolism, 51, 5–10. https://doi.org/10.1053/meta.2002.33184
Miller, G. E., Chen, E., & Parker, K. J. (2011). Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms. Psychological Bulletin, 137, 959–997. https://doi.org/10.1037/a0024768
Morgese, M. G., & Trabace, L. (2016). Maternal malnutrition in the etiopathogenesis of psychiatric diseases: Role of polyunsaturated fatty acids. Brain Sciences, 6, 24. https://doi.org/10.3390/brainsci6030024
Muneer, A. (2016). Bipolar disorder: Role of inflammation and the development of disease biomarkers. Psychiatry Investigation, 13, 18–33. https://doi.org/10.4306/pi.2016.13.1.18
Nielsen, P. R., Meyer, U., & Mortensen, P. B. (2016). Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring. Schizophrenia Research, 172, 35–40. https://doi.org/10.1016/j.schres.2016.02.025
O’Connor, T. G., Moynihan, J. A., & Caserta, M. T. (2014). Annual research review: The neuroinflammation hypothesis for stress and psychopathology in children—developmental psychoneuroimmunology. Journal of Child Psychology & Psychiatry, 55, 615–631. https://doi.org/10.1111/jcpp.12187
Parboosing, R., Bao, Y., Shen, L., Schaefer, C. A., & Brown, A. S. (2013). Gestational influenza and bipolar disorder in adult offspring. JAMA Psychiatry, 70, 677–685. https://doi.org/10.1001/jamapsychiatry.2013.896
Ronaldson, A., Gazali, A. M., Zalli, A., Kaiser, F., Thompson, S. J., Henderson, B., … Carvalho, L. (2016). Increased percentages of regulatory T cells are associated with inflammatory and neuroendocrine responses to acute psychological stress and poorer health status in older men and women. Psychopharmacology (Berl), 233, 1661–1668. https://doi.org/10.1007/s00213-015-3876-3
Segerstrom, S. C., & Miller, G. E. (2004). Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychological Bulletin, 130, 601–630. https://doi.org/10.1037/0033-2909.130.4.601
Slavich, G. M., & Irwin, M. R. (2014). From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140, 774–815. https://doi.org/10.1037/a0035302
Slopen, N., Kubzansky, L. D., & Koenen, K. C. (2013). Internalizing and externalizing behaviors predict elevated inflammatory markers in childhood. Psychoneuroendocrinology, 38, 2854–2862. https://doi.org/10.1016/j.psyneuen.2013.07.012
Southwick, S. M., Vythilingam, M., & Charney, D. S. (2005). The psychobiology of depression and resilience to stress, implications for prevention and treatment. Annual Review of Clinical Psychology, 1, 255–291. https://doi.org/10.1146/annurev.clinpsy.1.102803.143948
Stephens, M. A., & Wand, G. (2012). Stress and the HPA axis, role of glucocorticoids in alcohol dependence. Alcohol Research, 34, 468–483.
Tang, B., Jia, H., Kast, R. J., & Thomas, E. A. (2013). Epigenetic changes at gene promoters in response to immune activation in utero. Brain Behavior and Immunity, 30, 168–175. https://doi.org/10.1016/j.bbi.2013.01.086
Tsigos, C., Kyrou, I., Kassi, E., & Chrousos, G. P. (2000). Stress, endocrine physiology and pathophysiology. In L. J. De Groot, G. Chrousos, K. Dungan, K. R. Feingold, A. Grossman, J. M. Hershman, C. Koch, M. Korbonits, R. McLachlan, M. New, J. Purnell, R. Rebar, F. Singer, & A. Vinik (Eds.), Endotext. South Dartmouth, MA: mdtext.com.
Turner, B. M. (2009). Epigenetic responses to environmental change and their evolutionary implications. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 364, 3403–3418. https://doi.org/10.1098/rstb.2009.0125
Varriale, A. (2014). DNA methylation, epigenetics, and evolution in vertebrates, facts and challenges. International Journal of Evolutionary Biology, 2014, 475981. https://doi.org/10.1155/2014/475981
Weaver, I. C., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma, S., Seckl, J., … Meaney, M. J. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–854. https://doi.org/10.1038/nn1276
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Marino, J.H., Teague, T.K. (2019). The Immune System as a Sensor and Regulator of Stress: Implications in Human Development and Disease. In: Harrist, A., Gardner, B. (eds) Biobehavioral Markers in Risk and Resilience Research. Emerging Issues in Family and Individual Resilience. Springer, Cham. https://doi.org/10.1007/978-3-030-05952-1_1
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