Skip to main content

The Biology of Stress

  • Chapter
  • First Online:
Behavioral Medicine

Abstract

This chapter introduces the basic pillars of behavioral medicine. We begin with the effectors of the stress response and then focus on brain and vagal neuromodulation of stress. We then learn the basics of neuroimmunology – interactions between the nervous and immune systems. The topics of the effects of stress on immunity and on DNA damage are then reviewed by multiple empirical examples. This chapter represents the “hardware” of behavioral medicine and sets the knowledge basis for the psychoneuroimmunology (PNI) reviewed in each subsequent clinical chapter. This chapter is complex for the reader without biological background. However, it attempts to explain these issues clearly and it is essential for understanding in depth the clinical chapters.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 99.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adachi, S., Kawamura, K., & Takemoto, K. (1993). Oxidative damage of nuclear DNA in liver of rats exposed to psychological stress. Cancer Research, 53(18), 4153–4155.

    Google Scholar 

  • Agarwal, S. K., & Marshall, G. D., Jr. (2000). β-Adrenergic modulation of human type-1/type-2 cytokine balance. Journal of Allergy and Clinical Immunology, 105(1), 91–98.

    Article  Google Scholar 

  • Amat, J., Paul, E., Watkins, L. R., & Maier, S. F. (2008). Activation of the ventral medial prefrontal cortex during an uncontrollable stressor reproduces both the immediate and long-term protective effects of behavioral control. Neuroscience, 154(4), 1178–1186.

    Article  Google Scholar 

  • Becknell, B., & Caligiuri, M. A. (2005). Interleukin-2, interleukin-15, and their roles in human natural killer cells. In Advances in immunology (Vol. 86, pp. 209–239). New York: Academic Press.

    Google Scholar 

  • Bellingrath, S., Rohleder, N., & Kudielka, B. M. (2010). Healthy working school teachers with high effort–reward-imbalance and overcommitment show increased pro-inflammatory immune activity and a dampened innate immune defence. Brain, Behavior, and Immunity, 24(8), 1332–1339.

    Article  Google Scholar 

  • Boyman, O., & Sprent, J. (2012). The role of interleukin-2 during homeostasis and activation of the immune system. Nature Reviews Immunology, 12(3), 180.

    Article  Google Scholar 

  • Bucks, R., Gidron, Y., Harris, P., Wesnes, K., Telling, J., & Perry, V. H. (2008). Selective cognitive effects of upper respiratory tract infection symptoms. Brain, Behavior and Immunity, 22, 399–407.

    Article  Google Scholar 

  • Cerqueira, J. J., Catania, C., Sotiropoulos, I., Schubert, M., Kalisch, R., Almeida, O. F. X., Auer, D. P., & Sousa, N. (2005). Corticosteroid status influences the volume of the rat cingulate cortex–a magnetic resonance imaging study. Journal of Psychiatric Research, 39(5), 451–460.

    Article  Google Scholar 

  • Cerqueira, J. J., Almeida, O. F., & Sousa, N. (2008). The stressed prefrontal cortex. Left? Right! Brain, Behavior, and Immunity, 22(5), 630–638.

    Article  Google Scholar 

  • Chrousos, G. P. (2009). Stress and disorders of the stress system. Nature Reviews Endocrinology, 5, 374.

    Article  Google Scholar 

  • Critchley, H. D. (2005). Neural mechanisms of autonomic, affective, and cognitive integration. Journal of Comparative Neurology, 493, 154–166.

    Article  Google Scholar 

  • Dantzer, R., Konsman, J. P., Bluthé, R. M., & Kelley, K. W. (2000). Neural and humoral pathways of communication from the immune system to the brain: Parallel or convergent? Autonomic Neuroscience, 85(1–3), 60–65.

    Article  Google Scholar 

  • Davidson, R. J. (2004). Well-being and affective style: Neural substrates and biobehavioural correlates. Philosophical Transactions – Royal Society, London B, Biological Sciences, 359(1449), 1395–1411.

    Article  Google Scholar 

  • Davidson, R. J., Coe, C. C., Dolski, I., & Donzella, B. (1999). Individual differences in prefrontal activation asymmetry predict natural killer cell activity at rest and in response to challenge. Brain, Behavior, and Immunity, 13(2), 93–108.

    Article  Google Scholar 

  • Davidson, J., Abul, H. T., Milton, A. S., & Rotondo, D. (2001). Cytokines and cytokine inducers stimulate prostaglandin E2 entry into the brain. Pflügers Archiv, 442(4), 526–533.

    Article  Google Scholar 

  • De Couck, M., Mravec, B., & Gidron, Y. (2012). You may need the vagus nerve to understand pathophysiology and to treat diseases. Clinical Science, 122(7), 323–328.

    Article  Google Scholar 

  • Ek, M., Kurosawa, M., Lundeberg, T., & Ericsson, A. (1998). Activation of vagal afferents after intravenous injection of interleukin-1β: Role of endogenous prostaglandins. Journal of Neuroscience, 18(22), 9471–9479.

    Article  Google Scholar 

  • Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101(49), 17312–17315.

    Article  Google Scholar 

  • Garssen, B. (2004). Psychological factors and cancer development: Evidence after 30 years of research. Clinical Psychology Review, 24(3), 315–338.

    Article  Google Scholar 

  • German, L., Gidron, Y., Shahar, A., Yirmiyahu, T., Shahar, D. R., & Baham, E. (2006). Depressive symptoms are associated with both immune-suppression and leukocytosis among elderly with acute hospitalization. Geriatrics & Gerontology International, 6, 53–59.

    Article  Google Scholar 

  • Gidron, Y., Perry, H., & Glennie, M. (2005). Does the vagus nerve inform the brain about preclinical tumours and modulate them? The Lancet Oncology, 6(4), 245–248.

    Article  Google Scholar 

  • Gidron, Y., Russ, K., Tissarchondou, H., & Warner, J. (2006). The relation between psychological factors and DNA-damage: A critical review. Biological Psychology, 72(3), 291–304.

    Article  Google Scholar 

  • Gidron, Y., Deschepper, R., De Couck, M., Thayer, J. F., & Velkeniers, B. (2018). The vagus nerve can predict and possibly modulate non-communicable chronic diseases: Introducing a neuro immunological paradigm to public health. Journal of Clinical Medicine, 7, 371.

    Article  Google Scholar 

  • Gold, P. W., & Chrousos, G. P. (2002). Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/NE states. Molecular Psychiatry, 7(3), 254.

    Article  Google Scholar 

  • Goldin, P. R., McRae, K., Ramel, W., & Gross, J. J. (2008). The neural bases of emotion regulation: Reappraisal and suppression of negative emotion. Biological Psychiatry, 63(6), 577–586.

    Article  Google Scholar 

  • Gosling, S. D., Rentfrow, P. J., & Swann, W. B., Jr. (2003). A very brief measure of the Big Five personality domains. Journal of Research in Personality, 37, 504–528.

    Article  Google Scholar 

  • Guo, C. C., Sturm, V. E., Zhou, J., Gennatas, E. D., Trujillo, A. J., Hua, A. Y., Crawford, R., Stables, L., Kramer, J. H., Levenson, R. W., Rosen, H. J., Miller, B. L., & Seeley, W. W. (2016). Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia. Proceedings of the National Academy of Sciences, 113(17), E2430–E2439.

    Article  Google Scholar 

  • Herbert, T. B., & Cohen, S. (1993). Stress and immunity in humans: A meta-analytic review. Psychosomatic Medicine, 55(4), 364–379.

    Article  Google Scholar 

  • Herman, J. P. (2012). Neural pathways of stress integration: Relevance to alcohol abuse. Alcohol Research: Current Reviews, 34(4), 441.

    Google Scholar 

  • Herzog, D., Killianova, T., Pauwels, S., Germeys, F., & Gidron, Y. (2014). Hemispheric lateralization moderates the life events-distress relationship. Stress & Health, 32, 47–54.

    Article  Google Scholar 

  • Herzog, D., Farchi, M., & Gidron, Y. (2017). The relationship between exposure to missiles and PTSD symptoms as a function of hemispheric preference in Israelis. Journal of Trauma & Dissociation, 19(1), 59–74.

    Article  Google Scholar 

  • Hoeijmakers, J. H. (2001). DNA repair mechanisms. Maturitas, 38(1), 17–22.

    Article  Google Scholar 

  • Irie, M., Asami, S., Nagata, S., Miyata, M., & Kasai, H. (2000). Classical conditioning of oxidative DNA damage in rats. Neuroscience Letters, 288(1), 13–16.

    Article  Google Scholar 

  • Irie, M., Asami, S., Nagata, S., Ikeda, M., Miyata, M., & Kasai, H. (2001). Psychosocial factors as a potential trigger of oxidative DNA damage in human leukocytes. Japanese Journal of Cancer Research, 92(3), 367–376.

    Article  Google Scholar 

  • Khan, M. M., Strober, S., & Melmon, K. L. (1986). Regulatory effects of mast cells on lymphoid cells: The role of histamine type 1 receptors in the interaction between mast cells, helper T cells and natural suppressor cells. Cellular Immunology, 103(1), 41–53.

    Article  Google Scholar 

  • Korf, J., Aghajanian, G. K., & Roth, R. H. (1973). Increased turnover of norepinephrine in the rat cerebral cortex during stress: Role of the locus coeruleus. Neuropharmacology, 12(10), 933–938.

    Article  Google Scholar 

  • Kumar, A., Rinwa, P., Kaur, G., & Machawal, L. (2013). Stress: Neurobiology, consequences and management. Journal of Pharmacology and Bioallied Sciences, 5, 91–97.

    Article  Google Scholar 

  • Kuo, T. B., Lai, C. J., Huang, Y. T., & Yang, C. C. (2005). Regression analysis between heart rate variability and baroreflex-related vagus nerve activity in rats. Journal of Cardiovascular Electrophysiology, 16(8), 864–869.

    Article  Google Scholar 

  • Lei, J., Jin, H., Shen, S., Li, Z., & Gu, G. (2015). Influence of clinical practice on nursing students’ mental and immune-endocrine functions. International Journal of Nursing Practice, 21(4), 392–400.

    Article  Google Scholar 

  • Leiter, O., Kempermann, G., & Walker, T. L. (2016). A common language: How neuroimmunological cross talk regulates adult hippocampal neurogenesis. Stem Cells International, 2016, 1–13.

    Article  Google Scholar 

  • Lewis, R. S., Weekes, N. Y., & Wang, T. H. (2007). The effect of a naturalistic stressor on frontal EEG asymmetry, stress, and health. Biological Psychology, 75(3), 239–247.

    Article  Google Scholar 

  • Madden, K. S., Sanders, V. M., & Felten, D. L. (1995). Catecholamine influences and sympathetic neural modulation of immune responsiveness. Annual Review of Pharmacology and Toxicology, 35(1), 417–448.

    Article  Google Scholar 

  • Maes, M., Song, C., Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., Bosmans, E., De Meester, I., Benoy, I., Neels, H., Demedts, P., Janca, A., Scharpé, S., & Smith, R. S. (1998). The effects of psychological stress on humans: Increased production of pro-inflammatory cytokines and Th1-like response in stress-induced anxiety. Cytokine, 10(4), 313–318.

    Article  Google Scholar 

  • Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008). Cancer-related inflammation. Nature, 454(7203), 436–444.

    Article  Google Scholar 

  • Martelli, D., McKinley, M. J., & McAllen, R. M. (2014). The cholinergic anti-inflammatory pathway: A critical review. Autonomic Neuroscience, 182, 65–69.

    Article  Google Scholar 

  • McEwen, B. S. (2017). Neurobiological and systemic effects of chronic stress. Chronic Stress, 1, 2470547017692328.

    Article  Google Scholar 

  • Meador, K. J., Loring, D. W., Ray, P. G., Helman, S. W., Vazquez, B. R., & Neveu, P. J. (2004). Role of cerebral lateralization in control of immune processes in humans. Annals of Neurology, 55(6), 840–844.

    Article  Google Scholar 

  • Ogbonnaya, S., & Kaliaperumal, C. (2013). Vagal nerve stimulator: Evolving trends. Journal of Natural Science, Biology, and Medicine, 4(1), 8.

    Article  Google Scholar 

  • Ohira, H., Matsunaga, M., Osumi, T., Fukuyama, S., Shinoda, J., Yamada, J., & Gidron, Y. (2013). Vagal nerve activity as a moderator of brain–immune relationships. Journal of Neuroimmunology, 260(1–2), 28–36.

    Article  Google Scholar 

  • Radley, J. J., Arias, C. M., & Sawchenko, P. E. (2006). Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. Journal of Neuroscience, 26(50), 12967–12976.

    Article  Google Scholar 

  • Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001). Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry, 58(5), 445–452.

    Article  Google Scholar 

  • Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdés-Ferrer, S. I., Levine, Y. A., Reardon, C., Tusche, M. W., Pavlov, V. A., Andersson, U., Chavan, S., Mak, T. W., & Tracey, K. J. (2011). Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science, 334(6052), 98–101.

    Article  Google Scholar 

  • Rosenkranz, M. A., Busse, W. W., Johnstone, T., Swenson, C. A., Crisafi, G. M., Jackson, M. M., Bosch, J. A., Sheridan, J. F., & Davidson, R. J. (2005). Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation. Proceedings of the National Academy of Sciences, 102(37), 13319–13324.

    Article  Google Scholar 

  • Ross, R. (1999). Atherosclerosis--an inflammatory disease. New England Journal of Medicine, 340(2), 115–126.

    Article  Google Scholar 

  • Rozeboom, A. M., Akil, H., & Seasholtz, A. F. (2007). Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Proceedings of the National Academy of Sciences, 104(11), 4688–4693.

    Article  Google Scholar 

  • Schulz, R., & Beach, S. R. (1999). Caregiving as a risk factor for mortality: The caregiver health effects study. JAMA, 282(23), 2215–2219.

    Article  Google Scholar 

  • Segerstrom, S. C. (2005). Optimism and immunity: Do positive thoughts always lead to positive effects? Brain, Behavior, and Immunity, 19(3), 195–200.

    Article  Google Scholar 

  • Sieber, W. J., Rodin, J., Larson, L., Ortega, S., Cummings, N., Levy, S., Whiteside, T., & Herberman, R. (1992). Modulation of human natural killer cell activity by exposure to uncontrollable stress. Brain, Behavior, and Immunity, 6(2), 141–156.

    Article  Google Scholar 

  • Sousa, N., Cerqueira, J. J., & Almeida, O. F. (2008). Corticosteroid receptors and neuroplasticity. Brain Research Reviews, 57(2), 561–570.

    Article  Google Scholar 

  • Sullivan, R. M. (2004). Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine. Stress, 7, 131–143.

    Article  Google Scholar 

  • Sumner, R. C., Parton, A., Nowicky, A. V., Kishore, U., & Gidron, Y. (2011). Hemispheric lateralisation and immune function: A systematic review of human research. Journal of Neuroimmunology, 240, 1–12.

    Article  Google Scholar 

  • Takamoto, T., Hori, Y., Koga, Y., Toshima, H., Hara, A., & Yokoyama, M. M. (1991). Norepinephrine inhibits human natural killer cell activity in vitro. International Journal of Neuroscience, 58, 127–131.

    Article  Google Scholar 

  • Taylor, S. E., Burklund, L. J., Eisenberger, N. I., Lehman, B. J., Hilmert, C. J., & Lieberman, M. D. (2008). Neural bases of moderation of cortisol stress responses by psychosocial resources. Journal of Personality and Social Psychology, 95, 197.

    Article  Google Scholar 

  • Thayer, J. F. (2009). Vagal tone and the inflammatory reflex. Cleveland Clinic Journal of Medicine, 76, 823–826.

    Article  Google Scholar 

  • Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. J., III, & Wager, T. D. (2012). A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neuroscience & Biobehavioral Reviews, 36, 747–756.

    Article  Google Scholar 

  • Tracey, K. J. (2009). Reflex control of immunity. Nature Reviews Immunology, 9, 418–428.

    Article  Google Scholar 

  • Tsigos, C., & Chrousos, G. P. (2002). Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research, 53, 865–871.

    Article  Google Scholar 

  • Tuchscherer, M., Kanitz, E., Otten, W., & Tuchscherer, A. (2002). Effects of prenatal stress on cellular and humoral immune responses in neonatal pigs. Veterinary Immunology and Immunopathology, 86(3–4), 195–203.

    Article  Google Scholar 

  • Ullrich, P. M., Lutgendorf, S. K., & Stapleton, J. T. (2003). Concealment of homosexual identity, social support and CD4 cell count among HIV-seropositive gay men. Journal of Psychosomatic Research, 54(3), 205–212.

    Article  Google Scholar 

  • Uylings, H. B., Groenewegen, H. J., & Kolb, B. (2003). Do rats have a prefrontal cortex? Behavioural Brain Research, 146(1–2), 3–17.

    Article  Google Scholar 

  • Valenta, L. J., Elias, A. N., & Eisenberg, H. (1986). ACTH stimulation of adrenal epinephrine and norepinephrine release. Hormone Research, 23, 16–20.

    Article  Google Scholar 

  • Van Der Pompe, G., Antoni, M. H., Duivenvoorden, H. J., De Graeff, A., Simonis, R. F. A., Van Der Vegt, S. G., & Heijnen, C. J. (2001). An exploratory study into the effect of group psychotherapy on cardiovascular and immunoreactivity to acute stress in breast cancer patients. Psychotherapy and Psychosomatics, 70(6), 307–318.

    Article  Google Scholar 

  • Vlcek, M., Radikova, Z., Penesova, A., Kvetnansky, R., & Imrich, R. (2008). Heart rate variability and catecholamines during hypoglycemia and orthostasis. Autonomic Neuroscience, 143(1–2), 53–57.

    Article  Google Scholar 

  • Ward, D. G., Grizzle, W. E., & Gann, D. S. (1976). Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in the cat. Endocrinology, 99, 1220–1228.

    Article  Google Scholar 

  • Weber, C. S., Thayer, J. F., Rudat, M., Wirtz, P. H., Zimmermann-Viehoff, F., Thomas, A., Perschel, F. H., Arck, P. C., & Deter, H. C. (2010). Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers. European Journal of Applied Physiology, 109, 201–211.

    Article  Google Scholar 

  • Yehuda, R. (2005). Neuroendocrine aspects of PTSD. Handbook of Experimental Pharmacology, 169, 371–403.

    Article  Google Scholar 

  • Yerkes, R. M., & Dodson, J. D. (1908). The relation of strength of stimulus to rapidity of habit-formation. Journal of Comparative Neurology and Psychology, 18(5), 459–482.

    Article  Google Scholar 

  • Zhou, X., Ma, Z., Zhang, L., Zhou, S., Wang, J., Wang, B., & Fu, W. (2016). Heart rate variability in the prediction of survival in patients with cancer: A systematic review and meta-analysis. Journal of Psychosomatic Research, 89, 20–25.

    Article  Google Scholar 

  • Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., McCorkle, R., Seligman, D. A., & Schmidt, K. (2001). The relationship of depression and stressors to immunological assays: A meta-analytic review. Brain, Behavior, and Immunity, 15, 199–226.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gidron, Y. (2019). The Biology of Stress. In: Behavioral Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-18893-1_2

Download citation

Publish with us

Policies and ethics