Cohen (2005) outlines 20 years of research showing psychological stress is associated with increased risk of catching the common cold due to disruption of pro-inflammatory cytokines. Other stressors such as smoking, diet, exercise, alcohol consumption or lack of sleep, could not explain the relationship between exposure to a virus and catching it. There was a "graded relation with every increase in stress associated with an increase risk" in catching the virus (Cohen, 2005).  This evidence was listed as compelling in Jensen's (2016) commentary where immunity in mucosal tissue was associated with immunoglobulin A (IgA) which is highly sensitive to stress. Salivary IgA is diminished in response to perceived stress, reduced transport of IgA is associated with reduced immunity, It is unknown how the development or changes over time in mucosa interact with stressors (Jensen, 2016).

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There appears to be a different association between types of stressors such as work stress, interpersonal stress, perceived stress, etc. Previous studies have reported that interpersonal stress creates the most susceptibility to infectious illness (Jensen, 2016)--and it has been proposed that individual characteristics such as hardiness, conscientiousness and self-efficacy may have a role in immunity also (Marks et al., 2015). Cohen proposed social support as a big sparing factor in developing an infectious illness.

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In animal models, infants exposed to prenatal stress have shown altered immune cells, reduced white blood cell counts and other immune problems which lasted beyond infancy. The hypothalamic-pituitary-adrenal axis (HPA) has been implicated in the immune response in animals (Nielsen, Hansen, Simonsen & Hviid, 2010). The response is a little different in humans, as Nielsen et al (2010) showed in their study of 14,076 Danish and Icelandic births which included stressed conditions in mothers up to three years before conception. Infants born from mothers who were stressed within 11 months of birth were nearly twice as likely to develop a severe infection requiring hospitalization. The effects of stress on the infants were strongest before they reached one year of age. Risk of severe infection in stressed infants was 25% higher than that of infants without prenatal stress (Nielsen et al., 2010).

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                                               Effects of stress on risk of cancer or metastatic expression

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There has been speculation that stress causes breast cancer for over a century--yet large studies have not made an association. The nearest we have come to a case is a modest association between death of a spouse and the development of breast cancer. In the 2006 follow-up to the Copenhagen City Heart Study, stress was significantly not associated with the development of breast cancer. (Marks et al., 2015). Stress over-activates the HPA and sympathetic and other systems--and conversely implicated in DNA repair. The Breakthrough Generations Study of 113,000 women in the UK (2012) theorized cortisol directly affects breast tissues and estrogenic effect--and yet they found changes in family and lifestyle after a death in the family could also be factors in the development of breast cancer. For women under age 20, the death of a mother (but not a father) was significantly associated with the risk of developing breast cancer. But many of the mothers died from breast cancer, so this was instead representative of the genetic component of the disease (Shoemaker, Jones, Wright, Griffin, McFadden et al., 2016).

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Corticotrophins and corticotropin-releasing factor (CRF) are still investigates as the stress hormones which deregulate immune function. In a group of 20 patients with laryngeal cancer, the probiotic c. Butyricum given for the two weeks before surgery lowered anxiety, heart rate and levels of CRF (Yang, Zhao, Tang, Huang, Zhao et al., 2016). This natural remedy had a profound effect on these patients with cancer and the anxiety preceding surgery, which is a significant stressor.  Yang et al. (2016) provide information that chronic stress elevates catecholamine levels, which in turn promotes metastasis.  In a colon cancer mouse study, chronic stress was associated with macrophage infiltration, causing tumor growth and increased expression of metastatic genes.  Cancer of the liver is the leading cause of death in humans with colon cancer due to metastatis. A cancer diagnosis causes major distress and can activate the HPA and sympathetic nervous systems--but stress is expressed through the beta-andrenergic (B-AR) pathway to advance cancer progression (Yang et al., 2016). Zhao, Xu, Liang, Li, Zhang and Sun (2015) found that "chronic stress could promote the tumor growth of subcutaneously implanted colon carcinoma cells in a nude mice model through the B-AR signaling pathway" (p. 2). Epidemiological studies suggest that the beta blocker propranolol may reduce the risk of some cancers by reversing the effects of norepinephrine and epinephrine during the stress response (Zhao et al., 2015).

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                                            Stress and immune response to infectious disease and cancer

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In vitro studies have supported a theory that the cascade of stress hormones can create DNA breakage, transcription errors causing tumor growth, or cell death. This is said to affect humoral, cellular and mucosal immune responses. In vitro animal studies have upheld these stress-illness theories. The problem is that studies with humans show different types of stressors produce different results, and in breast cancer it appears that stress helps the body repair itself, rather than breaking down.

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The biggest differences between the study of cancer and catching the common cold, is that cancer is looked at in terms of physical cascades of chemistry on immune functioning.. Even psychological stressors are defined in terms of the oxidative stress it produces in the body, whereas infectious disease studies include social dimension, SES and social rank as stressors which result in lowered immunity. Where both types of studies meet is in the real of perceived stress, or having no control. Where Yang et al. (2016) state the diagnosis of cancer itself can promote major stress, and promote the growth of cancer--this is in agreement with Jensen's (2016) commentary that perceived stress is associated with decreased mucosal immunity against infectious disease.

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                                                 Another nexus between stress and disease

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There is also another platform where infectious disease and immunity go awry to create chronic inflammatory conditions : The auto-immune disorder. "Autoimmunity is a multifactorial, synergistically-derived process in which genetic, immunological, and environment factors act in concert to materialize a phenomenon known as the 'mosaic of autoimmunity'" (Temajo & Howard, 2014, p.636). Those with autoimmune disorders are highly susceptible to further infection, which it be viral, bacterial, fungal or from vaccines. The genetic predisposition for one of the more than 80 disorders, whether is be type 1 diabetes or other inflammatory disorder, may not be realized until the environmental component enters in. The environmental factor is either a non0infectious or an infectious viral invader (Temajo & Howard, 2014). The fact that stress completes the introduction of the virus into ones system, makes "the abrogation of viral latency by stress...an intrinsic prerequisite prelude" (Temajo & Howard, 2014, p. 635) to trigger an autoimmune disease.

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                                                                      References

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Cohen, S. (2005). The Pittsburgh common cold studies: Psychosocial predictors of susceptibility to respiratory infectious illness. International Journal of Behavioral Medicine, 2005, 12 (3), 123-131

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Jenkins, F. J., Houten, B. V., Bovbjerg, D. H. (2014). Effects of DNA damage and/or repair processes as biological mechanisms linking psychological stress to cancer risk. Journal of Applied Biobehavioral Research, 2014, 19 (1), 3-23

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Jensen, S. E. (2016). Psychological stress and infectious illnesses: One step closer to understanding the mechanisms. [Commentary]. Brain, Behavior and Immunity, 52 (2016), 9-10

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Marks, D. F., Murray, M., Evans, B., & Estacio, E. V. (2015). Health Psychology: Theory research and practice, 4th ed. Thousand Oaks, CA: SAGE Publications, Inc.

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Nielsen, N. M., Hansen, A. V., Simonsen, J. & Hviid, A. (2011). Prenatal stress and risk of infectious diseases in offspring. American Journal of Epidemiology, 2011, 173 (9), 990-997

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Schoemaker, M. J., Jones, M. E., Wright, L. B., Griffin, J., McFadden, E., Ashworth, A., & Swerdlow, A. J. (2016). Psychological stress, adverse life events and breast cancer incidence: A cohort investigation in 106,000 women in the United Kingdom. Breast Cancer Research, 2016, 18:72

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Temajo, N. O., & Howard, N. (2014). The mosaic of environment involvement in autoimmunity: The abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases. Autoimmunity Reviews 13 (2014), 635-640 DOI: 10.1016/j.autrev.2013.12.003

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Yang, H., Zhao, X., Tang, S., Huang, H., Zhao, X., Ning, Z., Fu, X., & Zhang, C. (2016). Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia-Pacific Journal of Clinical Oncology, 2016, 12: e92-e96

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Zhao, L., Xu, J., Liang, F., Li, A., Zhang, Y., & Sun, J. (2015). Effect of chronic psychological stress on liver metastasis of colon cancer in mice. PLoS ONE, October 7, 2015 DOI: 10.137/journal.pone.0139978

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