Stress: a risk factor for serious illness
Abstract
The body's principal adaptive responses to stress stimuli are mediated by an intricate stress system, which includes the hypothalamic-pituitary-adrenocortical (HPA) axis and the sympathoadrenal system (SAS). Dysregulation of the system, caused by the cumulative burden of repetitive or chronic environmental stress challenges (allostatic load) contributes to the development of a variety of illnesses including hypertension, atherosclerosis, and the insulin-resistance-dyslipidemia syndrome, as well as certain disorders of immune function. The brain's limbic system, particularly the hippocampus and amygdala, is also intimately involved in the stress response. Chronically elevated corticosteroid levels induced by persisting stress may adversely affect hippocampal structure and function, producing deficits of both memory and cognition. The ability of stress to cause illness in humans is most clearly exemplified by post-traumatic stress disorder (PTSD), which consists of a predictable constellation of distressing behavioral symptoms and physiological features. An appreciable proportion of the observed variance in vulnerability to PTSD is attributable to genetic factors. The relationship of this disorder to its precipitating cause-a recent, severely traumatic event-is unambiguous. The neuroendocrinology of PTSD is noteworthy, being characterized in many adult victims by enhanced negative feedback sensitivity of glucocorticoid receptors in the stress response system, and lower than normal urinary and plasma cortisol levels. Adult patients with PTSD also have been shown to exhibit exaggerated catecholamine responses to trauma-related stimuli. On the other hand, severely maltreated prepubertal children with PTSD continue to excrete greater than normal urinary cortisol, catecholamines, and dopamine years after disclosure of the causative abuse.
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Increased cardiovascular responses to emotional stress are pivotal in the development of hypertension.
“A number of studies implicate increased cardiovascular responses to emotional stress as being pivotal in the development of hypertension.28,29”
From Rapid Onset of Renal Sympathetic Nerve Activation in Rabbits Fed a High-Fat Diet (2012) · cites this paper as [28]
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“The well-known constellation of changes seen in emotional stress has been linked to important human health issues (Vanitallie, 2002).”
BackgroundSchloms, L., Storbeck, K., Swart, P., Gelderblom, W. C. A., & Swart, A. C. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.11.003 · Cited by 89 · see citing works
Multilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress
Agorastos, A., Nicolaides, N. C., Bozikas, V. P., Chrousos, G. P., & Pervanidou, P. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.01003 · Cited by 89 · see citing works
Sasse, S. K., Greenwood, B. N., Masini, C. V., Nyhuis, T. J., Fleshner, M., Day, H. E. W., & Campeau, S. (2008) · Stress · doi:10.1080/10253890801887453 · Cited by 85 · see citing works
Discrimination makes me sick! An examination of the discrimination–health relationship
Johnston, D. W., & Lordan, G. (2011) · Journal of Health Economics · doi:10.1016/j.jhealeco.2011.12.002 · Cited by 84 · see citing works
EMDR and early psychological intervention following trauma
Shapiro, E. (2012) · European Review of Applied Psychology · doi:10.1016/j.erap.2012.09.003 · Cited by 83 · see citing works
Huang, R., Hu, W., Yin, Y., Wang, Y., Li, W., & Li, W. (2014) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2014.2026 · Cited by 80 · see citing works
“Chronic stress has been reported to be associated with many neurodegenerative diseases, such as depression, AD and Parkinson's disease (22-24).”
Physiological dysregulation and changes in health in an older population
Goldman, N., Turra, C. M., Glei, D. A., Lin, Y., & Weinstein, M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.06.050 · Cited by 81 · see citing works
Growing up with Grief: Revisiting the Death of a Parent over the Life Course
Biank, N. M., & Werner‐Lin, A. (2011) · OMEGA - Journal of Death and Dying · doi:10.2190/om.63.3.e · Cited by 80 · see citing works
“The build up of daily stressors, or “allostatic load,” leading to chronically elevated cortisol increases adult risk of developing a host of health complications (McEwen & Seeman, 2006), including heart disease, chronic pain, hypertension, atherosclerosis, immune disorders, in addition to modifying brain structures th…”
BackgroundFarr, O. M., Sloan, D. M., Keane, T. M., & Mantzoros, C. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.009 · Cited by 80 · see citing works
“PTSD is one manifestation of the link between stress and metabolic outcomes, perhaps regulated through sympathetic nervous system activation and the release of stress hormones by the hypothalamic–pituitary–adrenal axis affecting both metabolic and brain processes [11,12].”
Is posttraumatic stress disorder related to development of heart disease? An update
Kubzansky, L. D., & Koenen, K. C. (2009) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.76.s2.12 · Cited by 78 · see citing works
Mental Illness and the Criminal Justice System
Hiday, V. A., & Burns, P. J. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511984945.029 · Cited by 77 · see citing works
Psychological Approaches to Mental Illness
Peterson, C. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511984945.008 · Cited by 76 · see citing works
Title: “Labels Matter: Is it stress or is it Trauma?”
Richter‐Levin, G., & Sandi, C. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01514-4 · Cited by 82 · see citing works
Mazloumi, A., Golbabaei, F., Dehghan, S. F., Abbasinia, M., Khani, S. M., Ansari, M., & Hosseini, M. (2016) · International Journal of Occupational Safety and Ergonomics · doi:10.1080/10803548.2016.1251137 · Cited by 75 · see citing works
“As a result, the human body is prepared to deal with the heat stress situation [13,44,45].”
BackgroundPost-traumatic Stress Disorder and Cardiovascular Disease
Burg, M. M., & Soufer, R. (2016) · Current Cardiology Reports · doi:10.1007/s11886-016-0770-5 · Cited by 72 · see citing works
Nature, smells, and human wellbeing
Bentley, P. R., Fisher, J. C., Dallimer, M., Fish, R. D., Austen, G. E., Irvine, K. N., & Davies, Z. G. (2022) · AMBIO · doi:10.1007/s13280-022-01760-w · Cited by 74 · see citing works
“High stress levels are a risk factor in a multitude of diseases, representing a significant global public health concern (VanItallie 2002; Nielsen et al. 2005; Bisht et al. 2018).”
BackgroundPrison employment and post‐traumatic stress disorder: Risk and protective factors
James, L., & Todak, N. E. (2018) · American Journal of Industrial Medicine · doi:10.1002/ajim.22869 · Cited by 70 · see citing works
Childhood Trauma and Health Outcomes in HIV-Infected Patients
Pence, B. W., Mugavero, M. J., Carter, T., Leserman, J., Thielman, N. M., Raper, J. L., Proeschold‐Bell, R. J., Reif, S., & Whetten, K. (2011) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e31824150bb · Cited by 69 · see citing works
Marital Status and Mental Health
Williams, K., Frech, A., & Carlson, D. L. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511984945.020 · Cited by 68 · see citing works
Babb, J. A., Masini, C. V., Day, H. E. W., & Campeau, S. (2014) · Stress · doi:10.3109/10253890.2014.905534 · Cited by 67 · see citing works
“associated with the etiology of both somatic and even psychological disorders such as major depression in humans (Chrousos & Gold, 1998; Claes, 2004; Ehlert et al., 2001; McEwen, 2004; Reagan et al., 2008; Vanltallie, 2002).”
BackgroundTauopathy and neurodegeneration: A role for stress
Sierra-Fonseca, J. A., & Gosselink, K. L. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.08.009 · Cited by 64 · see citing works
“ulation of the stress response, which can ultimately have negative impacts on the overall physiology of the body (Vanitallie, 2002; Glaser and Kiecolt-Glaser, 2005).”
The association between possible stress markers and vocal symptoms.
Holmqvist, S., Santtila, P., Lindström, E., Sala, E., & Simberg, S. (2013) · Journal of Voice · doi:10.1016/j.jvoice.2013.06.012 · Cited by 61 · see citing works
Well-Being across the Life Course
Mirowsky, J., & Ross, C. E. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511984945.023 · Cited by 60 · see citing works
Complementary therapies to reduce physiological stress in pregnancy.
Tiran, D., & Chummun, H. (2004) · Complementary Therapies in Nursing and Midwifery · doi:10.1016/j.ctnm.2004.03.006 · Cited by 72 · see citing works
Does the amygdala modulate adaptation to repeated stress?
Carter, R. N., Pinnock, S. B., & Herbert, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.01.018 · Cited by 58 · see citing works
“Chronic exposure to stress has been linked to numerous conditions such as hypertension, atherosclerosis and cardiac failure (Pasternac and Talajic, 1991; Vanitallie, 2002 ), aspects of the metabolic syndrome (Chrousos, 2000), as well as certain disorders of immune function (Vanitallie, 2002).”
BackgroundOuellet‐Morin, I., Dionne, G., Pérusse, D., LUPIEN, S. J., Arseneault, L., Barr, R. G., Tremblay, R. E., & Boivin, M. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.003 · Cited by 57 · see citing works
Markovic, V. M., Cupic, Z., Vukojevic, V., & Kolar-Anic, L. (2011) · Endocrine Journal · doi:10.1507/endocrj.ej11-0037 · Cited by 54 · see citing works
Akbar, F., Mark, G. J., Prausnitz, S. R., Warton, E. M., East, J. A., Moeller, M. F., Reed, M. E., & Lieu, T. A. (2021) · JMIR Medical Informatics · doi:10.2196/24014 · Cited by 52 · see citing works
“It is well established in the literature that short-term self-reported (ie, perceived) stress and acute physiological stress do not always align linearly in daily life settings [48-50]; however, both are important to monitor as they both have health and well-being implications [51-54].”
BackgroundIs there a relationship between PTSD and complicated obesity? A review of the literature
Aaseth, J., Roer, G. E., Lien, L., & Bjørklund, G. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108834 · Cited by 51 · see citing works
Applied Physiology in Intensive Care Medicine 1
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Wu, T., Chen, Y., Zhou, Y., Adi, D., Zheng, Y., Liu, F., Ma, Y., & Xie, X. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.004896 · Cited by 48 · see citing works
“This counterbalancing action might explain the relationship between DHEAS level and health outcomes known to be affected by chronically elevated cortisol levels, such as heart disease, diabetes mellitus, and cognitive impairment.(61,62) A direct role for DHEA in opposing atherosclerosis is suggested by its ability to…”
Trail, M., Nelson, N. D., Van, J. N., Appel, S. H., & Lai, E. C. (2004) · Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · doi:10.1080/14660820310016075 · Cited by 49 · see citing works
“Stress as a risk factor for illness is documented in the literature.(8) A recent study by Zautra(9) supports the premise that stressors are predictive of increased disease activity in rheumatoid arthritis.”
BackgroundIntroduction to health psychology
Dorrian, J., & Thorsteinsson, E. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316779156.001 · Cited by 49 · see citing works
Psychological and Physical Stress in Surgeons Operating in a Standard or Modern Operating Room
Klein, M. F., Andersen, L. P. H., Alamili, M., Gögenür, I., & Rosenberg, J. (2010) · Surgical Laparoscopy Endoscopy & Percutaneous Techniques · doi:10.1097/sle.0b013e3181ed851d · Cited by 48 · see citing works
The Association between Shift Work and the Metabolic Syndrome in Female Workers
Ye, H. H., Jeong, J. U., Jeon, M. J., & Sakong, J. (2013) · Annals of Occupational and Environmental Medicine · doi:10.1186/2052-4374-25-33 · Cited by 47 · see citing works
The Relationship between Childhood Parental Loss and Metabolic Syndrome in Obese Subjects
Alciati, A., Gesuele, F., Casazza, G., & Foschi, D. (2011) · Stress and Health · doi:10.1002/smi.1435 · Cited by 47 · see citing works
Cardiovascular biomarkers: increasing impact of laboratory medicine in cardiology practice
Vittorini, S., & Clerico, A. (2008) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2008.188 · Cited by 47 · see citing works
Work and Unemployment as Stressors
Lennon, M. C., & Limonic, L. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511984945.015 · Cited by 46 · see citing works
Can Psychologic Stress Elevate Intraocular Pressure in Healthy Individuals?
Abe, R. Y., Silva, T. C., Dantas, I., Curado, S. X., Madeira, M. S., de Sousa, L. B., & Costa, V. P. (2020) · Ophthalmology Glaucoma · doi:10.1016/j.ogla.2020.06.011 · Cited by 47 · see citing works
Hoppmann, C. A., & Klumb, P. L. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000238232.46870.f1 · Cited by 46 · see citing works
“chronic changes in the cortisol regulation that indicate an imbalance in the activity–recovery cycle, resulting in a heightened risk for negative tertiary effects such as hypertension (22,23).”
BackgroundGerra, G., Leonardi, C., Cortese, E., Zaimovic, A., Dell’Agnello, G., Manfredini, M., Somaini, L., Petracca, F., Caretti, V., Baroni, C. M., et al. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00086.x · Cited by 45 · see citing works
Dehydroepiandrosterone sulfate (DHEAS) and health: does the relationship differ by sex?
Glei, D. A., Goldman, N., Weinstein, M., & Liu, I.-W. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.11.003 · Cited by 46 · see citing works
“Because chronically elevated cortisol levels are implicated in many conditions including heart disease, diabetes, and cognitive impairments (Lupien et al., 1999; Vanitallie, 2002), a counterbalancing action of DHEA might explain the relationship between DHEAS and such health outcomes.”
BackgroundParkes, J. H. (2016) · doi:10.1002/9781119302728.ch9 · Cited by 46 · see citing works
Bernardi, J. R., Ferreira, C. F., Senter, G., Krolow, R., de Aguiar, B. W., Portella, A. K., Kauer-Sant'Anna, M., Kapczinski, F., Dalmaz, C., Goldani, M. Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062031 · Cited by 43 · see citing works
Mason, B. N., Kallianpur, R., Price, T. J., Akopian, A. N., & Dussor, G. O. (2021) · Headache The Journal of Head and Face Pain · doi:10.1111/head.14248 · Cited by 50 · see citing works
“These data show that lowering serum prolactin levels with bromocriptine treatment selectively attenuates the stress response and priming to SNP in females (F(3,36) = 18.”
BackgroundEffects of chronic stress and high-fat diet on metabolic and nutritional parameters in Wistar rats
Bruder-Nascimento, T. B., de Campos, D. H. S., Alves, C. A. B., Thomaz, S., Cicogna, A. C., & Cordellini, S. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000800010 · Cited by 45 · see citing works
Stress induces activation of stress‐activated kinases in the mouse brain
Liu, Y. F., BERTRAM, K. M., Perides, G., McEwen, B. S., & Wang, D. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02391.x · Cited by 45 · see citing works
Posttraumatic stress disorder and hypertension in Australian veterans of the 1991 Gulf War
Abouzeid, M., Kelsall, H. L., Forbes, A. B., Sim, M. R., & Creamer, M. C. (2011) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2011.08.002 · Cited by 44 · see citing works
Wan, R., Camandola, S., & Mattson, M. P. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00932.2003 · Cited by 41 · see citing works
“The ability to resist or adapt to stress is increasingly recognized as an important factor in resisting various diseases, including cardiovascular disease and diabetes (21, 30).”
BackgroundCrowding, an environmental stressor, blocks long-term memory formation in Lymnaea
Caigny, P. D., & Lukowiak, K. (2008) · Journal of Experimental Biology · doi:10.1242/jeb.020347 · Cited by 43 · see citing works
“Crowding has been used as a stressor in studies investigating behaviours such as memory formation, immune system functioning, and longevity in both vertebrates and invertebrates (Gems et al., 1998; Vanitallie, 2002; Bowman et al., 2003; Roman et al., 2004).”
BackgroundBrain Physiology and Pathophysiology in Mental Stress
Alkadhi, K. A. (2013) · ISRN Physiology · doi:10.1155/2013/806104 · Cited by 45 · see citing works
“Chronic stress influences the onset and/or severity of cognitive decline in various disorders [47], including Cushing’s syndrome [48], posttraumatic stress disorder [49], hypothyroidism [28, 45], Alzheimer’s disease [50–52], and depression [16, 53].”
Werner‐Lin, A., & Biank, N. M. (2012) · OMEGA - Journal of Death and Dying · doi:10.2190/om.66.1.a · Cited by 43 · see citing works
“…bereavement suggest early parental loss can lead to the development of poorly regulated neuro-emotional response systems (Brotman, Gouley, Klein, Castellanos & Pine, 2003) and the modification of brain structures that support memory and cognitive functioning (Lupien et al., 2006; Vanitallie, 2002).”
BackgroundInfluentialWyss, T., Boesch, M., Roos, L., Tschopp, C., Frei, K. M., Annen, H., & Marca, R. L. (2016) · Sports Medicine - Open · doi:10.1186/s40798-016-0057-9 · Cited by 42 · see citing works
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- Authors
- VanItallie, T. B.
- Affiliations
- Columbia University (US)
- Corresponding author
- VanItallie, Theodore B.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 51
- Issue
- 6
- Pages
- 40-45
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2063625099
- Cited by
- 414
- References
- 51
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 13 · 2023: 10 · 2022: 18 · 2021: 16 · 2020: 12 · 2019: 12 · 2018: 15 · 2017: 46 · 2016: 20 · 2015: 20 · 2014: 17 · 2013: 22 · 2012: 25
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- stress, allostatic load, hypothalamic-pituitary-adrenal axis, sympathoadrenal system, chronic stress, hypertension, atherosclerosis, insulin resistance, dyslipidemia, immune dysfunction, hippocampus, amygdala, memory impairment, post-traumatic stress disorder, cortisol, catecholamines, child abuse, neuroendocrinology
- MeSH terms
- Animals, Cardiovascular Diseases, Female, Hippocampus, Humans, Male, Neurosecretory Systems, Obesity, Risk Factors, Stress, Physiological, Stress Disorders, Post-Traumatic
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