Research Blog

February 19, 2022

Stress Biomarkers and Consequences Part 6: Disorders Associated with Stress

Welcome to part 6 of the ODX Stress Biomarkers Series. In this post, the ODX Research team reviews the chronic disorders associated with stress, especially prolonged stress.

The ODX Stress Biomarkers Series

  1. Stress Part 1: A Quick Overview
  2. Stress Part 2: How Do We Get Stressed Out?
  3. Stress Part 3: The Physiology of Stress
  4. Stress Part 4: Hormonal Control of the Stress Response
  5. Stress Part 5: Identifying Stress
  6. Stress Part 6: Disorders Associated with Stress
  7. Stress Part 7: Biomarkers of Stress Overview
  8. Stress Part 8: Biomarkers of Stress, Individual Markers
  9. Stress Part 9: Addressing Stress: Can We Treat It or Beat It?
  10. Stress Part 10: Nutrition and Stress
  11. Stress Part 11: Optimal Takeaways

Chronic disorders associated with stress include:[1]

  • Angina
  • Asthma
  • Autoimmune disease
  • Cancer
  • Cardiovascular disease
  • Common cold
  • Depression
  • Diabetes mellitus (type 2)
  • Headaches
  • Hypertension
  • Immune suppression
  • Irritable bowel syndrome
  • Menstrual irregularities
  • Rheumatoid arthritis
  • Ulcerative colitis
  • Ulcers

Cardiovascular Disease and Stress

Exposure to chronic stress is considered a CVD risk factor, likely through chronic activation of the HPA axis, inflammation, oxidative stress, and acceleration of the atherosclerotic process. Chronically elevated cortisol and aldosterone can contribute to hypertension and may promote myocardial necrosis and fibrosis as well. The CVD effects of stress may be especially significant for those experiencing stress-related anger, anxiety, and depression.[ii]

It is important to recognize that dysregulation of the endocrine, immune, and nervous systems due to prolonged stress can contribute to hypertension, vascular damage, and even cardiac arrest.[iii] Sources and effects of stress should be identified and addressed early on to reduce the risk of cardiovascular dysfunction and disease.

Stress Testing

Reaction and tolerance to stress reflects the health of the cardiovascular system. The conventional cardiac stress test uses physical activity (e.g., treadmill activity) as a stressor by increasing the heart rate to a target of 80-90% maximal (maximal heart rate is 220 minus a patient’s age). If advanced atherosclerosis or arterial occlusion are present, the arteries won’t be able to meet the increased demand for blood that the heart requires and symptoms such as fatigue, chest pain, tachycardia, arrhythmias, dyspnea, decreased blood pressure, and electroencephalogram abnormalities can occur.[iv]

Heart rate variability (HRV) appears to be a useful marker of stress as it reflects the heart’s ability to response to stimuli. The heart rate will normally vary with activities such as exercise, breathing, sleeping, stress, and metabolic and hemodynamic changes. Low HRV may indicate impaired autonomic nervous system function and a diminished ability to cope with stress. The heart rate is regulated by both the sympathetic and parasympathetic branches of the ANS, and dysregulation contributes to ventricular arrhythmias and coronary artery disease.[v]

Obesity and Stress

Chronic stress and prolonged activation of the HPA axis may promote weight gain, especially visceral adiposity. Chronically elevated cortisol promotes deposition of abdominal fat; decreases leptin signals and satiety; and increases ghrelin signals, appetite, and food intake. [vi] Increased aldosterone associated with stress can decrease insulin sensitivity by decreasing adiponectin, further promoting risk of inflammation and obesity.[vii]

Also, stress may amplify or trigger comorbidities in those who are already obese. The combination of psychological stress, impaired sleep, increased appetite and cravings, and decreased enthusiasm for physical activity can place someone who is stressed on the road to obesity, metabolic syndrome, and increased risk of chronic disease.[viii]

Therefore, it is imperative to address stressors and stress management when addressing the epidemic of obesity occurring in the developed world. It is important to note that individuals should be assessed for abdominal obesity and lean body mass and not just changes in BMI. Someone can be at an ideal BMI but have increased abdominal obesity and decreased muscle mass. On the other hand, an elevated BMI may reflect increased muscle mass and not adiposity.

Post-Traumatic Stress Disorder (PTSD)

Although our bodies are designed to respond acutely to stress and then reverse that response and return to homeostasis, the effects of stress may be extreme and may linger in some individuals. Severe effects and triggering events may cause an individual to relive a traumatic experience psychologically and physically. Disruption of the normal feedback loop involving cortisol and the HPA axis can further distort the reaction to ongoing stressors.

The occurrence of PTSD is associated with chronic disease including metabolic syndrome, CVD, autoimmune disorders, pulmonary disease, and additional psychiatric disorders. Research indicates that persistent low-grade inflammation may underlie PTSD and the chronic disorders associated with it. A review of the literature revealed significantly increased biomarkers of inflammation including acute-phase proteins, pro-inflammatory cytokines, and C-reactive protein in those with PTSD.[ix]

In one study of premenopausal women with PTSD, an increased release of DHEA in response to adrenal activation was associated with alleviation of adverse mood symptoms and severity of PTSD. Research suggests that DHEA may counteract the negative effects of cortisol on the brain including changes in brain structure and neurotransmitter balance.[x] The increased levels of DHEA and DHEA-S seen in PTSD are likely associated with the body’s attempt to manage stress and may facilitate coping in those affected.[xi]

Stress clearly affects physiological and psychological well-being and contributes to disease. An inventory of current stressors and coping mechanisms should be conducted in the evaluation of chronic disorders including cardiovascular disease, type 2 diabetes, depression, and gastrointestinal disorders.


[1] Murray, Michael T., and Joseph Pizzorno. The encyclopedia of natural medicine third edition. Simon and Schuster, 2012.

[ii] Kubzansky, Laura D, and Gail K Adler. “Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease.” Neuroscience and biobehavioral reviews vol. 34,1 (2010): 80-6. doi:10.1016/j.neubiorev.2009.07.005

[iii] Burford, Natalie G et al. “Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.” International journal of molecular sciences vol. 18,10 2150. 16 Oct. 2017, doi:10.3390/ijms18102150

[iv] Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

[v] Kim, Hye-Geum et al. “Stress and Heart Rate Variability: A Meta-Analysis and Review of the Literature.” Psychiatry investigation vol. 15,3 (2018): 235-245. doi:10.30773/pi.2017.08.17   

[vi] Ranabir, Salam, and K Reetu. “Stress and hormones.” Indian journal of endocrinology and metabolism vol. 15,1 (2011): 18-22. doi:10.4103/2230-8210.77573

[vii] Kubzansky, Laura D, and Gail K Adler. “Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease.” Neuroscience and biobehavioral reviews vol. 34,1 (2010): 80-6. doi:10.1016/j.neubiorev.2009.07.005

[viii] Geiker, N R W et al. “Does stress influence sleep patterns, food intake, weight gain, abdominal obesity and weight loss interventions and vice versa?.” Obesity reviews : an official journal of the International Association for the Study of Obesity vol. 19,1 (2018): 81-97. doi:10.1111/obr.12603

[ix] Speer, Kathryn et al. “Systemic low-grade inflammation in post-traumatic stress disorder: a systematic review.” Journal of inflammation research vol. 11 111-121. 22 Mar. 2018, doi:10.2147/JIR.S155903

[x] Rasmusson, Ann M et al. “An increased capacity for adrenal DHEA release is associated with decreased avoidance and negative mood symptoms in women with PTSD.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology vol. 29,8 (2004): 1546-57. doi:10.1038/sj.npp.1300432

[xi] Yehuda, R et al. “Clinical correlates of DHEA associated with post-traumatic stress disorder.” Acta psychiatrica Scandinavica vol. 114,3 (2006): 187-93. doi:10.1111/j.1600-0447.2006.00801.x

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