insights

Read Time: 5 Minutes

For centuries, people have contemplated the connection between the mind and body; the interplay is deep-rooted and complex, calling into question whether different mental states can positively or negatively affect biological functioning. In recent years, research has suggested that emotions like stress and worry, when they persist long-term, may contribute to imbalance in the body and increase risk for diseases ranging from depression to asthma, cancer, and heart disease.^1,2,3

A large meta-analysis of almost 300 independent studies published over 30 years indicated that psychological stress was associated with suppression of the immune system,⁴ and studies have continued to link stress with immune dysregulation and with a number of autoimmune and atopic diseases such as inflammatory bowel disease, allergy, atopic dermatitis, and celiac disease.^5,6 Both the rates of autoimmune diseases^7,8 and stress levels across the globe⁹ have increased exponentially over the last decade.

More recently, elevated levels of stress and anxiety have been documented among the US population during the continuing COVID-19 pandemic.^10-12 Public health actions such as social distancing can make people feel isolated and lonely, which can increase stress and anxiety. Some evidence suggests that stressful events may induce sympathetic nervous system and endocrine changes, among other biological responses, and that these changes can ultimately impair immune function.¹³ But whether stress or stress-related disorders play a direct role in the development of autoimmune disease remains an area of continuing research.

In the following video, IFM educator Robert Rountree, MD, describes how high levels of stress may alter immune function and change the progression of chronic illness.

In a large study published in JAMA in 2018, scientists found evidence that stress-related disorders are significantly associated with subsequent autoimmune disease.¹⁴ Researchers evaluated over 100,000 people diagnosed with stress-related disorders and compared their tendency to develop autoimmune disease at least one year later with 126,000 of their siblings and with another million people who did not have stress-related disorders. Study results indicated that:¹⁴

• Individuals diagnosed with a stress-related disorder were more likely to be diagnosed with an autoimmune disease and more likely to develop multiple autoimmune diseases.
• The increased rate of autoimmune disease was less significant among those individuals with post-traumatic stress disorder (PTSD) who were being treated with an SSRI.
• The findings were consistent with previous evidence linking psychological stress and stressful life events to immune dysregulation.
• Under stress, the activated autonomic nervous system may play a role in immune function impairment and may indirectly promote an inflammatory response.¹⁴

Among five-year-old children, researchers measured the association between high psychological stress in the family and immune response.⁴ Stress was assessed along four domains: serious life events, parenting stress, lack of social support, and parental worries. The results indicated that psychological stress may cause not only immune suppression but also an imbalance that may contribute to an autoimmune reaction against pancreatic ? cells. Moreover, in this study, children exposed to psychological stress (especially serious life events) induced an immune response against diabetes-related autoantigens. Researchers speculate whether this may indicate an autoimmune reaction against the insulin-producing ? cells, which, in some individuals, initiates progression toward type 1 diabetes.⁴

A more recent study evaluating the stress/depression levels of older patients age 55-65 found that natural killer cell activity is negatively affected by a depressed state.¹⁵ The researchers proposed that a combined treatment consisting of cognitive behavioral therapy and physical activity might improve patient outcomes.¹⁵

Stress Reduction: From Modifiable Lifestyle Habits to Mindfulness Practices

What stress-reducing interventions may positively affect the immune system and potentially prevent immune imbalance? Research suggests that people reporting stress may also engage in unhealthy behaviors more often than those who do not. For example, one study suggests that diet may be affected when people are under stress, with stressed people eating more “fast food,” higher-calorie meals.¹⁶ Sleep may also be altered, as stressors such as job demands and lack of control at work correlate with insomnia, sleep deprivation, and daytime fatigue.¹⁷ Alcohol intake is also likely to increase when individuals are under stress,¹⁸ as is cigarette use.¹⁹ Behavioral changes in these areas provide clinical points of leverage that may help lessen the impact of stress on the body.

In addition to modifying dietary and lifestyle trends for stressed patients, various psychological interventions, including cognitive behavioral therapy, mindfulness, and relaxation, have been found to effectively reduce stress.² Moreover, in a 2019 meta-analytic review of in-vitro and in-vivo models, researchers found that psychological interventions may improve immune function.²

One study evaluated the psycho-immune outcomes of an eight-week mindfulness-based stress reduction (MBSR) program for women newly diagnosed with breast cancer.²⁰ Compared to the control group, women randomized to MBSR exhibited decreasing trajectories of perceived stress, fatigue, sleep disturbance, and depressive symptoms. They also exhibited trajectories demonstrating significantly more rapid restoration of natural killer cell activity, accompanied by lower circulating TNF-alpha levels, lower IL-6 production, and greater IFN-gamma production.²⁰

Data from breast cancer patients also suggest that mind-body-based complementary therapies (e.g., mindfulness, meditation, yoga, tai chi, qigong, guided imagery, and affirmations) may influence the immune profile of patients.²¹ Breast cancer survivors who undertook Iyengar yoga sessions for 8 or 12 weeks showed reduced morning and evening cortisol levels along with improved fatigue and emotional well-being.²² In another study, breast cancer patients who received tai chi chuan training showed significant improvements in bone health, immune function, and quality of life.²³

Conclusion

Collectively, autoimmune disorders are one of the most prevalent diseases in the US and affect up to 10% of the US population, or an estimated 24 million people.^7,8 While it is clear that environmental factors play an important role in the underlying etiology of these diseases, whether or not there is a causal link to stress is yet to be fully illuminated. However, as interest in the topic grows, more and more evidence suggests that when done in tandem, modifying unhealthy coping habits and integrating mind-body interventions into a patient’s daily life may help to improve stress and prevent immune dysfunction. Learn more about tools and strategies to help patients achieve sustainable lifestyle change and improve their well-being through IFM’s new course Lifestyle: The Foundations of Functional Medicine.

Learn to recognize and reverse immune dysfunction 

Innate Immunity: Diet and Lifestyle Support

Non-celiac immune responses to gluten 

References

1. Thornton LM, Andersen BL. Psychoneuroimmunology examined: the role of subjective stress. Cellscience. 2006;2(4):66-91.
2. Schakel L, Veldhuijzen DS, Crompvoets PI, et al. Effectiveness of stress-reducing interventions on the response to challenges to the immune system: a meta-analytic review. Psychother Psychosom. 2019;88(5):274-286. doi:10.1159/000501645
3. Chu B, Marwaha K, Sanvictores T, Ayers D. Physiology, Stress Reaction. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK541120/
4. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601-630. doi:10.1037/0033-2909.130.4.601
5. Carlsson E, Frostell A, Ludvigsson J, Faresjö M. Psychological stress in children may alter the immune response. J Immunol. 2014;192(5):2071-2081. doi:10.4049/jimmunol.1301713
6. Morey JN, Boggero IA, Scott AB, Segerstrom SC. Current directions in stress and human immune function. Curr Opin Psychol. 2015;5:13-17. doi:10.1016/j.copsyc.2015.03.007
7. Hood E. Measuring autoimmunity in America. Environmental Factor. Published April 2018. Accessed December 10, 2021. https://factor.niehs.nih.gov/2018/4/science-highlights/autoimmunity/index.htm
8. National Institute of Environmental Health Sciences. Autoimmune diseases. Reviewed July 12, 2021. Accessed December 10, 2021. https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm – footnote1
9. Global Organization for Stress. Stress facts. Accessed December 10, 2021. http://www.gostress.com/stress-facts/
10.  American Psychological Association. Stress in America 2020: Stress in the Time of COVID-19, volume three. Published July 2020. Accessed December 10, 2021. https://www.apa.org/news/press/releases/stress/2020/report-july
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13.  Tizenberg BN, Brenner LA, Lowry CA, et al. Biological and psychological factors determining neuropsychiatric outcomes in COVID-19. Curr Psychiatry Rep. 2021;23(10):68. doi:10.1007/s11920-021-01275-3
14.  Song H, Fang F, Tomasson G, et al. Association of stress-related disorders with subsequent autoimmune disease. JAMA. 2018;319(23):2388-2400. doi:10.1001/jama.2018.7028
15.  Cañas-González B, Fernández-Nistal A, Ramírez JM, Martínez-Fernández V. Influence of stress and depression on the immune system in patients evaluated in an anti-aging unit. Front Psychol. 2020;11:1844. doi:10.3389/fpsyg.2020.01844
16.  Errisuriz VL, Pasch KE, Perry CL. Perceived stress and dietary choices: the moderating role of stress management. Eat Behav. 2016;22:211-216. doi:10.1016/j.eatbeh.2016.06.008
17.  Kalimo R, Tenkanen L, Härmä M, Poppius E, Heinsalmi P. Job stress and sleep disorders: findings from the Helsinki Heart Study. Stress Med. 2000;16(2):65-75. doi:10.1002/(SICI)1099-1700(200003)16:2<65::AID-SMI834>3.0.CO;2-8
18.  Armeli S, Todd M, Mohr C. A daily process approach to individual differences in stress-related alcohol use. J Pers. 2005;73(6):1657-1686. doi:10.1111/j.0022-3506.2005.00362.x
19.  Kouvonen A, Kivimäki M, Virtanen M, Pentti J, Vahtera J. Work stress, smoking status, and smoking intensity: an observational study of 46,190 employees. J Epidemiol Community Health. 2005;59(1):63-69. doi:10.1136/jech.2004.019752
20.  Witek Janusek L, Tell D, Mathews HL. Mindfulness based stress reduction provides psychological benefit and restores immune function of women newly diagnosed with breast cancer: a randomized trial with active control. Brain Behav Immun. 2019;80:358-373. doi:10.1016/j.bbi.2019.04.012
21.  Abrahão CA, Bomfim E, Lopes-Júnior LC, Pereira-da-Silva G. Complementary therapies as a strategy to reduce stress and stimulate immunity of women with breast cancer. J Evid Based Integr Med. 2019;24:2515690X19834169. doi:10.1177/2515690X19834169
22.  Banasik J, Williams H, Haberman M, Blank SE, Bendel R. Effect of Iyengar yoga practice on fatigue and diurnal salivary cortisol concentration in breast cancer survivors. J Am Acad Nurse Pract. 2011;23(3):135-142. doi:10.1111/j.1745-7599.2010.00573.x
23.  Janelsins MC, Davis PG, Wideman L, et al. Effects of tai chi chuan on insulin and cytokine levels in a randomized controlled pilot study on breast cancer survivors. Clin Breast Cancer. 2011;11(3):161-170. doi:10.1016/j.clbc.2011.03.013