The Engine of Mind-Body Medicine:

Psychoneuroimmunology

(c) B. Kristine Burneko, APRN, PMHNP-BC, APHN-BC. All rights reserved by the author.

PENDING PUBLICATION JANUARY 2026

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Introduction

Psychoneuroimmunology (PNI) is a multidisciplinary field that examines the tridirectional interaction of psychological processes, neurological activity, and immune function. Within clinical practice, PNI provides the mechanistic foundation for mind–body medicine, an evidence-based approach that complements conventional biomedical care by enhancing psychophysiological regulation and response to concurrent treatments.  Harnessing the power of PNI, mind-body medicine also tends to foster a sense of wellness and empowerment in the client population – perhaps driving the increased popular interest in these techniques.

Origins and Classification

The conceptual origins of PNI emerged from clinical and experimental observations in the late 20th century. Psychiatrist George Solomon identified a correlation between acute episodes of major depressive disorder and inflammatory exacerbation in rheumatoid arthritis. The research of physician Dr. Herbert Benson demonstrated reproducible reductions in blood pressure through meditation-induced autonomic regulation (Klyde, 2024).  Finally, Ader & Cohen (1993) determined that psychoemotional cues could directly influence immune responses (both humoral and cell-mediated) and vice versa.  Together, these breakthroughs initiated a momentum that began to challenge the traditional Cartesian separation of mind and body in Western medical practice.

The National Center for Complementary and Integrative Health (NCCIH, 2025) classifies mind–body practices into three categories: psychological (e.g., mindfulness meditation, spiritual practice, hypnosis, sound and music therapies), physical (e.g., acupuncture, massage, manual therapies), and psychophysical modalities (e.g., yoga, tai chi, and movement-based therapies). These approaches may be provider-administered—such as hypnosis and neurofeedback—or self-directed, including diaphragmatic breathing, biofeedback, progressive muscle relaxation, guided imagery, contemplative practices, and meditative movement disciplines although even the self-directed techniques are best instructed by licensed providers (Klyde, 2024).

The conscious regulatory techniques utilized in these mind-body techniques, when administered properly, can reduce activation of the sympathetic nervous system, increase function of the parasympathetic nervous system, and attenuate stress-related neuroendocrine output, including cytokines, prostaglandins, tumor necrosis factors, cortisol, epinephrine, and norepinephrine.

Nervous System Regulation

Central to PNI is nervous system regulation, particularly increased parasympathetic tone and moderated or reduced sympathetic activation. When the mind perceives an acute stressor and the sympathetic nervous system is activated, the hypothalamus secretes corticopin-releasing hormone (CRH), which in turn induces release of adrenocorticotropic hormone (ACTH) by the pituitary. The circulating ACTH stimulates the release of cortisol and adrenaline by the adrenal medulla, activating the body’s defense system but also flooding the system with glucose, increasing blood pressure, minimizing immune function, stopping digestion, and pausing cell repair. Uncontrolled for long periods of time, these sympathetic functions can drastically impair bodily homeostasis.

When a client learns to moderate their perception of danger through various mind-body interventions – thereby gaining control of the sympathetic nervous cascade – the cumulative damages of this process can be minimized. Repeated engagement in relaxation-based interventions can also encourage neuroplastic adaptations within stress-response circuits, leading to reduced nociceptive signaling, diminished anxious reactivity, healthier sleep cycling, and improved affective regulation. However, neurological activation of the sympathetic response described above is only the beginning. Shortly afterward, the immune system begins to dysregulate as well (O’Connor et al., 2014).

Endocrine Shifts and Immunoregulation

When the nerve cells of the sympathetic response are activated, they secrete norepinephrine – as does the adrenal gland. The norepinephrine, in turn, agonizes immune tissues in the thymus, bone marrow, spleen, and lymph nodes.  These secrete catacholamines, and the macrophages and lymphocytes produced by the immune organs carry the norepinephrine throughout the body.

From an immunological perspective, chronic dysregulation of cortisol, adrenaline, and sympathetic signaling can impair immune surveillance, and the increased circulation of cytokines can promote pro-inflammatory states such as metabolic syndromes (Kivimäki et al, 2023) and worsening autoimmune disease. Mind–body interventions mitigate these effects by restoring homeostatic signaling between neuroendocrine and immune pathways.

Alterations in Cellular Function

At the cellular and systemic levels, the increased circulation of cytokines inspired by severe or prolonged psychological stress can alter cell function and affect the development of multiple pathologies including dermatological disease (Tausk et al., 2008), osteoporosis, cardiovascular disease, asthma, type 2 diabetes, rheumatological disorders, and even certain cancers (Kiecolt-Glaser et al., 2002). In addition to this immune activation, another possible pathological process initiated by the stress cascade is the reactivation of latent viruses, e.g., cytomegalovirus (Klopack, 2023).

Psychological Effects

Mind–body interventions can improve outcomes in stress-sensitive conditions, including asthma, cardiovascular disease, functional gastrointestinal disorders, chronic pain syndromes, autoimmune diseases, and chemotherapy-related nausea and vomiting (Klyde, 2024). Additionally, consistent psychological benefits—including reductions in insomnia, anxiety, and depressive symptoms—underscore the reciprocal nature of these interventions and their physiological results.

As explained above, psychological stress can negatively impact physiological functioning in myriad ways – but these dysfunctional alterations themselves can also impact psychological health directly. For example, it is currently hypothesized that prolonged or acute sympathetic nervous system activation can increase cytokine, microglial, and prostaglandin activity in the brain – which subsequently inhibits dopamine activity, which can result in depressive symptoms and other psychological manifestations (Ishikawa and Furuyashiki, 2025).

Conclusion

The emerging subspecialty of psychoneuroimmunology unites the insights of psychology, neurology, and immunology in a way that is beginning to explain the powerful effects of mind-body medical interventions. It is becoming increasingly clear through PNI research that psychological stress is not merely an emotional experience but a biological cascade capable of altering cellular function, immune surveillance, disease progression, and nervous system regulation. Similarly, we are seeing how well-applied mind–body interventions can restore regulatory balance across these systems, resulting in measurable improvements in both physical and psychological health outcomes. Understanding the dynamics of psychoneuroimmunology can empower clinical providers to confidently employ mind-body medicine and offer to our clients a more holistic, patient-empowering model of care that honors the deep integration of the human mind and body.

References

Ader, R., & Cohen, N. (1993). Psychoneuroimmunology: Conditioning and Stress. Annual Review of Psychology, 44(1), 53–85. https://doi.org/10.1146/annurev.ps.44.020193.000413

Ishikawa, Y., & Furuyashiki, T. (2022). The impact of stress on immune systems and its relevance to mental illness. Neuroscience Research, 175, 16–24. https://doi.org/10.1016/j.neures.2021.09.005

Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002). Psychoneuroimmunology: Psychological influences on immune function and health. Journal of Consulting and Clinical Psychology, 70(3), 537–547. https://doi.org/10.1037/0022-006X.70.3.537

Kivimäki, M., Bartolomucci, A., & Kawachi, I. (2023). The multiple roles of life stress in metabolic disorders. Nature Reviews. Endocrinology, 19(1), 10–27. https://doi.org/10.1038/s41574-022-00746-8

Klopack, E. T. (2023). Chronic Stress and Latent Virus Reactivation: Effects on Immune Aging, Chronic Disease Morbidity, and Mortality. The Journals of Gerontology: Series B, 78(10), 1707–1716. https://doi.org/10.1093/geronb/gbad087

Klyde, M.B. (2024). Mind-Body Medicine. Research Starters | EBSCO Research. (n.d.). Retrieved December 26, 2025, from https://www.ebsco.com

National Center for Complementary and Integrative Health. (2025). Mind and body practices. Accessed 27 December 2025 from https://www.nccih.nih.gov/health/mind-and-body-practices

Tausk, F., Elenkov, I., & Moynihan, J. (2008). Psychoneuroimmunology. Dermatologic Therapy, 21(1), 22–31. https://doi.org/10.1111/j.1529-8019.2008.00166.x