Psychoneuroimmunology

by

Michelle A. Chen, Christopher P. Fagundes

• LAST REVIEWED: 12 January 2023
• LAST MODIFIED: 12 January 2023
• DOI: 10.1093/obo/9780199828340-0303

Introduction

The field of psychoneuroimmunology is concerned with how psychological factors “get under the skin” to impact the nervous system and immune system. Using observational longitudinal and experimental methods, researchers in the field of psychoneuroimmunology have found that psychological factors can dysregulate the immune system, the central and peripheral nervous system, and the endocrine system in ways that influence wound healing, latent herpesvirus reactivation, vaccine responses, susceptibility to viruses, and pro-inflammatory cytokine production (i.e., production of proteins that signal immune cells that promote inflammation). Specifically, neurotransmitters and hormones regulate immune cells, which in turn have vast clinical implications on health and immunity. Theories and methods within psychoneuroimmunology have been utilized to investigate a wide array of physical health problems from asthma to cardiovascular disease and some cancers. Interpersonal stressors appear to have a particularly significant impact on these systems in comparison to non-interpersonal stressors. Furthermore, stressors that occur early in life may have a lasting effect on the immune system, the endocrine system, and the nervous system into adulthood and old age. The field has become increasingly focused on how the immune system can impact mood and behavior. Indeed, certain types of depression and fatigue appear to be affected by dysregulated immunity. Emerging areas of investigation include a focus on interactions between the brain, gut, mitochondria, and diet. Finally, there is great interest in understanding how epigenetic processes (i.e., how genes are expressed) emerge from life experiences, impacting immunity and disease.

General Overviews

The field of psychoneuroimmunology has historically been concerned with how psychological processes get “under the skin” to impact the immune system. Ader and Cohen 1975 experimentally shows that it is possible to use classical conditioning methods to modulate immunity. Glaser 2005 provides a historical overview of the field of psychoneuroimmunology, explaining the field’s progression from animal to human models. O’Connor, et al. 2009 provides an overview of important methodological considerations for human work. Segerstrom and Miller 2004 provides a meta-analysis showing that both acute and chronic stressors promote immune dysregulation. Dantzer 2017; Glaser and Kiecolt-Glaser 2005; and Miller, et al. 2002 provide mechanistic overviews of psychological factors that get under the skin to impact immunity. Finally, Polsky, et al. 2022 provides a recent review on the relationship between stress, age-related disease, and biological aging, citing the role of neuroendocrine mediators, cellular metabolic activity, DNA damage, mitochondrial dysfunction, telomere shortening, and inflammation on this relationship.

• Ader, R., and N. Cohen. 1975. Behaviorally conditioned immunosuppression. Psychosomatic Medicine 37.4: 333–340.

  DOI: 10.1097/00006842-197507000-00007

  The authors paired saccharin (a sugar substitute) with an immunosuppressive compound in a group of rats. Two other groups received water rather than saccharin; one was injected with the same immunosuppressive compound and the other was administered a placebo. The rats exposed to saccharin and the immunosuppressive drug were significantly immunosuppressed after being injected with an antigen (i.e., a substance that triggers an immune response in the body) compared to those in the other conditions. This study demonstrates it is possible to behaviorally condition immunosuppression, giving experimental credence to the brain and immune link.

• Dantzer, R. 2017. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiological Reviews 98.1: 477–504.

  DOI: 10.1152/physrev.00039.2016

  A comprehensive review on the bidirectional pathways by which the brain, autonomic, neuroendocrine, and immune systems interact. The review highlights the differences between short-range and long-range interactions between each system. Specifically, Dantzer highlights the impact of the communication pathways between systems for mental and physical health.

• Glaser, R. 2005. Stress-associated immune dysregulation and its importance for human health: A personal history of psychoneuroimmunology. Brain, Behavior, and Immunity 19.1: 3–11.

  DOI: 10.1016/j.bbi.2004.06.003

  This is a well-written broad overview of how psychological stress impacts the immune system. This review summarizes a large body of work on how psychological stress can affect wound healing, herpesvirus latency, inflammation, immune responses to vaccines, as well as functional markers of immunity.

• Glaser, R., and J. K. Kiecolt-Glaser. 2005. Stress-induced immune dysfunction: Implications for health. Nature Reviews Immunology 5.3: 243–251.

  DOI: 10.1038/nri1571

  Overview written for a broad audience on how stress impacts different aspects of immune function. Glaser and Kiecolt-Glaser summarize how different hormones interact with the expression of receptors on immune cells to produce various clinically relevant outcomes. They also summarize how stress impacts wound healing, herpesvirus reactivation, inflammation, and aging.

• Miller, G. E., S. Cohen, and A. K. Ritchey. 2002. Chronic psychological stress and the regulation of pro-inflammatory cytokines: A glucocorticoid-resistance model. Health Psychology 21.6: 531–541.

  DOI: 10.1037/0278-6133.21.6.531

  This mechanistic paper explains the pathway by which cortisol, an anti-inflammatory hormone, can boost inflammation. Specifically, the authors explain how chronic stress can lead to glucocorticoid resistance (i.e., desensitization of receptors on the immune cells for cortisol). Thus, inflammation is released in an unregulated environment, thereby allowing for elevated inflammation in the periphery.

• O’Connor, M. F., J. E. Bower, H. J. Cho, et al. 2009. To assess, to control, to exclude: Effects of biobehavioral factors on circulating inflammatory markers. Brain, Behavior, and Immunity 23.7: 887–897.

  DOI: 10.1016/j.bbi.2009.04.005

  When researchers in the field of psychoneuroimmunology claim that a specific psychosocial factor is responsible for alterations in immune function in humans, they must account for potential third-variable influences. In this paper, O’Connor and colleagues propose several recommendations when studying how stress impacts pro-inflammatory cytokine production. Specifically, they make recommendations regarding what to adjust for statistically and what to exclude.

• Polsky, L. R., K. E. Rentscher, and J. E. Carroll. 2022. Stress-induced biological aging: A review and guide for research priorities. Brain, Behavior, and Immunity 104:97–109.

  DOI: 10.1016/j.bbi.2022.05.016

  This recent review highlights research on the relationship between stress and age-related disease, focusing on neurobiological mechanisms in which chronic stress impacts biological aging. The authors discuss neuroendocrine mediators (e.g., norepinephrine, epinephrine, and glucocorticoids), as well the role of cellular metabolic activity, DNA damage, mitochondrial dysfunction, telomere shortening, and inflammation, on the relationship between stress and aging. Furthermore, the authors provide a framework and conceptual model outlining these pathways and future research directions.

• Segerstrom, S. C., and G. E. Miller. 2004. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychological Bulletin 130.4: 601–630.

  DOI: 10.1037/0033-2909.130.4.601

  This landmark meta-analysis summarizes 30 years of research on how various psychosocial factors promote immune dysregulation. The authors find evidence for this link and summarize differences in the strength of the relationships depending on various psychosocial factors. Importantly, they found that acute stressors had a more significant impact on cellular immune function than humoral immune function. At the same time, chronic stress appeared to promote immune dysregulation across both branches of the immune system.