Research demonstrates that these systems communicate intricately and bidirectionally, influencing integral aspects of mental and physical health. In fact, a growing body of research reveals comorbidities between compromised immunity and psychiatric conditions.
A 2024 review indicative of PNI at play, demonstrated the intricacy among psychological stress, alterations in nervous system, immune response, and oral health. This comprehensive review found that stress—including anxiety and depression—was associated with suppressed immune function, alterations in oral microbiome composition, and the development of oral health disease.
Similarly, researchers also found that those with oral health conditions, such as periodontitis, had increased levels of systemic inflammation, which had negative effects on mental health through these interconnected pathways.
In addition to mental stress, dysbiosis—an imbalance in microbiota composition—has been shown to contribute to dysregulation of these pathways—while impeding permeability of the blood-brain-barrier. This has been shown to result in neuroinflammation, as evidenced in a 2022 review published in The Journal of Inflammation Research. These findings emphasize the pivotal role the immune system plays in regulating brain function and mental health, and are influenced by both top-down and bottom-up forms of communication.
The brain-gut-microbiota axis—comprising the vagus nerve, neural and immune system, and intestinal metabolites—serves as a critical communication network between the body and the brain. A growing body of research highlights the pivotal role this axis has in modulating immune function, inflammation and the central nervous system (CNS).
Immunity can be impacted by an overdrive in brain circuits due to chronic stress, underscoring the effects of stress on immune and nervous system pathways, as emphasized in findings published in Cell Reports. While sufficient amounts of cortisol have integral roles in modulating hormonal balance, brain function, and immune response—prolonged elevated levels can impede upon these systems.
Chronic stress puts the body in a heightened state of arousal due to overactivation of the sympathetic nervous system (SNS). Over time, this results in dysregulation of the HPA axis and abnormal cortisol production, as the body aims to adapt and compensate, compromising these regulatory bodily functions.
Inflammatory mediators, or cytokines, are released by immune cells in response to stress. Research highlights the effects of chronic stress on neuroimmune function, inflammation and microglia– all contributing to the neurobiological effects associated—as demonstrated in a review published in Biological Psychiatry.
Chronic stress is often a contributing factor to the onset of mental health conditions, as evidenced by a robust body of research. Notably, connections among Obsessive-Compulsive Disorder (OCD) and autoimmune conditions exist in the literature, as demonstrated in a 2023 review. This makes sense given the significant physiological and psychological effects induced in the body and mind as a result of chronic stress.
A host of psychiatric conditions have been associated with heightened systemic inflammation, such as increased levels of C-reactive protein (CRP) and other pro-inflammatory cytokines.
Elevated levels of IL-6 and tumor necrosis factor (TNF) were found in individuals with compromised immune function and depression, as evidenced in a 2021 systematic review published in Molecular Psychiatry of 38 studies representing over 58,000 participants.
The tryptophan-kynurenine pathway, which modulates immune responses and brain function, is also a pivotal system impeded by chronic stress. Alterations in this pathway have been implicated in depression and other psychiatric conditions. These findings underscore how chronic stress, through immune system alterations, can contribute to the development of mental health conditions.
Immune cells have also been shown to communicate to the brain by sending out neurotransmitters and hormone signals up to the prefrontal cortex and limbic system, further underscoring these novel bidirectional relationships. In fact, neurotransmitter receptors have been discovered on white blood cells, as well as on lymph glands. Immune to brain signaling pathways has effects on neural and psychological functions through inflammation and alterations in gut microbiome and hormonal balance.
Similarly, research reveals that the brain communicates with the immune system through top down mechanisms as emphasized through the effects of perceived stress, or brain to immune signaling.
Psychoneuroimmunology highlights how mind-body practices can support modulation of appropriate immune, hormonal and inflammatory responses in the face of stress. Meditation promotes restoring balance between the body and mind, helping to mitigate the toxic effects of chronic stress. Adhering to a nutrient-dense, anti-inflammatory diet that is supportive to microbiome and hormonal health may further promote balance amongst these systems.
Engaging in yoga and ayurvedic practices has been shown to improve immune function via these interconnected mechanisms. Compellingly, acupuncture appears to stimulate immunomodulating responses via vagus adrenal, brain-gut and anti-inflammatory pathways.
Sufficient sleep, hydration and body-mind attunement are further foundational ways of addressing the mechanisms involved in PNI. Simply being more mindful of these established connections and your relationship to stress is a great place to start.
Psychoneuroimmunology offers critical insights into the complex interplay between chronic stress, inflammation, and mental health via bidirectional immune to brain signaling pathways. Ongoing research is encouraged in exploring how immune system dysregulation can impede mental health.
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