Battling Bugs and Blues: The Interplay of Infection and Emotion

Understanding the intricate relationship between infection and emotions is at the forefront of research in the field of psychoneuroimmunology. This emerging discipline explores how mental health and immunity intersect, shedding light on the impact of stress on susceptibility to infection.

Psychoneuroimmunology is an interdisciplinary field that investigates the complex interplay between the mind, the nervous system, and the immune system. It explores how psychological and emotional factors can influence immune responses and ultimately impact the overall health and well-being of an individual.

Emotional states, such as stress, anxiety, and depression, have been found to influence susceptibility to infections. Chronic stress, for example, can weaken the immune system, increasing vulnerability to pathogens. Conversely, positive emotional states have been associated with enhanced immune function.

The connection between emotions and immune function

Extensive research has focused on exploring the influence of emotions, particularly stress and depression, on the immune system.1 Stress, whether experienced acutely or chronically, can disrupt immune function through multiple mechanisms. It stimulates the release of stress hormones, which, at excessive levels, can suppress immune responses.1

The presence of chronic stress has been associated with a reduction in immune cell activity.1 Similarly, depression has been found to be connected to dysregulation of the immune system, resulting in changes to cytokine levels, immune cell function, and inflammatory processes.1

The body’s stress response, commonly known as the “fight-or-flight” response, involves the activation of the sympathetic nervous system and the subsequent release of stress hormones.1 While this response is crucial for immediate survival in threatening situations, its chronic activation can have detrimental effects on immune function.1

Extensive research has examined the link between emotional well-being and susceptibility to infections.2 The autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis contribute to this immune dysregulation in response to stress.2 In a stressful situation, the brain activates the HPA axis and the sympathetic-adrenal medullary axis, leading to the release of hormones that modulate immune function, including adrenocorticotropic hormone, cortisol, growth hormone, prolactin, epinephrine, and norepinephrine.2

Chronic stress has the potential to dysregulate both innate and adaptive immune responses by altering the balance between type 1 and type 2 cytokines, leading to low-grade inflammation and the inhibition of immune-protective cell function. 1,3

On the other hand, chronic inflammation has been associated with an increased risk of various diseases, including infectious diseases, cardiovascular diseases, diabetes, certain cancers, and autoimmune disorders.2,3 One possible explanation for the mechanism linking chronic stress and inflammation is the development of glucocorticoid receptor resistance due to prolonged stressors.4 This resistance subsequently leads to dysregulation of the HPA axis and, consequently, of inflammation.4

Different experiments in animal models have shown how chronic inflammation provokes sickness and depressive-like behaviors in response to chronic stress.5

Stress can disrupt cellular and humoral immune responses, increasing the susceptibility to infectious diseases such as influenza.1 It is also associated with the reactivation of latent viruses (e.g., HSV and EBV) and altered T-cell responses to anti-viral vaccinations.1

Additionally, acute psychological stress induces rapid changes in leukocyte dynamics that can influence the body’s response to autoimmune and viral challenges.6

Infections influencing mental health

The relationship between emotions and infection susceptibility is bidirectional. The best example of this phenomenon is sepsis.

Antibodies eBook Compilation of the top interviews, articles, and news in the last year. Download the latest editionSepsis is an uncontrolled immune response to severe infection that can lead to long-term psychiatric disorders, including persistent anxiety and post-traumatic stress disorder.7

Using a mouse model of sepsis, researchers discovered that mice that recovered from sepsis developed anxiety-related behaviors.7 The study also found that sepsis caused pathological activation of specific neurons in the central nucleus of the amygdala.7 However, by temporarily silencing this neuronal subpopulation, the development of anxiety-related behaviors was prevented, suggesting that targeting anxiety/fear circuits in the brain during the acute phase of sepsis could be a preventive strategy to mitigate psychiatric consequences after infection.7

These bidirectional interactions are especially important in the context of COVID-19, as both SARS-CoV-2 infection and pandemic-related stress stimulate the immune system, resulting in mood, cognitive, and behavior changes.8

These symptoms are thought to be caused in part by unresolved peripheral inflammation after infection.8 Nonetheless, several investigations have found that viral infection might cause neuronal antibody production against multiple antigens in COVID-19 patients who have unexplained neurological symptoms.9

Classical hypotheses for depression pathogenesis include neurotransmitters, the HPA axis, neuroplasticity, and neuroimmunity.10 Currently, numerous investigations have indicated that it is intimately associated with glial cells.10

Furthermore, recent research found that some viral infections are linked to the development of depression (SARS-CoV-2, BoDV-1, HIV, ZIKV, HHV-6).10 These viruses can infect glial cells, and their damage/dysregulation can lead to depression. Viral infection can also influence the onset and course of depression by promoting the release of pro-inflammatory factors and regulating hormone release and protein expression.10

Stress, infection, and the vicious cycle

Research has highlighted the cyclical relationship between stress, the immune system, infection risk, and its impact on emotional well-being.

Breaking this detrimental cycle requires multifaceted strategies. Some of these are psychological interventions like cognitive-behavioral therapy, social support networks, and promoting a healthy lifestyle.

In some cases, medical interventions may be necessary. The use of drugs for treating mental health problems is a common approach in clinical practice. While these medications can be effective in alleviating symptoms, it is important to consider their potential impact on the immune system.

Future directions in research and therapy

The COVID-19 pandemic has brought mental health challenges to the forefront. Studies have shown that the pandemic has had a significant impact on collective and individual well-being, leading to an increased prevalence of anxiety, depression, and other mental disorders.

Enhancing diagnosis is the first step in resolving these problems. The application of AI in mental health diagnostics is one instance of this, as AI is being used to detect early indicators of mental illness and help with its prevention and treatment.11

Integrative treatment, which treats both the physical and emotional aspects of health, is receiving great attention in the field of health and wellness.12 For patients with physical and mental health comorbidities, an integrative, collaborative care model that combines cutting-edge adjunctive therapies with traditional pharmaceutical treatments to enhance patients’ quality of life has been proposed.


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