The Psychoneuroimmunology of Stress: Acute and Chronic

Research by: Shannon Connell

Psychoneuroimmunology (PNI) is a field of research that deals with the interaction of the central nervous system, the endocrine system, and the immune system, and how these systems can be altered through behavior and stress. The immune, nervous, and endocrine systems communicate to maintain health. PNI is interested in the effects of thoughts and emotion on immune functioning. Stress affects the entire being, nerves, cells, tissues, and systems of the body. Stress if held, can disrupt nervous, endocrine, and immune system functioning resulting in “dis-ease” of body and mind.

Homeostasis is the body’s ability to maintain a stable physiological internal environment. The immune system is actively involved in homeostasis. Stress is any sudden or intense disturbance, or disharmony of homeostasis balance. If homeostasis is not rebalanced, there is greater vulnerability to illness. The goals of PNI are to support homeostasis balance, and to study the psychological effects on the immune system, as well as the effects of immunity on psychology. This is an important concept for understanding health and disease and can be used as a predictor to disease vulnerability. PNI supports psychological interventions such as health psychology applications that may have positive effects in prevention and treatment of disease. The development of PNI, biological responses to acute and chronic stress, research, applications, and accomplishments will be discussed, as well as the current need for growth and education.

The interest in the relationship between psychiatric health and immune functioning has been a scientific interest for decades. During the 1940’s psychosomatic investigations became popular, investigating the connection of psychological behaviors, emotions, and characteristics with the onset and progression of disease. In 1964, George F. Solomon coined the term psychoneuroimmunology and published a popular description of his theories. Ader & Cohen, in 1975, were the first to demonstrate classical conditioning of the immune system and its functioning, providing research that immune function can be elevated or decreased through psychological tone. The 1980’s brought about the emergence of biopsychology, which greater supported the theory that stress can lead to a greater susceptibility of infection and disease. The PNI field’s popularity increased in the 1990’s, research and publications tripled. Research has proven PNI worthy of study.

From an evolutionary perspective, stress is not all bad. Stress is an adaptation that has supported species survival. Most of us would not be here if our ancestors did not have a well-tuned stress response system to survive predators or invaders. Just waking up in the morning creates a stress response, demanding an increase in blood pressure to activate the sympathetic nervous system and the release of hormones. Anytime a threat is perceived the sympathetic nervous system is activated. Phenotype plasticity describes the changes related to immunity due to situational stressors. An example of phenotype plasticity is sickness behavior. Sickness behavior preserves energy for the use of the immune system, and reorganizes behavior to adapt to the present need. During sickness behavior the brain interprets cytokines as signals of illness, resulting in loss of appetite, changes in sleeping patterns, and loss of energy or social motivations. Sickness behavior is caused by proinflammatory cytokines and is an adaptive behavior to ensure survival. For example, the loss of appetite supports a decrease in iron intake. Iron supports bacterial replication, therefore its decrease is a survival adaptation to protect against infection. The increase in sleep, energy loss, and loss of social motivations ensure a greater probability that the species will avoid conflict and danger.

Vulnerabilities to stress include age, pessimistic attitude, biology, poor coping abilities, lack of psychosocial support and resources, risky lifestyle, interpersonal issues, and marital stress. There has been research interest in the PNI of acute and chronic stress. Acute stress produces the release of immune defenders, however will rebalance once threat subsides. Chronic stress arises when there is no rebalance. The biological responses of acute and chronic stress are important areas of study for biopsychologists, as it assists health practitioners with approach, diagnosis, and treatment. The biological responses from acute and chronic stress will demonstrate the interaction and interconnection of the nervous system, the immune system, and the endocrine system.

The acute stress response stimulates hormonal release in order to create more energy for the body’s immediate use. Blood pressure elevates and the heart beats faster to bring blood into large muscles, to allow either defense or fleeing. The stress hormones create an important exchange of energy, where energy is moved into skeletal muscles and to the brain. Blood then rushes into the core to minimize potential blood loss. This is called shunting, and is another fight-or-flight coping mechanism. Blood will also begin to clot more easily in case of injury. All of the above alarms the immune system and prompts it to send white blood cells to their so called “battle stations,” sticking to the walls of the capillaries ready to metabolize if infection occurs. Fats and sugars become mobilized for energy use. Acute stress creates changes in the nervous system, such as increases in pain sensitivity, the suspension of digestion, and the suspension of hormonal development. As mentioned earlier, this creates sickness behavior, minimizing eating, sexual activity, and growth, to ensure survival.

Once a threat subsides, the body will shift into a restorative mode where the parasympathetic system will take over the sympathetic nervous system. Blood pressure and heart rate will return to normal. Stress hormones and blood sugar levels decrease, as does the levels of blood clotting. Today most threats to homeostasis are not physical, rather psychological; such as worries about job, relationship, money, security, and happiness. These worries, if not resolved quickly, will result in the stress response remaining activated, or constantly and repeatedly reactivated. This is when the body’s protection system can turn and cause disease.

Much of the brain’s influence in the stress response is exerted through the hypothalamic pituitary adrenal axis. The hypothalamic pituitary adrenal axis (HPA) is responsible for producing stress hormones. It regulates growth, reproduction, thyroid function, as well as appetite and sleep. The HPA helps to regulate homeostasis and adjusts functioning of the sympathetic nervous system and endocrine system as needed. Once stress hormones are released they travel to the adrenal medulla, and stimulate the production and release of epinephrine. Meanwhile, the paraventricular nucleus, which is a part of the hypothalamus, releases the hormone corticotrophin. Corticotrophin stimulates the pituitary gland and inspires the release of adrenocorlicotrophin, which stimulates the adrenal cortex in the release of cortisol.

High levels of cortisol can be linked to psychological and physiological diseases. High cortisol levels have been linked to increased fasting blood sugar, high systolic and diastolic blood pressure, increased triglyceride levels, and insulin resistance. High cortisol levels have also been linked to stress-related eating in laboratory rats and binge eating in humans. Psychological diseases such as depression, addiction, and anxiety disorders are all related to elevated levels of cortisol. Heart disease, diabetes, decreased bone density, cancer, memory loss, and other chronic diseases are physiological consequences. It is obvious that the functioning and teamwork of the nervous, endocrine, and immune systems are complex as well as the reactions they have on wellness and disease.

Physiological effects of acute stress include lipolysis, increased blood pressure, activation of the immune system, shunting of blood to major internal organs, leukocytosis, trafficking, and the migration of white blood cells. Lipolysis is the process of breaking down fat for energy use. Leukocytosis is when the defense cells are released into the blood stream, and trafficking is the production increase of white blood cells that detect invading cells and attack in a process termed phagocytosis.

The biological response to chronic stress begins as an acute stress response, however, homeostasis is not returned to a point balance. High blood pressure is sustained, resulting in elevated resting blood pressure, and an increased risk for heart distress and disease. Stress hormones continue to increase. As stress becomes chronic, the immune system’s functioning begins to decrease. The decrease in immunity creates a deficit in cytokine hormones and produces inflammation, resulting in immune function deficiency. Cytokines are hormone-like proteins that serve as communicators to other cells in the body. They are of PNI interest because they communicate between the nervous, immune, and endocrine systems. Such neuroimmune interaction is the basis of PNI. Cortisol decreases proinflammatory production. Immune cells begin to develop a resistance to cortisol. Cortisol is then no longer able to reduce inflammation, creating chronic sickness behavior. Allostasis is the result of chronic stresses that led to a biological loss. This is a similar process to the tolerance development associated with pharmacological and narcotic drug use. The withdrawal result can have physiological and psychological consequence.

Chronic delayed response to inflammation is a common feature of chronic diseases such as type 2 diabetes, cardiovascular disease, cancer, dementia, depression, etc. Research into n-3 fatty acids has proven their influence in the inflammation process. The inflammation response is directly correlated to the amount of phospholipid fatty acids present in the cell membrane. This is directly related to dietary intake. This research has strong implications for the PNI field and its application, as it is important for health care practitioner to educate on the importance in the consumption of whole foods. This shows the importance of individual behavior and the side effects of over consumption, which is a common coping mechanism to acute and chronic stress.

Feelings of acute stress may be triggered by fear, anger, and anxiety. Situations that may trigger such feelings are academic stress, public speaking, disagreements, and miscommunications. When stress situations become chronic, such as care taking for a sick loved one, psychological and physiological disease may develop as a means of coping or survival.

In a study conducted on the immune responses to hepatitis B vaccinations, 48 second year medical students on the last day of a three day examination were chosen to determine the effect of academic stress on the abilities of immune response (Glaser, et al., 1992). It was interesting that results showed that those students who felt they had social support reported less stress, and had greater activation of immune functioning (Glaser, et al., 1992). The research goals were to show the effects of psychological coping, and social support on the ability of the immune system to respond to a hepatitis B vaccine. Students ages ranged between 22 and 29, 25 were male, and 23 were female (Glaser, et al., 1992). Students had already been followed for a year in another study on stress and immune function so personality characteristics and coping abilities were known (Glaser, et al., 1992). Vaccinations were done three times during examinations for one year. Students were also tested between examination periods to observe stress levels. Blood was drawn prior to hepatitis B vaccination, and again later the same day of vaccination. Results showed decreases in immune response during examinations (Glaser, et al., 1992). Students who expressed less social support showed an even greater delay in antibody response, and these students also showed a 40% decrease in wound healing, as opposed to students observed during summer vacation (Glaser, et al., 1992). This study suggests that academic stress can result in a variety of physiological changes, and the importance of the health care provider’s considerations into all the systems that collaborate in the onset of disease. Such evidence supports the interrelation between mind and body, and the science of psychoneuroimmunology.

There is evidence that personal relationships have significant effects on physiological functioning. In a study on marital conflict and endocrine function, 90 newlywed couples were followed for a 24 hour period of in house observation (Kiecolt-Glaser, et al., 1996). Blood samples were collected hourly from 8 am through 10 pm to test epinephrine, norepinephrine and cortisol levels (Kiecolt-Glaser, et al., 1996). Couples agreed to be tested during a time in their relationships where there was conflict. Behavioral characteristics between genders were also recorded. Results of gender behavior correlated with physiological stress responses (Kiecolt-Glaser, et al., 1996). Women were shown to be more critical, and demanding, whereas men were shown to be more withdrawn during conflict (Kiecolt-Glaser, et al., 1996). Men generally had more drastic physiological responses to conflict, and it took longer for them to rebalance homeostasis, therefore withdrawal behavior in men is considered an evolutionary adaptation (Kiecolt-Glaser, et al., 1996). However, it was more common in women rather men to have consistent unbalanced epinephrine, norepinephrine, and cortisol levels throughout the day. Although such data may underestimate the true impact of marital difficulties, its conclusions are still of interest, as marital stress and conflict resulted in elevated hormones and decreases in immunity (Kiecolt-Glaser, et al., 1996).

The ability to recover after stressful experiences influences the total burden that stressors create on the individual. Stressors that are uncontrollable may become resistant to coping and behavior modifications, resulting in continued elevation of stress hormones and chronic stress responses. In a case study to determine whether chronic stress is associated with impaired immune response, 32 adults were selected from three local dementia evaluation centers that were long-term caretakers for their spouses suffering with progressive Alzheimer’s disease (Kiecolt-Glaser, et al., 1996). The caretaker’s spouses were diagnosed with severe dementia, which entails behavior problems, wandering, hallucinations, aggression, and incontinence (Kiecolt-Glaser, et al., 1996, Pinel, 2009), thus classifying such care taking as a chronic stressor. Caretakers were not only more susceptible to depression, but also showed a reduced immune system and antibody response following an influenza virus vaccination in comparison to a control group (Kiecolt-Glaser, et al., 1996). Blood tests were done once prior to vaccination and again three to five weeks after, for those individuals who failed to show an increase in anti-body release, blood was drawn at three and six months (Kiecolt-Glaser, et al., 1996). The increase in vulnerability to influenza infection was associated with poor cytokine responses (Kiecolt-Glaser, et al., 1996). Subjects showed similar antibody tilters prior to vaccination, however caretakers reduced response in both cellular and hormonal immune functioning following vaccination has strong implications into the psychoneuroimmunology of chronic stress (Kiecolt-Glaser, et al., 1996).

Health psychology is the scientific study of behavior and thought that relates to health enhancement, disease prevention, safety, and rehabilitation. It appreciates the interconnection of the biological perspective, such as in the field of PNI and biopsychology, as well as psychological, social, environmental, and cultural perspectives, and their effects on human behavior and stress coping abilities. The current intellectual climate is in need of collaboration, integrating medical and psychological practices. Studies are still currently in need of reworking, as they are limited to what they can tell us about the exact contribution of stressors and how they lead to disease, as some diseases take several years to develop. Studies have also not been able to control for exposure and do not incorporate individual differences, as everyone has different coping abilities and interpretations of situations. Studies on mindfulness meditation show beneficial potentials to the PNI field, and may be a cost effective approach for medical application and disease prevention.

A study of mindfulness meditation and its relation to brain and immune function was tested by administering magnetic resonance imaging (MRI) scans to participants who had been through a 10-week mindfulness meditation training course, as well as with a control group who had no mindfulness meditation training (Farb, 2007). Participants who had mindfulness training showed a significant increase in neural connectivity and plasticity throughout the brain in comparison to the control group (Farb, 2007). Farb (2007) suggested that awareness and concentration create more available stimuli in brain function and that meditation was significant in increasing self-reference and task control, creating the ability to reorganize brain functioning and coping abilities (Farb, 2007).

In a similar study, subjects went through eight weeks of mindfulness meditation training. Those who completed the course showed a greater activation of the left side anterior of the brain, which is associated with positive emotion, and a stronger immune response to an influenza vaccine compared to the control group (Davidson, 2002). These studies demonstrate that emotion and stress are not fixed and that changes in the brain correlate with changes in the immune response (Kabat-Zinn, 2005). Thus is applicable to the field of PNI.

Mindfulness meditation can be used as a tool by health psychologists to inspire cognitive awareness and responsibility for emotion and behavior. Such responsibility will support health and adherence to medical suggestion. The field of PNI proves that although the brain and the body do not work as a single unit, they are interwoven, or connected. The field of PNI offers biopsychologists the research necessary to prove that all of the systems of the body communicate in order to create health or disease. Evidence from the PNI field supports the concept that a person’s psychological state has the potential to alter the biochemical and physiological state, and that the biochemical and physiological state has the potential to alter the psychological state. The research is complex, and the conclusion is obvious, the mind and body are connected.

For example, during a yoga class the instructor suggests a challenging and uncomfortable yoga posture. This will initiate a biological and psychological stress response in the beginner student. Through the training and application of mindfulness, observing and accepting the present situation without judgment, the student will eventually be able to alter such reactions with tools such as breath awareness, discipline, concentration, and intention. Once these techniques are applied to daily life situations, the student will find greater coping abilities and experience less stress responses, as attachment decreases. Studies have proven that yoga and mindfulness meditation are worthy areas of study for biopsychology and neuroscience.

All of life faces threats to homeostasis. Survival depends on our adaptability with stress. Humans are exposed to stressors at societal, environmental, biological, personal, and psychological levels. Continued research will lead to improved health care and education. Psychology plays an important role in psychoneuroimmunology. As psychology’s interests are in human strengths, behaviors, and abilities. It has become obvious through research in biopsychology, neuroscience, biogenetics, and psychoneuroimmunology that psychological characteristics contribute to physical health and healing. Education in health psychology and its applications such as mindfulness meditation and yoga support a solid and cost effective protocol for preventative medicine and rehabilitation.

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