Psychoneuroimmunology
Psychoneuroimmunology (PNI) is an interdisciplinary field that examines the intricate connections between the mind, nervous system, and immune response. This area of study integrates aspects of neuroscience, immunology, physiology, and behavioral science to understand how psychological factors can influence physical health. Research in PNI suggests that mental states like anxiety, stress, and depression may weaken the immune system, impacting the body’s ability to fend off illness. PNI has roots in classical conditioning studies, notably those by Robert Ader, who demonstrated that learned associations could affect immune responses. For instance, his experiments showed that animals could develop conditioned immune suppression based on associations between tastes and illness. These findings have implications for medical treatments, particularly in reducing side effects from immunosuppressive drugs through conditioned responses. Currently, scientists are exploring how PNI can enhance therapeutic strategies and improve patient outcomes, especially among individuals with chronic illnesses or those undergoing immunosuppressive therapies. As research continues, PNI may pave the way for innovative approaches in healthcare that consider the holistic interplay of the mind and body.
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Subject Terms
Psychoneuroimmunology
Psychoneuroimmunology (PNI) is a scientific field of study that involves investigating the connections between the mind (psycho) and the body's central and peripheral nervous (neuro) and immune (immunology) systems. PNI incorporates the fields of neuroscience, immunology, physiology, and behavioral science. PNI aims to understand the connection between the mind and the body and explore how training the mind could lead to positive effects in the body. It works on the same premises that positive thinking can affect the body and help it ward off sickness. PNI has been used in several studies to test the potential for conditioned immune responses. The hope is to condition the body to respond to smaller drug doses in an effort to minimize the side effects of many drugs and reduce health care costs.
Background
The immune system allows the body to ward off pathogens such as viruses and diseases and abnormal cells and tissues. The immune system consists of cells, tissues, and organs that work with one another to attack anything trying to invade the body. Leukocytes, or white blood cells, are the most important cells of the immune system. They find and destroy invaders. Clumps of leukocytes form lymph nodes. By way of the lymphatic vessels and blood vessels, leukocytes travel through the body to the organs and nodes. The two basic types of leukocytes are phagocytes and lymphocytes. The phagocytes eliminate foreign bodies, and the lymphocytes remember previous foreign invaders and destroy them. Neutrophils are the most common phagocytes. They fight bacteria. B lymphocytes (B cells) and T lymphocytes (T cells) are the two types of lymphocytes. B cells are responsible for identifying antigens, and T cells destroy antigens found by the B cells.
When an antigen is detected, the B cells trigger antibodies to look for and attach to the invader. These antibodies stay in the body to ward off the antigens if they recur. This protects the body from future attacks by the antigen and usually ensures a person will not get sick from the same disease again. Antibodies cannot destroy antigens, so they need the help of T cells, which also assist the phagocytes.
All of these cells work together to fight off anything that tries to harm the body. They give the body immunity. Everyone's immune systems work differently. As people age, they are exposed to many germs and foreign invaders. Some people become immune to many of them, while others do not. This is why some people are more susceptible to sicknesses such as colds than other people. Scientists know how the immune system works and how people get sick, but in the twenty-first century, research increasingly focused on how the mind and nervous system influence the immune system. This study is called psychoneuroimmunology (PNI).
Many scientists have investigated how psychological events affect the immune system and established several connections. For example, anxiety, bereavement, depression, and stress have been known to weaken a person's immunity. These conditions can disrupt the gastrointestinal system and intensify conditions such as psoriasis, eczema, and asthma. They can also hinder healing and cause other complications in people who are ill.
Scientists have determined that a connection between neural activity and immunity exists, largely through animal studies. Experts have focused these studies on proving brain-immune communications in the hopes of conditioning the body and brain to respond to smaller drug doses to reduce harsh medication side effects.
Overview
Robert Ader, a psychologist from the University of Rochester in New York, became known as the father of psychoneuroimmunology. He worked on variations of the Pavlov experiment in the 1970s. Russian physiologist Ivan Pavlov conducted an experiment in the 1890s that proved a stimulus (in this case, a sound) made dogs salivate without the presence of food. He proved that stimuli could be used to condition a particular response.
Ader worked on a taste aversion study on rats. He gave the rats a sweet saccharin solution paired with the immunosuppression drug Cytoxan. The drug was toxic, but he only gave the rats tiny doses. The drug caused gastrointestinal issues in the animals. Since Ader paired it with a sweet drink, the rats associated the sickness with the saccharin solution. He stopped giving the rats the drug injections.
He then tried to give the rats just the sweet solution, but they would not drink it. He assumed the rats would forget the association, so he force-fed them the solution. However, they did not forget, and they began to die. Ader realized their brains influenced their bodies. They were no longer receiving Cytoxan, but their minds continued to believe they were. Their bodies began to suppress their immune systems in response, which made them weak and eventually die.
Pavlov proved that learned associations affect psychological responses. However, Ader proved that learned associations could affect immune responses. Ader's study showed how the brain was linked to the immune system and how taste or smell could influence health.
Ader was not the first person to propose this. During the 1920s, Russian scientists studying Pavlov made a similar discovery. Immunologist Sergey Metalnikov was working on an experiment to boost the immune system instead of suppressing it like Ader.
In Metalnikov's study, he warmed the skin of a group of guinea pigs while giving them small doses of bacteria. Next, he gave them a large dose of the Vibrio cholerae bacteria while warming their skin. He also did the same to a new group of guinea pigs who did not receive the initial conditioning. The second group of animals died within eight hours. Some of the animals from the first group died within thirty-six hours, while the rest survived. This experiment showed that the feeling of heat helped boost the immunity of the first group.
Ader's and Metalnikov's work was largely ignored because scientists could not understand how the animals could learn immune responses. At this time, the immune and nervous systems were believed to work independently. However, these studies proved that the immune and nervous systems worked together with the brain to have an effect on the body.
Other scientists began to study these connections. In 1981, neuroscientist David Felten found proof when he discovered nerves in the thymus and spleen that led to lymphocytes in the immune system. Four years later, Candace Pert discovered neurotransmitter and neuropeptide receptors in cells found in the immune system and brain. This showed that the nervous system could communicate with the immune system.
Manfred Schedlowski, a medical psychologist at the University of Essen in Germany, began conditioned immune response studies in the 1990s. He conducted a study similar to Ader's with rats and found the same conditioned immune responses. He wanted to see if Ader's findings could help him develop a therapy to benefit patients taking drugs that affected the immune system. He believed that conditioned responses could help patients with organ transplants who took medications to block their immune systems from attacking the foreign organs. He proposed that he could use conditioned responses to cut the amount of medication these patients needed. This would lessen the side effects caused by the drugs and lower the cost of the medications needed.
Schedlowski created experiments involving rats with hearts implanted into their stomachs. In the first group, he gave them the immunosuppressant drug CsA and sweetened water. He then stopped the drug and gave the rats just the sweetened water. A second group received just CsA, and a third group just got sweetened water. The rats that received the CsA with the sweetened water lived just as long as those that received the CsA alone. This showed that the conditioned response worked, as did the drug. A second experiment confirmed these findings. Schedlowski, however, feared that learned associations could weaken over long periods. He determined that combining a low dose of medication with conditioning could prevent this.
Ader was asked to try conditioning for a girl named Marette Flies who had the immune disease lupus. She was on a medley of drugs, which had harsh side effects. She eventually formed a bleeding disorder, and her heart began to fail. She was prescribed Cytoxan, which suppressed the immune system but had severe side effects. Her mother was aware of Ader's work and convinced him to design a conditioning trial for her daughter in hopes she could cut the doses of her medication to avoid further damage to her body. She took a mixture of rose perfume and cod liver oil as she received Cytoxan injections. She was able to cut her doses over time as she continued the rose mixture. Her body responded well. She lived until age twenty-two; however, her heart was too damaged from all the medication she took during her early life.
This case led to other human trials for conditioned immune therapy. While doctors and scientists were not sure these trials would be successful, they were hopeful that eventually, conditioning may help doctors adjust the dosing of certain medications with harmful side effects.
Scientists continue to investigate the field of PNI to understand the interaction of the brain, nervous system, endocrine system, and immune system and how to use this information to treat illness. Research focuses on the effects of stress and sleep on immune responses, such as the potential of chronic stress to cause inflammation and lead to illness. A body under stress produces small, immune response-regulating proteins called cytokines, and an overabundance of these proteins may be detrimental to health. Other research concerns the role of hormones like cortisol and neurotransmitters like norepinephrine in the function and behavior of immune cells like lymphocytes and macrophages.
Neuroscientist and assistant professor at Georgia State’s Neuroscience Institute, Jessica Bolton, received the Robert Ader New Investigator Award in July 2024 for her research concerning the impact of childhood trauma, stress, and adverse events on the brain’s formation of neural circuits. Bolton’s research explored the ability of anti-inflammatory agents to mitigate the negative impacts of certain childhood experiences. The response of the brain’s immune cells, microglia, to these threats and the way they interact with neurons in the brain’s hypothalamus and amygdala partially determine a person's susceptibility to certain life-long mental health conditions, such as substance use disorders or depression.
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