Mind Over Matter

Researchers are discovering connections between psychological well-being and immunity.

By Heather Millar featured image Illustration by Marina Muun

Linda Tucker spent most of her career in corporate America. But with the 2008 economic downturn, she decided to follow her life’s passion: caregiving for young and old. Within a few years, she had a thriving practice as a nanny and an elder caregiver. She also had almost no free time and a growing problem with serious insomnia.

“I didn’t know how to say no,” says Tucker, who is now 70. “Sometimes, I’d be working six or seven days a week, double shifts, filling in for other people. I loved it, but I wasn’t sleeping at all some nights.”

One day about five years ago, as Tucker was taking a 98-year-old client to an appointment at the University of California, Los Angeles (UCLA), she noticed a flyer recruiting volunteers for an academic study exploring the health benefits of weekly tai chi, a Chinese martial art that uses slow, controlled rhythmic movements to improve mental and physical well-being. She decided to sign up.

“After the first class, I thought, ‘This is a joke.’ But I went to the second class,” Tucker says. “Then I thought, ‘Oh my gosh, I like this.’ My sleep started to come back, and I just felt better. After class, I felt so peaceful and fulfilled.”


Mindfulness and Immunity

In addition to a good night’s sleep, Tucker’s new tai chi routine may have also given a boost to her immune system. Her experience helped form part of a body of evidence that focuses on psychoneuroimmunology (PNI), a branch of medicine that studies how the brain, the body, and the immune system are connected and have a profound influence on one another, particularly when it comes to the onset and progression of disease. Chronic stress, loneliness, depression, and traumatic experiences, to name a few, can leave the body more vulnerable to a wide range of illnesses, including everything from cancer to heart disease to eczema. But this mind-body connection is a two-way street. Just as a stress can affect physical health, ailments of the body can result in psychological conditions, such as stress and depression.

On the flip side, being in a happy, relaxed frame of mind can have a positive effect on a person’s health. One recent study even suggests that simply being in a good mood on the day you get your flu shot might make it more effective.    

“The benefits we’re seeing are robust: Lifestyle approaches that reduce stress can alter disease processes,” explains Michael Irwin, the director of UCLA’s Cousins Center for Psychoneuroimmunology and the lead researcher in the study that enrolled Tucker. “That can help people and also can save healthcare costs.”

Irwin’s studies have shown that mindfulness practices like tai chi, yoga, and meditation can reduce C-reactive protein (CRP), a substance produced by the liver in response to inflammation. While a high CRP level can be a result of a normal immune response to infection, it can also indicate the presence of a chronic autoimmune disease such as arthritis or lupus, or even heart disease. These diseases are a product of chronic inflammation, the result of an inappropriate inflammatory process arising when there is either no injury or a previous injury has already healed. Over time, chronic inflammation can damage DNA, which could potentially lead to the development of cancer or promote the build-up of plaque in blood vessels, increasing the risk of heart attack or stroke.

The benefits we’re seeing are robust: Lifestyle approaches that reduce stress can alter disease processes.”

So, by improving emotional health through stress-reducing measures, disease-causing inflammation is also reduced. In other words, a healthy mind can lead to a healthy body.


Wide-Ranging Research

Interest in PNI dates back thousands of years. Ancient Egyptian, Indian, Tibetan, and Greek texts reveal that many philosophers and physicians posited the brain-body connection, even if they did not know the exact biological details. Modern scientists first began to look more closely at this relationship in the 1960s at the University of Rochester, using mouse models to see if a pleasurable stimuli, such as sweetened water, could provoke an immune system response (they did). Other studies around this time showed that heightened emotional states could also provoke immune responses.

But the study of PNI didn’t really gain momentum until the AIDS/HIV crisis of the 1980s led to more funding for immunology research. That research resulted in seminal findings from Ohio State University, the University of California, San Francisco, and UCLA, among others, describing how the nervous system is connected to the immune system. Notably, researchers concluded that emotional stress, neuropeptides (small molecules used by nerve cells to communicate with each other), and the stress hormone cortisol provide links between the brain and immunity.

At the cellular level, researchers discovered that neurotransmitters (chemical agents released by nerve cells) have the ability to regulate immune responses, and conversely, cytokines (small proteins that regulate immune response, inflammation, and blood cell formation) have an impact on the brain. This “wet lab” research has inspired social science studies. In the last 15 years, many studies have linked social support, mood, and mindfulness practices to a variety of health outcomes.

“PNI is related to everything from Alzheimer’s to obesity to diabetes,” explains William Banks, president of the Psychoneuroimmunological Research Society and a researcher for the Veteran’s Administration and the University of Washington. “This has become one of the fundamental fields [of science].”

While thousands of PNI studies are currently underway worldwide trying to bring focus to these myriad findings, there are several areas in which brain-body connections are fairly well understood.

Early studies examining the brain-body connection involved caregivers, especially those caring for patients with difficult illnesses such as dementia. Caregivers of this patient population often suffer from chronic stress and depression, both of which are psychological conditions that are associated with increased levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6). High levels of IL-6 have been associated with heart disease, type 2 diabetes, and some cancers. Research also suggests that the chronically stressed are more likely to have some level of immune dysregulation, which can include a reduced immune response to vaccines and slow wound healing. Many subsequent studies have suggested that various ways of reducing stress seem to produce better immune outcomes.

For instance, a September 2017 paper in Brain, Behavior and Immunity showed that having a more positive attitude can improve the effectiveness of a flu vaccine. British researchers assessed the behavior (exercise, nutrition, sleep) and psychological state (stress, positive or negative mood) of 138 people living in an elder community. Researchers also checked each subject for their immune response to a flu vaccine by measuring their levels of antigens, antibodies, viruses, and bacteria. Researchers found that, of all the factors measured, participants who had positive moods on the day they received their flu vaccine had the highest levels of antibodies, indicating a high level of immune protection. Mood was the only factor that predicted the effectiveness of the vaccination.

Stress, depression, and other neuropsychological disorders can also exacerbate skin problems such as eczema, psoriasis, rosacea, and hives. A 2013 review published in Seminars in Cutaneous Medicine and Surgery showed that using nonpharmacological therapies, such as hypnosis, muscle relaxation, and cognitive behavioral therapy, as part of a dermatologic treatment plan can improve these conditions. Some are now pushing for recognition of what they call “psychodermatology,” a relatively new medical discipline that involves treating skin disorders with psychological and psychiatric techniques.

Recent research also has shown that a variety of neuro-immune signals — oxytocin, a hormone that regulates social and sexual interactions; vasopressin, which controls water levels; epinephrine, which mediates responses to stress or fear; cortisol, which helps to regulates immune, stress, and metabolic responses — have key roles in how quickly a wound heals. Observational studies have found that greater fear, distress, or depression before surgery is related to longer hospital stays, postoperative complications, and re-hospitalizations. For instance, a 2005 study in the American Journal of Critical Care followed 72 patients receiving stents for coronary artery blockages. Those who were more depressed when discharged had poorer wound healing and more infections six weeks after the procedure.

Such studies have helped solidify a field that some researchers had once referred to as “soft science,” often riddled with conflicting data and unknown clinical and biological relevance.

“We’ve come a long way from people saying, ‘There’s nothing here,’ ” says Irwin. “PNI mechanisms appear to be important for health outcomes. PNI-based interventions that target stress response pathways can alter inflammatory biology and the underlying gene expression, which is driving disease risk. That’s a considerable advance in the last decade.”


The Cancer Connection

Both community doctors and patients will probably be hearing more about PNI in the near future, experts say. Cancer treatment is one area that is poised to benefit from PNI research, particularly the psychological ailments experienced by cancer patients. Elevated inflammatory marker levels found in cancer patients have been linked to anxiety and depression. The thought is, if you inhibit inflammatory signaling, it could greatly improve a cancer patient’s quality of life.

“The field is really getting ready to move into the clinic at full speed,” says Annemieke Kavelaars, a researcher who studies neuroimmunology, a field that examines the interaction of the nervous and immune systems, at the MD Anderson Cancer Center in Houston. “Clinical trials are ongoing to determine whether inhibiting inflammatory signaling can be used to treat anxiety and depression.”

Those trials are testing drugs called cytokine antagonists to see if they can reduce depressive symptoms in cancer patients.

Other studies are looking into how reducing stress might result in better outcomes for those undergoing cancer treatment. An August 2017 study in the journal Cancer built on earlier work showing that chronic stress can increase cortisol levels. This, in turn, can “blunt” the body’s response to cortisol. This “blunting” effect may play a role in allowing tumor cells to escape detection by the immune system, which has been linked to reduced survival rates. In the Cancer paper, researchers reported findings suggesting that meditation can reduce the impact of this blunting mechanism, though they have not yet proved that it leads to better clinical results.

“The glory of all this is its complexity,” says Banks. “It connects things that we struggle to understand. That means we can really say your emotions can affect your risk of disease X.”

For people like Linda Tucker, knowing that better health can be jump-started by tai chi’s gentle movements is also glorious in its simplicity. It all boils down to a good night’s sleep.