The Mind's Impact on Health

Introduction to Psychoneuroimmunology

Growing the Psychoneuroimmunology (PNI) Connection

The idea that a positive outlook on life and a cheery disposition help to stave off illness is as old as the hills. Perhaps surprisingly, this adage is much more than an old wives' tale.


Over the last few decades, the intriguing and pervasive links between neuroscience and the immune system have slowly been uncovered. What might seem, at first, like an uneasy marriage between the brain and immunity has steadily grown into a full-fledged interdisciplinary area of study. This field is known as psychoneuroimmunology (PNI).

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Overview: Psychology and Immune System

Look at this overview of how psychology has been shown to influence the immune system:


Bereavement: stories of recently bereaved individuals dying soon after their partner are common. These tales are not just apocryphal. A study that followed 95,647 recently widowed individuals found that during the first week after bereavement, mortality was twice the expected rate. There is more to this than a metaphorical "broken heart."


The gut: it is now fairly well established that there is a strong association between sustained stressful life events and the onset of symptoms in functional gastrointestinal disorders, inflammatory bowel disease and irritable bowel syndrome.


Cancer: health professionals working with cancer patients know only too well that a patient's outlook and their quantity and quality of psychological support can hugely impact the outcome of their disease.


HIV (human immunodeficiency virus): studies have found significant evidence that elevated levels of stress and diminished social support accelerates the progression of HIV infection.


Skin complaints: psoriasis, eczema and asthma are all known to have psychological aspects to them. A stressful day at the office can have you scratching as you reach for the asthma pump.


Wound healing: the speed at which a surgical patient heals has been linked to psychological factors. For instance, increased levels of fear or distress before surgery have been associated with worse outcomes, including longer stays in the hospital, more postoperative complications and higher rates of re-hospitalization. In one study on patients with chronic lower leg wounds, those who reported the highest levels of depression and anxiety showed significantly delayed healing.

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Neurotransmitters and Neuropeptide Receptors

If the immune system was in cahoots with the nervous system, there must be points where they intersect. Soon, this too was demonstrated.


In 1981, David Felten made the next major discovery. He uncovered a network of nerves that led to blood vessels and, importantly, cells of the immune system.

Felten's team found nerves in the thymus and spleen that terminated near clusters of important immune system components: lymphocytes, macrophages and mast cells.

In 1985, Candace Pert found neurotransmitter and neuropeptide receptors on the cell walls of the immune system and the brain. This discovery showed that the communication chemicals of the nervous system could also speak directly to the immune system.


What made this finding particularly fascinating was the discovery of neuropeptide links to the immune system.


Neuropeptides are the latest molecules to join the ranks of the neurotransmitters. Neurons use them to communicate between themselves and, to date, more than 100 distinct neuropeptides appear to be utilized by the nervous system.

Rather than classic neurotransmitter's relatively short-lived action, neuropeptides have longer-lasting effects and can influence a number of operations, from gene expression to the building of new synapses.


Interestingly, neuropeptides are implicated in a wide array of functions involving an emotional aspect. For instance, neuropeptides are known to play a part in reward-seeking, social behaviors, reproduction, memory and learning.

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Hypothalamic-pituitary-adrenal axis

The HPA axis involves three small endocrine glands - glands that secrete hormones directly into the blood. The glands in question are the hypothalamus and the pituitary, which are neurological neighbors, and the adrenal glands, situated on top of the kidneys.

This triumvirate of tissues control reactions to stress and regulate processes including digestion, the immune system, sexuality, mood and energy usage.


The hypothalamic-pituitary-adrenal axis plays a vital role in immune-brain interaction and stress.

One chemical of note involved in the HPA axis' work is corticotropin-releasing hormone (CRH). The hypothalamus releases CRH in response to stress, illness, exercise, cortisol in the blood and sleep/wake cycles. It peaks soon after waking and slowly declines throughout the rest of the day.

In a stressed individual, however, cortisol levels are elevated for prolonged periods of time.

During stress, the body believes it is in imminent danger, so cortisol triggers a number of metabolic changes to ensure that enough energy is available in case a fight or flight is necessary.

One of these energy-saving tactics is to suppress the metabolically expensive immune system, saving vital glucose for the approaching life-threatening event.

Of course, in modern humans, stress levels can soar for a number of reasons. Very few of these situations involve a genuine threat to life, but the HPA axis evolved long before dissertation deadlines and job interviews.


In this way, ongoing stress can reduce the capabilities of the immune system as the body saves its energy for a physical exertion that never comes.

Conversely, there is some evidence that oxytocin, produced during positive social interactions, helps dampen the activity of the HPA axis. This has been shown to promote health benefits, such as increasing the speed of wound healing.

The interaction between the hypothalamus, pituitary and adrenal glands is complex, as is the influence of other brain centers on each of them. Although we have a picture of some of its workings, we are a long way from charting the entire range of influences and influencers. And, the HPA axis is but one of the systems PNI has uncovered.

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Different stress, different immune response

A meta-analysis of 300 empirical studies found that certain types of stress altered different aspects of the immune system. They compared brief stressors, like exams, with chronic stressors - events that change a person's entire life, like caring for a partner with dementia.

Brief stressors tended to suppress cellular immunity (the type that deals with cellular invaders, like viruses) while preserving humoral immunity (normally dealing with pathogens outside of cells, such as parasites and bacteria).

Chronic stressors tended to suppress both types of immunity.

Stress has a measurable effect on the strength of the immune system and therefore its ability to protect us. In a very real way, managing levels of stress can help maximize the virility of your immune system.

Research has shown time and time again that people in stressful situations have measurable changes in physical responses to injury. Whether it is slowed wound healing, a higher incidence of infection or a worse prognosis for cancer survival.

It rams home the message that managing stress is an important ability to learn and that supporting those in stressful situations is just as important.

For many years, the immune system was considered a stand-alone, autonomous mechanism. This, as we now know, is not the case. The brain speaks regularly and eloquently to the cells of the immune system and vice versa.

Stress is both psychological and physical.