7/13/2017 Psychoneuroimmunology: laugh and be well - Medical News Today

Psychoneuroimmunology: laugh
and be well
By Tim Newman | Published Wednesday 3 February 2016

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 fully fledged
interdisciplinary area of study.

The implications of psychoneuroimmunology cover the length and

This field is known as breadth of medical research.
psychoneuroimmunology (PNI).

It is well established, in the minds of most people, that stress can induce illness and that,
conversely, a fun-filled occasion with loved ones can soothe aches and pains and stave off
the very same illness.

What might have been referred to as pseudoscience a few decades ago now finds strong
support from many quarters. PNI has deep ramifications for the future of medical research, the
treatment of diseases and our attitude toward handling stress.

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7/13/2017 Psychoneuroimmunology: laugh and be well - Medical News Today

In this article, we will take a look at the birth of PNI, how the immune and nervous systems
interact and some of the ways in which these communication pathways affect us all.

The mind's impact on health

First, we will take a very brief look at a few examples 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.

Despite first-hand accounts of stressful or exhausting psychological events negatively

impacting physical well-being, the scientific evidence behind these stories was not initially
forthcoming.

How could neural activity influence the activity of the immune system? The immune system's
classical messaging system - the lymph system - is not present in the central nervous system,
so conversations between the two were considered impossible.

What sounds like medieval quackery is now considered science fact; the mechanisms that
underpin immune-brain interactions are steadily being uncovered.

As with so many scientific discoveries, it was a chance observation that got the ball rolling.

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7/13/2017 Psychoneuroimmunology: laugh and be well - Medical News Today

The birth of psychoneuroimmunology

Robert Ader is widely considered to be the father of modern PNI. His early research, involving
conditioning in rats, opened the floodgates for the study of brain-immune communication.

Ader, a psychologist by trade, worked closely

with Nicholas Cohen, an immunologist.

Their specialties made them the perfect team

for the job, even though they did not realize it
at the time.

Their landmark discovery was courtesy of

science's old friend - serendipity.

Ader was working on variations of the classic Experiments into psychological conditioning accidentally stumbled
Pavlov's dogs experiment: salivation in dogs upon the brain-immune interaction.

was conditioned by an auditory stimulus -

such as a metronome - before they were fed each day. Consequently, the stimulus induced
salivation without the presence of food.

In Ader's version of the experiment, he fed rats different quantities of saccharin solution and
simultaneously injected them with Cytoxan - a drug that induces gastrointestinal distress and
suppresses the immune system. The rats were conditioned to avoid drinking the solution, as
predicted.

Ader then ceased injecting the rats but continued to present the saccharin-laced water. The
rats avoided the solution but, strangely, some of them died. He noted that the avoidance
response and the level of mortality varied depending on the amount of saccharine water they
had been presented with.

The results intrigued Ader; it seemed that the avoidance response had been conditioned as
expected, but, unexpectedly, so had the corresponding drop in immunity. In an interview in
2010, he explained:

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7/13/2017 Psychoneuroimmunology: laugh and be well - Medical News Today

As
" a psychologist, I was unaware that there were no
connections between the brain and the immune system, so I
was free to consider any possibility that might explain this
orderly relationship between the magnitude of the
conditioned response and the rate of mortality.
A hypothesis that seemed reasonable to me was that, in
addition to conditioning the avoidance response, we were
conditioning the immunosuppressive eects [of Cytoxan]."

His next study, published in 1975, proved beyond doubt that his hunch, although surprising
and openly mocked by other scientists, was spot on.

The game truly had changed. A neural signal (taste) had managed to trigger a conditioned
reduction in the immune system. The results were replicable, and although the theory
received more than its fair share of flack, there seemed no other way to explain it.

All of a sudden, the central nervous system and immunity were bedfellows.

On the next page, we look at the mounting evidence for brain-immune interactions, the role
of neuropeptides and how the brain communicates with the immune system.

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References

A Rorschach tension score and the diurnal lymphocyte curve in psychotic subjects, Phillips L. et al., Psychosomatic Medicine,
published November 1947, abstract.

Behaviorally conditioned immunosuppression, Robert Ader et al., Psychosomatic Medicine, published July-August 1975.

Mortality after bereavement: a prospective study of 95,647 widowed persons, J Kaprio et al., American journal of Public
Health, published March 1987.

Neuropeptides and their receptors: a psychosomatic network, Pert CB et al., Journal of Immunology, published August 1987,
abstract.

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7/13/2017 Psychoneuroimmunology: laugh and be well - Medical News Today

Progression to AIDS: the effects of stress, depressive symptoms, and social support, Leserman J et al., Psychosomatic
Medicine, published May-June 1999.

Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry, Suzanne C. Segerstrom et

al., Psychological Bulletin, doi: 10.1037/0033-2909.130.4.601, published online 7 February 2007.

Psychoneuroimmunology, Janice K. Kiecolt-Glaser, Perspectives on Psychological Science, doi: 10.1111/j.1745-

6924.2009.01139.x, published online 1 July 2010.

Psychoneuroimmunology and cancer: fact or fiction?, Kiecolt-Glaser JK et al., European Journal of Cancer, doi:
http://dx.doi.org/10.1016/S0959-8049(99)00197-5, abstract.

Psychoneuroimmunology - cross-talk between the immune and nervous systems, Tjalf Ziemssen et al., Journal of Neurology,
doi: 10.1007/s00415-007-2003-8, published 2007.

Psychoneuroimmunology: the example of psoriasis, J. Moynihan et al., Giornale Italiano di Dermatologia e Venereologia,
published online 21 October 2013.

Social facilitation of wound healing, Courtney E Detillion et al., Psychoneuroendocrinology, doi:

http://dx.doi.org/10.1016/j.psyneuen.2003.10.003, published September 2009, abstract.

The impact of psychological stress on wound healing: methods and mechanisms, Jean-Philippe Gouin et al., Immunology
And Allergy Clinics of North America, doi: 10.1016/j.iac.2010.09.010, published February 2011.

The neurobiology of stress and gastrointestinal disease, E A Mayer, Gut, doi: 10.1136/gut.47.6.861, published 2000.

The relationship between blood sugar and lymphocyte levels in normal and psychotic subjects, Freeman, Harry et al.,
Psychosomatic Medicine, published July 1947, abstract.

University of Rochester Medical Center, Robert Ader, founder of psychoneuroimmunology, dies, accessed 2 February 2016.

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