PsychoNeuroImmunology
(and other stress
related diseases)
Overview
The importance of
PsychoNeuroImmunology
An introduction to the immune system
How immune-system
Function is measured in Psychoneuroimmunology research
Counting cells
Function test
Methodological issues
Research on Stress & Social Support with PNI, Cancer, HIV & CHD
The effect of stress on immune
functioning
The effect of mood on
immune functioning
Personality and Cancer
Social Support and immune
functioning
Proposed biological mechanisms to explain Psychoneuroimmunology
Future directions for Psychoneuroimmunology research
Psychoneuroimmunology
(and other stress
related diseases)
Key Considerations:
Review the psychological state, health
relationship, function of the immune system, the methodological issues for
researchers, evidence, and possible mechanisms.
The Importance of Psychoneuroimmunology
The relationship between immunocompetence, or one's functional efficacy of immune response, and psychological experiences and outcomes is central to this topic.
Psychoneuroimmunology (PNI) involves interest in the biological mechanisms responsible to specific and general responses of the bio-psycho-social agent. This field examines both possible ways to stave off or moderate stress along with assessments of immune system functioning or state.
As we have already considered, the field of health psychology places a great deal of stake in explanation and prediction of the relationship between mental and physiological states. Psychological tools for 'measuring' psychological states and traits is related to physiological and behavioural measures of immune activity and health promoting behaviours.
Methodological Issues
Poole et al. (2015)
Consideration of time frame is important in the
study of PNI,
where both acute or short-term stressors as well as
chronic or
long term effects are considered.
As such short term changes in the immune
system function
are measured in conjunction with short term stressors
(e.g.,
daily hassles, sudden events).
Small
fluctuations in the immune system function may be measured
over the
average day as well as over an period of months.
Where such longer term
stressors are considered
(e.g., trait anxiety, workplace stress, marital
problem,
financial challenges, chronic illness or terror).
As pointed out in
Selye's research on stress, longer term
stressors lead to the GAS, including the
reactive resistance
of parallel biological systems. Because of the multiplicity
of responses,
the singular effects of measurements of any specific
response
will be difficult to determine.
Statistical issues arise when considering multiple measures or variables.
Some of these are positive and some are negative. The positive ones are that, generally speaking, more (relevant) variables means better prediction of the outcome or target variable.
Multi-variable Methods typically used here are correlation, multiple regression, factor-analytical, or path analysis.
Factorial designs are also used under experimental treatments. Here the so called main and interaction effects are examined.
The
downfall of making multiple predictions in a given study is:
that the
more statistical relationships examined, the greater
the likelihood that an
erroneous relationship will be established.
In other words, each relationship
between variables is examined
and a decision about whether or not it is thought
to be real is made
based upon the probability that it will be true,
given known
parameters, 95 times out of 100.
Statistical
significance is this level of 05% chance of error,
sometimes placed
more conservatively at 01% chance of error.
While this level may be achieved
there may or may not be a
clinically significant difference
in outcome or change of symptoms or state.
Field
research offers the possibility of examining physiological
responses
to real stressors in natural situations. The challenges
here are that cohort
and contamination of data by extraneous variables
may be more likely. These are expected in cross-sectional
studies and
longitudinal studies, respectively.
Laboratory
research offers a greater degree of
confidence
in making 'cause and effect' attributions about the variables
through
controlled experimental studies.
However, the lack of natural situations may
alter the response
of the individual against their exposure to an known
antigen.
Limitations on
researchers ability to expose healthy people to
pathogens is an ethical
issue that leads to the use of
quasi-experimental or
natural experimental studies
(e.g., natural prevalence, disaster response).
An Introduction to the Immune System
Antigens
are microorganisms that are foreign to the human body
and may cause
disease (e.g, viruses, bacterial, fungi, parasites). you
tube
Pathogensare referred to as pathogens when they potentially cause death.
Infections
or diseases may be localized,
or situated in
only one area of the body which may also
be focalized
where they send toxins out throughout the body.
They may also be systemic,
affecting the entire body.
Internal systems of attack on these antigens take
various forms,
primarily through the development of specific and acquired immunity.
Lymphocytes
are a mainstay in the immune system,
including B-cells, T-cells and NK-cells (natural kills). utube
Immune
system memory maintains small numbers of "B memory cells"
that enable the body to create
immunoglobulins and antibodies
when
re-exposed to an antigen.
Taking about 5 days to produce a strong response the
B-lymphocytes
produce antibodies that are specific to that antigen
(e.g., water parasites).
The action of
B-lymphocytes to produce antibodies is aided through
helper T-cells (CD4) which produce cytokines
called
interleukins
(e.g., leukin-1, interleukins-2). Suppressor
T-cells (CD8)
work as "off switches" for the immune
system.
Tolerance
to one's own cells usually occurs where antibodies
are not produced against
one's own cells,
except in auto-immune disorders (e.g., arthritis).
Nonspecific
immunity operates through the general response
of swelling and phagocytosis.
How Immune-System Function is Measured in PNI Research
Counting cells
is the primary method used for dependent variables in PNI studies.
As such, one's immunocompetence is measured by one or more cell type
counts.
An enumerative
assay is performed to count levels of B-cells, T-cells and NK-cells
to determine a minimal number or varied balance among these white blood
cells.
Function tests are done to asses immunocompetence in action, across time.
These are done in vitro ( in the test tube)
as well as in vivo (in the human body)
for a specified period of time.
In vitro studies will involve the addition of a mitogen (agent to increase activity) to a blood sample (e.g., Con A, PHA, PWM), showing greater or lesser responses under various psychological states or conditions (e.g, confrontation).
A second common approach makes use of the NK cell cytotoxic assay that shows activity of NK cells. Others like the herpesvirus or Epstein-Barr virus counts may also be used to assess immune functioning.
Specific Ab responses may also be made at the infection or injection site.
Research
on Stress, Mood, Social Support & Personality
with PNI, Cancer & HIV
In various studies, the biological has been examined against a host of
psychological and social factors that have shown some impact on immune
functioning. Some such variable examined include: personality traits,
psychological states or moods, acute and chronic stress, social support
and coping styles.
The Effect of Stress on Immune Functioning
Immunosuppression is often observed in association with experiences of stress. Lazarus & Folkman (1984) define stress as "an aversive condition in which the demands of a situation are perceived to be greater than our ability to cope with them (Poole at al., p. 65) .
Responses may be observed in as few a five minutes or as long as 5 days. Some dispositional differences in physiological reactivity have been cited by Poole et al with respect to cortisol levels and URIs (upper respiratory infections).
Boscarino
(1997) reports that PTSD Viet Nam vets were more likely to have circulatory, metabolic
digestive or muscular ailments. They were 2.4
times more likely to have these medical problems, effects maintained at 20 year
follow-up.
Poole
et al. also cite studies on Three Mile Island residents, hurricane Andrew
survivors, Gulf War vets, earthquake victims and men and women going through
divorce. Here they point out that:
Three-Mile residences had elevated herpes virus
levels,
indicating compromised immunity after
10 years.
Gulf war vets had clusters of symptoms associated
with interleukin-1
apparently maintained partially
through classical
conditioning.
Divorced or separated women had immune compromise on a variety of
measures
while men who initiated the
break-up had better immune function than did those
whose partners initiated the
split.
Stress & URI
Studies
have shown that colds, flu and bronchitis are more likely among those who have
recently undergone traumatic life events or prolonged
daily hassles.
Poole
et al. report filed studies that subjective self-report measures are commonly
used to measure stress in conjunction with other characteristics like situation
and dispositional anxiety.
La
Via et al (1996) reported that people with generalized
anxiety disorder had
higher stress-intrusion scores (in vitro lymphocyte activity) as well as ( 3
times) more URI related sick days taken.
One
of the challenges of field studies is the lack of control over amount or level
of antigen
exposure. In
controlled experiments on URIs, antigens are often administered through nasal
sprays in viral
challenge studies.
On
the other hand, the impactof intact
social support systems can be examined through field studies, where it
has been found that larger and more diverse social support systems appear to
lessen the likelihood of cold infections (Cohen et al., 1997).
Other studies cited by Poole et al. have indicated that positive life events can have a negative impact on immune functioning.
Autoimmune diseases such as rheumatoid arthritis are exacerbated by stress. They occur as a result of the
body failing to maintain tolerance.
Stress & Cancer
Stress is expected to be brought on by cancer as well as it having an effect on the prognosis of cancer.
Spiegel et al (1988)
have shown that experience of major life events is
positively correlated with onset of cancer. Geyer (1991) also has shown a
greater likelihood of malignancy for women experiencing major life events.
Poole et al also
indicate that other studies have not demonstrated such results. While it is
difficult to determine the exact relationship between stress and cancer it
appears that it can potentiate cancerous growth
even if it may not initiate it.
Sergerstrom & Miller (2004) did a Meta-Analytic study of 300 studies across 30 years of study on psychological stress and the immune system found that acute stress was associate with an adaptive upregulation of immune functioning along with some specific down regulation. Chronic stresses, however were associated with cellular and humoural functioning of the immune system.
The Effect of Mood on Immune Functioning
Research on stress suggests that elevated emotional arousal is associated with compromised immune function, while other studies have shown that depression or diminished arousal is also associated with immune compromise.
Irwin et al (1987) found that women who had higher depression scores (having lost husband to cancer) also had most compromised immune function.
Schleifer (1983) also found pre-bereavement males had better lymphocyte proliferation than men who had recently lost their wives to cancer.
Another study (Glaser et al, 2000) had found that the stress of caring for a husband with dementia lead to more immuno-suppression than those women who had already lost their husbands
Herrmann
et al. (1998) also indicate that depression at the time of admittance is
correlated with mortality in a longitudinal study.
Levav et al (2003) report increased cancer incidence following bereavement due to accident or war.
Marks et al. (2015, p. 319) contest those results in the Copenhagen heart study by Nielsen et al. (2005) indicating women who expereinced higher levels of stress were less likely to be diagnosed with breast cancer.
Negative Mood and URI
Cohen at al (1995) examined negative state vs. trait mood, finding that state or transient negative affect could predict the presence of symptoms upon a viral challenge test.
Social Support and Immune Functioning
Social support, or the degree to which one has interpersonal resources to help in coping and providing health has been examined along with PNI & HIV
Miyazaki et al. (2003) report a beneficial relationship between perceived social support and immune function across CD and NK functioning.
Lee et al. (2001) report benefits from Korean Qi-therapy (Qi-Gong) on psychoneuroimmunological on anxiety; mood; cortisol; melatonin; neutrophil function; NK cells; natural killer cells.
Proposed
biological mechanisms
Poole et al propose four possible causes: endocrine system, sympathetic nervous system, immune system, and behaviour.
Hypothalamus and the sympathetic nervous system stimulate the immune system.
Reactivity hypothesis suggests that those whose sympathetic system is more reactive will also have a greater immunosuppression in the face of stress and the GAS.
It appears that we are evolutionarily prepared to respond to immediate stressors “flight or fight” but less so to fighting off slower acting antigens.
Immune system function has been associated with a number of chronic conditions including: cancer, hiv-aids, arthritis, mutiple sclerosis, lupis and many other conditions and diseases whic often lead to death.