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Project Literature Review

Erin McMurray & Alex Aquino


Veillette
Capstone I
May 10, 2018
According to the American Institute Stress, stress can be defined as “physical, mental, or
emotional strain or tension” (American Institute of Stress, n.d.). Stress is experienced by all
humans, and can be caused from a number of different things, depending on the individual. As
determined by the American Institute of Stress, there are two different types of stress that a
person can experience: acute stress or chronic stress. Acute Stress is stress that is experiences for
a short amount of time, and is triggered by the brain’s flight or fight response, which triggers the
release of stress hormones, like cortisol. Chronic Stress is stress that is endured over long periods
of time, that is usually ignored and left unmanaged (American Institute of Stress, n.d.). When left
unmanaged, chronic stress can have negative effects on the immune system and the body, which
can lead to health issues ​(Mayo Clinic, 2016)​. Common symptoms of untreated common stress
include insomnia, nightmares, tremors, back pains, angina, heartburn, and severe panic attacks
just to name a few ​(Mayo Clinic, 2016)​. Symptoms of chronic stress are experienced in
variations of severity depending on the amount of stress experienced by the individual, and the
individual’s ability to deal with challenges ​(Alvord, n.d.)​. According to a survey conducted by
the American Psychological Association, more than 40 percent of adults living in America said
that they have experienced insomnia like symptoms and severe lacks of sleep due to stress
(American Psychological Association, n.d.)​. In the same survey, 33 percent of adults responded
that they have never discussed the area of stress managements with their health care providers.
According to another survey conducted by the National Institute for Occupational Safety and
Health (NIOSH), it was found that 40 percent of respondents said that their job is extremely
stressful, and they sourced it as the main cause of stress in their lives ​(Murphy, n.d.)​. These
trends related to stress are similar in the educational world, where it was found in a different
survey administered by the American Institute of Stress, where eight in ten college students said
that they have experience unmanaged chronic stress ​(American Institute of Stress, 2008)​. These
statistics, along with the previously described symptoms of stress, are all evidence of a clear
problem in today’s society; a lack of awareness towards stress management. The symptoms of
chronic stress that were previously mentioned are considered to be common symptoms of
chronic stress. This being said, these symptoms should not be considered as “common”, because
they are among some of the most severe symptoms of chronic stress. This means that chronic
stress has become so widespread and untreated, that it’s most severe symptoms are now
considered to be normal. The statistics provided indicate that chronic stress is experienced by
many American citizens in both the workplace and in schools, and that there is a need for
research towards providing wats for this stress to be managed ​(American Institute of Stress,
2016)​.
The information included focuses on physical effects of stress, like body temperature
increase and heart rate changes. There is also information about how the brain and body responds
to stress with different stress responses, and how meditation can possibly act as a solution to
these responses. . Overall, these topics are all very important, because they all provide
information related to stress responses in the body, and the biological implication of chronic
stress.

Influence of Mental Stress on Heart Rate and Heart Rate Variability


The work done in this study was done to investigate if it is possible to measure stress
based off of measures of HRV (heart rate variability). The research and the paper itself were both
conducted and published in Leuven, Belgium, at Katholieke University in Leuven. The scientists
that conducted the study, J. Taelman and A. Spaepen, are from Katholieke University’s
Department of Biomedical Kinesiology, and scientists S. Vanderput and S. Van Huffel came
from the University’ Electrical Engineering Department. The work done in this study is valid,
because it was conducted by professors at a well established University. Heart rate variability
can be defined as the variation in time intervals between heartbeats, which is measured by
observing the intervals in which the heart beats (Campos, 2017). The study would also be done
to observe the autonomic nervous system’s activity, since the sympathetic nervous system
increases heart rate, and the parasympathetic nervous system decreases heart rate. This study was
done by inducing a stressful situation in the form of a mental stressor on 28 test subjects (15 men
and 13 women) of good health, and then measuring their heart rate and heart rate variability. The
participants were of a mean age of 22, with an average body mass index (BMI) of 22.2 The
participants in the experiment were students at Katholieke University, in Leuven, Belgium,
where the study took place. For each subject included in the study, data was collected in ways:
with and without a mental task. The Mensa Test, which is a difficult test that is used for
measuring IQ, was used a means of inducing mental stress (Mensa International, n.d.). Once in
the laboratory where the study was conducted, all of the participants were shown calming
images, which were used to lower their heart rates, and to put soothe their mind, preparing them
for the mental stress that the mensa test would induce. Heart rate was measured for each
participant throughout the test. HRV was calculated a different way; by examining the difference
in time between consecutive R-Peaks, which are the maximum amplitudes in the R wave of an
Electrocardiograph (ECG) (Heart Foundation, n.d.). The Electrocardiograph, which is used to
record electrical activity of the heart (Heart Foundation, n.d.), was used to measure heart rate
through the use of Nikomed brand electrodes of 10 millimeters, that were placed on the body.
Electromyography preamplifiers (EMG) were used to register the data collected in the study,
which was in the form of signals, because that is how the electrocardiograph processes data
(Heart Foundation, n.d.)
The data that was collected compared different aspects of both the resting heart rate and
the heart rate changes that occurred during the mental task. The mean RR intervals, which is the
term for heart rate variability when it is show on the electrocardiograph (Karius, n.d.), mean
standard deviation of heart rate variability, mean pNN50, which is a time domain measure of
heart rate variability that counts the number of consecutive heartbeats in increments of 50
milliseconds, and mean low frequency (LF) and high frequency (HF) values of the
electrocardiograph are all of the factors that were analyzed in this study. The RR intervals were
determined using the Pan-Tompkins algorithm, to detect the QRS complexes, which is the
combination of three graphs typically shown on the electrocardiogram (Karius, n.d.). Looking at
the QRS complex helped the scientists in the study to clearly see the RR intervals of their
subjects. HRV was calculated in this study by analyzing the time domain, and calculating it
from the RR interval. Standard deviation of RR, and standard deviation and mean of heart rate
were used as parameters for the time domain. The scientists working on the study used a Fourier
Transformation, which is a function that is used to break down functions of time into
frequencies, to determine the exact range of the time frequency. This method of calculating the
time domain by using the standard deviation and the fourier transformation is used because it
provides the most accurate solution, rather than just looking at one set of data. When looking at
the low frequency and high frequency values of the electrocardiograph, the data supported that
heart rate would increase with a mental task.
Overall among the participants in the study, it was found that 24 out of the 28 total
subjects had an increased mean heart rate when taking the mensa test. In this study, low
frequency and high frequency values of the electrocardiograph were used to measure
sympathovagal activity, which is the interaction between the sympathetic nervous system and
vagus nerve (Pagani, 2012). The vagus nerve is the tenth cranial nerve, which is found in the
upper part of the chest, that has parasympathetic control of the heart, lungs, and digestive tract
(Pagani, 2012). When analyzing sympathovagal activity, the low frequency has been shown to be
affected sympathetic and parasympathetic nervous system activity. The range of numbers found
within the low frequency of the electrocardiograph is related to activity of the sympathetic
nervous system, while the high frequency is related to activity in the parasympathetic nervous
system. In all of the participants in the study, the researchers found that both ratios for low
frequency and high frequency increased when doing the mensa test, which was used as a mental
task in this study. The researchers in the study came to the conclusion that the increases in heart
rate, low frequency, and high frequency occurred because of a heightened response of the
sympathetic nervous system while taking the mensa test. Based on all of their data that they
collected and the study as a whole, the scientists came to the conclusion that the sympathovagal
balance increased along with heart rate variability when performing a mental task. In the future,
the same research team plans to expand their research by continually analyzing heart rate
variability data, and by applying more linear and non-linear techniques to their research. A
similar study that yielded similar results was conducted by scientists from the University of Cape
Town’s Unit for Exercise Science and Sports Medicine Departments, in Cape Town, South
Africa, along with scientists from Columbia University's National Center for Addiction and
Substance Abuse in New York (Ian Lambert, 2011). This study focused on how induced
cognitive stress would affects both short term heart rate variability and mental performance. In
this study, eighteen males of good heath had that had been exposed to work related stress had
their heart rate variability examined for 10 minutes while performing a test that included
different mental challenged and puzzles. After the test, the male participants completed a survey
about their anxiety during the test. The data collected and the conclusions drawn by the scientists
in this study showed that short term heart rate variability and cognitive performance, when doing
a mental task, share a connection that relates to an experience of h. higher heart rate. This state of
a higher heart rate while taking the test, which was caused by induced stress, was concluded to
be caused by the sympathetic nervous system, which triggers the stress response in the body (Ian
Lambert, 2011). When the stress response is triggered by the sympathetic nervous system, heart
rate is one of the vitals in the body that is affected (American Institute of Stress, n.d.). Another
similar study was conducted at Texas A&M University, in the Department of Computer Science
and Engineering, where heart rate monitors were used to see if mental stress could be detected
(Choi, 2009). This experiment was conducted with the use of medical grade heart monitors, that
were placed on 4 human participants in the study. Heart rate was measured from these
participants on 2 different experimental conditions that caused mental stress, and two conditions
that induced a feeling of relaxation. Each participant underwent 20 totals trials, with the 4
different experimental conditions taking place 5 days in a row.The heart rate monitors used in
this study were in the form of sensors, that were placed on the body. The conclusions drawn
from this study were that, both medical grade and consumer grade heart rate monitors were able
to detect stress in the body (Choi, 2009). This indicated to the scientists in this study that
autonomic changes occurred in the body as their participants were undergoing stress (Choi,
2009). These two additional studies support the conclusions made by J. Taelman and A. Spaepen
from Katholieke University, because the scientists in these studies used very similar methods, in
which mental stress was induced upon participants through administering a test. They also
support J. Taelman and A. Spaepen because Jongyoon Choi, Ricardo Gutierrez-Osuna, and the
team from UNiversity of Cape Town all drew very similar conclusions to the conclusions drawn
by J. Taelman and A. Spaepen, which were that mental tasks increase heart rate and heart rate
variability in humans.
The topic of stress’s effects on the human body included in “Influence of Mental
Stress on Heart Rate and Heart Rate Variability”, is highly related to “Mechanisms and
Mediators of Psychological Stress-Induced Rise in Core Temperature”, which also talks about
how stress affects the body, but in a different way regarding to stress’s effect on body
temperature, rather than heart rate. The main similarity between the two studies conducted in
these two different papers is that both research teams focused on investigating how stress affects
the body. “Influence of Mental Stress on Heart Rate Variability” focused on how mental stress
affects heart rate, while “Mechanisms and Mediators of Psychological Stress-Induced Rise in
Core Temperature” focuses on how mental stress can cause rises in body temperature. Both
studies also focused on the responses related to mental stress in the body.“Influence of Mental
Stress on Heart Rate Variability” focused on how the different nervous systems of the body react
to stress and cause the stress response, and this “Mechanisms and Mediators of Psychological
Stress-Induced Rise in Core Temperature” discusses how neurotransmitters like serotonin
contribute to the stress responses of the human body. Both studies used mammalian test subjects,
and done by inducing mental stress.

Mechanisms and Mediators of Psychological Stress-Induces Rise in Core Temperature


“​Mechanisms and Mediators of Psychological Stress-Induced Rise in Core
Temperature”​ , focused on a study conducted on different laboratory animals, like rats, in which
an investigation was conducted looking into mammalian fever responses. This experiment was
conducted by Doctors Takakazu Oka from Harvard University, and Doctor Tetsuro Hori, who
are both members of the American Psychosomatic Society, which makes them and their work
credible, because there work was done through a prestigious University, and a national science
society. This experiment was conducted to investigate the natural phenomenon of psychogenic
fever, which is a stress induced, psychosomatic reaction that causes high body temperature (Oka,
2015). Psychogenic fever is caused by both chronic stress and emotional trauma (Oka, 2015).
With this study, the scientists set out to determine whether the noticeable rise in body
temperature experienced with chronic stress is a real fever, or in fact just a typical symptom of
hyperthermia. Hyperthermia is the condition of having an elevated body temperature, due to the
body’s inability to thermoregulate properly (Roland, 2017). As said by the writers of this paper,
the purpose of this study was to “review the mechanisms and mediators of PSRCT
(psychological stress induced rise in core temperature) in animals with the aim of understanding
psychogenic fever in humans” (Oka, 2001). In the mammalian body, whether it be an animal like
a dog or a human being, there are thermosensitive neurons that are located in the preoptic area of
the hypothalamus (Oka, 2001). The thermosensitive neurons, which can either be warm sensitive
neurons or cold sensitive neurons, interact with endogenous pyrogens, which are
proinflammatory cytokines that are a part of the immune system, which increase the
thermoregulatory functions of the hypothalamus, which causes fever (Oka, 2001). Endogenous
pyrogens increase the production and firing rate of cold sensitive neurons, while simultaneously
decreasing the production and firing rate of warm sensitive neurons (Oka, 2001). Cold sensitive
neurons are responsible for activating heat production, and warm sensitive neurons are
responsible for heat loss, which explains why the presence of both endogenous pyrons and
thermosensitive neurons would cause increases in body temperature (Oka, 2001).
To conduct this experiment, a variety of laboratory animals were used, like rats, lizards,
and pigs. Stress was induced on these subjects by engaging in typical behaviors that would
normally cause an animal to feel stress in a healthy way. This type of stress, when induced upon
an animal test subject, is called open field stress, which is when an animal is removed from it’s
home cage, and handled in a large open space. Stress was also induced upon animals through a
commonly used method by scientists called cage exchange stress, which is when an animal is
place into a new cage that is different from the one that they are normally used to (Oka, 2001). In
this study, when handling a stressed out rats, mice, and rabbits, it was found that their core
temperatures increased by an average of 2 degrees celsius. Another aspect of the experiment,
conducted on reptiles, focused on how ectothermic animals that rely on outside sources of heat to
survive would respond to both stress and calming. It was found that when conducting this
experiment that when taking a lizard away from it’s heating lamp for a very short period of time
using the experimental method of open field stress inducement, that it’s body temperature still
increased despite being away from its heat source (Oka, 2001). When handled in a gentle, and
calming way, it was found that the body temperature of the lizard then decreased, and the lizard
began to move towards it’s heat lamp seeking out warmth in attempt to raise it’s core body
temperature (Oka, 2001). This particular short experiment on the lizard showed that the body’s
hyperthermic responses are depend on both emotion and stimuli, because the stimuli from
changing the lizard’s environment caused it’s core body temperature to increase, and then the
feeling of being gently handled caused an emotional response, where the lizard’s core body
temperature decreased as stress was relieved. On a part of the experiment conducted on rats, it
was found that anti-inflammatory drugs like sodium salicylate can affect increases and decreases
in body temperature in the presence of stress (Oka, 2001). When administered either
intraperitoneally or intracerebroventricularly, it was found that sodium salicylate and
indomethacin significantly decreased the rise in core body temperature in rats exposed to open
field stress (Oka, 2001). This is because the anti-inflammatory properties of these drugs, that
provide oxygen to the body with the use of cyclooxygenase inhibitors, that worked hand in hand
to prevent core body temperature increases. Typically, the core body temperature of a rat rises
within a few minutes, and reached a peak temperature within 15 minutes, after being exposed to
open field stress (Oka, 2001). In a lizard called ​Callopistes maculatus,​ sodium salicylate
prevented fever, along with gentle handling of the lizard. In both rats and guinea pigs, it was
found that stress augmented the release of the neurotransmitter noradrenaline in the
hypothalamus, which is the main neurotransmitter of the sympathetic nerves of the
cardiovascular system (Oka, 2001). This altered release of noradrenaline caused a stress induced
rise core body temperature in both the rats and the guinea pigs, because the release of
noradrenaline in the preoptic area of the hypothalamus, causes the intra-preoptic area of the
hypothalamus to administer noradrenaline throughout the nervous system (Oka, 2001). In rats
and rabbits, local applications of noradrenaline activated cold sensitive neurons, and inhibited
warm sensitive neurons, causing an increase in core body temperature resemblant to that of a
fever (Oka, 2001). Intracerebroventricularly injecting beta adrenergic receptor antagonists in a
rat immersed in shallow water as a psychological stress model showed that core body
temperature increase was inhibited, because the release of neurotransmitters was blocked. When
using a different beta blocker, called nadolol, it was found that core body temperature increase
was not affected because this beta blockers is unable to cross the blood brain barrier (Oka, 2001).
This side study showed that beta adrenoreceptors in the central nervous system and in the
preoptic area of the hypothalamus are involved in psychological stress induced rise in core
temperature (Oka, 2001). Another neurotransmitter that affects core body temperature in
mammalian test subjects is serotonin. One short study showed that application of serotonin in the
body increased the functionality of warm sensitive neurons, while decreasing the functionality of
cold sensitive neurons in both rats and rabbits, causing core body temperature to very slightly
decrease. This response is typical to the hypothermic effects of intracerebroventricularly
administered serotonin (Oka, 2001). A more in depth study that used different mammal subjects
in a different trial of this research project showed that serotonin raised core body temperature
when it was injected in the preoptic area of the hypothalamus of cats. The scientists working on
this small study came to the conclusion that this hypothermic reaction is caused by the activation
of serotonin receptors. Anxiolytic drugs, like benzodiazepines, where found by the same research
team to have an inhibiting effect on anxiety-stress induced rises in core body temperature (Oka,
2001)). In rat test subjects, it was found that dopamine decreases core body temperature, because
it inhibits the activity of cold sensitive neurons in the preoptic area of the hypothalamus. Unlike
other neurotransmitters, dopamine agonists and antagonists had no effect on the anticipatory
anxiety stress-induced rise in core body temperature, which lead scientists to draw the conclusion
that dopamine has no effects or involvement in the stress induced rise in core body temperature
(Oka, 2001). “​Psychogenic Fever: How Psychological Stress Affects Body Temperature in the
Clinical Population”​ , supports the conclusions drawn in “​Mechanisms and Mediators of
Psychological Stress-Induced Rise in Core Temperature​”. In “​Psychogenic Fever: How
Psychological Stress Affects Body Temperature in the Clinical Population”​ , which was also
conducted by Dr. Takakazu Oka, it was found that core body temperature also increased in
mammals, and in this study humans, when experiencing chronic stress. Both studies drew the
same conclusions, which were that in mammals core body temperature is increased by engaging
in a mental task.
One of the main conclusions drawn by the scientists in this study is that there are two
different mechanisms of psychological stress-induced rises in core temperature: a mechanism
that depends upon PGE2, and one that is independent of PGE2, but is instead dependant upon
serotonin. The PGE2 (prostaglandin) dependent mechanism causes core temperature to increase
through PGE2 synthesis, while the second mechanism causes core body temperature to increase
with the presence of noradrenaline in the brain, without PGE2 synthesis. In the case of humans,
doctors usually treat psychogenic fever with cyclooxygenase inhibitors, because they lower the
core body temperature (Oka, 2001). This brings into question whether humans exhibit PGE2
dependendent psychogenic fever like the animals in the study did. Currently the answer to this
question is unknown, but it is known that psychogenic fever is suppressed by anxiolytic,
neuroleptic, and antidepressive drugs. In human patients with and without psychogenic fever, it
was found that blood levels of cytokines shared no difference between the normal core body
temperature state and the raised core body temperature state. The most important conclusion
drawn by the scientists from the animal studies was that the main mediators of psychogenic
fever are the neurotransmitters GABA, serotonin, noradrenaline, and PGE2. Future studies will
aim to investigate how these neurotransmitters interact with the occurrence of psychological
stress induces rise in core temperature in both lab animals and human beings.
The topic of stress induced rises in core body temperature discussed in “​Mechanisms and
Mediators of Psychological Stress-Induced Rise in Core Temperature”​ shares close relation to
“​Neurobiological and Systemic Effects of Chronic Stress”​ , which talks about the structural and
mental effects that stress has on the brain and body. These two topics share relation because
“​Neurobiological and Systemic Effects of Chronic Stress”​ provides insight on what the chronic
stress discussed in “​Mechanisms and Mediators of Psychological Stress-Induced Rise in Core
Temperature”​ does to the body and how it can have severe impacts on the body. “​Mechanisms
and Mediators of Psychologicals Stress-Induced Rise in Core Temperature​”, and
“​Neurobiological and Systemic Effects of Chronic Stress”​ both provide information about how
stress works in the brain, and the different effects that stress can have in the body.

Neurobiological and Systemic Effects of Chronic Stress


“​Neurobiological and Systemic Effects of Chronic Stress”​ provides a wealth of
information on how stress affects the brain, and the rest of the body. It goes in depth about the
physiological responses that occur in the brain when stress is detected, and it also provides
information on pathophysiology. “​Neurobiological and Systemic Effects of Chronic Stress​” also
discusses how structural plasticity of the adult brain can be changed in response to stress. This
article was written by Professor Bruce S. McEwen, in the Laboratory of Neuroendocrinology, at
Rockefeller University, in New York. Professor Bruce S. McEwen’s work and study is credible,
because he is a well known neuroendocrinologist in his field and the head of the neuroscience
department at the university he is employed at, meaning that his work was done with proper
funding and resources, making his work valid (Mirsky, 2017). “​Neurobiological and Systemic
Effects of Chronic Stress”​ focuses primarily on research conducted on the effects of stress on the
body, rather than focusing on a conducted experiment, where the data was then analyzed to draw
conclusions. Small experiments are described throughout this paper, but they are not it’s main
focus. Research conducted by team of scientists at Rockefeller University, lead them to establish
three distinguishable types of stress: eustress, tolerable stress, and toxic stress. Eustress, also
called good stress, is the type of stress that has a positive impact upon a person, like causing
someone to try something new, or to take a challenge. Eustress is most often followed by a
rewarding feeling and a positive outcome (McEwen, 2017). Tolerable stress, refers to situations
where stress in endured, but where the stress is manageable, and the individual knows how to
cope (McEwen, 2017). Toxic stress refers to situations where an individual has bad things
happen to him and or her, and they have no way of dealing with it. People that experience toxic
stress have most likely endured negative forms of stress in the past, that have changed the
structure of their brains, and impeded the development of proper impulse control and
management skills (McEwen, 2017). Based on Bruce S. McEwens’ research, who is a professor
of neuroendocrinology at Rockefeller University, there has been an established link between
toxic stress and allostatic overload. Allostatic overload is the term used to describe the negative
effects that long term exposure to chronic/toxic stress has on the brain. One of the negative
effects of allostatic overload is fluctuation in endocrine responses (McEwen, 2017).
When chronic stress causes structural changes in the brain, glutamate, which is an
excitatory amino acid, is usually to blame (McEwen, 2017). This is because glutamate is one of
the major excitatory neurotransmitters of the brain. When present in an excess amount, glutamate
causes inflammation, and can permanently damage to the brain (McEwen, 2017). In a separate
study done on rats that were induced with restraint stress, which causes autonomic and heart rate
increases, it was found that the presence of restraint stress in chronic amounts caused structural
changes in the brain. The apical dendrites of the hippocampus shrunk, which was caused by the
increase in extracellular glutamate levels in response to the presence of stress in the body
(McEwen, 2017). In a different study conducted by the same team, but on different rats, it was
found that overflows of glutamate in the brain caused depressive-like behavior. The rats isolated
themselves and refused to eat their food, which are two behaviors that signal depression in
animals. This was believed to have happened because the excess glutamate caused the dendrites
in the hippocampus to shrink (McEwen, 2017). A possible solution that was provided to the
excess glutamate release in the body is the use of the therapeutic, glucagon-like-peptide (GLP-1),
that has insulinotropic actions. GLP-1 promotes weight loss, exerts neuroprotective effects,
reduces plaque accumulation, and improves synaptic plasticity. All of these benefits of GLP-1
help to protect against inflammation and damage that can occur when glutamate is produced in
abundance.
A big finding from one of the experiments included in this study, was that male rodents
and female rodent displayed different patterns of neural structure change after experiencing
chronic stress. In male rodents, after experiencing chronic stress, the CA3 dendrites were slightly
reshaped, while for female rodents they stayed the same, although measures of stress hormones
showed that both genders of rodents were experiencing the same amounts of stress (McEwen,
2017). Instead, the female rodents displayed an expansion of the dendrites of their neurons,
found in the basolateral amygdala. Another difference is that after experiencing chronic stress,
male rodents experienced struggles with hippocampal dependent memories, while female rodents
did not. The findings lead the researchers to come to the conclusion that differences in gender
come with difference in brain systems, which controls how males and females react to stressful
stimuli (McEwen, 2017).
The main takeaway provided by “​Neurobiological and Systemic Effects of Chronic
Stress”​ is that there is a lot that needs to be done research wise, and socially to tackle the issue of
chronic stress. The researchers in “​Neurobiological and Systemic Effects of Chronic Stress”​ plan
to conduct more research, looking into how the female sex hormone estrogen, and the male sex
hormone androgen, effect the stress response, since it was found that brain structure changes
occur more in males. The researchers also plan on developing ways to inform, and educate the
general public about these findings. With this knowledge, they hope to inform people about how
important it is to properly manage stress, because when stress is poorly managed, a person is at
risk for structural brain change. Things that can be done to manage stress are maintaining a high
quality of sleep, promoting a positive life outlook, maintaining a healthy diet, avoiding smoking,
and engaging in physical activity. The research group also plans to do more research on
pharmaceutical agents that can help prevent the inflammation caused by excess production of
glutamate.
Randomized controlled evaluation of the effects of cognitive-behavioral stress management
on cortisol responses to acute stress in healthy subjects

The purpose of this study was to evaluate the effects of short-term, group-based
cognitive-behavioral stress management training on endocrine responses and cognitive appraisal
under acute stress in a population of healthy young male students. In order to find participants,
the research team sent out a recruiting email for a study involving stress management to all
students of the Swiss Federal Institute of Technology in Zurich, Switzerland. Within the email, a
link was provided to a website that briefly described the study. Those interested in partaking in
the study had the opportunity to enroll online. Following enrollment, each volunteer subject
received a screening questionnaire, which contained exclusion criteria. These criteria were
specifically designed to eliminate confounding factors that have been shown to affect
physiological dependent measures, and included the female gender and smokers. Additionally,
participants that reported any acute or chronic somatic or psychiatric disorder were excluded as
well. Subsequent to the providing of complete written and oral descriptions of the study, the
subjects were required to fill out written consent forms.
First, the research team needed to induce the same type of stress on each of the
participants, so they decided to use a psychosocial stress test. It has been found that the Trier
Social Stress Test (TSST) has consistently induced significant endocrine and cardiovascular
responses in a large majority of study participants (70-80%). Subjects were introduced to the
TSST subsequent to basal samples of salivary free cortisol. Then, they were ordered to go to a
different room, in which they had ten minutes to prepare and to complete a questionnaire
designed to assess cognitive appraisal processes regarding the anticipated stress scenario. Then,
the subjects returned to the testing room, where each of them took part in a simulated
five-minute job interview and a five-minute mental arithmetic task in front of an audience of two
people. To assess salivary free cortisol levels, saliva samples were taken immediately before and
after the Trier Social Stress Test, in addition to further samples taken at ten, twenty, thirty,
forty-five, and sixty minutes.
After stress was induced, all participants were subject to the stress management training. Each of
them attended group-based cognitive-behavioral stress management training following the
principles of stress inoculation training. Four groups attended group therapy sessions. Groups 1
and 2 met separately on two alternate Saturdays. Groups 3 and 4 also met separately on two
alternate Sundays. Each group consisted of twelve people and each session lasted from 1000
hours to 1700 hours. Each group was led by a qualified, postdoctoral psychotherapist in training
using a training manual. The groups were assisted on each training day by two psychology
students. The intervention mainly focused on the four cognitive–behavioral stress-reducing
techniques, including stress management (cognitive restructuring, problem-solving,
self-instruction) and relaxation training modules (progressive muscle relaxation). The first
session of group therapy consisted of a theoretical introduction and a group discussion regarding
transactional stress concepts. Two hours later, they had a one-hour lunch break. After, each stress
inoculation module was introduced and practiced in groups of four for one hour. At the end of
the first session, subjects received a training manual containing a summary of the transactional
stress concept and of all stress-reducing techniques that were introduced. The manual also
included a set of flash cards that briefly described what each stress-reducing technique entailed.
For “homework”, all study participants were encouraged to assess stress-relevant cognitions, to
carry and use the flashcards consistently, and to apply the techniques before the second group
session. The second group session began with a two-hour homework review, then a one-hour
lunch break, and afterwards, each technique was discussed and practiced again.
As for protocol, the research team implemented certain factors into their study. “Upon
return of all screening questionnaires, all subjects fulfilling the selection criteria were randomly
assigned to four groups by drawing numbers out of an envelope. Because the a priori power
calculation resulted in an optimal sample size of N = 48 (see below), only 48 subjects were
randomized. The remaining subjects were excluded. After randomization but before the group
treatment or waiting condition, all participants were given a set of questionnaires in order to
obtain comprehensive descriptions of relevant personality and stress factors (TICS, MESA,
FKK). Groups 1 and 2 underwent the TSST after completing the SIT while Groups 3 and 4
received the TSST before the SIT. Thus, Groups 1 and 2 served as treatment groups, while
Groups 3 and 4 formed the waiting control condition. The TSST committee did not know
whether or not the respective participant had performed the SIT beforehand. The TSST was
performed in different rooms from the SIT.”
In order to take measurements from the participants, sampling methods and biochemical
analyses were put in place. Saliva was collected by the subjects using Salivette collection devices
and stored at room temperature until completion of the session and stored at room temperature
until completion of the session. Samples were then stored at -20 degrees Celsius until they could
be biochemically analyzed. The free cortisol concentration in saliva was determined using a
time-resolved immunoassay with fluorometric detection. Inter- and intra-assay coefficients of
variance were below 10% for all analytes. In regards to psychometric measures, several
questionnaires were used in order to allow for comparison of relevant parameters between the
randomized groups. The first was the Trier Inventory of Chronic Stress (TICS), and this measure
was used to assess perceived chronic stress. The subjects were required to indicate how often
they individually experienced stressful situations throughout the past year. Trier Inventory of
Chronic Stress was constituted six subscales: work overload, work discontent, social stress, lack
of social recognition, worries, and intrusive memories. The second questionnaire was the
Competence and Control Orientation (FKK). This was comprised of thirty-two items that
assessed the following personality traits: “self-concept of own competence”, “internality”,
“powerful others control”, and “chance control”. The third questionnaire included in the study
was called Stress susceptibility (MESA). This was a thirty-six-item questionnaire, which
assessed stress susceptibility on six different subscales. Psychometric pre and post evaluation of
the stress inoculation training and the control-waiting condition was performed with the
Perceived Stress Scale (PSS). A German translation of the Perceived Stress Scale was used to
assess the degree to which situations in life experienced during the previous month are perceived
as stressful. Items in the PSS were designed to assess how predictable, uncontrollable, and
overloading participants find their own individual lives. The Primary Appraisal Secondary
Appraisal Scale (PASA) was the questionnaire that assessed anticipatory cognitive appraisal
processes in the TSST. This scale was specifically constructed to assess cognitive appraisal
processes in the TSST according to the transactional stress theory. The Primary Appraisal
Secondary Appraisal Scale is composed of four situation-specific subscales assessing primary
appraisals such as “Challenge” and “Perceived Threat”, as well as secondary appraisals like
“Self-Concept of Own Competence” and “Control Expectancy”. In order to assess anticipatory
cognitive appraisals, the PASA was administered at a time between the introduction and the
actual TSST. After collecting the data, statistical analyses were made. ANCOVAs and ANOVAs
for repeated measures were computed in order to analyze endocrine responses between groups,
controlling for differences in endocrine baseline levels when indicated. All reported results were
corrected by the Greenhouse-Geisser procedure where appropriate, and correlations were
computed as Pearson product-moment correlations. For all endocrine parameters, areas under
the total response curve (AUC), expressed as area under all samples, were calculated using the
trapezoidal method. Data were tested for normal distribution and homogeneity of variance using
a Kolmogorov–Smirnov and Levene’s test before statistical procedures were applied. The
optimal total sample size of N = 48 to detect an expected large effect size of f2 = 0.35
(representing a large effect size) with a power 0.85 and α = 0.05 was calculated a priori with the
statistical software G-Power (Buchner et al., 1997). For all analyses, significance level was α =
5%. Unless indicated, all results shown are means ± standard error of means (SEM).”
The Trier Social Stress Test had significant results involving salivary free cortisol
responses. The first saliva cortisol sample as covariate, ANCOVA, proved that baseline
differences between the groups did not substantially influence endocrine stress response. It was
found that groups had significant differences in their salivary free cortisol stress responses over
time, with subjects in the stress inoculation training group showing an attenuated salivary free
cortisol response. Also, subjects in the stress inoculation training group had a significantly lower
integrated salivary free cortisol response. In order to determine whether group differences in
cognitive appraisal of the Trier Social Stress Test had an influence on the salivary free cortisol
stress response, the PASA scales were included in the calculations as covariates. ANCOVA
results suggested that primary stress appraisal had a notable influence on the salivary free
cortisol stress response. The fact that this psychological factor was included was important
because it eliminated the observed significant group differences in the salivary free cortisol
response over time and the integrated salivary free cortisol response. It can also be concluded
that there was no significant association between the number of days between the stress
inoculation training and the Trier Social Stress Test and the integrated salivary free cortisol
response. It is also important to note that the groups differed significantly in their anticipatory
cognitive appraisal of the TSST. In comparison with controls, subjects in the stress inoculation
training group had lower primary stress appraisal and higher self efficacy appraisal. Groups did
not differ much in their perception of Novelty, with stress inoculation participants demonstrating
a decrease in perceived stress post treatment levels.
This study concluded that short, group-based, cognitive-behavioral stress management
training reduces the salivary free cortisol stress response to an acute stressor in healthy male
participants. These endocrine response differences were affected by the observed differences in
the cognitive appraisal of the situation. Subjects in the treatment group appraised the situation as
less stressful and displayed more competence in coping with the situation. It was found that all
reported effect sizes for significant endocrine and psychometric group differences in the Trier
Social Stress Test were large. On the other hand, the pre and post changes in perceived stress
were only of medium effect size.
The salivary free cortisol responses observed in our sample is somewhat higher than
those published by other groups using the TSST. This could be a consequence of the altered
TSST protocol we used in order to obtain data concerning the anticipatory appraisal processes.
However, this difference in the response magnitude does not seem to be a result of group
differences, since groups did not differ significantly in the basal cortisol levels and the respective
psychometric scales.
Female subjects were excluded from this study because had they been included, their
menstrual cycle phases would have to be controlled, along with the use of oral birth control. The
research team did this aware that it may have weakened the external validity of the study,
however they did it anyways in order to enhance the internal validity. However, since gender
differences of HPA axis stress responses seem to be mediated through differences in sex
hormone levels and the observed response differences in our study were mediated through
differences in the cognitive appraisal, the researchers were confident that the stress inoculation
training has similar neuroendocrine effects in females.
This is the first study to report that short, group-based, cognitive–behavioral stress
management training attenuates the endocrine and psychological response to acute stress in
healthy subjects. Alterations of HPA axis functioning have been linked to the development and
maintenance of psychosomatic and psychiatric disorder and somatic illness. According to the
concept of allostatic load, which represents a marker of cumulative biological burden exacted on
the body through attempts to adapt to life’s demands, several conditions of how stress leads to
alterations of the HPA axis can be distinguished. These include repeated activation during
chronic stress and failure to habituate to repeated stressors. With the observed attenuation of the
neuroendocrine stress response and the changes in cognitive appraisal of the stress situation, it is
possible that group-based, cognitive–behavioral stress management training could prove useful
in preventing detrimental consequences of stress-induced neuroendocrine responses, such as the
risk of developing hypertension and metabolic syndrome. However, it is important to note that
we have not assessed the effects of short, group-based, cognitive–behavioral stress management
training on markers of allostatic load, but rather on mechanisms that have been discussed to lead
to the development of allostatic load. There is consensus that the relation between HPA axis
parameters and health is not linear, thus both too much and too little HPA axis activity and
reactivity can be linked to disease and health complaints. As a consequence, the findings of a
reduced neuroendocrine stress response should not be considered to be protective per se, but
rather with regard to its possible role in the development of stress-related health complaints.
Since cortisol has been considered a primary mediator in the development of allostatic load,
further studies are necessary in order to evaluate possible long-term effects of the
neuroendocrine response differences that were observed.

Source #5: Meditation Programs for Psychological Stress and Well-being: A Systematic
Review and Meta-analysis

The purpose of this meta-analysis was to determine the effectiveness of mediation


programs in improving stress-related outcomes such as anxiety, depression, stress/distress,
positive mood, mental health, attention, substance use, eating habits, sleep, pain, and weight, in
diverse adult clinical populations. They research team felt their work was very important, since
many people meditate to reduce psychological stress and stress-related health problems. In order
for patients to be counseled appropriately, doctors and physicians must be aware of what the
evidence says regarding the health benefits of meditation. In summary, randomized clinical trials
with active controls for placebo effects through November 2012 from a variety of sources (e.g.
Medline, PsycINFO, Scopus, the Cochrane Library, etc.) were identified. Citations were
screened and data was extracted by two independent reviewers. Afterwards, the strength of
evidence was graded using four domains (risk of bias, precision, directness, consistency), and the
magnitude and direction of effect was determined by calculating the relative difference between
groups in change from baseline. Meta-analyses were conducted using standardized mean
differences as much as possible in order to obtain aggregate estimates of effect size with 95%
confidence intervals.
In order to find articles that could be used for this meta-analysis, the team developed a
Medline search strategy using PubMed medical subject heading terms and the text words of key
articles. Similar strategies were used through the other online sources. They reviewed the
reference lists of included articles, relevant review articles, and related systematic reviews for the
purpose of identifying articles that may have missed in the database searches, and they did not
restrict their analysis based on language or date of publication. However, they did include
randomized controlled trials in which the control group was matched in time and attention to the
intervention group, and they required that studies included subjects with a clinical condition,
broadly defined in order to include mental health and psychiatric conditions (e.g. back pain, heart
disease, old age).
To manage the screening process, they used a systematic review software. For each
meditation program, they extracted information on measures of intervention fidelity, including
dose, training, and receipt of intervention. The duration and maximal hours of structured training
in meditation, the amount of home practice recommended, description of instructor
qualifications, and description of participant adherence, if any, were recorded. Due to the fact
that numerous scales measured negative or positive affect, we chose scales that were common to
the other trials and the most clinically relevant to make comparisons more meaningful.
To display the outcome data, they calculated the relative difference in change scores (i.e.
the change from baseline in the treatment group minus the change from baseline in the control
group, divided by the baseline score in the treatment group). Also, they used the relative
difference in change scores to estimate the direction and approximate magnitude of effect for all
outcomes. However, a relative difference in change score for six outcomes owing to
incompletely reported data for statistically insignificant findings were unable to be calculated.
They considered a 5% relative difference in change score to be potentially clinically significant,
since the studies examined short-term interventions and relatively low doses of meditation. In
total, 18,753 unique citations and 1,651 full-text articles were screened. Of those, forty-seven
trails met the necessary criteria to be included in the meta-analysis.
Conclusively, this review indicated that meditation programs can, in fact, reduce the
negative dimensions of psychological stress. In particular, mindfulness meditation programs
were shown to slightly alleviate anxiety, depression, and pain with moderate evidence. On the
other hand, mantra meditation programs did not improve any of the outcomes examined, but
there was low to insufficient evidence for this claim. It was also found that the evidence from
some studies did not show any positive effects on well-being for any meditation program, despite
that the main purpose of most meditation programs is to seek positive health improvement.
Additionally, its relevant to note that there was no evidence that the meditation programs harmed
any individuals.
The ESs were small but significant for some of the individual outcomes and were seen
across a broad range of clinical conditions. During the course of 2 to 6 months, the mindfulness
meditation program ES estimates ranged from 0.22 to 0.38 for anxiety symptoms and 0.23 to
0.30 for depressive symptoms. These small effects are comparable with what would be expected
from the use of an antidepressant in a primary care population but without the associated
toxicities. These findings are extremely important, as they could open a window to alternate
treatment options for those with depression and other related mental illnesses. Overall, the
evidence was insufficient to indicate that meditation programs alter health-related behaviors
affected by stress, and low-grade evidence suggested that meditation programs do not influence
weight. Although uncontrolled studies have usually found a benefit of meditation, very few
controlled studies have found a similar benefit for the effects of meditation programs on
health-related behaviors affected by stress.
A number of observations provide context to the conclusions. First, very few mantra
meditation programs met their inclusion criteria. This lack significantly limited their ability to
draw inferences regarding the effects of mantra meditation programs on psychological
stress–related outcomes, which did not change when transcendental meditation were evaluated
separately from other mantra training. Second, differences may have existed between trials for
which the outcomes are a primary vs a secondary focus, although no evidence of this was found.
The samples included in these trials resembled a general primary care population, and there may
not be room to measure an effect if symptom levels of the outcomes are low to start with (ie, a
floor effect). This limitation may explain the null results for mantra meditation programs because
3 transcendental meditation trials enrolled patients with cardiac disease, whereas only 1 enrolled
patients with anxiety. Third, the lack of effect on stress-related outcomes may relate to the way
the research community conceptualizes meditation programs, the challenges in acquiring such
skills or meditative states, and the limited duration of RCTs. Historically, meditation was not
conceptualized as an expedient therapy for health problems. Meditation was a skill or state one
learned and practiced over time to increase one’s awareness and through this awareness to gain
insight and understanding into the various subtleties of one’s existence. Training the mind in
awareness, in nonjudgmental states, or in the ability to become completely free of thoughts or
other activity are daunting accomplishments. The interest in meditation that has grown during the
past 30 years in Western cultures comes from Eastern traditions that emphasize lifelong growth.
The translation of these traditions into research studies remains challenging. Long-term trials
may be optimal to examine the effect of meditation on many health outcomes, such as those
trials that have evaluated mortality. However, many of the studies included in this review were
short term (eg, 2.5 h/wk for 8 weeks), and the participants likely did not achieve a level of
expertise needed to improve outcomes that depend on mastery of mental and emotional
processes. Finally, none of our conclusions yielded a high strength of-evidence grade for a
positive or null effect. Thus, further studies in primary care and disease-specific populations are
indicated to address uncertainties caused by inconsistencies in the body of evidence, deficiencies
in power, and risk of bias.
Randomized controlled evaluation of the effects of cognitive-behavioral stress management
on cortisol responses to acute stress in healthy subjects

The purpose of this study was to evaluate the effects of short-term, group-based
cognitive-behavioral stress management training on endocrine responses and cognitive appraisal
under acute stress in a population of healthy young male students. In order to find participants,
the research team sent out a recruiting email for a study involving stress management to all
students of the Swiss Federal Institute of Technology in Zurich, Switzerland.
First, the research team needed to induce the same type of stress on each of the
participants, so they decided to use a psychosocial stress test. (Gaab, 2002) It has been found that
the Trier Social Stress Test (TSST) has consistently produced significant endocrine and
cardiovascular responses in a majority of study participants. (Gaab, 2002) Subjects were
introduced to the TSST subsequent to basal samples of salivary free cortisol. (Gaab, 2002) Then,
they were ordered to go to a different room, in which they had ten minutes to prepare and to
complete a questionnaire designed to assess cognitive appraisal processes regarding their
prospective individual stress scenario. (Gaab, 2002) After that, the subjects returned to the
testing room, where each of them took part in a simulated five-minute job interview and a
five-minute mental arithmetic task in front of an audience of two people. (Gaab, 2002) To assess
salivary free cortisol levels, saliva samples were taken immediately before and after the Trier
Social Stress Test, in addition to further samples taken at ten, twenty, thirty, forty-five, and sixty
minutes. (Gaab, 2002)
After stress was induced, all participants were subject to the stress management training.
(Gaab, 2002) Each of them attended group-based cognitive-behavioral stress management
training following the principles of stress inoculation training. (Gaab, 2002) Four groups
attended group therapy sessions. Each group was led by a qualified, postdoctoral psychotherapist
in training using a training manual. (Gaab, 2002) The intervention mainly focused on the four
cognitive–behavioral stress-reducing techniques, including stress management (cognitive
restructuring, problem-solving, self-instruction) and relaxation training modules (progressive
muscle relaxation). (Gaab, 2002) The first session of group therapy consisted of a theoretical
introduction and a group discussion regarding transactional stress concepts. (Gaab, 2002) After,
each stress inoculation module was introduced and practiced in groups of four for one hour.
(Gaab, 2002) At the end of the first session, subjects received a training manual containing a
summary of the transactional stress concept and of all stress-reducing techniques that were
introduced. (Gaab, 2002) The manual also included a set of flashcards that briefly described what
each stress-reducing technique entailed. (Gaab, 2002) For “homework”, all study participants
were encouraged to assess stress-relevant cognitions, to carry and use the flashcards consistently,
and to apply the techniques before the second group session. (Gaab, 2002)
In order to take measurements from the participants, sampling methods and biochemical
analyses were put in place. (Gaab, 2002) Saliva was collected by the subjects using Salivette
collection devices and stored at room temperature until completion of the session and stored at
room temperature until completion of the session. (Gaab, 2002) Samples were then stored at -20
degrees Celsius until they could be biochemically analyzed. (Gaab, 2002) The free cortisol
concentration in saliva was determined using a time-resolved immunoassay with fluorometric
detection. (Gaab, 2002) Inter- and intra-assay coefficients of variance were below 10% for all
analytes. In regards to psychometric measures, several questionnaires were used in order to allow
for comparison of relevant parameters between the randomized groups. (Gaab, 2002) The first
was the Trier Inventory of Chronic Stress (TICS), and this measure was used to assess perceived
chronic stress. (Gaab, 2002) The subjects were required to indicate how often they individually
experienced stressful situations throughout the past year. (Gaab, 2002) Trier Inventory of
Chronic (Gaab, 2002) Stress was constituted six subscales: work overload, work discontent,
social stress, lack of social recognition, worries, and intrusive memories. (Gaab, 2002) The
second questionnaire was the Competence and Control Orientation (FKK). (Gaab, 2002) This
was comprised of thirty-two items that assessed the following personality traits: “self-concept of
own competence”, “internality”, “powerful others control”, and “chance control”. (Gaab, 2002)
The third questionnaire included in the study was called Stress susceptibility (MESA). (Gaab,
2002) This was a thirty-six-item questionnaire, which assessed stress susceptibility on six
different subscales. (Gaab, 2002) Psychometric pre and post evaluation of the stress inoculation
training and the control-waiting condition was performed with the Perceived Stress Scale (PSS).
(Gaab, 2002) A German translation of the Perceived Stress Scale was used to assess the degree
to which situations in life experienced during the previous month are perceived as stressful.
(Gaab, 2002) Items in the PSS were designed to assess how predictable, uncontrollable, and
overloading participants find their own individual lives.(Gaab, 2002) “The Primary Appraisal
Secondary Appraisal Scale (PASA) was the questionnaire that assessed anticipatory cognitive
appraisal processes in the TSST. This scale was specifically constructed to assess cognitive
appraisal processes in the TSST according to the transactional stress theory.” (Gaab, 2002) The
Primary Appraisal Secondary Appraisal Scale is composed of four situation-specific subscales
assessing primary appraisals such as “Challenge” and “Perceived Threat”, as well as secondary
appraisals like “Self-Concept of Own Competence” and “Control Expectancy”. (Gaab, 2002) In
order to assess anticipatory cognitive appraisals, the PASA was administered at a time between
the introduction and the actual TSST. (Gaab, 2002)
The Trier Social Stress Test had significant results involving salivary free cortisol
responses. (Gaab, 2002) The first saliva cortisol sample as covariate, ANCOVA, proved that
baseline differences between the groups did not substantially influence endocrine stress response.
(Gaab, 2002) It was found that groups had significant differences in their salivary free cortisol
stress responses over time, with subjects in the stress inoculation training group showing an
attenuated salivary free cortisol response. (Gaab, 2002) Also, subjects in the stress inoculation
training group had a significantly lower integrated salivary free cortisol response. (Gaab, 2002)
In order to determine whether group differences in cognitive appraisal of the Trier Social Stress
Test had an influence on the salivary free cortisol stress response, the PASA scales were
included in the calculations as covariates. (Gaab, 2002) ANCOVA results suggested that primary
stress appraisal had a notable influence on the salivary free cortisol stress response. (Gaab, 2002)
The fact that this psychological factor was included was important because it eliminated the
observed significant group differences in the salivary free cortisol response over time and the
integrated salivary free cortisol response. (Gaab, 2002) It can also be concluded that there was no
significant association between the number of days between the stress inoculation training and
the Trier Social Stress Test and the integrated salivary free cortisol response. (Gaab, 2002) It is
also important to note that the groups differed significantly in their anticipatory cognitive
appraisal of the TSST. (Gaab, 2002) In comparison with controls, subjects in the stress
inoculation training group had lower primary stress appraisal and higher self efficacy appraisal.
(Gaab, 2002) Groups did not differ much in their perception of Novelty, with stress inoculation
participants demonstrating a decrease in perceived stress post treatment levels. (Gaab, 2002)
This study concluded that short, group-based, cognitive-behavioral stress management
training reduces the salivary free cortisol stress response to an acute stressor in healthy male
participants. (Gaab, 2002) These endocrine response differences were affected by the observed
differences in the cognitive appraisal of the situation. (Gaab, 2002) Subjects in the treatment
group appraised the situation as less stressful and displayed more competence in coping with the
situation. (Gaab, 2002) It was found that all reported effect sizes for significant endocrine and
psychometric group differences in the Trier Social Stress Test were large. (Gaab, 2002) On the
other hand, the pre and post changes in perceived stress were only of medium effect size. (Gaab,
2002)
The salivary free cortisol responses observed in the sample were somewhat higher than
those published by other groups using the TSST. (Gaab, 2002) This could be a consequence of
the altered TSST protocol they used in order to obtain data concerning the anticipatory appraisal
processes. (Gaab, 2002) “However, this difference in the response magnitude did not seem to be
a result of group differences, since groups did not differ significantly in the basal cortisol levels
and the respective psychometric scales.”(Gaab, 2002) Another study yielded similar results that
cognitive-behavioral stress management reduced cortisol levels, and in turn minimized stress.
(Antoni, 2000)
The research team made the decision to exclude female subjects from this study because
their menstrual cycle phases would have to be controlled, along with the use of oral birth control.
(Gaab, 2002) They made this decision knowing that it may have weakened the external validity
of the study, however they did it anyways in order to enhance the internal validity.(Gaab, 2002)
However, since gender differences of HPA axis stress responses seem to be mediated through
differences in sex hormone levels and the observed response differences in our study were
mediated through differences in the cognitive appraisal, the researchers were confident that the
stress inoculation training has similar neuroendocrine effects in females. (Gaab, 2002)
This is the first study to report that short, group-based, cognitive–behavioral stress
management training attenuates the endocrine and psychological response to acute stress in
healthy subjects. (Gaab, 2002) Alterations of HPA axis functioning have been linked to the
development and maintenance of psychosomatic and psychiatric disorder and somatic illness.
(Gaab, 2002) “With the observed attenuation of the neuroendocrine stress response and the
changes in cognitive appraisal of the stress situation, it is possible that group-based,
cognitive–behavioral stress management training could prove useful in preventing detrimental
consequences of stress-induced neuroendocrine responses, such as the risk of developing
hypertension and metabolic syndrome.” (Gaab, 2002) However, they have not assessed the
effects of short, group-based, cognitive–behavioral stress management training on markers of
allostatic load, but rather on mechanisms that have been discussed to lead to the development of
allostatic load. (Gaab, 2002) There is consensus that the relation between HPA axis parameters
and health is not linear, thus both too much and too little HPA axis activity and reactivity can be
linked to disease and health complaints. (Gaab, 2002) “As a consequence, the findings of a
reduced neuroendocrine stress response should not be considered to be protective per se, but
rather with regard to its possible role in the development of stress-related health complaints.”
(Gaab, 2002) Since cortisol is considered a primary mediator in the development of chronic
stress, further studies are necessary in order to evaluate possible long-term effects of the
neuroendocrine response differences that were observed. (Gaab, 2002)

Meditation Programs for Psychological Stress and Well-being: A Systematic Review and
Meta-analysis

The purpose of this meta-analysis, conducted by Madhav Goyal, a doctor at Johns


Hopkins University, was to determine the effectiveness of mediation programs in improving
stress-related outcomes such as anxiety, depression, stress/distress, positive mood, mental health,
attention, substance use, eating habits, sleep, pain, and weight, in diverse adult clinical
populations. (Goyal, 2014) Their work was very important, since many people meditate to
reduce psychological stress and stress-related health problems. In order for patients to be
counseled appropriately, doctors and physicians must be aware of what the evidence says
regarding the health benefits of meditation. (Goyal, 2014) In summary, randomized clinical trials
with active controls for placebo effects through November 2012 from a variety of sources (e.g.
Medline, PsycINFO, Scopus, the Cochrane Library, etc.) were identified. (Goyal, 2014) Citations
were screened and data was extracted by two independent reviewers. (Goyal, 2014) Afterwards,
the strength of evidence was graded using four domains (risk of bias, precision, directness,
consistency), and the magnitude and direction of effect was determined by calculating the
relative difference between groups in change from baseline. (Goyal, 2014) Meta-analyses were
conducted using standardized mean differences as much as possible in order to obtain aggregate
estimates of effect size with 95% confidence intervals. (Goyal, 2014)
In order to find articles that could be used for this meta-analysis, the team developed a
Medline search strategy using PubMed medical subject heading terms and the text words of key
articles. (Goyal, 2014) Similar strategies were used through the other online sources. They
reviewed the reference lists of included articles, relevant review articles, and related systematic
reviews for the purpose of identifying articles that may have missed in the database searches, and
they did not restrict their analysis based on language or date of publication. (Goyal, 2014)
However, they did include randomized controlled trials in which the control group was matched
in time and attention to the intervention group, and they required that studies included subjects
with a clinical condition, broadly defined in order to include mental health and psychiatric
conditions (e.g. back pain, heart disease, old age). (Goyal, 2014)
To manage the screening process, they used a systematic review software. (Goyal, 2014)
For each meditation program, they extracted information on measures of intervention fidelity,
including dose, training, and receipt of intervention. (Goyal, 2014) The duration and maximal
hours of structured training in meditation, the amount of home practice recommended,
description of instructor qualifications, and description of participant adherence, if any, were
recorded. (Goyal, 2014) Due to the fact that numerous scales measured negative or positive
affect, we chose scales that were common to the other trials and the most clinically relevant to
make comparisons more meaningful. (Goyal, 2014)
To display the outcome data, they calculated the relative difference in change scores (i.e.
the change from baseline in the treatment group minus the change from baseline in the control
group, divided by the baseline score in the treatment group). (Goyal, 2014) Also, they used the
relative difference in change scores to estimate the direction and approximate magnitude of
effect for all outcomes. (Goyal, 2014) However, a relative difference in change score for six
outcomes owing to incompletely reported data for statistically insignificant findings were unable
to be calculated. (Goyal, 2014) They considered a 5% relative difference in change score to be
potentially clinically significant, since the studies examined short-term interventions and
relatively low doses of meditation. (Goyal, 2014) In total, 18,753 unique citations and 1,651
full-text articles were screened. Of those, forty-seven trails met the necessary criteria to be
included in the meta-analysis.(Goyal, 2014)
Conclusively, this review indicated that meditation programs can, in fact, reduce the
negative dimensions of psychological stress. (Goyal, 2014) In particular, mindfulness meditation
programs were shown to slightly alleviate anxiety, depression, and pain with moderate evidence.
(Goyal, 2014) On the other hand, mantra meditation programs did not improve any of the
outcomes examined, but there was low to insufficient evidence for this claim. (Goyal, 2014) It
was also found that the evidence from some studies did not show any positive effects on
well-being for any meditation program, despite that the main purpose of most meditation
programs is to seek positive health improvement. (Goyal, 2014) Additionally, its relevant to note
that there was no evidence that the meditation programs harmed any individuals. (Goyal, 2014)
Another study conducted by Vidya Anderson in 1999 supported Goyal’s conclusions. They
found that standardized meditation significantly reduced teachers’ perceived stress levels.
(Anderson, 1999)
The ESs were small but significant for some of the individual outcomes and were seen
across a broad range of clinical conditions. (Goyal, 2014) During the course of 2 to 6 months, the
mindfulness meditation program ES estimates ranged from 0.22 to 0.38 for anxiety symptoms
and 0.23 to 0.30 for depressive symptoms. (Goyal, 2014) These small effects are comparable
with what would be expected from the use of an antidepressant in a primary care population but
without the associated toxicities. (Goyal, 2014) These findings are extremely important, as they
could open a window to alternate treatment options for those with depression and other related
mental illnesses. (Goyal, 2014) Overall, the evidence was insufficient to indicate that meditation
programs alter health-related behaviors affected by stress, and low-grade evidence suggested that
meditation programs do not influence weight. (Goyal, 2014) Although uncontrolled studies have
usually found a benefit of meditation, very few controlled studies have found a similar benefit
for the effects of meditation programs on health-related behaviors affected by stress. (Goyal,
2014)
A number of observations provide context to the conclusions. (Goyal, 2014) First, very
few mantra meditation programs met their inclusion criteria. (Goyal, 2014) This significantly
limited their ability to draw inferences regarding the effects of mantra meditation programs on
psychological stress–related outcomes, which did not change when transcendental meditation
were evaluated separately from other mantra training.(Goyal, 2014) Second, differences may
have existed between trials for which the outcomes are a primary vs a secondary focus, although
no evidence of this was found. (Goyal, 2014) The samples included in these trials resembled a
general primary care population, and there may not be room to measure an effect if symptom
levels of the outcomes are low to start with (ie, a floor effect). (Goyal, 2014) This limitation may
explain the null results for mantra meditation programs because 3 transcendental meditation
trials enrolled patients with cardiac disease, whereas only 1 enrolled patients with anxiety.
(Goyal, 2014) Third, the lack of effect on stress-related outcomes may relate to the way the
research community conceptualizes meditation programs, the challenges in acquiring such skills
or meditative states, and the limited duration of RCTs. (Goyal, 2014) Historically, meditation
was not conceptualized as an expedient therapy for health problems. (Goyal, 2014) Meditation
was a skill or state one learned and practiced over time to increase one’s awareness and through
this awareness to gain insight and understanding into the various subtleties of one’s existence.
(Goyal, 2014) Training the mind in awareness, in nonjudgmental states, or in the ability to
become completely free of thoughts or other activity are daunting accomplishments. (Goyal,
2014) The interest in meditation that has grown during the past 30 years in Western cultures
comes from Eastern traditions that emphasize lifelong growth. (Goyal, 2014) The translation of
these traditions into research studies remains challenging. (Goyal, 2014) Long-term trials may be
optimal to examine the effect of meditation on many health outcomes, such as those trials that
have evaluated mortality. (Goyal, 2014) However, many of the studies included in this review
were short term (eg, 2.5 h/wk for 8 weeks), and the participants likely did not achieve a level of
expertise needed to improve outcomes that depend on mastery of mental and emotional
processes. (Goyal, 2014) Finally, none of our conclusions yielded a high strength of-evidence
grade for a positive or null effect. (Goyal, 2014) Thus, further studies in primary care and
disease-specific populations are indicated to address uncertainties caused by inconsistencies in
the body of evidence, deficiencies in power, and risk of bias. (Goyal, 2014)
Each of the studies previously discussed provide critical insight on potential impacts. The
first, most evident potential impact is associated with health and safety. Chronic stress is one of
the most prevalent health disorders, especially within the United States. The conclusions drawn
from each of the sources stress the importance of maintaining low stress levels, and some
identify specific strategies to do so. Utilizing these stress management techniques have the
potential to reduce stress and physical symptoms of stress. Secondly, there are also educational
impacts. Informing the public on stress and how it can be reduced is crucial in maintaining
healthy populations. In addition to health and education, there are also technical impacts. The
results from the studies investigating different forms of stress management can be analyzed and
used to create biomedical technology that could potentially help patients reduce stress in their
everyday lives.
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