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R. J. Ryznar et al.
It has long been understood that stress leads to elevated
cortisol levels, and the negative health outcomes from stress
are only due to consistently elevated cortisol. Literature is
now showing that this is most likely an oversimplication.
Losing synchronicity of cortisol levels with the inherent
internal circadian rhythm has many poor health effects, even
if average levels of cortisol are only minimally changed. In
patients with primary hypocortisolism, the current treatment
protocol is to administer steroids three times a day. Although
peak levels of cortisol are achieved in the daytime, with low
levels during sleep hours—the natural anticipatory rise in
cortisol prior to awakening is absent. This shifts cortisol levels away from the natural cycle. These patients report
increased morbidity and mortality from cardiovascular disease, malignancy, and infectious disease. They also often
report fatigue and difculty concentration. These patients are
not exposed to chronically high levels of cortisol, but even
just the disruption in the pulsatile release of cortisol produces symptoms analogous to chronic hypercortisolism.
Synthetic glucocorticoids are one of the most widely used
medications today. More than 75% of patients prescribed
synthetic glucocorticoids report adverse side effects, even at
low doses [1].
The chaotic schedules of trauma teams can affect more
than just cortisol levels related to circadian disturbances.
Sleep itself is an essential process. Sleep plays an important
role in metabolism, immunity, brain function, and cardiovascular health. It is well understood that sub-optimal sleep has
signicant outcomes on health. Optimal sleep is dened by
having sufcient duration, regularity, appropriate timing,
and absence of disturbances. Maintaining all of these criteria
is becoming increasingly difcult for trauma teams.
The downstream effects of sleep disruption include disruption of the circadian rhythm, which has previously been
described to have dramatic implications with uctuating cortisol levels. Additionally, sleep disruption increases the
secretion of catecholamines, ACTH, and cortisol. It causes
upregulation of proinammatory cytokines such as IL-1,
IL-6, and TNF.Sleep disturbance also has dramatic metabolic effects, including decreasing insulin sensitivity and
disrupting the hormonal balance that controls appetite, leading to an increase in hunger. All of these effects cumulatively
lead to a high risk of cardiovascular disease, type 2 diabetes,
obesity, and cancer [12].
The health of trauma teams is obviously of utmost importance, but the safety of patients and overall efcacy of
trauma teams is also hampered by fatigue and sleep disturbance. There are many studies that demonstrate how specic tasks, such as driving or tracking objects, are severely
impaired in sleep-deprived subjects. In individual cases
where fatigue or falling asleep has resulted in a poor patient
outcome, these cases are generally viewed as isolated incidents. Currently, the general consensus within the health-
care industry is that fatigue or sleep deprivation of healthcare
personnel is not associated with harm to patients. The current workplace culture of the healthcare industry, particularly emergency and trauma care, is that long hours and
on-call time are necessary to provide enough exposure to
trainees. Additionally, requiring continuous 24/7 coverage
365days a year often requires long hours for those with the
highest specialized training.
Other industries have been less hesitant to address to the
potential harms of sleep-deprived workers. The aviation
industry has very stringent, federally mandated rules to manage stress of pilots and other crewmembers. Additionally,
when investigating accidents, the National Transportation
Safety Board formally recognizes “fatigue” as a factor or
cause in causing accidents [13]. Historically, aviation has a
phenomenal safety record and is extremely safe for its customers. Further studies are necessary to see if the same strategies would have benecial outcomes if applied to other
elds related to trauma care.
It is clear that increases in overall concentrations of cortisol and other stress response molecules have implications for
human health [1]. Their relation to times of day is also
extremely important—particularly in the context of trauma
teams. Understanding that the impact of stressful events can
be potentiated when they occur outside of daytime hours has
major implications for anyone who works unusual hours.
Additionally, the direct effects of loss or disturbed sleep have
dramatic consequences on the health and performance of
trauma teams. Sleep hygiene, rotating schedules, mandatory
rest/sleep times, and fatigue management may have greater
implications in the health of trauma teams than previously
anticipated.
Recognizing Chronic Versus Acute Stress
A simplified model for understanding how to discriminate between acute and chronic stress on human physiology has been described as “General Adaptation
Syndrome.” This term describes in general, the stressinduced physiologic changes through three separate
stages: the alarm reaction stage, the resistance stage, and
the exhaustion stage. The second two stages of this syndrome represent pathologic changes of prolonged exposure to stress, and it is important to recognize them as
signs that chronic stress may be accumulating so that a
response can be mounted.
The alarm response stage refers to the acute signs and
symptoms in response to a stressor, as well as the “ght-oright” response. After resolution of the initial stressor, the
body lowers catecholamine and cortisol levels, begins repairing any damage, and returns physiologic response to their
resting levels (heart rate, blood pressure, etc.).
12 Biological andPsychological Interactions oftheStress Response: How toBuild Resilient Trauma Teams
77
If the stressor continues to persist, the body’s response
will adapt to better cope with this chronic exposure to stress.
Continued secretion of stress hormones will maintain the
body’s physiological stress mechanisms—this is called the
resistance stage. Poor concentration, frustration, and irritability are common psychological consequences.
If the stressors still continue beyond this stage, the body
will then begin to enter the exhaustion phase. This is where
individuals will experience fatigue, depression, anxiety,
burnout, and reduced tolerance to other stressors.
Hypertension, immunosuppression, metabolic disturbances,
and increased risks of malignancy are some of the physiologic consequences of the exhaustion stage [14].
One of the most effective ways to maintain resilience and
avoid the long-term health consequences of stress can be
avoidance of unnecessary exposure. Understanding the
symptoms of each stage can help individuals recognize when
they are experiencing a pathologic response to a prolonged
stressor, prompting them to evaluate and change their behavior and exposures if necessary.
Psychological Basis fortheHuman Stress
Response
While an understanding of the biological basis for the
human stress response is certainly helpful, perhaps the
most pragmatic lessons on this topic involve an analysis of
the perceived experiences of people in their daily lives,
which can be dened in psychological terms. The number
of yearly articles on the psychology of trauma has increased
exponentially over the last few decades, ramping up from
dozens per year in the 1970s to hundreds and thousands by
2020. Clearly, this is a rising eld of study, and it especially bears relevance in the medical community, which
both treats trauma and is itself frequently a traumatic
occupation.
Trauma andIts Lifelong Impacts: Brain
Changes, Substance Abuse, Chronic Disease
The impact of psychological trauma on a person can begin
very early, with adverse childhood experiences (ACEs) being
correlated with both mental and physical health impacts
[19]. Traumatic experiences in adulthood are also substantial, as professions such as rst responders and trauma
healthcare teams often undergo intensely stressful experiences and not uncommonly develop PTSD [20]. Although
stress can be a valuable factor in human development, traumatic experiences can have lasting psychological and indeed
neurobiological impacts, with pathologic brain morphology
changes of PTSD overlapping with those of traumatic brain
injuries [21].
ACEs have been correlated with decreases in prefrontal
paralimbic gray matter volume (GMV) in the lower ventral,
rostral and dorsolateral prefrontal, and insular cortical areas
[22]. These morphological changes are not mere curiosity. In
particular, the lowered insular GMV has been associated
with a higher frequency of alcohol and cannabis use, which
in turn has their own health consequences and professional
risks [22]. Poor coping skills, such as self-blame, bingeeating, and substance abuse, have also been correlated with
increased burnout [23]. It is easy to see that the combination
of a stressful work environment with poor coping skills creates a vicious cycle, highlighting the need for stress management education and training.
Other consequences of chronic stress include an increased
chronic disease burden. Occupational stress in rst responders has been correlated with cardiovascular disease risk,
including decreased cardiorespiratory tness and sleep quality, as well as increased arterial stiffness [24]. These physical
changes not only represent a risk of acute health events, but
they also can affect work performance, decrease overall
wellness through physical detriments that carry psychological consequences, and create a cycle of health-related stress
and work-related stress that compounds on itself.
Why WeCare: Burnout
Burnout, a state of mental exhaustion, depersonalization, and
decreased sense of personal accomplishment, is common
among trauma team workers and can lead to impaired functioning and reduced happiness [15]. Factors leading to burnout include a physically and emotionally stressful work
environment, risk of personal harm, low pay, and compounding sleep debt [16]. Burnout has been shown to have a negative effect on EMS worker performance and has been
correlated with an increased number of sick days taken by
those workers, as well as greater reported intention to leave
the job [17, 18]. It is clearly a priority of trauma team leaders
to address this issue.
Bias inStudying PTSD: Variable Responses
andStigma
One of the more perplexing phenomena surrounding the
human stress response is that people respond differently to
comparable stressors, that some may develop PTSD while
others apparently undergo only transient disruptions in their
normal functioning [25]. We won’t discuss the cultural, biological, or other sundry variables that lead to those individual
responses because they are far too numerous and do not produce generalizable insight, and besides the risk of PTSD is
high enough to warrant education regardless. However, this
is an apt opportunity to point out that there is likely substantial
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R. J. Ryznar et al.
bias underlying many studies in this area, although the slant
of that bias is difcult to parse out; many people who cope
do not seek treatment and are therefore not observed, and
likewise, many who fail to cope also do not seek treatment or
even exhibit external evidence of distress [26]. Another confounding variable is that there still exists signicant stigma
surrounding mental health, especially among professions
with “cultures of toughness,” such as in police forces, but
also even in professions that are inherently educated in the
biological and psychological ramications of stress, such as
the medical eld, both of which have been shown to have
higher rates of PTSD than the general population [26, 27]. In
these cultures, it may be seen as “weak” to seek help because
the individual is perceived as lacking self- sufciency. That
pervasive stigma is a primary reason why people who could
benet from mental health aid do not seek it, why it may go
underreported even in anonymous surveys, and, practically
speaking, why mental health education is so imperative.
Education Helps
It has been demonstrated that people with higher levels of
education on mental illness, such as psychiatrists in comparison to medical students or non-healthcare workers, exhibit
less mental health stigma and improved self-care [28]. This
is why professional education on the human stress response
and how to manage it are important, especially in the setting
of stressful occupations: people who are more aware of mental health issues are empowered to take action or seek help
by volition of that awareness. People with mental health education are also less likely to contribute to cultural stigma
against seeking help, thereby affording others more chance
to do so.
Practical Strategies forAlleviating Stress
Education is only one piece of the puzzle. Emerging research
suggests that there are many practical strategies that can be
employed in order to mitigate the effects of a stressful occupation and augment resilience in team members. Those strategies include individual approaches such as mindfulness,
emotional regulation, and communication skills training; team
approaches such as resiliency training and stress management
workshops; as well as structural/organizational methods such
as workload/schedule rotations, debrieng sessions, and focus
groups [29]. Although genetics apparently do play a role in
determining one’s resilience, with some people being
extremely predisposed to either developing PTSD or being
hyper-resilient, these strategies have been shown to be effective for those in the window of opportunity that lies between
those extremes [30]. These proven effective strategies have a
wide range of benets that may be tailored into approaches to
suit team and individual goals (Table12.1). The most recent
literature reviews suggest that a bundled, multifaceted
approached is best for achieving optimal results [29].
Mindfulness and mind-body practices, which train the
individual to be cognizant of their physical and emotional
states to better control those states, have been shown to
have positive effects on PTSD symptoms, such as anxiety,
depression, and intrusive memories [31]. Yoga, for example, has been highly studied, and implementing even a
single session per week has been shown to reduce subjective stress and anxiety [32]. Improvements from yoga and
mindfulness training have been shown to improve regulation of the sympathetic nervous system and the HPA axis,
demonstrating improvements in physiological parameters
such as blood pressure, heart rate, cortisol, and cytokine
levels [33].
Table 12.1 Coping strategies and notable effects
Coping strategies Effect
Mindfulness, mind-body practices Decreased anxiety and depression
Fewer intrusive memories
Yoga Decreased subjective stress and anxiety
Improved SNS and HPA axis regulation
General self-care (sleep, diet, exercise, social/spiritual activities) Decreased burnout
Particular benet for newer team members
Reinforcement/reminders of coping strategies Improved adherence to strategies
Improved cooperation
Decreased workplace stigma
Stress management workshops Decreased burnout
Debrieng sessions Improved resiliency
Reduced compassion fatigue
Fewer symptoms of PTSD
Shifts <12hours, working <40hours per week Fewer adverse events
Fixed night shifts Synchronization, improved performance
Decreased job satisfaction
Higher burnout rates
Note that not all effects are entirely positive
12 Biological andPsychological Interactions oftheStress Response: How toBuild Resilient Trauma Teams
79
Self-care strategies, such as improving sleep hygiene,
focusing on physical, spiritual, and social wellness, have
demonstrated benets particularly inexperienced trauma
team members [34]. Coping styles that emphasize social
integration and spiritual engagement, as well as specic
strategies such as art therapy, have been correlated with
decreased burnout rates [23, 35]. However, it is important for
team leaders and members to appreciate that being informed
on these strategies is not always ample for individuals to
actually carry out these tasks, which admittedly can seem
like additional work. It is therefore important to nd ways to
reinforce the importance of self-care on a regular basis, such
as posting signs, encouraging healthy snacks, building a culture of support and civility, and organizing healthy group
activities [36].
Team activities, such as stress management workshops,
have also been proven effective, having been shown to
decrease burnout measures in the medical eld [37].
Debrieng sessions have also demonstrated efcacy, such as
in improving resiliency and reducing compassion fatigue
among emergency department staff [38]. While medical
teams always strive to provide optimal care, mistakes do
happen and result in not only patient harm, but also harm to
care providers who are sometimes termed “second victims”
of medical error [39]. In the setting of adverse events, Critical
Incident Stress Debrieng (CISD) has been shown to reduce
the risk of PTSD-like symptoms in emergency service personnel, although some reviews of the literature also demonstrate uncertainty this area [40, 41].
Structural strategies, such as organizing shift schedules to
prevent burnout, are also important to consider. A 2016 literature review found that, although there is signicant complexity in studying the effects of shift work, employees
working shifts longer than 12hours, working over 40hours
per week, and overly limiting break times are associated with
adverse events [42]. Interestingly, an analysis of whether or
not to implement rotating shifts does not provide clear recommendations; not surprisingly, working xed night shifts
results in lower job satisfaction, but working xed night
shifts also enables resynchronization to a sleep schedule,
meaning it is up to leaders to appraise their team’s situation
and enact policy accordingly [42]. A 2017 review also found
it difcult to make a conclusion on the impact of shift work
due to multiple contextual and individual factors, but sufce
to say that other studies have shown that shift irregularity and
more frequent night shifts are correlated with higher burnout
rates [43, 44].
With the realm of stress reduction being so complex, it is
perhaps pertinent for teams and individuals to focus on only
the most efcacious strategies with the highest amount of
empirical evidence, while promoting an overall culture of
valuing wellness. Fortunately, modern research techniques
are becoming more and more suited to facilitating that goal.
Hyper-realistic Simulation Training
The eld of self-care is vast and expanding with each year,
but it is not always as efcient as would be suited to a professional environment. There are many pseudoscientic and
even fantastical frameworks for self-care, some that may
warrant expedient dismissal while others should be viewed
with skeptical optimism. While most frameworks are anecdotally helpful to at least some individuals, when efciency
is a priority, they can actually represent a distraction from the
pursuit of an effective strategy. With that in mind, one of the
most promising methods for optimizing the psychological
response to stressful scenarios is hyper-realistic simulation
training. Simulation training has been shown to not only
improve the subjective experience of individuals as well as
physiologic, biochemical, and epigenetic parameters, but
also to improve the quality of care during actual situations,
including in the trauma team setting specically [45].
The concept behind simulation training relies on an
understanding of Inverted U Theory, which postulates that
optimal performance is attained when there is a balance
between pressure and stress. Pressure can be viewed as a
positive motivator, whereas stress is translated into performance decits. A person who has too little pressure to perform is unmotivated, but a person who has too much stress
often experiences a decrease in performance. Stress can
present as distracting thoughts, such as being worried about
failure, or physical barriers to functioning, such as lack of
sleep. Based on the evidence previously discussed that rst
responders and trauma teams have an abundance of stress,
the goal of simulation training should be to acclimate team
members to stressful scenarios so that real experiences are
less intense. This allows team members to interpret situations more in terms of positive pressure and less in terms of
negative stress on a cognitive level, and we can see the efcacy of simulation training by measuring biochemical markers of stress.
Development ofaStress Measurement Tool
One of the most difcult aspects of studying stress and creating mitigating strategies is the development of an accurate
and precise screening tool for stress. Historically, these
screening tools have been questionnaires that query an individual about their subjective experience in an effort to obtain
quantiable data. Although these tools have been validated
clinically, the survey strategy presents several confounding
variables.
One issue is the limitation of language; the meaning of
words can be interpreted differently by different cultures, by
different people within a culture, and even by the same people at different times. Finding effective ways to communi-
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R. J. Ryznar et al.
cate is particularly difcult for surveys of feelings, and even
more so when those feelings involve levels of conscious and
unconscious understanding, such as they do in the setting of
trauma.
Another issue is, again, stigma. People that live in a society or cultural niche where mental health is stigmatized may
be hesitant to provide honest answers to questions about
their own mental health. It is often benecial to have mental
health professionals administer surveys, which allows the
use of counseling strategies to get more accurate information. Although clinically useful, that method also introduces
a whole new level of bias.
One of the tools we have currently is the Brief Resilience
Scale (BRS), which measures “resilience” and is a relatively
strong predictor of mental health quality in the setting of
traumatic experiences [46]. The BRS can help predict the
effect of traumatic experiences such as ACEs on mental
health, thereby allowing clinicians to make informed decisions on prognosis and treatment [47]. Another common tool
that is popular in the primary care setting and which has been
widely validated is the PHQ-9, a 9-item survey that straties
patients into mild, moderate, and severe depression categories [48]. But even though tools like the BRS and PHQ-9
offer substantial clinical utility, there is still a clear impetus
for more quantiable and generalizable tools.
The next section will introduce new and upcoming
research into biological markers of stress and mind wellness,
or the ability to respond to stress. These methods are arguably more objective than survey screening tools and may
serve as a bridge to further validate those methods as well as
to explore new directions for research.
We know that HPA activity is quite individualized, resulting in cortisol levels and reactivity to stress that is highly
variable depending upon the person. In order to avoid burnout or other disorders related to chronic stress, cortisol levels
and stress reactivity must be regulated. Individuals with
major depression, baseline cortisol concentrations appear to
be increased; whereas, for bipolar disorder, cortisol concentrations are only increased in patients with a late age-ofonset. On the contrary, in patients with anxiety (generalized
anxiety disorder, panic disorder), cortisol levels are decreased
compared to healthy individuals. The same has been reported
for posttraumatic stress disorder and individuals who have
attempted suicide, where after an initial increase in cortisol
release, the cortisol output decreases below baseline [57].
Both exaggerated/high and blunted/low stress reactivity of
the HPA axis at baseline has been shown to correlate with
mental health and disease outcomes. Interestingly, exaggerated stress reactivity at baseline predicted an increase in risk
factors for cardiovascular disease and decreased telomere
length at follow-up. In contrast, blunted stress reactivity predicted future increased adiposity and obesity, more depression, anxiety and PTSD symptoms, greater illness frequency,
musculoskeletal pain and regulatory T-cell percentage,
poorer cognitive ability, poorer self-reported health, and
physical disability and lower bone mass [58]. Additionally, a
pro-inammatory state has been observed across many mental health disorders, including PTSD and individuals attempting suicide, including an increase in IL6 levels [59].
Altogether, it is clear that an imbalance in the concentration
and reactivity of molecules that regulate the stress response
is a hallmark of low resilience and poor coping. What can be
done for individuals who struggle with low resilience?
Resilience Is Individualized
Resilience is a key factor in determining the success of any
trauma team dynamic. Resilience refers to the ability to
bounce back, biologically and psychologically. This requires
a combination of strong body and mind. For a trauma team to
be resilient, the requirements are two-fold. Each individual
member of the team must have developed resilience, and the
team functioning in response to trauma must be resilient.
Optimal team performance would fall under the optimum
stress peak of the inverted U model of stress [54]. We are
relying on individuals who have built their own resilience to
stressful events by developing appropriate coping mechanisms and maintaining mental, emotional, physical health,
and avoiding chronic social defeat and chronic substance
abuse [49]. Resilience is critical for establishing a highly
functional team that can handle stress appropriately without
medical errors. The following sections highlight valuable
points of understanding and improving resilience in a highstress environment.
Factors Contributing toResilient Phenotypes
What determines an individual’s resilience? Complex interactions between an individual’s gene variants, his or her particular history of exposure to environmental stressors and an
array of epigenetic changes that result in variable gene expression patterns, determine the degree of adaptability to novel
challenges. The combination of genetics and epigenetics
determines the function of the neural circuitry involved in
stress responses whether they are acute, chronic, novel, or not
(Fig.12.2). Allelic variants in the following genes have been
most tightly connected to resilient phenotypes: FKP5 (regulator of glucocorticoid sensitivity), CRHR1 (corticotropin
releasing hormone receptor 1), SLC6A4 (human serotonin
transporter), COMBT (regulator of dopamine and noradrenaline), NPY (Neuropeptide Y), and BDNF (brain-derived neurotrophic factor) [68]. Recent studies have begun to yield
evidence of gene-gene and gene- environment interactions
determining individual in stress responses. For example,
12 Biological andPsychological Interactions oftheStress Response: How toBuild Resilient Trauma Teams
Fig. 12.2 Factors
contributing to individualized
resilience phenotypes. A
combination of genetics,
epigenetics, and environment
all interplay to determine an
individual’s ability to cope
with stress. (Figure made with
BioRender)
81
interactions between 5-HTTLPR (region of SLC6A4),
COMBT, and traumatic life events have been shown to affect
the risk for depression and emotional reactivity to stressful
stimuli. An additional example of gene-environment interactions determining resilience would be the observation that
social support seems to mitigate the effects of the short allele
of 5-HTTLPR, and the 5-HTTLPR and higher risk BDNF
genotypes interact with stressful life events to result in higher
risk for depression [67]. Lastly and most importantly, epigenetics contributes to individual resilience. Epigenetics
refers to inheritance of biochemical information that is not
encoded in the DNA sequence. This biochemical information
in the form of modications to histone tails and methylation
to DNA causes stable changes in chromatin structure that
underlies long- lasting alterations in gene expression. An
additional form of an epigenetic mark includes non-coding
RNA.Non-coding RNA typically functions to regulate gene
expression though inhibition of mRNA translation, rather
than altering chromatin structure directly. Genes that seem to
be epigenetically modied in response to and regulating coping to traumatic stress fall under categories of players in the
neural, endocrine, and immune pathways [68].
Epigenetic changes in genes regulating the HPA axis, specically FKPB5 and NR3C1, are correlated with resilient
phenotypes [79]. Key to note here is that the epigenome is
different according to cell type and tissue, but studies are
nding that alterations in the periphery can be indicative of
epigenetic CNS dysregulation [67]. Studies have shown that
DNA methylation of FKBP5 and NR3C1in lymphocytes has
been measured as predictors of psychotherapy outcome in
combat veterans with PTSD.Results showed that increased
NR3C1 DNA methylation measured pre-treatment did predict positive treatment outcome, although DNA methylation
itself was not altered between pre- and post- treatment. On
the other hand, FKBP5 DNA methylation pre-treatment did
not predict treatment outcome but did decrease among those
who responded to therapy. Among treatment-responders,
FKBP5 mRNA expression was elevated, compared to nonresponders. Also, as measured in peripheral blood, mononuclear cells in combat veterans with PTSD compared to
combat veterans without PTSD.Methylation patterns at this
location were also associated with three measures of functional GC activity. Results highlight that decreased NR3C1
methylation could either confer risk of PTSD development
or be a result of PTSD development, and that epigenetic
alteration of NR3C1 could functionally alter neuroendocrine
system outputs [69, 70]. Both of these genes code for proteins that are key players in the stress response, so it is not
surprising they are linked with susceptibility or protection to
stress-related disorders.
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R. J. Ryznar et al.
Epigenetic variability contributing to resilience has also
been detected in genes regulating the immune system.
Activity of the HPA axis can result in changes to immune
system components and overall inammation. As mentioned
in our earlier section of this chapter, glucocorticoids can
serve an anti-inammatory role and determine immune system responses in addition to regulating expression of various
cytokines. These cytokines, in turn, can regulate functions of
the central nervous system. A genome wide scale investigating epigenetic changes in peripheral blood cells of trauma
exposed versus controls showed changes in genes regulating
T-cell activation and immune networks [69]. Follow-up studies found differences in methylation patterns of IL6, IL8,
IL17, IL18, and IFN-gamma based on traumatic stress exposure [70]. An additional study found differential DNA methylation in the IL-2A gene of highly traumatized individuals
[71]. Lastly, miRNA expression of transcripts targeting
immune system genes was observed to be dysregulated in
individuals diagnosed with PTSD [72]. Overall, it is clear
that epigenetic regulation of genes functioning in the immune
system play a role in individual resilience patterns.
Variability of gene expression in the central nervous system undoubtedly contributes to individual resilient phenotypes. The challenge here is that unlike with the HPA and
immune system networks where you can more accurately
detect associated changes in related genes within the periphery, to denitively make conclusions about epigenetic
brain tissue. This is not a trivial task unless samples are collected post-mortem. Nevertheless, research investigations
looking at epigenetic changes of CNS function related genes
in the blood cells have been conducted and provide some
insight into individual stress coping and resilience. One
study has found that variable genotypes of the COMT gene
correlate with methylation patterns and fear responses. More
specically, the MET/MET genotype of COMT showed an
increase in promoter DNA methylation and also increased
fear expression [73]. Additionally, a large-scale study analyzing epigenomes of rst responders at the World Trade
Center disaster, implicated differential methylation in genes
associated with synaptic plasticity, oxytocin signaling, cholinergic synapse and inammatory disease pathways.
Biological andPsychological Resilience
Dynamics
Though both biological and psychological resiliencies are
similarly dened as the “ability to bounce back,” decline in
the biological resilience with age could possibly coincide
with the improvement in the psychological resilience in the
same individuals. An accumulation of experienced trauma
and chronic stress over time has been shown to speed up the
aging process [78]. Even without experiencing trauma, resilience has been shown to decline with age. Specically, there
is a loss of resilience of neural architecture with aging, or a
reduction in neuroplastic adaptation to stressful stimuli [75].
Other aging components that contribute to the decline in
aging include depletion of body reserves with age such as
HSCs (hematopoietic stem cells) losing the ability to selfrenew and regenerate, slowdown of physiological processes
and responses with age, and dysfunction and breakdown of
cell repair and tissue cleaning, increasing allostatic load
[76]. Fortunately, both trauma-induced aging and observed
reduction in resilience as we age can be re-directed or even
reversed with appropriate lifestyle choices and pharmacological interventions. Proposed practical anti-aging interventions to help reduce the rate of aging components and
maintain or even improve resilience over time include caloric
restriction and physical exercise. For example, BDNF may
be a key feature of the depressive state, and elevation of
BDNF by diverse treatments ranging from antidepressant
drugs to regular physical activity may be a central feature of
maintaining resilience over time. Some of the more cuttingedge techniques to slow down [80, 81] include stem cell
therapy, mitochondrial transplantation, and a broad array of
pharmacological interventions [76].
The beauty of epigenetics playing a major role in determination of resilience is the fact that it is dynamic. Individuals
who are programmed epigenetically to have low resilience
can be reprogrammed to have improved resilience. In some
cases where genetically individuals may be at high risk for
dysregulation of stress reactivity, epigenetics can help to
bring the system back to balance. According to multiple
studies conducted with animals and humans, it has been
shown that there is a “window of epigenetic plasticity,” or a
duration of time during which appropriate lifestyle and occupational training can improve resilience, especially in individuals who are more genetically susceptible to negative
effects of stress.
Many studies have provided insight into trends in stress
responsiveness that can be used to predict susceptibility to
poor stress coping skills and low resilience following future
trauma. Tests are designed to measure HPA axis activity,
such as cortisol, CRF, or ACTH.As mentioned in a previous
section of this chapter, cortisol secretion follows along a circadian rhythm, and this rhythm has been found to change in
patients experiencing stress. As a result, ACR (awakening
cortisol response) can be used as a litmus test for both physiological and psychological wellness. Additionally, HPA axis
or cortisol reactivity can also be utilized as an indicator of
stress coping. Cortisol reactivity can be determined either
pharmacologically, by exposure to real-life stressful events,
or experimentally designed stressful events.
The Trier Social Stress Test (TSST) is an example of an
experimentally designed tool to stimulate a cortisol stress
12 Biological andPsychological Interactions oftheStress Response: How toBuild Resilient Trauma Teams
83
response [77]. Studies have shown that salivary cortisol levels after the TSST show a two to threefold increase in cortisol levels above baseline within a half hour. Cortisol levels
can also be analyzed during hyper-realistic stress inoculation
trainings to determine HPA axis reactivity [55]. In addition
to cortisol, alpha-amylase has been described as a potential
indicator of stress coping through noradrenergic activity and
has also been assessed in hyper-realistic stress inoculation
trainings [55]. Stress inoculation trainings have shown that
stress conditioning is pretty uniform for the sympathetic nervous system, but cortisol reactivity can be stratied into high
or low responders, indicating variable stress coping responses
[64]. A prospective study conducted with police academy
cadets to correlate startle responses to PTSD found that
hypersensitivity to contextual threat (indexed by greater fear
under low threat), elevated sympathetic nervous system reactivity to explicit threat (indexed by larger responses under
high threat), and failure to adapt to repeated aversive stimuli
(evidenced by slower habituation) are all unique preexisting
vulnerability factors for greater PTSD symptom severity following traumatic stress exposure [66]. Measuring biomarkers indicative of HPA axis or sympathetic activity can provide
insight into an individual’s stress coping capacity.
Training Is Key
Since stress has been shown to compromise cognitive skills
and patient outcomes [63], it is imperative to develop mechanisms for stress conditioning for trauma teams in order to
maintain optimal team performance for patients. Trauma
team stress inoculation training has been shown to reduce
some of these biomarkers associated with low resilience,
therefore also lowering probability of development trauma
related disorders [51–53]. Multiple medical teams are currently exploring various stress simulations to aid in resilience
development [56], including exploring virtual reality immersive simulators [57, 58], emotional excitation simulation
[59], and debrieng/communication. Simulation-based
training has been found to stimulate cortisol production during stress inoculation training with clinicians [61] and medical students [59, 60] immersed in a hyper-realistic simulation
for emergency medical procedures. Interestingly, the hyperrealistic stress training improved self-perception and stress
management categories according to results from the EQi-
2.0 model of emotional intelligence [62]. Psychological
debrieng and positive communication have also shown to
reduce stress for individual’s teams experiencing trauma. For
example, psychiatric morbidity was studied in 106 British
soldiers returning from UN peacekeeping duties in the former Republic of Yugoslavia. The group of 106 soldiers
received an Operational Stress Training Package prior to
their deployment and a randomly selected group also
received a post-operational PD.Results show that very low
rates of PTSD and other psychopathology were found overall, and the Operational Stress Training Package may have
contributed to this. CAGE scores (used to determine substance abuse) diminished signicantly in the debriefed group
by the end of the follow-up period suggesting that PD may
have been of benet despite the apparent absence of PTSD
[50]. Additionally, effect of positive communication during
medical handover with anesthesia teams on the subsequent
team-based clinical performance in a simulated critical situation has been to decrease the stress response and improve
clinical performance [65].
Future ofResilience Building
Newly conducted studies with military medical students at
Rocky Vista University and, subsequently, rst responders in
the re academy at South Metro Fire Rescue in Colorado to
study the stress response and resilience of participating individuals are opening a window to the future of resilience
screening. Resilience was assessed by measuring levels of
cytokines and steroid hormones from reghters engaging in
re academy training and comparing those biomarker levels
to LEC-5 Life Events Checklist results, resilience scores as
determined by the Hardiness Resilience Gauge (HRG) questionnaire, and previous occupational experience in high- stress
jobs such as military, EMS, or law enforcement. Results suggested that immune biomarkers and steroid- thyroid hormones
correlate with the stress response, resilience scores, and life
trauma. More specically, our preliminary results show that
salivary Fgf2 levels may be predictive for cortisol reactivity
to stress. Additionally, we were able to show that Fgf2 levels
increase following a stressful event. Together, these lead us to
conclude that Fgf2 levels exhibited a negative correlation to
the cortisol stress response, indicating that Fgf2 is neuroprotective and may represent a novel marker for resilience and
stress coping. Finally, analyzing multiple cytokines associated with severity of life trauma experienced by an individual
based on a comparison of their LEC-5 results to cytokine levels captured from that same study subject experiencing physical and psychological stress revealed that levels of Fgf2, IL-6,
GCSF, and IL-18 correlate with severity of life trauma experienced by the study participants. Ultimately, our preliminary
studies have shown that a multitude of immune biomarkers
and hormones detected in saliva correlate with the stress
response and traumatic life events linked to PTSD and resiliency measures. It is possible from these results to develop a
liquid biopsy-screening test to determine risk for poor stress
coping and low resilience.
In the future, we will be able to more accurately monitor
an individual for stress coping and resilience by combining
information from self-reported measures, vital sign and
84
demographic data, psychosocial, stress reactivity, genomics,
proteomics, transcriptomics, metabolomics, and epigenetics
to apply more of a comprehensive systems approach to diagnosis and treatment of stress-induced disorders. For example, groups are already working on development and
validation of an algorithm for prediction of post-traumatic
stress disorder with promising results. Results demonstrate
externally validated accuracy to discriminate PTSD risk with
high precision [74]. In this study, investigators combined
measures of vetted mental health screening questionnaires,
psychophysiological stress response, threat perception, psychophysiological arousal, immune and inammatory markers, and psychosocial determinants [74]. More variables to
consider here would be brain imaging, both structural and
functional MRI, in response to stressful stimuli, with tissuespecic epigenetic data and biomarker levels, in addition to
the above-mentioned components. In the future, we will also
be able to more accurately determine which stress inoculation or stress simulation tests are the most valuable, by continuing to monitor individuals engaged in these training
sessions for stress biomarkers, stress reactivity, and follow up for mental health related disorders. This will allow development and optimization of the best training curriculum. In
the meantime, members of trauma teams must stay committed to staying educated how to best and make sure to build
their own individual resilience.
Key Points
• The human response to stress is a homeostatic
mechanism allowing adaptation to environmental
stressors, involving multiple organ systems and
being both adaptive and maladaptive.
• Acute stress involves an immediate, coordinated
body response via the SNS and HPA axis, while
chronic stress results from prolonged exposure,
leading to dysregulation and health issues.
• The SNS, known for the “ght-or-ight” response,
releases catecholamines (norepinephrine, epinephrine) to promote survival in stressful situations.
• The HPA axis releases cortisol in response to stress,
regulating metabolism, immune responses, and
maintaining homeostasis.
• The cardiovascular response to stress includes
increased heart rate, blood pressure, and blood glucose levels, with chronic stress contributing to cardiovascular diseases.
• Acute stress enhances humoral immunity while
suppressing cellular immunity, whereas chronic
stress leads to immunosuppression and increased
risk of infection and disease.
R. J. Ryznar et al.
• HRV serves as an indicator of autonomic nervous
system balance, with low HRV linked to poor health
outcomes and increased mortality.
• Psychological stress can mimic physiological stress
responses, with the limbic system, especially the
amygdala, playing a key role in emotional and
stress responses.
• Trauma can lead to long-term psychological and
neurobiological changes, with PTSD and burnout
being common in high-stress professions like
trauma care.
• ACEs are linked to long-term health and psychological issues, with early trauma affecting brain
morphology and increasing the risk of substance
abuse.
• Resilience training and stress management workshops are effective, with mindfulness, yoga, and
other self-care practices improving stress response
and resilience.
• Hyper-realistic simulation training improves physiological and psychological responses to stress,
helping trauma teams perform better in real-life
stressful situations.
• Genetic and epigenetic factors inuence individual
stress response and resilience, with epigenetic
changes being targeted for improving resilience.
• Measuring cortisol, cytokines, and other biomarkers helps assess stress and resilience, guiding personalized interventions for stress management.
• Disruption of circadian rhythms exacerbates the
effects of stress, making the maintenance of proper
sleep hygiene crucial for health and performance.
• Practical strategies for alleviating stress include
individual approaches like mindfulness, emotional
regulation, and communication skills training; team
approaches such as resiliency training and stress
management workshops; and organizational methods like workload and schedule rotations, debriefing sessions, and focus groups.
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