The
Neurobiology of Stress and Emotions
By: Emeran A. Mayer, M.D.
UCLA Collaborative Centers for Integrative Medicine, UCLA School of
Medicine, California
We often hear the
term "stress" associated with functional gastrointestinal
(GI) disorders, such as irritable bowel syndrome (IBS). Many patients
experience a worsening of symptoms during times of severely stressful
life events. But what is stress? How often does it occur? How does our
body respond to stress? This article explores the mechanisms that link
stress and emotions to responses that have evolved to ensure survival
and that, in the modern world, affect healthincluding gastrointestinal
function.
Introduction
Stress is an adaptive response that is not unusual or unique to only
certain individuals. In humans and animals, internal mechanisms have
developed throughout evolution, which allow the individual to maximize
their chances of survival when confronted with a stressor. A stressor
in this context is any situation that represents an actual or perceived
threat to the balance (homeostasis) of the organism. In a wide variety
of real, life threatening situations-such as an actual physical assault
or a natural disaster-stress induces a coordinated biological, behavioral,
and psychological response.
In many ways, the
stress response of an organism can be understood in analogy to the response
of a nation confronted with an actual or perceived threat to its stability.
As we are all too familiar, such a threat will result in the activation
of a series of preprogrammed civilian (economic, security) and military
measures, optimizing the chances of the nation to overcome or avoid
the threatening situation. On the one hand, the readiness to quickly
mount such a response is paramount to the long-term survival of the
nation; on the other hand, the longer this response has to be maintained,
the greater the toll will be on other functions of the society. We will
return to this analogy later.
The organism's
stress response often, but not necessarily, includes subjective emotional
feelings like fear and/or anger. However, similar responses can also
be observed in situations that are perceived as threats but which do
not represent actual life-threatening situations, such as public speaking
or the memory of a natural disaster. The associated subjective emotion
associated with such non-life threatening stressors is frequently referred
to as anxiety.
Emotions, stress,
and conscious feelings
One environmental situation that triggers a distinct emotional response
of the body is a real or perceived threat to the organism. The stressor
is the event that triggers this particular response; fear and/or anger
is the emotional feeling that may be associated with the bodily response.
However, stress and fear are not the only emotions that our organism
is programmed to respond to. Emotions are stereotypic patterns of the
body, which are triggered by the central nervous system in response
to distinct external environmental situations or to the recollection
of memories related to such situations. In evolution, the basic mechanisms
generating an emotional response of the body evolved long before the
conscious feeling of emotions evolved in humans and in non-human primates.
The reason for this is simple: Emotional responses are essential for
the survival of all living organisms. For example, the emotion of fear
and/or anger, and the associated fight or flight response is essential
to avoiding harm from an aggressor; the emotion of love (attachment)
is essential for bonding between individuals; the emotion of disgust
may have evolved initially as food aversion to avoid ingestion of harmful
materials.
In these different
situations, the body consistently responds in an automatic, stressor-specific
way, at times without our being aware of the response. Conscious emotional
feelings may or may not be associated when the body responds to a stressful
situation. It is important to realize that the frequently associated
conscious feelings of emotions, such as fear, anger, sadness, disgust,
or love, are not essential to the understanding of the basic biological
mechanisms underlying the emotions. As expressed by Joseph E. LeDoux,
Ph.D., author of The Emotional Brain, in a concise way: From the perspective
of the lover, the conscious feeling of love is the only thing that is
relevant. For the scientist who wants to understand the biological mechanism
underlying the emotion of love, the biological responses of the organism
are the only relevant aspects.
Basic biological
mechanisms by which stressors are translated into distinct bodily responses
Whenever an emotion is triggered, a network of brain regions (traditionally
referred to as the "limbic system") generates a pattern of
stereotypic outputs, which ultimately induce a biological response of
the body. The circuits within the brain that generate the emotional
responses can be referred to as the emotional motor system (EMS). Via
parallel outputs of the autonomic nervous and neuroendocrine systems,
the EMS plays out an emotional response in the "theater of the
body." For example, every human being produces similar facial expressions
associated with specific emotions. Facial expressions of fear, anger,
and sadness are so universal that a primal tribe member living in the
Amazonian jungle has the identical pattern as a broker at the New York
stock exchange. Specific circuits of the emotional motor system have
evolved to both generate this stereotypic emotional facial response,
as well as instantaneously recognize it when it occurs in somebody else.
Other examples of musculoskeletal responses associated with emotions
include tightening of muscles or changes in posture.
Even though most
of us are completely unaware of it, similar stereotypic emotion-specific
responses are also generated within our internal (visceral) organs.
In a stressful situation they include responses such as stimulation
of the cardiovascular system (increased blood pressure, heart rate,
cardiac output) required to prepare the body for the "fight or
flight" response. Of particular relevance for those with a functional
GI disorder like IBS, is the fact that the emotion of fear is associated
with inhibition of upper GI (stomach and duodenum) contractions and
secretions, and with stimulation of lower GI (sigmoid colon and rectum)
motility and secretions. The former may contribute to a sensation of
fullness and lack of appetite, the latter to diarrhea and lower abdominal
pain. This response pattern of the digestive tract may have evolved
in order to minimize the exposure of the small and large intestine to
ingested food and waste material during a time when all energy is shunted
toward the skeletomotor system to maximize success of the fight and
flight response. Interestingly, when the emotion shifts to anger, the
pattern of upper GI activity is reversed, with stimulation of gastric
contractions and acid secretion.
The beneficial
and detrimental effect of the stress response
In addition to elaborate mechanisms that have evolved to activate the
stress response when needed to protect the organism, equally effective
mechanisms have evolved to turn it off immediately when no longer needed,
or to rapidly habituate to repeated occurrences of the same stressor.
Apparently these systems of activation and inactivation of the stress
response, which have evolved over millions of years, have been perfected
to deal with the daily threats to survival for all organisms involved
in the cycle of prey and predators. However, in humans living in modern
societies we are increasingly beginning to realize a phenomenon that
has been referred to as the wear and tear, or the allostatic load, of
stress. This detrimental effect of stress may manifest following a one
time severe stressor (life threatening situation), following repeated
smaller stressors, or following a major sustained stressor over a period
of time.
Let us again take
the example of a nation responding to an acute or perceived threat by
mounting a massive mobilization of civilian and military resources ("fight
response" or "defense reaction"). In the majority of
situations, mounting the response will be sufficient to avoid the potential
damage, and the country can return to its normal civilian function within
a relatively short time. However, if the threat persists, or the response
is maintained over a long period of time, there will be substantial
costs to the society (i.e., allostatic load) such as the channeling
of resources from civilian to military projects, and dealing with psychological
and physical impact of military conflicts.
What is the wear
and tear of severe, repeated, or sustained chronic stress in humans?
The remarkable thing is that in the absence of predisposing "vulnerability"
factors (e.g., genetic factors, adverse early life experiences) or in
the presence of "resilience" factors (e.g., possibly genetic,
strong social support system), a large number of people are remarkably
resilient to this wear and tear of chronic stress. However, in the vulnerable
person, it has frequently severe consequences. For example, the acute
increase in heart rate and blood pressure is an essential response to
optimize the physical strength of a threatened organism, but the chronic
changes developing with persistent increase in cardiovascular function
lead to hypertension and coronary artery disease. An acute increase
in vigilance is important to better recognize an enemy, however persistent
hypervigilance is associated with a variety of common chronic conditions
such as anxiety disorders. Finally, while acute stimulation of the immune
system has a beneficial effect, chronic stress can be associated with
suppression of cellular immunity, and detrimental effects on health.
Men vs. women:
Fight and flight vs. tend and befriend
A problem with research into the biology of stress is that the preponderance
of such research has been conducted in males. Prior to 1995, females
constituted only about 17% of participants in laboratory studies of
physiological and neuroendocrine responses to stress, while in recent
years, the gender bias has somewhat decreased.
Could it be that
the majority of research studies on the stress response apply only to
men, and not to women? In an article, reviewed in May 2000, by the New
York Times, a prominent Professor of Psychology from UCLA, Shelley
Taylor and colleagues, summarized published scientific evidence from
behavioral and biological studies and made a strong argument for differences
in the way male and female animals, and men and women, respond to stressful,
threatening situations. The authors made the following theoretical assumptions
about the evolution of gender-specific stress response patterns:
- Traditionally
and throughout evolution, males have been selected that mount a successful
behavioral response to a threat, which maximizes the survival of self
by either defeating the enemy or overcoming the threat. A similar
evolutionary advantage exists for males that are able to flee from
a superior enemy. However, the same fight and flight response, which
is advantageous for the survival of the male individual, puts defenseless
and unprotected offspring at significantly greater risk of being harmed.
- The fight and
flight response should result in the selection of males that maximizes
biological mechanisms to assure superior fight or flight responses,
such as cardiovascular performance, motor planning, and necessary
neuroendocrine responses, such as activation of the sympathetic nervous
system and the hypothalamic-pituitary-adrenal (HPA) axissystems
essential to self-preservation.
Different considerations
apply to females:
- Compared to
males, females make a greater investment initially in pregnancy and
nursing, and typically play the primary role in bringing offspring
to maturity. Therefore, behavioral responses to threats that were
successfully passed on would have been those that protected offspring
as well as self.
- This maternal
investment should result in selection of female stress responses that
do not jeopardize the health of both the female and her offspring,
and maximize the likelihood that they will survive.
- This response
pattern should favor the development of biological mechanisms that
inhibit the fight and flight response, and shift the individual's
attention to caring and tending to the young (attachment behavior)
and to forming networks of females for the defense of the group.
Men and women:
Biological differences in the stress responses
Based on these considerations, the authors make a convincing argument
that high sympathetic nervous system activation (targeted primarily
at the cardiovascular system, thereby optimizing physical performance),
effective activation of pain inhibition systems (to prevent distraction
of fight and flight performance from injury related pain), and high
cortisol responses (that mitigate the immune response and repress inflammation)
are characteristic biological components of the male stress response.
These responses are related to higher male sex hormone levels.
In contrast, in
females, greater activation of vagal mechanisms (associated with parasympathetic
nervous system "relax and restore" responses and increased
gastrointestinal activation), and greater release of oxytocin (a calming
hormone amplified by estrogen) and endorphins within the brain will
inhibit the underlying fight and flight response, and promote attachment
behavior both to the offspring as well as to other females.
Do these differences
also apply to the non-life threatening stressors of daily life, and
could the differences in biological mechanisms play a role in the well
known fact that men are more likely to die of chronic diseases of the
cardiovascular system (hypertension, coronary artery disease), while
women appear more likely to suffer from a wide range of functional disorders,
such as IBS, fibromyalgia, and interstitial cystitis?
What does this
have to do with IBS
Converging evidence from different laboratories and research groups
are consistent with the concept of an "enhanced stress responsiveness"
as a major vulnerability factor in many IBS patients. As outlined above,
such an enhanced stress responsiveness may not be obvious to the affected
individual, until he or she is exposed to a period of sustained threatening
stress (financial or employment problems, divorce, aftermath of a major
disaster with consequences on daily life), repeated mild to moderate
stressors, or a one time severe (life threatening) type stressor (robbery
or physical assault). Under these circumstances the mechanisms that
normally turn off the stress response are overwhelmed, and attempts
of the nervous system at adaptation or habituation fail. Many of the
vulnerability factors for such enhanced stress responsiveness have been
identified and many of them occur in a particular vulnerable period
of the developing brain (before age 10). Some of the best-studied factors
include loss of the primary care giver, distant mother-child relationship,
emotional neglect, and physical and verbal or sexual abuse.
In order to understand
how a chronically enhanced stress response can produce the cardinal
symptoms of IBS (abdominal pain and discomfort associated with altered
bowel habits) we have to go back to the earlier section on the emotional
motor system: activation of the stress system will stimulate contractions
and secretion in the sigmoid colon and rectum. Depending on the specific
emotional context (fear vs. anger), the upper GI tract will be either
inhibited (fear) or stimulated (anger). In addition, recent research
in animals has demonstrated a phenomenon referred to as stress-induced
visceral hyperalgesia. What this means is that in vulnerable animals,
exposure to an acute moderate stressor will make the colon more sensitive
to distension (and the perception of discomfort or pain).
Why do the symptoms
go away after one stressful situation has resolved and persist in another?
Amongst many factors, anxiety and fear generated by IBSsymptoms themselves
are sufficient in many patients to maintain the stress responsiveness
in a chronically enhanced state. Some of the more common symptom related
anxieties include: Am I close enough to a bathroom when my symptoms
come on? Will I be OK for the rest of the day, unless I completely empty
my colon in the morning before leaving the house?
What can IBS
patients do to guard against the detrimental effects of allostatic load
and enhanced stress responsiveness
Based on our current state of knowledge, little can be done in the affected
patients to reverse vulnerability factors that have been programmed
into our genes or have been hardwired into our nervous system during
the first few years in life. Nevertheless, a variety of cognitive and
behavioral approaches may be useful in protecting ourselves against
the effects of allostatic load, or the wear and tear, of stress. These
include: 1) Developing effective coping styles towards life stress and
IBS symptoms; 2) Learning to activate mechanisms in the body that oppose
the stress response and induce what has been referred to as the "relaxation
response" through various relaxation techniques (e.g., breathing
exercises, progressive relaxation, hypnosis, meditation); and 3) Moderate
but sustained exercise.
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A Simple
Relaxation Technique
Breathing is the only bodily function that, in the normal state,
is fully under automatic control by circuits in the central nervous
system, but which can instantly be switched to conscious control.
This unique property is probably responsible for the fact that
for thousands of years, breathing techniques have been essential
components of meditation techniques and healing practices.[1]
Typically,
our breathing is either shallow and irregular (chest or thoracic
breathing), or deep and regular (abdominal or diaphragmatic).
Shallow chest breathing is often associated with muscle tension
and distress. Deeper abdominal breathing, on the other hand, is
associated with reduced muscle tension and relaxation. There are
many breathing techniques that can be quickly and easily learned.
While initially the positive effects are often subtle, benefits
increase over time. Here is a simple breathing technique to enhance
relaxation and release tension:[2]
- Sit straight
in a comfortable position with your arms and legs uncrossed
- Breathe
in comfortably into your abdomen. (If your are not used to diaphragmatic
breathing, place your palm over your abdomen to feel it rise
and fall with each breath.) Pause briefly before you exhale.
- Each time
your exhale, count silently to yourself, "One
two
three
four."
- Repeat
this cycle, counting your exhalations in sets of four, for five
to ten minutes.
- Notice
your breathing gradually slowing, your body relaxing, and your
mind calming as you practice this breathing technique.
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[1] Mayer E. The
Neurobiology Basis of Mind Body Medicine, IFFGD, 2000.
[2] Davis M, Eshelman E, McKay M. The Relaxation and Stress Reduction
Workbook, MJF Books, 1995.
Source: Reproduced
with permission from the International
Foundation for Functional Gastrointestinal Disorders (IFFGD). Copyright
IFFGD 2001. PO Box 170864, Milwaukee, WI 53217, USA