Background: Yawning consistently
poses a conundrum to the medical profession and
neuroscientists. Despite neurological evidence
such as parakinesia brachialis oscitans in
stroke patients and thermo-irregulation in
multiple sclerosis patients, there is
considerable debate over the reasons for yawning
with the mechanisms and hormonal pathways still
not fully understood. Cortisol is implicated
during yawning and may link many neurological
disorders. Evidence was found in support of the
Thompson cortisol hypothesis that proposes
cortisol levels are elevated during yawning just
as they tend to rise during stress and
fatigue.
Objectives: To investigate whether
saliva cortisol levels rise during yawning and,
therefore, support the Thompson cortisol
hypothesis.
Methods: We exposed 20 male and
female volunteers aged between 18 and 53 years
to conditions that provoked a yawning response
in a randomized controlled trial. Saliva samples
were collected at the start and again after the
yawning response, or at the end of the stimuli
presentations if the participant did not yawn.
In addition, we collected electromyographic data
of the jaw muscles to determine rest and yawning
phases of neural activity. Yawning
susceptibility scale, Hospital Anxiety and
Depression Scale, General Health Questionnaire,
and demographic and health details were also
collected from each participant. A comprehensive
data set allowed comparison between yawners and
nonyawners, as well as between rest and yawning
phases. Collecting electromyographic data from
the yawning phase is novel, and we hope this
will provide new information about neuromuscular
activity related to cortisol levels. Exclusion
criteria included chronic fatigue, diabetes,
fibromyalgia, heart conditions, high blood
pressure, hormone replacement therapy, multiple
sclerosis, and stroke. We compared data between
and within participants.
Results: In the yawning group, there
was a significant difference between saliva
cortisol samples (t10 = &endash;3.071, P = .01).
Power and effect size were computed based on
repeated-measures t tests for both the yawning
and nonyawning groups. There was a medium effect
size for the nonyawners group (r = .467) but low
power (36%). Results were similar for the
yawners group: medium effect size (r = .440) and
low power (33%).
Conclusions: There was significant
evidence in support of the Thompson cortisol
hypothesis that suggests cortisol levels are
elevated during yawning. A further longitudinal
study is planned to test neurological patients.
We intend to devise a diagnostic tool based on
changes in cortisol levels that may assist in
the early diagnosis of neurological disorders
based on the data collected.
-Thompson
SBN. The dawn of the yawn: is yawning a
warning? linking neurological disorders. Medical
Hypotheses 2010;75(6):630-633
-Thompson
SBN. Born to yawn? Cortisol linked to
yawning: A new hypothesis. Medical Hypotheses
2011;77(5):861-862
-Thompson
SB. Is Yawning A Warning, Neurologically?
12-2011. http://www.webmedcentral.com
Introduction
Yawning consistently poses a conundrum to
neurologists and neuroscientists [1].
Increasingly, evidence is found to link
neurological disorders through the commonality
of yawning episodes and contagious yawning.
Despite discrete incidences (such as parakinesia
brachialis oscitans) in brain stem ischemic
stroke patients, there is considerable debate
over the reasons for yawning, with the mechanism
of yawning still not fully understood
[2]. Cortisol is implicated during
yawning and may link many neurological
disorders. Evidence was found in support of the
Thompson cortisol hypothesis [3,4] that
proposes cortisol levels are elevated during
yawning just as cortisol levels are known to be
raised in instances of stress and fatigue
[5].
There have been several explanations about
the yawning mechanism. Yawning is a
physiological behavior that has been described
as a transition between wakefulness and sleep
[6]. According to Walusinski
[7], yawns exteriorize the activity of
the motor centers of the brain stem (cranial
nerves V, VII, IX, X, XI, and XII) and of the
spinal cord under the control of the
hypothalamic paraventricular nucleus. The
hypothalamic paraventricular nucleus is a point
of integration between the central and
peripheral autonomic systems. Walusinski
[7] comprehensively presents several
disorders due to deregulation of yawning:
anhedonia (frustration because of an
incomplete or inharmonious development of a yawn
possibly due to unconscious inhibition of the
letting go that underlies a complete yawn)
the disappearance of a yawn (indicating the
activity state of the dopaminergic neurons of
the hypothalamic paraventricular nucleus, which
are necessary for yawning)
excessive yawning (possibly linked to hunger
and arousal) and famously illustrated in
Charcot's Leçons du Mardi de la
Salpêtrière [8] by his
patient who yawned eight times in a minute.
Yawning is a powerful reflex that may serve
to evacuate the palatine tonsillar fossae
[9]. This is a possible explanation
because the strong reflex does not have any
immediate urgency, is reflected in our circadian
rhythm, and is allocated to times that cause us
minimal inconvenience. However, McKenzie
[9] suggests that, due to our social
sanctions in the Western world to generally
suppress the yawning reflex, perhaps we are
leading to endemic tonsillitis.
Spontaneous yawning is present in humans
from the early stages of development
[10]. It has been observed in infants
and newborns and in fetuses of 12- to 14-weeks'
gestational age. The time course of yawning
seems to differ with age [6], with
adults yawning in the early morning and late
evening [11]; in young adults, yawning
seems to be linked to a low level of vigilance,
increasing before and after the sleep episode
[12]. Yawning is also contagious and can
be elicited by seeing or even hearing someone
else yawn [13]. Yet yawning has also
been observed in other species [14,15],
which has led to suggestions that yawning may
serve communicative as well as physiological
functions.
Some authors do believe that the
physiological explanations given by some
researchers do not adequately explain the
reasons why we yawn. For example, Guggisberg and
colleagues [16] argue that research
tends to support yawning as a communicative
function. Gallup [17] suggests it is
likely that there is not just one theory to
explain the functions of yawning, and it is
unlikely that yawning serves primarily as a
communicative function, since experimental
evidence of contagious yawning is observed in
only a small number of species in one lineage
(primates). We tend to agree with this notion
and believe the evidence of yawning in patients
with neurological disorders and stroke (such as
parakinesia brachialis oscitans) tends to
suggest that there are specific mechanisms for
yawning that are excited under special
circumstances. However, it is acknowledged that
yawning may be elicited because of empathy in
Homo sapiens [18,19].
The debate for clarity continues
[20]. Some authors argue that
physiological explanations are imprecise and
that there is evidence that neural networks
responsible for empathy and social skills may be
implicated and activated during the yawning
episode. There is a problem with comparing some
studies due to methodological differences and
inadequacies [21].
However, evidence from neurological patients
has led to a new line of enquiry that focuses on
thermoregulation. Corey and colleagues
[22] examined physiological measurements
taken before, during, and after yawns in humans.
They concluded their data are most consistent
with the brain-cooling hypothesis and advocate
that yawning increases blood flow. Indeed, it is
known that painful headaches [23] and
thermoregulatory disorders [24] may
arise from excessive yawning. Corey and
colleagues [22] suggest that the yawning
experienced during these times may be due to
circulatory dysfunction.
Gallup and Gallup [25] reported on
repetitive yawning in patients with multiple
sclerosis, showing that thermoregulatory
dysfunction is a symptom of multiple sclerosis.
Furthermore, yawning seems to provide symptom
relief in patients with multiple sclerosis.
Gallup and Eldakar [26] also showed that
the incidence of yawning in humans is associated
with seasonal climate variation.
Researchers are constantly striving to find
commonality in disorders via their metabolic or
neuronal pathways. It is interesting to note in
past years how the treatment of Parkinson
disease could be modified because of the
exploration of dopaminergic and serotonic
pathways [1,27,28]. Uncertainty in the
functions of some neurotransmitters and their
possible multiple implications in chemical
pathways presents a complicated picture that is
not unlike the clinical signature of Alzheimer
disease in those with comorbid Down syndrome
[29]. Having Alzheimer disease together
with Down syndrome does not necessarily result
in the clinical symptoms of dementia in later
life [30].
The overlap between symptoms and
neurochemical pathways may be more apparent than
initially thought. New evidence has emerged of
overlapping pathways involving DISC1, a scaffold
protein that interacts with multiple
neurodevelopmental, cytoskeletal, and signaling
proteins [31], and Huntingdon disease
[32]. In time, it is hoped that yawning
and its role in neurological disorders may be
understood by exploring its presence as a
symptom in different neurological
disorders.
Indeed, Collins and Eguibar [33]
stated that antagonist interaction studies have
now clearly defined at least 3 distinct neural
pathways involved in the induction of yawning.
Scientists are beginning to understand the
hierarchical order through which these different
neurotransmitter systems interact to regulate
yawning. So far, the following neurotransmitters
and neurohormones have been implicated:
acetylcholine, dopamine, glutamate, serotonin,
oxytocin, gamma-aminobutyric acid, opioids,
adrenergics, nitric oxide, adrenocorticotropic
hormone, and alpha-melanocyte stimulating
hormone. Yet advanced techniques, such as
functional magnetic resonance imaging, are yet
to yield conclusive evidence to assist in fully
explaining the yawn [34].
Yawning has often been associated with
fatigue, stress, and exposure to cold
[1]. During exposure to cold, the
cortisol level in humans rises dramatically,
except when they are exposed quickly (as in the
cold face test), when there are reduced cortisol
rises, perhaps due to vagal inhibition
[35]. It is suspected that exposure to
extreme cold temperature gives rise to a similar
stress-like response with respect to cortisol
levels in humans.
Cortisol is known to be present and elevated
during stressful situations. Blood cortisol
levels are directly related to salivary cortisol
levels [36], which have been documented
in various paradigms. The cortisol level and
stress correlation is curvilinear. However, in
preterm infants, cortisol levels may be lower
during the heel-stick pain procedure
[37], and in girls whose parents had
depressive problems, cortisol levels were
blunted [38]. In animal models, the
cortisol level profile is also similar to that
in humans during stressful situations
[39]. Cortisol levels appear higher
after being subjected to stress-induced
situations [40].
What is unknown is the cortisol level during
yawning. The cortisol level may be higher when
yawning occurs after exposure to cold than after
exposure to a stressful situation. Are cortisol
levels elevated when neurologically impaired
patients yawn, perhaps in those with multiple
sclerosis?
The link between fatigue and hormonal
changes is well documented. A greater level of
neuromuscular fatigue and larger responses in
serum hormone concentrations have been seen, for
example, after hypertrophic variable resistance
loadings [41]. This has led to
identifying markers of fatigue [42],
particularly following postmatch professional
rugby [43] and in young athletes
[44]. Elevated salivary cortisol levels
have also been seen in elite tennis players
[45]. Sleep deprivation and fatigue have
been linked with salivary cortisol levels; in
this instance, cortisol levels are lowered
[46].
Cortisol is a lipophilic steroid with low
molecular weight. Following binding with
adrenocorticotropic hormone to membrane
receptors and cells of the adrenal cortex,
cortisol is then synthesized and released into
the blood stream. Since most (about 95%) is
bound to large proteins, such as albumin, only
the small fraction of unbound free cortisol is
thought to be biologically active and enters
cells by passive diffusion. This makes it
feasible to measure the free cortisol fraction
in all bodily fluids, for example, saliva
[47].
Levels of cortisol are regulated by the
hypothalamic-pituitary-adrenal axis, which is a
complex set of interactions between the
hypothalamus (known to regulate body
temperature) and the pituitary and adrenal
glands. The hypothalamic-pituitary-adrenal axis
also assists in digestion, the immune system,
sexuality, mood, and energy usage [48].
It is implicated in stress, trauma, and
particular disorders such as fibromyalgia and
chronic fatigue syndrome.
Curiously, the compound glycyrrhizic acid,
found in licorice, has been found to increase
the activity of cortisol in the kidney
[49]. This is thought to be due to
inhibition of the enzyme 11?-hydroxysteroid
dehydrogenase type 2, which normally inactivates
cortisol in the kidney; hence, licorice tends to
inhibit this enzyme and in turn deregulates,
resulting in an increase of, cortisol levels.
Anecdotally, we asked 1 of our study
participants to eat licorice after providing a
saliva sample and observed a rise in cortisol
levels. This would need to be investigated
further to discern significance in this
finding.
Discussion
Several interesting findings have emerged
from the study, which are consistent with the
original hypothesis. Among those who yawned,
there was a significant difference in cortisol
levels between sample 1 and sample 2. A t test
confirmed that there were no significant
differences in salivary cortisol levels between
those who yawned and those who did not for the
first baseline sample (sample 1). Furthermore,
there were no significant differences in a
repeated-measures t test between sample 1 and
sample 2 for those who did not yawn.
It was a concern while designing the study
that age, recent anxiety and depression levels,
and general health could all potentially be
factors affecting participants' baseline
cortisol levels. If this were the case, these
factors could also have contributed toward the
change in cortisol levels, and the experiment
could have been measuring interference from
these, rather than a change due to the
independent variable (whether or not
participants yawned during the experiment).
However, correlation analysis suggested that
these did not play a significant part in
cortisol levels, with nonsignificant
correlations across all variables. There were no
significant differences in baseline cortisol
levels between those who yawned and those who
did not.
Age, recent anxiety and depression levels,
or general health could also have had a
potential impact on cortisol levels, which could
have affected whether a participant yawned or
not during the study. The t tests for each of
the above variables confirmed that there were no
significant differences in these factors between
groups.
Although we used a relatively low sample
size, inspection of data (Table 3) suggests that
the differences between groups in terms of
cortisol change between sample 1 and 2 were not
vast. We intend to investigate these findings
further by conducting the experiment on a larger
scale, with a proposed 100 participants.
Calculation using G*Power suggests that for a
power size of 80%, 27 participants will be
required for each group; therefore, 100
participants should permit random allocation of
50 participants per group. Investigation of
participants with different neurological
disorders, such as multiple sclerosis, is also
planned. We hope to achieve an understanding of
yawning and its role in neurological disorders,
together with the potential development of a
diagnostic test for the early identification of
neurological sequelae.
As well as being of interest to clinical
scientists and practitioners, yawning is clearly
of interest in the media. A newspaper article
has cited interest by the US Department of
Homeland Security, which warned that apparently
innocuous yawning behavior in passengers could
signal a would-be terrorist [57].
Although this reported observation can be argued
as perhaps being rather tangential to the
pursuit of an explanation of yawning, this tends
to highlight the importance of other
contributing factors such as the social milieu
and cultural norms.
Social and physiological factors as well as
cortisol activity are all important
considerations, not only because they may
potentially provide the answer to why we yawn
but also because they may help in the
development of a potential diagnostic test. The
research team led by the first author at
Bournemouth University is interested in
determining whether we are truly born to yawn as
a protective indicator of untoward neurological
dysfunction. Yawning is perhaps a warning,
neurologically speaking.
