Dr. Ron’s Research Review – February 1, 2017

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This week’s research review focuses on yawning as a sign of low cortisol.

Yawning consistently poses a conundrum to the medical profession and neuroscientists. Neither its mechanisms nor its functions are entirely known. (Guggisberg et al., 2010)

Yawning is associated with some diseases, including digestive issues. It is associated with hunger, and occurs at the beginning of hypoglycemia in a diabetic under insulin therapy.
Antidepressants, in particular serotonergic antidepressants (SSRIs) are most often found to be involved. Yawning occurs in Parkinson’s disease and its treatment with neuroleptics.
The migraine prodrome may include yawning possibly due to a dysfunction in dopaminergic transmission. (Walusinski, 2009)

Yawning stimulates mechanically the carotid body which gives rise to increased arousal, alertness and wakefulness. (Matikainen and Elo, 2008)

The Thompson Cortisol Hypothesis

The Thompson cortisol hypothesis proposes cortisol levels are elevated during yawning just as they tend to rise during stress and fatigue. A recent study supported this hypothesis. (Thompson and Bishop, 2012) (Thompson, 2014)

Crocin and Safranal

A study showed that yawning induces central histamine. Crocin and safranal (the major constituents of saffron) increased histamine-induced yawning, and also produced yawning when the histamine action is blocked. (Taati et al., 2016)

 

Dr. Ron


 

Articles

Why do we yawn
            (Guggisberg et al., 2010) Download
Yawning is a phylogenetically old behaviour that can be observed in most vertebrate species from foetal stages to old age. The origin and function of this conspicuous phenomenon have been subject to speculations for centuries. Here, we review the experimental evidence for each of these hypotheses. It is found that theories ascribing a physiological role to yawning (such as the respiratory, arousal, or thermoregulation hypotheses) lack evidence. Conversely, the notion that yawning has a communicative function involved in the transmission of drowsiness, boredom, or mild psychological stress receives increasing support from research in different fields. In humans and some other mammals, yawning is part of the action repertoire of advanced empathic and social skills.

Does yawning increase arousal through mechanical stimulation of the carotid body
            (Matikainen and Elo, 2008) Download
Yawning is a stereotyped event that occurs in humans and animals from fish to mammals, but neither its mechanisms nor its functions are entirely known. Its widespread nature suggests that it has important physiological functions. It is associated with stretching of muscles in a large area, but the function of this stretching is understood far from completely. It has been proposed that yawning increases arousal and that it is an arousal defense reflex, whose aim is to reverse brain hypoxia. Whilst yawning has been speculated to have an important role in reversing hypoxia, there is a structure in the neck that is known to be intimately involved in the regulation of oxygen homeostasis, namely the carotid body. It senses acute changes in oxygen levels. In spite of this, a connection has never been proposed either between the carotid body and arousal, or between yawning and the carotid body. We propose that yawning stimulates mechanically the carotid body (and possibly other structures in the neck). We further propose that this stimulation gives rise to increased arousal, alertness and wakefulness and that one important physiological function of yawning is increase of arousal through this stimulation. We also propose that mechanical effects on the shunt system of the carotid body may be involved in this stimulation. Our hypothesis is supported by several facts. For example, yawning causes movements and compressions that may affect the carotid body that is situated strategically at the bifurcation of the common carotid artery. Thus, yawning may stimulate the carotid body. The carotid body is highly vascular and compressions may affect its shunt system and blood flow and for example give rise to release of hormones or other substances. Also several facts related to situations where people yawn or do not yawn support our hypothesis and are discussed. Further support comes from facts related to somnogenic substances, hormones and transmitters, and from facts related to the interconnection of homeostatic mechanisms, sleep, arousal and ventilation.

The effects of crocin and safranal on the yawning induced by intracerebroventricular injection of histamine in rats.
            (Taati et al., 2016) Download
OBJECTIVE:  Crocin and safranal, as the major constituents of saffron, have many biological activities. This study investigated the effects of crocin and safranal on yawning response induced by intracerebroventricular (i.c.v.) injection of histamine in rats. MATERIALS AND METHODS:  In ketamine/xylazine-anesthetized rats, a guide cannula was implanted in the right ventricle of the brain and yawning induced by i.c.v. injection of histamine. Crocin and safranal were intraperitoneally (i.p.) injected alone and before i.c.v. injection of histamine. RESULTS:  Histamine at the doses of 10 and 20 µg/rat produced yawning. Mepyramine (a histamine H1 receptor antagonist) 40 µg/rat significantly (p<0.05) prevented histamine (20 µg/rat)-induced yawning. Crocin (30 mg/kg) and safranal (1 mg/kg) significantly (p<0.05) increased histamine (10 µg/rat)-induced yawning. Crocin and safranal also induced yawning when injected before mepyramine plus histamine administration. CONCLUSION:  The results of the present study showed a yawning-inducing effect for central histamine, which was inhibited by mepyramine. Crocin and safranal increased histamine-induced yawning, and also produced yawning when the histamine action is blocked.

Born to yawn? Understanding yawning as a warning of the rise in cortisol levels: randomized trial.
            (Thompson and Bishop, 2012) Download
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 = -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. TRIAL REGISTRATION:  International Standard Randomized Controlled Trial Number (ISRCTN): 61942768; http://www.controlled-trials.com/ISRCTN61942768/61942768 (Archived by WebCite at http://www.webcitation.org/6A75ZNYvr).

Yawning, fatigue, and cortisol: expanding the Thompson Cortisol Hypothesis.
            (Thompson, 2014) Download
Yawning and its involvement in neurological disorders has become the new scientific conundrum. Cortisol levels are known to rise during stress and fatigue; yawning may occur when we are under stress or tired. However, the link between yawning, fatigue, and cortisol has not been fully understood. Expansion of the Thompson Cortisol Hypothesis proposes that the stress hormone, cortisol, is responsible for yawning and fatigue especially in people with incomplete innervation such as multiple sclerosis. This informs our understanding of the functional importance of the brain stem region of the brain in regulating stress and fatigue.

Yawning in diseases.
            (Walusinski, 2009) Download
Yawning is a physiological behavior, an emotional stereotypy that indicates the homeostatic process of the mechanisms regulating rhythms, such as sleeping/waking, hunger/satiety or mating/relaxation, generated by the diencephalon. As with all physiological behaviors, its deregulation reveals disorders. In daily practice, yawning as a symptom is generally neglected. That is why we propose a wide overview of yawning in diseases, its consequences and significance.

 

References

Guggisberg, AG, et al. (2010), ‘Why do we yawn’, Neurosci Biobehav Rev, 34 (8), 1267-76. PubMed: 20382180
Matikainen, J and H Elo (2008), ‘Does yawning increase arousal through mechanical stimulation of the carotid body’, Med Hypotheses, 70 (3), 488-92. PubMed: 17709210
Taati, M, et al. (2016), ‘The effects of crocin and safranal on the yawning induced by intracerebroventricular injection of histamine in rats.’, Avicenna J Phytomed, 6 (4), 442-48. PubMed: 27516985
Thompson, SB and P Bishop (2012), ‘Born to yawn? Understanding yawning as a warning of the rise in cortisol levels: randomized trial.’, Interact J Med Res, 1 (2), e4. PubMed: 23611879
Thompson, SB (2014), ‘Yawning, fatigue, and cortisol: expanding the Thompson Cortisol Hypothesis.’, Med Hypotheses, 83 (4), 494-96. PubMed: 25169036
Walusinski, O (2009), ‘Yawning in diseases.’, Eur Neurol, 62 (3), 180-87. PubMed: 19602891