Do they even exist? ― that would likely be the first question that pops up in people’s heads. And rightly so. Besides ubiquitous symptoms such as drowsiness and a shortened attention span, it seems as if there’s little else to go on. Indeed, the exact mechanism of sleeping is still somewhat of a mystery, even to scientists. Sleep-related illnesses such as insomnia often have no particular underlying cause. Narcolepsy is less of an enigma, but still puzzling. Hypersomnia, and Insufficient Sleep Syndrome, particularly, tend to have plausible explanations. More-or-less, they correlate with one’s personal choice, behavior and overall lifestyle. However, there are, by-and-by, readily recognized as symptoms and, a correlation having been made with some observable disorder, as syndromes― but what specifics bring them about is anyone’s guess.

Have you ever tried your hand at guessing why you couldn’t get a good shut-eye the night before some appointment? Why does your headache even if you had? Maybe you’ve written it off as ‘stress,’ ‘anxiety’ or something else, caused by anticipation. Well, you might as well be correct, but the exact problem  ― what caused this negative bodily reaction ― is a probably a tad bit more complex. Going through regular and irregular routines, our sleep-adjustment changes and modifies itself in turn. But what in our body brings this change about? What is it? That’s precisely the overarching question we’d like to share with you.

What Their Discovery Entails

Experts all around the world would relish the chance to get to the bottom of this problem. More than anything else, it would provide a coherent set of measurables. Once measured and ascertained, this problem would be reduced to something more quantifiable. We would have a clearer picture of the exact graphs and numbers behind our sleep and sleeping schedule. And this alone should prove a great impetus to aspiring chemists and doctors. Ideally, the discovery of such a biomarker would give us insight into:

  1. The relationship between bodily functions and the quality and quantity of sleep
  2. The way certain sleep disorders function in regard to the presence/absence of particular biomarkers
  3. Finally, how we might effectively manage these biomarkers and even get the better of them in the long run

Plainly put, these biomarkers would indicate with great precision the many variables involved with sleep. They would show us people’s personal propensity to sleep and the mechanisms behind sleep disorders. Perhaps, but only perhaps, we would even have a glimpse into the anthropological history of  such a mundane activity. The answer is, you’ll have noticed, really of great importance, scientifically. But it is also tremendously important to every non-specialist and us as its repercussions affect that great third part of our lives ― our convalescence in dreamland.

Since a good deal of life is indeed spent dozing off, one way or another, wouldn’t it be nice if we knew why we had to sleep? If that’s asking far too much, then it would be undoubtedly handy if we at least knew what causes it. Is it not true that all mysteries are made to be unraveled. If not that, then at least pondered. It does affect both our memory and mental, as well as physical well-being, after all. And so finding, or coming close to finding sleep biomarkers, might not be just a scientific adventure, chemicals, brains and all that jazz. It might also be a deeply human search for the meaning of our nocturnal and diurnal visitations into dreams. Still, better not get ahead of ourselves!

Sleep Biomarkers, Sleep Disorders and Sleep Debt

Quite a few articles in recent years have shown a correlation between sleep or lack thereof, and the multitude of effects it can have on us. From our daily jobs to personal relationships, and from physical consequences to mental health, it does seem to be one of the pressing issues of the modern world. More and more, in fact. Not knowing how to manage one’s sleep can lead to loneliness, social withdrawal, ill health, and so on. Hence, resolving the issue of sleep biomarkers is fast becoming, if it has not already become, an urgent matter. The pace of life is such that one simply has to optimize one’s sleep or, sadly, suffer the consequences. This is why we’d like to draw attention to this. For the everyman, it could make all the difference between a quality life and one of just ‘getting by’  ― getting by tired, baggy-eyed and wretched.

More to the point, the human body is, needless to say, a complex organism. The intricacies of its many biomarkers and their relationship can be hard to pinpoint. How many times have you felt something ― a back-pain or a headache ― and been unable to specify its cause? Science tells us there are usually several. The same, in all probability, holds true for anything that bothers or enhances our ability to sleep. One thing leads to the next and back again. Many conditions, whatever they are, exist in a sort of link. For example, some studies have shown parallels between ADHD and sleep disorders. Other such cases abound and show us a profound interconnectedness between one facet of our body and another. And this is where we encounter a major problem ― in this vast matrix of cause-and-effect, how are we to determine what is primary and what secondary? Well, no objective methods have been as yet employed on a large scale to give a satisfactory answer. But this is just some food for thought. Raising awareness of this issue is but the first step to solving it, especially in this technology-dominated age. And on that point, it might be wise to consider how tech influences our biorhythm. It is of such profound importance to modern society that it just cannot be overlooked. Indeed, the developments in technical sciences have added yet another layer on top of this. Our biorhythm is less and less in tune with the ‘natural’ world and more and more ‘online.’ For better or worse, this certainly makes finding select biomarkers that much more difficult.

In any case, it can be safely assumed that sleep disorders and abnormalities must have something to do with their putative biomarkers. More often than not, however, they can also be misleading in regards to biomarkers of sleep per se. For example, biomarkers for sleep debt status showed little overlap with previously identified biomarkers for circadian phase. Biomarkers for acute and chronic sleep loss also showed little overlap. We can see, then, that even amongst themselves, sleep disorder biomarkers can diverge into separate categories. If it’s like that regarding relatively similar biomarkers, then we can only imagine how subtle the one we’re searching for is!

In (Re)Search of the Elusive Sleep Biomarkers

So far, there has been experimental research conducted in order to identify the chemical basis of sleep. How? This is done mostly by analyzing subjects in instances of sleep deprivation and chronic sleep restriction or sleep reduction. The samples taken are usually blood, urine, and saliva. And though the nature of these tests is a bit of a hit-and-miss affair, some facts can at least be established.  This study shows several things. Firstly, a change in metabolism has been observed in both humans and non-human animals, as well as certain changes in the bloodstream. Whether this is indicative of a biomarker is questionable. Still more promising, however, is the usual saliva test which has shown reduced mRNA encoding amylase in sleep-deprived patients. This, again, may be a useful signal for showing us the culprit. And many other tests ― the so-called multivariate tests ― have been performed to that end.  These have so far been used to detect biomarkers for cancer and dementia, for example. So they show some promise, despite the rather more complex nature of the biomarkers we’re talking about.

The main problem with this is the very nature of sleep. It is an emergent property of the brain that takes over when enough cortical columns go to sleep. There is not a point in time in which all ‘shut down’ ― some are always active. Thus the presence or absence of certain chemicals in the blood/saliva is simply not precise enough to determine, by itself, whether a person is asleep, or even sleepy. And even if handled with greater precision, this method still sorely lacks the ability to specify what the trigger was. So the specific biomarker again eludes us.

An even more perplexing issue emerges, however, when we take into consideration variable daily sleep. It is become all the more common, especially for younger people, to have flexible sleeping schedules. This is, technically speaking, unhealthy. Not only that, but it appears that it can further muddle the precise nature of the underlying sleep biomarkers. Apparently, changing your sleeping schedule can shift the balance of bodily and sensory secretions. However, bluntly put, it is most noticeable when going to bed later than usual. This is as apparent from changes in body temperature and specific inflammatory functions. From this, we see that sleep variability is associated with a biomarker strongly influenced by sleep and circadian regulations. So we can see the change, yet again, and what set off at least one biomarker ― the one showing a shift in sleeping behavior. Alas, though it may exist, no study has yet shown us what it is exactly. Who knows? It might even be that it’s not a single biomarker, a sole culprit. Perhaps it is. But then again, it just as well might be a whole array of processes that bring sleep about. After all, there is so much we don’t know about it. Besides the peripheral knowledge of what influences sleeping, the question still stands open.

Sleep or Sleepiness Biomarkers?

Could it all be a mistake? ― would be the appropriate punchline. Well, not quite. But I would draw your attention this anyway. Namely, what’s been so far neglected is the rather significant difference between sleep and sleepiness. And, of course, the difference between their biomarkers. That is if they even correspond on a one-to-one basis. A die-hard skeptic may also ask, ‘Do they correspond at all?’ In certain points, sleepiness and actual sleep are assuredly linked, however tentative that bond may be. But as to whether one leads to the other  ― well, let’s get down to that.

All of us yawn, and most of us yawn when other people yawn. It is also one of the most socially-recognized cues that one is tired. The latter has little scientific backing, though. Still, this is what most people would conjure up when asked what they thought was a prototypical sign of sleepiness. And the relationship between sleep and sleepiness is just as deceptive as this. This is why I’ve mentioned yawning, as a sort of symbol for this divide.

Droopy-eyes, on the other hand, is a quite clear indication of one’s fatigue. You can be as dopey when utterly tired as when you’ve had an excellent meal (and a lot of it). In the first case, if one is genuinely exhausted after a long day, this might be indicative of a biomarker playing its part. But is it the sleep biomarker, and is it possible to differentiate it from the others? In the second case, we might be tempted to say that the lack of blood supply to the brain is responsible. And partially it is. But how then to separate this biomarker of a metabolic function, i.e., digestion, from another that is, nonetheless, noticed by us through the same symptoms — droopy eyes, in this case.


The precise sleep biomarker or biomarkers remain an enigma. But a less puzzling one, we would like to think. To wrap this up, we do hope this article has offered its readers some good food for thought (from which you won’t get droopy eyes!) and stimulated them to think about the role sleep plays in their own lives.


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