What is cortisol and how bad it actually is?

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Mon Nov 07, 2022

According to John Hopkins Medicine, more than a quarter of Americans over 18 years old are suffering from a mental illness. Is it not weird, considering the pace at which our living conditions are consummating, becoming theoretically less onerous? At first glance, it definitely is, and the reason is unclear. To explain this baffling statistic, people appeal to the broad term “stress” and the so-called “high cortisol.” Although this rationale is not unreasonable, which makes establishing direct relationships between stress and any disease extremely tempting, it is not as straightforward as we want it to be and requires a little more insight.

Cortisol is a hormone. To be more specific, it is a glucocorticoid, and the mechanism of its action has been extensively described in a paper published in the Dialogues in Clinical Neuroscience and a study reported by Molecular Systems Biology. When there is a threat, a small region in the brain responsible for processing different emotions, including fear, called the amygdala, signals to another part of the brain – the hypothalamus – to turn on the parasympathetic nervous system, commonly known as a fight-or-flight response. This results in the release of two neurotransmitters: norepinephrine and epinephrine (noradrenaline and adrenaline). If the threat perseveres, the hypothalamus-pituitary-adrenal axis (HPA) gets activated. Basically, what happens is the hypothalamus releases another hormone – corticotropin-releasing hormone (CRH) – which triggers the pituitary gland, or hypophysis, to produce adrenocorticotropic hormone (ACTH). ACTH, in turn, stimulates the adrenal cortex, and thus, cortisol enters the bloodstream. How does the synthesis of the glucocorticoid stop? Our remarkably complex bodies have yet another organ performing this function: the hippocampus. In addition to being involved in learning, memory, and spatial navigation, it also inhibits HPA. Despite being quite sophisticated, the mechanism of cortisol production aids the understanding of the key role the hormone plays in the body as well as the potential consequences of the basal glucocorticoid levels staying elevated for a prolonged period. 

First, it is not hard to guess that if a person is under constant stress, their HPA axis is always activated. What does it imply? It means there is no need for an organ that turns it off – in the hippocampus. The reduction of the hippocampal volume and the hippocampus-related memory lapses due to cortisol levels remaining high for a substantial amount of time is a scientifically proven fact. I do not think you would be surprised if I told you that the shrinking of the hippocampus hastens the onset of Alzheimer’s. 

Curiously, the effect of short-term stress on memory performance depends not only on the type of cognitive tasks to be solved but also on the severity of the stressor, as follows from the article published in Neuropsychopharmacology. Thus, an increased level of cortisol positively affects memory consolidation but hinders our ability to retrieve already memorized information. However, for all the enthusiasts out there, it is also worth noting that very high levels of cortisol have a detrimental effect on memory.

Moving on to the next point, while suppressing the hippocampus function, constant stress makes the neurons in the amygdala more sensitive, according to American neuroendocrinologist and Stanford University professor Robert Sapolsky. As you might have assumed based on the role this area plays, the hyperreactivity of the amygdala is the reason behind anxiety, depression, and PTSD. Therefore, permanent stress is partially to blame for the increase in the frequency of mental disorders in modern society. However, sadly, it is not the only problem with persistently high glucocorticoid levels. 

Stress is known to cause the suppression of many body functions, which makes total sense if you think about it. The fight-or-flight response is a developed evolutionary mechanism to increase our life expectancy from 30 seconds to at least a few more years, and, of course, it comes with a cost. Devoting all of our resources to escaping the danger and minimizing the threat, our bodies shut down – not completely, do not get me wrong, but considerably – the reproduction system, digestive system, and growth, and it is not a problem as long as it happens reasonably often. Reasonably is a keyword. When the stress turns into a constant inescapable threat, systems whose work was supposed to be put on hold temporarily end up never being prioritized. As a result, instead of enhancing the immune system as glucocorticoids usually do by inhibiting the synthesis of the pro-inflammatory peptides, they suppress it making us more susceptible to infections.

Moreover, constant stress and, therefore, high cortisol levels increase the risk of ulcers and alter the fat distribution pattern. In a paper published in the Metabolism: Clinical and Experimental, it has been reported that in case of elevated glucocorticoid production the fat tends to accumulate in the abdominal area which is believed to be associated with the high density of the glucocorticoid receptors (GR) in visceral fat. On a positive and amazing note, though, according to the British Journal of Cancer, there is almost no data linking high cortisol with cancer except for the two independent studies postulating the increase in odds of endometrial cancer due to raised plasma cortisol.

At this point, chances are, as you read this, you are pestered by an annoying thought: “Why is cortisol a glucocorticoid? Why exactly gluco-?” Surprisingly enough, there is a reason for that. In the presence of a threat, one of cortisol’s primary functions is to supply the brain with enough glucose. To achieve this, the hormone, among other things, induces the production of glucose, increases the breakdown of proteins which can then be used to generate more of a much-needed monosaccharide, and negatively affects the concentration of insulin responsible for glucose metabolism. Simply, cortisol increases blood sugar levels, and this is where its name comes from. Now, after satisfying your curiosity, I have to make a disappointing but expected conclusion: prolonged elevation of cortisol is directly related to the higher probability of type-II diabetes occurrence.
A reasonable question is, how to reduce our spiking cortisol? Some may tell you to drink green matcha, do journaling, or assemble an aesthetically pleasing breakfast. Personally, I am insensitive to the matcha charms, to say the least. Luckily for other like-minded people and me, research has something nice to say. 

The Neuroscience and Pain journals document the experiments conducted on rats being given electric shocks – I would want to claim that not a single rat was harmed, but at least we have some fascinating data – which led to several important conclusions. Rats that could either escape a shock or let out the frustration by nagging at a piece of wood or being around another rat they had a good relationship with after receiving an electric shock showed a significantly lower stress response compared to rodents who were not given such options. The same effect was observed when animals were warned before the stimulation. What does it mean? It means exactly what it states: being able to predict or escape a stressful situation, let out negative emotions it caused, or simply having social support affects our perception of stress not just on an emotional but also on a physiological level. Thus, we have arrived at an obnoxiously trite thought – stress is subjective, and we can mitigate it by implementing a few quite inelaborate ideas our four-legged friends helped us to arrive at.

On a final note, cortisol does a plethora of wonderful things in our bodies: it improves the immune system, facilitates memory consolidation, makes us more alert, and mobilizes a huge bulk of our resources – all of it to save us from the potential imminent death, which, let’s be honest, is not a problem a regular person is faced frequently with. The more often you turn this highly effective but very pricey mechanism on, the harder it becomes for all other systems to pay for it. However, even with that knowledge, it can still be hard to suppress an urge to panic over the upcoming exams or stress over the heavy traffic being the reason for your missed flight. The good thing is, now you know what to do – find a big chunk of nice-smelling wood!

List of some of the used sources:

https://www.ncbi.nlm.nih.gov/books/NBK538239/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306649/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619133/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677120/

https://doi.org/10.1038/s41416-021-01505-8

Video lecture "Why Zebras Don't Get Ulcers: Stress and Health" by Dr. Robert Sapolsky

https://sci-hub.se/https://doi.org/10.1016/0026-0495(92)90171-6

https://www.ncbi.nlm.nih.gov/books/NBK538239/

https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response

https://en.wikipedia.org/wiki/Cortisol

 

 

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