Body and Mind: Drivers of Stress (Stressors)

Our body has a way to deal with the many different stressors found in our environment. Anything from variation in temperature to infections, changes in our diet or use of drugs are considered stressors. Psychological factors are also important, and they include any alterations of our optimal state of mind. All these stressors, psychological or physical activate responses in our body¹.

Key Points

• Sources of stress can be psychological or biological and both affect the function of various systems in the body.
• Psychological stressors can be defined as any situation that threatens our mental health and wellbeing.
• Psychological stressors can include social evaluation or exclusion, marital and family problems, work-related problems, economic hardship, among others.
• Biological stress includes any physical factors that can alter the body’s function, including drastic changes in temperature, chronic poor diet, infections or inflammation, drugs, and many others.
• Both psychological and physical stressors elicit specific biochemical pathways in the body, called stress responses.
• Stress responses aim to maintain the homeostasis or equilibrium within our body.

What causes stress?

There are virtually countless sources of stress, but they can broadly be classified as physical and psychological sources of stress. In broad terms, three main types of stress can be defined^1-3:

Physical stress – This is a broad category of stress, which includes any physical factors that can interact with our body and alter the function of specific systems. Examples of physical stressors include extreme changes in temperature, environmental pollutants, chronic poor diet, alcoholism or any other drug use, altered sleep patterns, infections or injuries, among many others.

Psychological stress – This is a form of stress caused by stressors that target well-being of the mind, including social pressure, family or marital problems, financial hardship, social pressure, and many others. Psychological stressors can alter the function of our body, potentially leading to both mental and physiological problems.

Cellular stress – This is a specific form of biological stress that occurs when cells are exposed to adverse environmental conditions, which affect the optimal equilibrium of chemicals and biomolecules inside and outside the cell. Cellular stressors include sudden changes in chemical or pH levels, extreme temperatures, presence of infectious agents or pollutants, among others. When the cellular equilibrium is altered, damage can occur at the level of proteins, DNA or RNA.  Hence, cellular stress can affect multiple parts of our body, including the nervous, cardiovascular, endocrine, and immune systems.

Our body’s response to stress and stressors

Stressors elicit responses in our body aimed at restoring the balance or homeostasis our cells and organs need to function. These stress responses are aimed at restoring the balance or homeostasis in chemicals, pH, temperature and other factors that affect cell function².

Stressors can cause alterations to the function of the HPA axis, leading to either abnormally high or low HPA activity^2-3. These alterations to HPA function have been associated with many diseases, including depression, diabetes, obesity, asthma, chronic fatigue syndrome, among many others (Table 1).

Table 1. Conditions associated with alterations to the function of the HPA axis.
Data from Chrousos, 2009.

The most important players in our body’s response to stress are hormones.

Stressors: Hormones

Hormones are a very important type of signalling molecule (molecules that help with cell-cell communication), in charge of regulating the function of different organs. Hormones communicate with cells through their unique chemical structure, which interacts with specific chemical receptors found in target cells. In broad terms, hormones are involved in three major body functions⁴:

• development and growth;
• maintenance of the internal environment; and
• regulation of metabolism and nutrient supply

Each of these functions may be regulated by one or more hormones, and, at the same time, a single hormone may be involved with more than one function. For example, blood glucose levels are regulated by insulin, glucagon, cortisol, the human growth hormone and epinephrine. In other words, hormones function as a team, so when a person suffers from problems in a hormone-regulated function, like blood glucose levels, it is important to focus on all the hormones involved⁴.

Most hormones can also be classified into three major categories, based on the how they formed. There are i) lipid-derived hormones, which includes testosterone, ii) amino acid-derived hormones, which include adrenaline, and iii)peptide hormones, which include oxytocin.

Hormones are produced by specialised glands in different parts of our body, and they are all part of the endocrine system. The endocrine system is composed several major glands, including the pituitary and pineal glands in the brain, the thyroid gland, the adrenal gland and the male and female reproductive glands, the testes and ovaries, respectively.

Stress responses, like many other processes in the body, are regulated by hormones⁵. Some of the most important hormones linked to stress responses include:

Cortisol

This is a type of lipid-derived hormone, also called a glucocorticoid hormone, that is produced by the adrenal glands. Commonly known as the stress hormone, this hormone is the first to be released when our body is under stress. It is also released under other, non-stressful circumstances, like when you wake up or exercise. Cortisol affect various systems in our body, including the musculoskeletal, cardiovascular, respiratory, endocrine and nervous systems⁶.Key functions of this hormone include:

• Stress response – cortisol is a key component of the response that our body mounts against a stressor, helping the body stay on “high alert”. This helps maintain the anti-stress mechanisms in place, such as the release of hormones known as catecholamines, which include dopamine, norepinephrine and epinephrine.
• Glucose – The presence of cortisol increases the amount of glucose available for the brain and in other parts of the body. In the liver, high cortisol levels promote the process of glucose formation, called gluconeogenesis. In the presence of cortisol, muscle cells decrease their use of glucose and, instead, increase protein degradation. This is important, as this process generates amino acids needed by the liver to continue with the process of gluconeogenesis. Cortisol play similar functions in adipose tissue and in the pancreas. In adipose tissue, cortisol promotes the process of lipolysis, which results in the production of free fatty acids, molecules needed by other cells to produce glucose. Finally, in the pancreas cortisol increases the levels of glucagon, a hormone that promotes liver gluconeogenesis⁶.

Adrenaline

This is a hormone derived from the amino acids phenylalanine and tyrosine. It belongs to a type of hormones known as catecholamines, which also include hormones like dopamine and norepinephrine. These hormones are all synthesised by the adrenal glands, and function as modulators of the stress response⁷.Also known as epinephrine, this hormone increases muscle strength, specifically it stimulates the function of smooth muscles, these are the muscles found in blood vessels and internal organs like the stomach, intestine, and bladder.  Adrenaline also increases sugar metabolism, heart rate and heart contractility, the strength with which the heart contracts.

Norepinephrine

Also known as noradrenaline, is another member of the catecholamine family of hormones with a function very similar to adrenaline. Just like adrenaline, noradrenaline, affects the function of the heart, and blood vessels, and can influence blood sugar levels. In addition, noradrenaline can also cause the blood vessels to become narrower, which results in an increase in blood pressure. This effect is further enhanced by the fact that noradrenaline causes the heart muscle to increase the output of blood.Noradrenaline also functions as a neurotransmitter – a chemical that helps nerve cells communicate⁷.In its role as a neurotransmitter, norepinephrine regulates the activity of various neuronal and non-neuronal cells. It is also involved in cellular energy metabolism, and with inflammatory responses.

Beyond stress hormones and stressors

In recent years, studies have also established links between hormones, stress and the gut microbiota. Studies in mice, for example, have shown that stressful events in pregnant mice are associated with dysbiosis in their offspring, which can lead to altered gene function, particularly in genes related to brain development. Likewise, stress early in life seems to affect the functioning of the HPA axis, which is underdeveloped in newborns⁸.

Some studies, also in mice, have suggested that the use of probiotics may help ameliorate stress-related problems^9-10. A recent study treated mice exposed to chronic mild stress (CMS) with a probiotic treatment that included the gut bacteria Lactobacillus helveticus, Lactobacillus plantarum, and Bifidobacterium longum. Results showed that mice receiving probiotics had reduced levels of anxiety- and depressive-like behaviours, compared to control mice (mice that did not receive any probiotics)¹⁰.

The potential link between gut microbiota and stress, including the use of probiotics to treat dysbiosis and stress-related disorders, is an exciting and promising venue. Future studies may one day reveal how gut microbes interact with our brain to influence our stress response and therapeutic approaches involving probiotics may become a reality.

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References

1. Kogler L, Müller VI, Chang A, Eickhoff SB, Fox PT, Gur RC, Derntl B. Psychosocial versus physiological stress—Meta-analyses on deactivations and activations of the neural correlates of stress reactions. Neuroimage. 2015 Oct 1;119:235-51. Read it!
2. Chrousos GP. Stress and disorders of the stress system. Nature reviews endocrinology. 2009 Jul;5(7):374. Read it!
3. Frodl T, O’Keane V. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans. Neurobiology of disease. 2013 Apr 1;52:24-37. Read it!
4. Nussey S, Whitehead S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001. Chapter 1, Principles of endocrinology. Read it!
5. Kyrou I, Tsigos C. Stress hormones: physiological stress and regulation of metabolism. Current opinion in pharmacology. 2009 Dec 1;9(6):787-93. Read it!
6. Thau L, Sharma S. Physiology, Cortisol. [Updated 2019 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Read it!
7. Dalal R, Grujic D. Epinephrine. [Updated 2019 Apr 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Read it!
8. Frankiensztajn LM, Elliott E, Koren O. The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Current Opinion in Neurobiology. 2020 Jun 1;62:76-82. Read it!
9. Li N, Wang Q, Wang Y, Sun A, Lin Y, Jin Y, Li X. Oral probiotics ameliorate the behavioral deficits induced by chronic mild stress in mice via the gut microbiota-inflammation axis. Frontiers in behavioral neuroscience. 2018 Nov 6;12:266. Read it!
10. Guo Y, Xie JP, Deng K, Li X, Yuan Y, Xuan Q, Xie J, He XM, Wang Q, Li JJ, Luo HR. Prophylactic effects of Bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: A role of the gut microbiota-inflammation axis. Frontiers in behavioral neuroscience. 2019;13. Read it!