CHRONIC: when STRESS is no longer ACUTE

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Written by: Aashna Sahni

Edited by: Abhishek Chari

Imagine having a relaxing evening on a camp site in the mountains. You’ve put together your tent and you’re ready to enjoy your time outdoors when all of a sudden you hear a growling sound. You turn around to see a large grizzly bear that doesn’t seem too happy to see you. You feel your heart begin to race, your blood pumping faster, and you might then do your best impression of an Olympic sprinter. But, let’s hit the pause button on this hypothetical scenario for a moment. Ever wondered how and why our bodies allow us to react like that?

To answer that question, we need to understand how and why our bodies experience stress. When experiencing a dangerous and fearful event, like a wild animal’s attack, our body processes it as a challenge or a threat to our safety. Biologically, this event is known as a stressor. Stressors can be physical, such as suffering a bodily injury, or psychological, such as facing a raging beast or experiencing the loss of a loved one. Our responses to being provoked in such ways are triggered by a variety of brain regions. These regions help interpret the stressors in our environment and release ‘stress mediator’ molecules that enable our bodies to  handle the difficult situation. Being attacked by an animal is an example of an acute, or short-term, stressor which compels our bodies to exhibit the famous ‘fight-or-flight response’. This exceedingly fast reaction allows us to respond quickly to life-threatening situations and increases our chances of survival. 

The ‘fight-or-flight response’ is coordinated by the hypothalamus and brainstem which play a role in regulating basic physiological functions such as heart rate, breathing, and body temperature. Other regions of the brain that help process the fearful and emotional aspects of memories, such as the amygdala, are also involved. So, when the grizzly bear begins approaching you, and based on whatever related fearful memories you may have, a stress response is induced. This increases activity in the hypothalamus and associated regions, producing various stress mediator molecules. These mediators act on many biological targets, including the adrenal glands which secrete hormones like adrenaline and cortisol. These hormones act on various parts of the body to increase heart rate, blood pressure, and provide the energy surge which would allow you to run away from danger. In many cases, once the danger has passed, this quick response automatically shuts down. But, our natural resilience to stress is dependent on other factors.

Flowchart explaining the fight or flight response in humans. Image created by Jvnkfood (original), converted to PNG and reduced to 8-bit by Pokéfan95; (CC BY-SA 4.0)

Supportive childhood experiences could increase our ability to effectively cope with stress as adults. Studies in rodents have shown how changes in gene expression could be involved in such effects. Some rat mothers are very attentive towards their pups, licking and grooming them extensively. Such nurture modifies gene expression in the pups, and strongly shapes their behaviour. These pups grow up to be calmer and respond better to stressful situations when compared with pups that lacked this aspect of maternal nurture. 

Constant and long-term exposure to stressful situations can decrease our ability to effectively deal with additional stress, contributing to the development of many kinds of psychiatric illness, such as post traumatic stress disorder. Recurrent stressful situations can include problems in our daily lives, such as work pressures, difficult interpersonal relationships, socio-economic inequities, and other issues. Such chronic stress, lasting for months or years, can have insidious and harmful consequences on our brains and bodies. 

In experiments performed on animals, chronic stress can change gene expression and modify how neurons in the brain connect and communicate with each other. The neural effects of chronic stress have also been studied in humans. Long term work-related stress has been connected to unhealthy changes in the size of certain brain regions.

In addition to impaired brain functioning, chronic stress can also leave its mark on other parts of the human body. Chronic stress can lead to cardiovascular diseases including elevated blood pressure, leading to damaged arteries as well as pathologically overworked and overgrown heart regions. Prolonged periods of stress can also lead to increased levels of stress hormones, like cortisol; in such situations, cortisol is unable to act effectively as an anti-inflammatory factor, resulting in excessive amounts of inflammation.

So, while acute stress, and the ‘fight-or-flight’ response it generates, is important for survival and does not degrade normal bodily functions, chronic stress can have a whole range of negative impacts. Many scientific studies use animal models to understand the mechanisms underlying stress. In such research, rodents and non-human primates serve as biological models, or proxies, for human beings. But experiments conducted on either of these kinds of biological models have their own advantages and disadvantages. 

Rodent studies can take advantage of genetically altered rats and mice to pinpoint the roles of important genes on stress, its outcomes and possible treatments. In the course of experiments, these animals can be exposed to a variety of acute and chronic stressors such as forced swim tests and mother-pup separation. Rodent models also allow us to use invasive techniques like microsurgery and brain implants to better understand stress. 

Primate studies benefit from the higher degree of similarity that their behaviour has with human behaviour. So, primate research has greater relevance for understanding how stress and stress hormones can influence the development of mental disorders in humans. While ethical considerations limit the use of some invasive techniques, studying monkeys and apes can help shed more light on the psychosocial aspects of stress. This extends even to the ways in which stress affecting parents could affect their children, and how exposure to prolonged stress in childhood could affect people throughout their lives. 

Despite the limitations of using animal models to improve our understanding of human biology, such research is fundamentally important. Extensive research has uncovered new mechanisms and pathways through which stress influences behaviour. Every point of genetic, biochemical and behavioural connection between model organisms and humans offers an additional target for suggesting and testing prospective therapies for stress disorders. Additionally, research on chronic stress could also impact other aspects of human health. New findings suggesting interactions between stress and factors as diverse as substance abuse disorders, psychosocial burden, mood disorders, and memory impairment continue to increase the wide-ranging therapeutic potential of understanding stress.  

References: While the original sources for all the information in this article are present as hyperlinks within the body of the text, IndSciComm would like to acknowledge that Wikipedia was also useful in the editing process, and for tracing some background information.

The featured image was made using, and is based on the text of this article.

Aashna Sahni is currently a senior at Emory University studying Neuroscience and Behavioral Biology. She has been conducting research with Dr. Larry Young at the Yerkes National Primate Research Center for the last few years. Her research work is focused on characterizing a new model of psychosocial stress by investigating the mechanism underlying the effects of psychosocial stress arising from threat to a privileged bond in prairie voles.

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