Civilized to Stress?

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At first glance, the notion that the color of our thoughts can dye our very biology seems like a giant leap. Upon closer inspection, however, it doesn’t seem so far fetched. Take the placebo effect or the healing power of faith, for example. These are things that – for the most part – have no scientific explanation yet are common and predictable factors in our world.

Recently, researchers have operationalized this notion by examining the effects of negative and positive emotions on key markers of human health. Indeed, negative emotions and cognitions including hopelessness, pessimism, and anger have not only been associated with depression, but also with disturbance in normal cardiovascular function, morbidity and mortality from a wide range of chronic illnesses, and even increased risk for coronary artery disease. Conversely, positive emotions and cognitions have been found to play a protective role in the development of disease. While the mechanisms underlying the relationship between positive/negative emotions and health are not yet clearly understood, models of emotion and health identify both direct (dysregulation of the HPA axis) and indirect (health and coping behaviors) pathways by which cognition and emotion could modulate health.

I gladly interrupt my elitist university banter to highlight the Homo Sapien Brain. Weighing in at roughly three pounds, it’s as powerful as it is misunderstood. And it’s powerful. Despite the immense amount of sensory information floating around it, the Spaien brain takes it all in where ~ 100 billion neurons reconcile it into a single narrative. That narrative is your conscious life. It’s the memories mummified in your mind; it’s the producer of your Truman Show; it’s your story.

Even when extremely confounding conditions create holes in your story, your brain fills in the gaps. But how does the Brain decide what to fill the gaps with? Interestingly, the brain is probably as susceptible to the influence of cognition, emotion, and environment – both past and present – as it is a shaper of them.  

If we are to understand the link between human stress, cognition, emotion, and health, then, we must respect the neurobiological and psychosocial context in which it operates.

The first line in the brain’s job description is to make sense of the world around it. Most primitively, the most important distinction your brain has to make is whether or not you are in danger. But its job is not over after it makes such a determination. It also has to let the rest of the body know what to do with that information. To this end, the hippocampus, amygdala, and prefrontal cortex have evolved an elaborate system of split-second bidirectional communication with the body’s autonomic, cardiovascular, digestive, and immune systems. The communication between these parts of the brain and the rest of the body occur on a neuroendocrine highway. At any given moment, yes even right now, neurochemicals and hormones are steadily traveling along these highways, taking information to and from the brain – making you, well, you.

Note: Traffic picks up substantially when the brain detects a threat.

Even if this is your first time hearing about the biological underpinnings of your stress response system, you are very familiar with how it makes you feel, what it makes you think, and what it makes you do.

How many times have you driven home only to realize you have almost no recollection of what kind of cars you drove by, how fast you were going, how many red lights you stopped at, or even what you were thinking about? If you’re like most people, probably many more times than you’re willing to admit without sounding like a reckless driver. Now think back to a time when you just nearly missed slamming into the car in front of you at a stop light.

Or maybe right after something like this:

Woman Driving And Texting Hits Pedestrian

Your eyes widened, your muscles tightened, and your heart rate skyrocketed – all before your foot even grazed the brake pedal.

Note: I’m glad you and grandpa are okay, but you really shouldn’t text and drive.

For the rest of the ride you analyzed everything. Every car, every light, every thought. That’s the power of the human stress response at work. Next time you get startled, remember all the biology that is the puppeteer of what is seemingly simple fear and relief.

But here is a more frightening hypothetical:

Recently, Elizabeth was asleep in her apartment when there was an intensely severe thunderstorm, during which a huge tree fell on her apartment building. The loud noise of thunder and the tree crashing awoke Elizabeth from a sound sleep.  Everyone, including Elizabeth, ran out of the building.  Ultimately the building had to be completely evacuated so the fire department could check the damage.  This event caused extensive damage to the building and her apartment was flooded by both the extensive rain and activation of the sprinkler system.

Elizabeth’s apartment was one of the most severely damaged.  Ultimately she had to stay with friends for a number of weeks until the damage was repaired. Most of her possessions were so damaged that they had to be replaced. She lost almost all of the data (school and work) on her computer and her finances were impacted such that she was strapped for money.

Shortly after moving back into her apartment, Elizabeth began to notice that she was very nervous and uncomfortable when entering the building and frequently felt anxious when she was at home, especially when rain was predicted. It seemed to be continuing over a number of months. In addition she was not sleeping well and seemed to be getting colds and viruses more often than usual.  Further, she was less effective getting her work done and seemed forgetful at times.

It is not often we hear of stories in which a hero is simultaneously a villain. With Elizabeth’s story, however, we come face to face with the confounding reality that very few things in life are exclusively good or evil. Like the activation of the sprinkler system, which ultimately destroyed her belongings, the activation of Elizabeth’s sympathetic nervous system exists as insurance against the worst case scenario. Interestingly, both of these mechanisms had effects that proved detrimental to the very things they were designed to protect. In the moments after the tree came crashing down onto her apartment building, Elizabeth’s sympathetic nervous system was the hero that saved her life; her senses were heightened and her heart rate increased, facilitating a speedy exit to safety. Yet, in the weeks and months that followed, her sympathetic nervous system became the villain set on wreaking havoc on her body and mind.

To be sure, in positing the human stress response as a bizarre marriage between good and evil, I am gravely oversimplifying a complex process (and I do so quite facetiously). With that being said, the nuance and interplaying mechanisms that underlie the human stress response, and their effects on the human body, cannot be fully appreciated unless we blind ourselves to the notion that stress is exclusively good or evil.

On that fateful night, Elizabeth’s sympathetic nervous system worked as designed to help her deal with an actual physical stressor. It all began in her brain, specifically an almond sized region called the hypothalamus. As quickly as she opened her eyes, her Sympatho-adrenal-medullary System (SAM) kicked into gear, sending lightning quick instructions from the base of her skull to the adrenal glands atop her kidneys, making the hormones epinephrine and norepinephrineavailable to every cell in her body. Like a Super Star to Mario, these hormones give Elizabeth super powers. Blood and glucose are rerouted from the peripheries and digestive system toward the brain, sharpening memory and heightening senses, all in order to facilitate quick and accurate evaluation of the threat; extra blood rushes to her lungs and muscles: preparing her for action.

Much like Mario, though, these super powers are not designed to last forever. Indeed, the body, in its never ending quest to maintain homeostasis, has developed mechanisms to stop the stress response and help the body recover. Elizabeth’s Hypothalamic-Pituitary-Adrenocortical System (HPA Axis) is a key player in this regard; it was triggered alongside her SAM on that momentous night and follows a very similar path:

The hypothalamus releases Corticotropin-releasing hormone (CRH)signaling the pituitary to release adrenocorticotropic hormone (ACTH). The ACTH then takes a ride through the blood until it reaches the adrenal cortex atop the kidneys with a decree from the brain to begin secreting corticosteroids, including cortisol. Cortisol is similar to the hormones that gave Elizabeth her superpowers, but its effects are more delayed. As an added bonus, cortisol goes back to the hypothalamus with a message to stop further release of CRF, effectively shutting down the stress response.

Screen Shot 2016-07-08 at 7.07.19 PM

While the SAM is crucial in the initial response to a stressor, the HPA axis is responsible for coordinating a complex and appropriate game plan during and after the stressor. When these two systems work harmoniously it’s a beautiful thing to watch. Unfortunately, in our world, that’s not always the case.

Because of the storm, most of Elizabeth’s possessions were so damaged they had to be replaced, she lost important work and school data on her computer, and she was strapped for money; her stress become chronicHer body embraced a low level fight or flight response everyday.

The body is not well adapted for this kind of stress; the white-coats call it allostatic load and it produces wear and tear throughout the body. In fact, studies have shown that chronic stress has sweeping effects on the body including, but not limited to, heightened risk of infection, accelerated progression of coronary artery disease, damage to the structural and functional integrity of brain systems; a greater risk of autoimmune disorders, depression, diabetes, and even poorer wound healing. Now that we know what chronic stress can do to the body, we can begin to examine Elizabeth’s symptoms through a bio-psycholgical lens.

The fact that Elizabeth began getting sick more often than usual is likely a function of chronic stress suppressing her immune function. While the mechanisms at play here aren’t clearly understood, Miller et al. (2002) present a glucocorticoid receptor resistance (GCR) model in which exposure to high concentrations of glucocorticoids cause white blood cells to mount a counter-regulatory response; this response down regulates glucocorticoids receptors which, in turn, diminish the immune system’s sensitivity to these hormones.Glucocorticoid hormones, including cortisol,  are what normally terminate the inflammatory response. When this process is disrupted, inflammation takes over the body, unchecked and undeterred. This could lead not only to increased risk of getting a cold, but also to increased risk of developing an autoimmune disorder. Indeed, Cohen et al. (2012) found that people with recent exposure to long-term stressful experience, like Elizabeth, demonstrated GCR and those with GCR were subsequently at a higher risk of developing a cold.

Interestingly, Cohen et al. (2012) found no effects of circulating cortisol levels on GCR or inflammation (p. 5997), suggesting that how target tissue responds to cortisol is a better indicator of disease risk than the levels of the hormone itself.

Elizabeth also had trouble concentrating at work and even seemed forgetful at times. Numerous brain regions, including the hippocampus, the prefrontal cortex, and the amygdala, contain many adrenal steroid receptors.  Studies show that, in non human animals, chronic psychosocial stress results in cellular changes in the hippocampus that actually decrease its overall volume. This reduction in hippocampal volume is also seen in humans; Gianaros et al. (2007) found that chronic perceived stress predicted decreased grey matter volume in the right hippocampus in post menopausal women (p. 800).

Functional deficiencies in the brain have also been associated with chronic stress. After a dose of synthetic glucocorticoids, dexamethasone, was administered, rats that underwent treatment showed impaired working memory and cognitive flexibility during a Morris water maze test. In addition, long term potentiation (LTP) is suppressed in the presence of high levels of corticosteroids at the glucocorticoid receptors in the hippocampus. Moreover, psychological stress, such as Elizabeth feeling anxious when she was back in her apartment (especially when rain was predicted), causes decreased activity in the orbitofrontal cortex and decreased volume overtime.

Here we see that chronic stress, and the hormones associated with it, have functional and structural effects on key areas of the brain that regulate memory and emotion. It is important to note, however, that, in humans, it is perceived psychological stress that has a greater impact on these brain regions than physical types of stress.

The precipitating factor to Elizabeth’s current state of malaise is the night that tree came tumbling down onto her life, something that was as much out of her control as the storm that triggered it. If Elizabeth’s stress continues to be chronic she is at risk of adversely changing her brain and developing a myriad of physical diseases.

The brain’s ability to turn sensory information into a plan of action so quickly and effortlessly, then, is a double edged sword. On one hand, this autonomic response certainly helped you avoid hitting grandpa at the last second. In the past, it helped our ancestors avoid predation well before guns and agriculture made us the apex predators on Earth. Yet, in this world, the same mechanisms that allowed our ancestors to survive thousands of years ago can have terrible effects on human health.

If you think about it, the world has seen so much change in the last 100 years that its hard to imagine how the brain could keep up. In 1900, the main method of transportation was horseback. 69 years later, in 1969, we went to the Moon. We went from horseback to rocketship in one human generation. This is tremendous change, but it pales in comparison to the changes we’ve seen in just the last 10 years.

The human brain is a tremendously adaptive piece of hardware. But perhaps the stark increase in stress related diseases indicates the operating system, culture/technology, is changing too quick for the hardware, resulting in bugs and glitches. Your brain has no idea WTF WiFi is, but when you freak out because it doesn’t work for a few minutes, it freaks out too; when you freak out because you can’t choose between a burger or a salad, it freaks out too; if you go crazy because someone cuts you off on the road – your brain goes crazy too.

Here’s the good news: if we change our perspective about the problems in our life we can greatly reduce our risk of disease. It sounds crazy, right? That we can think our problems away as much as we can think them into existence? It’s not crazy. But it’s not easy either. We can’t always do it alone, and tangible social support is a major key. The reality is that shit, pardon my French, will always hit the fan, and our conscious evaluation of a situation goes a long way to how our brain reacts to a stressor. By understanding our own attitudes and feeelings, we can do the job our brain has done for our psyche for 10,000 generations; we can give it time to catch up; we can fill in the gaps – we can relax.

So it is: Bobby McFerrin was on to something, “don’t worry, be happy” turns out to be some pretty solid scientific advice.

Easier sung than done, of course.




Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012). Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proceedings of the National Academy of Sciences of the United States of America109(16), 5995–5999.

Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A. (2007). Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus. NeuroImage35(2), 795–803.

McEwen, B. S., & Gianaros, P. J. (2010). Central role of the brain in stress and adaptation: Links to socioeconomic status, health, and disease. Annals of the New York Academy of Sciences1186(1), 190–222.

Miller, G. E., Cohen, S., & Ritchey, A. K. (2002). Chronic psychological stress and the regulation of pro-inflammatory cytokines: A glucocorticoid-resistance model. Health Psychology21(6), 531–541.

Kubzansky, L. D., Davidson, K. W., & Rozanski, A. (2005). The clinical impact of negative psychological states: expanding the spectrum of risk for coronary artery disease. Psychosomatic Medicine67, S10–S14.

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  1. Me Dave Burns Reply

    Typo? “Spaien brain takes it all in where”

    This is an important and interesting topic. But the article is a bit long on dire and short on solution. Still pretty good.

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    Your writing taste has been surprised me. Thank you, very great

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