Kyle Kellams: It's hard to believe you haven't experienced stress sometime in your memorable past. We're still learning much more about the triggers of stress and what it can do to us. A class next fall, hosted by the University of Arkansas Honors College, will explore stress and its consequences.
Grant Shields, assistant professor of human neuroscience in the Department of Psychological Science at the University of Arkansas, will lead the class. By the end of the course, students will have discussed how stress is measured, how stress can influence cognitive functioning, and well — Shields says the course will cover many topics.
Grant Shields: Ranging from kind of what stress is and like a research perspective, which is surprisingly controversial, to how stress affects real-world behaviors like eating, and everything in between. So why do we get more symptoms of chronic illness when we're stressed? Why are we more likely to develop autoimmune disorders? How does stress contribute to early mortality? What's it doing to our cognitive function? What are all the mediating mechanisms that stress acts through to change the things that we see following stress?
Kellams: I think everyone at some point has said, "Oh, I'm stressed" or "I feel so much stress." But you say the clinical definition is somewhat controversial?
Shields: Well, I'm not sure about the clinical definition, but in terms of the definition from a research perspective, there are a few different ways that different kinds of schools of thought within stress research define stress. Some are more kind of biological and others are more subjective. There isn't a great definition that we can apply to non-human animal research and human research in a way that covers the whole gamut of things that we call stress. So if it's a subjective definition, we can't ever say that a non-human animal is stressed because we can't ask it how it's feeling most of the time.
Like a rodent, definitely not. But if our definition is more biological, where does that come from in the first place? How do we know that it's stress biology without having some understanding of stress? So there's kind of this controversy and, depending upon who you talk to, some folks lean more on one side or the other. I actually had an interview one time where somebody made me defend my definition for like 40 minutes out of the hour-long interview.
Kellams: Oh my God.
Shields: Yeah. So it's surprisingly controversial. If you're curious about the definition and how different people think about it, there's a great paper that Elissa Epel was the first author back in 2018. It's called "More Than a Feeling," and then the subtitle is something about defining stress. It's a great paper. That's my go-to for where to find more about that.
Kellams: I can only imagine being asked to defend your definition of stress for 40 minutes — in and of itself, that can produce stress.
Shields: Yeah. And this was in a discussion with probably the biggest titan of the field.
Kellams: Oh gosh.
Shields: He was nearing retirement. And this person had developed, like, the perceived stress scale that everyone uses. And I was in awe of this guy just being around him. And so when he's, you know, saying, "Hey, you need to defend this definition. I don't think this is correct," I was like, "Yeah, you're probably right. Like, OK." And he's like, "No, no, you said this. Let me know your thoughts." And I was sweating bullets.
Kellams: Is stress research something relatively new?
Shields: To a degree, yes. I mean, it depends upon your definition of new. It was first really kind of studied scientifically around 100 years ago. Originally, what we now call stress or stress biology was referred to as the general adaptation syndrome. There was a great science paper that came out, and this researcher — that I can't ever pronounce the name correctly of — showed that a variety of different kinds of aversive experiences in a variety of different animals were eliciting the same kinds of biological responses. And so this general adaptation syndrome was a way to kind of deal with all of these adverse experiences. There was some kind of benefit to this physiological response.
Eventually that morphed into the concept of stress. And people kind of started to study the specific characteristics of situations that would elicit this physiological response and the subjective experience of it as well. So around 100 years, including non-human animal research. More recent than that — since, like, the 1960s, '70s — for like the human side of things.
Kellams: We now know that there are physiological effects of stress. What can they be?
Shields: I'm actually briefly writing about this in a review that I'm writing at the moment. The shortest answer is basically everything. Stress, how we currently understand it, achieves kind of stability — it increases the chances of survival through this broad multisystem pattern of change. Some people call it allostasis rather than homeostasis, stability through change. The kind of standard response that most people think of is a conjunction of the sympathetic adrenal medullary and hypothalamic pituitary adrenal axis, which basically kick off kind of a peripheral fight-or-flight and kind of glucose-ready state, tunes your muscles, provides more energy to them, etc. There's a lot more than that, though.
For one, stress is doing a lot within your brain during the time that those kind of peripheral physiological things are still kind of getting into gear, and those neural effects persist for a while after the stressor exposure. Some of the genomic effects of stress within various brain regions start to kind of get back to normal around like 60 to 90 minutes. Changes in neurotransmission persist regardless of these peripheral physiological things. In addition, more of the current research on how stress influences health has focused on some other peripheral physiological effects of stress, namely the immune system, so that sympathetic adrenal medullary and hypothalamic pituitary adrenal axis response both concurrently shape immune system activity. And those also aren't the only parts of stress that shape immune activity. But most of the kickoff comes from that, I'm going to call it the SAM axis for short.
Noradrenergic activity that's prompted by SAM axis activation tells immune system cells to produce some of these inflammatory proteins that there might potentially be an injury or an infection that often happens following stress. And that preemptive immune response — there's some excellent research that Firdaus Dhabhar has done, like 20 years ago or so — that preemptive response actually facilitates recovery from a potential injury or infection should one occur. So kind of the preemptive immune response is beneficial to health because otherwise we might die. In our current kind of social context, where we're exposed to all sorts of social stressors fairly regularly, that can contribute to runaway kind of systemic inflammatory activity if you're constantly activating the immune system. What ends up happening is the very receptors that are used to downregulate immune system activity kind of lose their effectiveness. What's called glucocorticoid receptor resistance happens as a function of just repeated activation of the HPA axis and immune system activity. So our bodies lose the ability to effectively downregulate this immune system activity, leading to kinds of states of chronic illness or a greater likelihood of developing them, things like that.
So that's kind of the most famous parts of stress biology. There's also changes to sex hormones, and that may be why, for example, folks who live in chronically stressful environments during childhood go into puberty earlier. That's a little bit more speculative. But we know that acute stress changes circulating sex hormones, things like that, which is also good for muscular activity and recovery. Kind of the entirety of stress biology is aimed around increasing survival. But the resources have to come from somewhere, so they come at long-term costs.
Kellams: Right. Many of us know people who say — especially if you know newspaper reporters — "I thrive on the deadline." Like, "I've got 40 minutes to get this in to my editor." And I know a newspaper reporter who said it just starts flowing, and everything else zooms out, and there's almost endorphins for them. Is that really stress? Or is that something different?
Shields: So it depends upon your definition of stress. But I would say yes. And it could be that one of two things is happening. So for everyone, irrespective of one's initial cognitive state, stress is going to facilitate only thinking about the stressor. That's quite beneficial. If you can't wonder, "Have I finished my laundry today?” or something like that. When you're dealing with somebody who has a knife on you, that's probably going to facilitate dealing with somebody that has a knife on you. So there's kind of an evolutionary reason that we would expect that stress would kind of make you zone in on the stressor. And sure enough, research supports that that happens.
So maybe, for those folks that really thrive on the deadline, they're just really thinking about the project that they have and they can't think about anything else. From a different perspective, it could be that those folks are maybe more along the lines of the typical example that I use to illustrate, some work that Amy Arnsten has done, which is essentially showing that there's an inverted U with noradrenergic and dopaminergic activity in how these things influence cognitive function. Most people sit just under the peak of the U. So a little bit of physiological arousal is beneficial, but too much is harmful to higher cognitive function. This is kind of like the Yerkes-Dodson type of thing. Some folks have a little bit too little dopamine and norepinephrine, and so a lot of stress will actually push them to their cognitive peak.
Kellams: Interesting.
Shields: Now an extreme amount of stress would push them over it, but maybe that's what's going on, and Amy Arnsten's work is really cool because she's shown kind of the receptor mechanisms through which those things occur — it has to do with different kinds of dopamine and norepinephrine receptors and relative saturations of these things. So this is one of my favorite things to teach about in any class I teach. She has this great figure. So this will be something that I cover within that “Stress and Its Consequences” course as well.
Kellams: The symposium classes will have students from across campus, from all colleges and disciplines. That's kind of exciting. I mean, because some people will come in from the arts, some from engineering — you'll get all sorts of, I think, interesting comments and experiences about stress.
Shields: Yeah. One of my favorite parts about doing this research is the fact that because everyone has some kind of experience with it, there are really unique perspectives that I can get from talking to people in and outside of my area of research. Usually a little bit of translation has to occur from folks that have never discussed stress from a research perspective, but because people can apply their own expertise to the problems in their lives, you can get some really cool interdisciplinary collaborations going. I know there are some folks who are in some universities working with engineers to develop certain things that will lightly grab your attention and maybe tell you to relax without being, like, beating you over the head with it or something like that. There's just a lot of cool interdisciplinary things that can come out of really anytime you get a bunch of folks together with different perspectives. So I'm really looking forward to the class for that reason, too. I always learn something from my students, and I'm expecting to maybe learn even more this time.
I guess one of the things that I like talking about most when I talk about stress and its consequences is all of the little ways that you might not expect that at least an acutely stressful experience can benefit you. I'm excited to discuss some of those — especially the cognitive effects — during this symposium. Just like your friends who really benefit from the deadline, there are some beneficial effects of stress that I'm trying to figure out in a bit more detail with respect to mechanism. So can we produce this same benefit through some other physiological thing that doesn't come with all the negative consequences that stress does? So that's one thing that I like within stress research, and I'm kind of pushing in terms of my own research direction. And I'll discuss some of the positive effects — maybe not like if we can mimic them, but positive effects — in class.
Kellams: Grant Shields, Thanks so much for your time.
Shields: Yeah. Thanks for having me.
Kellams: Very enjoyable. Grant Shields is assistant professor of human neuroscience in the Department of Psychological Science at the University of Arkansas and will teach the Honors College course "Stress and Its Consequences" next fall. We spoke at the Carver Center for Public Radio last month.
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