Recalibration of Early Life Stress Systems: Impact of puberty with Dr. Megan Gunnar

you're reproductively ready to have offspring, right? Sort of a reasonable time to readjust.

recognized stress experts from UCSF, UCLA and Yale. In this episode, I speak with Dr. Megan Gunnar about the calibration and recalibration of human stress systems. Dr. Gunnar has explored these ideas in the context of early adversity and with a focus on the importance of puberty as a window for recalibration. We're joined today by Dr. Megan Gunnar, who is a regents professor and distinguished McKnight University professor at

the University of Minnesota. Her doctoral training was in developmental psychology at Stanford University, and she then completed her post doctoral fellowship in psychoneuroendocrinology at Stanford Medical School. Since then, she's built a remarkable career studying how stress biology affects neuro behavioral development and all the

processes that help children regulate stress hormones. Dr. Gunnar is a fellow of the National Academy of Sciences and has numerous lifetime achievement awards across many societies and disciplines, including the Association for Psychological Science and the International Society for Psychoneuroendocrinology, I especially admire her interdisciplinary approach to addressing questions of early

life adversity, stress biology and developmental timing. So, welcome, Dr. Gunnar, we're so happy you could join us here on the Stress Puzzle.

six to 12 months of our lives. And that is, you calibrate if I'm going to be living in a really hot climate, I better be able to sweat more than if I'm living in a cold climate.

Calibration of the stress system is similar to that. It's the idea that if the environment you have been born into is full of challenges, perhaps from famines, perhaps from extreme cold or extreme heat, or are from a lot of various kinds of adversity, a lot of people die, etc, etc, you need to calibrate your systems to your stress systems to be able to manage

that degree of challenge, that harshness. However, if you're born into a pretty benign setting where there's plenty of food and everything is wonderful and people aren't dying all around you, then your systems get calibrated to that more benign kind of context. The calibration is calibrating according to the demands that you are likely to experience during your lifetime, but we have a very long lifetime as

compared to a rat or some other much shorter lived species. A number of us have wondered whether there are periods of recalibration during the course of development.

adrenal axis, especially during puberty. And so, I'm curious, what if you could talk us through sort of what's special about puberty, especially for stress systems?

to show that, oh yeah, it also is true in us as humans. And the early period is a very important period, the first few years of life, two, maybe three years of life, a very important for that initial calibration. Puberty is this amazing period of time when there's vast hormonal changes and others have began before me to notice that reactivity of the HPA axis actually increased over

the course of puberty for a period of time.Probably, along with all of the other steroid hormone changes that are going on at puberty that have to do with maturations of our capacity

to reproduce. So, and there was some rat work suggesting that that period of time was also another sensitive period in that dressers that confronted the rat during this peripuberty, around puberty, peripuberty means around puberty period, would have longer lasting effects than the same stressors encountered in the mature rat.

may bridge to later life health and stress responses. So, I guess I'm curious if you could talk about how you've approached working with both animal and human model research to support the hypotheses that you have?

The other thing, no, we would not want to, and which is why I say it happens to kids all the time, and worse than we would ever do if it was experimental. But we, Yeah, and we have to remember that it's not that children don't experience real awfulisms. The animal models also allow us to get a mechanism with kids, especially with young kids, we can't even really draw blood in order to to find out what's going on in their bodies, we're we're pretty well stuck with

really non- invasive measures. Of course, we can image the brain, but we aren't going to go in and dissect it. So, to really get at mechanisms and where things are happening and so forth, you need the animal models, but nature never put an animal on earth to model a human that way. So, we call them animal models, but they're really in many respects, to answer the question of, how did this species evolve to function

puberty with the rat. I started thinking, well, you know, it would be really tasteful if we evolved so that during this period of really marked biological change of puberty and marked hormonal regulatory change of puberty, maybe that helped open up the system again to sample how harsh or benign is my context, and to sort of adjust systems, a stress system accordingly, right before you reach the time when you're reproductively ready to have offspring, right? Sort of a

reasonable time to readjust. So, that's what led me to think about that there's other periods. I have a wonderful student, Marian Howland, who is really interested in the possibility that pregnancy, and for both the woman and possibly for the man, as he to start, if he gets really involved in taking care of his babies, might be a period that opens up the system again for a bit ofrecalibration.

you were really looking for in a sample to test this theory? And you know what you found when you did find that sample?

anticipate. biologically, we evolved to be cared for by one or a few people, cared for by a whole mixture of people with no identifiable attachment figure, and on and on and on. In atmospheres, it's very, very difficult when you put a 20 babies together not to have a lot of germs and babies are dirty, especially when you put them all together, it's hard to

maintainthat. So, the system would be challenged both by pathogens and parasites, and, you know, lack of responsive care, and on and on and on. Okay, we got that now, unfortunately, for most people, the conditions of your early life are fairly predictive of the conditions of later life, right? Threat tends to follow threat and good things tend to follow good things don't have a dramatic reshuffling of our

social classes. There is some, but it's not very dramatic. So, I wanted to test really, whether there was an early calibration period for the stress system. I needed kids who experience radical change in conditions, and that is absolutely true for kids adopted internationally from orphanages. It's not that

life becomes perfectly sweet. Many of them are being adopted into homes with white parents when they're their children of color, and are moving into the US or other countries where they're then also discriminated against, so that everything's not perfect, but in terms of radical change, in moving to high resource homes with people who really want to be responsive to you and care for you and raise you and do all the great

things for you, is a radical change. And so, I initially sought this group as a way of testing the initial calibration of the stress systems and whether it would revamp as soon as they got to goodness, and it doesn't. And that was what was blew me up. It didn't, well did blow me away. I really expected more flexibility in the system, and instead, what I found was that there's a down regulation. There's a hypo functioning of

the adrenal gland. I don't know about the rest of the system. I can't find out about that in the kids who are adopted internationally, and the degree of hypo functioning is associated with problems with ADHD and peer relations and etc, etc, permanent friendliness and problems in attachment. So then, I began to wonder, well, does puberty give an opportunity for the system to reawaken and recalibrate, or are these kids

going to be hypo functioning the rest of their life? So, the question grew out of my original seeking of the sample to

and things like that. So, it I just want to take a step back and say how important that contribution itself is.

Volkswagen. So, we were actually seeing that the heightened reactivity with this recalibration is predictive of increased internalizing issues.

incredible improvements in functioning. I mean, it's not like, gee, it has no effect. No, they, many of them, just showthese massive, incredible rebalance in language and

cognition and growth, and they still struggle with problems. I mean,they're doing incredibly better than were they to stay in the institution, but this period of recalibration of the stress system may raise additional challenges, and I think what we need to understand is whether providing additional support and training and emotion regulation, you may or may not remember, when you went through puberty as a girl.

new hormonal self. Make sense? So, I've been wondering with this recalibration issue, don't get the same kind of emotive feedback from cortisol that you do from estrogen, and progesterone and all those lovely things, but there's a

change in the way the body is working. And I've wondered if whether helping kids understand that they're going through this change process, or perhaps especially because they're going through puberty at the same time, understanding that whole change in biology is not necessarily meaning anything emotionally. It's just your body's adjusting. Right? Don't get all wrapped up in trying to understand why you're upset, because it's just your body. It's going through its thing.

hypo responsivity in response to early life stress. And I was curious if you could just speak to this distinction, and if it was surprising to you, and sort of how you might have navigated that publishing those findings when that wasn't necessarily the dominant view in secondary endocrinology at the time?

years before we began to get our findings. Everybody and their dog absolutely expected that people with PTSD would have elevated cort, and she was finding low cortt, you know, all the silver backs, because it was mostly males, at that time. You know, we're poo pooing or finding, oh, nice little girl,

you've got that wrong. Well, she was absolutely right. Then we came along, and once we had, once we had salivary cortisol measures, we the feel and people could leave the lab and actually have people sample as they went about their everyday lives. Weird stuff began to happen, and people like Dirk Hellhammer and others who were getting Clemens, but especially Dirk here for adults and biorhythms, began to notice that there were not

everybody had a high morning and low evening. There were these people had low and low, I mean, and not, you know, there were these weirdos. And they wrote he and Christine Heim, I think was the first paper. Wrote the first paper on the possibility that hypo cortisolism was a real phenomenon in humans and perhaps associated with problems like chronic fatigue, etc, etc. It's not clear how associated it is with those problems, but that

was their first paper. So when Millie Vasquez and I observed this, kids exposed to significant early adversity, and we wrote our paper. We had, we were not the lone people out in the wilderness saying, Whoa, maybe human beings go sort of hypo under chronic stress. And more and more of those findings began to come in. There are depression. Chronic depression is associated with slightly elevated morning cortisol and

elevated evening, so sort of a tend towards higher cort. But a lot of other adversities is not or, you know, people who are experienced the same adversity and don't get depressed. Christine Hein has shown the hypo functioning. But those you know, the push was so hard to believe that had to be sort of a prelude to hyper that then there was the expectation that those people would become hyper reactive, and maybe not. There's

a lot, lot, lot more evidence that in humans. Now the question is, why and where is it that your stress system, your central brain, central stress system, has become hypo functioning, or is this down regulation happening more in the periphery? And we have data that at least raises the possibility that it might even be at the adrenal level, and the brain is, yeah,

the brain is going on being hyper stress reactive. But, you know, chronic elevations in cort really rough on the body, and so tend to be followed by mechanisms like, get it back down, get it back down. And there's old, very nice data that if in rodents, not in kids, if you inject corticosterone into

the ventricles, so it's going throughout the brain. It tends to upregulate corticotropin releasing hormone in the amygdala and maybe down regulated in that in the hypothalamus, like it's unhooks the different parts of the stress system. Oh, fascinating, yeah, absolutely fascinating. Nature doesn't like to be put in a box, and so if, if she needs, if nature needs to have us become hyper vigilant, pay

attention. There's chronic threat. But if we run really high levels of the peripheral hormones, it's going to, you know, wear and tear us out way too fast. We'll have cushions and other things down regulated the periphery, but keep the

brain going. And then, maybe there's also some possibility that that unhooking, which may save us initially, also may make it hard to ever ramp down what's going on in the brain, because elevations and some cortisol are part of turning off that central system, as well.

about what happens in daily rhythms. So, we need the capacity to also look at the daily rhythms that can get so bollocks up under chronic stress, everybody and their dog would love to be able to measure cortisol with just like a dipstick or something, or, you know, to be able to spit in something, and 10 seconds later, know what the cortisol level is. And there's been a lot of attempts to go and create that technology. It's likely to happen at some point. And that

sort of immediate feedback would be potentially very helpful. You could imagine designing studies, biofeedback, kind of studies to do with that, but we already can do that with heart rate and other things as well. The AI is likely to be critically important, because the body responds in patterns, and not just in one system at a time. So, while all the systems talk to each other in different individuals of different genetics, the way they talk to each other and the sensitivity

and the patterns that emerge are going to be somewhat unique. And the prediction, I mean, heterogeneity is something we really, really need to understand, and we can't really understand it when we go with just one measure at a time, or even two, or even three, and then as we get way into all the nomics, and we need AI to and machine learning to help us put all that in.

patterns of outcomes are are driven by different inputs. In doing that, one of the challenges we have of do we go to dust bowl empiricism, like we don't care that we understand something about biology, just throw them all in a pot and let artificial intelligence sort it out. Or do we guide the work that is part of your answer to that you know, looking with some understanding of gene networks, of understanding of sort of how systems enter. And I think my gut goes biologically informed

AI would be probably what we want to do. But right now, we it's, we're sort of getting really happy with just straightforward machine learning and seeing what it turns out.

the medical lab could do them. So, initially, since I needed blood, I did work with, and I wanted healthy babies, I was confined to the newborn nursery because you could take extra drops of blood when they did the metabolic screening dance, the little heel sticks. Then, I just would, I hired a nurse, and we would take the blood for those, so the phlebotomist didn't have to come, or whoever didn't have to come in. And we would organize that sampling around questions like, What was the

response to circumcision? What all the rest of the things I did in the nursery I was doing all that well, the saliva assays were really coming online. Once I had those, I was like, Yes, I can go out and I can look at the development of individual differences in stress reactivity. And the first study we did and temperament, I was temperament, stress reactivity. Those were my that those that linkage was what I was

interested in. And, we did a whole set of assessments of temperament using the Louisville temperament measure at nine months of age, and I was going to predict stress reactivity to separation at 12 months of age, not at nine months. I was getting reactions just to the temperament assessment. And at

12 months, holy mother, the kids didn't respond. And I'm like, wait a minute, separation from the parent is like the biggest stressor we can use in a non human, in a non human primate, it's like big, and so that was when I called up Gig Levine, my former PhD mentor, and said the adrenal is not doing what it's supposed to. And he sort of laughed, and he says it's doing what it's supposed to, you just don't understand, you're absolutely right and you're not much.

parent away. First of all, I also started thinking about the difference between separating the mother monkey from her infant, and she does not like that idea, and so you are battling. Mother is screaming and yelling, don't take my baby, and you're taking the baby. And that's not what happens in human shoes. Say, mom, would you go out of the room? And she says, Yes, of course. So, it wasn't the same degree of stress. I didn't think, and I began to wonder. I said, you know, I knew

the literature on social regulation of stress. There was some literature there. I thought, well, maybe the attachment system Bowlby said it would be a buffer, and maybe it really was. And so then we did the studies that really showed the buffering effect, the powerful buffering effect of a secure attachment relationship. I also then began to think, well, you know, it would make very little sense if every time a baby got upset, they wrecked their HPA axis pp to this guy.

But also, you. in non human, in rodents, there's this period of stress, hypo responsivity, but our system is much more mature at birth, so it's unlikely to be within the system. But even in the rodent, that capacity to remain high, you know, to not react, is maintained by the mom licking and grooming the baby. And you take those things away, you take away milk into the gut and the licking of the anus, which we don't do, but they do,

and the system becomes reactive. So, even in the rodent, this immature period is being maintained by signals from the mother. So, let's leap forward to humans, much more mature system does react earlier in the first year, but by the, okay, now we've got a kid who's gonna look him up, can go out and get itself into trouble, can cry and return to the mother figure. And maybe, as long as the mothering figure is responsive and is

this, attachment is secure. The crying is just a good signal to the attachment figure that I need help, and if help comes, Well, why do I have to kick off my system? My mothering figure can elevate his or her stress system, which is what happens. So, now on that path and design a set of studies that would show that, yeah, that's what happens.