How do our biological systems work together to respond to chronic stress? What do these responses mean for early learning and lifelong health? And when we say that early experiences matter, what do we mean by early? This episode of The Brain Architects podcast addresses all these questions and more!
To kick off this episode, Center Director Dr. Jack Shonkoff describes the body’s stress response system, how our biological systems act as a team when responding to chronic stress, and the effects chronic stress can have on lifelong health.
This is followed by a discussion among a panel of scientists including Dr. Nicki Bush (University of California-San Francisco), Dr. Damien Fair (University of Minnesota), and Dr. Fernando Martinez (University of Arizona). The panelists discuss how our bodies respond to adversity, inflammation’s role in the stress response system, the effects of stress during the prenatal period and first few years after birth, and how we can use this science to prevent long-term impacts on our health.
Transcript
Sally: Welcome to The Brain Architects, a podcast from the Center on the Developing Child at Harvard University. I’m your host Sally Pfitzer. Our center believes that advances in science can provide a powerful source of new ideas that can improve outcomes for children and families. We want to help you apply the science of early childhood development to your everyday interactions with children and take what you’re hearing from our experts and panels and apply it to your everyday work.
In today’s episode, we’ll discuss how early experiences, especially during the prenatal period and first few years after a baby is born, get inside the body and can have long–term impacts on lifelong health. Here to help us dig into that science around the early years and lifelong health is Dr. Jack Shonkoff who is the Professor of Child Health and Development, and the Director of the Center on the Developing Child at Harvard University. Hi Jack. It’s really great to have you back.
Jack: Hi Sally. Great to be with you. Thanks very much.
Sally: Let’s dive right in. In previous podcasts, we’ve discussed the impacts of stress and specifically you referred to this term of toxic stress, but we never really went too much into the detail about the body’s stress response system. I’m wondering if you could explain how the body responds to stressors or adverse experiences and environments.
Jack: Yeah. That’s a really good question. For starters, the fact that we have a stress response system is really good. It’s protective for us. It actually can be lifesaving. It’s built into our body because this is how we deal with threat or challenges or hardships. This is the basis of the fight or flight response. So, what’s going on inside our body? Well, when we are stressed, a number of systems in the body get activated. Stress hormone levels are elevated and distributed all through the body. Our heart rate goes up, our blood pressure goes up. This is controlled by signals from the brain to the heart and the cardiovascular system. Our immune system is activated and there’s an inflammatory response. Our metabolic systems are activated to produce more energy for our body—more energy for our muscles, if we have to run or if we have to fight or more energy to think more clearly.
The important message here is that the stress response is not just in our brain, it’s in all of the biological systems in our body that are constantly communicating with each other. They’re all reading the environment, they’re getting feedback, they’re communicating with each other. And this is what allows us to deal with challenges, to deal with an acute threat. The best way to think about this is to think about your brain and your immune system and your metabolic system and your cardiovascular system as all different members of a team. Success as a team depends upon each member of the team having a specific contribution to make. And a successful team depends upon interaction and alignment with each other. If any one part is not pulling its own weight, that affects the whole team.
The immune system is another one of those team players. It is our body’s defense against infection. It’s our body’s ability to respond to injuries that require wound repair, and also helps us to be protected against other kinds of toxic exposures that might come in. Inflammation is the first response of the immune system to the threat of let’s say infection, or let’s say a wound like a cut. Think of it as the mobilization of the kind of first responders of our biological system. Now, everybody knows what inflammation looks like outside the body. When you have a cut or some kind of an injury that’s bleeding, and as it starts to heal, you notice that the area around the cut is red, it can be warm in the beginning, it may be particularly sensitive or painful. That’s the inflammatory response that is actually fighting against germs coming in. It’s kind of cleaning out body tissue that may have been injured by bacteria or viruses or trauma, physical trauma and it is beginning to initiate the healing process. And then over time the redness goes away and it’s less painful and the wound is healed.
Well, that inflammation also can happen internally in the body. Now, in the beginning in a stressful situation, inflammation is very helpful internally. It mobilizes your body’s defenses against infection, and it’s meant to then deal with that acute injury or threat and suppress it. But what happens if the stress continues? This is what we refer to as toxic stress. So, in the beginning, it’s protective, but over time, that inflammation can then start to have a wear and tear effect on the body. It can actually start to disrupt organ systems. Here’s one or two examples. We know that inflammation accelerates atherosclerosis, kind of forming plaques that can clog up your arteries around your heart. Inflammation can also affect metabolic systems leading to insulin resistance internally and increasing the risk for diabetes. Individuals who have severe depression have elevated inflammatory markers in their body, evidence of elevated inflammation.
We know that chronic inflammation internally doesn’t automatically mean you’ll get any of the diseases that I just mentioned, but it means that it increases your risk, which is now beginning to help us understand what is it about chronic severe stress that makes people more likely to develop chronic diseases, not just mental health problems, but physical health problems.
Sally: That’s really interesting. And hearing you talk about how early experiences of chronic stress can have more of a long–term impact, I’m imagining that these impacts are not likely evenly distributed. Right? And I’m wondering if you can talk a little bit more about that.
Jack: We have a very serious problem certainly in this country of unequal access to healthcare and unequal treatment in the health care system. And those are very important and clearly need a lot of work. But that’s not the whole story about disparities in health outcomes. Before we get to issues about healthcare, how does it happen that we have inequalities in the prevalence of many stress-related diseases like heart disease and hypertension and stroke? The new science is helping us get inside the body and say what is it about chronic stress and chronic hardship that leads to health problems? How does that happen? Some of this we’ve talked about already, which is the chronic activation of multiple parts of the stress response system that can have a wear and tear effect on different organs and biological systems leading to the most common and the most expensive chronic diseases in adult life.
So, when we think about that problem of chronic adversity, and we know there are some very consistent and predictable differences in terms of racial and ethnic disparities in health outcomes, starting with prematurity and low birth weight, and then extending all the way up to obesity and heart disease and type 2 diabetes and a variety of other chronic disorders. So how do we understand this? Well, here is some of the things that are very important for all of us to focus on. Number one, the differences by race and ethnicity are not genetic. There may be for some individuals, a greater risk for some diseases related to genetics, but from a population basis, certainly for race, race is a social construct, there’s no biological basis for race and certainly not when we’re talking about illnesses.
This gets us back to the discussion that we’ve been having about how chronic stress and chronic stress activation lays the foundation for greater risk for health problems later in life. Often, we make a list of sources of chronic adversity. We talk about poverty, we talk about racism, we talk about exposure to violence, we talk about a serious mental illness in a family, a young child living alone with a mother with severe depression who loves her child as much as any mother does but can’t be consistently responsive because of depression which is an illness. The body’s stress system and its response is the same regardless of the source of the stress.
There’s something about systemic racism and the kind of interpersonal discrimination that’s part of the daily lives of people who are subjected to structural inequities, things that are built into society, that really requires us to take a careful look and say on the one hand, racism is a source of stress like many other sources of stress, but on the other hand, systemic racism and being constantly subjected to the indignities of discrimination raises a different question, which is: what do we do about that? How do we protect young children from the racism that their families and other caregivers have to deal with?
The real solution to this is to go upstream and to deal at the source with the hardships and the threats of systemic racism that are bearing down on families, rather than focusing on helping families to cope with that racism. This is prevention in its true sense, which is not just to kind of put a band–aid on things, but to go to the source. I think the increased consciousness that we have in our society right now about systemic racism in a way that has always been known to families of color, but has sometimes been invisible—many times been invisible to families who do not know what it’s like to be victimized by chronic racism presents a really important opportunity for us to be much smarter and much more effective about how we think about this issue.
Sally: You brought up some really important points. And we’re actually going to be getting more into the policy and system solutions in the next episode, so stay tuned. But can you tell us a little bit more about why early in childhood development is so important? So, I know we say early a lot, but what does that actually mean?
Jack: Yeah. This is a really important question about what we mean by early and this is one of the real game changers about connecting the brain to the rest of the body. There’s an increasing public understanding that chronic stress activation can affect the development of the brain and ultimately affect your readiness to come to school prepared to succeed. But what this new science is telling us as we connect the brain to the rest of the body, is it’s not just about early learning, it’s also about the foundations of lifelong health.
And if you think about the way we approach early childhood policies and early childhood programs, we have over the years realized that kindergarten is a nice time to start school, but actually it’d be better to start school earlier especially for children who are living under difficult circumstances. We have been increasing our investment in preschool for three and four-year-olds. Makes a lot of sense, good decision in terms of public policy. But for the children who are experiencing the most severe stress, that’s not early because the effects of this serious adversity begin very early.
In fact, they begin even before you’re born. A pregnant woman who is in an environment where there’s very little support, where there’s constant stress activation, and also may be problems with inadequate nutrition, exposure to pollutants in the environment, these kinds of stressors and adversities can actually affect the development of the fetus before a baby is born. And certainly, in early infancy in an environment that is constantly stressed, this can really affect the environment of relationships in which very young children grow up.
When we start to talk about health and not just learning, and we think about how all of these biological systems are responding to the environment, the science is sending us a very clear message. In the face of significant chronic adversity, we need to begin way before age three and four, in terms of providing an environment that’s more supportive of healthy development to reduce those sources of external stress. Metabolic systems and the immune system begin to show effects that may be more difficult to change later as early as the prenatal period and certainly in the first two years after birth.
And so, that’s the important message of this new science for the early childhood period. It’s about health as well as about learning. And early in the face of severe adversity means prenatal and the first two or three years after birth. The bottom line for all of this is we are now learning that what happens early on prenatally and in the first couple of years sets you on a pathway to be either more at risk for some problems or more protected for some problems. But it’s not an absolute prediction. It’s never too late to make things better, but in the long run, you’re always better off by having the best health-promoting experiences as early as possible.
Sally: Yeah. I’ve often heard you use that phrase that early is better, but it’s never too late. And I’m really glad to hear that continue to come up in our podcast because it’s such an important message for listeners to take home. When we come back, we’re going to have Jack answer a question that was submitted by a listener, and we’re going to dive into that question together.
Musical interlude
Sally: And we’re back, and now we’re going to answer a question from one of our listeners. I know how much I enjoy getting a chance to ask you questions, Jack. And this time we thought we’d ask the audience. Here’s one from Sid Gardner.
Sid: Hello. I’m Sid Gardner, President of Children and Family Futures. And my question for Dr. Shonkoff is the impact of prenatal substance exposure is mentioned briefly as one item in the list of toxic effects. How does this affect physical and mental health and what can we do about it?
Jack: Sid, that’s a really important question and I really appreciate it. There’s a very well-described phenomenon of fetal alcohol effects or fetal alcohol syndrome that exposure to alcohol at different times during pregnancy can have significant effects on brain development and also physical features that are very noticeable after a baby is born.
We have lots of examples of how certain exposures to substances that are particularly disruptive to different organ systems based on where they are in their development before birth can have significant consequences after birth. This is about sensitive periods in development, which by definition are periods when that particular organ or that particular function is optimally responsive to environmental influences, even the environment in the uterus. And so, positive experiences promote healthy development and adverse experiences or exposures can disrupt development. That question about prenatal substance exposures, substance abuse is a critical question because it’s the poster child for how we need to pay attention to making sure that we promote a healthy environment in which pregnancy takes place.
All of the systems, the biological systems that we’ve been talking about, the brain, the immune system, the metabolic system develop over time. And when we’re very young, including before we’re born, these systems are relatively immature and they are developing their capacities and they’re developing their structures in part on a timetable that’s genetically determined. When things develop is pretty much genetically determined, but how they develop is literally shaped by the environment in which that development is taking place.
So, if we think about alcohol, whether this is threatening or not to health depends not simply on exposure, but on the timing. And so that’s why from a prevention point of view, the more we know about when are the sensitive periods and how can we prevent exposure to substances or infections that can influence later development, that’s how we promote and preserve good health and promote healthy development. It’s about timing and it’s about the differential sensitivity, the different levels of sensitivity of different parts of the developing brain and developing body as the normal processes of growth and development take place.
Sally: Thanks Jack. And thanks Sid for that great question. Remember if you have a question for Dr. Shonkoff, you can always send us a message on one of our social media channels. We’re on Twitter, Facebook, Instagram, and LinkedIn. Up next, our panel will dig even deeper into the science of early childhood development.
Musical interlude
Sally: Joining us on this podcast today is Dr. Damien Fair. Dr. Fair is the Redleaf Endowed Director of the Masonic Institute for the Developing Brain, Professor in the Institute of Child Development, College of Education and Human Development, Professor in the Department of Pediatrics at the University of Minnesota Medical School and a 2020 MacArthur Fellow. Thanks for being on the podcast today, Dr. Fair.
Dr. Fair: Thanks, Sally. Glad to be here.
Sally: Also joining us is Dr. Nicole Bush, Associate Professor in the University of California, San Francisco Department of Psychiatry and Pediatrics, the Director of the Division of Developmental Medicine and the Lisa and John Pritzker Distinguished Professor of Developmental and Behavioral Health. Welcome to the podcast, Dr. Bush.
Dr. Bush: Thank you. It’s a pleasure to be here.
Sally: We also have Dr. Fernando Martinez, University of Arizona Regents Professor of Pediatrics and the Director of the Asthma and Airway Disease Research Center. Nice to speak to you, Dr. Martinez.
Dr. Martinez: Nice to be here.
Sally: I’m going to start by asking this question to you Dr. Fair. Science is now telling us more about how the brain works with other systems in the body to respond to adversity, and could you say more about what’s actually happening in a child’s body developmentally among these systems?
Dr. Fair: That’s a great question. Now, some would argue that the two most complex systems of the body are the brain and the immune system. Of course, I’m a neuroscientist so I always put the brain at number one. But unlike other organs in the body, like the heart or the lungs or the gut, which are located in very specific parts of our body, the immune system is simply everywhere. Immune cells and the chemical messengers flow freely through our bloodstream. They wiggle their way into different parts of our body everywhere.
For many years, it was very difficult to identify or even think about how the brain might interact with the immune system in response to stress or adversity, anxiety, things like that. And it’s now quite clear that they interact in lots of ways and very specifically in development. For example, immune cells, and again, the chemical messengers that are generated in these immune organs like bone marrow, the spleen, lymphatic system, which kind of cleans out a lot of stuff related to the immune system, all have very intricate ties to the brain.
And we know that stress in particular has a very large effect on the immune system in development. The highest vulnerabilities are likely in younger ages. The immune system is critical for normative development. It may actually come to some surprise to most, but all the neurons that we’re ever going to have for our lives typically are at their final resting place right about the time that we’re born.
And then by the time we’re two, you have this proliferation of connections that go throughout the entire brain related to all those neurons. And then over time, over development, we slowly start to prune away these neurons and these different connections. That’s what it means to mature. Now it’s almost like a sculpture where you’re slowly chipping away to get the final product. Well, it turns out that the immune system is really important for that pruning and that cleaning things up. It probably doesn’t come to too much surprise that the changes in the activity of the immune system have very big impacts on brain development over our lifetime.
Dr. Martinez: I think it’s important to stress what Damien was saying. There’s no one system that reigns. We are one thing. And therefore, while we’re developing, if there are extreme sources of stress, it is the whole system that responds wrongly. That’s why none of these effects are on just one organ. Of course, they may be more important for one organ, for example exposures to pollution may affect more the lungs, but now we know that it affects all other organs, including the heart, the brain, of course, the immune system and so forth. That’s an important concept, that we respond like a whole body, not like a single organ.
Sally: That’s actually a really good segue into the next question which I have for you Dr. Martinez. Could you for our listeners go into more detail about inflammation’s role in the stress response system and how it can help or actually hurt us, especially young children whose systems are still developing.
Dr. Martinez: Well in the face of exposures, the body has a system of recognition of these exposures. This process of recognizing what is out there that is not dangerous and what is out there that is dangerous. The response is that of activating the cells that are there, that are part of the immune system that are kind of the first stage of response. That first stage of response is perhaps the most primitive that we have, but it’s very effective sometimes and it’s enough for this danger to go away.
When we are unable to completely clear that first stage, then the second stage occurs. And during that second stage, other cells come from other organs, and a full-blown response develops. Inflammation then is the result of these two phases of the response. Its main objective is to get rid of an acute insult, whatever that insult may be. But when these insults become chronic, in other words, when they develop for a long period of time, or when we have learned not to recognize what is acute and what is dangerous, we start developing what is called a chronic inflammatory response. It’s almost as if we are overdoing it as thinking that we have to be defending ourselves constantly. And that is what is called the chronic inflammatory response.
It’s important to understand that there are these two dimensions of inflammation. One is inflammation as a good thing. Inflammation is a way in which the body responds to an insult to get rid of the insult, to control the insult, to destroy bacteria, viruses, whatever it is that is attacking. But there is a second aspect to it which is this chronic aspect. When you have all these chemical signals and all these cells hanging around the organs that are affected by chronic inflammation, what starts happening is that the organ starts something that we call remodeling. In other words, it starts reorganizing itself. And this is very important during development when the organs are growing. Because now, together with the normal signals of growth and development, you’re seeing these other signals that are interfering with the normal signals that tell the organs how is it that they have to grow. And they start growing “the wrong way.” Asthma, for example, becomes a disease that has transformed the organ. And now we don’t only have to reverse the inflammation that caused this in the first place, but we have to reverse the remodeling of the organ, the remaking of the organ. That’s why it’s important to understand that avoiding the factors that determine chronic inflammation is very important because it has long-term consequences for the individual.
Sally: Dr. Bush, what does the science say about the effects of adversity and stress during the prenatal period and the first few years after a baby is born?
Dr. Bush: It’s a great question. Young children’s brains are remarkably malleable and they constantly are seeking and absorbing information from their environments that their brains need and use to adapt. And this helps ensure their survival and optimize capacity to learn and thrive. But childhood adversities have the potential to affect these systems in a way that leads to impacts on things such as cardio-metabolic health, depression, diabetes, and multiple other health domains across the life course.
People have been getting kind of earlier and earlier in the chain of development to understand where can we make the biggest impact? Where can we understand both the influence and opportunity for intervention? And so
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