‘Harvard Thinking’: The things we carry

Kate McLaughlin: While we know a lot about the long-term impact that adverse experiences can have on our health, we’re still very much in the infancy of understanding why that is the case. Why is it that experiencing a traumatic event in childhood impacts your risk for cardiovascular disease 30, 40 years later? Why does it increase risk for so many kinds of mental health problems, and why does that risk persist over time?

Samantha Laine Perfas: We know that abuse, violence, neglect, and other kinds of adverse events damage our physical and mental health. But given scientific advances, we’re now able to see these effects at the cellular level, and we’re finding that in some cases, the harms run dangerously deep in our bodies and minds. Where’s the science today, how should we respond, and what does the future hold for protecting people from their worst experiences?

Welcome to “Harvard Thinking,” a podcast where the life of the mind meets everyday life. Today we’re joined by:

McLaughlin: Kate McLaughlin. I am the Executive Director of the Ballmer Institute for Children’s Behavioral Health at the University of Oregon.

Laine Perfas: She was formerly a professor of psychology at Harvard. Then:

Jason Buenrostro: Jason Buenrostro. I’m a professor at Harvard University in the Department of Stem Cell and Regenerative Biology.

Laine Perfas: He’s also the director of the Biology of Adversity Project at the Broad Institute. And finally:

Karestan Koenen: Karestan Koenen. I’m a professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health.

Laine Perfas: She is also an institute member at the Broad Institute and directs the Broad Trauma Initiative.

And I’m your host, Samantha Laine Perfas. I’m a writer for The Harvard Gazette.

Today we’ll talk about how adversity affects our biology and what that might mean for healthcare in the future. We know that these adverse experiences affect our well-being, specifically our physical and mental health. What are some of the most common ways that we see ourselves being affected?

Koenen: Some of the observations that have been now made for decades is that adverse experiences, particularly adverse childhood experiences, are related to a host of negative outcomes. Mental health — we usually think of post-traumatic stress disorder, depression, anxiety — but we’ve also traced these things out, and you see increased risk of cardiovascular disease, Type 2 diabetes, autoimmune diseases, and now growing evidence of dementia. You really see this connection between these adverse experiences, mental health, and physical health across the life course.

McLaughlin: The work linking adversity to mental health in particular has been robust and well replicated. What you tend to see is that experiencing adversity early in life, as a child or during adolescence, increases your risk of developing pretty much every type of mental health problem: anxiety, depression, externalizing behaviors or being aggressive, substance use, and even psychosis. And what’s interesting is that you see that risk is elevated not just early in life — in close proximity to when the experiences happened — but you actually see that risk persists across the life course. Someone who experienced abuse as a child is more likely to become depressed, even in middle age, than someone who didn’t experience that early childhood adversity. It stays with us.

Koenen: There also are better and better studies showing that the adversity effects can persist across generations. Those initial studies were with grandchildren of Holocaust survivors, for example, or refugees; very specific groups. But now we have population-based studies, which are showing that maternal experiences can not just impact her offspring, but the next generation of offspring. And I think as more and more data like that come online, we will be able to understand that better.

McLaughlin: Something that you tend to see, really across the board, is what people call a dose-response relationship, where the more types of adversity you experience, the higher your risk becomes for experiencing physical and mental health challenges. And it suggests that even if we’re really good at coping with stress, even if we have lots of sources of support and resilience, at a certain point, the more of these kinds of experiences you encounter, the likelihood that it’s going to have a meaningful impact on your health rises dramatically.

Laine Perfas: I feel like we’ve known for a long time that if you have an adverse experience as a child or at some point in your life, it clearly affects your mental health or your physical well-being. It’s fascinating to see that we’re now discovering that goes as deep as the cellular level. I’d love to talk a little bit about what connections we are finding at the cellular level to these adverse experiences.

Buenrostro: It’s useful to first start and remember that we are this beautiful constellation of different kinds of cells, right? When you think of the brain, the heart, the lungs, a lot of cells have to come together, of different types, to work together to enact a function. And as we look across these kinds of cells that live in the body, all of them have a role to play in the stress response pathway. In the context of a fight-or-flight response, you might imagine a metabolic need in the heart; you might imagine increased immune-cell activation as we prepare for infection; you might imagine a reaction in the nervous system. All those things are happening. Each one of these cells has a role to play. And when cells see too much of those adverse experiences, some cells will learn to become really good at activating, which we might say, “Oh, maybe that’s adaptive, good is better.” But it might also predispose you to future activation. Other cells we expect to see get fatigued from that overwork, and that starts to lead to dysfunction. The challenge in this space is to understand how diverse exposures map on to these diverse kinds of cells that live in our body. And to build that connection to understand how things like load might occur. As you accumulate dose, as we talked about, where are they accumulating? How are they having the impact? And then what happens to them over time?

McLaughlin: While we know a lot about the long-term impact that adverse experiences can have on our health, we’re still very much in the infancy of understanding why that is the case. So why is it that experiencing a traumatic event in childhood impacts your risk for cardiovascular disease 30, 40 years later? Why does it increase risk for so many kinds of mental health problems, and why does that risk persist over time? The thread that ties together all of the work across these different levels of biological systems is trying to understand what those key mechanisms are. Because of course, if we understand, it gives us interesting targets to think about how we might intervene, how we might promote resilience, how we might prevent some of those health problems from emerging down the line.

Koenen: And I think it gets at potential for stratifying and subtyping things that we think of as one thing. So people might say major depression. Some people who have major depression might have more genetic influences on risk. And then there are folks at increased risk of major depression with childhood adversity. And maybe there are some different mechanisms why two people who have depression get depression, which have implications for treatment. So I think the work that Jason does and that Kate has done can have big impacts down the line, both in terms of clinical intervention and also how we think of prevention.

McLaughlin: One way we can think about a model that ties all of the stress biology together is that our bodies, our brains have responses that are adaptive in the short term, and these responses are exquisitely designed to keep us alive in an emergency, ensure that our bodies continue to function as they should when something is immediately important for us to respond to. But where we often see things become challenging is where those short-term responses continue to get activated over long periods of time, where they can have long-term negative consequences, even if they’re quite adaptive in the short term. And that’s certainly something we see when we look at how the brain tends to be impacted by adversity even down to the cellular level; that’s maybe a useful way to think about stress biology in a more general way.

Laine Perfas: I think it challenges some preconceptions we’ve had. There’s this idea that time heals all wounds: Just give it some space and you’ll eventually get to a place where you can proceed as normal. Is that a misnomer? Does it turn out that time does not heal all wounds?

McLaughlin: I think that’s an interesting question. There’s truth in what you’re saying, but we also need to be mindful that what we’re talking about here are averages. On average, people who experience adversity are more likely to experience mental health challenges. They’re more likely to experience physical health challenges, but it’s not a one-to-one. There are many people who experience adversity and never develop depression, never develop anxiety, never develop PTSD or a substance-use problem. There’s remarkable resilience in the face of adversity as well. It’s an important nuance to keep in mind as we talk about all of these biological pathways: None of this is deterministic. Everybody’s body doesn’t respond the same way to a stressor or to a traumatic event. And understanding that variability is part of what makes it so challenging to chart these mechanisms and understand how to intervene.

Buenrostro: What we’ve learned in the field that I come from, this field of epigenetics, is that cells have their own way of keeping memories, so cells can remember past exposures in the absence of the control of the neurons in your brain. And with that in mind, while what Kate said is definitely true, it might be important to know if, me or you, where we fall in that distribution, so that we could better understand our health. The challenge is that because we know these cells can record their own memories, even if you’ve forgotten, or you don’t actively think about these sorts of effects and how that affects your mental health, we might still see these changes manifest in the cells in your body. This creates even more motivation for the work we’re trying to do as a team here, and where we need to really be able to understand, how are these signals being remembered in different cells in your body?

Koenen: One of the things that’s really exciting is this idea that perhaps we could get to the point where we could see the effects of adversity or trauma on cells before it manifests mental health problems or disease and then know about where to intervene or where people might need support.

Laine Perfas: I wanted to ask this earlier, and I got carried away with my other questions, but how prevalent is adversity in this context, and how often does it affect our cells?

McLaughlin: When we talk about these sorts of experiences that feel or sound extreme, the reality is they’re remarkably common. In fact, most people will experience some form of adversity in their lifetime. When we look at childhood experiences of adversity, both in the U.S. and all around the world, most studies that are population-representative show that about half of kids are going to encounter some meaningful form of adversity before they become adults. Most people are going to experience some meaningful form of trauma at some point in their life.

Koenen: In the U.S., it’s about 75 to 80 percent, which is common across many countries.

Buenrostro: Your question had two pieces to it, right, Samantha? You said, how common is adversity? And then you also asked, how common is it that it affects our cells? I think that latter question is what we have very limited insight into. We know and we can, of course, gather information from a population and ask them how common adverse experiences are in the community, but how they inscribe into cells, and to which cells, and whether or not those are the reason why they have a mental health disorder or an autoimmune disorder or heart disease later in life? We still need to make those molecular measurements to make that connection more clear.

Koenen: We also don’t know even if we see a cellular change related to adversity, we don’t know how long that lasts. Is it stable, or what could alter it? Is that true?

Buenrostro: Yeah, that’s certainly an open question. And we have in the field of epigenetics many case studies where the field has of course studied this quite intensely. One example is in smoking. It’s known that in response to smoke exposure, we think of lung cancer. Most people don’t realize that it has a profound effect on your immune system as well. Turns out your body remembers whether or not you smoked 10 years after you stopped smoking. These stressful exposures in general could be imprinted for your lifetime, or for short times or times in between. A lot of that needs to be worked out.

McLaughlin: I think one place where there’s been fairly reliable signals that changes in biology have impacts on mental health is when we look at patterns of brain development. We see some reliable changes that happen in the brain when kids experience certain kinds of adversity, particularly when they experience traumatic events — events that are threatening to your survival, things that are dangerous, being exposed to violence, being exposed to abuse, growing up in a violent neighborhood, or in a household where there’s violence. What we tend to see is that the brain’s patterns for processing emotional information shift in a way that are really prioritizing identifying information in your environment that could signal something dangerous is going to happen. This makes a lot of sense, right? If you’re growing up in a dangerous environment, you want your alarm bell signaling to you, “Hey, something dangerous could be happening right now,” to be sensitive because it’s much more costly to make a mistake of missing a cue in your environment that something dangerous could happen than it is to be overly reactive.

A concrete example, a pattern we see repeatedly in kids who’ve been exposed to traumas, is that this region of the brain called the amygdala is much more responsive whenever there’s a cue that could signal something bad might happen: an angry face, a fearful face, even a neutral face. Neutral faces are ambiguous; you’re not sure what might happen. And we see that in kids who’ve experienced trauma, the amygdala responds much more strongly to those signals that something could be dangerous in your environment. Coming back to this point about adaptivity in the short term, or adaptation, it makes a ton of sense for you to become really sensitive, highly attuned to when something dangerous in your environment might be happening. However, in the long term, we see that this pattern of brain activity — having a sensitive amygdala that’s responding in a strong way anytime you see something that could be negative or could be potentially dangerous — actually predicts the later development of a whole range of mental health problems. If you’ve got a sensitive amygdala and then a traumatic event happens, you’re more likely to develop PTSD in relation to that traumatic event than somebody who doesn’t have a more sensitive amygdala. And we saw that in kids in Boston who were exposed to the Boston Marathon bombing. You see it in military samples where they look at brain imaging before folks go into combat and then experience trauma. It’s just one example that addresses your question of what’s a biological signature: something we measure that’s related to adversity and then predicts mental health challenges down the line.

Buenrostro: We’re also seeing that same phenomenon molecularly. In the last five or so years, the field has developed these single-cell tools, these tools to measure every single cell and what’s happening to them and respond to, say, exposure like adversity. In study after study now, more and more examples are emerging that there is a cellular change associated in the same places in the brain that Kate’s highlighting. So two very different ways of looking at the same parts of the human body, and yet you’re still finding shared consequences from the molecular to the kind of brain activity and connectivity that Kate’s talking about.

Koenen: And there are also colleagues at Massachusetts General Hospital who’ve looked at the same amygdala signatures that Kate’s talking about and link those to markers of cardiovascular disease. So that seems to be a pathway via which adversity links to physical health problems, not only mental health problems.

Laine Perfas: Do we know if the type of experience has an effect? For example, there are experiences that are acute, like you experienced one traumatic event, or there are prolonged-exposure experiences, like growing up in an abusive environment. Do we see those different types of experiences affecting our biology differently?

McLaughlin: The simple answer is yes. One way to think about this is, if we use a concept like stress, it can refer to a lot of different types of experiences. Something that our research has focused on a lot is thinking about, are there key ingredients in those experiences that are likely to lead to particular biological responses? The example I just gave you about amygdala reactivity to threat, we see that pattern specifically in kids who have experienced trauma. Whereas in contrast, kids who’ve experienced adversity that involves more like what we call deprivation — nobody in their household was violent to them, but they were neglected as a child — that’s an extreme form of adversity. Even in the most extreme form — you can think about kids who have grown up in orphanages, like work that’s been done at Harvard on Romanian orphans —  you don’t see the same impacts on the amygdala. Instead, what you see is big impacts on brain systems that are involved in cognitive and social aspects of development. That’s just a simple example, but it captures the bigger idea that you’re asking about. I’d be curious to hear from Jason if you see that similar kind of differentiation at a cellular level.

Buenrostro: Yeah. I’d love to piggyback off of that. We’ve been pursuing this work and the Biology of Adversity project at the Broad, and one thing that we’re doing is using mouse models of these sorts of stressors, either of threat or neglect. And in some of the recent data, there are these places where the two stressors, adverse exposures, converge on common cell types. But then we also see, of course, things that are specific to each. I think in the end the answer will be that there are some common shared effects and there are some things that are specific. And one idea that we have, though we’ll need more data to really be sure this is the case, is that the more thinking part of your brain, the more you go up in the brain, the more experience-specific it’ll be. But the deeper you go into these base functions, like in the hypothalamus that controls your physiology, what your body’s doing in response, probably converges a lot more. Of course, we’ll have to do more studies to really separate those two things, but it is an interesting thought of like, your experience and your recollection of the adverse experience is probably very different across individuals, but the ways it impacts your body and physiology probably has a lot of points of convergence.

Koenen: What Kate was talking about, threat versus deprivation — one thing I’ve been struck by is if you look, there can be many different types of threatening experiences, which can have the same effect. For example, a lot of our work focuses on experiences of trauma and cardiovascular disease, and we see that whether the trauma is a sexual assault, something that happens directly to someone physically, or something like being stalked, where there’s no contact, there’s no physical violence, we see the similar effects on cardiovascular disease. And what these experiences have in common are the threat. So I think the way Kate thinks about this, with dimensions of threat versus deprivation, is a way of then looking at why experiences that may on their face seem quite different actually have a similar effect.

McLaughlin: The more work that’s done on this topic, the more we’re identifying the critical ingredients of the experience. One ingredient we know matters a lot is threat, experiencing something that’s actually dangerous, where your survival is threatened in some way. But to the point Jason raised earlier about lots of different kinds of adversity having some convergence or common features and then some that are specific, I would say is something we see peripherally in systems that are much higher-level than measuring cells. So for example, if you look at patterns of cortisol, either in response to a stressor or just the normal pattern across the day that we all experience, lots of kinds of adversity — threat, deprivation, loss — tend to lead to fairly similar patterns of changes in how your body produces this stress hormone cortisol. But as we move into parts of the brain that are more about appraising your experience and engaging in complex cognition, those are the places where we start to see the type of experience having a more differential impact.

Buenrostro: Yeah, just to add, we’re discussing quite a lot about the experience itself, but we haven’t yet talked about when in your life these things occur. Obviously, as a child or even as a developing fetus, as you’re developing all the tissues and organs you need to be a thriving adult, the impact of stress can be very different, and at different stages of your life, than it would be as an adult or even as an elderly individual. We do know there’s a lot of impact of development, but also, of course, there’s a lot of sex-specific effects, males versus females, that could also alter the response. And then, something we haven’t talked about yet is, of course, your genetic predisposition to diseases. One way we think about it is that stress accelerates the path to disease, but you might already need to have a genetic predisposition for something like cardiovascular disease for the stress or adversity exposure to push you over that limit.

Laine Perfas: What are the implications of knowing that, and what does that reveal about how adversity affects not just an individual, but generations of people?

Buenrostro: I do think it’s more than just healthcare. I think it’s also about history. And words in our field have been used like personalized medicine, right? This idea that we’ll be able to use your genetic and your lifestyle data to then better understand who’s at risk for what and to be able to better tailor therapies, medicines, to help you recover or even prevent other diseases. It’s important that we’re able to understand what kind of traumatic exposures that communities and populations have faced, not just in the current day today, but also into the future, and how we might better support those communities to thrive

Koenen: I envision a future where we’re not just focused on the individual. We need to focus on the individual, but we already have a lot of information on what can support people to reduce adversity and improve the lives of people who are experiencing adversity. A colleague of mine, Natalie Slopen, just published a paper on housing support payments. Even if you had other kinds of childhood experience, other kinds of adversity, if their families received housing support, then they had less of these negative outcomes. We need to help individuals, but we could also shift the curve as a society to where all people are experiencing less adversity, and also the adversity that they’re experiencing has less of a negative effect.

McLaughlin: Yeah, I’d love to build on what Karestan just said. Of course, it’s important to think about individuals, but if we really want as a society to think about how we promote adaptive outcomes, how we support people who have experienced adversity, thinking about policy-level solutions is obviously going to give us the biggest bang for our buck. Some work we did in my lab was looking at the impact of economic disadvantage on kids’ brain development. We used this large-scale national study. It’s got 12,000 kids in it across a range of different states. One of the areas of the brain we also see impacted by adversity is the hippocampus, and you actually see the size of this brain region gets smaller in people who experience trauma as kids and people who grew up in poverty. But we saw that in states where families who are living in poverty get more cash assistance from the state, the impact of that economic adversity on their kids’ brains was substantially smaller, like more than a third less than in states that did not have a generous social safety net. And we saw an even bigger effect on their mental health. So the impact of growing up in chronic poverty on developing anxiety and depression was two-thirds smaller in states that provided these kinds of supports to families than in states that didn’t. There are policy solutions and levers that can be pulled to protect kids, families, people who experience adversity if we have the political will to implement them.

Laine Perfas: We’re still in the early stages of learning about the biology of adversity. But I’m wondering what your thoughts are on things we might be able to begin implementing now, and also where you hope we’ll be 20 years from now.

Koenen: Another benefit of understanding how adversity and trauma affect our whole bodies, not solely our brains, has been the development and new evidence for bottom-up treatments for things like PTSD. There was a big study a couple of years ago that compared cognitive processing therapy, one of the evidence-based cognitive behavioral therapies for PTSD, with trauma-informed yoga. In the trauma-informed yoga, they did not talk about the trauma at all. It was completely body-based, focusing on understanding sensations in your body, choice in terms of what you do with your body. They had equal effects in reducing PTSD. I think this has opened up a question, a whole new area, very different than I was trained as a clinical psychologist: Are there treatments or ways of intervening on trauma, on adversity, on the mental health consequences that are based in our bodies and not completely focused on our brains and our thinking? Which is a huge question, but it’s a big area of interest now that we have these large-scale studies showing this evidence. The reason it’s exciting to me is because some of these things are much more accessible, so it can open up different opportunities for people who’ve suffered from trauma and adversity and are struggling. There may be many different ways to heal.

Buenrostro: We all have different ways of promoting wellness, different coping mechanisms, different approaches to caring for our past exposures. One thing that we hope that the work does in the next 20 years is to create objective quantitative measurements of the effect of treatment. How will you ever get reimbursed in the healthcare setting if there isn’t a measurement you can do, that a doctor could prescribe to quantify the positive effect of that intervention or that therapy? It’s super important for the medical system to have those objective measures. It’s also probably important for the individual who doesn’t want to go on a road trip of trying different interventions and then seeing what works for years of their life.

Koenen: That’s something that I’m excited about. When people are seeking help, to better match them to help that will have the impact they want rather than trial and error, or sort of luck — people get whatever their provider is offering — and that people can be better matched to the help that will best serve them.

Buenrostro: It goes both ways. This is a treatment approach that we’re talking about now, but there are also approaches to resilience, and there are lots of conceivable ways we can imagine promoting that in the community. It could be anything from diet to good sleep, other sorts of supportive networks — and as you think about the factors that best promote resilience, we also need an objective way to measure that. But with objective measures like molecular measurements, we think we can do that in a way that’s much more efficient.

McLaughlin: One of the things that can facilitate resilience is allowing people to access what is probably our most powerful source of resilience, which is the support of other people. You see this in studies of primates and studies even of rodents, all the way up through people, that even in the face of extreme trauma, one of the most powerful factors that promotes recovery — better mental health, better physical health, better immune system functioning, differences in your brain, across the spectrum — is having emotional support. Having somebody, even if it’s just one person in your life, who you can turn to who provides emotional support in the face of that stressor. And kids, even kids exposed to horrific forms of adversity, having that one adult in their life, whether it’s a coach, a teacher, a family member, a neighbor, who provides support, can be incredibly powerful in protecting them against many of these negative consequences we’ve talked about today. One way that I hope society’s becoming more supportive of people who’ve had these kinds of experiences is through this sort of increased public awareness because of what you’re doing today, Samantha. Putting information out there, helping people understand the impact that these experiences have, has led to a sort of shift in a lot of people’s minds in how we think about how best to support people who have come through these kinds of experiences.

Laine Perfas: What gives you all hope as you continue to research this field?

Buenrostro: I just wanted to take a moment and say just how exciting a time we’re in, in the ability to measure molecularly what’s happening in our bodies, and also the opportunity to use new computational approaches like artificial intelligence. We’re able to understand what’s happening mechanistically to cells. And this is just a recent advance in the field. So what we think is, these technologies will create this foundation that allows us to make a bigger societal impact. That’s exciting, not just from the problem we’re talking about today, but also from the opportunity to translate a lot of the challenges we’re talking about into actionable things that might help individuals in future generations.

McLaughlin: We’ve talked a lot about the negative impacts that adversity can have on our health and our brains and our biology, but it’s really important to keep in mind that the average response, for most people who experience even extreme adversity, the most common response is resilience. The second piece that gives me hope is that the kind of ingredients in resilience, the things that are the most powerful protective factors, are what a researcher named Ann Masten at the University of Minnesota calls “ordinary magic.” It’s nothing extreme or out of the capacity of most of us to access. It’s things like social support, having somebody that you can talk to, being a person who is determined or who perseveres in your goals. The kinds of things that can protect us aren’t even necessarily expensive treatments or finding the right therapist — of course, that can help and is important — but for many of us, the most powerful ingredients that can protect us are things that we already have access to, like the other people in our lives. That gives me a lot of hope that there are already a lot of natural sources of resilience and that many kids, many people who experience trauma and adversity, are able to thrive despite those experiences.

Koenen: As someone who’s worked in the trauma field for now, it’s going on 30 years, people often ask me, “What keeps you going? How can you keep studying this?” And one of the things I always come back to is every single person I’ve talked to who experiences trauma or adversity is a survivor. So anyone who’s listening to this episode who may have experienced trauma and adversity and be struggling with it, you are a survivor because you’re still here, and you’re here to listen and you’re here to learn. And then the other piece I’ll add onto what Kate said: When we study resilience in our cohorts of women, one of the key ingredients is meaning and purpose. People can even be suffering from a lot of anxiety and be in distress. But something that really buffers them and improves outcomes over the long haul is finding meaning in whatever you’ve experienced and translating it to a higher purpose. That could be helping other people who’ve experienced what you’ve experienced, serving your community, connecting with other people. Those are some of the things that give me hope in terms of how we move forward.

Laine Perfas: Thank you all for this really great conversation. I appreciate it.

McLaughlin: Thank you.

Koenen: Thank you. It was fun.

Buenrostro: Thank you.Laine Perfas: Thanks for listening. To find a transcript of this episode and all of our other episodes, visit harvard.edu/thinking. And if you like this podcast, rate and review us on Spotify and Apple Podcasts. Every review helps others find us. This episode was hosted and produced by me, Samantha Laine Perfas. It was edited by Ryan Mulcahy, Paul Makishima, and Sarah Lamodi. Original music and sound design by Noel Flat. Produced by Harvard University, copyright 2026.