The Deepest Well: Healing the Long-Term Effects of Childhood Trauma and Adversity—A Transformative Guide to Understanding Childhood Trauma and Health

by Nadine Burke Harris

If you broke it down, the core issue was a dysregulated stress response. From there you simply followed the thread, looking at how that dysregulation affected each of the body’s systems. We made a choice to start our investigations with the underlying systems. If we wanted to identify and treat what was wrong, we had to know what was happening on a molecular level. We turned back to the literature and tried to break it down system by system, figuring out as best we could exactly how toxic stress was disrupting the normal functions of the body.

the cast of characters in the stress response: the amygdala, the prefrontal cortex, the hippocampus, and the noradrenergic nucleus of the locus coeruleus

Because these parts of the brain are on front lines of the stress response, it makes sense that a severe and prolonged disruption of the norm would hit them hardest, changing how they fundamentally do their jobs.

Another very important region of the brain in understanding how ACEs create long-term problems is the ventral tegmental area (VTA). This is the pleasure and reward center of the brain a...

When the amygdala is repeatedly triggered by chronic stressors, it becomes overactive, and what we see is an exaggerated response to a stimulus like the bear or, as I was beginning to notice in clinic, a nurse with a needle.

The other thing that happens when the amygdala is chronically or repeatedly activated is that it starts messing up its predictions about what’s scary and what’s not. The amygdala begins sending false alarms to the other parts of your brain about things that shouldn’t actually be scary,

This part of the brain is the driving force behind aggressive behavior (sorry, Raiders fans, I’m still looking at you). It works closely with the prefrontal cortex, which is why we see overlap in how they both regulate impulse control. The dysregulated locus coeruleus releases too much noradrenaline (the brain’s version of adrenaline) and can result in increased anxiety, arousal, and aggression. It can also seriously mess with your sleep-wake cycles by overloading your system with hormones that tell it to remain vigilant because (hello!) a bear is in your cave.

The prefrontal cortex (PFC)

is often referred to as the seat of “executive functioning,” which is the ability to differentiate among conflicting thoughts and inputs, consider future consequences of current activities, work toward a defined goal, and exhibit “social control” (that is, suppress urges that, if not suppressed, lead to socially unacceptable outcomes).

For kids with toxic stress, the activity of the prefrontal cortex is inhibited in two ways. First, the overactive amygdala sends messages to the PFC telling it to decrease its functioning because something scary is happening; you don’t want reason getting in the way of survival. The second is that the locus coeruleus is flooding the brain with noradrenaline, compromising the ability to override instincts and impulses. The PFC is the part of the kid’s brain that puts the brakes on impulses and helps him or her make smarter decisions. Telling a kid to sit still, concentrate, and ignore stimuli that are flooding his brain with the need to act is a lot to ask. This down-regulation of the PFC can have different consequences for different people. For some, it results in an inability to concentrate and solve problems, but in others it manifests as impulsive behavior and aggression.

The hippocampi are two cute little seahorse-shaped parts of the brain responsible for creating and maintaining memory. When the amygdala gets activated during a major stress event, it sends signals to the hippocampus that disrupt its ability to knit together neurons, essentially making it more difficult for the brain to create both short-term and long-term memories.

Resulting in fragmented memories and fragmented identity into before event and after event, or dvlpmt of DID in extreme cases

When your body’s stress-response system is overloaded again and again, it messes with the sensitivity of your dopamine receptors. You need more and more of the good stuff to feel the same amount of pleasure. The biological changes in the VTA that lead people to crave dopamine stimulators like high-sugar, high-fat foods also lead to an increase in risky behavior. The ACE Study shows that there is a dose-response relationship between ACE exposure and engaging in many activities and substances that activate the VTA. A person with four or more ACEs is two and a half times as likely to smoke, five and a half times as likely to be dependent on alcohol, and ten times as likely to use intravenous drugs as a person with zero ACEs.

Due to the impact it has on the hormonal systems, the stress response can affect everything from menstrual cycles to libidos to waistlines.

Hormones are the body’s chemical messengers, responsible for kicking off a wide range of biological processes. Big ones include growth, metabolism (how your body gets and stores energy from food), sexual function, and reproduction. So, basically, everything. The hormonal system is very sensitive to the stress response.

Just about every one of the body’s hormonal systems is affected by stress. Growth hormones, sex hormones (including estrogen and testosterone), thyroid hormone, and insulin (which regulates blood sugar) all tend to decrease during stress. Some of the major health impacts are dysfunction of the ovaries and testes (also known as gonads), psychosocial short stature, and obesity. In the case of gonadal dysfunction, for women this can lead to not ovulating, not having a period, or menstrual irregularity.

our patients with zero ACEs lived in the same neighborhood and had the same access to health care, the same lack of safe places to play and nutritious food as our patients with high ACEs. When you realize what toxic stress does to the hormonal systems of kids who have experienced multiple ACEs, you understand that it’s not just because they subsist primarily on a diet of fast food that they are overweight. It’s not just that they are living in a food desert (a term that refers specifically to a neighborhood with a dearth of nutritious food) and are being brought up by parents who think Taco Bell is a healthy alternative to McDonald’s. Those things compound the problem, to be sure, but they are not the whole story. Our data suggested how powerful the underlying mechanism of toxic stress can be—that the metabolic disruption was also an important driver. If you grow up in a food desert, of course it’s going to be difficult for you to be healthy. But if you also have higher cortisol levels that are driving you to crave high-sugar, high-fat foods, it’s going to be that much harder for you to choose broccoli over French fries.

Dysregulation of the stress response has a profound impact on immune and inflammatory responses because virtually all the components of the immune system are influenced by stress hormones. Chronic exposure to stress hormones can suppress the immune system in some ways and activate it in others, and unfortunately none of it’s good. Stress can lead to deficiency in the part of the immune system that fights off the common cold, tuberculosis, and certain tumors.

a person with an ACE score of two or more had twice the odds of hospitalization for autoimmune disease as someone with zero ACEs.

getting a good read on the reality of the threat is difficult when there is an adrenaline and cortisol overload. This kind of disruption early on in development can lead to lifelong alterations in the function of the immune system and, in many cases, to disease.

The more inflammation there is in the body, the greater the chance that some of that inflammation will attack the body’s own tissues, leading to autoimmune diseases like rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis.

which is more important, nature or nurture. People have been arguing over this for a long time, but as science gets more and more advanced, there is less and less to argue about. Scientists can now say pretty definitively that there is no separating the two. In fact, we now know that both environment and genetic code shape both biology and behavior. Considering how closely genes and environment work together, it’s no surprise that the debate raged on for hundreds of years with no winner in sight. Luckily, with the advances in science, we are finally able to see that there is a vital synchronicity that determines what we look like, how our bodies work, and ultimately who we are.

Most people know that DNA is the genetic code, the basic blueprint for your biology. To take that understanding a step further, your body uses this code as a template to produce the proteins that make up new cells and ensure that all the things inside those cells function. Every cell has your entire genetic code in it as well as the machinery to read the code and decide which parts of the sequence to translate into proteins. Environment and experience play a huge role in determining which parts of your genetic code are read and transcribed in each new cell your body creates. How does your experience or environment do that? Well, it turns out that the body doesn’t actually “read” every “word” of its DNA. What scientists have discovered is that baked into the cells are both the genome (your entire genetic code) and the epigenome, another layer of chemical markers that sit on top of your DNA and determine which genes get read and transcribed into proteins and which ones don’t. The term epigenetic actually means “above the genome.” These epigenetic markers are handed down from parent to child along with the DNA. One way to think about it is this: The genome is like the musical notes in sheet music and the epigenetic markers are like the notations that tell you how loudly, quietly, quickly, or slowly to play the notes. There might be a notation to skip an entire section of music altogether. These epigenetic notations are subject to experience, to being rewritten by your environ...

Activation of the stress response is one big way the environment can change epigenetic notations. As your body tries to adapt to the stress of your experiences, it turns certain genes on or off, particularly genes that regulate how you’ll respond to stressful events in the future. That process of the epigenome working with the genome to respond to your environment is called epigenetic regulation and it’s critical to our understanding of why toxic stress is so damaging to our lifelong health. When a four-year-old breaks a bone, that trauma is not encoded in his epigenome; it doesn’t affect him in the long term. But when a four-year-old experiences chronic stress and adversity, some genes that regulate how the brain, immune system, and hormonal systems respond to stress...

This study was a showstopper for me for a couple reasons. It showed the mechanism of these long-term changes was not simply genetic. The adverse experiences of my Bayview patients were factors that extended down to their DNA and likely changed them epigenetically. Meaney’s work showed me not only how moms can negatively affect their pups by not licking them enough but also how they can help them by licking them more. The fact that environment is something we can modify means there is a lot of hope for human pups born to “low-licker” moms. These pups are not damaged goods; they are not defective. If they can get a safe, stable, and nurturing environment at an early age, the biology says that this sets them up to develop a healthy stress-response system in adulthood. As we’ve mentioned, the key to keeping a tolerable stress response from tipping over into the toxic stress zone is the presence of a buffering adult to adequately mitigate the impact of the stressor. In the case of the rat pups, it’s the mom’s licking and grooming. In the case of a human, it could be a dad hugging and listening. The buffer is hugely important, not just to attenuate the stress hormones but also to prevent the kind of epigenetic changes that lead to a dysregulated stress response and the major health issues that come with it.

Dr. Blackburn is one of three scientists who received the Nobel Prize for discovering how telomeres, the sequences on the ends of chromosomes, work to protect DNA from the kind of damage that can lead to premature aging and death. Blackburn teamed up with health psychologist Elissa Epel and the two took off on a research tear, exploring how exactly telomeres could be shortened or damaged and, more important, how to stop it. Blackburn and Epel looked at how food, exercise, and even mental focus affected the health of telomeres. But to me, the most interesting part of what they found was that stress had a major impact on the length and health of telomeres, and that in turn had a major impact on the risk of disease.

telomeres protect DNA strands, making sure that every time it is replicated by cells, the copy is true to the original. Telomeres are very sensitive to the environment, which means that, like good car bumpers, they always take the first hit. Anything biochemically harmful (like stress) is going to damage the telomeres much more than the DNA. When the telomeres are hurt, they send signals to the rest of the cell letting it know that the bumpers have taken too many hits and that the cell should respond. The cell reacts in two major ways. The first is that when the telomeres get too short (too many bad parallel-parkers in the neighborhood), the cell can become senescent, which is a science-y word for old. This means the cell retires and doesn’t do its job anymore. Take collagen (the protein in skin that makes it supple and prevents wrinkles). If too many of the fibroblast cells that are supposed to be making collagen hit the road to play shuffleboard at Del Boca Vista, you’re left looking a decade older than you actually are.

Lots of things can damage the telomeres and lead to premature cellular aging, but chronic stress is a big one. When a cell becomes old or dies, it’s not the end of the world, but if there is too much cell death in one place, it can lead to poor health. For instance, if there is too much cell death in the pancreas, you won’t be able to make enough insulin, which can lead to diabetes. The response a cell can have to damaged and shortened telomeres other than senescence is that it can become precancerous or cancerous. When that happens, it means the ability of the cell to copy its DNA correctly has been compromised, and it begins coding for mutations that say, “Keep making cells forever!” This causes the cells to replicate uncontrollably and grow into a tumor that continues to grow and grow and grow. Simply put, if there is too much damage to your telomeres and they become excessively shortened, it can lead to premature cellular aging and disease or cancer.

adult adversity on its own was not significantly associated with telomere shortening. For each childhood adversity a study participant experienced, his or her odds of having short telomeres increased by 11 percent. Epel and Puterman’s data also showed that household adversities, such as abuse or having a parent who used alcohol or drugs, were a stronger predictor of telomere shortening than household financial stress.

The good news is that even if you have shortened telomeres, maintaining healthy telomeres can protect you from further shortening. How do you keep your telomeres healthy? One important way is by boosting levels of telomerase, which is an enzyme that can actually lengthen the telomere. Once again, the science is new, but it suggests that even if you start out with shorter-than-normal telomeres, you can still slow decline by increasing your telomerase with things like meditation and exercise.

The research on epigenetic regulation and telomeres reinforced what I already suspected—early detection is critical. Now more than ever, I believed if we could identify those at risk for toxic stress by screening for ACEs, we had a better chance of both catching related illnesses early and treating them more effectively. Not only that, but we could also possibly prevent future illness by treating the underlying problem—a damaged stress-response system. If we put the right protocols into place in pediatric offices across the city, country, and world, we could intervene in time to walk back epigenetic damage and change long-term health outcomes for the roughly 67 percent of the population with ACEs and their children. And, someday, their great-grandchildren.

toxic stress is an unseen epidemic affecting every single community. Since the original ACE Study was published, thirty-nine states and the District of Columbia have collected population ACE data. Those reporting their data show that between 55 and 62 percent of the population have experienced at least one category of ACE, and between 13 and 17 percent of the population have an ACE score of four or more. The states with the highest rates of ACEs among young children were Alabama, Indiana, Kentucky, Michigan, Mississippi, Montana, Oklahoma, and West Virginia. Left unchecked, the effects of ACEs and the toxic stress they create were being handed down by well-meaning parents in families all across the country and, undoubtedly, around the world.

I was trained to believe in the power of clinical medicine and public health to improve lives, yet it is clear from these conversations that many people who have experienced ACEs and are grappling with their lifelong effects don’t know what they are dealing with. No doctor has ever told them that there might be a problem with their stress-response system, much less suggested what to do about it.

one of the best approaches for helping doctors who care for patients with ACEs and toxic stress (which, statistically speaking, is every single doctor in America) is integrated behavioral health services. That simply means having mental-health services available at the pediatrician’s (or primary-care clinician’s) office. Later I would find out that this was an emerging best practice, one now being endorsed by just about every national health-care oversight agency, including the U.S. Department of Health and Human Services.

Dr. Lieberman debunked the long-held myth that young children and babies don’t need treatment for trauma because they somehow don’t understand or remember the chaotic experiences they faced. Her work is built on research that shows that early adversity often has an outsize effect on infants and young children, just like it did on Dr. Hayes’s tadpoles. After years as a clinician, Dr. Lieberman came to understand that children’s need to create a story or narrative out of confusing events is actually very normal. Children are compelled to give meaning to what is happening to them. When there is no clear explanation, they make one up; the intersection of trauma and the developmentally appropriate egocentrism of childhood often leads a little kid to think, I made it happen.

Dr. Lieberman sought to explore ways in which both parents and children could talk openly and honestly about trauma. She also rightly recognized that parents’ own rough childhoods and the scars that they still carried might affect the way they responded to their child in stressful or traumatic circumstances, hindering their ability to act as a protective buffer. She learned from her mentor Selma Fraiberg that families can learn how to “speak the unspeakable” and that parents can discover tools to support and buffer their children, even in moments of crisis. Eventually, Dr. Lieberman would go on to codify the CPP protocol and demonstrate its efficacy in five separate randomized trials. Supported by the latest science, CPP is now one of the country’s leading trauma treatments for young children, and it is instrumental in helping the whole family begin to heal.

CPP takes into consideration all the other pressures and drama that both parent and child have to deal with—other family members, the community, work (or lack thereof)—everything that affects the parent-child bond. This allows patients to make connections between the traumas of the past and the stressors of the present, so they can better recognize their triggers and manage their symptoms. Traditionally, if a mom is depressed, she finds her own therapist and they work one on one. CPP’s approach is based on the understanding that the qu...

Childhood adversity significantly increases the risk for just about every sleep disorder there is, including nightmares, insomnia, narcolepsy, sleepwalking, and psychiatric sleep disorders (sleep-eating, anyone?). Nighttime sleep plays a powerful role in influencing brain function, hormones, the immune system, and even the transcription of DNA. Sleep helps properly regulate both the HPA and the SAM axes. During sleep, levels of cortisol, adrenaline, and noradrenaline drop. As a result, lack of sleep is associated with increased levels of stress hormones and increased stress reactivity. As you know from Chapters 5 and 6, these stress hormones kick off the party, triggering brain, hormone, immune, and epigenetic responses to stress. The downstream effects are impaired cognitive function, memory, and mood regulation. Sleep deprivation doesn’t just make you groggy and cranky; it also makes you sick. Lack of sleep is associated with increased inflammation and reduced effectiveness of the immune system. While you’re catching z’s, your immune system does a systems upgrade, using the downtime to calibrate its defenses. Everyone knows it’s important to get sleep when you’re sick, but it’s just as important when you’re healthy. Lack of sleep leaves people more susceptible to illness because the immune system doesn’t appropriately fight off the viruses and bacteria that it is constantly exposed to.

Poor sleep is also associated with reductions in hormones such as growth hormone and with changes to DNA transcription, which for children can be especially problematic, opening the door to issues with growth and development.

Instead of just treating the symptoms of Nia’s failure to thrive, we had been able to treat the root of it—the stress caused by depression and trauma and an unhealthy family dynamic. Despite setbacks along the way, the child-parent psychotherapy had been a real success, changing the dynamic that was affecting Nia’s health and strengthening Charlene’s ability to act as a buffer for her child when problems arose.

While there were certainly challenges and stumbling blocks, we were having great success finding ways to help our patients with ACEs soothe their disrupted stress-response systems and manage their symptoms more effectively. We found that a focus on the underlying biology of toxic stress and the factors that helped balance the dysregulated pathways—sleep, integrated mental-health services, and healthy relationships—made a big difference for our patients.

addressing ACEs as part of a weight-reduction

program was essential. But in an interesting twist, we found that if our goal had been simply to address ACEs instead of obesity, exercise and nutrition would still have been an important part of that. It wasn’t our initial intention to treat our patients’ toxic stress with dodgeball and cooking classes, but we were pleasantly surprised to see how much the kids improved when we added healthy diet and exercise incentives to therapy. I sat down to check in with the moms and grandmas each week, and they reported that when they changed their children’s diet and their levels of exercise went up, the kids slept better and felt healthier, and in many cases, their behavioral issues and sometimes their grades improved. We found that there was plenty of science to support what we were seeing clinically. The data showed that regular exercise helped increase the release of a protein called BDNF (brain-derived neurotrophic factor), which basically acts like Miracle-Gro for brain and nerve cells. BDNF is active in parts of the brain important for learning and memory, like the hippocampus and the prefrontal cortex. We’ve long known that exercise improves cardiovascular health, but the research is piling up in exciting new directions, showing us that moving our bodies builds our brains as well as our muscles. When it comes to combating toxic stress, addressing the dysregulated immune system is as important as supporting brain function. Regular exercise has also been shown to help regulate...

some strong strategies for specifically targeting and healing the dysregulated stress response: sleep, mental health, healthy relationships, exercise, and nutrition. Not surprisingly, these are the same things that, as Elizabeth Blackburn and Elissa Epel’s research showed, boost levels of telomerase (the enzyme that helps to rebuild shortened telomeres).

Researchers doing a similar study on meditation and cardiovascular health found a difference in arterial-wall thickness. Meditation was shown to be associated with reversing the narrowing of arteries, which for patients suffering from ischemic heart disease can be nothing short of lifesaving. In another study involving breast and prostate cancer patients, researchers found that meditation was associated with decreased stress symptoms, increased quality of life, and improved functioning of the HPA axis. Other studies have shown that meditation decreases cortisol levels, enhances healthy sleep, improves immune function, and decreases inflammation—all critical parts of keeping our biological systems balanced and able to mitigate the effects of toxic stress.

While stress activates the fight-or-flight system (also called the sympathetic nervous system), meditation activates the resting-and-digesting system (also called the parasympathetic nervous system). The parasympathetic nervous system is responsible for things like lowering heart rate and blood pressure, and it directly counters the effects of the stress response. Given the profound connection between the stress response and the neurological, hormonal, and immune systems, a calmer, healthier mind seemed like a good place to start reversing the effects of toxic stress.

Slowly but surely, we were building our toolkit of clinical interventions to combat the effects of toxic stress. Sleep, mental health, healthy relationships, exercise, nutrition, and mindfulness—we saw in our patients that these six things were critical for healing. As important, the literature provided evidence of why these things were effective. Fundamentally, they all targeted the underlying biological mechanism—a dysregulated stress-response system and the neurologic, endocrine, and immune disruptions that ensued.

Dr. Dowd decided to do a chart review of all the pediatric firearm injuries in Kansas City for that year, looking for any factors that might be a common thread and possibly preventable. She obtained the health records, hospital admissions, EMS records, and coroner’s reports of every child who had been killed by gun violence in the preceding year. What she found was that their medical histories revealed a pattern that repeated itself with tragic consistency. A typical story looked like this: A patient first comes in as a nine-month-old baby with a suspicious bruise, and the case is referred to Child Protective Services. The investigation is inconclusive. The next notation in his chart is from his pediatrician and details several missed visits for immunizations. At age four his preschool teacher complains that he won’t sit still, has frequent tantrums, and hits other kids when he gets upset. He is diagnosed with ADHD and put on meds. At age ten, he’s fighting and disruptive in school. This time, he’s diagnosed with oppositional defiant disorder and put on more meds. At age fourteen he comes into the ED with a fracture of the fifth metacarpal, the bone in the hand that forms the knuckle of the pinky finger. Doctors call it a boxer’s fracture because that’s the bone that typically breaks when someone punches an object. The final entry in his medical record is at sixteen when he’s brought into the ED for multiple gunshot wounds. This time he doesn’t walk out.

it seemed obvious to me that Dr. Dowd’s prototypical patient was a clear example of untreated toxic stress.

After talking more about the ACE Study and other research on toxic stress, Harris and I agreed that we were looking at the same problem, just from different vantage points. I was trying to address kids’ medical problems and she, like Dr. Dowd, was trying to keep kids safe. But what if we could put our heads together and address the potential root of both problems—ACEs.

When statistics have faces, they feel a lot heavier.