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

Twenty years of medical research has shown that childhood adversity literally gets under our skin, changing people in ways that can endure in their bodies for decades. It can tip a child’s developmental trajectory and affect physiology. It can trigger chronic inflammation and hormonal changes that can last a lifetime. It can alter the way DNA is read and how cells replicate, and it can dramatically increase the risk for heart disease, stroke, cancer, diabetes—even Alzheimer’s.

I believed, ever since we’d opened the clinic in 2007, that something medical was happening with my patients that I couldn’t quite understand. It started with the glut of ADHD cases that were referred to me. As with Diego’s, most of my patients’ ADHD symptoms didn’t just come out of the blue. They seemed to occur at the highest rates in patients who were struggling with some type of life disruption or trauma, like the twins who were failing classes and getting into fights at school after witnessing an attempted murder in their home or the three brothers whose grades fell precipitously after their parents’ divorce turned violently acrimonious, to the point where the family was ordered by the court to do their custody swaps at the Bayview police station. Many patients were already on ADHD medication; some were even on antipsychotics. For a number of patients, the medication seemed to be helping, but for many it clearly wasn’t. Most of the time I couldn’t make the ADHD diagnosis. The diagnostic criteria for ADHD told me I had to rule out other explanations for ADHD symptoms (such as pervasive developmental disorders, schizophrenia, or other psychotic disorders) before I could diagnose ADHD. But what if there was a more nuanced answer? What if the cause of these symptoms—the poor impulse control, inability to focus, difficulty sitting still—was not a mental disorder, exactly, but a biological process that worked on the brain to disrupt normal functioning? Weren’t mental disord...

That there is a connection between poor health and poor communities is well documented. We know that it’s not just how you live that affects your health, it’s also where you live.

But Bayview Hunters Point was the only zip code where the number one cause of early death was violence. Right next to Bayview (94124) in the table was the zip code for the Marina district (94123), one of the city’s more affluent neighborhoods. As I ran my finger down the rows of numbers, my jaw dropped. What they showed me was that if you were a parent raising your baby in the Bayview zip code, your child was two and a half times as likely to develop pneumonia than a child in the Marina district. Your child was also six times as likely to develop asthma. And once that baby grew up, he or she was twelve times as likely to develop uncontrolled diabetes.

In the 1960s, the U.S. Navy decontaminated radioactive boats in the shipyard, and up until the early 2000s, the toxic byproducts from a nearby power plant were routinely dumped in the area.

Environmental injustice etiology ruled out?

My day-to-day experience working in Bayview tells me that the struggles are real and ever present, but it also tells me that’s not the whole story. Bayview is the oily concrete you skin your knee on, but it’s also the flower growing up between the cracks. Every day I see families and communities that lovingly support each other through some of the toughest experiences imaginable. I see beautiful kids and doting parents. They struggle and they laugh and then they struggle some more. But no matter how hard parents work for their kids, the lack of resources in the community is crushing.

Before we opened the Bayview Child Health Center, there was only one pediatrician in practice for over ten thousand children. These kids face serious medical and emotional problems. So do their parents. And their grandparents. In many cases, the kids fare better because they are eligible for government-assisted health insurance. Poverty, violence, substance abuse, and crime have created a multigenerational legacy of ill health and frustration.

As budding public-health crusaders, my classmates and I focused on the sexy part of the parable of the well, the bit where Snow topples the miasma theory. But I also took away a larger lesson: If one hundred people all drink from the same well and ninety-eight of them develop diarrhea, I can write prescription after prescription for antibiotics, or I can stop and ask, “What the hell is in this well?”

Everything I’d learned in my training told me that adversity was a social determinant of poor health outcomes, but what was never examined was how it affected physiology or biological mechanisms. There wasn’t any research that I could fall back on to help me understand how my patients’ traumatic experiences could be affecting their biology and their health.

there is a molecular mechanism behind every natural phenomenon—you just have to look for it.

Why was exposure to the stress hormone so bad for the younger tadpoles? That’s the tricky part. High levels of corticosterone affects the function of other hormones and body systems. For the tadpoles, early and prolonged exposure to corticosterone threw all of these other hormone levels and biological processes out of whack. The effects were maladaptive, meaning that instead of helping the tadpole thrive and survive, the response made things much, much worse. In fact, early exposure often led not only to irreversible developmental changes but, eventually, to death. For instance, levels of corticosterone can have an impact on levels of thyroid hormone, which regulates metabolism. In the case of the tadpoles, corticosterone knocked out the thyroid hormone completely, which is why those tadpoles didn’t grow and develop to the metamorphosis stage. Corticosterone also affects the production of surfactant, which plays a key role in lung development, allowing them to absorb oxygen out of the air. Because I was on the premed track, I had learned in anatomy and physiology how hormones work together in a kind of symphony of homeostasis (the body’s biological balance or equilibrium). But it wasn’t until I worked in the Hayes lab that I really got it. The unlucky frogs served as a critical object lesson. If you have the right amount of each hormone, they all work together to keep the body functioning normally, but if you change one of those levels, the delicate interplay gets thrown o...

For most of early human history, the biggest stressors (stress-inducing events) were predators (short-term stressors) and food shortages (long-term stressors). Back in the day on the savanna, a major purpose of cortisol was to help the body manage that long-term stress. Maintaining homeostasis is the key to survival, so cortisol shows up when the body detects a change in the environment that threatens to push it off balance. With a shortage of supermarkets (and iPhone apps) in prehistoric Africa, early humans spent most of their days finding food, killing food, and preparing food for eating. When times were tough, the body would detect a lack of nutrients and begin the chain reaction that is the stress response. One of the biggest parts of this process is the increased production of cortisol, and a major effect of cortisol is an increase in blood sugar. The brain needs enough blood sugar to be able to think and plan, so this extra punch of cortisol helps keep blood sugar on an even keel, despite a shortage of gazelle BBQ. The steady stream of glucose swimming in your veins also helps fuel your muscles, so in the event that you do see a gazelle, you have the energy to chase it down. Cortisol also helps maintain normal blood pressure by regulating the body’s water and salt levels. And it inhibits growth and reproduction, because if you are living through a food crisis, it’s not a good time to be doing any optimistic long-term family planning; it makes more sense to divert al...

Suddenly, my patients’ physical reactions didn’t seem so crazy. If their systems were flooded with stress hormones just like Sarah’s or the tadpoles’, it stood to reason that their bodies, including their blood pressure, blood sugar, and neurological functions, might react in similar ways; all could be seen as side effects of stress hormones. It made biological sense that a high dose of stress hormones at the wrong developmental stage could have an outsize impact on my patients’ downstream health. It was exactly what happened to the younger tadpoles versus the closer-to-metamorphosis froglets—the difference between adaptive and maladaptive reactions is all about the when.

I had a distinct memory of sitting in Professor Ichiro Kawachi’s classroom in Boston as he presented some striking data about obesity rates in high-risk communities and asking myself, Could this be related to cortisol? Is it possible that the daily threat of violence and homelessness breathing down your neck is not only associated with poor health but potentially the cause of it? It occurred to me, horribly, that people living in crowded public housing in Chicago might not be all that different from tadpoles living in a shrinking pond.

Felitti wondered if she might be subconsciously protecting herself from what must have seemed like a recurring trauma by gaining weight. What if he had been looking at this all wrong? He, as a doctor, had perceived a patient’s weight to be the problem. What if it was actually a solution? What if his patient’s weight was a psychological and emotional barrier, something protecting her from harm? That would go a long way toward explaining why his most successful patients, the ones who had peeled off that protective layer, were so desperate to put it back on.

Emotional abuse (recurrent) Physical abuse (recurrent) Sexual abuse (contact) Physical neglect Emotional neglect Substance abuse in the household (e.g., living with an alcoholic or a person with a substance-abuse problem) Mental illness in the household (e.g., living with someone who suffered from depression or mental illness or who had attempted suicide) Mother treated violently Divorce or parental separation Criminal behavior in household (e.g., a household member going to prison) Each category of abuse, neglect, or dysfunction experienced counted as one point. Because there were ten categories, the highest possible ACE score was ten.

First, they discovered that ACEs were astonishingly common—67 percent of the population had at least one category of ACE and 12.6 percent had four or more categories of ACEs. Second, they found a dose-response relationship between ACEs and poor health outcomes, meaning that the higher a person’s ACE score, the greater the risk to his or her health. For instance, a person with four or more ACEs was twice as likely to develop heart disease and cancer and three and a half times as likely to develop chronic obstructive pulmonary disease (COPD) as a person with zero ACEs.

The original ACE Study was done in a population that was 70 percent Caucasian and 70 percent college-educated. The study’s participants, as patients of Kaiser, also had great health care. Over and over again, further studies about ACEs have validated the original findings. The body of research sparked by the ACE Study makes it clear that adverse childhood experiences in and of themselves are a risk factor for many of the most common and serious diseases in the United States (and worldwide), regardless of income or race or access to care.

The ACE Study strongly establishes a dose-response relationship, which is an important step toward demonstrating causality. A person with an ACE score of seven or more has triple the lifetime odds of getting lung cancer and three and a half times the odds of having ischemic heart disease, the number one killer in the United States.

the stress response can do its job a little too well sometimes. This happens when the response to stimuli goes from adaptive and lifesaving to maladaptive and health-damaging. For example, almost everyone knows that soldiers sometimes come back from the front lines with posttraumatic stress disorder. This condition is an extreme example of the body remembering too much. With PTSD, the stress response repeatedly confuses current stimuli with the past in such a dramatic way that it becomes hard for these vets to live in the present. Whether it’s a B-52 bomber in the sky or a commercial airliner overhead taking tourists to Hawaii, their bodies feel the same—in mortal danger. The problem with PTSD is that it becomes entrenched; the stress response is caught in the past, stuck on repeat.

What I know now is that what happened in my body that night in the Mission district is the same thing that happens to my patients’ bodies when they experience a whole host of adversities ranging from abuse to abandonment. The body senses danger, and it sets off a firestorm of chemical reactions aimed to protect itself. But most important, the body remembers. The stress-response system is a miraculous result of evolution that enabled our species to survive and thrive into the present. We all have a stress-response system, and it is carefully calibrated and highly individualized by both genetics and early experiences. What makes the stress response of a child with zero ACEs different from Diego’s stress response is a complicated question that we will begin to unravel, but it all starts with the same system. When it’s in good working order, it can help save your life, but when it’s out of balance, it can shorten it.

The amygdala: the brain’s fear center Prefrontal cortex: the front part of the brain that regulates cognitive and executive function, including judgment and mood and emotions Hypothalamic-pituitary-adrenal (HPA) axis: initiates the production of cortisol (longer-acting stress hormone) by the adrenal glands Sympatho-adrenomedullary (SAM) axis: initiates the production of adrenaline and noradrenaline (short-acting stress hormones) by the adrenal glands and brain Hippocampus: processes emotional information, critical for consolidating memories Noradrenergic nucleus in the locus coeruleus: the within-the-brain stress-response system that regulates mood, irritability, locomotion, arousal, attention, and the startle response

When you see the bear, your amygdala immediately sounds the alarm telling your brain to be afraid because bears are scary! Your brain then activates your SAM and HPA axes, triggering the fight-or-flight response. Signals from the SAM axis travel along nerves from the brain to the adrenal glands telling them to make adrenaline, which is responsible for many of the feelings that we associate with being terrified. Adrenaline causes the heart to beat stronger and faster, sending blood to all the places that need it. It causes your airways to open so that you can take in more oxygen. It raises your blood pressure and shunts blood toward your skeletal muscles (necessary for running and jumping) and away from that tiny muscle that holds your bladder closed, which is why scared people feel like they’re going to pee in their pants and sometimes do. It also converts fat to sugar for energy. The SAM axis also activates the noradrenergic nucleus of the locus coeruleus, which, as I like to say, is the scientific term for the part of the brain responsible for “I don’t know karate but I do know c-razy!” This is the within-the-brain stress-response center, and it gets you amped up. (Picture Oakland Raiders fans after a winning game or, worse, a losing game.) Adrenaline and noradrenaline are powerful stimulants, designed to help you think more clearly so that you can figure out the quickest path to safety. They also create feelings of euphoria, that adrenaline rush that makes you think you...

Once you do get away and are back in the safety of your cave, both the SAM and the HPA axes are designed to shut themselves down. The body uses a sort of stress thermostat called feedback inhibition that triggers the stress response to turn itself off once it has done its job. High levels of adrenaline and cortisol feed back to the parts of the brain that initiate the stress response and turn them off. What an incredibly evolved system! Especially if you live in a forest and there are bears. But what happens when you can’t experience safety in your cave because the bear is living in the cave with you?

It turns out that cortisol has a predictable daily pattern: it’s high in the morning to help wake you up and get you ready for the day and then gradually decreases, reaching its lowest point in the evening, just when you need to go to sleep. As a result, it’s possible to determine if someone’s cortisol pattern is disrupted. Fisher and Bruce found that children who had experienced maltreatment had higher overall cortisol levels as well as a disruption of the normal daily pattern of cortisol secretion. The morning peak wasn’t quite as high and the daily decline was not as steep, leading to higher levels in the evening and higher total daily cortisol.

We all know that adversity, tragedy, and hardship are a part of life. As much as we’d like to shield our children from illness, divorce, and trauma, sometimes these things happen. What the research tells us is that those daily challenges can be overcome with the right support from a loving caregiver.

The main issue is that when the stress response is activated too frequently or if the stressor is too intense, the body can lose the ability to shut down the HPA and SAM axes. The term for this is disruption of feedback inhibition, which is a science-y way of saying that the body’s stress thermostat is broken. Instead of shutting off the supply of “heat” when a certain point is reached, it just keeps on blasting cortisol through your system.

Positive stress response is a normal and essential part of healthy development, characterized by brief increases in heart rate and mild elevations in hormone levels. Some situations that might trigger a positive stress response are the first day with a new caregiver or receiving an injected immunization.

Tolerable stress response activates the body’s alert systems to a greater degree as a result of more severe, longer-lasting difficulties, such as the loss of a loved one, a natural disaster, or a frightening injury. If the activation is time-limited and buffered by relationships with adults who help the child adapt, the brain and other organs recover from what might otherwise be damaging effects.

the effects are temporary if a solid support network is in place.

Toxic stress response can occur when a child experiences strong, frequent, and/or prolonged adversity—such as physical or emotional abuse, neglect, caregiver substance abuse or mental illness, exposure to violence, and/or the accumulated burdens of family economic hardship—without adequate adult support. This kind of prolonged activation of the stress-response systems can disrupt the development of brain architecture and other organ systems, and increase the risk for stress-related disease and cognitive impairment, well into the adult years.

Healthy development of the stress-response system requires that a child experience both positive and tolerable stress. This allows the SAM and HPA axes to be calibrated to react normally in the face of stressors.

for every ACE a child has, the risk of tolerable stress tipping over into toxic stress increases, as the system responds more frequently and intensely to multiple stressors.

children are particularly sensitive to repeated stress activation. High doses of adversity affect not only the brain structure and function but also the developing immune system and hormonal systems, and even the way DNA is read and transcribed. Once the stress-response system gets wired into a dysregulated pattern, the biological effects ripple out, causing problems within individual organ systems. Because the body is like one big, intricate Swiss watch, what happens in your immune system is deeply connected to wha...

When you put a kid who had experienced adversity in an MRI machine, you could see measurable changes to the brain structures.

They found that the more symptoms a kid had, the higher his cortisol levels were and the smaller the volume of his hippocampus. After the first measurement of the hippocampus, they measured the same kids again twelve to eighteen months later and found their hippocampi were even smaller. Despite the fact that these kids were no longer experiencing trauma, the parts of their brains responsible for learning and memory were still shrinking, showing us that the effects of earlier stress were still acting on the neurological system.

focus would be on the association between ACE scores and two of the most common issues I saw in my patients: obesity and learning/behavior problems.

the profound discovery was that our patients with four or more ACEs were twice as likely to be overweight or obese and 32.6 times as likely to have been diagnosed with learning and behavioral problems.

From Felitti and Anda’s research, I was beginning to understand that the prognosis of toxic stress, the long-term risks that my patients faced, looked very different from run-of-the-mill ADHD. We have a ways to go before we fully understand whether the behavioral symptoms of toxic stress represent a totally different diagnosis. Part of the problem has been that, unlike ADHD, the diagnosis of toxic stress doesn’t yet exist in the medical literature.

when I looked at my patients with high ACE scores, I couldn’t help but think that if I treated just the asthma or the obesity or the behavior problem, I was a really poor student of history. We know from the research that the life expectancy of individuals with ACE scores of six or more is twenty years shorter than it is for people with no ACEs. For a patient with a high ACE score, it may not be the obesity that shortens his or her life but the underlying toxic stress that the obesity is signaling. To treat the root of the problem I had to look at both stories my patients’ symptoms were telling me: the story on the surface and the story underneath.

With Trinity’s complaint of learning and behavior problems, if her ACE score had been zero, a standard ADHD workup would have been warranted. But now I knew that if a patient had four or more ACEs, she was thirty-two times as likely to have learning or behavior problems, which suggested that the underlying issue was probably not ordinary ADHD. In those cases, I was convinced that the problem was chronic dysregulation of the stress-response system, which inhibited the prefrontal cortex, overstimulated the amygdala, and short-circuited the stress thermostat—in other words, toxic stress. When I flipped through Trinity’s chart, I saw that she had an ACE score of six.

The next day, the EKG confirmed the abnormality with her heart. According to the results, it was beating faster and the muscle was working harder than normal. The cardiologist who interpreted the EKG included a note that reinforced my suspicions: possible Graves’ disease. Slim builds and strong heartbeats (as well as hair breakage) can be signs of Graves’, which is an autoimmune disease that results in the thyroid gland being overstimulated. Unlike the example I gave earlier of hypothyroidism (when the thyroid gland doesn’t make enough thyroid hormone), Graves’ disease is a case of hyperthyroidism, where the thyroid gland makes too much thyroid hormone. If you remember, adults with hypothyroidism gain weight easily and can be somewhat lethargic. By contrast, people with Graves’ disease are often hyperactive and can’t seem to keep weight on.

In Europe, hyperthyroidism is often called Basedow’s disease, after Karl Adolph van Basedow, the German physician who described the condition contemporaneously with Dr. Robert Graves. In my research on toxic stress, I had come across some data describing the high number of cases of hyperthyroidism among refugees from Nazi prison camps. In fact, the term kriegs-Basedow (kriegs means “war,” so kriegs-Basedow is “hyperthyroidism of war”) was coined following the observation of an increased incidence of hyperthyroidism during major wars.

It turns out that since 1825, researchers have known that Graves’ disease is often correlated with stressful life events,

many busy physicians do their entire assessment of ADHD based on behavioral symptoms alone, without a stethoscope even touching the patient’s chest.

Once again, I saw how critical it was to take a whole-system approach to examining kids who were at high risk.

Even if I didn’t always know exactly what I was looking for, using the ACE score as a measure of risk for toxic stress was making me a better doctor, helping me put the right lens on the problem...

After prescribing medication to treat Trinity’s Graves’ disease, which was the first story her symptoms were telling me, I prescribed family therapy to treat the second story her symptoms were pointing to—underlying toxic stress. The purpose of family therapy was to teach Trinity and her aunt how to create an environment that would limit the reactivation of her SAM and HPA axes. The goal was to give them the tools to prevent scary or stressful si...

for kids with impaired impulse control and inattentiveness due to toxic stress, PFC function is likely to be on the downslope of the inverted U (kind of like if you drink way too much coffee, you can’t focus to save your life). In those cases, our clinical team tends not to use stimulants like methylphenidate (Ritalin) or drugs derived from amphetamines. Instead, we often use guanfacine, a nonstimulant that was originally developed to treat high blood pressure but has also been used to treat ADHD. Guanfacine targets specific circuits in the prefrontal cortex where adrenaline and noradrenaline exert their action, improving impulsiveness and concentration, even in situations of high stress.

if a dysregulated stress-response system was the source of the problem, it could have far-reaching effects. A disrupted stress response doesn’t affect only the neurological system, it affects the immune system, the hormonal system, and the cardiovascular system as well. Because everyone’s biological and genetic makeup is different, how that dysregulation manifests itself will be similarly diverse.