Tierra Lemon was just 13 when she had her first experience with gun violence. She was playing with friends at a park on Chicago’s South Side when nearby gunfire sent people racing for cover—but not before many of her friends were struck. In high school, Lemon says, “there was so much loss and grief from friends and family suffering gunshot wounds.” In her closest circles, at least 10 people would be shot, some fatally.

Lemon survived her childhood and earned a graduate degree in social work. She returned to the South Side to serve as an advocate for youth who have been injured. As a violence recovery specialist at University of Chicago Medicine, Lemon helps traumatized young people heal, a process that begins with providing emotional and psychological support for teens who arrive in the hospital’s emergency department.

Lemon often shares her own stories of surviving violence in the neighborhood, and she remembers trying to comfort one anguished 16-year-old, injured in a shooting, when he found out his best friend had died in the attack. “People often naturally turn to the coping strategies they know, but those strategies may not always be the healthiest,” Lemon says. “Being able to support patients by adding new coping skills to their toolboxes has had many positive impacts.”

Researchers have a term for the kinds of terrible things that Lemon encounters in her work with children. They’re called adverse childhood experiences, and they include a long list of horrors: violence; parental neglect; emotional, physical and sexual abuse; the death or incarceration of a parent; growing up in a household with substance use problems; and having a family member attempt or die by suicide.

More than two-thirds of children have experienced at least one traumatic event by age 16, according to the U.S. Substance Abuse and Mental Health Services Administration. One in seven kids has experienced child abuse or neglect in the past year, and every day, more than 1,300 children are treated in emergency departments for violence-related injuries.

The COVID-19 pandemic has added a new kind of trauma. By July 2022, more than 218,000 children in the United States had lost a primary caregiver to COVID-19, according to estimates by researchers from Imperial College London. “These deaths were unpredictable and sudden, and children often weren’t allowed to see a dying loved one or attend a memorial service to help process the death,” says Sarah Edwards, director of Child and Adolescent Psychiatry at the University of Maryland School of Medicine. “Those circumstances can make grieving traumatic in itself.”

Opening the black box of early adversity is crucial, researchers say.

Kids growing up with adversity are about twice as likely to develop a mental disorder as children with uneventful childhoods. And the damage persists. Researchers have found associations with 60 mental and physical illnesses, as well as premature death, in adults who experienced extreme stress during childhood. One recent study estimates that these childhood experiences ultimately result in more than 400,000 deaths each year in the United States. That mortality—largely tied to heart disease, cancer and chronic respiratory disease—accounts for 15% of all deaths. More than a third of suicide attempts and sexually transmitted infections can also be associated with childhood adversity.

“Many adult diseases should be viewed as developmental disorders that begin early in life and are associated with poverty, discrimination, maltreatment or violence,” says Jack Shonkoff, a researcher at Massachusetts General Hospital and director of the Center on the Developing Child at Harvard University. Preventing heart disease shouldn’t be only about better nutrition and more exercise in adult years, says Shonkoff. “We should also focus much earlier on prenatal exposures and early childhood experiences that increase risk for cardiovascular problems that won’t appear until decades later,” he says.

Now, research measuring biological and genetic processes in kids living through harsh experiences may drive more attention to these consequences. “There have been tremendous advances, especially during the past five years, in our understanding of how genetic variation, the environment and timing operate together to influence the outcomes of children’s exposure to trauma and adversity,” says W. Thomas Boyce, chief of the Division of Developmental Medicine at the University of California, San Francisco.

Opening the black box of adversity is crucial, researchers say. “The currency for physicians and basic science researchers is understanding biological mechanisms,” says Greg Miller, co-director of the Foundations of Health Research Center at Northwestern University in Illinois. Getting a handle on the biology of adversity will also help researchers and clinicians identify which kids are most at risk so that they can intervene and mitigate the clinical effects. Adds Shonkoff: “We need to leverage advances in biology to develop more refined, science-informed strategies to protect the developing immune responses, metabolic regulation and brain circuits from the disruptive effects of excessive stress activation.”

When someone is threatened or afraid, the body produces large quantities of epinephrine, cortisol and other stress hormones, and the autonomic nervous system ramps up, creating a “fight or flight” response. Those reactions affect blood sugar and insulin levels, blood pressure and heart rate, and cause the immune system either to underperform, impairing the body’s ability to resist pathogens, or to go into overdrive, creating excessive inflammation.When stress responses are activated too frequently, they can become toxic.

Young children are particularly vulnerable to the effects of overwhelming stress. Imaging studies show that being raised in harsh or dangerous environments can change the architecture of growing brains, resulting in faulty neural connections and reduced brain electrical activity.

Developing brains are exquisitely sensitive to their environments, says Margaret Sheridan, assistant professor in the Clinical Psychology Program at the University of North Carolina at Chapel Hill and director of a child imaging research lab there. A child living under constant threat develops an enhanced ability to predict danger because of differences in how their amygdala and ventral medial frontal cortex—brain regions that process risk and fear—activate, she says. This can make it difficult to keep emotions in check as an adult. Neglect or deprivation, meanwhile, can cause the brain to adapt in other ways, which Sheridan says can lead to deficits in the structure and function of the frontal lobe, causing trouble with impulse control, working memory, problem-solving and goal-setting.

Other effects of adversity could manifest through epigenetic changes in DNA that affect gene expression. In children exposed to harsh environments, researchers have found alterations in epigenetic markers, which may provide a cellular explanation for differences in cellular responses to stress and immune function. These can increase chronic inflammation, a major contributor to obesity, diabetes and cardiovascular disease. “Epigenetic changes shape children’s biology in ways that could have lifelong consequences,” says Erin Dunn, associate investigator at MGH and associate professor of psychiatry at Harvard Medical School.

Such changes can also accelerate biological aging, causing children who have grown up in harsh environments to reach puberty ahead of schedule. Their neural networks sometimes develop faster, perhaps to help them deal with adversity. But growing up more quickly could make children more vulnerable to chronic adult diseases. Childhood adversity has been associated with heightened risk of strokes, cancer, asthma, chronic obstructive pulmonary disease, kidney disease, arthritis, gastrointestinal disorders and immune disorders.

In a new study of more than 700 children, Dunn and her colleagues compared epigenetic changes in kids who did not experience adversity with those in children exposed to certain kinds of adverse experiences: physical abuse by caregivers, sexual or emotional abuse, maternal mental illness, poverty and others. She wanted to uncover whether the magnitude of epigenetic alterations depended on how many kinds of adversity a child suffered, the child’s age when the adversity happened and whether recent exposures were the most potent.

Dunn found that for every type of adversity, children under three had the most profound epigenetic changes. Now she is studying how long those changes last. “Some might be short-term to help a child adapt to a stressful environment, but others may persist and cause long-term health problems,” she says.

Complicating efforts to study childhood adversity is that its impact is uneven. “Many kids who sustain these events go on to have absolutely successful, healthy lives,” says UCSF’s W. Thomas Boyce, who has spent decades working out why some children are more susceptible to adverse events than others. In one experiment, he gave three- to eight-year-olds a 20-minute standardized test of nonthreatening but challenging tasks and measured the children’s stress responses, testing cortisol in saliva and using electrodes on the kids’ chests to record electrical events in the heart. He found tremendous variation in how non-traumatized children reacted to stress, with about 20% of kids showing a very high response and an equal percentage with a remarkably subdued reaction.

Boyce then applied this data to the general population of children and found that the most reactive kids, when they grew up in conditions of adversity and trauma, “had terrifically high rates of all of the health outcomes that we were concerned with—respiratory disease, injuries, mental disorders, behavioral disorders,” he says.

Highly reactive kids who grew up in nurturing environments, in contrast, had lower levels of respiratory disease, behavior problems and injuries, and in the general population of children, they were the healthiest of all. The highly reactive children, he says, “were the most responsive and sensitive to both good and bad environments.” Boyce believes that improving the environment of the most reactive kids facing adversity could have a profound impact on their health, perhaps through adulthood.

In looking for ways to help all at-risk children—highly reactive kids among them— Greg Miller at Northwestern teamed up with Gene Brody, professor of human development and family science at the University of Georgia. Brody had developed a program for improving the psychological and academic trajectory of low-income African American youth growing up in rural Georgia. His initial trial randomly assigned 667 mothers and their 11-year-old children to either a seven-week intervention or to a control group. The intervention focused on factors he thought would best mitigate early trauma: building supportive families, enhancing communication between kids and parents, teaching coping strategies for managing stress, and encouraging parents to stay vigilant and engaged when their children were struggling. The intervention led the youth who participated to have fewer conduct issues, delayed the onset of sexual behavior and decreased drug use.

Eight years after the trial ended, Miller. Brody and their colleagues revisited the study participants—who were then 19—to measure markers of inflammation in their blood. The ones who had participated in the intervention had significantly less inflammation than those in the control group. And in a neuroimaging study of some participants when they were 25, the team found that those who had the brief childhood intervention showed improved brain connectivity, particularly in brain networks that help regulate emotions, cope with stress and make decisions under stress. Now a larger study underway, with a new group of children, will evaluate cardiovascular and metabolic disease markers and inflammation before and after a similar intervention.

Other researchers are attempting to mitigate the effects of poverty starting at birth. A recent trial randomly assigned 1,000 low-income new mothers in New Orleans, New York City, Omaha and Minneapolis/St. Paul to receive $333 a month or $20 per month for one year. When the scientists measured the brain activity of the children at age one, toddlers in the intervention group that had received $333 a month had more high-frequency brain activity—which is associated with development of thinking and learning—than those in the control group. The researchers don’t yet know whether those brain changes will persist and ultimately lead to better cognitive and behavioral development, but the trial has been extended, with payments to the mothers to continue until the children are four years and four months old.

Other researchers are trying to mitigate the effects of poverty starting at birth.

Although it appears that interventions during the vulnerable first years of life may have the greatest potential, the teen years could also offer an opportunity to right the wrongs of childhood adversity. “There is an explosion of studies and a renewed excitement about plasticity in the adolescent brain,” says Sheridan. Adds Boyce: “The literature suggests there is a reopening of susceptibility to positive interventions during adolescence.”

At the University of Maryland Children’s Hospital in Baltimore, clinicians expect the children who are admitted to have suffered a broad range of traumatic experiences. “About 80% of our kids have had layers upon layers of trauma and adversity in their lives,” says child and adolescent psychiatrist Sarah Edwards. Last year, the university opened Maryland’s first “trauma informed” child and adolescent inpatient unit, designed to provide kids with a safe and healing place to recover.

“Victims of trauma feel a tremendous loss of control,” says Edwards. “It’s important for kids to have a voice and be actively involved in making choices about their own treatment.” Every patient room has a white board for kids to express emotions through drawing or writing. They can choose the music or sounds they want to hear, and Edwards notes that their voice matters when determining treatment goals and plans.

On the South Side of Chicago, where violence is common and 12 is a common age for children to be recruited into gangs, UChicago Medicine is using some of a recent $9.1 million gift to expand its “ecosystem” of trauma-informed care for children and their families. “So many of the kids we see are basically child soldiers just trying to survive,” says Bradley Stolbach, associate professor of pediatrics at UChicago Medicine. When they’re brought to the emergency room after being injured by gun violence or physical or sexual abuse, they receive one-on-one crisis support, and patients and their families may be visited by a trauma intervention specialist, social worker, psychologist, psychiatrist or chaplain.

Also in Chicago, a hospital-based violence intervention program called Healing Hurt People–Chicago helps youth injured by community violence cope with the trauma, avoid retaliation and stay off the streets. Staff members bond with the kids, mentor them, accompany them to appointments, and help them find safe housing and stay in school. “We focus on their goals, not ours,” says Stolbach, and it seems to be working: “Ninety percent of people who are in our program for six months avoid reinjury and we see reductions in post-traumatic stress disorder.”

At the University of Maryland Children’s Hospital, Sarah Edwards prescribes trauma-focused cognitive behavioral therapy for kids six and older who meet the criteria for PTSD—which affects some children who have traumatic experiences. The youngest may receive psychotherapy with their parents, an approach that in clinical trials has reduced depression and PTSD and led to greater resilience and better performance on cognitive tests. “We don’t want people to remain hopeless—treatments do buffer traumatic stress and help kids develop resiliency,” says Edwards.

She and other child-adversity researchers say their work is hindered by a lack of recognition and funding. “The United States spends massive amounts of money studying and treating cancer and heart disease,” says Northwestern University’s Greg Miller. “But by failing to invest in children’s health, we are missing opportunities to help kids with challenging backgrounds thrive psychologically and build sustainable healthy behaviors.”

The need to respond to what researchers now know about childhood adversity couldn’t be more pressing. “Culturally, scientists are very conservative,” says Erin Dunn of MGH and Harvard. “We hedge, saying that more research is needed or we don’t know how our findings apply to the real world. But the evidence that childhood adversity causes long-term damage is undeniable. We must be ready to take action now.”