Negative early-life experiences, such as abuse or the loss of a parent, shape how the brain copes with future stress.
Each year, nearly one million children in the United States are victims of physical abuse, sexual abuse, or neglect. As a result of their early life stress, they are more likely to develop anxiety, depression, or aggression later on. But scientists still don’t fully understand what makes these children vulnerable.
In a new study from the University of Wisconsin, Madison that appeared in Child Development, researchers discovered one of the biological ways that abuse changes the brain. In a strange twist, childhood stress seems to cause genetic changes that make the children less able to cope with high levels of stress hormones later in life.
Researchers gathered 56 children ages 11 to 14, 18 of whom had records with Child Protective Services. To control for factors like family status, the researchers assessed whether the children’s parents were married, how well their jobs paid, and what level of education they had received. Then, the researchers drew a blood sample from each child and analyzed his or her DNA.
The researchers looked at a gene called NR3C1, which codes for a type of hormone docking site called a glucocorticoid receptor. Its job is to offer a site for one of the body’s stress hormones, cortisol, to connect and communicate with cells. Specifically, they studied the promoter region of the NR3C1 gene, which tells the gene how many times to express itself and how many glucocorticoid receptors to make. In children who had suffered abuse, these promoter regions were methylated at much higher rates than in children who had not been abused.
“Methylation is a biochemical process that essentially turns genes ‘on’ or ‘off’ by affecting whether genes can be expressed,” said Sarah Romens, lead author on the study, in an interview with Healthline. “We observed that maltreated children had more methylation of [NR3C1 promoter] sites … compared to non-maltreated children. This suggests that maltreated children have less expression of NR3C1, which would likely result in production of fewer glucocorticoid receptors.”
Cortisol is a double-edged sword. It causes wakefulness and alertness, and lets people respond to their environment. The more cortisol, the more you can pay attention and focus. Up to a point.
After cortisol has docked with about 50 percent of the glucocorticoid receptors in the brain’s hippocampus, any more cortisol will cause performance to decline. You become stressed, nervous, or irritable, and have a harder time focusing. With high enough stress levels, you experience anxiety and panic. Long-term exposure to high stress levels causes other wear and tear on the body as well, including wear on the heart and a weakened immune system.
The more glucocorticoid receptors you have in your hippocampus, the more stress you can tolerate before your performance suffers and you break down. And so the more methylated NR3C1 is, the fewer glucocorticoid receptors you have, and the more vulnerable you are to the effects of cortisol.
That’s how it works in rodents, anyway. To confirm this in humans, scientists would have to examine the brain tissue of children. “Of course, it is not ethical, feasible, or desirable to examine brain tissue of living human children,” said Romens. “However, our data on methylation differences in children directly parallel the data on methylation differences in rodents.”
This finding might help explain why people with a history of abuse are at a greater risk for developing mood disorders. “Excessive or prolonged exposure to stress hormones, like cortisol, can cause people to stay chronically upset, alert, and vigilant for danger,” explained Romens.
In her paper, she wrote, “These individuals not only experience more physical and emotional harm than other children, but they may also develop interpretations that the world is dangerous and unpredictable. As a result, these children become more likely to attend to threat in their environments, which may serve as a risk factor for both anxiety and aggression problems.”
Another recent study published in PLOS Medicine looks at the very long-term effects of childhood stress and trauma.
The study examined data from all children in Denmark born between 1968 and 2008, all children in Sweden born between 1973 and 2006, and a random sample of 89 percent of children born in Finland from 1987 to 2007.
Out of everyone in this group, 189,094 had lost a parent before the age of 18. Even after controlling for social and economic factors, people who had lost a parent had 50 percent higher risk of death than those who did not.
Specifically, children of parents who died an unnatural death had an 84 percent higher mortality risk, while children of parents who died of natural causes had a 33 percent higher risk. If the parent’s cause of death was suicide, it boosted the child’s likelihood of natural death by 65 percent and unnatural death by 126 percent. These effects lasted well into adulthood.
“Many studies have suggested that this adverse life event could affect the long-term development of children, by affecting many aspects of one’s life, and mortality risk is the hardest endpoint of all these effects, and at the same time, it is the tip of the iceberg,” said Jiong Li, associate professor at Aarhus University in Denmark and lead author on the study, in an interview with Heathline. “If long-term morality does increase, this will suggest that this … population may have more problems in their life than what we had thought, which are related to not only physical and psychological health, but also other social aspects, which persists into their adult life.”
In fact, Li might be seeing the long-term effects of Romens’ discovery. “Our findings suggest that genetic factors, psychological stress, social-behavioral changes, and social support may be among the underlying pathways,” Li said. “I think the suggested biological mechanisms in [Romens’] study are perfectly in line with our findings. [The glucocorticoid] receptor gene may play a significant role in the pathway linking adverse or stressful life events and health problems, or even social difficulties.”