We begin to understand why childhood adversity leaves its mark

People who experience severe hardship early in life appear to have higher amounts of a certain protein in their brains, a finding that could explain why childhood adversity often causes lifelong mental health problems. What’s more, drugs that target this protein may one day help alleviate these effects.

About 1 in 5 teenagers in the United States report experiencing at least four potentially traumatic events in their childhood, such as abuse, neglect, homelessness, or the death of a parent. Research shows that these can affect brain development and increase the risk of mental disorders, such as depression, well into adulthood.

“We still don’t really understand the mechanisms by which adversity or stress experienced early in life can have such lasting effects,” says Christoph Anacker of Columbia University in New York. “People who have had childhood trauma also tend to be less responsive to currently available antidepressants.”

Previous research shows that people with depression have elevated levels of the protein SGK1, or serum and glucocorticoid-regulated kinase 1, in their blood. Little is known about this protein, although it appears to affect how brain cells process and transmit information.

To better understand its effects, Anacker and his colleagues analyzed SGK1 in the brains of 50 men after they died, 36 of whom died by suicide. All the men had completed a survey on whether they had experienced physical or sexual abuse before they turned 16.

The researchers found that in the hippocampus—a brain region involved in stress and memory—the levels of genetic material that codes for SGK1 were, on average, about 33 percent higher in the men who died by suicide than in those who did not, rising further among those who also experienced childhood adversity.

In another part of the study, the team looked at more than 8,500 children aged 9 to 10 and found that those diagnosed with depression were more likely to have increased activity in genes that code for SGK1, with this increased activity also associated with childhood adversity.

Finally, the researchers gave 10 adult male mice injections of an experimental drug that inhibits SGK1 every day for 10 days. 30 minutes after each dose, the animals were placed inside a cage with an aggressive mouse for 5 minutes, which raised their stress levels.

At the end of the 10 days, the injected mice showed fewer signs of anxiety and depression than a separate group of mice exposed to an aggressive animal after being injected with saline. For example, the former mice spent more than twice as much time on average in the center of an empty cage—rather than huddled in a corner—as the control animals.

“When we reduce the level of SGK1 in this brain region, the hippocampus, mice are more resistant to the effects of stress,” says Anacker. A similar pathway appears to occur in humans, so targeting SGK1 may help alleviate depression among people who have experienced difficulties early in life. It is not entirely clear how SGK1 can lead to poorer mental health, but one explanation is that it interferes with the formation of brain cells in the hippocampus.

The drug used in this study is not approved for use in humans, but other SGK1 inhibitors are in clinical trials for certain heart conditions. If these prove to be safe, they can be reused for mental disorders, says Anacker. Still, “this kind of basic research in rodents is many, many steps away from the kind of evidence that would be needed to say that we have [an] actionable drug target in humans,” says Katie McLaughlin of Harvard University.

Do you need a listening ear? British Samaritans: 116123; US National Suicide Prevention Lifeline: 1 800 273 8255; hotlines in other countries.