Childhood difficulties can leave their mark throughout life
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People who experience severe adversity 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. Additionally, drugs targeting this protein could one day help alleviate these effects.
About one in five adolescents in the United States report experiencing four or more potentially traumatic events during 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 health problems, such as depression, 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 experienced childhood trauma also tend to be less responsive to currently available antidepressants.”
Previous research shows that people with depression have high levels of the protein SGK1, or glucocorticoid-regulated kinase 1, in their blood. Little is known about this protein, although it appears to influence the way brain cells process and transmit information.
To better understand its effects, Anacker and colleagues analyzed SGK1 in the brains of 50 men after they died, 36 of whom committed suicide. All the men had completed a survey to find out whether they had been victims of physical or sexual violence before the age of 16.
The researchers found that in the hippocampus – a region of the brain involved in stress and memory – levels of genetic material encoding SGK1 were on average about 33% higher in men who committed suicide than in those who did not, increasing even more in those who also experienced childhood difficulties.
In another part of the study, the team looked at more than 8,500 children ages 9 to 10 and found that those diagnosed with depression were more likely to have increased activity in genes encoding SGK1, with this increased activity also associated with childhood adversity.
Finally, the researchers injected 10 adult male mice daily with an experimental drug that inhibits SGK1 for 10 days. Thirty minutes after each dose, the animals were placed in a cage with an aggressive mouse for 5 minutes, increasing 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 receiving a salt water injection. For example, early mice spent on average twice as much time in the center of an empty cage – rather than huddled in a corner – as control animals.
“When we reduce SGK1 levels in this region of the brain, the hippocampus, mice are more resilient to the effects of stress,” says Anacker. A similar pathway appears to occur in humans, so targeting SGK1 could help alleviate depression in people who experienced difficulties early in life. It’s unclear exactly how SGK1 may harm 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 safe, they could be repurposed to treat mental health problems, Anacker says. Still, “this type of basic rodent research is many, many steps beyond the type of evidence that would be needed to say that we have [an] actionable drug target in humans,” says Katie McLaughlin of Harvard University.
Need a listening ear? UK Samaritans: 116,123; US National Suicide Prevention Lifeline: 1-800-273-8255; telephone helplines in other countries.
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