Individuals facing significant adversity in their early years show elevated levels of specific proteins in their brains, a discovery that may shed light on the connection between childhood difficulties and persistent mental health issues. Moreover, medications targeting this protein could potentially mitigate these effects in the future.

About 1 in 5 adolescents in the U.S. report having experienced at least four potentially traumatic events, such as abuse, neglect, homelessness, or losing a parent. Studies indicate that these experiences can hinder brain development, leading to an increased risk of mental health conditions, including depression, persisting into adulthood.

“The mechanisms through which early life stress and adversity exert lasting effects are still not fully understood,” states Christoph Anacker from Columbia University, New York. “Individuals who have endured childhood trauma usually exhibit lesser responsiveness to current antidepressant treatments.”

Prior studies have indicated that individuals with depression show elevated symptoms such as heightened levels of the protein SGK1 (serum and blood glucocorticoid-regulated kinase 1). While little is known about this protein’s exact role, it seems to affect brain cell processing and information dissemination .

To investigate its effects further, Anacker and colleagues examined SGK1 levels in the postmortem brains of 50 men, 36 of whom had died by suicide. Each participant had completed a questionnaire detailing experiences of physical or sexual abuse before the age of 16.

The research revealed that in the hippocampus—a brain region linked to memory and stress—the levels of genetic material for SGK1 were approximately 33 percent higher in men who had died by suicide compared to those who had not, with even higher levels in those who faced childhood adversity.

In another segment of the study, over 8,500 children aged 9-10 were analyzed, revealing that those diagnosed with depression were more likely to exhibit heightened activity of the SGK1-encoding gene, which was also connected to instances of childhood adversity.

Finally, the researchers conducted an experiment injecting 10 adult male mice daily for 10 days with a novel drug designed to inhibit SGK1. After each injection, the mice were placed in a cage with aggressive counterparts for 5 minutes to elevate stress levels.

At the conclusion of the 10-day study, the treated mice exhibited fewer signs of anxiety and depression than a control group that received saline injections. Notably, the treated group spent more than double the time in the center of a vacant cage rather than cowering in a corner, compared to the control subjects.

“Lowering SGK1 levels in the hippocampus enhances resilience to stress in mice,” states Anacker. A similar biological pathway appears to exist in humans, suggesting that targeting SGK1 may alleviate depression in those who faced early hardships. Although the exact mechanism by which SGK1 contributes to mental health issues remains unclear, one theory is that it inhibits the formation of brain cells in the hippocampus.

While the drug utilized in this study is not yet approved for human use, other SGK1 inhibitors are undergoing clinical trials for specific heart conditions. If proven safe, these could potentially be repurposed for treating mental health disorders, according to Anacker. However, “this fundamental research in rodents is still far from providing the conclusive evidence needed to identify practical drug targets for humans,” notes Katie McLoughlin at Harvard University.

If you need someone to talk to, reach out to the British Samaritans at 116123; the U.S. National Suicide Prevention Lifeline at 1-800-273-8255; or find hotlines in other countries.