Scientists from Columbia University and McGill University have discovered that high levels of a brain chemical called SGK1 may be responsible for depression and suicidal thoughts in people who experienced trauma or neglect during childhood.
The finding could lead to a new type of antidepressant that targets this chemical and works better for those who suffered early life adversity.
The study, published in the journal Molecular Psychiatry, offers an important breakthrough for understanding why traditional antidepressants often fail to help people with a history of childhood trauma.
About 60% of American adults with major depression and nearly two-thirds of those who attempt suicide have experienced some form of childhood abuse or neglect.
“Current antidepressants are often less effective for people with a history of childhood adversity, who represent a large proportion of adults with depression,” explained Christoph Anacker, the study’s lead author and assistant professor of clinical neurobiology at Columbia University.
“What’s exciting about our study is that it opens the door to new treatments, as SGK1 inhibitors are already being developed for other medical conditions.”
Childhood adversity—such as growing up in a violent home, experiencing neglect, or suffering abuse—is one of the strongest predictors of depression in adulthood.
While antidepressants like SSRIs can be effective for many people, they frequently fail for those whose depression stems from early trauma. Researchers believe this is because the biological causes of depression are different in these individuals.
About ten years ago, Anacker and his colleagues discovered unusually high levels of SGK1, a protein produced by the body in response to stress, in the blood of patients with depression who had not taken medication. In the new study, they examined brain tissue from people who had died by suicide.
They found much higher SGK1 levels in those who had suffered childhood trauma—up to twice as high as in other individuals.
The team also analyzed data from children who had faced early life adversity and found that those with genetic variants increasing SGK1 levels in the brain were more likely to develop depression as teenagers. This suggests that SGK1 may play a direct role in how trauma leads to depression and suicidal behavior later in life.
The researchers then tested their theory in mice. When mice were exposed to chronic stress, they began showing behaviors similar to depression in humans.
But when the scientists gave them an SGK1 inhibitor—a compound that blocks the protein’s activity—the mice did not develop these depressive behaviors. This finding suggests that SGK1 inhibitors could be used to prevent or treat depression in people who have suffered early trauma.
Some SGK1 inhibitors are already being tested for other conditions, such as heart rhythm disorders, which means clinical trials for depression could start relatively soon. The study also points to the potential of genetic screening to identify which patients might benefit most from this type of treatment.
“There’s an urgent need to identify and treat people at the highest risk of depression and suicide after early life adversity,” Anacker said. “SGK1 gives us a promising new direction to explore.”
If further research confirms these findings, SGK1 inhibitors could represent the next generation of antidepressants—designed specifically for people whose depression began with childhood trauma. This would mark an important step toward more personalized mental health treatment.
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The study is published in JAMA Pediatrics.
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