Neuroscientists at Columbia University and McGill University have found a stress-related protein called SGK1 that appears to drive depression and suicidal thinking in people who experienced trauma or hardship as children. The discovery could reshape how we treat depression in the roughly 60% of American adults with major depression who endured early-life adversity.
The research reveals something important: depression that follows childhood trauma may work differently in the brain than depression without that history. Current antidepressants like SSRIs help many people, but they're often less effective for trauma survivors. "This suggested to us that the biological processes that lead to depression and suicidality in general may differ from those with less stressful childhoods," says Christoph Anacker, the study's lead author and an assistant professor of clinical neurobiology at Columbia.
About ten years ago, Anacker's team noticed unusually high levels of SGK1 in the blood of unmedicated patients with depression. In their latest work, they examined the brains of adults who had died by suicide and found elevated SGK1 levels — with those who'd suffered childhood trauma showing the highest concentrations, up to twice as much as others who had also died by suicide. When researchers studied children exposed to early adversity, they found that those carrying genetic variants that increase SGK1 production were more likely to experience depression as teenagers.
We're a new kind of news feed.
Regular news is designed to drain you. We're a non-profit built to restore you. Every story we publish is scored for impact, progress, and hope.
Start Your News DetoxA new treatment pathway
These findings point to SGK1 as a biological driver of depression and suicidal behavior, particularly among trauma survivors. The practical implication is striking: drugs designed to block SGK1 might prevent or treat depression in people with a trauma history. In mouse studies, SGK1 inhibitors prevented animals from developing depressive-like behaviors during chronic stress.
What makes this especially promising is that SGK1 inhibitors are already in development for other conditions, like atrial fibrillation. Anacker's team now hopes to begin clinical trials in people with depression and a background of early-life adversity. They also propose that genetic screening could identify individuals most likely to benefit from an SGK1-targeted antidepressant — a way to match treatment to biology rather than guessing.
"There's an urgent need to identify and treat people with the greatest risk of depression and suicide after exposure to early life adversity and SGK1 is a promising avenue to explore," Anacker says.
The research was published in Molecular Psychiatry.
