Scientists Link Brain Chemical SGK1 to Childhood Trauma, Depression, and Suicide Risk
Researchers from Columbia University and McGill University have identified a brain chemical that may explain why people exposed to childhood trauma are more vulnerable to depression and suicidal thoughts.
The study points to a stress-related protein called SGK1 (serum- and glucocorticoid-regulated kinase 1) as a key biological link between early adversity and later mental health struggles. Elevated SGK1 levels were detected in the brains of suicide victims and in individuals carrying genetic variants associated with heightened SGK1 activity.
According to lead author Christoph Anacker, assistant professor of clinical neurobiology at Columbia University, the findings could pave the way for a new class of antidepressants targeting SGK1 — potentially offering relief to patients for whom standard treatments like SSRIs often fail.
“Current antidepressants are less effective for people with a history of childhood adversity,” Anacker said. “Our study suggests SGK1 inhibitors — some already in development for other conditions — could form the basis of faster, more precise treatments, while also helping identify those at greatest risk.”
Why Trauma-Linked Depression Differs
Childhood adversity — including abuse, neglect, or dysfunctional family environments — is among the strongest predictors of adult depression. However, biological mechanisms behind this link have remained unclear.
Anacker’s earlier work, about a decade ago, found elevated SGK1 levels in the blood of unmedicated patients with depression. The new study builds on that by analyzing postmortem brain tissue from suicide victims, revealing that SGK1 levels were highest in those with traumatic childhoods — in some cases, nearly double those without such histories.
Further genetic studies in children exposed to early adversity found that variants boosting SGK1 expression were associated with a higher likelihood of depression during adolescence.
Toward SGK1-Based Treatments
In mouse experiments, drugs that blocked SGK1 activity prevented the development of depressive-like behaviors under chronic stress — strengthening the case for SGK1 as both a biomarker and a therapeutic target.
Since SGK1 inhibitors are already being tested for conditions such as atrial fibrillation, the researchers say these compounds could be rapidly repurposed for psychiatric use. They also propose genetic screening to identify individuals most likely to benefit from such therapies.
“There’s an urgent need to identify and help those at highest risk after childhood trauma,” Anacker noted. “SGK1 gives us a promising biological handle to do that.”
The study, titled “Hippocampal SGK1 promotes vulnerability to depression: the role of early life adversity, stress, and genetic risk,” was published in Molecular Psychiatry.
It was authored by scientists from Columbia University, McGill University, Dartmouth College, and the Karolinska Institute, and supported by the Brain & Behavior Research Foundation (NARSAD) and Columbia’s Department of Psychiatry.
