NEW YORK — Scientists have pinpointed a key brain chemical that explains why childhood trauma casts such a long shadow, dramatically increasing the risk of depression and suicide in adulthood. This discovery opens a direct path to a new type of antidepressant specifically designed for individuals whose depression stems from early-life adversity.
Neuroscientists from Columbia University and McGill University have identified a stress-responsive protein called SGK1 as a central driver of depression and suicidal thinking in people who experienced trauma during childhood. The findings, published in Molecular Psychiatry, offer a biological explanation for a long-observed clinical challenge and a promising solution.
Key Findings of the Research:
A Direct Biological Link: Researchers found significantly elevated levels of SGK1 in the brains of adults who died by suicide, with the highest concentrations—up to double—in those who had suffered childhood trauma.
A Genetic Culprit: Children exposed to early adversity who carried genetic variants that increase SGK1 production were more likely to develop depression as teenagers.
A New Treatment Pathway: Drugs that inhibit SGK1, already in development for other conditions, prevented depressive-like behaviors in stressed mice, suggesting they could rapidly be repurposed as a new class of antidepressants.
Addressing a Critical Treatment Gap
Approximately 60% of adults with major depression and two-thirds of those who attempt suicide have a history of childhood trauma. Current first-line antidepressants, like SSRIs, are often less effective for this large population.
"This suggested to us that the biological processes that lead to depression and suicidality in people with stressful childhoods may be different," explained lead author Dr. Christoph Anacker, assistant professor at Columbia University. "What's exciting is that this raises the prospect of quickly developing new treatments, as SGK1 inhibitors are already in development, and gives us a screening tool to identify people at greatest risk."
From Lab to Clinic: The Future of SGK1-Targeted Therapy
The research team proposes a two-pronged approach moving forward:
Genetic Screening: Identifying individuals with genetic variants that lead to high SGK1 production, flagging them for early intervention.
Clinical Trials: Testing existing SGK1 inhibitor drugs in patients with depression and a history of childhood trauma.
"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," Dr. Anacker stated.
The study, titled “Hippocampal SGK1 promotes vulnerability to depression: the role of early life adversity, stress, and genetic risk,” was funded by the Brain & Behavior Research Foundation and the Columbia University Department of Psychiatry.