A new international study has identified a key brain chemical that could explain why people who experience trauma or neglect early in life are more vulnerable to depression and suicidal thoughts later on.
Researchers from Columbia University and McGill University found that high levels of a stress-related protein called SGK1 were consistently associated with depression in individuals who had faced childhood adversity.
The findings, published in Molecular Psychiatry, suggest that blocking this protein could pave the way for a new generation of antidepressant drugs —particularly for patients who do not respond well to standard treatments.
Depression remains one of the world’s most prevalent mental health disorders, and studies have long shown that people exposed to physical abuse, neglect, or other forms of early hardship face a significantly higher risk. In the United States alone, around 60% of adults diagnosed with major depression, and nearly two-thirds of those who attempt suicide, report traumatic experiences in childhood.
The research team examined brain tissue from adults who had died by suicide and found that SGK1 levels were higher than in those who had not. Among the victims who had experienced early trauma, concentrations of SGK1 were up to twice as high, indicating that the chemical may play a direct role in shaping long-term vulnerability to mental illness.
Further evidence came from genetic studies in children exposed to early adversity. Those carrying specific genetic variants that increase SGK1 activity were found to be more likely to develop depression as teenagers, reinforcing the protein’s connection to stress-related brain changes.
Previous antidepressants - most commonly selective serotonin reuptake inhibitors (SSRIs) - have been less effective in patients with a history of early trauma. The Columbia–McGill research suggests that this may be because the biological mechanisms underlying depression differ for this group, with SGK1 acting as a central mediator between early stress and later depressive symptoms.
In laboratory experiments, blocking SGK1 activity in mice prevented the onset of depressive-like behaviour even under chronic stress. Since SGK1 inhibitors are already being explored for other medical conditions, scientists believe it may be possible to adapt these compounds for psychiatric use in the near future.
The team also proposed that genetic screening could help identify individuals most likely to benefit from an SGK1-targeted antidepressant. Such personalised approaches could significantly improve outcomes for people whose depression stems from traumatic experiences rather than purely chemical imbalances.
The study involved researchers from Columbia, McGill, Dartmouth, and the Karolinska Institute. It was funded by the Brain & Behavior Research Foundation and Columbia University’s Department of Psychiatry.
The discovery offers fresh hope for millions living with trauma-related depression, pointing toward a biological pathway that may finally bridge the gap between early life experiences and adult mental health.