Brain Chemical Linked to Trauma, Depression, and Suicide Risk

Neuroscientists at Columbia University and McGill University have identified a brain chemical, Serum and Glucocorticoid-regulated Kinase 1 (SGK1), as a key factor connecting childhood trauma to an increased risk of depression and suicidal behavior. Elevated levels of SGK1 have been found in the brains of individuals who have experienced early life adversity.

The Link Between Childhood Trauma and Depression

Approximately 60% of adults diagnosed with major depression and two-thirds of those who attempt suicide have a history of childhood adversity or trauma ¹. This suggests that the biological processes underlying depression may differ in individuals with and without a history of early trauma.

SGK1: A Key Player in Depression Development

Researchers discovered unusually high levels of SGK1, a stress-responsive protein, in the blood of individuals with depression ¹. Further investigation of brain tissue from individuals who died by suicide revealed elevated SGK1 levels, particularly in those who had experienced childhood trauma, with concentrations up to twice as high as in those without such a history ².

Genetic Predisposition and SGK1

Studies also indicate a genetic component. Individuals exposed to early adversity who carry genetic variants that increase SGK1 production are more likely to experience depression as teenagers ². This suggests SGK1 plays a significant role in the development of depression and suicidal behavior, especially in those with a history of trauma.

Potential for New Antidepressant Treatments

These findings open the door to the development of a new class of antidepressants that specifically target and inhibit SGK1 activity. In experiments with mice, blocking SGK1 prevented the development of depressive-like behaviors during chronic stress ², ¹. Importantly, SGK1 inhibitors are already under evaluation for other medical conditions, such as atrial fibrillation, potentially accelerating their availability for depression treatment ³.

Future Directions

Researchers are planning clinical trials to assess the effectiveness of SGK1 inhibitors in individuals with depression and a history of early life adversity ¹. They also propose that genetic screening could help identify individuals who would benefit most from this targeted approach to treatment.

“There’s an urgent require 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,” says Christoph Anacker, assistant professor of clinical neurobiology in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons ¹.

The research was published in Molecular Psychiatry ⁴ and was supported by a NARSAD Young Investigator award from the Brain & Behavior Research Foundation and the Columbia University Department of Psychiatry ¹.