We’re starting to understand why childhood adversity leaves its mark

Research suggests that those who face significant difficulties during their early years may exhibit higher levels of a specific protein in the brain. This finding could shed light on why adversities in childhood are often linked to long-lasting mental health challenges. Additionally, medications targeting this protein might eventually offer relief from these consequences.

Approximately 20% of teenagers in the U.S. indicate they’ve gone through at least four traumatic events during their childhood, such as abuse, neglect, homelessness, or losing a parent. Studies reveal that these experiences can negatively impact brain development and increase the likelihood of mental health issues, like depression, into adulthood.

“Our understanding of how early-life adversity or stress leads to such prolonged effects remains limited,” notes Christoph Anacker from Columbia University, New York. “Individuals with childhood trauma generally exhibit a lower response to current antidepressant medications.”

Prior studies have indicated that individuals with depression possess higher levels of SGK1 protein (serum and glucocorticoid-regulated kinase 1) in their bloodstream. While the intricacies of this protein are not fully understood, it appears to play a role in how brain cells handle and transmit information.

To delve deeper into its implications, Anacker and his team examined SGK1 concentrations in the brains of 50 deceased men, 36 of whom had taken their own lives. Each participant had previously answered questions regarding any experiences of physical or sexual abuse before they turned 16.

The investigation revealed that men who died by suicide had approximately 33% higher levels of SGK1 genetic material in the hippocampus – a brain area crucial for stress and memory – compared to those who did not, with levels showing a further increase among individuals who faced childhood adversity.

In another phase of the research, more than 8,500 children aged 9 to 10 were studied, revealing that those with a diagnosis of depression were more likely to exhibit elevated gene activity related to SGK1, a trend also linked to childhood adversities.

Finally, researchers administered daily injections of a novel drug that inhibits SGK1 to ten adult male mice for ten consecutive days. Following each dose, the mice were placed in an enclosure with a more aggressive mouse for a duration of five minutes, inducing stress.

By the conclusion of the study period, the treated mice exhibited significantly fewer signs of anxiety and depressive behaviors compared to a control group that received saline injections instead. For example, the former spent over twice as much time on average in the center of an empty cage rather than relegating themselves to a corner like the control group.

“Reducing SGK1 levels in the hippocampus equips mice with greater resilience against stress,” says Anacker. A parallel mechanism appears to function in humans, indicating that targeting SGK1 could provide relief from depression in those who experienced early hardships. Although the precise relationship between SGK1 and mental health issues remains unclear, one theory proposes that it hinders the generation of new brain cells in the hippocampus.

While the drug used in this research is not currently authorized for human use, other SGK1 inhibitors are undergoing clinical trials for various heart conditions. If they demonstrate safety, there may be potential for repurposing them for mental health treatments, according to Anacker. However, he cautions that “this foundational research in animal models is a long way from establishing a viable drug target for humans,” adds Katie McLaughlin from Harvard University.

Need support? UK Samaritans: 116123; US National Suicide Prevention Lifeline: 1 800 273 8255; hotlines available in other countries.