Erasing traces of trauma from the young brain

Countless studies have shown that exposure to warfare, abuse, and other traumatic events at a young age significantly raises the risk of mental and emotional issues later in life. Now, a new study provides a reason for optimism. In research published last year in Science Advances, a team headed by Prof. Alon Chen has discovered brain mechanisms in mice that go awry as a result of exposure to trauma in infancy and showed that these changes may be reversible if treated early. 

Our brains have a wonderful quality known as plasticity, the ability to change throughout our lives. Brains are most plastic in early youth, as we develop. This flexibility manifests in, for example, the aptitude for learning languages, but also entails a heightened sensitivity to traumatic events, which are liable to leave a scar that only intensifies with age. Many studies provide evidence for the latter effect, but very little is known about the way that exposure to trauma at a young age affects different kinds of brain cells and communication among them in adulthood. 

Prof. Chen and his team in the Department of Brain Sciences are experts on the neurobiology of stress. In this study, they combined single-cell genomics, intensive behavioral measurements, and artificial intelligence tools to generate a comprehensive understanding of responses to being exposed to a traumatic event shortly after birth — in this case, mice being neglected by their mothers. The mice displayed a variety of behaviors indicating their position at the bottom of the social dominance hierarchy. [In human terms, such behaviors might include extreme introversion and social anxiety.] 

A group of adult mice that had experienced such trauma in infancy were then exposed to a new stressful social situation—bullying by other mice. The researchers found that early trauma left a mark on different types of brain cells, primarily affecting gene expression in two subpopulations of neurons: those that send/receive stimulating (excitatory) electrical signals via the brain chemical glutamate, and those that send/receive inhibitory electrical signals via the chemical GABA (gamma-aminobutyric acid). This effect was most pronounced in mice that had experienced both trauma in infancy and bullying in adulthood, but was also present in mice that had only experienced trauma in infancy (as compared to mice who had only been bullied as adults or who had never experienced any trauma at all). 

Multiple studies have linked excitatory/inhibitory (E/I) imbalance in the brain with neuropsychiatric and neurodegenerative conditions. Is there a way to fix an E/I imbalance triggered by childhood trauma so that it doesn’t trigger problems in adulthood? 

During a brief treatment window shortly after the early trauma, the Chen group gave the mice a well-known antianxiety drug—diazepam, known commercially as Valium— which affects the GABA inhibitory system. This short course of treatment produced stunning results: The medicated mice were able to fully or almost fully avoid the behavioral future that awaited them and were no longer at the foot of the social ladder. 

While this finding certainly should not be seen as a recommendation to treat young trauma patients with drugs, it does highlight the importance of early treatment for successful rehabilitation, and better rehabilitation capabilities. 

“Our new study identifies a key brain mechanism that is especially sensitive to childhood trauma. But the most exciting part is the prospect of using the plasticity of the young brain to help it recover, avoiding the toll this trauma can exact in adulthood,” says Prof. Chen. 

ALON CHEN IS SUPPORTED BY: 

• Edmond de Rothschild Foundation 
• Licht Family 
• Ruhman Family Laboratory for Research in the Neurobiology of Stress 
• Vera and John Schwartz Professorial Chair in Neurobiology