Can you screen for post-traumatic stress disorder in the same way you screen for breast cancer? A new paper from researchers at the Mount Sinai School of Medicine suggests that gene expression could reveal which individuals are most likely to develop PTSD, a development that could accelerate the search for a therapy to effectively pretreat the disorder through a pill.
The researchers from the Icahn School of Medicine at Mount Sinai took a group of male and female rats and traumatized them by exposing them to the smell of cat urine. Seven days later, the researchers separated those rats that were displaying PTSD-like symptoms from those that coped with the stressful event. An analysis of the gene expression in the animals showed suppressed glucocorticoid receptor signaling in their brain and blood of the PTSD-stricken rodents.
The way your glucocorticoid receptors signal in the face of traumatic stimuli affects the way the hippocampus and the amygdala process the memory of events. The hippocampus serves, in a way, as the brain’s Google. When a person is confronted with new experiences in the form of visual, auditory, and other stimuli, it’s the hippocampus that searches through the brain’s memory to find relevant files to inform the person’s response. Loud noise = explosion = run. The amygdala controls the brain’s fear level, affecting how we experience stimuli and how charged are our memories after the fact. To carry the Google metaphor a bit further, the amygdala affects page rank. Glucocorticoid receptor signaling can change the way all of these parts of the brain work together. The research revealed some of the pathways and networks of gene expression that allow the receptors to go off track.
“We measured 22,500 genes and when you measure all those genes you can do computational analysis that gives you the transcription factors and the pathways. So what you can do is you can understand, through computation, what the networks are,” Dr. Rachel Yehuda, director of the Traumatic Stress Studies Division at Icahn School of Medicine at Mount Sinai and the study’s lead author, told Defense One.
Here’s what Yehuda’s research means: We’re one step closer to treating PTSD long before it ruins the lives of those it affects and, in the case of soldiers, costs the government a lot of money. To further test their theory, the researchers gave some of the rats a hormone called corticosterone, (CORT—equivalent hormone of cortisol for rodents) about an hour after exposing them to the cat urine. They then re-tested them seven days later and found “in both sexes, CORT preventive treatment was associated with lower anxiety behavior in [predator-scent-stress-exposed] rats,” according to their paper, "Expression Profiling Associates Blood and Brain Glucocorticoid Receptor Signaling with Trauma-Related Individual Differences in Both Sexes," which was published in the Proceedings of the National Academy of Sciences on August 11.
The relationship between low cortisol, stress, and susceptibility to PTSD has been established for decades, but therapies that use cortisol to prevent or pre-treat stress are still in the experimental phase, and some of the most ambitious work is taking place outside of the United States.
To understand the future of PTSD diagnostics, you have to go to an emergency room in Israel.