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In Combat Veterans With PTSD, Neurons React Differently to Stress
Stem cell-derived neurons from combat veterans reacted differently to a stress hormone depending on whether the individual had post-traumatic stress disorder (PTSD), according to findings published online in Nature Neuroscience.
“Two people can experience the same trauma, but they won’t necessarily both develop PTSD,” said corresponding author and study co-lead Kristen Brennand, PhD, Yale School of Medicine, New Haven, Connecticut. “This type of modeling in brain cells from people with and without PTSD helps explain how genetics can make someone more susceptible to PTSD.”
Related: Women with PTSD Show Accelerated Cognitive Decline in Midlife
The study included 39 combat veterans with and without PTSD who underwent skin biopsies and had their skin cells reprogrammed into induced pluripotent stem cells.
“Reprogramming cells into induced pluripotent stem cells is like virtually taking cells back in time to when they were embryonic and had the ability to generate all the cells of the body,” said senior author Rachel Yehuda, PhD, of the Icahn School of Medicine at Mount Sinai, New York City, and the James J. Peters Veterans Affairs Medical Center in the Bronx, New York. “These cells can then be differentiated into neurons with the same properties as that person’s brain cells had before trauma occurred to change the way they function.”
When researchers exposed the induced neurons to the stress hormone hydrocortisone to simulate the biological effect of combat, they observed hypersensitivity in neurons from participants with PTSD and identified specific gene networks that responded differently depending on an individual’s PTSD status.
“Importantly, the gene signature we found in the neurons was also apparent in brain samples from deceased individuals with PTSD, which tells us that stem cell models are providing a pretty accurate reflection of what happens in the brains of living patients,” said corresponding author and study co-lead Daniel Paull, PhD, of the New York Stem Cell Foundation Research Institute.
Based on their discovery, researchers believe the induced neurons represent a platform for investigating biological mechanisms underlying PTSD, biomarkers of stress response, and possibly new drugs for treatment.
“We’re working on finding already-approved drugs that could reverse the hypersensitivity we’re seeing in neurons,” said Dr Brennand. “That way, any drugs we discover will have the fastest possible path to helping patients.”
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