How Genetics Might Affect PTSD Susceptibility

Stem cell-derived neurons from combat veterans with post-traumatic stress disorder (PTSD) react differently to a stress hormone than those from veterans without PTSD, according to a new finding published October 20 in Nature Neuroscience. The article provided insights into how genetics affect susceptibility to developing PTSD following trauma exposure.

With the collaboration of scientists from the Icahn School of Medicine at Mount Sinai, the James J. Peters Veterans Affairs Medical Center, the Yale School of Medicine, and The New York Stem Cell Foundation Research Institute (NYSCF), the study claims to be the first to use induced pluripotent stem cell (iPSC) models to study this specific mental disorder. 

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Novel Model to Investigate Genetic Susceptibility of PTSD

PTSD is a mental health condition triggered by experiencing or witnessing a terrifying event. Two people can experience the same trauma, but the two are not guaranteed to develop PTSD, so how genetic and environmental risk factors contribute to individual clinical outcomes remains unknown. To bridge this information gap, the research team studied a cohort of 39 combat veterans with and without PTSD. 

Most similar studies of PTSD to date have used blood samples from patients; however,  since PTSD is rooted in the brain, scientists need a way to capture how the neurons of prone individuals are affected by stress. As pulling neurons from a living person’s brain seems impossible, the team opted to use stem cells, as they are uniquely equipped to provide a patient-specific, non-invasive window into the brain. 

In this study, the veterans later underwent skin biopsies, and researchers reprogrammed their skin cells into induced pluripotent stem cells.

Transitioning the Research into Practical Uses

The scientists exposed the iPSC-derived neurons to the stress hormone hydrocortisone, one of our body’s cortisol that is used as part of the “fight-or-flight” response to mimic the stress response that triggers PTSD.

Gene expression profiling and imaging showed that neurons from individuals with PTSD were hypersensitive to this pharmacological trigger. The scientists also identified the specific gene networks that responded differentially following exposure to stress hormones. 

The distinctions between how PTSD and non-PTSD neurons responded to stress could help predict which individuals are at higher risk for PTSD. To help patients with urgent needs, finding already-approved drugs that could reverse the hypersensitivity seen in neurons is essential.

In the future, scientists will leverage the iPSC models to investigate further the genetic risk factors pinpointed by this study while investigating how PTSD affects other types of brain cells. This valuable research would help broaden therapeutic discovery opportunities and provide new treatment alternatives for patients.

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Author

Nai Ye Yeat