Mechanism behind PTSD patients' neuronal reaction to stress explained

Post-traumatic stress disorder can develop following severe trauma and is an enormous public health problem for both veterans and civilians. However, the extent to which genetic and environmental factors contribute to individual clinical outcomes remains unknown. In a recent study, published in Nature Neuroscience, induced pluripotent stem cell models were used to study PTSD. 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, a finding that could provide insights into how genetics can make someone more susceptible to developing PTSD following trauma exposure.

To mimic the stress response that triggers PTSD, the scientists exposed the induced pluripotent stem cell-derived neurons to the stress hormone hydrocortisone, a synthetic version of the body's own cortisol that is used as part of the "fight-or-flight" response.

"The addition of stress hormones to these cells simulates biological effects of combat, which allows us to determine how different gene networks mobilize in response to stress exposure in brain cells," explained one of the researchers.

Using gene expression profiling and imaging, the scientists found that neurons from individuals with PTSD were hypersensitive to this pharmacological trigger. The scientists also were able to identify the specific gene networks that responded differently following exposure to the stress hormones.

"What's really exciting about our findings is the opportunities they offer for accelerating the diagnosis and treatment of PTSD,"the researchers noted. "Importantly, having a robust stem cell model provides an ideal avenue to drug screening 'in the dish,' even across diverse patient populations."

Reference:

Rachel Yehuda et al,Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression,Nature Neuroscience, DOI10.1038/s41593-022-01161-y