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
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