Witnessed Trauma Exposure Induces Fear in Mice Through a Reduction in Endogenous Neurosteroid Synthesis

This study investigates the role of neurosteroids in PTSD, focusing on mice exposed to direct and witnessed trauma. Both groups showed decreased plasma levels of allopregnanolone and reduced expression of 5α-reductase type 2 in the basolateral amygdala, a key area for emotional processing. Genetic knockdown or pharmacological inhibition of this enzyme increased fear responses, while treatment with a synthetic neuroactive steroid (SGE-516) reduced these responses. The findings suggest that impaired neurosteroidogenesis contributes to PTSD and that treatments targeting neurosteroid pathways could benefit individuals with PTSD from both direct and witnessed trauma.