Relationships Between Cerebrospinal Fluid GABAergic Neurosteroid Levels and Symptom Severity in Men with PTSD

This study found that cerebrospinal fluid (CSF) levels of the neurosteroids allopregnanolone and pregnanolone (allo + pregnan) were negatively correlated with PTSD severity and negative mood symptoms in unmedicated, tobacco-free men with PTSD (n = 13) compared to trauma-exposed healthy controls (n = 17). Specifically, lower allo + pregnan levels were associated with higher Clinician-Administered PTSD Scale (CAPS-IV) scores. Additionally, a decrease in the ratio of 5α-dihydroprogesterone (5α-DHP) to progesterone suggested a block in allopregnanolone synthesis at the enzyme 5α-reductase. These findings indicate that CSF allo + pregnan levels and the function of specific enzymes involved in their synthesis may be important factors in PTSD and could inform targeted neurosteroid-based treatments, with potential sex-specific differences in enzyme activity.