Precision phenotyping of elevated arousal in posttraumatic stress disorder: implications for personalized GABAergic pharmacotherapy

Posttraumatic stress disorder (PTSD) is a common and disabling condition, and current first-line medications have remission rates as low as 20-30%. Novel agents targeting the GABAergic system offer a promising alternative approach to treatment given converging evidence for a central role for this system in PTSD pathophysiology. However, overall progress in PTSD psychopharmacology has been hampered by the substantial heterogeneity in this population, which has been highlighted by recent research on both subjective symptoms and underlying biological mechanisms. In this mini review, we examine the literature on heterogeneity in PTSD, particularly with respect to anxious arousal. We examine heterogeneity in arousal based on both clinical symptoms and objective behavioral or biological markers. We also examine evidence for a specific role for GABAergic dysfunction in causing elevated anxious arousal. These lines of research suggest that novel GABAergic agents may be particularly effective in a high arousal PTSD subgroup. Future research should incorporate individual subjective and objective measures of anxious arousal into clinical trials of GABAergic agents for PTSD, with the ultimate aim of developing personalized treatments for selected individuals within this population.