Potential of Neurosteroids for Precision Medicine in Psychiatry.
One of the most significant challenges in treating individuals suffering from psychiatric illnesses is the biological heterogeneity that exists throughout the patient population. This heterogeneity has hindered both timely diagnoses for those impacted as well as the development of new treatment options to combat these disorders. Ongoing efforts have been centered around stratifying individuals based on comprehensive phenotyping; however, biological heterogeneity remains a critical driver of psychiatric illness and poses a significant challenge in the field. Here, we review the current state of the field in biomarker development and the need for personalized medicine in psychiatry. Neurosteroid-based treatments have proven effective for the treatment of postpartum depression, but failed to gain approval for major depressive disorder, likely due to the inability to stratify patients amenable to this treatment approach. We discuss the potential of a biomarker approach to identify individuals with disruption in endogenous neurosteroid synthesis that may have transdiagnostic potential. Exciting emerging studies suggest that a biomarker indicating altered or a reduced capacity for endogenous neurosteroidogenesis would be beneficial for identifying individuals at risk for postpartum depression and could potentially predict treatment response to neurosteroid-based treatments. This review aims to provide a comprehensive report on the production of endogenous neurosteroids in the brain, the current clinical landscape for the use of neurosteroid-based therapies in psychiatry, and the potential utility of measuring neurosteroidogenesis capacity as a biomarker for the diagnosis and treatment of psychiatric illnesses.