How induced pluripotent stem cells are informing drug discovery in psychiatry

Compared with other medical fields, psychiatry is particularly challenging for rational drug discovery. The therapeutic endpoints are abstract measures of cognitive and behavioral performance, for which we have a very limited understanding of the underlying biological mechanisms. Existing preclinical disease models are also limited in their translational fidelity. Recently, there have been active discussions on the use of human induced pluripotent stem cells (iPSCs) as a catalyzing research tool in psychiatry, but very few review articles in the field have given specific considerations to their use at the interface between psychiatric research and drug discovery. Here, we discuss recent perspectives emerging from this interface. For physicians and researchers on the clinical side, we explain how iPSC-based experimental approaches are placed at the crossroads with psychiatric genetics and how representative studies in the field are addressing biological mechanisms underlying psychiatric disorders. For researchers who directly work with iPSCs and aspire to develop new research techniques, we direct their attention to the utility of this approach for unmet needs in drug discovery workflows.