Modeling psychiatric disorders with patient-derived iPSCs

•Psychiatric disorders are heterogeneous disorders with complex genetic origins.•Patient-specific hiPSCs can shed light on disease mechanisms.•Region-specific neuronal subtypes have been generated for disease modeling.•Patient-derived iPSCs provide a novel approach for drug discovery.

Psychiatric disorders are heterogeneous disorders characterized by complex genetics, variable symptomatology, and anatomically distributed pathology, all of which present challenges for effective treatment. Current treatments are often blunt tools used to ameliorate the most severe symptoms, often at the risk of disrupting functional neural systems, thus there is a pressing need to develop rational therapeutics. Induced pluripotent stem cells (iPSCs) reprogrammed from patient somatic cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue and organ development, and provides new approaches for understanding disease mechanisms and for drug discovery with higher predictability of their effects in humans. Here we review recent progress and challenges in using human iPSCs for modeling neuropsychiatric disorders and developing novel therapeutic strategies.