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The mechanistic links between patient genotype and the phenotypic changes associated with neuropsychiatric disease have been difficult to establish, owing in part to the lack of live brain tissue from clinical cases. In fact, for many brain disorders, it remains unclear whether disease progression reflects developmental aberrations during neural differentiation or activity-dependent perturbations in mature neurons. Fortunately, the ability to reprogram cells from patients and healthy controls into human induced pluripotent stem cells (hiPSCs) (1) has conferred the ability to generate a nearly limitless source of genetically matched human neural cells with which to model neuropsychiatric disease across a variety of neural cell fates. Already, hiPSC-based models have provided molecular and cellular insights into disease mechanisms underlying far-ranging brain disorders from autism spectrum disorder (2) to schizophrenia (3), Alzheimer’s disease (4), Parkinson’s disease (5), and even zika-virus induced microcephaly (6). These models are being increasingly applied to drug screening, successfully identifying compounds to enhance neural proliferation (7), modulators of lithium signaling (8) and inhibitors of zika virus infection (9). While many of these early screens have been conducted on neural progenitor cells (NPCs), screening has recently been extended to stem cell-derived neurons and astrocytes (10-12).

stem cell investigation

Personalized medicine in a dish: the growing possibility of neuropsychiatric disease drug discovery tailored to patient genetic variants using stem cells