Below, we will discuss existing hiPSC-based models of neurodevelopmental disorders, both those that involve a single disease-penetrant mutation and complex disorders in which hundreds of genes have been implicated. We define neurodevelopmental disorders as including any disorders that alter the course of normal human brain development and for which etiological factor(s) are active in prenatal or early postnatal life. Such disorders include Rett Syndrome, Timothy Syndrome, Fragile X, Autism, Tourette syndrome, and Schizophrenia. While there is some evidence that Bipolar disorder has developmental origins [see review 58 and a few prominent hiPSC studies 59–61 have been carried out] overall the evidence is not conclusively pointing to a definite developmental etiology. It is important to note that because of the high resource and time requirements of hiPSC studies, some of the published works on the subject are only able to conduct n=1 i.e., one control vs. one affected hiPSC without any genetic risk variant assessment. It is unlikely that these papers can add any conclusive evidence on disease pathology and so we purposely tried to exclude them from our analysis unless there is something especially novel about the experiment and/or its design.
