Stem cell models of schizophrenia, what have we learned and what is the potential?

Schizophrenia is a complex disorder with clinical manifestations in early adulthood. However, it may start with disruption of brain development caused by genetic or environmental factors, or both. Early deteriorating effects of genetic/environmental factors on neural development might be key to described disease causing mechanisms. Establishing cellular models with cells from affected individual using the induced pluripotent stem cells (iPSC) technology could be used to mimic early neurodevelopment alterations caused by risk genes or environmental stressors. Indeed, cellular models have allowed identification and further study of risk factors and the biological pathways in which they are involved. New advancements in differentiation methods such as defined and robust monolayer protocols and cerebral 3D organoids have made it possible to faithfully mimic neural development and neuronal functionality while CRISPR-editing tools assist to engineer isogenic cell lines to precisely explore genetic variation in polygenic diseases such as schizophrenia. Here we review the current field of iPSC models of schizophrenia and how risk factors can be modelled as well as discussing the common biological pathways involved.