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In vitro human cell models for probing functional deficits relevant to neuropsychiatric disorders

It is widely accepted that functional alterations of brain cells and neuronal circuitry cause neuropsychiatric disorders such as schizophrenia, but the underlying biological mechanisms are still unclear. Recent technical advances in human neuronal cell culture methods have provided opportunities to examine neuronal cells derived from accessible patient tissues/cells. Here we report the optimization and utilities of human cell models to probe functional deficits relevant to neuropsychiatric disorders, induced neuronal (iN) cells, and olfactory epithelium‐derived cells (olfactory cells). By using iN cells with feature of immature postmitotic glutamatergic neuronal cells, we have found a novel functional phenotype in Dravet syndrome, a form of severe myoclonic epilepsy in infancy, which was not suggested by previous studies of classical mouse models and human autopsied brains. By analyzing gene expression profiles of olfactory cells, we have revealed that altered susceptibility to cellular stress responses underlie schizophrenia. Taken together, these studies demonstrate that in vitro human cell models are useful for probing functional deficits relevant to neuropsychiatric disorders.