01722nas a2200193   4500000000100000000000100001008004100002260001200043653001800055653001500073100002500088700002200113245009300135856005500228300001000283490000700293520121400300022001401514       2023                            d  c2023-0110aSchizophrenia10aStem cells1 aThomas Anthony Dixon1 aAlysson R. Muotri00aAdvancing preclinical models of psychiatric disorders with human brain organoid cultures  uhttps://www.nature.com/articles/s41380-022-01708-2  a83-950 v283 aPsychiatric disorders are often distinguished from neurological disorders in that the former do not have characteristic lesions or findings from cerebrospinal fluid, electroencephalograms (EEGs), or brain imaging, and furthermore do not have commonly recognized convergent mechanisms. Psychiatric disorders commonly involve clinical diagnosis of phenotypic behavioral disturbances of mood and psychosis, often with a poorly understood contribution of environmental factors. As such, psychiatric disease has been challenging to model preclinically for mechanistic understanding and pharmaceutical development. This review compares commonly used animal paradigms of preclinical testing with evolving techniques of induced pluripotent cell culture with a focus on emerging three-dimensional models. Advances in complexity of 3D cultures, recapitulating electrical activity in utero, and disease modeling of psychosis, mood, and environmentally induced disorders are reviewed. Insights from these rapidly expanding technologies are discussed as they pertain to the utility of human organoid and other models in finding novel research directions, validating pharmaceutical action, and recapitulating human disease.  a1476-5578