Kathuria A, Lopez-Lengowski K, Jagtap SS, et al. - Considering the possible utility of three-dimensional cerebral organoids generated from patient-derived induced pluripotent stem cells (iPSCs) to interrogate cellular-molecular underpinnings of schizophrenia, researchers here investigated transcriptomic profiles and functional characteristics of cerebral organoids from patients with schizophrenia employing gene expression studies, complemented with investigations of mitochondrial function through measurement of real-time oxygen consumption rate, and functional studies of neuronal firing with microelectrode arrays. In this case-control study, they performed transcriptomic profiling of iPSC-derived cerebral organoids from 8 patients with schizophrenia and 8 healthy control individuals to determine cellular pathways that are aberrant in schizophrenia. Findings revealed disparities in the pattern of expression of genes involved in synaptic biology, neurodevelopment, and immune response, as well as genes involved in mitochondrial function and modulation of excitation/inhibition balance, in cerebral organoids from patients with schizophrenia. Specific deficits in mitochondrial physiology and a diminished response to stimulation and depolarization were observed in cerebral organoids. Per these findings, differences in specific biological pathways may be assessed in schizophrenia using patient-specific 3-dimensional brain organoids.