Cortical cellular diversity and development in schizophrenia: A survey of cortical development and the state of the art in profiling cell type-resolved transcriptomic and epigenomic changes in the context of schizophrenia

While a definitive understanding of schizophrenia etiology is far from current reality, an increasing body of evidence implicates perturbations in early development that alter the trajectory of brain maturation in this disorder, leading to abnormal function in early childhood and adulthood. This atypical development likely arises from an interaction of many brain cell types that each follow distinct developmental paths. Because both cellular identity and development are governed by the transcriptome and epigenome, two levels of gene regulation that have the potential to reflect both genetic and environmental influences, mapping ‘omic changes over development in diverse cells is a fruitful avenue for schizophrenia research. In this review, we provide a survey of human brain cellular composition and development, levels of genomic regulation that determine cellular identity and developmental trajectories, and what is known about how genomic regulation is dysregulated in specific cell types in schizophrenia. We also outline technical challenges and solutions to conducting cell type-specific functional genomic studies in human postmortem brain.