Cortical cellular diversity and development in 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 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.

Automated summary

Schizophrenia's etiology is likely related to disruptions in early development, altering brain maturation and resulting in abnormal function in early childhood and adulthood. Cellular identity and development are governed by genomic regulation, which may reflect genetic and environmental influences, making investigating omic changes in diverse cells a valuable avenue for schizophrenia research.