Genetic insights into the neurodevelopmental origins of schizophrenia

Abstract

Schizophrenia is a severe neuropsychiatric disorder with a longstanding history of neurobiological investigation. Although the underlying causal mechanisms remain unknown, early neurodevelopmental events have been implicated in pathogenesis, initially by epidemiological and circumstantial data but more recently by brain-specific molecular and genetic findings. Notably, genomic research has recently uncovered discrete risk variants and risk loci associated with schizophrenia, with the potential to elucidate disease mechanisms. This Review revisits the neurodevelopmental model of schizophrenia from a current genetics perspective, delineating the complex genetic basis of the disorder and highlighting gene expression and epigenetic analyses of post-mortem cortical tissue that suggest that early brain development mediates genetic risk associated with schizophrenia. Future functional genomics investigations will accordingly need to characterize schizophrenia risk loci in relevant neurodevelopmental models.