Genomic insights into schizophrenia

Abstract

Schizophrenia is a common, complex, heterogeneous psychiatric syndrome which can have profound impacts on affected individuals and imposes significant burdens on society. Despite intensive research, it has been challenging to understand basic mechanisms and to identify novel therapeutic targets. Given its high heritability and the complexity and inaccessibility of the human brain, much hope has been invested in the application of genomics as a route to better understanding. This work has identified many common and rare risk alleles and laid the foundations for a new generation of mechanistic studies. Genomics has also thrown new light on the relationship between schizophrenia and other psychiatric disorders and revealed its previously unappreciated aetiological relationship with childhood neurodevelopmental disorders, providing further evidence that it has its origins in disturbances of brain development. In addition, genomic findings suggest that the condition reflects fundamental disturbances in neuronal, and particularly synaptic, function that impact broadly on brain function, rather than being a disorder of specific brain regions and circuits. Finally, genomics has provided a plausible solution to the evolutionary paradox of how the condition persists in the face of high heritability and reduced fecundity.