The many roads to psychosis: recent advances in understanding risk and mechanisms

Schizophrenia is a chronic and severe mental illness which frequently leads to substantial lifelong disability. The past five years have seen major progress in our understanding of the complex genetic architecture of this disorder. Two major barriers to understanding the core biological processes that underlie schizophrenia and developing better interventions are (1) the absence of etiologically defined biomarkers and (2) the clinical and genetic heterogeneity of the disorder. Here, we review recent advances that have led to changes in our understanding of risk factors and mechanisms involved in the development of schizophrenia. In particular, mechanistic and clinically oriented approaches have now converged on a focus on disruptions in early neurodevelopment and synaptic plasticity as being critical for both understanding trajectories and intervening to change them. Translating these new findings into treatments that substantively change the lives of patients is the next major challenge for the field.