Molecular mechanisms of schizophrenia: Insights from human genetics

Schizophrenia is a debilitating psychiatric disorder that affects millions of people worldwide; however, its etiology is poorly understood at the molecular and neurobiological levels. A particularly important advance in recent years is the discovery of rare genetic variants associated with a greatly increased risk of developing schizophrenia. These primarily loss-of-function variants are found in genes that overlap with those implicated by common variants and are involved in the regulation of glutamate signaling, synaptic function, DNA transcription, and chromatin remodeling. Animal models harboring mutations in these large-effect schizophrenia risk genes show promise in providing additional insights into the molecular mechanisms of the disease.