The NMDA receptor 'glycine modulatory site' in schizophrenia: D-serine, glycine, and beyond

Schizophrenia is a severe psychiatric illness that is characterized by reduced cortical connectivity, for which the underlying biological and genetic causes are not well understood. Although the currently approved antipsychotic drug treatments, which primarily modulate dopaminergic function, are effective at reducing positive symptoms (i.e. delusions and hallucinations), they do little to improve the disabling cognitive and negative (i.e. anhedonia) symptoms of patients with schizophrenia. This review details the recent genetic and neurobiological findings that link N-methyl-D-aspartate receptor (NMDAR) hypofunction to the etiology of schizophrenia. It also highlights potential treatment strategies that augment NMDA receptor function to treat the synaptic deficits and cognitive impairments.