Thinking glutamatergically: changing concepts of schizophrenia based upon changing neurochemical models.
Clinical schizophrenia & related psychoses October 1, 2010 Joshua T Kantrowitz, Daniel C Javitt
Schizophrenia has long been understood as a disorder of dopamine neurotransmission, but this framework has limited research to dopamine-rich brain regions. About twenty years ago, an alternative model emerged based on how dissociative anesthetics like PCP and ketamine induce psychosis by blocking NMDA-type glutamate receptors. Unlike dopamine, glutamate is widespread in the brain and central to sensory processing and cortical analysis, suggesting that schizophrenia involves diffuse but process-specific cortical dysfunction. NMDA receptors also interact with other neurotransmitter systems and have binding sites for endogenous compounds like glycine and D-serine. This glutamatergic theory opens new treatment approaches, many now entering clinical evaluation.