Phenomenology, aetiology and treatment of schizophrenia.
Novartis Foundation symposium January 1, 2008 Daniel C Javitt
Schizophrenia affects up to 1% of the global population. While traditional models focused on dopamine dysfunction, glutamatergic models have become mainstream over the last 15 years, explaining features poorly accounted for by dopamine alone. These models are based on observations that PCP and ketamine induce psychotic symptoms by blocking NMDA-type glutamate receptors. NMDA receptors are widespread, causing information-processing deficits in sensory and subcortical systems as well as higher cortical regions. They also regulate dopamine release, suggesting dopaminergic deficits may be secondary to glutamatergic dysfunction. Agents stimulating glutamatergic transmission, such as glycine-site agonists and glycine transport inhibitors, have shown promise in preclinical studies and are undergoing clinical development, potentially leading to new treatments.