DISC1 dynamically regulates synaptic N-Methyl-D-aspartate responses in excitatory neurons

摘要

Schizophrenia and related mood disorders are complex psychiatric disorders that affect ~2% of the population (1,2). The fortuitous finding of chlorpromazine and other phenothiazines in the early 1950s and subsequent development of clozapine and related antipsychotic drugs ameliorated a subset of syndromes of psychosis and resulted in deinstitutionalization of many patients with psychiatric disorders. The drugs seem to benefit patients by modulating dopaminergic or serotoninergic function, or both. The exact mechanisms of action of the drugs are unknown. There are still no good answers 50 years after the discovery of these drugs as to why the medications fail to treat the negative symptoms and cognitive deficits, and this lack of answers has hampered the development of more effective medications (1,2).