Reviewing the ketamine model for schizophrenia
Journal of Psychopharmacology November 20, 2013 Joel Frohlich, John D Van Horn 310 citations
The glutamate hypothesis of schizophrenia, which arose from observations that NMDAR antagonists like ketamine and PCP induce schizophrenia-like symptoms, may explain negative and cognitive symptoms better than the dopamine hypothesis and even account for dopamine dysfunction itself. Ketamine primarily acts at the NMDAR, and genetic and molecular evidence points to NMDAR hypofunction in schizophrenia. This hypofunction can explain connectional and oscillatory abnormalities through weakened excitation of GABAergic interneurons and disinhibition of principal cells. Individuals with prenatal NMDAR aberrations might experience symptom onset in adolescence when synaptic pruning reduces network connectivity below a critical threshold. Ketamine challenge is useful for studying multiple aspects of acute schizophrenia.