Background: Schizophrenia has been hypothesized to be caused by a hypofunction of
glutamatergic neurons. Findings of reduced concentrations of glutamate in the cerebrospinal
fluid of patients with schizophrenia and the ability of glutamate-receptor antagonists to cause
psychotic symptoms lend support to this hypothesis. N-acetylaspartylglutamate (NAAG), a
neuropeptide that is highly concentrated in glutamatergic neurons, antagonizes the effects of
glutamate atN-methyl-d-aspartate receptors. Moreover, NAAG is cleaved to glutamate andN …