Introduction
hypofunction, schizophrenia, schizophrenia [A, cognitive impairment
HYPOFUNCTION
The N-methyl-D-aspartate (NMDA) hypofunction hypothesis of schizophrenia [A reasonable approach to enhance NMDAR function has been to elevate synaptic glutamate co-agonists, such as glycine and D-serine. These amino acids bind to a specific site in NMDAR [D-serine is degraded by D-amino acid oxidase (DAAO) [Event-related potentials (ERPs) have emerged as reliable biomarkers to capture target engagement of glutamatergic drugs. Mismatch negativity (MMN) and auditory steady-state response (ASSR) stand out as endpoints impaired in schizophrenia [Luvadaxistat (also known as TAK-831 and NBI-1065844) is a potent investigational DAAO inhibitor that was considered for the treatment of negative symptoms and is being developed for the treatment of cognitive impairment associated with schizophrenia (CIAS). Here, we evaluated the impact of luvadaxistat on NMDA- and cognition-associated biomarkers, as well as on cerebellar-circuitry-related biomarkers in patients with schizophrenia. Because DAAO has the highest expression in the cerebellum [