Tong J, Zhou Y, Huang J, et al. - Treatment-resistant schizophrenia (TRS) has been linked with cerebral white matter and N-methyl-D-aspartate receptor (NMDAR) hypofunction, two apparently unrelated observations. Given the significance of NMDARs for axonal myelination and signal transduction, researchers theorized, that in cases with schizophrenia, the presence of NMDAR antibody (Ab) may weaken NMDAR functions and white matter microstructures, contributing to TRS. They enrolled 50 patients with TRS, 45 patients with nontreatment-resistant schizophrenia (NTRS), 53 patients with schizophrenia at treatment initiation schizophrenia (TIS), and 90 healthy controls. Findings revealed patients with TRS had significantly higher serum NMDAR Ab levels vs the NTRS patients. In patients with TRS, they noted a significant association of higher NMDAR Ab levels with reduced whole-brain average fractional anisotropy, with the strongest effect at the genu of corpus callosum. Findings here indicate that, in schizophrenia, there may be a NMDAR mechanism on white matter microstructure impairment that could be contributing to therapy resistance to antipsychotic medications.