Effects of Glycine on Mismatch Negativity and the Underlying Theta-Band Signature in the Ketamine Model of Schizophrenia in Healthy Men.
Schizophrenia bulletin December 14, 2025 Stjepan Curic, Moritz Haaf, Darius Zokai et al.
Deficits in automatic auditory processing, measured by mismatch negativity (MMN), are linked to poor outcomes in schizophrenia and involve glutamate dysfunction. In a placebo-controlled crossover EEG study with 25 participants, ketamine—which induces schizophrenia-like symptoms—reduced MMN amplitudes, theta power, and P3a. Pretreatment with glycine, an NMDAR coagonist, did not prevent ketamine's effects on MMN or P3a amplitude but did block ketamine's reduction of theta power and phase consistency associated with duration deviant MMN. Elevated theta activity due to glycine predicted improvement in negative symptoms. The findings confirm the glutamate system's role in pre-attentive auditory processing deficits and suggest MMN's theta signature may help identify patients responsive to glutamatergic treatments.