Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective

• Published in: Schizophrenia bulletin 2024-08, Vol.50 (5), p.1104-1116
• Main Authors: Bianciardi, Bianca, Mastek, Helena, Franka, Michelle, Uhlhaas, Peter J
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Animals; Evoked Potentials, Auditory - drug effects; Evoked Potentials, Auditory - physiology; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Gamma Rhythm - drug effects; Gamma Rhythm - physiology; Humans; Magnetoencephalography; Psychotic Disorders - drug therapy; Psychotic Disorders - physiopathology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Regular; Schizophrenia - drug therapy; Schizophrenia - physiopathology
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbae090

Abstract Background and Hypothesis N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity. Study Design This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power. Study Results Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients. Conclusions Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.