65. Effects of NMDA Receptor Antagonism in Patients With Schizophrenia: Improvement in Markers of Cortical Oscillatory Dynamics

Abstract

Background: NMDA receptor-associated oscillations in the gamma frequency band (30-80 Hz) are thought to underlie a variety of cognitive processes known to be disrupted in patients with schizophrenia (SZ). NMDA receptor functioning can be assessed in subjects by measuring evoked power and phase synchronization of gamma frequency oscillations in response to auditory steady state stimulation (ASSR). Therefore, both evoked power and phase synchronization of gamma frequency have promising applications as translational biomarkers for procognitive therapeutics. In previous work, we reported the low-to-moderate affnity NMDA-receptor antagonist, memantine, enhanced prepulse inhibition of startle and mismatch negativity in SZ patients. Here, we report the effects of a single dose of memantine on evoked power and phase synchronization of ASSR obtained in our previous study. Methods: SZ patients (n = 18; M:F=11:7; mean age = 37.7 years; range:21-48) and healthy comparison subjects (n = 14; M:F = 10:4; age = 26.6 years; range:19-36) completed 2 test days separated by 1 week. On each test day, subjects received either memantine 20 mg (p.o.) or placebo in a double-blind, randomized, counterbalanced, within-subject, crossover design. The ASSR paradigm was used to measure evoked gamma power and phase locking in response to 40 Hz click trains. Results: Patients with SZ had reduced evoked gamma power and phase locking, consistent with previous reports (main effect of group-Power: F = 5.89, df = 1.30, P