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© 2016 Society of Biological PsychiatryBackground Working memory (WM) deficits are a core feature of schizophrenia. Electrophysiological studies suggest that impaired early visual processing may contribute to impaired WM in the visual domain. Abnormal N-methyl-D-aspartate (NMDA) receptor function has been implicated both in WM and in early visual processing deficits in schizophrenia. We investigated whether ketamine, a noncompetitive NMDA antagonist, would replicate in healthy volunteers the WM performance and early visual processing abnormalities we and others have reported in patients with schizophrenia. Methods Forty-four healthy volunteers were randomly assigned to receive intravenous ketamine or placebo. During infusion, the effects of ketamine were recorded using standardized psychiatric scales. Visual evoked potentials (P100 and P300 components) were recorded during performance of a delayed matching to sample task. Results Ketamine induced mild psychosis-like symptoms and impaired WM performance. It also significantly increased the P100 amplitude, while P300 amplitude decreased in a load-dependent manner. Amplitudes of P100 during retrieval correlated with cognitive performance only in the placebo group. Conclusions We confirmed previous studies showing that ketamine reproduces the impairment of WM performance and smaller P300 amplitudes observed in schizophrenia. However, ketamine increased visual P100 amplitude in contrast to our observation of reduced P100 amplitudes in established schizophrenia. The effects of ketamine on WM and P300 are likely to involve impaired NMDA function, as these receptors are implicated in changes of synaptic strength underlying associative learning and memory. Increased P100 amplitude may reflect the secondary disinhibition of cortical glutamate release that occurs after NMDA blockade.

Original publication

DOI

10.1016/j.bpsc.2016.09.008

Type

Journal article

Journal

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Publication Date

01/04/2017

Volume

2

Pages

253 - 262