RT Journal Article SR Electronic T1 Glutamatergic deficit and schizophrenia-like negative symptoms: new evidence from ketamine-induced mismatch negativity alterations in healthy male humans JF Journal of Psychiatry and Neuroscience JO J Psychiatry Neurosci FD Canadian Medical Association SP 273 OP 283 DO 10.1503/jpn.160187 VO 42 IS 4 A1 Stephanie Thiebes A1 Gregor Leicht A1 Stjepan Curic A1 Saskia Steinmann A1 Nenad Polomac A1 Christina Andreou A1 Iris Eichler A1 Lars Eichler A1 Christian Zöllner A1 Jürgen Gallinat A1 Ileana Hanganu-Opatz A1 Christoph Mulert YR 2017 UL http://jpn.ca/content/42/4/273.abstract AB Background: Targeting the N-methyl-d-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers.Methods: We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization.Results: Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus.Limitations: The sample included only men within a tight age range of 20–32 years.Conclusion: The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.