Stephanie Thiebes1, Gregor Leicht1, Stjepan Curic1, Saskia Steinmann1, Nenad Polomac1, Christina Andreou1, Iris Eichler1, Lars Eichler1, Christian Zöllner1, Jürgen Gallinat1, Ileana Hanganu-Opatz1, Christoph Mulert1. 1. From the Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Thiebes, Leicht, Curic, Steinmann, Polomac, Andreou, Mulert); the Center for Gender Research and Early Detection, University of Basel Psychiatric Clinics, Basel, Switzerland (Andreou); the Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Eichler, Zöllner); the Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Gallinat); and the Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Hanganu-Opatz).
Abstract
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.
RCT Entities:
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.
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Authors: Stephanie Thiebes; Saskia Steinmann; Stjepan Curic; Nenad Polomac; Christina Andreou; Iris-Carola Eichler; Lars Eichler; Christian Zöllner; Jürgen Gallinat; Gregor Leicht; Christoph Mulert Journal: Neuropsychopharmacology Date: 2018-02-05 Impact factor: 7.853
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Authors: Stjepan Curic; Christina Andreou; Guido Nolte; Saskia Steinmann; Stephanie Thiebes; Nenad Polomac; Moritz Haaf; Jonas Rauh; Gregor Leicht; Christoph Mulert Journal: Front Psychiatry Date: 2021-06-10 Impact factor: 4.157