PMID- 30758327 OWN - NLM STAT- MEDLINE DCOM- 20191210 LR - 20210109 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 44 IP - 7 DP - 2019 Jun TI - Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine. PG - 1239-1246 LID - 10.1038/s41386-019-0328-5 [doi] AB - Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior. In a placebo-controlled, randomized crossover design, the aeGBR power, phase-locking factor (PLF) during a choice reaction task, the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale were assessed in 25 healthy subjects. Ketamine was applied in a subanaesthetic dose. Low-resolution brain electromagnetic tomography was used for EEG source localization. Significant reductions of the aeGBR power and PLF were identified under ketamine administration compared to placebo (p < 0.01). Source-space analysis of aeGBR generators revealed significantly reduced current source density (CSD) within the anterior cingulate cortex during ketamine administration. Ketamine induced an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01) and increased response times (p < 0.001) and error rates (p < 0.01). Only negative symptoms were significantly associated with an aeGBR power decrease (p = 0.033) as revealed by multiple linear regression. These findings argue for a substantial role of the glutamate system in the mediation of dysfunctional gamma band responses and negative symptomatology of schizophrenia and are compatible with the NMDAR hypofunction hypothesis of schizophrenia. FAU - Curic, Stjepan AU - Curic S AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. S.Curic@uke.de. AD - Institute for Sex Research and Forensic Psychiatry, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. S.Curic@uke.de. FAU - Leicht, Gregor AU - Leicht G AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Thiebes, Stephanie AU - Thiebes S AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Andreou, Christina AU - Andreou C AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. AD - Center for Psychotic Disorders, University Psychiatric Hospital, University of Basel, Basel, Switzerland. FAU - Polomac, Nenad AU - Polomac N AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Eichler, Iris-Carola AU - Eichler IC AD - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Eichler, Lars AU - Eichler L AD - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Zollner, Christian AU - Zollner C AD - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Gallinat, Jurgen AU - Gallinat J AD - Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Steinmann, Saskia AU - Steinmann S AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Mulert, Christoph AU - Mulert C AD - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. AD - Centre for Psychiatry and Psychotherapy, Justus Liebig University, Giessen, Germany. LA - eng GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International GR - SFB 936 C6/Deutsche Forschungsgemeinschaft (German Research Foundation)/International PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190206 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Excitatory Amino Acid Antagonists) RN - 3KX376GY7L (Glutamic Acid) RN - 690G0D6V8H (Ketamine) SB - IM MH - Acoustic Stimulation MH - Adult MH - Brain/drug effects/*physiology MH - *Evoked Potentials, Auditory/drug effects MH - Excitatory Amino Acid Antagonists MH - *Gamma Rhythm/drug effects MH - Glutamic Acid/physiology MH - Humans MH - Ketamine/*administration & dosage MH - Male MH - Schizophrenia/*chemically induced/physiopathology MH - Young Adult PMC - PMC6785009 COIS- The authors declare no competing interests. EDAT- 2019/02/14 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/02/06 CRDT- 2019/02/14 06:00 PHST- 2018/07/16 00:00 [received] PHST- 2019/01/29 00:00 [accepted] PHST- 2019/01/28 00:00 [revised] PHST- 2019/02/14 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/02/14 06:00 [entrez] PHST- 2019/02/06 00:00 [pmc-release] AID - 10.1038/s41386-019-0328-5 [pii] AID - 328 [pii] AID - 10.1038/s41386-019-0328-5 [doi] PST - ppublish SO - Neuropsychopharmacology. 2019 Jun;44(7):1239-1246. doi: 10.1038/s41386-019-0328-5. Epub 2019 Feb 6.