Journal article

Publication year: 2019

Pages: 1239-1246

Journal: Neuropsychopharmacology

Volume number: 44

Issue number: 7

ISSN: 0893-133X

eISSN: 1740-634X

Open access status: Hybrid

DOI Link: https://doi.org/10.1038/s41386-019-0328-5

Publisher: Springer Nature [academic journals on nature.com]

Abstract: 
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. Lowresolution 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.

Harvard Citation style: Curic, S., Leicht, G., Thiebes, S., Andreou, C., Polomac, N., Eichler, I., et al. (2019) Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine, Neuropsychopharmacology, 44(7), pp. 1239-1246. https://doi.org/10.1038/s41386-019-0328-5

APA Citation style: Curic, S., Leicht, G., Thiebes, S., Andreou, C., Polomac, N., Eichler, I., Eichler, L., Zoelliner, C., Gallinat, J., Steinmann, S., & Mulert, C. (2019). Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine. Neuropsychopharmacology. 44(7), 1239-1246. https://doi.org/10.1038/s41386-019-0328-5