Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine
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Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine. / Curic, Stjepan; Leicht, Gregor; Thiebes, Stephanie; Andreou, Christina; Polomac, Nenad; Eichler, Iris-Carola; Eichler, Lars; Zöllner, Christian; Gallinat, Jürgen; Steinmann, Saskia; Mulert, Christoph.
in: NEUROPSYCHOPHARMACOL, Jahrgang 44, Nr. 7, 06.2019, S. 1239-1246.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine
AU - Curic, Stjepan
AU - Leicht, Gregor
AU - Thiebes, Stephanie
AU - Andreou, Christina
AU - Polomac, Nenad
AU - Eichler, Iris-Carola
AU - Eichler, Lars
AU - Zöllner, Christian
AU - Gallinat, Jürgen
AU - Steinmann, Saskia
AU - Mulert, Christoph
PY - 2019/6
Y1 - 2019/6
N2 - 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.
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.
U2 - 10.1038/s41386-019-0328-5
DO - 10.1038/s41386-019-0328-5
M3 - SCORING: Journal article
C2 - 30758327
VL - 44
SP - 1239
EP - 1246
JO - NEUROPSYCHOPHARMACOL
JF - NEUROPSYCHOPHARMACOL
SN - 0893-133X
IS - 7
ER -