Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia
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Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia. / Haaf, Moritz; Curic, Stjepan; Steinmann, Saskia; Rauh, Jonas; Leicht, Gregor; Mulert, Christoph.
In: NEUROIMAGE, Vol. 251, 119004, 01.05.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia
AU - Haaf, Moritz
AU - Curic, Stjepan
AU - Steinmann, Saskia
AU - Rauh, Jonas
AU - Leicht, Gregor
AU - Mulert, Christoph
N1 - Copyright © 2022. Published by Elsevier Inc.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease. Moreover, this oscillatory change can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR, through NMDA-receptor co-agonism, accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the PANSS. S-Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment.
AB - Although a substantial number of studies suggests some clinical benefit concerning negative symptoms in schizophrenia through the modulation of NMDA-receptor function, none of these approaches achieved clinical approval. Given the large body of evidence concerning glutamatergic dysfunction in a subgroup of patients, biomarkers to identify those with a relevant clinical benefit through glutamatergic modulation are urgently needed. A similar reduction of the early auditory evoked gamma-band response (aeGBR) as found in schizophrenia patients can be observed in healthy subjects following the application of an NMDA-receptor antagonist in the ketamine-model, which addresses the excitation / inhibition (E/I) imbalance of the disease. Moreover, this oscillatory change can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR, through NMDA-receptor co-agonism, accompany an improvement concerning negative symptoms in the ketamine-model. The impact of subanesthetic ketamine doses and the pretreatment with glycine was examined in twenty-four healthy male participants while performing a cognitively demanding aeGBR paradigm with 64-channel electroencephalography. Negative Symptoms were assessed through the PANSS. S-Ketamine alone caused a reduction of the aeGBR amplitude associated with more pronounced negative symptoms compared to placebo. Pretreatment with glycine attenuated both, the ketamine-induced alterations of the aeGBR amplitude and the increased PANSS negative scores in glycine-responders, classified based on relative aeGBR increase. Thus, we propose that the aeGBR represents a possible biomarker for negative symptoms in schizophrenia related to insufficient glutamatergic neurotransmission. This would allow to identify patients with negative symptoms, who might benefit from glutamatergic treatment.
U2 - 10.1016/j.neuroimage.2022.119004
DO - 10.1016/j.neuroimage.2022.119004
M3 - SCORING: Journal article
C2 - 35176492
VL - 251
JO - NEUROIMAGE
JF - NEUROIMAGE
SN - 1053-8119
M1 - 119004
ER -