Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia
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 subg...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | NeuroImage |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1053811922001331 |
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| author | Moritz Haaf Stjepan Curic Saskia Steinmann Jonas Rauh Gregor Leicht Christoph Mulert |
| author_facet | Moritz Haaf Stjepan Curic Saskia Steinmann Jonas Rauh Gregor Leicht Christoph Mulert |
| author_sort | Moritz Haaf |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T02:02:11Z |
| format | Article |
| id | doaj.art-4f1699473859444f8995c03209e58384 |
| institution | Directory Open Access Journal |
| issn | 1095-9572 |
| language | English |
| last_indexed | 2024-12-13T02:02:11Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage |
| spelling | doaj.art-4f1699473859444f8995c03209e583842022-12-22T00:03:15ZengElsevierNeuroImage1095-95722022-05-01251119004Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophreniaMoritz Haaf0Stjepan Curic1Saskia Steinmann2Jonas Rauh3Gregor Leicht4Christoph Mulert5Department of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Psychiatry and Psychotherapy, Psychiatry Neuroimaging Branch (PNB), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Center of Psychiatry, Justus-Liebig University, Giessen, Germany; Corresponding author at: Center of Psychiatry, Justus-Liebig University, Klinikstrasse 36, D-35392 Giessen, Germany.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.http://www.sciencedirect.com/science/article/pii/S1053811922001331EEGNegative symptomsGlycineS-ketamine |
| spellingShingle | Moritz Haaf Stjepan Curic Saskia Steinmann Jonas Rauh Gregor Leicht Christoph Mulert Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia NeuroImage EEG Negative symptoms Glycine S-ketamine |
| title | Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia |
| title_full | Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia |
| title_fullStr | Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia |
| title_full_unstemmed | Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia |
| title_short | Glycine attenuates impairments of stimulus-evoked gamma oscillations in the ketamine model of schizophrenia |
| title_sort | glycine attenuates impairments of stimulus evoked gamma oscillations in the ketamine model of schizophrenia |
| topic | EEG Negative symptoms Glycine S-ketamine |
| url | http://www.sciencedirect.com/science/article/pii/S1053811922001331 |
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