PT  - JOURNAL ARTICLE
AU  - Haaf, Moritz
AU  - Curic, Stjepan
AU  - Steinmann, Saskia
AU  - Rauh, Jonas
AU  - Leicht, Gregor
AU  - Mulert, Christoph
TI  - Glycine attenuates impairments of stimulus-evoked gamma oscillation in the ketamine model of schizophrenia
AID  - 10.1101/2021.04.15.439976
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.15.439976
4099  - http://biorxiv.org/content/early/2021/04/16/2021.04.15.439976.short
4100  - http://biorxiv.org/content/early/2021/04/16/2021.04.15.439976.full
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 in the ketamine-model, which addresses the putative excitation / inhibition (E/I) imbalance of the diseases. Moreover, this change in gamma-band oscillations can be related to the emergence of negative symptoms. Accordingly, this study investigated whether glycine-related increases of the aeGBR 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 Positive and Negative Syndrome Scale (PANSS). 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.Competing Interest StatementThe authors have declared no competing interest.