Glycine attenuates impairments of stimulus-evoked gamma oscillation in the ketamine model of schizophrenia
Moritz Haaf, Stjepan Curic, Saskia Steinmann, Jonas Rauh, Gregor Leicht, Christoph Mulert
bioRxiv Preprint Server April 15, 2021 preprint DOI: 10.1101/2021.04.15.439976 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Sample size | 24 |
| Population | Healthy male participants |
| Interventions | Ketamine Glycine |
| Dose | subanesthetic ketamine doses |
| Topics | Esketamine Ketamine |
| Keywords | Schizophrenia Psychosis Mental disorder Neurological disorder Psychiatric condition Brain disorder Brain rhythms Brain waves Neural oscillations EEG Neurophysiology Brain activity Glycine Amino acid Compound Medication Therapy Intervention Negative symptoms Symptom management Clinical symptoms Psychiatric symptoms Symptom reduction Biomarkers Diagnostic markers Prognostic indicators Predictive markers Personalized medicine Treatment response indicators |
| Key findings | Glycine pretreatment attenuated ketamine-induced reductions in the early auditory evoked gamma-band response and associated negative symptoms, suggesting the aeGBR could be a biomarker for identifying schizophrenia patients who may benefit from glutamatergic treatment. |
Abstract
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.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cites 6
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model Current Pharmaceutical Biotechnology June 21, 2018
- Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine Neuropsychopharmacology February 6, 2019
- Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology Molecular Psychiatry January 3, 2012
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