Glycine attenuates ketamine induced schizophrenia-like alterations of the auditory evoked gamma-band response

rationale: A reduction of the early auditory evoked gamma-band response (aeGBR) has been shown to be associated with schizophrenia across different stages of the disease and may impair cognitive and perceptual processes. Comparable impairments as well as schizophrenia-like positive, negative and cognitive symptoms can be temporarily induced in healthy volunteers by means of an application of N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as ketamine. NMDAR hypofunction can explain many schizophrenia symptoms directly due to excitatory-to-inhibitory imbalance, but also dopaminergic dysfunction itself. Thus, we chose to investigate (i) whether changes of aeGBR during ketamine administration are associated with the emergence of schizophrenia-like symptoms in healthy volunteers and (ii) whether these symptoms can be mitigated by a pre-treatment with glycine, an amino acid acting as co-agonist at the NMDAR. method: 24 healthy male participants were included in a randomized, counter-balanced, placebo-controlled within-subject study. The impact of ketamine and the pre-treatment with glycine during a auditory choice reaction task was examined by means of 64-channel electroencephalography (EEG). In addition, the Positive and Negative Symptom Scale (PANSS) was used to assess the psychopathological status. results: We observed reductions of the aeGBR amplitude and an increase in all PANSS scores in the ketamine condition. Smaller aeGBR amplitudes were associated with more pronounced symptoms. Strikingly, pre-treatment with Glycine attenuated the observed ketamine-induced schizophrenia-like alterations of the aeGBR amplitude. discussion: These results point towards a putative applicability of the aeGBR as biomarker for negative symptoms related to an insufficient glutamatergic neurotransmission in schizophrenia. This could allow to identify patients with negative symptoms due to NMDAR dysfunction, who might benefit from treatment with glycine.