The glutamate hypothesis of schizophrenia presumes a hypofunction of the N-methyl-d-aspartate receptor (NMDAR), which is essential for glutamate neurotransmission. The ketamine model of schizophrenia utilizes the administration of subanesthetic doses of the NMDAR antagonist ketamine in order to reduce NMDAR dependent glutamatergic neurotransmission, which causes the emergence of schizophrenia-like symptoms in healthy volunteers.
Christoph Mulert (Gießen) will present work on ketamine-induced alterations of different EEG biomarkers related to different symptoms of schizophrenia such as cognitive disturbances, negative symptoms and auditory hallucinations and compare the results with findings in patients with schizophrenia. The potential biological underpinnings will be discussed.
Peter Uhlhaas (Berlin/Glasgow) will summarize MEG-data that from early-stage psychosis and schizophrenia patients as well as the effects of Ketamine in healthy volunteers to assess the overlap of alterations in resting-state as well as task-related activity.
Moritz Haaf (Hamburg) will focus on the potential utility of the ketamine model of schizophrenia as means of ensuring target engagement in the development of glutamatergic antipsychotics. Recent studies that suggest the potential feasibility of electrophysiological and functional MRI biomarkers in this context as well as own work focusing on NMDA receptor modulation in the ketamine model will be summarized and discussed.
Ulrich Ettinger (Bonn) will present work on the effects of ketamine on biomarkers of schizophrenia. This work aims at validating the ketamine model by testing the extent to which oculomotor, cognitive and neuroimaging alterations that are observed in schizophrenia can be reproduced by acute administration of ketamine in healthy individuals. The findings of this work suggest that ketamine is a promising yet incomplete model of schizophrenia, as only some of the known impairments in schizophrenia were replicated.
10:15 Uhr
Different symptoms of schizophrenia and the ketamine model of the disease: clinical perspectives from EEG research
C. Mulert (Gießen, DE)
10:37 Uhr
Neural oscillations, ketamine and schizophrenia: is the NMDA-R model of schizophrenia compatible with electrophysiological findings from MEG studies?
P. Uhlhaas (Berlin, DE)
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P. Uhlhaas (Berlin, DE)
A considerable body of work over the last 20 years combining non-invasive electrophysiology (electroencephalography/magnetoencephalography) in patient populations with preclinical research has contributed to the conceptualization of schizophrenia as a disorder associated with aberrant neural dynamics and disturbances in excitation/inhibition (E/I) balance parameters. We have carried out several studies which have tested the importance of neural oscillations in the pathophysiology of schizophrenia through a combination of MEG-measurements in ScZ-patients and pharmacological manipulations in healthy volunteers which target the NMDA-receptor. These results highlight a pronounced impairment in high-frequency activity in both chronic and unmedicated patients which could provide novel insights into basic circuit mechanisms underlying cognitive and perceptual dysfunctions.
Our recent work has employed MEG to develop a biomarker for early detection and diagnosis of ScZ. We have obtained MEG- and MRS-data from 125 participants meeting clinical high-risk criteria (CHR), 90 controls and 30 FEP-patients. We found marked changes in the synchrony of gamma-band oscillations in visual and auditory cortices during sensory processing which predicted clinical outcomes. In addition, CHR-participants were characterized by elevated broad-band gamma-band activity at rest which correlated with increased glutamate levels. Together, these findings highlight the potential of MEG-based biomarkers for the early diagnosis of ScZ.
10:59 Uhr
The role of the ketamine model of schizophrenia in the development of glutamatergic antipsychotics
M. Haaf (Hamburg, DE)
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M. Haaf (Hamburg, DE)
While the ketamine model of schizophrenia can model some aspects of the disease, the question remains whether it can be utilized as a translational model for the development of therapies. Ensuring target engagement in the development of glutamatergic antipsychotics and the identification of corresponding biomarkers are potential areas of application.
In this talk, recent electrophysiological and functional MRI studies employing the ketamine model in this context will be summarized and discussed – complemented by our own work focusing on the modulation of NMDA receptors by the co-agonist glycine
11:21 Uhr
Effects of ketamine on brain function, cognition and oculomotor control
U. Ettinger (Bonn, DE)
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U. Ettinger (Bonn, DE)
This talk will provide an overview of results from studies that investigate the effects of ketamine on well-established biomarkers of schizophrenia. This work aims at validating the ketamine model by testing the extent to which oculomotor, cognitive and neuroimaging alterations that are observed in schizophrenia spectrum populations can be reproduced by acute administration of ketamine in healthy individuals. The findings of these pharmacological fMRI studies in healthy humans demonstrate that ketamine is a promising yet incomplete model of schizophrenia, as only some of the known impairments in schizophrenia were replicated. Specifically, these include a robust deficit in smooth pursuit eye movements that is accompanied by reductions in BOLD in visual and oculomotor areas. Effects on other domains of cognition and brain function, such as inhibitory control or metacognitive bias, however, were inconsistent, in contrast to replicable deficits in those domains in schizophrenia.