Neuroimaging of NMDA-sensitive Biomarkers in the Schizophrenia Spectrum

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The glutamate hypothesis is currently one of the most promising theories of the pathophysiology of schizophrenia. Despite intense research efforts into the role of glutamatergic dysfunction in schizophrenia and attempts to develop novel antipsychotic drugs that act on the glutamate system, very little is known about the role of glutamate in the wider spectrum of schizophrenia. Specifically, there is little evidence concerning the involvement of the glutamate system in schizotypy, the widely investigated subclinical expression of this dimensional disease phenotype. Additionally, no direct comparisons in schizophrenia biomarkers have been carried out so far between individuals under the influence of ketamine and patients with schizophrenia. Therefore, the present project has two major aims. First, it will investigate the effects of a subclinical, psychotomimetic dose of ketamine on perceptual-cognitive-motor behaviours and their underlying neural substrates using functional magnetic resonance imaging (fMRI) in people stratified by their level of schizotypy. Second, results from this study will be compared to results from schizophrenia patients, in order to delineate the boundaries of the glutamatergic basis of the schizophrenia spectrum.