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Vollenweider Andel Benz

Fakultäten » Medizinische Fakultät » Psychiatrische Universitätsklinik » Psychiatrie, Psychotherapie und Psychosomatik, Klinik für » Prof. Dr. F. X. Vollenweider » Vollenweider Andel Benz

Completed research project

Title / Titel Cortical organisation and the role of serotonin-2A receptors in the NMDA antagonist model of cognitive deficits: A H2O-PET study in healthy human volunteers
PDF Abstract (PDF, 14 KB)
Publications / Publikationen Schizophrenic patients have a prominent deficiency in attention and focusing on information in a context-related way. Attentional deficits have been linked to sensory and perceptual dysfunctions that arise from disturbed stimulus selection or inhibition or “gating“ of intrusive mental and motor activity. The assessment of sensorimotor gating deficits in animal and humans has been operationalized by measuring prepulse inhibition (PPI), the reduction of the startle reflex produced by a prepulse. Indeed, symptomatic (Braff and Geyer, 1990;Ludewig et al., 2002a) and unmedicated schizophrenia patients exhibit dramatic deficits in PPI deficits associated with formal thought disorder and attentional deficits (Ludewig et al., 2002b) suggested to be central to schizophrenic symptomatology. Indeed, the most striking correlate of deficient PPI in schizophrenia is a measure of thought disorder derived from the Rorschach test (Perry et al., 1999). Schizophrenic patients show dramatic deficits in PPI.
The neuronal basis of deficient prepulse inhibition in animal models of psychopathology is strikingly consistent with findings from brain imaging and neuropathological studies in humans that have identified abnormalities within cortico-striato-thalamic circuitry. Furthermore, in animal and human model of schizophrenia, also NMDA antagonists such as S-ketamine disrupt information processing (PPI) and exhibit cognitive deficits in normals similarly to those seen in schizophrenic psychoses by interference with the glutamate, serotonin and dopamine systems within cortico-striato-thalamic pathways (Lahti et al., 2001;Vollenweider and Geyer, 2001). Moreover, animal and human studies indicate that S-ketamine may produce these cognitive deficits in humans via interference with glutamatergic NMDA and serotoninergic 5-HT2A receptors (Vollenweider et al., 1999b;Varty et al., 1999;Aghajanian and Marek, 2000). However, to translate these basic research findings into clinical advances more research into the role of 5-HT2 receptors in the effects of S-ketamine on cognition is needed.

By elucidating the neuronal substrates of S-ketamine-induced cognitive impairments in normals, it might be possible to obtain critical information about the contribution of specific brain abnormalities to cognitive deficits in schizophrenia patients. Morover, the role of 5-HT2A receptors in cognitive deficits has not yet been studied with [H215O]PET in humans.
The first aim of this project is to localize the functional neuroanatomy underlying ketamine-induced attentional deficits by means of [H215O]PET in normal human adults. This aim will be accomplished by comparing regional brain activation produced by moderate doses of S-ketamine during an attentional task (AX- continuous performance task; CPT) with those produced under placebo conditions.
A second aim is to explore the role of 5-HT2A receptors in S-ketamine-induced attentional deficits by investigating the effect the 5-HT2A antagonist ketanserin on S-ketamine-induced brain activation patterns using [H215O]PET. Finally, these data shall be compared in a parallel study in normals receiving the mixed 5-HT2/D2 antagonist clozapine.

Keywords / Suchbegriffe attentional deficits, S-ketamine, 5-HT2 receptor, ketanserin, clozapine, positron emission tomography (PET), normals
Project leadership and contacts /
Projektleitung und Kontakte
Prof. F.X. Vollenweider (Project Leader) vollen@bli.uzh.ch
Dr. D. Andel (Project Leader)  
Dr. M. Benz (Project Leader)  
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung), Foundation
 
In collaboration with /
In Zusammenarbeit mit
Prof. G. von Schulthess, PET Center USZ, University of Zürich Switzerland
Duration of Project / Projektdauer May 2008 to Sep 2013