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Vollenweider Holstein

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

Completed research project

Title / Titel The effect of sertindole on sensory gating and cognition in schizophrenic patients
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood and cognitive disability is nearly fully developed at the first episode of psychosis in most patients. However, the neural underpinnings of cognitive deficits in schizophrenia are not well understood. Recent evidence suggests that of cognitive deficits in schizophrenia are linked to deficits in different domains of early information processing. Specifically, disruption in sensory/sensorimotor gating may cause schizophrenic patients to become overloaded with excessive exteroceptive and interoceptive stimuli which in turn could lead to a break down of cognitive integrity (McGhie & Chapman, 1961;Karper et al., 1996; Brebion et al., 1996). This view is evidenced by recent findings of significant positive correlations between deficits in sensory information processing as indexed by prepulse inhibition of the acoustic startle reflex (PPI) and thought disturbance (Perry & Braff, 1994;Perry et al., 1999) as well as deficits in attentional performance (Karper et al., 1996) in schizophrenia. In regard to the pathophysiology of cognitive deficits in schizophrenia it has been proposed that atypical antipsychotic drugs such as clozapine, risperidone or sertindole which are potent antagonism at serotonin-2A receptors may be more effective in reducing cognitive impairments that classic D2 antagonists (Azorin et al., 2006). Along this line it is noteworthy that atypical antipsychotics appear also to be superior over classic D2 antagonists in improving PPI deficits in schizophrenia (Kumari et al., 2002). In addition, recent studies in rodents suggest that antagonists at 5-HT6 receptors normalize NMDA antagonist-induced cognitive deficits in rodents without producing the sedative effects of atypical antipsychotics such as clozapine (Arnt et al. 2008).

This study aims to investigate whether the atypical antipsychotic and mixed mixed 5-HT2A/6A and D2 receptor antagonist sertindole in comparison to the atypical 5-HT2A modulates or improves both subcortical and cortical information processing in schizophrenic patients who had not or insufficiently responded to previous antipsychotic medication. This goal shall be accomplished by investigating the effect of sertindole of both prepulse inhibition of the acoustic startle (PPI) and P50 suppression of auditory evoked potentials in schizophrenic patients. These effects shall be compared to the effect risperidone and shall also be compared to untreated healthy controls.
A second aim is to further elucidate whether improvement in sensory gating after antipsychotic treatment is linked to cognitive performance. This goal shall be accomplished by using subset of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess attentional set-shifting, working memory, visual memory, and executive functioning.
The study shall help to clarify whether atypical drugs produce significant differences in specific cognitive functions in schizophrenic patients. Such differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance.
Project leadership and contacts /
Projektleitung und Kontakte
Prof. F.X. Vollenweider (Project Leader) vollen@bli.zuh.ch
MS D. Holstein (Project Leader)  
Dr. P. Csomor  
Funding source(s) /
Unterstützt durch
Foundation, Private Sector (e.g. Industry)
 
In collaboration with /
In Zusammenarbeit mit
Prof. M. Geyer, Dept. of Psychiatry, University of California San Diego United States
Duration of Project / Projektdauer Jan 2008 to Dec 2011