Will Decreased Noradrenergic Activity Normalize Information Processing in Patients With Schizophrenia?

Overview

The investigators want to try to improve information processing in schizophrenic patients via pharmacological intervention. The hypothesis is that decreased noradrenergic activity will normalize information processing (PPI, P50 gating, P300, and mismatch negativity) in patients with schizophrenia.

A number of reports in literature provide evidence for, among others, an increased central noradrenergic activity in schizophrenia. In addition to this increased noradrenergic activity, patients with schizophrenia often show reduced filtering of sensory information, which is reflected in reduced P50 suppression and reduced prepulse inhibition of the startle reflex (PPI). In two separate initial studies in our laboratory, we found reduced sensory gating following administration of imipramine (a combined noradrenergic and serotonergic agonist) and desipramine (a highly specific noradrenergic agonist) to healthy volunteers. This provides evidence for a direct causal relation between the increased noradrenergic activity and the disturbed gating of sensory information, as both commonly found in patients with schizophrenia. Therefore, in a follow-up study, the effects of a noradrenergic antagonist will be investigated on the sensory gating of patients with schizophrenia. To further extend the data of our initial studies, the patients will additionally be tested for two psychophysiological parameters of attention that are usually found to be disturbed in patients with schizophrenia, i.e. mismatch negativity and selective attention. The design will conform to a double blind, placebo controlled experiment, in which either four doses (0.25 ug, 50 ug, 75 ug or 150 ug)of clonidine or placebo will be added to the current medical treatment of 20 male patients with schizophrenia on five occasions, separated by at least a week, after which they are tested in the Copenhagen Psychophysiological Test Battery (CPTB).In order to test the effects of clonidine in healthy volunteers, 20 healthy males will receive a fixed dose of 0.15 mg clonidine or placebo on two separate occasions separated by at least a week, after which they will be tested in the CPTB as well.

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