Nicotine Effects on Endophenotypes of Schizophrenia
The purpose of this study is to test the effects of nicotine on cognition with the following schizophrenia endophenotypes: prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Schizophrenia patients, unaffected first-degree relatives of schizophrenia patients and healthy controls receive transdermal nicotine in a double-blind, placebo-controlled, crossover study.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||Nicotine Effects on Endophenotypes of Schizophrenia|
- Change in cognitive functioning [ Time Frame: Three hours after patch application ] [ Designated as safety issue: No ]About three hours after the application of a nicotine/placebo patch, the change in cognitive functioning is assessed. The cognitive functions being assessed include prepulse inhibition, antisaccade eye movements, the continuous performance task, spatial working memory, and a verbal memory task.
- Change in cognitive functioning as a function of genotype [ Time Frame: Three hours after patch application ] [ Designated as safety issue: No ]It will be assessed whether there is an association between nicotine-induced changes in cognitive functioning and polymorphisms in the nicotinic acetylcholine receptor genes.
|Study Start Date:||July 2008|
|Study Completion Date:||March 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Nicotine Patch
Transdermal nicotine patch
Drug: Transdermal nicotine patch
7mg transdermal nicotine patch (non-smoking subjects) 14mg transdermal nicotine patch (smoking subjects)
Other Name: NiQuitin Clear, GlaxoSmithKline Germany
Placebo Comparator: Placebo patch
Drug: Placebo patch
Other Name: band-aid by Fink and Walter GmbH, Germany
Convergent findings suggest that an altered neuronal nicotinic acetylcholine receptor system may contribute to the pathophysiology of schizophrenia. Nicotine consumption through cigarette smoking might represent a form of self-medication in schizophrenia as nicotine reduces cognitive and physiological deficits in schizophrenia. The present study aims to investigate how nicotine affects attentional and executive schizophrenia endophenotypes and how genetic polymorphisms relating to the cholinergic system might play a role in inter-individual differences in the magnitude of nicotine effects.
Schizophrenia patients, first-degree relatives of schizophrenia patients as well as healthy controls will receive transdermal nicotine in a double-blind, placebo-controlled, crossover study and will be assessed with prepulse inhibition, antisaccades, the continuous performance test, spatial working memory and a verbal memory task. Subjects will be overnight-abstinent smokers and non-smokers. However, the investigators will particularly test non-smokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement.
- Schizophrenia patients will perform worse than matched controls in all cognitive tests (validating our endophenotypes).
- Nicotine administration will enhance cognitive performance in overnight-abstinent smokers.
- Improvement of cognitive performance in smokers with schizophrenia will be stronger than in control smokers.
- Improvement of cognitive performance in smoking first-degree relatives of schizophrenia patients will be stronger than in control smokers.
- Nicotine administration will affect cognitive functioning in non-smoking subjects.
- Nicotine administration will improve cognitive functioning in non-smoking schizophrenia patients.
- The effects of nicotine in non-smoking subjects are stronger in those subjects who are cognitively more impaired (i.e. performing below the median of the respective group).
The present research contributes to the issue whether nicotinic cholinergic receptor agonists may have therapeutic value in the treatment of cognition in schizophrenia.
|Principal Investigator:||Michael Wagner, Prof. Dr.||University Hospital, Bonn|
|Principal Investigator:||Wolfgang Maier, Prof. Dr.||University Hospital, Bonn|