Nicotine Effects on Endophenotypes of Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.

      Main hypotheses:

        -  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.
    

Intervention name(s): Transdermal nicotine patch; Placebo patch
Intervention type(s): Drug; Drug
Intervention description(s): 7mg transdermal nicotine patch (non-smoking subjects) 14mg transdermal nicotine patch (smoking subjects); Placebo patch
Other intervention name(s): NiQuitin Clear, GlaxoSmithKline Germany; band-aid by Fink and Walter GmbH, Germany
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: nicotine; schizophrenia; endophenotype