Nicotine Effects on Endophenotypes of Schizophrenia

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.