Effects of Nicotine on Areas of Impaired and Preserved Functioning in Schizophrenia

Overview

Background: * Some people with schizophrenia have problems with their working memory and paying attention for extended periods. These difficulties cannot be treated with antipsychotic medications or with many standard therapies. * The prevalence of cigarette smoking among individuals with schizophrenia is about three times higher than in the general population. Research has shown that nicotine, the addictive component found in cigarettes, can help improve attentional and working memory performance. Researchers are interested in learning more about whether there may be an overlap in the cognitive functions beneficially affected by nicotine and areas of dysfunction in individuals with schizophrenia. Objectives: * To evaluate the potential of transdermal nicotine to alleviate cognitive deficits in schizophrenia, and to determine whether naturally maintained cigarette-smoking, in comparison, is an effective self-medication. * To gather preliminary data on genetics that may account for individual and group differences in the performance effects of nicotine. Eligibility: \- Current smokers (25 or more cigarettes per week for at least 1 year) between 18 and 55 years of age who are either healthy volunteers or have been diagnosed with schizophrenia/schizoaffective disorder. Design: * The study will require five visits to the research center, with an initial screening visit, a training session, and three test sessions. Ideally, all visits will occur 1 week apart. * Training session: Participants will receive training on the types of computerized cognitive and attentional behavior tests that will be given during the active portion of the study. Participants will also fill out questionnaires on nicotine use and other alcohol and drug use. * Test sessions: Participants will be assigned to random groups and will complete tests that assess cognitive performance (a) while maintaining their usual smoking behavior, (b) after minimal deprivation (3.5 hours without smoking) while wearing a placebo patch, and (c) under the influence of a standard nicotine patch. The order of these sessions will be different for individual participants. * Participants will provide blood samples throughout the research study for evaluation purposes.

Objective: 1. To evaluate the potential of transdermal nicotine to alleviate distinct cognitive deficits in schizophrenia, and to determine whether naturally maintained cigarette-smoking, in comparison, is an effective self-medication. 2. To gather preliminary data on genotypes that may account for interindividual and group differences in the performance effects of nicotine. Study population: 45 regular smokers with schizophrenia, 45 matched control smokers (greater than or equal to 5 cigarettes/day). Design: Double-blind, placebo-controlled, within-subject study, evaluating cognitive functions under conditions of normal smoking, transdermal nicotine (14 mg/day), and placebo (minimal tobacco deprivation). Outcome measures: Measures of cognitive task performance, measures of subjective state, plasma concentrations of nicotine and metabolites, and genotype with regards to genes coding for nicotinic receptor subunits, MAO, and COMT.