Influence of Nicotine on Cognitive Function in Schizophrenic Patients With and Without Comorbid Drug Dependence

Overview

Background: * Individuals with schizophrenia have a significantly higher tendency to develop substance abuse or dependence than the general population. For instance, people with schizophrenia smoke much more than the general population, and many are dependent on street drugs such as cocaine and heroin. However, these individuals are rarely included in research studies that might provide more information about treatments for both schizophrenia and substance abuse. * Strong evidence suggests that schizophrenia and substance dependence have similar effects on the brain, affecting attention, memory, and eye movement. Other research indicates that schizophrenia and substance dependence affect the same parts of the dopamine system, contributing to problems in brain function that require treatment. These new developments provide a strong rationale to study the combination of schizophrenia and substance dependence. * Nicotine may help improve brain function and thinking in individuals with both schizophrenia and drug dependence. Some of the thinking and memory problems experienced by these individuals can be treated with nicotine. However, more research is needed to determine exactly how nicotine affects individuals with both schizophrenia and drug dependence. Objectives: * To determine whether individuals with schizophrenia and drug dependence show impairment in tests of eye tracking, attention, and memory compared with healthy control subjects. * To evaluate the effect of nicotine on eye tracking, attention, and memory in individuals with both schizophrenia and substance dependence. Eligibility: \- Current smokers (at least 10 cigarettes per day for the past year) between 18 and 55 years of age who (1) have been diagnosed with schizophrenia/schizoaffective disorder, (2) have been diagnosed with schizophrenia/schizoaffective disorder and are currently using heroin and/or cocaine, or (3) are healthy individuals with no family history of psychotic illness. Design: * The study will consist of one training session and three testing sessions. Each session will last about 2 hours. * The training session will introduce participants to the study tests and evaluate their tolerance of the nicotine nasal spray used in the study. Participants who cannot tolerate the higher dose of the spray will not continue in the study. * At the start of each testing session, smokers will have one cigarette to standardize the time of the most recent exposure to nicotine. * During the testing sessions, participants will receive a placebo spray, a lower dose of nicotine, or a higher dose of nicotine, and then will be asked to perform tests that evaluate attention, memory, and other thinking tasks.

Objective: Specific aim 1: To test the hypothesis that individuals with comorbid schizophrenia and drug dependence will show impaired neurocognitive functions in anticipatory learning of eyetracking, attention, and memory performance compared to healthy controls subjects. Specific aim 2: To test the hypothesis that nicotine will dose-dependently improve anticipatory learning of eyetracking, attention, and memory performance in individuals with comorbid schizophrenia and substance dependence. Study Population: Male and nonpregnant-female smokers 18 to 55 years of age, from the following subject groups: (1) patients with a DSM IV diagnosis of schizophrenia (2) patients with dual DSM IV diagnoses of schizophrenia and heroin and/or cocaine dependence or abuse, or on methadone or beprenorphine maintenance and (3) healthy individuals with no family history of psychotic illness. Design: This study will be a double-blind, placebo controlled trial of nicotine or placebo nasal sprays. Participants will have four visits. After the training session, participants will be administered one dose (0, 1 or 2 mg) of nicotine nasal spray during each of the 3 experimental sessions. The dose will be given 5 minutes prior to the cognitive task batteries. Outcome Measures: Vital signs, moods, and performance on tasks assessing eye movement (initiation latency, initiation acceleration, closed-loop pursuit gain), attention (Continuous Performance and Digit Symbol Substitution Tasks), and memory (delayed recognition and nback).