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

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).