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).

• INCLUSION CRITERIA:

All participants must meet the following criteria:

• age 18 60
• smoke 10 or more cigarettes/day for at least the past year

Experimental groups 1 and 2, additional criteria:

-DSM-IV diagnosis of schizophrenia or schizoaffective disorder (assessments pertaining to these diagnoses will be done in other MPRC screening protocols).

Experimental group 2, additional criteria:

-DSM-IV diagnosis of abuse or dependence on cocaine and/or heroin or on methadone or buprenorphine maintenance.

Exclusion criteria

Comprehensive medical history:

-Exclusions: Heart disease, uncontrolled blood pressure (persistent systolic above 155 or diastolic above 95), neurological conditions (stroke, seizure, history of head injury), asthma, emphysema, chronic bronchitis, chronic obstructive pulmonary disease, pathology of nasal passages that precludes the effective administration of nicotine nasal spray.

Drug Use Survey

All subjects:

• Exclude if treatment for tobacco dependence during the previous 6 months.
• Healthy controls and schizophrenic patients without comorbid drug abuse or dependence: Exclude if history alcohol or other substance dependence ever, or alcohol or other substance abuse in the past year. Verify abstinence from controlled substances with urine screen (Iscreen). Participants in the above 2 groups who are positive for any illicit drug (with the exception of marijuana) will be excluded.

Structured Clinical Interview for DSM-IV

-Healthy controls: exclude if any current psychiatric disorder

Urine pregnancy for females:

-Exclude if positive.