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

Objective:

• 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.
• 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.

• INCLUSION CRITERIA:

All participants:

• Age 18 through 55. The aim is to minimize population inhomogeneity related to cognitive decline due to normal aging.
• Smoker of 5 or more cigarettes, cigarillos or cigars per day, on 5 or more days/week, for at least the last 12 months
• Normal or corrected to normal visual acuity (at least 20/100).

Participants with mental illness, additional inclusion criteria:

• DSM-IV diagnosis of schizophrenia or schizoaffective disorder
• Ability to give written informed consent
• Four weeks of stable pharmacological treatment (same psychiatric medication at same dose)

Exclusion criteria

All participants:

• History of myocardial infarction, heart failure, angina, stroke or severe arrhythmias, EKG abnormalities as specified under Screening methods
• Uncontrolled high blood pressure (resting systolic above 150 or diastolic above 90 mm Hg)
• Neurological conditions such as stroke, seizures, dementia or organic brain syndrome
• Any condition likely to impair cognitive function such as mental retardation, attention deficit disorder or severe pharmacological sedation
• Treatment for tobacco dependence in the last four months
• Alcohol or substance abuse or dependence other than nicotine within the last 12 months
• Pregnancy, verified by urine pregnancy test for females at first visit and in the beginning of each of the two patch administration sessions
• Lactating

Healthy controls, additional exclusion criterion:

• Current psychiatric Axis I disorder or Axis II schizophrenia spectrum disorder, verified by Structured Clinical Interview for DSM-IV (SCID)

Participants with mental illness, additional exclusion criterion:

• Treated with benztropine (a nicotinic and muscarinic antagonist) or with an acetylcholine esterase inhibitor currently or within the last four weeks