fMRI Study of Nicotinic Effect on Neurophysiology of Schizophrenia
Condition: Schizophrenia; Psychopathology; Nicotine Dependence
MeSH terms: Tobacco Use Disorder; Schizophrenia
Study type: Observational

Summary: 
      Background:

        -  Individuals who have schizophrenia are significantly more likely to smoke than the
           general population, which leads to increased smoking-related illnesses and high rates of
           nicotine dependence. Research suggests that high rates of smoking and nicotine addiction
           in people with schizophrenia are related to the fact that nicotine temporally improves
           performance in several cognitive tasks, including sensory gating, long-term memory, and
           visual tracking-all of which are affected by schizophrenia.

        -  Smoking among schizophrenia patients may be a form of self-medication, since nicotine
           may temporarily treat and improve cognitive deficits caused by schizophrenia.
           Researchers are interested in studying the effects of nicotine on the brain activity of
           individuals with schizophrenia to better understand how nicotine affects the brain
           regions connected to memory, visual tracking, and attention.

      Objectives:

        -  To identify specific brain regions involved in the anticipatory learning deficits found
           in schizophrenia patients who smoke.

        -  To determine whether and how nicotine enhances performance in these regions.

      Eligibility:

      - Smokers (at least 10 cigarettes per day) between 18 and 50 years of age who either are
      healthy volunteers or have been diagnosed with schizophrenia/schizoaffective disorder.

      Design:

        -  Participants will be asked to avoid consuming alcohol and restrict consuming caffeinated
           beverages for 24 hours before the study days. Participants will provide urine and breath
           samples at the start of the study to be tested for chemicals that may interfere with the
           study.

        -  The study will require two to four visits, with two fMRI sessions and other visits for a
           clinical interview or training.

      Participants will have a training session with a possible mock MRI scan to learn how to do
      tasks that track eye movement and measure ability to pay attention.

        -  During the fMRI scanning sessions, participants will receive either a nicotine patch or
           a placebo patch without nicotine. After the patch is in place, participants will perform
           tasks while receiving MRI scans. The scans will take up to 2 hours.

        -  Participants will provide blood samples after finishing the MRI sessions.
    

Detailed description: 
      The prevalence rate of smoking among schizophrenia patients is as high as 88 percent. This is
      associated with a 2-fold increase in deaths due to smoking related diseases-compounded by
      high rates of nicotine dependence and low abstinence rates following cessation programs.
      Converging lines of evidence suggest that high rates of smoking and nicotine addiction among
      schizophrenic patients is influenced by the presence of disease-related abnormalities in
      brain function. Genetic and post mortem studies show that patients exhibit abnormalities in
      neuronal nicotinic receptors, which are involved in a number of cognitive functions.
      Pharmacological studies show that nicotine temporally improves performance in several
      cognitive tasks including sensory gating, long-term memory, and visual tracking. These data
      support a growing consensus that smoking among schizophrenic patients is a form of
      self-medication, and suggest that the success of targeted smoking cessation programs will
      depend, in part, on finding alternative means of treating the underlying cognitive deficits.
      One of the most reproducible neurocognitive and biological changes in schizophrenia is
      abnormal visual tracking, or smooth pursuit eye movements. Preliminary data show that
      previously reported deficits in visual tracking are related to anticipatory learning deficits
      and that nicotine enhances performance in patients by temporarily treating this learning
      deficit. A better understanding of these processes may lead to better behavioral and/or
      pharmacological therapeutic interventions for excessive nicotine abuse and recidivism in this
      clinically vulnerable population. In order to identify brain regions underlying this learning
      deficit we propose to compare brain activations in 30 healthy controls and 30 patients with
      schizophrenia during anticipation of target motion using functional magnetic resonance
      imaging (fMRI). In order to identify the brain regions involved in nicotine-induced
      enhancement of anticipatory learning we will compare activation in patients under conditions
      of unexpected and anticipated target motion following administration of nicotine and placebo.
    

Time perspective: Other
Keywords: Psychopathology; Nicotine Patch; Eye Tracking; Attention; Schizophrenic Participants