Brain Circuits in Schizophrenia and Smoking
Condition: Schizophrenia; Smoking Cessation; Nicotine Abuse
MeSH terms: Schizophrenia
Study type: Observational

Summary: 
      Background:

      - Smoking is associated with serious health risks. People who have mental illness are more
      likely to smoke. Researchers are studying the brain circuits linked with smoking and nicotine
      craving. This study will look at whether a specific brain circuit can explain the high rate
      of smoking in people with schizophrenia.

      Objectives:

      - To study brain activity in smokers and nonsmokers with and without schizophrenia, as well
      as their family members.

      Eligibility:

        -  Current smokers (at least 100 cigarettes in the past year) and nonsmokers between 18 and
           62 years of age in one of the following groups:

        -  Have been diagnosed with schizophrenia.

        -  Family members of those with schizophrenia.

        -  Healthy adults with no history of severe mental illness or brain trauma.

        -  Family members of the healthy adults.

      Design:

        -  People in the study will be screened with a physical exam, medical history,
           questionnaires, and blood tests.

        -  They will have up to three visits: the screening visit and two study visits (each given
           1 year apart).

        -  At the first study visit, those taking part will be trained in the tests they will do
           during the magnetic resonance imaging (MRI) scan. Then they will have the MRI scan.

        -  After the first study visit, current smokers will receive phone calls from the study
           researchers every other month for 1 year. They will be asked about their smoking habits.

        -  At the second study visit, current smokers and some nonsmokers will have another MRI
           scan and the same tests as before.

        -  Current smokers will receive a final phone call 1 year after the second study visit.
           They will be asked to give information about their smoking habits.
    

Detailed description: 
      Objective

      The health risk associated with tobacco use is high, and is even higher in people with severe
      mental illness. The underlying brain circuitry for smoking-mental illness comorbidity is
      unknown. Identifying brain comorbidity circuitry is important for new therapeutic
      development. This study will examine whether a specific brain circuitry can explain the high
      rate of smoking in patients with schizophrenia. Identifying the key brain circuits associated
      with smoking, especially smoking in a high risk population, will provide concrete biomarkers
      for new therapeutic development, and ultimately reducing the smoking related health burden.

      Study Population

      Schizophrenic patients and their family members, non-schizophrenia controls and their family
      members, including smokers and nonsmokers in each of the four groups will be included in this
      study.

      Design

        1. A cross-sectional study for all subjects at baseline. They will receive clinical and
           diagnostic interviews, functional, symptom, and cognitive testing, and MRI. They will
           also have blood drawn, to identify brain circuits and covariates associated with the
           severe smoking problem in schizophrenia.

        2. A prospective longitudinal study design where smokers will be encouraged to quit smoking
           and smoking cessation support is provided if needed, followed by retesting of imaging
           and some clinical assessments, to identify brain circuits associated smoking cessation
           or the difficulty of quitting in schizophrenia and non-schizophrenia smokers.

      Outcome Measures

      Combining event-related and resting fMRI techniques, we propose to test the hypothesis that
      an abnormal dorsal anterior cingulate cortex (dACC) and ventral striatum (VS) circuit
      underlies the high prevalence of comorbid smoking in schizophrenia. We also propose to test
      specific clinical implications of this circuit including a within-subject event-related fMRI
      study to test the mechanistic implication of the rsFC signals, a prospective follow-up to
      test the circuit s predictive validity on smoking behavior change, and genetic studies to
      describe the path from genes to brain circuits to smoking behaviors.
    

Time perspective: Other
Keywords: Smoking Cessation; Schizophrenic Smokers; fMRI; Neural Circuits