The Partners Genetics Collaborative Study of Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Observational

Summary: 
      We will collect DNA from 500 rigorously diagnosed patients with schizophrenia to allow us in
      the future to examine phenotypic subtypes in relation to genetic variants. Phenotypes will
      include subgroups based on clinical symptoms, medication response, or other biological
      markers including neuroimaging or pharmacologic challenges.
    

Detailed description: 
      Specific Aims:

      We will collect DNA from 500 rigorously diagnosed patients with schizophrenia to allow us in
      the future to examine phenotypic subtypes in relation to genetic variants. Phenotypes will
      include subgroups based on clinical symptoms, medication response, or other biological
      markers including neuroimaging or pharmacologic challenges.

      Subjects:

      DNA samples and clinical characterization will be obtained from 500 schizophrenia patients
      treated at the Freedom Trail Clinic of the Erich Lindemann Mental Health Association and the
      MGH First Episode Psychosis Program.

      The diagnostic interview will be conducted by a research psychiatrist and will typically take
      between 1-3 hours. The following clinical data will be obtained for all subjects:

      Demographics (age, gender, ethnicity) Weight, height Current medications and doses Age of
      onset (prodrome and psychosis) Incidence of psychotic disorders in first-degree family
      members (without identifiers) Diagnosis with subtype History of hallucinations, delusions,
      negative symptoms, disorganization and mood disorder History of response (full, partial, or
      no response) of symptoms (hallucinations, delusions, disorganization and negative symptoms)
      to conventional antipsychotics, atypicals or clozapine Number of hospitalizations Smoking
      behaviors (using the Fagerstrom)

      The additional clinical assessment will take approximately 2-3 hours and will include the
      following clinical rating scales and cognitive tests:

      Symptom Rating Scales:

      Positive and Negative Symptom Scale (PANSS) Scale for Assessment of Negative Symptoms (SANS)
      Abnormal Involuntary Movements Scale (AIMS) (examination) Clinical Global
      Impressions-Severity of Illness Scale (CGI) (observational) Beck Depression Inventory
      (BDI-II) Simpson-Angus Scale (SAS)

      Cognitive Battery:

      Wechsler Adult Intelligence Scale (selected subtests) (WAIS-III) North American Adult Reading
      Test (NAART) Stroop Test Wisconsin Card Sorting Test (WCST) California Verbal Learning Test
      (CVLT) Verbal Fluency (FAS) Finger Tapping CPT-IP

      Collection of Blood Samples:

      Four tubes of blood will be drawn from an antecubital vein from each participant using an
      EDTA and non-EDTA vacutainers. Tubes will be labeled with the study, date, and an encrypted
      identification of the subject. Samples will be used for DNA extraction and measurement of
      serum and RBC folate and homocysteine.

      Genetic Analysis:

      Genes will be studied that have been identified in linkage studies of patients with
      schizophrenia that have compelling biology relevant to potential mechanisms of etiology or
      drug response. Approximately 20 candidate genes have been identified with varying levels of
      evidence-this number is rapidly expanding. We will review the potential list of candidate
      genes when we have completed collecting the sample and will identify the most promising
      genotypic targets for analysis. If approved by the IRB, comparisons with other populations
      (such as depressed patients or nonpsychiatric controls) may be performed in collaboration
      with other investigators.

      Risks:

      While the clinical assessment may be stressful, the questions contained in the diagnostic
      instruments do not differ from those asked in routine clinical evaluations. Phlebotomy may
      produce discomfort, bruising, and rarely, infection. In theory, release of genetic
      information to patients could be upsetting and release to other parties could represent a
      serious breach of privacy. Extensive precautions will be taken to prevent such an occurrence.

      All DNA analyses will be performed on anonymous samples.

      Subject Remuneration:

      Subjects who agree to phlebotomy and complete the psychiatric evaluation will be remunerated
      $25 for their time. Subjects who complete the additional cognitive battery and clinical
      rating scales will be remunerated a total of $50 for their time.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adults with Schizophrenia
      
Biospecimen description: 
      DNA is extracted and stored for future anaysis of genes that may be associated with
      schizophrenia
    
Keywords: Schizophrenia; DNA