Psychosis and Affective Research Domains and Intermediate Phenotypes
Condition: Bipolar I Disorder, Unspecified, With Psychotic Features; Bipolar I Disorder, Unspecified, Without Psychotic Features
MeSH terms: Psychotic Disorders; Mental Disorders
Study type: Observational

Summary: 
      The objective of this multi-site research collaboration is to test the manifestation and
      distribution of biological markers for psychosis and affect dimensions across the
      schizophrenia/bipolar (SZ-BD) diagnostic boundary, and to examine heritability and genetic
      associations for these biological markers.
    

Detailed description: 
      The B-SNIP research consortium previously obtained dense phenotypes across the psychosis
      spectrum in an effort to observe features both (i) distinctive to and (ii) shared between
      DSM-type categorical diagnoses. Despite the broad range of extra-clinical phenotypes, we had
      limited success finding clinical SZ-BD diagnosis-specific features; instead, most phenotypes
      were distributed continuously across DSM diagnoses. To describe more biologically homogeneous
      groups, therefore, we combined all psychosis probands and implemented a multi-stage analysis
      procedure, beginning with identification of psychosis biomarkers (variables with the largest
      effect sizes for differentiating psychosis and healthy groups) including cognitive,
      electrophysiological, and oculo-motor measures ('classical' endophenotypes). We then
      estimated the number of subgroups that efficiently optimized variance among the biomarkers
      (n=3) and differentiated the individual psychosis cases into these subgroups. Subsequently,
      the subgroups were tested for biological uniqueness using meaningful external validators
      (structural and functional brain imaging, social functioning, and familial data). Given the
      neurobiological distinctiveness of these subgroups, we called them psychosis Biotypes. DSM
      diagnoses were distributed across all Biotypes. Compared to DSM diagnoses, Biotype membership
      enhanced group separations on biomarkers. These results indicate that groups of psychosis
      cases can be generated with homogeneous phenotypic characteristics independent of DSM
      diagnoses. The proposed study aims to further develop Biotype definitions and demonstrate
      that psychosis Biotypes constructed from a dense biomarker panel (i) are replicable, (ii)
      neurobiologically distinctive, and (iii) have unique genetic characteristics.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population will be comprised of individuals between the ages of 18-60 years old
        who meet DSM-IV criteria for Bipolar I disorder, read/speak/understand the English
        language, and are deemed capable of completing the study procedures by the research
        investigators.
      
Biospecimen description: 
      DNA will be extracted from blood (or buccal swab) and stored at the UT Southwestern Human
      Genetic Center in a departmental freezer at -80 degrees. Part of the blood sample will be
      used to create an immortalized lymphocyte culture (a lymphoblastoid cell line) for future
      genetic analysis, and will be stored in a Cell Bank at the UT Southwestern Human Genetic
      Center. The blood samples will be labeled by a coded identifier (number) and will not be
      personally identifiable. Only specifically designated research staff from Dr. Tamminga's
      group and from the UT Southwestern Human Genetic Center will have an access to stored DNA
      samples. All samples will be de-identified. The genetic data will be in password-protected
      computers in the Investigators' research offices.
    
Keywords: Bipolar disorder; Psychosis; Schizophrenia