Bipolar and Schizophrenia Consortium for Parsing Intermediate Phenotypes

We propose to recruit 100 case probands with a diagnosis of SZ, 100 case probands with a
diagnosis of BP Disorder I with history of psychosis; BPI-P) and 400 1st degree case
relatives. All 1st degree family members who are willing to participate will provide clinical
information and blood sample, only a proportion will be eligible for endophenotypic studies).
Individuals with psychotic disorder not otherwise specified are also eligible for testing.
Their data will be incorporated with the schizophrenia or bipolar data upon confirmation of
diagnosis. Family members of individuals with psychotic disorder not otherwise specified will
not be tested unless the individual has a later confirmed diagnosis of schizophrenia or
bipolar disorder. Probands will not be tested during the acute phase of the illness as judged
clinically e.g., significant increase in core symptoms from their stable baseline that
requires a change in treatment such increased dose of medication, drug change, or
hospitalization). As part of another existing protocol, we have collected most of the
endophynotypic information in schizophrenia probands and 1st degree relatives other than
brain imaging and few other tests. We will attempt to recruit these subjects to complete the
imaging studies and the data will be used in the current study.

We will recruit 100 healthy comparison subjects from the community in order to describe the
distribution of normal values for our endophenotype procedures in a demographically matched
sample. The SZ and BPI-P probands, and 50 healthy control subjects, will be frequency matched
on age, sex ratio, and head of the household's socio-economic status (SES). Another group of
50 healthy control subjects will be similarly matched to the relative groups recruited.

Participants will undergo a number of clinical, electrophysiological, structural brain
imaging, perceptual, and cognitive assessments. These data will be used to identify
phenotypes likely to be associated with genetic risk for schizophrenia and/or bipolar
disorder, and to determine how these phenotypes aggregate in families. Some of the analyses
will focus on examining associations between candidate genes and these alternative
phenotypes. Thus if we are not able to recruit relatives we may still collect these
phenotypic data in probands and their genetic sample for future genotype/phenotype
association studies. Family members may elect to participate only in the clinical and blood
draw portions of the study. Testing procedures require a 12 -15 hour time commitment and
testing will be completed over 2 or more days. Participants will be asked to give a blood (or
saliva if difficult to obtain blood sample for instance because of fear of blood draws),
which will be stored for future genetic analyses. Data from the previous family study will be
combined with the data collected in this protocol for some of the analyses.

Inclusion Criteria:

- Male and female participants 15 years of age and above.

- Case probands will include individuals who meet DSM-IV criteria for schizophrenia,
schizoaffective, or bipolar disorder with psychosis

Exclusion Criteria:

- Control subjects who meet DSM-IV criteria for any lifetime psychotic illness or BP, or
have a family history of psychotic or BP disorders in their first or second-degree
relatives will be excluded.

- A number of exclusions are necessary because they potentially affect
neurophysiological measures. Exclusions will be applied to all groups to maintain
consistency in recruitment. As a result, the following individuals will be excluded:

- Subjects under 15 years of age will be excluded. Subjects with serious medical,
neuro-ophthalmological or neurological illness (e.g., cancer, seizure disorders,
encephalopathy) will be excluded, with the exception of family member subjects
participating for clinical interview and blood sample only.

- Subjects with current substance abuse (within 6 months), dependence within 2 years or
extensive history of drug dependence will be excluded, with the exception of family
member subjects participating for clinical interview and blood sample only.

- Subjects with mental retardation will be excluded, with the exception of family member
subjects participating for clinical interview and blood sample only.

- Subjects with ferromagnetic objects lodged in body will be excluded, with the
exception of family member subjects participating for clinical interview and blood
sample only.

- Schizophrenic patients who are judged to be incompetent to provide voluntary informed
consent based on the ESC evaluation.

- Any participant who would require an x-ray to rule out the presence of metal in their
body prior to an MRI scan