CSP #572 - Genetics of Functional Disability in Schizophrenia and Bipolar Illness

We propose to identify the genetic basis of Veterans developing either of two major
psychiatric (or "mental health") diseases: schizophrenia and bipolar disorder. The study
will also examine the genetic basis of disability in everyday functions (such as employment,
independent living, and self care) among the same patients. By "genetic basis," we mean how
a person's genes might be a risk for developing these illnesses or being affected by them.
We will compare information gathered from Veterans with these illnesses to "psychiatrically
healthy" Veterans. Participants will be recruited from multiple Veterans Health
Administration medical centers; the analysis of blood samples will be done in designated and
approved laboratories.

Both schizophrenia and bipolar disorder are chronic psychiatric diseases associated with
considerable lifelong disability; in particular, these illnesses are common in Veterans
served by the Veterans Health Administration. Both of these conditions are also known to be
caused in part by genes or so-called heredity; studies of the entire set of human genes
(referred to as the genome) can be a tool to identify specific reasons why certain people
develop certain conditions. In addition, patients with schizophrenia or bipolar disorder
often have difficulty functioning in the real-world-including problems in attention and
memory, or the ability to perform tasks of everyday living or have normal emotional
experiences-and these "functional impairments" may also be inherited genetically. The
current study is designed to help identify who is at higher risk for these diseases and
related problems, so that better methods to diagnose and treat the conditions can be
developed in the future.

Among other aspects of schizophrenia and bipolar disorder, suicide stands out as a very
important issue to Veterans, their families, and the Veterans Health Administration. Suicide
attempts and completed suicides are more common in Veterans with schizophrenia and bipolar
illness (compared to Veterans without these illnesses), and this tendency may be inherited
as well. Part of this study will involve determining whether specific genes might be
associated with suicidal behavior. Similarly, the study will look at the genetic basis of
side effects related to taking medications for these diseases.

For this research, participants will be recruited from VA sites that have extensive
experience in conducting projects involving psychiatric disorders. We will collect
information about the genes of these Veterans from a blood sample, and we will ask questions
about health and related factors. We will also establish a repository which allows for
future genomic studies related to SZ, BP, and related disorders or sequelae. The total study
duration is indefinite in the setting of creating a SZ and BP repository, although the
required time period for addressing the primary aims is 3.5 years. Data for a comparison
("reference") group of Veterans with medical, but not psychiatric, illnesses, will be
obtained from a research initiative entitled the "VA Million Veteran Program" (VA-MVP).

Ultimately, this study attempts to advance the state-of-the-art regarding our understanding
and treatment for two common mental health disorders affecting Veterans and will also serve
as part of a major initiative to support "personalized" healthcare. It represents a major
effort to link specific genes to illnesses, and eventually to treatments intended to relieve
suffering.

Inclusion Criteria:

Case participants:

- All participants must be 18 years of age or older

- SZ patients must meet lifetime (DSM-IV) criteria for schizophrenia, any subtype

- BP patients must have a confirmed bipolar type I diagnosis, which requires a history
of a mixed or manic episode at some prior point, regardless of subsequent affective
episodes

- all patients must have medical records available in the VA CPRS

- all patients must be competent to provide informed consent for the research

Control participants:

- Enrollment in the VA Million Veteran Program

Exclusion Criteria:

Case participants:

- SZ and BP patients that have participated in a previous GWAS study or are currently
participating in a clinical treatment study

- patients with physical, sensory, or intellectual limitations that preclude their
assessment with performance-based measures

- patients with active illicit drug use that might hamper assessments. Potential
participants who present under the apparent influence of alcohol or drugs will be
rescheduled once and excluded if they are intoxicated at their next appointment;
patients identified via electronic medical record review will be screened for
evidence of active drug abuse and excluded

Control participants:

- a personal history identifiable in the VA EMR of a major psychiatric disorder related
to psychosis or a first degree family member with either schizophrenia or bipolar
disorder

- major neurologic illnesses, or systemic medical illnesses, that could interfere with
central nervous system function

- current treatment with psychotropic medications aimed at psychosis, bipolar disorder,
or major depression

- anyone participating in an ongoing randomized trial of therapy for SZ or BP