This study looks to identify genes that may affect a person's chances of developing bipolar disorder (BP) and related conditions....

Study Description:

This project uses genetic mapping and whole exome sequencing methods to identify genetic markers and variations that contribute to the risk of bipolar disorder, an often severe, heritable condition affecting about one percent of the population. Individuals diagnosed with bipolar disorder are studied, along with their relatives. Phenotypic information obtained from clinical interviews and family history is correlated with genotypic information obtained from genetic marker and whole exome sequencing methods.

Objectives:

Primary Objective:

Identify genes involved in bipolar disorder and related conditions so that better methods of diagnosis, treatment, and prevention can be developed.

Secondary Objectives:

1. To identify genes that shape the clinical picture or influence response to treatment.
2. To replicate our findings in independent samples. Genome-wide genotyping, whole exome sequencing, demographic, and phenotype data will be requested under the usual dbGaP Data Access procedures and analyzed along with existing phenotypic and genetic data.
3. To analyze the clinical data, including but not limited to the diagnostic categories, in order to identify between-family differences which might identify genetically meaningful subgroups of families.
4. To submit coded phenotypes, genotypes, and DNA from informative families to a national archival database.
5. To establish a catalog of induced pluripotent stem cells suitable for functional genomic studies of neurons and glia in culture.

Endpoints:

Primary Endpoint:

The primary endpoint of this study is the identification of genes involved in risk for developing bipolar disorder.

Secondary Endpoints:

1. Pedigree structure, representing known relationships and reported mental health of first, second, and third-degree relatives
2. Dimensional data on mental health symptoms obtained from the Past History Schedule, Mood Disorders Questionnaire, and Symptom Checklist (SCL-90)
3. Cognitive data based on measures of executive function, working memory, attention, verbal memory, visuospatial reasoning, and affect recognition.
4. Lithium response data collected through the Retrospective Assessment of the Lithium Response (Alda) Scale
5. History of traumatic life events elicited with the Life Events Checklist for DSM-5 (LEC-5)
6. Genotype data obtained from SNP arrays or whole-exome sequencing
7. Skin biopsy or additional blood sample from selected participants
8. Induced pluripotent stem cells obtained from reprogramming of skin or blood cells.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study.
2. Male or female, aged 18 years and over. Children are excluded for the following reasons: age at onset of BD is usually later than age 18, the diagnostic and assessment instruments we use are not validated in children.
3. In good general health as evidenced by medical history or diagnosed with or exhibiting symptoms of bipolar disorder or related conditions not attributable to substance abuse, or neurological disease; OR a 1st or 2nd degree relative of an enrolled participant. Related conditions are defined as those found more often among relatives of people with bipolar disorder or which have been shown to be genetically correlated with bipolar disorder through molecular genetic studies. These include major depression, schizophrenia, panic disorder, and attention deficit hyperactivity disorder.
4. Ability to safely provide a blood or saliva sample.
5. Ability of subject to understand and willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Active alcohol or substance abuse.
2. Subjects who suffer cognitive impairment and are unable to provide an accurate psychiatric history are excluded since much of the diagnostic information relies on selfreport and recall of past events.

community samples and clinical samples