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

Bipolar affective disorder is a severe, heritable condition affecting about one percent of the population. The mode of inheritance is poorly understood and probably involves multiple loci of small to moderate effect. Genetic linkage has been reported to a number of chromosomal regions; some findings have been replicated. In 1988 the NIMH began a national archival database to search for susceptibility loci/genes in this condition. Its purpose was to collect a large sample of interviews and cell lines from families suitable for linkage and association studies. Since 1988, the NIMH-IRP has been an active site in this multi-center study. The protocol was originally supervised by Elliot Gershon, MD (1988-July 1998) and Dennis L. Murphy, MD (July 1998 - January 2004). In January 2004, Francis J. McMahon, M.D, took over supervision of the protocol. An expanded Consortium of sites concentrating on families identified through a sib pair was approved in August 1998 by the NIMH Extramural Program (MH 59535) via a competitive application. This Consortium added 450 new families and 2500 cell lines. Cell lines, clinical data, and 2 genome-wide sets of microsatellite genotypes have been made freely available to the scientific community under the auspices of the NIMH Center for Genetic Studies. In 2003, the IRB approved an amendment to expand the ascertainment criteria to include sib-pairs with a diagnosis of bipolar II disorder. Families ascertained in this manner are contributed to a second, large sample being collected in collaboration with The Johns Hopkins University and the University of Chicago, known as the CHIP study. In October 2003, the NIMH Extramural Program approved, via a competitive application, an additional 4 years of support for the Consortium collection, now including 11 extramural sites in addition to the IRP site. In this round, the focus shifted from affected sibling pairs to parent-affected offspring triads, with the goal of accruing a large sample suitable for future association studies. Both the Consortium and CHIP projects have similar study design and essentially identical recruitment, evaluation, and analysis procedures, so both projects are described together in what follows. In 2007, probands from the Consortium sample were selected for genome-wide genotyping under the Genetic Association Information Network (GAIN) initiative; a project aimed at producing genome-wide data for use by the scientific community in the discovery of genes involved in common disorders.

• Mania
• Bipolar, Disorder
• Depression
• Mood Disorder
• Schizoaffective
• Manic Depression

• Berrettini WH, Ferraro TN, Goldin LR, Weeks DE, Detera-Wadleigh S, Nurnberger JI Jr, Gershon ES. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918-21.
• Detera-Wadleigh SD, Badner JA, Goldin LR, Berrettini WH, Sanders AR, Rollins DY, Turner G, Moses T, Haerian H, Muniec D, Nurnberger JI Jr, Gershon ES. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q. Am J Hum Genet. 1996 Jun;58(6):1279-85.
• Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach J. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152-4.

• INCLUSION AND EXCLUSION CRITERIA:

The major goal of this project is to collect a sample of affected sibling pairs and cases with familial bipolar disorder, and to use this sample, along with control samples independently available, to identify vulnerability genes for bipolar disorder.

For the Consortium collection, the DSM-IV diagnosis of BPI is our definition of affected status. It is anticipated that a small number (less than 5%) of subjects ascertained as BPI is judged at the time of best estimate to have another diagnosis (primarily BPII, SA (BP) or organic mood disorder) and they are flagged in the dataset so as not to include them in primary analyses.

For the CHIP collection, we will screen families of treated BP I probands who by family history have at least 2 other siblings with recurrent major mood disorders including BP I, BP II, recurrent major depression, or schizoaffective disorder, bipolar type. This strategy has allowed us to include in our sample the full range of natural clinical variation associated with BPD.

Probands are recruited from a broad range of sources, including clinic populations, inpatient admissions, patient advocacy groups, and the public media. Prospective probands are asked to provide information about themselves and their first-degree relatives, using the screening and checklist questions for mood disorders contained in the FIGS. All probands aged 21 or over who can provide informed consent for interview and phlebotomy are enrolled.