Bipolar Disorder Phenome Database May Aid Search for Related Genes

October 2, 2007 • Science Update

Early findings from the recently launched Bipolar Disorder Phenome Database were published in the August 2007 issue of the American Journal of Psychiatry. The database contains publicly accessible research information that seeks to describe, in the fullest detail possible, the signs and symptoms of bipolar disorder. Some day, such information may help scientists find the genes responsible for causing bipolar disorder.

The classic definition of bipolar disorder includes extreme, sustained mood swings that range from over-excited, elated moods and irritability—the manic phase of the disorder—to depression. Inheritance studies have suggested that genes play a vital role in increasing risk for the disorder, but identifying the exact genes has been difficult.

In recent years, genetic research has been boosted by the completion of the Human Genome Project in 2003, which identified all of the genes in human DNA. Then in 2006, the International HapMap Project was completed, which identified common points of genetic variation, helping researchers focus their studies on specific areas of the genome that may be linked with a certain illness. Additional technological advances have helped considerably to speed up the process and lower the cost of genetic research.

Given rapid advances in the collection and understanding of genomic information, the next logical step was to catalogue the observable symptoms or characteristics of a disorder and link them to their genetic underpinnings—in other words, to develop a phenome database. Such projects have already begun for autism and epilepsy. The Bipolar Disorder Phenome Database comprises merged datasets collected over 20 years from two large studies, and contains research information on 5,721 people (3,186 of whom have bipolar disorder or a related illness) from 1,177 families.

In early studies using this dataset, researchers working with James Potash, MD, MPH, of Johns Hopkins University, and Francis McMahon, MD, of the NIMH Mood and Anxiety Program, found that most people with bipolar disorder had missed work because of their illness, and most had co-occurring illnesses, especially alcohol and/or substance abuse and panic disorders. Most people had been treated or hospitalized for bipolar disorder. The researchers also identified certain traits that appeared to run in families, including a history of psychiatric hospitalization and the presence of co-occurring obsessive-compulsive disorder (OCD). Some traits were identified as being much more likely to be inherited than others, including the age at first manic episode, as well as the number and frequency of manic episodes. Further study of these traits may be useful in genetic studies.

As the methods and technologies for genetic research continue to improve, tools such as the Bipolar Disorder Phenome Database are key to understanding the link between genes that confer risk for bipolar disorder and the observable signs of illness that they cause.

Collaborating institutions on the Bipolar Disorder Phenome Database include NIMH, Johns Hopkins University, the University of Colorado Health Sciences Center, and the University of Heidelberg (Germany.

Potash JB, Toolan J, Steele J, Miller EB, Pearl J, Zandi PP, Schulze TG, Kassem L, Simpson SG, Lopez V; NIMH Genetics Initiative Bipolar Disorder Consortium, MacKinnon DF, McMahon FJ. The bipolar disorder phenome database: a resource for genetic studies . Am J Psychiatry. 2007 Aug;164(8):1229-37.