Bipolar disorder with rapid cycling is defined as four or more episodes of illness within a 12-month period. This form of the illness tends to be more resistant to treatment than non-rapid-cycling bipolar disorder.

The particular combinations and severity of symptoms vary among people with bipolar disorder. Some people experience very severe manic episodes, during which they may feel "out of control," have major impairment in functioning, and suffer psychotic symptoms. Other people have milder hypomanic episodes, characterized by low-level, non-psychotic symptoms of mania such as increased energy, euphoria, irritability, and intrusiveness, that may cause little impairment in functioning but are noticeable to others. Some people suffer severe, incapacitating depressions, with or without psychosis, that prevent them from working, going to school, or interacting with family or friends. Others experience more moderate depressive episodes, which may feel just as painful but impair functioning to a lesser degree. Inpatient hospitalization is often necessary to treat severe episodes of mania and depression.

Many patients with bipolar disorder are initially misdiagnosed. This occurs most often either when a person with bipolar II disorder, whose hypomania is not recognized, is diagnosed with unipolar depression, or when a patient with severe psychotic mania is misjudged to have schizophrenia. However, since bipolar disorder, like other mental illnesses, cannot yet be identified physiologically (for example, by a blood test or a brain scan), diagnosis must be made on the basis of symptoms, course of illness, and, when available, family history.

Data from family, twin, and adoption studies unequivocally demonstrate the involvement of genetic factors in the transmission of bipolar disorder. Research to date leads to the conclusion that in most families the etiology of bipolar disorder is complex, with vulnerability being produced by the interaction of multiple genes and nongenetic factors. Scientists expect that identification of genes conferring vulnerability to bipolar disorder, and the brain proteins they code for, will make it possible to develop better diagnostic procedures, treatments, and preventive interventions targeted at the underlying illness process.

The NIMH Bipolar Disorder Genetics Initiative, launched in 1989, continues to gather genetic material and state-of-the-art diagnostic and clinical data from families with two or more members affected by bipolar disorder. The primary goal of this initiative is to establish a national resource that makes DNA and clinical information widely available to qualified investigators in the scientific community. The genetic and clinical information is distributed in a way that keeps the research volunteers anonymous. Ten major research groups worldwide are currently studying DNA and clinical data from over 650 individuals with bipolar disorder and related conditions in an effort to find genes that confer vulnerability to bipolar disorder. Further information on the Initiative is available at http://www.medhelp.org/nihlib/GF-230.html.

Successful genetic studies of complex disorders like bipolar disorder will require very large samples drawn from diverse populations, and/or samples drawn from genetically isolated populations. In order to facilitate such research, NIMH recently funded three major collaborative projects to collect data that will significantly augment the information already available in the NIMH Bipolar Genetics Initiative. In one study, scientists at nine research institutions across the United States will gather clinical and genetic data from at least 500 families in which two or more siblings suffer from bipolar disorder. In another, American and Israeli researchers will use shared methods of data collection, diagnosis, and clinical assessment to study 300 additional families. A third project will study over 300 families collected from the population of the Azores, a nine-island archipelago off the coast of Portugal. NIMH also recently issued a Program Announcement (http://grants.nih.gov/grants/guide/pa-files/PA-99-120.html) to encourage collaborations among genetic research groups worldwide, by which multiple samples of bipolar disorder pedigrees can be assembled into one large data set for combined analysis. New genetic analytic methods and technologies like gene chips offer great potential for identifying specific gene sites responsible for vulnerability to bipolar disorder in such large samples of families.