Bipolar biobank helps identify at-risk patients for early intervention

Although the genetic contribution to bipolar disorder has been unequivocally demonstrated, few specific genetic risk factors have been confirmed. The factors identified explain only a small proportion of the genetic contribution to bipolar disorder. The Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder provides a resource for the bipolar research community working to confirm those risk factors and discover additional contributors to bipolar disorder susceptibility and response to treatment.

Primary research focuses on the identification of risk factors for development of bipolar disorder, including specific genetic variations. Researchers will also study factors that contribute to differences in response to various treatments. The identification of genetic risk factors associated with disease onset may lead to early treatment in at-risk patients.

Early intervention is particularly important for people with bipolar disorder, for whom the initiation of treatment is often delayed by more than a decade when the disorder is misdiagnosed. People with the earliest onset of recurrent episodes of mania and depression generally experience the longest delays to first treatment and poor outcomes.

The biobank project is a multisite endeavor. Mayo Clinic in Rochester, Minnesota, serves as the primary location, but researchers from the University of Minnesota, Lindner Center of Hope in Cincinnati, Ohio, Mayo Clinic's Arizona and Florida campuses, and Mayo Health System sites are contributing to the effort and will continue to collaborate following completion of infrastructure development in 2012. The large-scale biobank will collect biological samples and clinical data from 2,000 individuals between the ages of 18 and 65 years. Nearly 500 adults have been enrolled already.

"Studies of complex genetic traits require large, well-characterized sample collections," says Joanna M. Biernacka, Ph.D., a biostatistician and coprincipal investigator for the project. Analyses aimed at identifying genomic risk factors for bipolar disorder and specific aspects of the illness such as response to different types of treatment will be undertaken once an adequately sized sample is available.

"This resource has the potential to identify the right treatment for the right patient at the right time," says Mark A. Frye, M.D., a psychiatrist and coprincipal investigator for the project. "Once we understand what factors predict how a person will respond to various treatments, personalized treatment options can be considered for patients with bipolar disorder." Identification of genomic predictors of treatment response may allow greater selectivity of treatment recommendations, as well as help prevent serious adverse events such as antidepressant-induced mania.

Biobank expands to include children

Funding for an individualized medicine biobank for pediatric bipolar disorder was approved in May 2010. Several linked studies are planned. A study of children at risk of bipolar disease will include participants whose parents are included in the adult study. Additional participants will be recruited for the pediatric bipolar biobank study, which focuses on children in whom bipolar disorder has already developed. Researchers will begin recruitment after the study protocol is approved.

The existence of bipolar disorder in children is controversial. "If a child receives several different diagnoses, parents become confused and remain concerned," says Peter S. Jensen, M.D., a psychiatrist and primary investigator for the pediatric bipolar biobank study. The pediatric biobank will track crucial data, such as responses to medication, to allow investigators as well as parents of bipolar children to better understand the risks and benefits of various treatment options. "We are working to understand the biological commonalities in bipolar children. The pediatric bipolar biobank is an important step in that direction," says Dr. Jensen.

Christopher A. Wall, M.D., a psychiatrist and primary investigator for the study of children at bipolar risk, notes that many parents realize that their own signs occurred and were trackable from their youth. "The parents' bipolar disorders may have been misdiagnosed. The children of affected parents have a 10-fold risk of inheriting bipolar disorder. If we identify gene sequences that may indicate pediatric onset, we can begin to provide treatment early and help prevent crises by monitoring signs over time," says Dr. Wall.

Biobanking is becoming an increasingly important research tool at Mayo Clinic. Its biobank will consist of more than 20,000 Mayo Clinic patients and community members. "The success of this research," notes Dr. Frye, "depends on seasoned clinicians, rigorous descriptions, and collaboration with other biobanks."