Specific genetic linkages to bipolar disorder

Despite an intensive effort, researchers have yet to identify the genes that cause bipolar disorder, yet the practical benefits of such a discovery could reap rich rewards for those suffering from the mental illness.

New research findings presented today at the Sixth International Conference on Bipolar Disorder suggest specific genetic linkages that are associated with the mental illness, bringing researchers much closer to finding the elusive gene or genes. Another study finds an association between an abnormal thyroid condition and bipolar disorder, pointing to the possibility that a simple blood test could help identify those at risk.

To further investigate more specific genetic linkages, Marion Leboyer, M.D., Ph.D., of the University of Paris Faculty of Medicine, studied 87 bipolar sibling pairs from 70 European families who were participants in the European Collaborative Study on Early Onset Bipolar Affective Disorder and identified eight regions of genetic linkages that, while not necessarily the sole or unique ones associated with this disease, zeroed in on what may be the specific genes that predispose individuals to early onset of this debilitating disease.

According to Dr. Leboyer, his studies of families with members who developed the illness as children or adolescents reduces those genetic and clinical variabilities that can complicate efforts to identify susceptibility genes. Finding these genes would help researchers develop more effective treatments or even prevent the disorder from occurring in at-risk individuals.

Other genetic clues come from results of two related studies involving adolescent and young adult offspring of bipolar parents and of twins with bipolar disorder, suggesting a genetic link between bipolar disorder and an abnormal thyroid condition.

Willem Nolen, M.D., Ph.D., of the University of Groningen Medical Centre, Netherlands, found that bipolar patients were twice as likely as healthy subjects to develop autoimmune thyroiditis (AT). Among the offspring of parents with bipolar disorder, who usually have an increased prevalence of bipolar and other mood disorders, there also was an increased prevalence of AT. Surprisingly, this finding did not seem to be related to whether their offspring themselves had been diagnosed with a psychiatric illness.

Among identical twins (who share all their genes) with at least one twin having bipolar disorder, prevalence of AT was increased in the other twin, irrespective of whether the other twin also had bipolar disorder. However among fraternal twins (who share 50 percent of their genes) with at least one fraternal twin having bipolar disorder, prevalence of AT was increased only in the other fraternal twin who also had bipolar disorder, but was not increased in the fraternal twin without the illness.

Dr. Nolen's research highlights the increasing importance of identifying endophenotypes – clinical information unique to certain groups of individuals that may be predictive of risk for disease and course of illness. Although associated genes for bipolar disorder and AT have yet to be identified, AT may be an endophenotype for bipolar disorder. As such, the findings suggest that relatives of patients with bipolar disorder not only inherit the vulnerability for bipolar disorder and other mood disorders, but that some also may share the genetic vulnerability for developing AT.

If proven valid in further studies, the research suggests that members of families in which bipolar disorder occurs could be tested for autoimmune thyroiditis by means of a simple blood analysis, thereby helping to identify those who also may be at risk for developing bipolar disorder.

"Why hasn't a gene for bipolar disorder been identified when clearly the illness affects some families more than others and what is science telling us about who is most vulnerable and how the onset of the illness can be prevented? While a number of genes have been suspected to be associated with bipolar disorder, we thus far have failed to isolate any definitive bipolar gene, but are making sure progress that will ultimately bring answers about how and why this debilitating disease affects so many. By exploring these genetic connections, we inch closer to surer diagnosis and more rational and effective treatments," commented Michael Thase, M.D., professor of psychiatry at the University of Pittsburgh School of Medicine.

Held every two years, the International Conference on Bipolar Disorder is the only venue in the world devoted exclusively to highlighting new research into bipolar disorder. The Sixth Conference is being held June 16 to18 at the David L. Lawrence Convention Center, located in the heart of downtown Pittsburgh, and is being sponsored by the University of Pittsburgh School of Medicine and Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center.