Genetic research on mood disorders can be expected to make substantial contributions to our understanding of treatment mechanisms and, ultimately, to lead to more effective treatment options and disease management.
Although there is substantial evidence that bipolar disorder has a genetic etiology, the mode of inheritance is unknown. Most researchers agree that bipolar disorder is a heterogeneous condition with distinct genetic mechanisms. As a result, molecular genetic approaches have not yet been successful.
The first step towards identifying genes is developing a clear definition of the phenotype “bipolar disorder.” Definitions temporarily change and the extent of the phenotype spectrum in bipolar disorder is uncertain. Therefore, it may be advantageous to use other, intermediate phenotypes in genetic studies.
The IGSLI developed the concept of homogenizing the sample of bipolar patients by limiting the sample to the phenotype of excellent lithium response. The response to lithium can be regarded as a factor independent of the underlying illness, and can be used for characterizing an illness subtype.
In 1992, IGSLI started collecting blood samples from bipolar patients in the Canadian and European centres who had shown an excellent response to long-term lithium treatment. Extensive analysis revealed a positive association with the gene for phospholipase C gamma l (Turecki et al. 1998). Researchers also tested additional candidate genes for enzymes and receptors considered relevant to the etiology of bipolar disorder, but the findings were negative (Turecki et al. 1999, Alda et al. 2000, Duffy et al. 2000).