From The Quarterly, Summer 2011

Many studies point to bipolar disorder as having a very strong genetic base. As with most mental illnesses, it is suspected that a large number of genes are involved. Bipolar disorder is a very heterogeneous illness, with different subtypes and symptoms. At present, only about half of patients with bipolar disorder are helped by the treatments available. Researchers are looking for implicated genes in the hope that their findings will open the way to more effective, individualized treatments.

A number of developmental disorders share symptoms with bipolar disorder. One approach being taken by Dr. Kerner and others is to compare the genomes of bipolar disorder patients with the genomes of patients with those other disorders, which, though mostly rare, are better defined genetically.



One such disorder is Prader-Willi syndrome, whose patients share the  symptoms of psychosis with bipolar disorder patients. The neurocardial fasciocutaneous syndromes, a group of disorders that includes neurofibromatosis, share the  symptoms of anxiety and depression. In Coffin-Lowry syndrome, there are disturbances in a cellular pathway comparable to a pathway in bipolar disorder. An enzyme in this pathway has been identified as a target for lithium, valproate and lamotrigine, the medications most widely used to treat bipolar disorder.



Also under study is velo-cardio-facial syndrome. About 30 percent of patients with this disorder experience psychosis and/or bipolar disorder. An interesting aspect of velo-cardio-facial syndrome is that these patients often have malfunctioning thyroid metabolism, a well-known cause for mood disorders in general and bipolar disorder in particular. Abnormalities in the protein thyroglobulin cause Grave’s disease, autoimmune thyroiditis as well as psychosis and depression.



Gene hunters now have the ability to perform genome-wide association studies (GWAS) in which they can scan entire genomes at one time. Dr. Kerner did a GWAS search on a data base of 1,000 patients.  Among the genes she found ubiquitous was the thyroglobulin gene, as suspected, and two other genes of unknown function, which the lab is now working to characterize.  Thyroglobulin is also a target for lithium, and further study may show that patients who have mutations in this gene are ones who do not respond to lithium.  This finding is an early step toward what is hoped will open the path to better screening tools that will make personalized medicine more of a reality.