BIPOLAR DISORDER

Discovery of a gene for bipolar disorder on chromosome 22

The UCSD Laboratory of Psychiatric Genomics under Dr. John Kelsoe has recently identified a gene on chromosome 22 which we believe plays a role in the susceptibility to both bipolar disorder and schizophrenia. Over the last several years, we have scanned the entire genome in a set of families with bipolar disorder attempting to identify a chromosomal region that was consistently associated with the illness. This approach termed linkage analysis, led to very strong evidence for the presence of a gene on chromosome 22. The surprising aspect of this analysis was that this region had already been implicated in many studies of schizophrenia. This is consistent with other data arguing that many genes may contribute to the susceptibility for both of these disorders, and that they may be more alike genetically than had been previously suspected.

Subsequently, we used a separate approach to study an animal model of mania and psychosis using amphetamine. We examined the role of 8,000 genes in the response to amphetamine and found that the gene with the biggest response to amphetamine mapped in man to that exact region on chromosome 22 that we identified in our clinical family studies. Since then we have examined this gene in detail and found what we believe are several abnormalities that prevent it from working properly in a portion of people with bipolar disorder.

This genes normal role is to regulate the response and level of sensitivity to several neurotransmitters including dopamine. It has long been argued that a supersensitivity to dopamine may play a role in these illnesses. We believe we have identified one of probably several mechanisms at the molecular level which cause this. It is our hope that this will aid in the discovery of new and more effective medications and in better diagnostic tests.