The new genetics of bipolar affective disorder: clinical implications

Underrecognition and undertreatment of affective disorders (i.e., major depressive disorder and bipolar affective disorder) constitute a serious public health problem in this country. The recent availability of sufficient mapped restriction fragment length polymorphism (RFLP) probes to cover the human genome and of improved methods of genetic linkage analysis make the definition of the genetic basis of bipolar affective disorders (and recurrent depressions) feasible within the foreseeable future. However, the degree of genetic heterogeneity involved might make the use of tightly linked RFLPs for diagnostic testing, as has been done for Huntington's disease or cystic fibrosis, impractical. Assuming multiple disease loci, then widely applicable and useful "molecular" diagnostic tests will await the cloning of the disease genes or identification of pathogenic gene products. In addition, the combination of genetic heterogeneity and a substantial degree of assortative mating (i.e., people with affective disorders marrying each other) in families with these disorders could make the search for linked loci a "bottleneck" in the path toward developing such diagnostic tests. Recently, three disease loci have been tentatively identified on chromosome 6, 11, and X.