Bipolar Disorders: Review of Molecular Genetic Linkage Studies

This chapter reviews evidence of the heritability of bipolar (BP) and recurrent unipolar (RUP) disorders. This evidence has accumulated through family, twin, adoption, linkage, and candidate gene studies. Both the twin and family studies suggest that unipolar and bipolar disorders share some fraction of genetic susceptibility. Data from the twin and family studies can be used for genetic counseling, and this will be discussed briefly from a clinical perspective. Efforts to find susceptibility genes through linkage studies have yielded several confirmed regions of the genome where such genes will be found. These linkage studies will be discussed and summarized frommethodologic perspectives. Candidate gene approaches to BP and RUP disorders will be reviewed, with some suggestions for improving methods. A few of the most promising candidate genes will be noted. Mechanisms on nonmendelian inheritance may be involved in the complex genetics of BP and RUP disorders. Imprinting, triplet repeat expansion, and mitochondrial inheritance are reviewed briefly as examples of nonmendelian mechanisms possibly involved in these disorders. Finally, the implications of the Human Genome Project for future progress will be discussed.