New Genetic Findings in Recurrent Mood Disorders

Abstract

Affective disorders, and in particular, manic depression, have been the subject of many classic genetic studies. Table 1 summarizes concordance rates for manic depression in twin studies of manic-depressive probands (Mendlewicz 1988). Table 1 concordance rates are consistently higher in monozygotic (MZ) than dizygotic pairs, but they do not reach the 100% value in MZ pairs, indicating that nongenetic (environmental) factors may also be operating in this illness and interacting with the genetic predisposition. Such interactions between nature and nurture can be best examined through the use of more sophisticated strategies such as the adoption method and the new linkage analyses. The adoption method has been applied to manic depression with conclusive results demonstrating the necessary presence of important genetic factors in the etiology of the illness (Table 2; Mendlewicz and Rainer 1977). More recent linkage studies with classic genetic markers such as color blindness and G6PD deficiency have provided consistent evidence of the presence of a major single gene located on the distal end of the long arm of the X chromosome in bipolar manic depression (Mendlewicz 1986, 1988) despite the fact that this type of inheritance has not been observed in all families studied (Mendlewicz 1988). In addition, using the DNA recombinant method in molecular genetic studies of manic depression, a close linkage has recently been demonstrated between manic depression and factor IX (hemophilia B) on the distal end of the long arm of chromosome X in a new set of pedigrees (Mendlewicz et al. 1987), as illustrated in Fig. 1.