Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

286 K. Merikangas and K. Yulatter; McGuffin and Katz, 1989; Kendler et al., 1992). Differences in the results ofthe two studies could be attributable to difference in sampling (i.e., hospitalizedpatients in the former study and inclusion of only females from the generalpopulation in the latter), or to other methodologic differences.In addition, Tsuang and Faraone (1990) estimated that the heritability ofbipolar depression is 0.59, and a recent meta-analysis of community-based twinstudies of MDD yielded a substantially lower heritability estimate of 0.37 (95%confidence interval ¼ 0.28–0.42; Sullivan et al., 2000). This latter estimate alsoindicates that nearly two-thirds of the liability to MDD cannot be attributed togenes. The concordance rates were somewhat lower for males than for females: therange for males was 0.23–0.41 for monozygotic and 0.14–0.34 for dizygotic and therange for females was 0.47–0.67 for monozygotic and 0.32–0.43 for dizygotic pairs.Early studies of the specificity of transmission of polarity in twin studies werereviewed by Zerbin-Rudin (1969). The largest twin study which systematicallyinvestigated differences in concordance among bipolar and MDD twins waspresented by Bertelsen and colleagues in 1977. Studies which examined the concordancerates among twins by polarity support a strong degree of specificity oftransmission of the two subtypes of mood disorders, with little cross-transmissionbetween bipolar index twins with MDD co-twins, and the converse. The averagerelative risk for cross-transmission for probands with either MDD or bipolardisorder was 1.5. In contrast, bipolar disorder was found to exhibit a strong degreeof specificity, with an eightfold greater risk of bipolar disorder among the co-twinsof bipolar monozygotic probands compared to their dizygotic counterparts.The major conclusion that can be drawn from the current evidence from twinstudies is that mood disorders are strongly heritable, with bipolar disorder exhibitinga much greater degree of involvement of genetic factors in its etiology thanMDD. Moreover, there is little evidence for the cross-transmission of the twosubtypes of mood disorder. Faraone et al.(1987) calculated the aggregate variancecomponents from the twin studies of MDD then available and found a significantdegree of heritability (i.e., 0.51), a significant contribution of the common environmentof the twins (variance 0.42), and nearly no effect of the unique environmentin the development of mood disorders. Twin studies of milder mooddisorders are difficult to interpret because of differences in diagnostic definitionsand inconsistent application of the criterion of hospitalization for affected status(Stenstedt, 1966; Shapiro, 1970; McGuffin and Katz, 1989).Adoption studies of the mood disordersAdoption studies are the most powerful design to test the relative contributions ofgenetic and environmental factors to the etiology of the mood disorders. There are