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

285 Challenges in the genetics of bipolar disorderTable 13.2 Twin studies a of mood disordersMonozygoticDizygoticn Concordance (%) n Concordance (%) Relative riskBipolar disorderRosanoff et al. (1935) 23 70 67 16 4.4Kallman (1953) 27 93 55 24 3.9Harvald and Hauge (1965) 15 67 40 5 13.4Allen et al. (1974) 15 33 34 0Bertelsen et al. (1977) 55 51 11 14 3.6Major depression disordersMcGuffin et al. (1991) b 62 53 79 28 1.9Kendler et al. (1992) b , c 590 48 440 42 1.2a Studies with 15 twin pairs.b Diagnostic and Statistical Manual of Mental Disorders, 3rd edn revised (DSM-IIIR) criteria.c Females only.mood disorders appears to be associated with an early age of onset of mooddisorders in probands, the bipolar subtype, and recurrent episodes, but not withthe sex of the affected proband.Twin studies of mood disordersThere have been numerous studies which compare the rates of mood disordersamong monozygotic and dizygotic twins. The majority of the earlier studiesselected probands from inpatient settings or treatment registries. Table 13.2presents the twin studies of probands with bipolar disorder and MDD in whichthere were at least 15 twin pairs. The average concordance for mood disordersamong monozygotic twins was 60% and 12% for dizygotic twins. There is afivefold greater rate of concordance for mood disorders among monozygoticthan dizygotic twins, thereby indicating the importance of the role of geneticfactors in the familial aggregation of bipolar disorder.Twin studies of mood disorders reveal that genetic factors have a far greateretiologic role in bipolar disorder than in MDD. The relative risks comparingmonozygotic and dizygotic twins in two studies were 1.9 (McGuffin and Katz,1989) and 1.2 (Kendler et al., 1992). Nevertheless, the application of quantitativemodels that estimate the relative components of the variance attributable to sharedgenes, common environment, or unique non-shared environment yielded significantdegrees of heritability in both studies (i.e., 0.39 in the former and 0.84 in the