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

288 K. Merikangas and K. YuControlled studies of offspring of parents with bipolar disorder exhibit a widevariation in the frequency of mood disorders among offspring of affected parents(a range of 23–92%; Hammen et al., 1990; Radke-Yarrow et al., 1992), butcollectively suggest a familial component. Rates of mania and bipolar disorderare generally low due to the young age of adolescent offspring in these studies;however, children of bipolar parents show greater specificity of transmission ofmood disorders than do children of parents with unipolar depression (Merikangasand Angst, 1995).Although these studies provide evidence of familial influence in the etiology ofmood disorders, they shed little light on possible mechanisms through which suchfactors may operate to produce affective psychopathology in children. Familialaggregation of depression may result from shared genes, common environmentalfactors, or a combination thereof.Twin studiesThe role of genetic factors underlying the familial aggregation of depression has beeninvestigated by several twin studies of depressive symptoms and disorders amongyouth. Reports by Thapar and McGuffin (1994, 1995, 1997), Murray and Sines(1996), Eley and Plomin (1997), and O’Connor et al.(1998) conclude that there is amodest degree of genetic influence for childhood depressive symptoms, with greaterheritability with age. However, some of these studies suggest that the age-relatedincrease in heritability is limited to males, whereas the influence of the sharedenvironment tends to increase with age in females (Eley and Stevenson, 1999).Genetic factors may also play a role in the recurrence and stability of depression.The twin study of O’Connor et al. (1998) found that the stability of depressivesymptoms over a 3-year period was primarily explained by genetic influence;Silberg et al. (1999) found similar results among girls but not boys. Although astrong genetic component is implicated, O’Connor et al. (1998) warn that it ispremature to accept the conclusion that the identified influence of heritability is,in fact, purely genetic, given that recent reports suggest strong and pervasivegene–environment correlations (e.g., evocation of stressful events based upon agenetic predisposition). Consistent with this, Silberg et al. (1999) found thatindividuals who inherited a genetic predisposition for depression also inheriteda tendency to experience negative life events. Finally, adoption studies of depressionsymptoms in children and adolescent found only negligible genetic influence(van den Oord et al., 1994; Eley et al., 1998).Although evidence suggests that the vulnerability for depression may be inherited,the environmental stressors have also been implicated in the development of