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

287 Challenges in the genetics of bipolar disordervery few adoption studies of mood disorders, and those that are cited weretypically quite small and conducted more than 20 years ago. The chief impedimentto adoption studies of mood disorders is the lack of valid information on depressionin biologic parents, particularly the biologic father.The aggregate adoption study data on mood disorders reveal a moderateincrease in rates of mood disorders among the biologic compared to adoptiverelatives of adoptees with mood disorders (Tsuang and Faraone, 1990). Withrespect to bipolar disorder, there is little evidence for differential risk amongbiologic compared to adoptive relatives of adoptees with bipolar disorder.However, the small numbers of bipolar adoptees who have been studied (i.e.,fewer than 50) do not provide an adequate test of genetic and environmentalinfluences (Goodwin and Jamison, 1990). The most compelling finding fromadoption studies, however, is the dramatic increase in completed suicide amongbiological relatives of mood-disorder probands (Mendlewicz and Rainer, 1977;Wender et al., 1986).Genetic epidemiology of mood disorders in youthFamily studiesDespite the abundance of well-controlled family and genetic studies that haveemployed sophisticated methodology to investigate the transmission of mooddisorders among adults, there are only a limited number of controlled familystudies that have focused on the manifestation of mood disorders among adolescents(Merikangas and Swendsen, 1997).Controlled family studies of adult relatives of children with depression as well asoffspring of adults with depression provide consistent evidence that MDD has astrong familial component (Weissman, 1987; Neuman et al., 1997; Beardslee et al.,1998; Kovacs and Devlin, 1998). Children of depressed parents are three timesmore likely to have an episode of MDD than children whose parents are notdepressed (Birmaher et al., 1996) and are four times more likely to develop mooddisorders (Lavoie and Hodgins, 1994). By the age of 25, children of affectively illparents have a 60% chance of developing MDD (Beardslee et al., 1993). Risk tochildren is even greater when both parents exhibit mood disorders (Merikangaset al., 1988). Studies of parents of children with MDD reveal a strong associationbetween child and parent MDD (Puig-Antich et al., 1989; Williamson et al., 1995).Although several studies suggest that early age of onset is associated with increasedfamilial aggregation of depression, the results of recent family and twin studies ofyouth conclude that prepubertal depression is less heritable than postpubertaldepression (Harrington et al., 1997; Silberg et al., 1999).