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

289 Challenges in the genetics of bipolar disordermood disorders in youth (Warner et al., 1995; Goldsmith et al., 1997). Indeed, thefamily environment of depressed adults is consistently characterized by family andparental discord, divorce, inattention, rejection, and abuse (Angold, 1988;Downey and Coyne, 1990; Rutter, 1989). Parker (1979) found that a parentaldiscipline pattern of affectionless control was strongly associated with depressivedisorders in adolescents; studies of bipolar depressives reveal normal parentallevels on these dimensions (Parker, 1979). Community studies have documentedassociations between family dysfunction and depression in children and adolescents(Kandel and Davies, 1982; Garrison et al., 1985; Bird et al., 1988). Theseassociations appear to be a reciprocal relationship between parental depressionand child maladjustment (Downey and Coyne, 1990).AgeThere is great variability in the estimates of the initial age of onset of depression.Based on retrospective recall of the onset of depression among adults, the onset ofdepression has been previously estimated to occur in the late 20s and early 30s.However, the results of recent prospective studies reveal that depression oftenoccurs in childhood. Prior to the recent generation of studies of children andadolescents, estimates of the age of onset of depression were derived from retrospectivestudies of adults with depression (Angst, 1988) and suggested mid to lateadolescence as the most common age of onset of first episode of MDD (Burkeet al., 1990; Hammen and Rudolph, 1996; Lewinsohn et al., 1998), although theNCS suggests an average age of onset during early adulthood (24 years for men and23.5 years for women; Kessler et al., 1993).Genetic marker studies of mood disordersAssociation studies of mood disordersAssociation studies investigate the relationship between disease status and aparticular marker or allele across families and individuals. Most associationstudies employ the traditional case-control design in which the prevalence of aputative disease marker is compared among persons with a disorder to personswithout the disorder. The most common methodologic error in associationstudies is the lack of equivalence between the cases and controls on factorswhich may confound the association between the purported marker and disease.After exclusion of spurious associations due to methodologic factors or populationstratification, associations between a disease and a marker could be attributedto either linkage disequilibrium between genes for the disease and for the marker,or the effect of a single gene that encodes both the marker and the disease.