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320 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENTa history of ADHD (Sachs, Baldassano, Truman, & Guille, 2000), supporting theconcept of ADHD as one initial presentation of a familial early-onset BD.Another symptom complex commonly predating mania is depression. Prospectivestudies have found high rates (20–30%) of switching to mania in children whoinitially presented with prepubertal major depressive disorder (Geller, Fox, & Clark,1994; Geller, Zimerman, Williams, Bolhofner, & Craney, 2001). The rate of conversionto BD in depressed children who are bipolar offspring would seem to be evengreater, but no studies have yet specifically examined this cohort longitudinally.Given the above epidemiological and phenomenological data, a specific subgroupat highest risk for developing BD can be identified. Clearly, there exists ahigh familial vulnerability in offspring with first-degree relatives with BD. However,in addition to this familial vulnerability, the above-cited literature suggeststhat offspring who also have a depressive disorder or ADHD are at even higherrisk of developing BD. Moreover, it can be hypothesized that those offspring withboth ADHD and significant mood symptoms would be at the highest risk of developingBD and may be experiencing a prodromal form of the illness (Carlson& Weintraub, 1993; K. Chang et al., 2003; Wozniak et al., 1995). Data from retrospectivestudies of adults (Egeland, Hostetter, Pauls, & Sussex, 2000; Lish et al.,1994; Perlis et al., 2004) and children with BD (Fergus et al., 2003) support thatthese children are at extremely high risk for eventual BD development.The few longitudinal studies published also have been supportive of this hypothesis(Carlson & Weintraub, 1993; Egeland et al., 2003; Hodgins, Faucher,Zarax, & Ellenbogen, 2002). Carlson and Weintraub (1993) found that attentionaland behavioral problems in childhood were specifically associated with the developmentof mood disorders in young adulthood for bipolar offspring and notoffspring of parents with other psychiatric illness or offspring of healthy controls.Similarly, in another prospective longitudinal study of offspring of affectively illmothers, having a mother with either BD or major depressive disorder as well asbehavior problems in childhood greatly increased the risk of BD in offspring comparedto control families (Hodgins et al., 2002). All but one of the offspring whodeveloped BD by age 27 had a history of childhood disruptive behavior disorder.Finally, in a 7-year follow-up of Amish children, children of parents with BDshowed significantly more mood, attentional, and behavioral problems, and thosechildren were felt to be at significantly higher risk for BD than children of Amishparents without psychiatric illness (Egeland et al., 2003). These studies supportthat behavioral disorders and nonbipolar mood disorders in bipolar offspring areoften a prodromal exhibition of BD. Additional prospective studies of childrenidentified with these putative prodromal presentations are necessary to documentillness progression and actual rates of conversion to fully developed BD.A limitation of using these symptom complexes to identify children at high riskfor BD is the relatively low specificity of this approach. That is, ADHD is one ofthe more common disorders of childhood, with an estimated prevalence in the