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

278 K. Merikangas and K. Yuchildhood have been quite controversial, and several prospective studies are nowunder way to define the early manifestations of bipolar illness (National Instituteof Mental Health Research Roundtable on Prepubertal Bipolar Disorder, 2001).Genetic epidemiology of mood disorders in adultsThe role of genetic factors in the etiology of bipolar disorder has been suspected formore than a century. Numerous reviews have demonstrated conclusively thatgenetic factors are involved in the susceptibility to mood disorders, particularlybipolar disorder (Tsuang and Faraone, 1990; Merikangas and Swendsen, 1997;Moldin, 1997 ; Reus and Freimer, 1997; Sullivan et al., 2000).Several study designs have been employed to assess the role of genetic factors indisease etiology, including:(1) family studies, which assess the degree of aggregation of a trait among relativesof affected probands compared to expected rates from the general population(2) twin studies, which compare concordance rates for monozygotic twins, whohave identical genotypes, with those among dizygotic twins, who share anaverage of half of their genes(3) adoption studies, which compare the degree of similarity between an adopteeand his or her biological parents, from whom he or she was separated, andbetween the adoptee and the adoptive parents(4) association and linkage studies of genetic markers, which examine the relationshipsbetween a known genetic trait and disease status either acrossfamilies or within pedigrees.Family studiesAlthough family studies cannot yield direct evidence for the involvement of genesin the causation of a disease, they are a rich source of evidence for examining thecorrespondence between the observed patterns of expression of a disease and thepatterns predicted by specific modes of transmission. A second application offamily studies, particularly with respect to clinically defined syndromes such asmood disorders, is the investigation of the validity of diagnostic categories andsubtypes thereof through inspection of the degree to which particular symptomsor symptom constellations breed true in families. Whereas the homogeneity ofexpression of disorders is the goal of the latter studies, information on heterogeneityof expression within families may also be employed to identify variableexpressivity of transmitted disorders.