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

13Challenges in the genetics of bipolar disorderKathleen Merikangas and Kelly YuNational Institute of Mental Health, National Institutes of Health, Bethesda, MD, USAEpidemiology of mood disordersMajor depressive disorder (MDD) is the leading cause of disability among those age 5and over, and the second leading source of disease burden, surpassing cardiovasculardiseases, dementia, lung cancer, and diabetes (Murray and Lopez, 1996). The dramaticimpact of mood disorders on distress to the affected individual and his or her family,lifetime disability, and suicide highlights the importance of etiologic research toinform treatment and prevention.Community-based rates of mood disorder are essential to deriving estimates ofpopulation familial recurrence risk (l) (Risch,1990). Population prevalence estimatesof mood disorders are available from two community surveys of the USA: theEpidemiologic Catchment Area (ECA) study of five sites in the USA (Robins andRegier, 1991), and the National Comorbidity Survey (NCS) of a probability sampleof the USA conducted 10 years later (Kessler et al., 1994). Estimates of base rates ofbipolar disorder (or manic episodes) were very low in both studies, averaging 0.8% inECA and 1.6% in NCS. In contrast, there is a very high lifetime prevalence of MDDin the US population (females, 12% ECA; 21.3% NCS, and males, 5% ECA, 12.7%NCS). Similar base rates of mood disorders have been obtained in internationalstudies as well (Weissman et al., 1996). With respect to demographic factors, thedifferences between the bipolar and major depression subtypes of mood disordersinclude the sex ratio that favors women for MDD but is nearly equal for men andwomen for bipolar disorder, and the age of onset that occurs nearly a decade earlier inMDD than in bipolar disorder (Weissman et al., 1991).Manic episodes, bipolar disorder, and hypomania are generally rare in childrenand adolescents. In the few studies reporting rates of these disorders, point,12-month, and lifetime estimates rangedfrom0%to2.0%(Kashaniet al., 1987;Costello et al., 1996; Lewinsohn et al., 1998; Pine et al., 1998). The wide variationin base rates has been attributed to methodologic differences rather than truedifferences in prevalence. Likewise, the diagnostic criteria for bipolar disorder in# Cambridge University Press, 2005.