Nurnberger, John I. Jr.McInnis, MelvinReich, WendyKastelic, ElizabethWilcox, Holly C.Glowinski, GlowinskiMitchell, PhilipFisher, CarrieErpe, MarianoGershon, Elliot S.Berrettini, WadeLaite, GinaSchweitzer, RobertRhoadarmer, KellyColeman, Vegas V.Cai, XueyaAzzouz, FaouziLiu, HaiKamali, MasoudBrucksch, ChristineMonahan, Patrick O.2015-11-062015-11-062011-10Nurnberger, J. I., McInnis, M., Reich, W., Kastelic, E., Wilcox, H. C., Glowinski, A., … Monahan, P. O. (2011). A High-Risk Study of Bipolar Disorder: Childhood Clinical Phenotypes as Precursors of Major Mood Disorders. Archives of General Psychiatry, 68(10), 1012–1020. http://doi.org/10.1001/archgenpsychiatry.2011.126https://hdl.handle.net/1805/7367CONTEXT: The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy. OBJECTIVE: To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects. DESIGN: A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures. SETTING: Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009. PARTICIPANTS: Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91). MAIN OUTCOME MEASURE: Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression). RESULTS: At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders. CONCLUSIONS: Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.AdolescentBipolar Disorder -- EtiologyBipolar Disorder -- PsychologyCase-Control StudiesKaplan-Meier EstimatePsychotic Disorders -- EtiologyArticle