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Original Article
Oct 2011

A High-Risk Study of Bipolar Disorder: Childhood Clinical Phenotypes as Precursors of Major Mood Disorders

Author Affiliations

Author Affiliations: Departments of Psychiatry (Drs Nurnberger, Laite, Schweitzer, Rhoadarmer, and Coleman and Ms Fisher) and Medicine (Drs Liu and Monahan and Messrs Erpe and Azzouz), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis; Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor (Drs McInnis and Kamali and Ms Brucksch); Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri (Drs Reich and Glowinski); Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, Maryland (Drs Kastelic and Wilcox); School of Psychiatry and Black Dog Institute, University of New South Wales, Sydney, Australia (Dr Mitchell); Department of Psychiatry, University of Chicago Pritzker School of Medicine, Chicago, Illinois (Dr Gershon); Department of Psychiatry, University of Pennsylvania Health System, Philadelphia (Dr Berrettini); and University of Iowa Carver College of Medicine, Iowa City (Dr Cai).

Arch Gen Psychiatry. 2011;68(10):1012-1020. doi:10.1001/archgenpsychiatry.2011.126

Context 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.