title: A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, 46202-4887, USA. jnurnber@iupui.edu
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.forename: Wendy
authors.initials: W
authors.lastname: Reich
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kastelic
authors.forename: Holly C
authors.initials: HC
authors.lastname: Wilcox
authors.forename: Anne
authors.initials: A
authors.lastname: Glowinski
authors.forename: Philip
authors.initials: P
authors.lastname: Mitchell
authors.forename: Carrie
authors.initials: C
authors.lastname: Fisher
authors.forename: Mariano
authors.initials: M
authors.lastname: Erpe
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Gina
authors.initials: G
authors.lastname: Laite
authors.forename: Robert
authors.initials: R
authors.lastname: Schweitzer
authors.forename: Kelly
authors.initials: K
authors.lastname: Rhoadarmer
authors.forename: Vegas V
authors.initials: VV
authors.lastname: Coleman
authors.forename: Xueya
authors.initials: X
authors.lastname: Cai
authors.forename: Faouzi
authors.initials: F
authors.lastname: Azzouz
authors.forename: Hai
authors.initials: H
authors.lastname: Liu
authors.forename: Masoud
authors.initials: M
authors.lastname: Kamali
authors.forename: Christine
authors.initials: C
authors.lastname: Brucksch
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Monahan
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000209:etiology* / Q000523:psychology; D016022:Case-Control Studies; D002648:Child; D003865:Major Depressive Disorder / Q000209:etiology / Q000523:psychology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D019964:Mood Disorders / Q000209:etiology* / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000209:etiology / Q000523:psychology; D012306:Risk; D012307:Risk Factors