title: Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar Spectrum Disorders in At-Risk Youths.
abstract: The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths).
  
  
  
  Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders.
  
  
  
  Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion.
  
  
  
  Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Danella M
authors.initials: DM
authors.lastname: Hafeman
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: John
authors.initials: J
authors.lastname: Merranko
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Tina
authors.initials: T
authors.lastname: Goldstein
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Kelly
authors.initials: K
authors.lastname: Monk
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hickey
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Dara
authors.initials: D
authors.lastname: Sakolsky
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Rasim
authors.initials: R
authors.lastname: Diler
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: David
authors.initials: D
authors.lastname: Brent
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: David
authors.initials: D
authors.lastname: Kupfer
authors.affiliation: From the Department of Psychiatry and the Department of Statistics, University of Pittsburgh, Pittsburgh; the Department of Psychiatry, Nationwide Children's Hospital and Ohio State University, Columbus; and the Department of Psychiatry, University of Toronto, Toronto.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology*; D002648:Child; D005163:Factor Analysis, Statistical; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D062706:Prodromal Symptoms; D018570:Risk Assessment