title: Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity.
abstract: BACKGROUND
  The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders.
  
  
  METHODS
  A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998-2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA.
  
  
  RESULTS
  The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives.
  
  
  CONCLUSIONS
  The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.
authors.affiliation: Department of Biostatistics,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: P O
authors.initials: PO
authors.lastname: Monahan
authors.affiliation: Department of Biostatistics,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: T
authors.initials: T
authors.lastname: Stump
authors.affiliation: Department of Psychiatry,Roy J. and Lucille A. Carver College of Medicine,University of Iowa,Iowa City,IA,USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Coryell
authors.affiliation: Department of Biostatistics,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: J
authors.initials: J
authors.lastname: Harezlak
authors.affiliation: Research Methods & Statistics Program,Graduate School of Education,University of California-Riverside,Riverside,CA,USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Marcoulides
authors.affiliation: Department of Biostatistics,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Psychology,College of Arts and Letters,University of Notre Dame,Notre Dame,IN,USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Steeger
authors.affiliation: School of Psychiatry,University of New South Wales,Sydney,NSW,Australia.
authors.forename: P B
authors.initials: PB
authors.lastname: Mitchell
authors.affiliation: Department of Psychiatry and Behavioral Sciences,Johns Hopkins School of Medicine,Baltimore,MD,USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Wilcox
authors.affiliation: Department of Psychiatry,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Hulvershorn
authors.affiliation: Department of Psychiatry,Washington University School of Medicine,St Louis,MO,USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Glowinski
authors.affiliation: Department of Psychiatry,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Iyer-Eimerbrink
authors.affiliation: Department of Psychiatry,School of Medicine,University of Michigan,Ann Arbor,MI,USA.
authors.forename: M
authors.initials: M
authors.lastname: McInnis
authors.affiliation: Department of Psychiatry,Indiana University School of Medicine,Indianapolis,IN,USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Nurnberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000523:psychology*; D015331:Cohort Studies; D015897:Comorbidity; D005163:Factor Analysis, Statistical; D005190:Family / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007389:Internal-External Control; D008297:Male; D008875:Middle Aged; D008960:Models, Psychological; D009315:National Institute of Mental Health (U.S.); D014481:United States; D055815:Young Adult
keywords: Bipolar disorder; co-morbidity; confirmatory factor analysis; confirmatory latent class analysis; subtypes